 |
|
|
|
|
|
|
|
|
 |
 |
 |
 |
 |
 |
 |
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Background
During surgical procedures for a skin cancer, the pathologist is often called upon to evaluate the adequacy of the surgical margins, to ensure the surgeon has completely removed the tumor. A frozen section is performed by the pathologist where a small portion of the tissue is frozen, cut on a microtome, stained, and interpreted under the microscope by the pathologist. In this manner, the surgical margins can be completely cleared and the patient can be spared a second procedure.
Acrochordon (Skin Tag, Fibroepithelial polyp)
Actinic Cheilitis
Actinic Keratosis
Aggressive Digital Papillary Adenocarcinoma
Apocrine Tumors (Hidradenoma Papilliferum, Apocrine Cystadenoma)
Basal Cell Carcinoma
Basal Cell Carcinoma-Treatment and Prognosis
Birt-Hogg Dube Syndrome
Bowen's Disease
Chondroid Syringoma (Mixed Tumors)
Chronic Papillomatous Dermatitis
Cowden's Syndrome
Cylindroma of the Skin (Turban Tumors)
Cysts of the Skin
Eccrine Carcinoma (Porocarcinoma, Adenoid Cystic Carcinoma)
Epidermodysplasia verruciformis
Extramammary Paget Disease
Favre-Racouchot Disease (Nodular Elastosis with Cysts and Comedones)
Fibrous Papule (Angiofibroma of the skin)
Keratoacanthoma
Keratoses (Seborrheic Keratosis, Acanthomas)
Merkel Cell Carcinoma
Metastatic Tumors to the Skin
Microcystic Adnexal Carcinoma
Mixed Tumors (Chondroid Syringoma)
Myelomeningocele
Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome)
Nevus Sebaceus
Onychomatricoma
Pilomatricoma
Poroma (Eccrine Poroma)
Sebaceous Carcinoma (Sebaceoma, Sebaceous Adenoma, Sebaceous Epithelioma)
Soft Tissue Tumors (Neurofibroma, Granular Cell Tumor)
Spiradenoma (Eccrine Spiradenoma)
Squamous Cell Carcinoma
Squamous Cell Carcinoma-Treatment and Prognosis
Syringocystadenoma Papilliferum
Syringoma
Trichoblastoma
Trichodiscoma (Fibrofolliculoma)
Trichoepithelioma
Tricholemmal Tumors
Tumor of the Follicular Infundibulum
Verruca Vulgaris (Warts)One of the most puzzling questions is why don't more people get skin cancer? The familiar scenario is a fair skinned, fair haired, and blue eyed individual is at greater risk for skin cancer. Yet, even the majority of these individuals do not get skin cancer. Recently investigators at M.D. Anderson Cancer Center in Houston, TX, have discovered that the Fas ligand gene may provide a vital defense against basal cell and squamous cell carcinomas. This is discussed under Pathogenesis in the outline below.
Dermatologists also classify patients by skin types.
SKIN TYPE CHARACTERIZATION I Usually very fair, burns easily and severely and cannot tan II Usually fair, burns easily but minimally tans III Average White skin, burns slightly then tans light brown IV Generally darker, never burns, always tans rapidly V Never burns, tans brown VI Never burns, tans to black
OUTLINE
PATHOGENESIS CHARACTERIZATION APOPTOSIS Proliferation, apoptosis, and survivin expression in keratinocytic neoplasms and hyperplasias.
Bowen AR, Hanks AN, Murphy KJ, Florell SR, Grossman D.
Department of Dermatology, University of Utah, Salt Lake City, Utah, USA.
Am J Dermatopathol. 2004 Jun;26(3):177-81. Abstract quote
The dysregulation of apoptosis occurs in many cutaneous disease states. Several apoptosis inhibitors have been shown elevated in neoplasms and in some inflammatory conditions, but their relation to proliferative and apoptotic states has not been defined.
We examined the expression of the apoptosis inhibitor survivin in a panel of keratinocytic neoplasms and hyperproliferative skin lesions using both immunohistochemistry and a newly developed in situ hybridization technique. Proliferation and apoptotic indices were also assessed by immunohistochemical staining for proliferating cell nuclear antigen and TUNEL, respectively.
We found the highest rate of proliferation in verrucae and psoriasis followed by actinic keratosis, squamous and basal cell carcinoma, lichen simplex chronicus, and seborrheic keratosis; all were significantly (P < 0.05) higher than normal skin. Apoptotic rate was increased in squamous (P = 0.05) and basal cell carcinoma (P = 0.03), but not significantly different from normal skin in the other lesions tested. Survivin expression was seen in most neoplasms and hyperproliferative lesions, but not normal skin. Survivin expression was often restricted to the upper third of the epidermis in psoriasis and lichen simplex chronicus, whereas all the other lesions stained diffusely.
Survivin expression appears to be a consistent feature of keratinocytic neoplasms and hyperproliferative lesions and may contribute to the formation of epidermal hyperplasia seen in all of these disease states.CD95 (FAS LIGAND) Role of the Fas ligand and UVR Arch Dermatol 1997;133:1263-1270
The study was conducted in equal numbers of mice exposed to UV lamps. One group had the normal Fas ligand protein and the other group lacked it. Fourteen of the twenty mice lacking the protein developed genetic mutations after repeated UV exposure compared to only 1 of the 20 normal mice. The normal mice had three times the number of sunburned cells in their skin as compared to the Fas lacking mice.
What does this mean? The Fas ligand is a sentinel for cells exposed to UV irradiation. When these cells are present, Fas induces them to die by apoptosis, programmed cell death. This eliminates the damaged cells preventing further mutations which could lead to cancer. The next step is to investigate whether the same mechanism occurs in humans.What is it about UV radiation (UVR)? It is thought to lead to skin cancer by two mechanisms: mutation of cellular DNA and induction of a state of relative immunosupression. DNA absorbs UV light leading to production of an excited state in DNA, rearrangement of electrons, and finally production of a photoproduct. The products are usually dipyrimidine structures that lead to substitution of incorrect nucleic acids during replication, leading to mutations. UVB is definitely more mutagenic, commonly causing substitutions of thymine to cytosine. UVA is 1000x less likely to mutate the DNA, most commonly causing a thymine to guanine mutation. UVR also alters Langerhans antigen-presenting cell function and induces cytokines that promote suppressor immune pathway stimulation and inhibits helper pathways. UVR depletes Langerhans cells within the skin and stimulates keratinocytes to produce urocanic acid, tumor necrosis factor-alpha, and interleukin 10, which all lead to production of T-suppressor cells.
One may ask why the body evolved this elaborate mechanism. Some speculate that these immunosuppressive mechanisms exist to prevent any autoimmune reactions to new antigens fromed by the UVR exposure.COX-2 Immunohistochemical expression of cyclooxygenase-2 in skin cancers
Masayori Kagoura, etal.
Journal of Cutaneous Pathology 2001;28 (6): 298-302
Background: Cyclooxygenase (COX), also known as prostaglandin endoperoxide synthase, catalyses the conversion of arachidonic acid to prostanoids. There are two different isoforms of COX, referred to as COX-1 and COX-2. Overexpression of COX-2 has been demonstrated in various neoplasms, such as experimentally promoted tumors, gastrointestinal cancers and breast tumors.
Methods: In this study, we used immunohistochemistry to investigate COX-2 expression in a series of basal cell epitheliomas (BCE), Bowen’s disease, squamous cell carcinomas (SCC) and metastatic tumors of the skin.
Results: Four of 16 BCE showed a positive reaction for COX-2 and the adenoid type of BCE was the most strongly positive. In Bowen’s disease, the extent of positive staining for COX-2 was even higher than that in BCE. Eleven of 15 SCC showed a positive reaction for COX-2 and the pattern of staining was heterogeneous with more intense staining in the center of the tumor nests. In metastatic tumors, the percentage of COX-2-positive tumor cells and the intensity of their staining was low compared with Bowen’s disease and SCC.
Conclusions: These results indicate that the intensity of COX-2 staining and its heterogeneous distribution are related to the degree of cellular differentiation and the various phenotypes of tumor cells, but the extent of COX-2 staining did not correlate with the degree of malignancy.
DESMOGLEIN I Expression of desmoglein I and plakoglobin in skin carcinomas
HideyukiTada, MitsuoHatoko, AyaTanaka, MasamitsuKuwahara and TsutomuMuramatsu
J Cutan Pathol 2000;27 (1), 24-29 Abstract quote
Reduction or absence of cell-cell adhesion molecules has been reported in various carinomas and the abnormal expression of these molecules contributes to the invasive and metastatic behavior of malignant tumor cells. In epidermal keratinocytes, the main cell-cell adhesion systems are adherens junctions and desmosomes. Previous studies have shown that, in skin carcinomas, the decreased expression of E-cadherin, major constitutional glycoprotein of adherens junctions, is associated with the invasive and metastatic ability of the tumor cells.
In the present study, we examined the expression of desmoglein I and plakoglobin, the constitutional components of desmosomes, in various skin carcinomas such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), extramammary Paget's disease and Bowen's disease by an immunofluorescence method.
In normal human skin, desmoglein I and plakoglobin were strongly expressed in the intercellular space of the epidermis except for the basal cell layer. In BCC and SCC, the expression of desmoglein I and plakoglobin was markedly reduced or absent in tumor cells. In carcinoma in situ of Paget's disease, compared with the normal epidermal cells surrounding tumor cell nests, the expression of these molecules was reduced in tumor cells. In Paget's disease with dermal infiltration of tumor cells, the expression of these molecules was almost absent throughout the epidermis. In Bowen's disease, the expression of desmoglein I was reduced in the clumping cells and dyskeratotic cells.
These results suggest that the expression of desmosomal cadherin is reduced or absent in human skin carcinomas, and that reduction of these molecules may also contribute to the invasiveness and metastasis of skin carcinomas.
E-CADHERIN
E-cadherin promoter hypermethylation in preneoplastic and neoplastic skin lesions.
Chiles MC, Ai L, Zuo C, Fan CY, Smoller BR.
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Mod Pathol. 2003 Oct;16(10):1014-8 Abstract quote.
E-cadherin is a calcium-dependent, intercellular adhesion molecule that is specifically expressed in epithelial tissues and plays an important role in maintaining epithelial stability. E-cadherin is widely regarded as a prognostic marker in many types of human cancers. The inactivation of the E-cadherin gene is linked to increased potential for tumor invasiveness and distant metastasis.We previously demonstrated reduced expression of E-cadherin protein immunohistochemically in invasive squamous cell carcinomas of the skin as compared with adjacent normal skin. An epigenetic alteration in association with promoter hypermethylation is one important mechanism of gene silencing. In the present study, we analyze the E-cadherin gene promoter hypermethylation in preneoplastic and neoplastic skin lesions to determine whether epigenetic alteration of the E-cadherin gene also plays an important role in cutaneous squamous carcinogenesis. A total of 33 cases was examined for evidence of E-cadherin promoter hypermethylation, and these consist of nine cases of spongiotic dermatitis as nonneoplastic skin control, nine cases of actinic keratosis, eight cases of squamous cell carcinoma in situ, and seven cases of invasive squamous cell carcinoma. Promoter hypermethylation of the E-cadherin gene was detected in 6 of 7 cases (85%) of invasive squamous cell carcinoma, 4 of 8 cases (50%) of squamous cell carcinoma in situ, 4 of 9 cases (44%) of actinic keratosis, and 2 of 9 cases (22%) of nonneoplastic skin.
We conclude that E-cadherin promoter hypermethylation occurs frequently and may represent an important mechanism of E-cadherin inactivation in cutaneous preneoplastic and neoplastic lesions. The frequencies of E-cadherin promoter hypermethylation appear to be correlated with more advanced stage of squamous carcinogenesis in skin.
Ets-1
Ets-1 immunohistochemical expression in non-melanoma skin carcinoma.
Keehn CA, Smoller BR, Morgan MB.
Department of Pathology, University of South Florida College of Medicine, Tampa, FL, Department of Pathology, University of Arkansas for the Medical Sciences, Little Rock, Arkansas, The James A. Haley Veterans Hospital, Tampa, FL, and Bay Area Dermatopathology Ameripath Tampa, FL, USA.
J Cutan Pathol. 2004 Jan;31(1):8-13 Abstract quote.
BACKGROUND: Ets-1 oncoprotein is a transcription factor known to regulate the expression of numerous genes important in extracellular matrix remodeling and angiogenesis. Up-regulation of Ets-1 has been shown to be important in a variety of human malignancies and to correlate with prognosis. To our knowledge, this oncoprotein has not been examined in non-melanoma skin carcinomas.
DESIGN: A series of 26 primary cutaneous skin lesions with patient records were independently examined for diagnosis confirmation and immunohistochemical expression by two dermatopathologists. The immunohistochemical expression for Ets-1 (Novocastra, Newcastle Upon Tyne, England, UK) was scored by an average of the mean labeling intensity (MLI), where no nuclear staining = 0, weak nuclear staining = 1, moderate nuclear staining = 2, and strong nuclear staining = 3.
RESULTS: All basal cell carcinoma (BCC) and Merkel cell carcinoma (MCC) cases exhibited negative nuclear staining, for an average MLI of 0. Keratoacanthomas, squamous cell carcinoma in situ (SIS), and well-differentiated squamous cell carcinomas (SCCs) exhibited negative to weak nuclear staining, for an average MLI of 0.4 +/- 0.3. Moderately differentiated SCCs exhibited moderate nuclear staining, for an average MLI of 1.8 +/- 0.6. Poorly differentiated SCCs and metastatic SCCs exhibited very strong nuclear staining, with an average MLI of 2.8 +/- 0.2.
CONCLUSIONS: Ets-1 is not expressed in cutaneous BCC or MCC and is weakly expressed in SIS and forms of well-differentiated SCC. Although the intensity of Ets-1 immunostaining distinguished between well-differentiated and poorly differentiated SCC (p < 0.0001), it failed to discriminate between in situ and well-differentiated SCCs. The preliminary data suggests Ets-1 may be important in the pathogenesis of invasive SCC.INSULIN-LIKE GROWTH FACTOR-1 RECEPTOR
Expression of insulin-like growth factor-I receptor in primary cutaneous carcinomas.
Keehn CA, Saeed S, Bickle K, Khalil FK, Morgan MB.
Department of Pathology, University of South Florida College of Medicine, Tamp, FL, USA.
J Cutan Pathol. 2004 May;31(5):368-72. Abstract quote
Background: Insulin-like growth factor-I (IGF-I) is the principal mediator of growth hormone, exerting its effects through binding of the insulin-like growth factor-I receptor (IGF-IR). Post-receptor activation leads to the production of transcription factors involved in cell proliferation, differentiation, transformation, and survival. Data indicate that IGF-IR is involved in tumorigenesis. To our knowledge, this receptor has not been previously studied in primary cutaneous carcinomas.
Methods: Twenty-five cases of primary cutaneous carcinomas consisting of three keratoacanthoma-type squamous cell carcinomas (KAs), two squamous cell carcinomas in situ (SCCs in situ), eight squamous cell carcinomas (SCCs), three conventional basal cell carcinomas (BCCs), two morpheaform basal cell carcinomas (M-BCCs), and seven Merkel cell carcinomas (MCCs) were analyzed for IGF-IR immunohistochemical expression using IGF-IR mouse monoclonal antibody (dilution 1 : 50) using the avidin-biotin-peroxidase complex method.
Results: Normal epidermis was negative for IGF-IR expression. Normal eccrine glands and outer root sheath strongly expressed IGF-IR. All KAs, SCCs in situ, SCCs, and BCCs were negative for IGF-IR expression. Six of seven (86%) of the MCCs stained with IGF-IR strongly, showing cell membrane accentuation and a perinuclear dot-like pattern.
Conclusion: The data suggest that IGF-IR immunopositivity in MCCs might constitute a diagnostic tool in discriminating between SCCs and BCCs. Although the possible pathogenic significance of the perinuclear dot-like staining pattern observed in these neoplasms is unknown, its pattern is similar to what has been previously described with cytokeratin-20 immunostaining.MAGE-A4 (CANCER TESTIS ANTIGEN)
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Background: Lifetime risk for squamous cell carcinoma (SCC) of the skin is 1:30. Risk in organ-transplant recipients (OTR) is increased over 60-fold through long-term drug-induced immunosuppression. MAGE family-derived peptides are cancer/testis antigens recognized by specific CD8(+) T cells and employed for immunotherapy. We were interested in the frequency and distribution of MAGE-A4 in epithelial skin tumors of OTR and immunocompetent patients.
Methods: mAb 57B predominantly recognizing MAGE-A4 was used to stain 119 formalin-fixed, paraffin-embedded epithelial skin tumors (actinic keratosis, bowenoid actinic keratosis, Bowen's disease, and SCC; n = 17, 25, 61, 16, respectively) in immunocompetent patients (n = 84) and OTR (n = 35).
Results: All four epithelial skin tumors showed comparable immunoreactivity ranging from (25-71%, p = 0.361). Scattered immunoexpression pattern was more frequent in OTR (p = 0.025). SCC showed polarized immunoreactivity basally (p = 0.002).
Conclusion: MAGE-A4 was expressed in a large part of epithelial skin tumors with predominantly scattered immunoexpression pattern in OTR. The difference in immunoexpression pattern for immune status was limited, suggesting important non-immunosuppressor-mediated mechanisms for increased skin carcinogenesis in OTR. mAb 57B may be a helpful tool for immunohistochemistry and micrographic surgery using formalin-fixed paraffin-embedded tissue.MICROSATELLITE INSTABILITY
Microsatellite instability and its relevance to cutaneous tumorigenesis.Hussein MR, Wood GS.
The Department of Medicine (Dermatology), University of Wisconsin and William S. Middleton Memorial Veteran Hospital, Madison, WI, USA.
J Cutan Pathol 2002 May;29(5):257-67 Abstract quote Increasing evidence suggests that human tumors sequentially accumulate multiple mutations that cannot be explained by the low rates of spontaneous mutations in normal cells (2-3 mutations/cell).
The mathematical models estimate that for the solid tumors to develop, as many as 6-12 mutations are required in each tumor cell. Therefore, to account for such high mutation rates, it is proposed that tumor cells are genetically unstable, i.e. they have genome-wide mutations at short repetitive DNA sequences called microsatellites. Microsatellite repeats are scattered throughout the human genome, primarily in the non-coding regions, and can give rise to variants with increased or reduced lengths, i.e. microsatellite instability (MSI). This instability has been reported in an increasing number of cutaneous tumors including: melanocytic tumors, basal cell carcinomas and primary cutaneous T-cell lymphomas. Moreover, MSI has been observed in skin tumors arising in the context of some hereditary disorders such as Muir-Torre syndrome, Von Recklinghausen's disease and disseminated superficial porokeratosis. While MSI in some of these disorders reflects underlying DNA replication errors, the mechanism of instability in others is still unknown.
Thus far, MSI is considered to be a distinct tumorigenic pathway that reveals surprising versatility. The ramifications for cutaneous neoplasms warrant further investigation.
NITRIC OXIDE SYNTHASE Immunohistochemical study of inducible nitric oxide synthase in skin cancers
Masayori Kagoura, Chihiro Matsui, Masahiko Toyoda and Masaaki Morohashi
Department of Dermatology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan
Journal of Cutaneous Pathology 2001;28 (9), 476-481 Abstract quote
Background: Nitric oxide (NO) is synthesized from the amino acid L-arginine by NO synthase (NOS). Experimental evidence suggests that increased express of inducible NOS (iNOS), which is an NOS isoform and calcium independent, is related to various pathological processes, such as inflammation and cancer.
Methods: In this study, we used immunohistochemistry to investigate iNOS expression in a series of basal cell carcinomas (BCC), Bowen’s disease, squamous cell carcinomas (SCC), extramammary Paget’s disease (EPD) and metastatic tumors of the skin.
Results: Only 1 of 16 BCC cases was positive for iNOS and the intensity of staining was weak. In most of the 10 cases of Bowen’s disease, iNOS was weakly expressed and there was a wide range in the percentage of positive tumor cells. Twelve of the 16 cases of SCC were positive for iNOS and the extent of positivity was greater than in Bowen’s disease. Two of the 7 cases of EPD were positive for iNOS, and 12 of the 15 cases of metastatic cancer were positive. Well-differentiated adenocarcinomas were diffusely positive, whereas poorly-differentiated ones showed strong and heterogeneous staining.
Conclusions: These results indicated that the expression of iNOS may reflect the proliferation of tumor cells and that a heterogeneous distribution of iNOS may correlate with a wide variety of biological behavior of tumor cells.
NUCLEOLAR ORGANIZER REGIONS
- Nucleolar organizer region staining patterns in paraffin-embedded tissue cells from human skin cancers.
Romao-Correa RF, Maria DA, Soma M, Sotto MN, Sanches JA Jr, Neto CF, Ruiz IR.
Genetics Laboratory, Butantan Institute, Sao Paulo, SP, Brazil.
J Cutan Pathol. 2005 May;32(5):323-8. Abstract quote
Background: Increased number of nucleoli (nucleolar organizer regions, NORs) with abnormal shapes and sizes, including small dots, has been used as prognostic tools to evaluate tumor proliferation levels and troublesome borderline lesions. In this study, NOR patterns of skin cancers were performed in the search of a valuable prognostic method to complement other histological procedures.
Methods: Paraffin-embedded tumor tissue was obtained from basal and squamous cell carcinomas, cutaneous malignant melanoma, premalignant lesions, and Skmel-28 human melanoma cells. Slices were dewaxed and AgNOR stained. The patterns were scored and submitted for statistical analyses.
Results: All types of cancer cells showed variable numbers of abnormally shaped nucleoli and dot-like structures. Only tumor cells presented four or more nucleoli, with or without dots, while 85% of the normal cells had one single NOR without dots. Most data were statistically significant when compared to normal cells. As a whole, squamous cell carcinoma and malignant melanoma tumor cells had less NOR alterations than basal cell carcinoma (BCC) tumor types.
Conclusions: Changes in the number and shape of nucleoli present in malignant cells could be attributed to increased levels on rDNA transcription on cancer cells, besides abnormal remodeling of chromatin, which could disrupt proper nucleoli association. Increased genetic alterations on malignant basal cells could contribute to impair invasive and migration abilities of BCC tumors.RETINOBLASTOMA GENE
Retinoblastoma gene expression in human non-melanoma skin cancer.
Edwards MJ, Thomas RC, Wong YL.
University of Wales Institute, School of Applied Sciences, Llandaf Campus; and Department of Dermatology, University of Wales College of Medicine, Heath Park, Cardiff, UK
J Cutan Pathol. 2003 Sep;30(8):479-85. Abstract quote
BACKGROUND: The aberrant expression of both the retinoblastoma and p53 tumor suppressor genes has been associated with more aggressive tumors, metastasis and lower survival.
METHODS: We have evaluated immunohistochemically the expression of pRB in a panel of non-melanoma skin cancers containing p53 somatic mutations.
RESULTS: Nuclear anti-p53 staining was detected in 18 (72%) differentiated squamous cell carcinomas, six (100%) undifferentiated squamous cell carcinomas and seven (28%) basal cell carcinomas. A correlation was observed between p53 expression and the proliferative activity of differentiated squamous cell carcinomas (P < 0.066), undifferentiated squamous cell carcinomas (P < 0.05) and basal cell carcinomas (P < 0.01). Tumors were selected for mutant p53 expression by PCR-directed DNA sequencing and pRB expression measured immunohistochemically. Anti-pRB reactivity was detected in the nuclei of basal and suprabasal layer cells of normal epidermis, and in the proliferative compartment of all the differentiated squamous cell carcinomas, and basal cell carcinomas. A correlation was observed between pRB expression and the proliferative activity of the differentiated squamous cell carcinomas (P < 0.01) and basal cell carcinomas (P < 0.025). However, anti-pRB reactivity was not detected in the six anti-p53 reactive undifferentiated squamous cell carcinomas.ULTRAVIOLET RADIATION
- Ultraviolet radiation and skin cancer: molecular mechanisms.
Hussein MR.
Pathology department, Assuit University Hospitals, Assuit University, Assuit, Egypt.
J Cutan Pathol. 2005 Mar;32(3):191-205. Abstract quote
Every living organism on the surface of the earth is exposed to the ultraviolet (UV) fraction of the sunlight. This electromagnetic energy has both life-giving and life-endangering effects. UV radiation can damage DNA and thus mutagenize several genes involved in the development of the skin cancer. The presence of typical signature of UV-induced mutations on these genes indicates that the ultraviolet-B part of sunlight is responsible for the evolution of cutaneous carcinogenesis.
During this process, variable alterations of the oncogenic, tumor-suppressive, and cell-cycle control signaling pathways occur. These pathways include (a) mutated PTCH (in the mitogenic Sonic Hedgehog pathway) and mutated p53 tumor-suppressor gene in basal cell carcinomas, (b) an activated mitogenic ras pathway and mutated p53 in squamous cell carcinomas, and (c) an activated ras pathway, inactive p16, and p53 tumor suppressors in melanomas.
This review presents background information about the skin optics, UV radiation, and molecular events involved in photocarcinogenesis.
CLINICAL
VARIANTSCHARACTERIZATION SCHOPF-SCHULZ-PASSARGE
SYNDROME
Syndrome of cystic eyelids, palmo-plantar keratosis, hypodontia and hypotrichosis as a possible autosomal recessive trait.
Schopf E, Schulz HJ, Passarge E.
Birth Defects Orig Artic Ser. 1971 Jun;7(8):219-21. Abstract quote
Description is given of two sisters, offspring of a first cousin marriage, who exhibited the following identical lesions: 1) cysts of the borders of upper and lower lids; 2) hypodontia; 3) hypotrichosis; 4) palmo-plantar keratosis and 5) onychodystrophy.It is suggested that this combination represents a previously unrecognized autosomal recessive trait in man.
HISTOLOGICAL VARIANTS CHARACTERIZATION ADNEXAL CARCINOMA, LOW GRADE WITH DIVERGENT DIFFERENTIATION
Sikl's Department of Pathology, Charles University Medical Faculty Hospital, Pilsen, Czech Republic.
The conjoint occurrence of follicular, sebaceous, or apocrine differentiations in a cutaneous adnexal neoplasm is a known event, more often encountered in benign neoplasms, whereas reports of cutaneous malignant adnexal tumors with bilineage or trilineage differentiation are few.
A new case of a cutaneous malignant adnexal neoplasm with multidirectional differentiation is reported here. A 57-year-old woman presented with a long-standing, slowly growing, asymptomatic solitary tumor the size of a large nut in the coccygeal area, which was surgically excised. Ten years after the surgery, there was no evidence of recurrence or metastasis.
Microscopically, the neoplasm was located in the dermis with focal extension into the subcutis. It was asymmetric, horizontally oriented, and mostly composed of small nodules that varied in shape from round and oval aggregations to elongated strands and irregular islands; the nodules were either clustered, formed a jigsaw puzzle-like pattern or were dispersed. The nodules were composed of small basaloid cells sometimes intermixed with larger cells with ample cytoplasm forming glandular structures. Rare nodules resembled elements seen in a spiradenoma by containing scattered lymphocytes and globules of hyalinized eosinophilic basal membrane material. The stroma was paucicellular, but focally it resembled that seen in perifollicular mesenchyme. Mitotic figures, including abnormal ones, were infrequent, but mild nuclear pleomorphism, nuclear crowding, and individual cell necrosis were easily appreciable in both small basaloid cells and cells with clear cytoplasm. Perineural invasion was apparent.
We classified this tumor as a well-differentiated adnexal carcinoma demonstrating combined follicular and apocrine differentiation. It differs from previously published cases of malignant adnexal tumors with multidirectional differentiation and further exemplifies the spectrum of diversity encountered in malignant proliferations with differentiation toward the folliculosebaceous-apocrine unit.BASALOID FOLLICULAR HAMARTOMA
Familial basaloid follicular hamartoma: lesional characterization and review of the literature.Jih DM, Shapiro M, James WD, Levin M, Gelfand J, Williams PT, Oakey RJ, Fakharzadeh S, Seykora JT.
Am J Dermatopathol 2003 Apr;25(2):130-7 Abstract quote Basaloid follicular hamartoma (BFH) is a rare cutaneous lesion associated with the acquisition of small papules that remain stable for many years. Basaloid follicular hamartoma lesions can present sporadically or as part of an inherited syndrome. Occasionally, biopsies of BFH lesions are interpreted as basal cell carcinoma (BCC), which necessitates complete removal of the lesion.
In this report, we characterize a case of a familial BFH syndrome and discuss the clinical, histologic, and molecular features of BFH lesions that help to distinguish it from BCC. The BFH lesions in our patients remained stable for many years.
Histologically, BFH lesions exhibit fewer mitoses and decreased single cell necrosis when compared with BCC. Immunohistochemical staining for the proliferation markers proliferating cell nuclear antigen and Ki-67 demonstrated less staining in BFH than in BCC. In addition, levels of PTCH (patched) mRNA were increased relative to unremarkable epidermis in familial BFH lesions but to a lesser degree and in a different pattern than that seen in BCC. In summary, familial BFH can be distinguished from BCC based on clinical, histologic, and molecular features and is associated with deregulation of the PTCH pathway.
Basaloid follicular hamartoma may represent an indolent lesion within the spectrum of basaloid epithelial neoplasms associated with deregulation of the PTCH signaling pathway. We discuss this case in parallel with a growing body of literature that supports the nosologic designation of BFH.CHONDROID SYRINGOMA
- Chondroid syringoma. Cytokeratin 20 immunolocalization of Merkel cells and reappraisal of apocrine folliculo-sebaceous differentiation.
Salama ME, Azam M, Ma CK, Ormsby A, Zarbo RJ, Amin MB, Lee MW.
Department of Pathology, Henry Ford Hospital, Detroit, Mich 48202, USA.
Arch Pathol Lab Med. 2004 Sep;128(9):986-90. Abstract quote
CONTEXT: Chondroid syringoma (CS) is a benign cutaneous adnexal tumor with epithelial and stromal components. Epithelial components derived from folliculo-sebaceous-apocrine germ are evident in apocrine but not in eccrine CS.
OBJECTIVES: To further characterize pilosebaceous differentiation and to identify the presence of Merkel cells in the areas of follicular differentiation.
DESIGN: Histologic type, folliculo-sebaceous differentiation, character of stroma, and presence or absence of Merkel cells by cytokeratin (CK) 20 immunoreactivity were evaluated in 25 CSs (22 apocrine and 3 eccrine) from the surgical pathology files of Henry Ford Hospital (Detroit, Mich).
RESULTS: Most CSs occurred in the head and neck region of patients aged 40 years or older. We found no significant difference in sex, age, or location between apocrine and eccrine types. The stroma varied from myxoid (100%) to chondroid (59%), with various amounts of fat (59%) and ossification identified in 2 cases (9%) of apocrine type, but was homogeneously myxoid in the eccrine type. Follicular and sebaceous differentiation was found in 64% and 32% of apocrine CSs, respectively. Only 2 (14%) apocrine CSs with follicular differentiation were positive for CK20 (a few scattered cells in one case and numerous grouped cells in the other in association with follicular epithelium). No correlation was found between type of stroma and the presence of Merkel cells. Scattered Merkel cells were identified in 83% of normal hair follicles and in 33.3% of normal epidermis.
CONCLUSION: A high proportion of apocrine CSs show folliculo-sebaceous differentiation. The presence of Merkel cells in foci of follicular differentiation of CS supports the hypothesis that Merkel cells may be an integral constituent of follicles. To our knowledge, the presence of Merkel cells in CS, particularly in proliferative form, has not been described previously in the literature.CLEAR CELL MESENCHYMAL NEOPLASM
- Distinctive dermal clear cell mesenchymal neoplasm: clinicopathologic analysis of five cases.
Lazar AJ, Fletcher CD.
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Am J Dermatopathol. 2004 Aug;26(4):273-9. Abstract quote
Dermal clear cell tumors are not common. This group of lesions is comprised primarily of clear cell adnexal lesions, balloon cell melanocytic lesions, and metastatic clear cell carcinomas.
We report the clinicopathologic features of five cases of a novel dermal clear cell neoplasm that appears mesenchymal in nature. The affected patients included 3 men and 2 women ranging in age from 38 to 70 (median, 45 years). All the lesions occurred on the lower limb. Clinically described as smooth cutaneous nodules, size ranged from 0.5 to 2.5 cm in greatest dimension and the lesions were present from weeks to 5 years prior to excision. Situated in the reticular dermis, the tumors usually extended to involve the subcutis with sparing of the papillary dermis. The tumors were composed of large optically clear cells with vesicular nuclei. The lesions entrapped adnexal structures and thin dermal collagen fibers. Mitoses were rare (less than 1 per 25 hpf). A single case showed more pleomorphic nuclei as well as quite frequent mitoses and was considered of uncertain biologic potential. Immunohistochemistry revealed reactivity only for NKI-C3 (5/5 cases), CD68 (2/5 cases), and vimentin (2/3 cases); melanocytic, epithelial, and lymphoid markers were uniformly negative. All five lesions were locally excised; the more pleomorphic and mitotically active lesion was widely re-excised and given subsequent radiation therapy. In follow-up ranging from 1.5 to 11 years (median, 5.5 years), none of these lesions has recurred.
These tumors appear to be mesenchymal in nature, but their precise line of differentiation is unknown. Recognition of these lesions is important to avoid confusion with better-known malignant neoplasms.CONGENITAL PANFOLLICULAR NEVUS
- Congenital panfollicular nevus: report of a new entity.
Finn LS, Argenyi ZB.
The Department of Pathology at The University of Washington, Seattle, WA, USA.
J Cutan Pathol. 2005 Jan;32(1):59-62. Abstract quote
The various forms of non-melanocytic nevi (hamartomas) are usually encountered in pediatric patients, and nevus sebaceous of Jadassohn is the most common to have undifferentiated pilosebaceous units.
We report a unique congenital follicular nevus that fails to meet the criteria of any previously described follicular neoplasm, despite the plethora of alternatives. Clinically considered a syringocystadenoma papilliferum, the excised lesion contained multiple dermal nodules that exhibited nearly all stages of follicular differentiation. The periodicity of the follicular proliferations was akin to normal terminal hair, and a prominent perifollicular sheath surrounded each.
This benign lesion of abortive hair follicles was unassociated with any established genodermatous syndrome or other adnexal neoplasm.GIANT FOLLICULO-SEBACEOUS CYSTIC HAMARTOMA
Giant folliculosebaceous cystic hamartoma of the upper extremity
David E. Sturtz, David J. Smith, Marlene S. Calderon and Douglas R. Fullen
Journal of Cutaneous Pathology
Volume 31 Issue 3 Page 287 - March 2004 Abstract quote
Background: Folliculosebaceous cystic hamartoma (FSCH) is a rare cutaneous hamartoma consisting of dilated folliculosebaceous units invested in mesenchymal elements. These lesions have a striking predilection for the central face and scalp of adults. The vast majority of lesions present as 0.5-1.5-cm papules or exophytic nodules. A single case of giant FSCH has been reported on the upper back.Methods: A 32-year-old woman presented with a (15 cm in greatest dimension) plaque-like, multinodular lesion on her left upper arm for several years. The lesion was clinically suspected to be a nevus sebaceus.
Results: The skin excision showed numerous dermal and subcutaneous dilated follicular structures with peripherally radiating sebaceous lobules, hair follicles, and surrounding mesenchymal elements consistent with FSCH.
Conclusion: To our knowledge, this is the second case of giant FSCH. Our case is unique for its larger size, more plaque-like growth, and location on an extremity when compared to the seminal case of giant FSCH.
LYMPHOEPITHELIOMA-LIKE CARCINOMA
Department of Pathology, Penrose Hospital, Colorado Springs, CO, USA.
We report a case of a primary lymphoepithelioma-like carcinoma of the skin (LELCS) associated with scar from a previous excision of basal cell carcinoma.
The patient was a 68-year-old female with a 3.0 mm skin-colored pearly papule on her forehead that developed over 2-3 months. The patient had a history of a basal cell carcinoma in the same location, which was completely excised 1 year earlier. A biopsy and subsequent excision of the tumor were performed. The tumor consisted of small islands of large pleomorphic mitotically active epithelioid cells surrounded by a very dense lymphoplasmacytic infiltrate. The tumor was associated with dermal scar. There was no connection of tumor with the unremarkable epidermis. Immunohistochemical examination showed that the epithelioid tumor cells were positive for pan-cytokeratin and epithelial membrane antigen, supporting the morphologic impression of LELCS. The lesion was negative for Epstein-Barr virus. Retrospective review of the original excision specimen confirmed the diagnosis of an ordinary basal cell carcinoma. Forty-five cases of LELCS have been reported to date.
We report the first case of LELCS to arise in the scar from an excision of a cutaneous malignancy.
Am J Dermatopathol. 2006 Jun;28(3):211-215. Abstract quote
We report a case of a primary lymphoepithelioma-like carcinoma (LELC) of the skin. The patient was a 73-year-old man with a lump on his back for 18 months. A biopsy and subsequent excision was performed. He also had axillary node clearance for metastatic disease. The tumor was composed of islands of pleomorphic cells with a lymphocytic infiltrate.
Differential diagnoses included squamous cell carcinoma, adnexal carcinoma, Merkel cell tumors, lymphoepithelial lesions, lymphomas, and skin metastases. The histopathologic and immunohistochemical features were those of a LELC of the skin. It was negative for Epstein-Barr virus. Just over 30 cases of primary LELCs arising in the skin have been reported with only 1 documented fatality.
We report a case with extensive vascular involvement and bilateral lymph node metastases.
- Lymphoepithelioma-Like Carcinoma of the Skin in a Tunisian Patient.
Fenniche S, Zidi Y, Tekaya NB, Ammar FB, Yaacoub K, Mokni M, Mokhtar I, Osman AB, Zitouna MM, Haouet S.
From the *Dermatology Department, Habib Thameur Hospital, Tunis, Tunisia; daggerHistopathology Department, La Rabta Hospital, Tunis, Tunisia; double daggerDermatology Department, La Rabta Hospital, Tunis, Tunisia; and section signORL Department, La Rabta Hospital, Tunis, Tunisia.
Am J Dermatopathol. 2006 Feb;28(1):40-44. Abstract quote
Lymphoepithelioma-like carcinoma of the skin (LELCs) is a rare cutaneous neoplasm with histologic features resembling lymphoepitheliomatous tumors of the nasopharynx. The association of lymphoepitheliomas with Epstein-Barr Virus (EBV) at some extracutaneous sites is well documented. In contrast, the presence of EBV in LELCs has never been shown in either Caucasians or Asian patients.
We present the first case of LELCs in a Tunisian patient, a 78-year-old woman who presented with a nodule of the right cheek of 2 months' duration. The patient underwent surgical excision and there was no evidence of local recurrence 6 months later.
Histologically, the entire dermis was occupied by lobules composed of atypical epithelial cells surrounded by a dense lymphoplasmacytic infiltrate. Immunohistochemical examination showed that the epithelial tumor cells were positive for cytokeratin and epithelial membrane antigen. In situ hybridization investigations for the presence of EBV-encoded RNA showed negative results.
Our findings suggest that LELCs is not related to EBV among North African patients.
- Lymphoepithelioma-like carcinoma of the skin with spindle cell differentiation.
Clarke LE, Ioffreda MD.
Department of Pathology, Penn State Univerity of Medicine/Hershey Medical Centre, Hershey, PA, USA.
J Cutan Pathol. 2005 Jul;32(6):419-23. Abstract quote
Background: Primary cutaneous LELC is a cutaneous neoplasm with histopathologic features identical to those seen in the undifferentiated subtype of nasopharyngeal carcinoma. It is extremely rare, with only approximately 30 cases reported in the literature.
Methods: We report a case of primary cutaneous LELC arising on the forehead of a 72 year-old male in which a proportion of the neoplastic cells demonstrated distinctive spindle cell morphology.
Results: Microscopic examination showed a dense lymphoplasmacytic infiltrate admixed with large spindle-shaped cells with vesicular nuclei, prominent nucleoli, and frequent mitotic figures. These cells were negative for an extensive panel of immunohistochemical markers and positive only for broad-spectrum cytokeratins and epithelial membrane antigen. There was no connection between the tumor and the epidermis and no epidermal dysplasia. In situ hybridization for Epstein-Barr virus was negative.
Conclusions: The spindle cell differentiation in this case is unusual and suggests that in some cases the differential diagnosis of cutaneous spindle cell neoplasms might include primary cutaneous LELC.NEUROFOLLICULAR HAMARTOMA Neurofollicular hamartoma: a light microscopic and immunohistochemical study.
Barr RJ, Goodman MM.
Department of Dermatology, University of California, Irvine.
J Cutan Pathol 1989 Dec;16(6):336-41 Abstract quote
Neurofollicular hamartoma is an unusual, previously undescribed neoplasm characterized by a proliferation of spindle cells and hyperplastic pilosebaceous units.
Five cases were reviewed. The lesions presented as single, asymptomatic, smooth, flesh-colored papules. Four were on the nose, and one on the adjacent nasolabial fold. Immunoperoxidase studies performed on two cases utilizing antibodies to S-100 antigen were positive in both.
These lesions share some histological and clinical features with angiofibroma and neurofibroma.
NODULAR HIDRADENOMA
Section of Histopathology, Department of Pathology and Microbiology, The Aga Khan University Medical Centre, Karachi, Pakistan.
Background: Nodular hidradenoma is a distinctive sweat gland neoplasm. In addition to the well-known histological and cytological features, we hereby describe for the first time nuclear grooving as a useful morphological feature to aid in its diagnosis.
Methods: All cases were analyzed for anatomic location, size, age, sex and histology, with attention focused mainly on the nuclear features. A semiquantitative method was used to estimate the percentage of nuclear grooves in five consecutive high-power fields (x40), with confirmation on x100. Electron microscopy was also performed to confirm light microscopic observation.
Results: Totally, 34 cases of nodular hidradenoma were studied. All the tumors showed two types of cells. One type of cell contained clear cytoplasm with small, round nuclei. The second type of cell, which was the predominant type, had elongated nuclei. In 30 (88%) of the 34 cases, about 30% of these cells at x40 and x100 magnification showed nuclear grooving. Electron microscopy on these samples confirmed nuclear grooves.
Conclusions: In this study, we reviewed 34 cases of nodular hidradenoma. In addition to the classical features, both histologically and cytologically, we describe for the first time the nuclear grooves as a frequent finding in these neoplasms. This finding was also confirmed by electron microscopy. We believe that this newly described histological feature will aid the practicing pathologist to make this important diagnosis.PANFOLLICULOMA
- Cystic panfolliculoma.
Hoang MP, Levenson BM.
Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9073, USA.
Arch Pathol Lab Med. 2006 Mar;130(3):389-92. Abstract quote
Panfolliculoma is a rare follicular neoplasm with differentiation toward both upper (infundibulum and isthmus) and lower (stem, hair matrix, and bulb) segments of a hair follicle.
We present an unusual case of cystic panfolliculoma. A 33-year-old Hispanic woman presented with an 8-month history of a 3.0-cm cystic scalp mass. The lesion was excised, and the histologic sections showed a cystic follicular neoplasm that contained corneocytes in basket-woven and laminated array, trichohyalin granules of the inner root sheath, germinative cells, papillae, matrical cells, and "shadow" cells.
Cytokeratin 903 and cytokeratin 5/6 immunostains uniformly highlight the tumor cells. Ber-EP4 strongly labels the germinative cells but not the follicular papillae. CD34 labels the surrounding fibrotic stroma and focally the epithelial component.
SARCOMATOID CARCINOMA
- Cutaneous carcinosarcoma: adnexal vs. epidermal types define high- and low-risk tumors. Results of a meta-analysis.
Tran TA, Muller S, Chaudahri PJ, Carlson JA.
Department of Pathology, Florida Orlando Hospital, Orlando, FL.
J Cutan Pathol. 2005 Jan;32(1):2-11. Abstract quote
Objective: We report four cases of cutaneous carcinosarcoma (CS) and perform a meta-analysis of the cutaneous CS literature.
Results: CS occurred in elderly patients (mean of 80 years) on sun-damaged skin, and were keratotic papules of short duration. They did not recur after excision. CS exhibited basal cell carcinoma mixed with atypical fibroxanthoma cell populations. Immunophenotyping revealed vimentin+/keratin- spindle cells and vimentin-/keratin+ epithelial cells. Three cases exhibited p53 protein expression of both carcinomatous and sarcomatous components. Literature review identified 38 cases of cutaneous CS that could be broadly classified into two distinct groups. Epidermal-derived (basal or squamous cell carcinoma epithelial component) CS arose on the sun-damaged skin of the head and neck of elderly males (mean age 72 years) and had a 70% 5-year disease-free survival. In contrast, adnexal CS (spiradenocarcinoma, porocarcinoma, proliferating tricholemmal cystic carcinoma, or matrical carcinoma) occurred in younger patients (mean age 58 years), showed recent growth in a long-standing nodule and had a 25% 5-year disease-free survival. Age less than 65 years, recent growth, long-standing skin tumor, and tumor size greater than 2 cm significantly correlated with poor outcome.
Conclusions: Cutaneous CS is an aggressive skin cancer with high risk for advanced disease. Significant risk factors exist whose identification will allow for better management of CS patients.
Monophasic sarcomatoid carcinoma of the scalp: a case mimicking inflammatory myofibroblastic tumor and a review of cutaneous spindle cell tumors with myofibroblastic differentiation.Winfield HL, Rosenberg AS, Antonescu CR, Weil M, Wang AR.
Tulane University Health Sciences Center, New Orleans, LA, USA, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
J Cutan Pathol. 2003 Jul;30(6):393-400. Abstract quote BACKGROUND: The evaluation of malignant cutaneous spindle cell tumors is challenged by a diagnostic differential that comprises neoplasms of diverse histogenesis, and a broad immunohistochemical panel may confound the diagnosis when the results suggest multiple lines of differentiation, such as with a combined myofibroblastic and epithelial phenotype.
METHODS: We report the case of a solitary scalp nodule that quickly became locally metastatic. A comprehensive panel of immunohistochemistry markers and electron microscopy was evaluated to determine the differentiation of the spindle cells.
RESULTS: The tumor, consisting of wavy and slender spindle cells with predominantly bland nuclei, showed immunoreactivity to vimentin, smooth muscle actin, and muscle-specific actin. AE1/AE3, CK5/6, and MNF-116 antibodies were weakly positive in rare cells. However, 34betaE12 showed diffuse positivity in the spindle cell population, thus supporting the diagnosis of a sarcomatoid carcinoma with myofibroblastic differentiation.
CONCLUSIONS: The use of 34betaE12 is essential for the evaluation of myofibroblastic spindle cell tumors with rare cytokeratin reactivity. However, even with immunohistochemical and electron microscopic studies, the diagnosis of spindle cell tumors can be confounded by the multiplicity of nosologic equivalents, such as carcinosarcoma, spindle cell carcinoma, and metaplastic carcinoma. The nomenclature of these spindle cell tumors is discussed.
SPECIAL STAINS/
IMMUNOPEROXIDASEGENERAL Expression profiles of p63, p53, survivin, and hTERT in skin tumors.
Park HR, Min SK, Cho HD, Kim KH, Shin HS, Park YE.
Department of Pathology, College of Medicine, Hallym University, Anyang, Korea.
J Cutan Pathol. 2004 Sep;31(8):544-9. Abstract quote
Background: p63 is a p53 homolog and a marker expressed in replicating keratinocytes. Survivin is a recently characterized inhibitor of apoptosis protein that is abundantly expressed in most solid and hematologic malignancies. Telomerase reverse transcriptase (TERT) is the major determinant of human telomerase activity, and its expression is indicative of unlimited replication. We herein evaluated the expression profiles of p63, p53, survivin, and hTERT in usual skin cancers, including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) and putative preneoplastic epidermal lesions, including actinic keratosis (AK), Bowen's diasease, and porokeratosis.
Methods: Immunohistochemistry using antibodies against p63, p53, survivin, and hTERT was performed. Semi-quantitative evaluation (-, +, 2+, 3+) was carried out.
Results: BCCs showed diffuse p63 expression and SCCs heterogeneous p63 expression with negativity in terminally differentiated squamous cells. All preneoplastic epidermal lesions showed p63 expression in all cell layers. p53 was found in seven of 10 cases of BCCs, all 10 cases of SCCs, and nine of 10 cases of Bowen's disease. AK and porokeratosis revealed focal to moderate p53 expression. Survivin was found in eight of 10 cases of SCCs and eight of 10 cases of Bowen's disease. Six of 10 cases of BCCs revealed weak survivin positivity. AK and porokeratosis showed survivin expression confined to the basal layer. hTERT expression was found in most cases of skin cancers and preneoplastic lesions.
Conclusions: p63 expression may be a marker of basal/progenitor cells and a diagnostic marker in skin tumors. p63 expression is not related to p53 expression in these tumors. This study points to a putative role of survivin and hTERT in the development of certain skin cancers. In addition, our data support the concept of porokeratosis being a premalignant condition.
The diagnostic utility of p63, CK5/6, CK 7, and CK 20 in distinguishing primary cutaneous adnexal neoplasms from metastatic carcinomas.
Qureshi HS, Ormsby AH, Lee MW, Zarbo RJ, Ma CK.
Department of Pathology, Henry Ford Hospital, Detroit, MI, USA.
J Cutan Pathol. 2004 Feb;31(2):145-52. Abstract quote
BACKGROUND: Distinguishing primary cutaneous adnexal neoplasms (PCANs) from metastatic carcinomas (MCs) can be difficult. We study the utility of p63, CK 5/6, CK 7, and 20 expression in PCAN vs. MC.
METHODS: Twenty-one PCAN with sweat gland differentiation (six benign, 15 malignant), one sebaceous carcinoma, and 15 MC (14 adenocarcinomas, one urothelial carcinoma) to skin were retrieved from the pathology files. Immunostains for p63, CK 5/6, CK 7, and CK 20 were performed and graded as follows: 1, <10; 2, 11-50; and 3 >50% of tumor cells stained.
RESULTS: Twenty of 22 PCAN expressed p63 and CK 5/6. Four of 15 and two of 15 MC were positive for CK 5/6 and p63, respectively. Thirteen of 22 PCAN and 13 of 15 MC were positive for CK 7, respectively. All PCAN were negative for CK 20, two of 15 MC were positive. The sensitivity and specificity for the diagnosis of PCAN were 91 and 73% for CK 5/6, 91 and 100% for p63, and 60 and 13% for CK 7, respectively.CONCLUSIONS: For distinguishing PCAN from MC: (1) positivity for p63 and CK 5/6 are relatively specific and sensitive for PCAN, (2) CK 7 and 20 are neither sensitive nor specific, and (3) CK 7 positivity in PCAN was focal with a specific pattern in contrast to the diffuse positivity for MC.
CD5
- Cluster designation 5 staining of normal and non-lymphoid neoplastic skin
Bogner PN, Su LD, Fullen DR.
Department of Pathology, University of Michigan Medical Center, Ann Arbor, MI, USA.
J Cutan Pathol. 2005 Jan;32(1):50-4. Abstract quote
Background: Immunohistochemical staining for cluster designation 5 (CD5) has been found to label a variety of non-lymphoid tumors.
Methods: A variety of eccrine, apocrine, follicular, epithelial, and pagetoid lesions were selected and stained with an anti-CD5 monoclonal antibody (Novocastra Labs, Newcastle upon Tyne, UK, clone 4C7) by immunohistochemistry. The intensity of positive cytoplasmic staining was graded semiquantitatively (1+ weak staining, 2+ strong staining). Additionally, the percentage of positive lesional cells was placed in one of four categories: >75%, 25-75%, 1-25%, and <1%.
Results: Within normal skin, CD5 labeled lymphocytes, apocrine glands, deep dermal eccrine glands, and smooth muscle (weak). The majority of benign and malignant apocrine lesions demonstrated strong focal (36%, n = 11)-to-diffuse (64%, n = 16) staining. In contrast, labeling of benign eccrine tumors was more focal, tending to localize around ducts (79%, n = 19). Microcystic adnexal carcinoma demonstrated focal staining of deeper ductal structures (71%, n = 7), whereas desmoplastic trichoepithelioma and basal cell carcinoma showed only rare positive cells. All cases of mammary (n = 7) and extramammary (n = 8) Paget's disease labeled diffusely for CD5. Pagetoid Bowen's disease (n = 6), intraepidermal sebaceous carcinoma (n = 3), nor melanoma in situ (n = 6) showed any CD5 staining.
Conclusions: Immunohistochemical staining for CD5 is extremely useful in the differential diagnosis of pagetoid epidermal lesions and will mark mammary and extramammary Paget's disease, but not pagetoid Bowen's disease, melanoma in situ, or sebaceous carcinoma.CD10
- CD10 is expressed in cutaneous clear cell lesions of different histogenesis.
Perna AG, Smith MJ, Krishnan B, Reed JA.
Department of Pathology, Baylor College of Medicine, Houston, Texas.
J Cutan Pathol. 2005 May;32(5):348-51. Abstract quote
Background: CD10, the Common Acute Lymphoblastic Leukemia Antigen, is a neutral endopeptidase commonly used as a marker of early B-cell differentiation in the classification of lymphomas. Neoplasms of other histogenesis may express CD10, including renal cell carcinoma. Renal cell carcinoma metastatic to the skin (MRCC) can simulate other more common clear cell lesions in which expression of CD10 has not been described.
Methods: Fifty-two cutaneous clear cell lesions including xanthomas (CX), xanthelasmas (XA), xanthogranulomas (XG), balloon cell nevi (BCN), nodular/clear cell hidradenomas (CCH), and MRCC were examined by immunohistochemistry for the expression of CD10, noting frequency and pattern of labeling.
Results: CD10 was expressed in 32/35 of the xanthomatous lesions (CX, XA, and XG), 3/3 MRCC, but only 2/8 BCN and 2/6 CCH. BCN and CCH expressed CD10 in fewer than 10% of the clear cells, whereas all MRCC and most xanthomatous lesions had labeling in greater than 10% (p < 0.001). Xanthomatous lesions exhibited a predominantly membranous pattern of labeling compared to the cytoplasmic pattern of MRCC (p < 0.025).
Conclusions: Cutaneous clear cell lesions of different histogenesis express CD10, limiting its use as a specific diagnostic marker for MRCC. Among other clear cell lesions, however, BCN and CCH have a lower frequency of labeling than does MRCC, and xanthomatous lesions show a membranous pattern compared to the cytoplasmic pattern of MRCC, BCN, and CCH. This latter observation may be indicative of altered protein function or trafficking.
DIFFERENTIAL DIAGNOSIS CHARACTERIZATION CUTANEOUS HORN Cutaneous horns of the eyelid: a clinicopathological study of 48 cases.
Mencia-Gutierrez E, Gutierrez-Diaz E, Redondo-Marcos I, Ricoy JR, Garcia-Torre JP.
Department of Ophthalmology, 12 de Octubre Hospital, Complutense University, Madrid, Spain.
J Cutan Pathol. 2004 Sep;31(8):539-43. Abstract quote
Background: Cutaneous horn (cornu cutaneum) is a morphological designation for a protuberant mass of keratin that resembles the horn of an animal. It results from unusual cohesiveness of keratinized material from the superficial layers of the skin or implanted deeply in the cutis. This lesion may be associated with a benign, premalignant, or malignant lesion at the base, masking numerous conditions.
Methods: A retrospective analysis of 48 cases of cutaneous horns of the eyelid treated between 1992 and 2002 has been performed.
Results: Twenty-four men and 19 women, with a mean age of 62 years (range 16-90), were treated by surgery. Histologically, 77.1% were associated with benign specimens at the base pathology, 14.6% were premalignant, and finally, 8.3% were caused by malignant skin tumors. The most common lesion was seborrheic keratosis among the benign lesions, actinic keratosis among the premalignant ones, and basal cell carcinoma and squamous cell carcinoma among the malignant ones.
Conclusion: Cutaneous horns usually appear on exposed skin areas in elderly men. The important issue in this condition is not the horn itself, which is just dead keratin, but rather the nature of the underlying disease, although the horns are usually benign.
Gigantic cutaneous horns of the scalp: lesions with a gross similarity to the horns of animals: a report of four cases.Michal M, Bisceglia M, Di Mattia A, Requena L, Fanburg-Smith JC, Mukensnabl P, Hes O, Cada F.
Department of Pathology, Laborator Spec. Diagnostiky Medical Faculty Hospital, Pilsen, Czech Republic.
Am J Surg Pathol 2002 Jun;26(6):789-94 Abstract quote Gigantic cutaneous horns, grossly similar to the horns seen in animals, are exceedingly rare in humans. After finding one case in practice, we searched our departmental files for similar cases and examined them grossly and microscopically.
Four cases were identified. All occurred as solitary lesions in older women on the parietal-occipital region of the scalp. They had a growth history of up to 30 years; the women hid these horns in their hair.
Grossly, the horns were yellow-grey, and there were shallow furrows running along the length of the horns. The length ranged from 17 to 25 cm, and the width was up to 2.5 cm. All four lesions showed similar histologic changes. Microscopically, the gigantic horns consisted of a mixture of squamous epithelial cells and tricholemmal keratinized debris. In one case the base of the horn was directly connected with a mass composed of benign tricholemmal cysts of the scalp. Mitoses were common, but atypical mitoses were not observed. The nuclei of the squamous cells were bland without pleomorphism, hyperchromasia, or atypia.
Follow-up of all patients was uneventful: all patients were well and without signs of recurrence or metastasis 2-15 years after the surgical excision.
Gigantic cutaneous horns are rare and benign. We think that they represent an extremely well-differentiated variant of proliferating tricholemmal tumor with an unusual and remarkable gross pattern.
ECCRINE NEVUS Eccrine nevus presenting as a perianal skin tag: a case report and review of the literature.
Mahdavy M, Smoller BR.
Departments of Pathology (M.M., B.R.S.) and Dermatology (B.R.S.), University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.A.
Am J Dermatopathol 2002 Aug;24(4):361-3 Abstract quote We present the case of a 9-year-old girl with a perianal skin tag. This asymptomatic lesion was removed for cosmetic reasons and demonstrated a polypoid lesion with a slightly acanthotic epidermis.
The dermis was filled with mature-appearing eccrine ducts and glands but with no other cutaneous appendages, adipocytes, or abnormal vascularity. We believe this to represent a polypoid eccrine nevus and that its presentation is unique.
ECTOPIC BREAST TISSUE Ectopic breast tissue and breast-like sweat gland metaplasias: an overlapping spectrum of lesions.
Pfeifer JD, Barr RJ, Wick MR
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri, USA.
J Cutan Pathol 1999 Apr;26(4):190-6 Abstract quote
There are many similarities in the morphology of benign and malignant lesions of the sweat glands and the breasts. The recently described cutaneous mammary-like sweat glands, also known as mixed sweat glands or apoeccrine glands, are also a likely source of selected proliferations that closely mimic those of the breast.
We present three cases of breast-like lesions arising in the skin that demonstrate the ways in which the morphologic and pathologic continuum of the mammary glands, cutaneous mammary-like glands, and sweat glands can produce difficulties in precise diagnosis. The examples demonstrate that an anatomic location outside the milk line does not preclude the diagnosis of ectopic mammary tissue, and that lesions closely resembling those of the breast may also arise outside the milk line from conventional sweat glands or mixed sweat glands.
The concept of homologous lesions of the breast, breast-like glands and sweat glands, in which morphology is partially mirrored by biochemical similarities, provides a perspective for classification of problematic cases of breast-like cutaneous lesions.
HOMOLOGOUS CARCINOMAS Homologous carcinomas of the breasts, skin, and salivary glands. A histologic and immunohistochemical comparison of ductal mammary carcinoma, ductal sweat gland carcinoma, and salivary duct carcinoma.
Wick MR, Ockner DM, Mills SE, Ritter JH, Swanson PE.
Division of Surgical Pathology, Washington University Medical Center, St Louis, MO 63110, USA.
Am J Clin Pathol 1998 Jan;109(1):75-84 Abstract quote
Morphologic mimicry among human malignant neoplasms is a well-known phenomenon in surgical pathology; both undifferentiated and "committed" neoplasms may exhibit this trait. One particularly common group of histologic simulants includes ductal carcinomas of the breasts, the cutaneous appendages, and the salivary glands.
One hundred three tumors in this structural cluster were analyzed microscopically and immunohistologically to codify points of potential pathologic similarity and difference. All the lesions were typified by irregularly permeative clusters and cords of atypical polygonal cells with variable luminal differentiation. A proportion of primary neoplasms in each site demonstrated in situ ductal components; in the absence of the latter elements, however, it was not possible to make topography-related morphologic distinctions among them.
Immunostains for gross cystic disease fluid protein-15 (GCDFP-15), carcinoembryonic antigen, S100 protein, c-erbB-2 oncoprotein, estrogen receptor protein, and progesterone receptor protein also showed largely overlapping phenotypes in each of the three tumor categories, with selected exceptions.
These differences were elucidated through paired chi 2 analysis and included a statistically significant infrequency of GCDFP-15 in eccrine sweat gland carcinomas, a paucity of carcinoembryonic antigen in breast cancers, and an absence of estrogen receptor protein in salivary duct carcinomas. Such findings may be useful in predefined differential diagnostic settings involving the distinction between primary and metastatic ductal cancers of the breasts, skin, and salivary glands. Nevertheless, because of the striking homologies between such tumors at structural and protein-synthetic levels of comparison, it is mandatory that all available clinicopathologic information be used in this context.
SYRINGO-METAPLASIA Syringometaplasia: mucinous and squamous variants.
King DT, Barr RJ.
J Cutan Pathol 1979 Aug;6(4):284-91 Abstract quote
The eccrine sweat ducts are normally lined by cuboidal epithelial cells which may rarely undergo metaplasia, i.e. syringometaplasia.
Two lesions were observed in which eccrine sweat ducts displayed the mucinous and squamous variants of syringometaplasia. The first lesion clinically and histologically appeared to be a plantar wart. Microscopically, it consisted of a central invagination surrounded by marked epidermal acanthosis and hyperkeratosis. The invagination was lined by keratinocytes admixed with mucin-filled goblet cells. The mucin was positive by the Alcian blue (pH 2.5) and mucicarmine stains. Numerous eccrine sweat ducts led into the invagination and were focally lined by the mucin-laden cells.
Recognition of mucinous syringometaplasia is important since it may be confused with primary or metastatic adenocarcinoma of the skin. The second lesion occurred on the outer ear and was clinically believed to be chondrodermatitis nodularis helicis.
Microscopically, there were many islands of atypical squamous cells within the papillary and reticular dermis. These epithelial islands represented squamous syringometaplasia since many contained central lumina with eosinophilic cuticles and blended with normal ductal structures. It is important not to confuse this metaplastic change with invasive squamous cell carcinoma. Squamous syringometaplasia may be analogous to necrotizing sialometaplasia, a recently described phenomenon which occurs in minor salivary glands.
PROGNOSIS AND TREATMENT CHARACTERIZATION COST
Skin cancer is among the most costly of all cancers to treat for the Medicare population.Housman TS, Feldman SR, Williford PM, Fleischer AB Jr, Goldman ND, Acostamadiedo JM, Chen GJ.
Center for Dermatology Research, Winston-Salem, North Carolina, USA.
J Am Acad Dermatol 2003 Mar;48(3):425-9 Abstract quote BACKGROUND: Compared with other malignancies, nonmelanoma skin cancer (NMSC) is associated with much less morbidity and mortality. NMSC is, however, far more common than other malignancies. The cost of managing NMSC has not been assessed.
OBJECTIVE: The purpose of our study was to determine where the cost of NMSC management ranks among other cancers in the Medicare population.
DESIGN: Representative Medicare part A and B claims data were obtained from the Medicare current beneficiary survey, 1992 to 1995. Claims associated with cancer costs were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. Weights were applied to obtain nationally representative estimates.
RESULTS: Average Medicare expenditure on cancer management was $13 billion per year. The 5 most costly cancers to Medicare were lung and bronchus, prostate, colon and rectum, breast, and NMSC. The mean annual cost per patient using Medicare for all cancers was $17,094. Malignancies of lung and bronchus, colon and rectum, breast, and prostate were 11 to 19 times more costly per affected patient than NMSC.
CONCLUSION: In addition to classifying cancers by number of cases and number of deaths, the financial impact of treatment can also be used to prioritize different malignancies. Such a scheme ranks NMSC far higher than would death statistics. In light of its already high and rising incidence, the cost of NMSC care to Medicare is likely to increase. However, to maintain the cost-effective management of NMSC, it is essential to preserve the current low per-patient cost of its management.
SKIN CANCER SCREENING
The first 15 years of the American Academy of Dermatology skin cancer screening programs: 1985-1999.Geller AC, Zhang Z, Sober AJ, Halpern AC, Weinstock MA, Daniels S, Miller DR, Demierre MF, Brooks DR, Gilchrest BA.
Department of Dermatology, Boston University School of Medicine, Massachusetts 02118, USA.
J Am Acad Dermatol 2003 Jan;48(1):34-41 Abstract quote BACKGROUND: In response to the precipitous increase of melanoma, the American Academy of Dermatology (AAD) has coupled melanoma/skin cancer education with free skin cancer screening programs throughout the United States since 1985. The purpose of this analysis is to investigate the risk factors, access to dermatologic services, and screening results of participants in AAD-sponsored programs during the first 15 years that this service was available to the US public.
METHODS: Before screening, participants completed a standardized AAD screening form. Screening forms were counted in the AAD central office and recorded in annual summaries. Forms were sent for keypunching and returned to the AAD on a computer disk annually. In 1999, disks were sent to Boston University and a master file was created.
RESULTS: Computerized records were available for 819,019 screening forms and 639,835 individuals. In all, 65% of screenees had at least 1 risk factor and 33% had at least 2 risk factors. Of screenees, 33% reported a changing mole and 37% had skin type I or II. Among all screenees, nearly 80% did not have a regular dermatologist, 78% reported no prior AAD skin cancer screening, 60% had never had their skin checked by any doctor, and 51% would not have seen a doctor for skin cancer without the free screening. Nearly 30% of screenees had a presumptive diagnosis of skin cancer or a precursor lesion. Melanomas confirmed by postscreening biopsy were more likely than those in population-based registries to be less than 1.50 mm in thickness.
CONCLUSIONS: AAD national screening and educational programs have expanded to all 50 states, provided educational messages about sun protection and early detection to millions, and served many US citizens with an above average risk for skin cancer and suboptimal access to dermatologic care. Screenees had a disturbingly high point prevalence of malignant and premalignant skin lesions. Sustained commitment by the AAD leadership and membership to the screening program is critical to reducing the morbidity and mortality of skin cancer.
The Environmental Protection Agency's National SunWise School Program: Sun protection education in US schools (1999-2000).Geller AC, Cantor M, Miller DR, Kenausis K, Rosseel K, Rutsch L, Brooks DR, Zhang Z, Demierre MF.
Boston University School of Medicine, Department of Dermatology, Environmental Protection Agency, Washington, DC, Boston University School of Public Health, Department of Epidemiology, and Massachusetts Department of Public Health.
J Am Acad Dermatol 2002 May;46(5 Pt 1):683-9 Abstract quote BACKGROUND: Melanoma, the most fatal form of skin cancer, is rising at a rate faster than that of all preventable cancers except lung cancer in the United States. Childhood exposure to ultraviolet (UV) light increases the risk for skin cancer as an adult; thus starting positive sun protection habits early may be key to reducing incidence.
METHODS: We evaluated the US Environmental Protection Agency's SunWise School Program, a national, environmental education program for sun safety of children in primary and secondary schools (kindergarten through eighth grade). The program was evaluated with surveys administered to participating students. An identical 18-question, self-administered survey was completed by students (median age, 10 years) in the classroom before and immediately after the SunWise educational program.
RESULTS: Surveys were completed by students in 40 schools before (pretests; n = 1894) and after the program was presented (post-tests; n = 1815). Significant improvement was noted for the 3 knowledge variables: appropriate type of sunscreen to be used for outdoor play, highest UV Index number, and need for hats and shirts outside. Intentions to play in the shade increased from 73% to 78% (P <.001), with more modest changes in intentions to use sunscreen. Attitudes regarding healthiness of a tan also decreased significantly.
CONCLUSIONS: Brief, standardized sun protection education can be efficiently interwoven into school health education and result in improvements in knowledge and positive intentions for sun protection.
Skin cancer screening by dermatologists: prevalence and barriers.Federman DG, Kravetz JD, Kirsner RS.
Veterans Affairs Connecticut Health Care System, West Haven, CT 06516, USA.
J Am Acad Dermatol 2002 May;46(5):710-4 Abstract quote BACKGROUND: The incidence of skin cancers is increasing at an alarming rate, and there is currently no consensus by major health policy organizations regarding skin cancer screening. It has previously been shown that primary care physicians do not screen a majority of patients for skin cancer.
OBJECTIVE: This study was undertaken to determine the prevalence of skin cancer screening among dermatologists and to detect barriers to screening. As a secondary objective, we set out to determine the prevalence of dermatoscopy use.
METHODS: With the use of membership data from the 1999-2000 directory of the American Academy of Dermatology, a random sample of 464 American dermatologists was surveyed to assess their skin cancer screening practices and perceived obstacles to this practice. We then determined whether differences in knowledge of skin cancer screening recommendations, emphasis of skin cancer screening in training, or physician age affected the prevalence of screening.
RESULTS: A total of 190 dermatologists responded (41%). Fifty-seven respondents (30%) reported performing full-body skin cancer screening on all of their adult patients and 93 more (49%) reported screening only patients perceived to be at increased risk. Eighty respondents (42%) reported lack of time as an impediment to screening. Only 18 (9%) did not screen patients because of potential patient embarrassment, whereas 17 (9%) did not perform screening because of lack of financial reimbursement. Sixty-two dermatologists (33%) reported being aware of official skin cancer screening recommendations, but they were not more likely to screen all patients (P =.64) or partake in screening of all patients or only those at increased risk (P =.84). One hundred nineteen respondents (63%) reported that skin cancer screening was emphasized during their medical training and they were more likely to screen all patients (P =.04) or either all or high-risk patients (P =.02). Younger age groups of dermatologists were significantly more likely to screen all patients for skin cancer (P =.03). Twenty-two percent of respondents reported using dermatoscopy for suspicious lesions.
CONCLUSION: Dermatologists report a high rate of screening for skin cancer despite not having knowledge of skin cancer screening recommendations. Inadequate time to perform full-body skin examinations and lack of emphasis during training were identified as possible barriers to this practice.
Sun Protection Policies and Environmental Features in US Elementary Schools.Buller DB, Geller AC, Cantor M, Buller MK, Rosseel K, Hufford D, Benjes L, Lew RA.
Center for Health Communication, AMC Cancer Research Center, 1600 Pierce St, Denver, CO 80214.
Arch Dermatol 2002 Jun;138(6):771-4 Abstract quote OBJECTIVE: To assess current sun protection policies and the receptiveness to new policies at elementary schools in the United States.
DESIGN: A cross-sectional telephone survey.
SETTING: General educational community.
PATIENTS OR OTHER PARTICIPANTS: In 1998, a random sample of 1000 public elementary schools in the United States was selected (proportional to population size) from 27 metropolitan areas chosen from the 58 US cities regularly reporting the UV index in 1997. A final sample of principals from 412 elementary schools completed the survey.
INTERVENTION: None.
MAIN OUTCOME MEASURES: Only 3.4% of schools had a sun protection policy. The most common reasons for not having a policy included the principal's lack of awareness (n = 113) or organizational barriers in the school districts (n = 77). Most principals (84.2%) said that students were outdoors during midday hours. Many principals (48.3%) were willing to adopt a sun protection policy. Most schools (72.8%) had shade structures but the majority (67.3%) reportedly covered less than one fifth of the grounds. Most principals (76.4%) were willing to increase the amount of shade structures.
CONCLUSIONS: The low frequency of sun protection policies and shade structures calls for national efforts to change policies and environments to increase sun protection at US schools. Research is needed to demonstrate the efficacy of these changes.
Should the skin cancer examination be taught in medical school?Geller AC, Venna S, Prout M, Miller DR, Demierre MF, Koh HK, Gilchrest BA.
Boston University School of Medicine, 720 Harrison Ave, DOB801A, Boston, MA 02118.
Arch Dermatol 2002 Sep;138(9):1201-3 Abstract quote BACKGROUND: The fact that thin melanomas are associated with a greater than 95% survival rate, while later, more deeply invasive melanomas have a 5-year survival rate of less than 10%, demonstrates the potential personal and public health impact of early detection. The majority of patients with skin lesions are seen by nondermatologists who infrequently counsel patients about skin cancer prevention or perform a complete skin examination as part of routine care. We documented the antecedents of physician practice by evaluating medical students' observation, training, performance, and self-reported skill level for the skin cancer examination and sun protection counseling.
METHODS: Surveys were administered and completed in classrooms and student workshops in each of the 4 medical school years during the spring of 1996 and 1997. We concentrate our analysis on the graduating fourth-year students.
RESULTS: Of the 302 fourth-year students enrolled at Boston University School of Medicine, Boston, Mass, in 1996 and 1997, 223 (74%) completed surveys. Among fourth-year students, 52% rated themselves as unskilled in skin cancer examinations. Twenty-eight percent of fourth-year students had never observed a skin cancer examination, 40% had received no training, and 35% had never practiced the examination. However, fourth-year students reporting at least 1 opportunity to observe, train, or practice an examination were 3 times as likely to report themselves as moderately to very skilled as students without such opportunities.
CONCLUSION: If medical student training rates for the skin cancer examination are equally low elsewhere, as is likely, the present data suggest that even brief additions to the current curriculum, integrated into systems teaching, would augment student exposure and likely boost student skill levels.
SUNSCREEN
- Photoprotection.
Kullavanijaya P, Lim HW.
Department of Dermatology, Henry Ford Hospital, Detroit, MI 48202, USA.
J Am Acad Dermatol. 2005 Jun;52(6):937-58; Abstract quote
Many agents affect the transmission of ultraviolet light to human skin. These include naturally occurring photoprotective agents (ozone, pollutants, clouds, and fog), naturally occurring biologic agents (epidermal chromophores), physical photoprotective agents (clothing, hats, make-ups, sunglasses, and window glass), and ultraviolet light filters (sunscreen ingredients and sunless tanning agents). In addition, there are agents that can modulate the effects of ultraviolet light on the skin (antioxidants and others). All of the above are reviewed in this article.
LEARNING OBJECTIVE: At the conclusion of this learning activity, participants should be able to provide an overview of all aspects of photoprotection.
Cutaneous photodamage, oxidative stress, and topical antioxidant protection.Pinnell SR.
Duke University Medical Center.
J Am Acad Dermatol 2003 Jan;48(1):1-19 Abstract quote New methods to protect skin from photodamage from sun exposure are necessary if we are to conquer skin cancer and photoaging. Sunscreens are useful, but their protection is not ideal because of inadequate use, incomplete spectral protection, and toxicity. Skin naturally uses antioxidants (AOs) to protect itself from photodamage.
This scientific review summarizes what is known about how photodamage occurs; why sunscreens-the current gold standard of photoprotection-are inadequate; and how topical AOs help protect against skin cancer and photoaging changes. This review is intended to be a reference source, including pertinent comprehensive reviews whenever available. Although not all AOs are included, an attempt has been made to select those AOs for which sufficient information is available to document their potential topical uses and benefits.
Reviewed are the following physiologic and plant AOs: vitamin C, vitamin E, selenium, zinc, silymarin, soy isoflavones, and tea polyphenols.
Their topical use may favorably supplement sunscreen protection and provide additional anticarcinogenic protection. (J Am Acad Dermatol 2003;48:1-19.)
Learning objective: At the completion of this learning activity, participants should have an understanding of current information about how the sun damages skin to produce skin cancer and photoaging changes, how the skin naturally protects itself from the sun, the shortcomings of sunscreens, and the added advantages of topical AOs for photoprotection.
American Academy of Dermatology Consensus Conference on UVA protection of sunscreens: Summary and recommendations Washington, DC, Feb 4, 2000 J Am Acad Dermatol 2001;44:505-8. Abstract quote
The following are the AAD's final recommendations for UVA protection of sunscreens:
1. Sunscreen UVB protection, as reflected by SPF, should be the primary consideration for sunscreen potency.
2. The in vitro critical wavelength (c) method is a criterion for broad-spectrum claim. The threshold for this claim should be 370 nm.
3. The critical wavelength method must be combined with an in vivo method; the latter could be either PPD or PFA. A minimum of a 4-fold increase in PPD or PFA value in the presence of sunscreen is recommended.
4. Only sunscreens that fulfill the above in vitro and in vivo criteria can be labeled as “broad spectrum.”
5. No sunscreen that has only UVA protection may claim to be a “broad-spectrum” sunscreen.
6. An increase in the SPF must be accompanied with a proportional increase in the UVA protection value. It is recommended that these “proportional” values be determined jointly by the FDA and the industry.
7. A threshold pass/fail labeling for broad-spectrum/UVA protection is recommended. Therefore sunscreens fulfilling the above criteria would be labeled simply as “broad spectrum.” This would minimize confusion to consumers. The specifics of the threshold (critical wavelength, PPD/PFA value, and the UVA/UVB proportionality) could be displayed in fine print on the back of the container.
8. More funding should be provided for radiation biology research to help elucidate UVA mechanisms of injury.In summary, the AAD recommends use of a sunscreen with SPF 15 or higher that meets the UVA protection criteria described above.
Mechanisms of sunscreen failure
Mandy Wartha Wright, etal.
J Am Acad Dermatol 2001;44:781-4 Abstract quote
Sunscreen is used as a primary strategy to prevent sunburn and later skin cancer. However, sunscreen use has paradoxically been associated with the increasing incidence of skin cancer. One explanation for this puzzling observation is sunscreen failure (sunburn in the setting of sunscreen).
Our purpose was to evaluate mechanisms of sunscreen failure in a sunscreen-using population.
We carried out an epidemiologic comparison of sunburned and nonsunburned beachgoers who used sunscreen. We found that men were less likely to use sunscreen than women (2 = 11.3, df = 1, P = .001), and when it was used, men were less likely to apply sunscreen to all sunlight-exposed skin (2 = 18.4, df = 1, P = .0001). Swimmers who used sunscreen were significantly more likely to be sunburned compared with nonswimming sunscreen users (Fisher exact test, df = 1). Sunscreen may fail to prevent sunburn if it is washed off during swimming or if it is not applied to all exposed skin.
Epidemiologic studies that link sunscreen use to skin cancer should evaluate whether sunburn occurred in this setting.
Reduction of ultraviolet transmission through cotton t-shirt fabrics with low ultraviolet protection by various laundering methods and dyeing: Clinical implications
Steven Q. Wang, etal.
J Am Acad Dermatol 2001;44:767-74 Abstract quote
Background: The public has long been instructed to wear protective clothing against ultraviolet (UV) damage.
Objective: Our purpose was to determine the UV protection factor (UPF) of two cotton fabrics used in the manufacture of summer T-shirts and to explore methods that could improve the UPF of these fabrics.
Methods: Each of the two types of white cotton fabrics (cotton T-shirt and mercerized cotton print cloth) used in this study was divided into 4 treatment groups: (1) water-only (machine washed with water), (2) detergent-only (washed with detergent), (3) detergent-UV absorber (washed with detergent and a UV absorber), and (4) dyes (dyed fabrics). Ultraviolet transmission through the fabrics was measured with a spectrophotometer before and after laundry and dyeing treatments. Based on UV transmission through these fabrics, the UPF values were calculated.
Results: Before any treatments, the mean UPFs were 4.94 for the T-shirt fabric and 3.13 for the print cloth. There was greater UVA (320-400 nm) than UVB (280-320 nm) transmission through these fabrics. After 5 washings with water alone and with detergent alone, UPF increased by 51% and 17%, respectively, for the cotton T-shirt fabric. Washing the T-shirt fabrics with detergent plus the UV-absorbing agent increased the UPF by 407% after 5 treatments. Dyeing the fabric blue or yellow increased the UPF by 544% and 212%, respectively. Similar changes in UPFs were observed for the print cloth fabric.
Conclusion: The two cotton fabrics used in this study offered limited protection against UV radiation as determined by spectrophotometric analysis. Laundering with detergent and water improves UPF slightly by causing fabric shrinkage. Dyeing fabrics or adding a UV-absorbing agent during laundering substantially reduces UV transmission and increases UPF. More UVA is transmitted through the fabrics than UVB.
When should sunscreen be reapplied?
Brian L. Diffey, DSc
Newcastle upon Tyne, United Kingdom
J Am Acad Dermatol 2001;45:882-5 Abstract quote
Background: A common recommendation by many public health agencies is to reapply sunscreen every 2 to 3 hours. Is this recommendation effective in minimizing ultraviolet exposure of the skin during time in the sun?
Objective: The purpose of this article is to determine how the time of sunscreen reapplication affects the solar ultraviolet exposure of the skin.
Methods: A mathematical model was derived that took into account typical amounts of sunscreen application and sunscreen substantivity to determine how these factors, when combined with the time of sunscreen reapplication, influence the photoprotection provided by sunscreen during exposure for several hours around mid day in strong sunshine.
Results: Using a sunscreen that is readily removed from the skin achieves little in the way of sun protection, no matter when it is reapplied. For sunscreens that bind moderately or well to skin, typical of modern waterproof or water-resistant products, the lowest skin exposure results from early reapplication into the sun exposure period, and not at 2 to 3 hours, after initial application. Typically reapplication of sunscreen at 20 minutes results in 60% to 85% of the ultraviolet exposure that would be received if sunscreen were reapplied at 2 hours.
Conclusions: Advice given to sunscreen users should be to apply sunscreen liberally to exposed sites 15 to 30 minutes before going out into the sun, followed by reapplication of sunscreen to exposed sites 15 to 30 minutes after sun exposure begins. Further reapplication is necessary after vigorous activity that could remove sunscreen, such as swimming, toweling, or excessive sweating and rubbing.
Celecoxib, a Cyclooxygenase 2 Inhibitor as a Potential Chemopreventive to UV-Induced Skin Cancer: A Study in the Hairless Mouse Model.Orengo IF, Gerguis J, Phillips R, Guevara A, Lewis AT, Black HS.
Department of Dermatology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030.
Arch Dermatol 2002 Jun;138(6):751-5 Abstract quote OBJECTIVE: To assess the preventive effect of a cyclooxygenase 2 inhibitor, celecoxib (Celebrex; G.D. Searle & Co, Skokie, Ill), in UV-induced skin cancer in hairless mice.
DESIGN: Randomized dose-response study. A total of 75 SKH-HR-1 female hairless mice, aged 2 months, were randomized into control, low-dose (200 mg twice daily human dose equivalent), and high-dose (400 mg twice daily human dose equivalent) celecoxib treatment groups. Animals received 1 J/cm(2) daily (5 d/wk) total irradiation. The animals were evaluated weekly for appearance of tumors, and the data were analyzed with respect to tumor latency period and tumor multiplicity using statistical software and Wilcoxon rank sum analyses, respectively. Prostaglandin E(2) levels in the blood and skin were assessed in each group.
SETTING: Veterans Affairs Medical Center, Research and Dermatology Services.
INTERVENTION: Animals received restricted diets containing the Food and Drug Administration-approved human equivalent doses of 200 mg (low dose) and 400 mg (high dose) of celecoxib twice daily. Controls received no drug. Tumors were induced in all animals with an equivalent UV dose.
MAIN OUTCOME MEASURES: Animals were evaluated weekly for the appearance of tumors, and data were analyzed with regard to tumor latency period and tumor multiplicity. Constitutive prostaglandin E(2) levels in blood and epidermis were assessed in each group.
RESULTS: Low doses and high doses of celecoxib significantly lengthened the tumor latency period (P<.03 and P<.003, respectively) and reduced tumor multiplicity (P<.005 and P<.001, respectively) compared with controls. There were no differences in the constitutive levels of blood or epidermal prostaglandin E(2) in the low- or high-dose treated animals compared with controls when analyzed at study termination.
CONCLUSIONS: Celecoxib is an effective and safe chemopreventive agent in UV carcinogenesis. The epidemiologic, laboratory, and animal studies of the influence of celecoxib on cancer incidence and its low association with systemic adverse effects have led to a potentially new therapeutic approach for the prevention of skin cancer.
Application patterns among participants randomized to daily sunscreen use in a skin cancer prevention trial.Neale R, Williams G, Green A.
Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane 4029, Queensland, Australia.
Arch Dermatol 2002 Oct;138(10):1319-25 Abstract quote BACKGROUND: Despite many investigations of sunscreen use, there have been few among adults in the community at large. Better understanding of sunscreen application patterns will lead to more strategic skin cancer prevention strategies among sun-exposed populations.
OBJECTIVE: To explore patterns of sunscreen use, particularly the quantity of sunscreen used and the application frequency, among participants in a community-based sunscreen intervention.
DESIGN: Follow-up of patterns of sunscreen use over 4.5 years.
SETTING: Nambour, a subtropical town in Queensland, Australia.
PARTICIPANTS: People drawn randomly from the electoral register who were later randomized as part of a skin cancer prevention trial.
INTERVENTIONS: Daily application of a standard sun protection factor 15+ broad-spectrum retail sunscreen to the head and neck, arms, and hands.
OUTCOME MEASURES: Frequency of application of sunscreen, weight of sunscreen applied, and quantity applied per unit area of skin.
RESULTS: Fifty-six percent of participants reported applying sunscreen on at least 5 days per week, with 27% using sunscreen infrequently on 2 or fewer days per week. The median daily amount of sunscreen applied averaged over the duration of the trial was 1.5 g/d (range, 0-7.4 g/d). The median quantity of sunscreen applied was 0.79 mg/cm(2), which was less than half the amount needed to achieve the labeled sun protection factor.
CONCLUSIONS: It is possible to implement the daily application of sunscreen in sun-exposed populations, although protection would be increased if the quantity of sunscreen applied were greater.
SURVIVAL
Defining the clinical course of metastatic skin cancer in organ transplant recipients: a multicenter collaborative study.Martinez JC, Otley CC, Stasko T, Euvrard S, Brown C, Schanbacher CF, Weaver AL.
Mayo Clinic, 200 First St SW, Rochester, MN 55905.
Arch Dermatol 2003 Mar;139(3):301-6 Abstract quote OBJECTIVE: To evaluate the demographic characteristics, clinical course, and outcome in organ transplant recipients with metastatic skin cancer.
DESIGN AND SETTING: An international, multicenter, Internet-coordinated collaborative group retrospectively analyzed data from 68 organ transplant recipients with 73 distinct metastatic skin cancers.
MAIN OUTCOME MEASUREMENTS: The Kaplan-Meier method was used to estimate the cumulative incidence of relapse, overall survival, and disease-specific survival after metastatic skin cancer. Univariate Cox proportional hazards models were fit to evaluate factors for an association with survival.
RESULTS: Metastasis from skin cancer in organ transplant recipients most commonly consisted of squamous cell carcinoma in regional nodal basins. It was predominantly treated with a combination of surgery and irradiation. By 1 year after metastasis, the cumulative incidence of relapse was 29%, and the 3-year disease-specific survival was 56%. Patients whose initial metastases were distant or systemic had a significantly poorer disease-specific survival than those whose initial metastases were in-transit or regional (risk ratio, 6.5; P<.001).
CONCLUSIONS: Metastatic skin cancer in organ transplant recipients has a poor prognosis. Preventive, early, and aggressive therapeutic interventions are required to minimize this serious complication of transplant-associated immunosuppression.
Prognostic factors for life expectancy in nonagenarians with nonmelanoma skin cancer: Implications for selecting surgical candidates.Charles AJ Jr, Otley CC, Pond GR.
Division of Dermatologic Surgery and the Section of Biostatistics, Mayo Clinic, Rochester.
J Am Acad Dermatol 2002 Sep;47(3):419-22 Abstract quote BACKGROUND: Controversy exists over surgical intervention for nonmelanoma skin cancer in the very elderly.
OBJECTIVE: We sought to define variables that are prognostic for survival in the elderly after surgery for skin cancer.
METHODS: We reviewed 99 charts of nonagenarians who had Mohs micrographic surgery for nonmelanoma skin cancer and recorded data on comorbid conditions and date of death. Comorbid conditions were quantified by the Charlson index.
RESULTS: Patients with Charlson scores of zero (no comorbidities) had a statistically significant longer survival than patients with Charlson scores of >/=3 (multiple comorbidities). Women survived longer than men at both 1 and 5 years. No patient died within 30 days of operation.
CONCLUSION: Charlson scores of >/=3 in nonagenarians predict shorter survival. Although this parameter may predict shorter survival when skin cancer surgery is considered in a cohort of elderly patients, it remains difficult to predict accurately the survival of individual patients with scores >/=3.
TREATMENT MOHS SURGERY Mohs Micrographic Surgery vs Traditional Surgical Excision A Cost Comparison Analysis
Tracy L. Bialy, MD, MPH ;James Whalen, MD ;Emir Veledar, PhD ;Denis Lafreniere, MD ;Jeffrey Spiro, MD ;Timothy Chartier, MD ;Suephy C. Chen, MD, MS
Arch Dermatol. 2004;140:736-742. Abstract quote Objective To compare the cost and margin adequacy of Mohs micrographic surgery (Mohs) and traditional surgical excision (TSE) for the treatment of facial and auricular nonmelanoma skin cancer (NMSC).
Design Prospective cost analysis with each patient serving as his or her own control.
Setting Study was performed from 1999 to 2001 at the University of Connecticut dermatology clinic, a tertiary care referral center.
Patients A total of 98 consecutive patients with a primary diagnosis of NMSC on the face and ears.
Main Outcome Measures The average cost of Mohs and TSE per patient for the treatment and repair of NMSC; adequacy of TSE margins after the initial procedure(because this outcome affects overall cost).
Results Mohs was cost comparable to TSE when the subsequent procedure for inadequate TSE margins after permanent section was Mohs ($937 vs $1029; P = .16) or a subsequent TSE ($937 vs $944; P = .53). When facility-based frozen sections were requested for TSE, Mohs was significantly less costly ($956 vs $1399; P<.001). The cost difference between Mohs and TSE was sensitive to the type of repair chosen.
Conclusions If the end point is clear margins, Mohs is cost comparable to TSE performed by otolaryngologic surgeons. Some caution is needed when evaluating the cost of facial and auricular NMSC treatment because the choice of repair can significantly affect the cost conclusions.
A prospective evaluation of the incidence of complications associated with mohs micrographic surgery.Cook JL, Perone JB.
Department of Medicine (Dermatology), Duke University Medical Center, Box 3915, Durham, NC 27710.
Arch Dermatol 2003 Feb;139(2):143-52 Abstract quote BACKGROUND: Because outpatient surgery is being increasingly scrutinized in the lay press, it is important that dermatologists and dermatologic surgeons accurately characterize the safety of office-based surgery. Although there is abundant anecdotal evidence to support the inherent safety of dermatologic surgery, there are few data that support the safety of Mohs micrographic surgery (MMS) as performed by appropriately trained dermatologic surgeons in outpatient settings.
DESIGN: All patients presenting for MMS micrographic surgery during the calendar year 2000 were prospectively enrolled in this study designed to evaluate the incidence of multiple complications associated with scalpel-based cutaneous surgery (postoperative hemorrhage, hematoma formation, wound infection, wound dehiscence, and flap/graft necrosis).
SETTING: An academic MMS practice.
PATIENTS: A total of 1052 patients (1358 MMS cases) were prospectively enrolled. Complete follow-up information was available for 1343 cases (98.9%).
RESULTS: Complications associated with MMS were very infrequent, with an overall complication incidence of 1.64% (22/1343). Most surgical complications involved difficulties with hemostasis. No complications were significant enough to involve the assistance of another specialist or to require the hospitalization of the patient.
CONCLUSIONS: Mohs micrographic surgery is a very safe outpatient procedure when performed by appropriately trained physicians. The types of complications seen in our patients were identical to those seen in hospitalized patients described in previous studies. Our complication rates were equal to or lower than the published complication rates from specialists in other surgical disciplines.
SENTINEL LYMPH NODE
Sentinel node biopsy for high-risk nonmelanoma cutaneous malignancy.
Wagner JD, Evdokimow DZ, Weisberger E, Moore D, Chuang TY, Wenck S, Coleman JJ 3rd.
Division of Plastic Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, USA.
Arch Dermatol. 2004 Jan;140(1):75-9 Abstract quote.
OBJECTIVE: To evaluate the feasibility of sentinel node staging for detection of occult regional lymph node metastasis in high-risk cutaneous nonmelanoma malignancies.
DESIGN: Consecutive clinical case series.
SETTING: Referral university medical center.
PATIENTS: A consecutive sample of patients with a variety of high-risk nonmelanoma cutaneous malignancies without evidence of regional lymph node metastases.
INTERVENTION: Sentinel node biopsies were performed using preoperative lymphoscintigraphy, blue dye, and intraoperative radiolocalization.
MAIN OUTCOME MEASURE: Sensitivity, determined by comparing the results of biopsy specimen evaluation with those of completion lymphadenectomy and/or clinical follow-up.
RESULTS: Twenty-four patients underwent sentinel node biopsy for the staging of 29 nodal basins identified by lymphoscintigraphy. Primary diagnoses were squamous cell carcinoma (n = 17), Merkel cell carcinoma (n = 5), and adenocarcinoma (n = 2). Seven patients (29%) had a tumor-positive sentinel node. Sentinel node biopsy followed by complete lymphadenectomy was performed in 12 patients and sentinel node biopsy alone in 12 patients. Tumor-positive lymph nodes were noted in 8 patients, 7 of whom also had positive sentinel nodes. There was 1 false-positive result (1/8 [12%]), in a patient with recurrent squamous cell carcinoma of the scalp. At a median follow-up of 10 months, no recurrences in a sentinel node-negative basin have been noted. Compared with all information, the sensitivity of sentinel node staging was 88% and the negative predictive value was 0.94.
CONCLUSIONS: Sentinel node biopsy is a minimally invasive staging procedure useful in identifying occult regional lymph node disease in selected patients with nonmelanoma cutaneous malignancies. Further studies to verify these findings and develop formal guidelines are indicated.TACROLIMUS
Treatment of chronic actinic dermatitis with tacrolimus ointment.Uetsu N, Okamoto H, Fujii K, Doi R, Horio T.
Department of Dermatology, Kansai Medical University.
J Am Acad Dermatol 2002 Dec;47(6):881-4 Abstract quote BACKGROUND: Chronic actinic dermatitis (CAD) is difficult to treat. Topical corticosteroids induce adverse effects after long-term use, especially on light-exposed skin.
OBJECTIVE: Our purpose was to study the effects of tacrolimus ointment in the treatment of elderly patients with CAD.
METHODS: In an open trial, 6 male patients between 51 and 80 years old with CAD applied 0.1% tacrolimus ointment twice a day to the face and neck. According to improvements, the frequency of application was reduced. Sunscreen agents were also applied outdoors.
RESULTS: Tacrolimus ointment effectively treated cutaneous changes in all patients. Symptoms were moderately improved in 2 weeks, and greatly in 4 weeks. A brief and localized irritating sensation occurred in all patients, but no other adverse events developed throughout the study course from 0.5 to 2.5 years.
CONCLUSION: Topical tacrolimus ointment for facial lesions of CAD appears to be effective and well tolerated and may provide long-term benefits.
Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fifth Edition. Mosby Elesevier 2008
MOHS Surgery-A specialized surgical excisional procedure where close frozen section control is performed at every step. It is performed by a specialized MOHS surgeon.
Basic Principles of Disease
Learn the basic disease classifications of cancers, infections, and inflammation
Commonly Used Terms
This is a glossary of terms often found in a pathology report.Diagnostic Process
Learn how a pathologist makes a diagnosis using a microscopeSurgical Pathology Report
Examine an actual biopsy report to understand what each section meansSpecial Stains
Understand the tools the pathologist utilizes to aid in the diagnosisHow Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurate
Got Path?
Recent teaching cases and lectures presented in conferences
Last Updated June 19, 2008
Send mail to The Doctor's Doctor with questions or comments about this web site.
Read the Medical Disclaimer.
Copyright © The Doctor's Doctor