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Background
Sebaceous carcinoma is a rare but deadly form of skin cancer arising from the sebaceous glands. A diagnosis of this disease should prompt a question to the treating physician about the possibility of a rare familial syndrome known as the Muir-Torre syndrome. This syndrome is associated with multiple sebaceous and squamous neoplasms of the skin and associations with multiple visceral malignancies including ovarian and gastrointestinal tract. These tumors are most common in the head and neck, especially occurring on the eyelids.
OUTLINE
DISEASE ASSOCIATIONS CHARACTERIZATION Muir-Torre syndrome Any diagnosis of a sebaceous adenoma, epithelioma, or carcinoma or any histologically unusual sebaceous neoplasm may be associated with this syndrome Sebaceous Carcinoma, Trichoblastoma, and Sebaceoma With Features of Trichoblastoma in Nevus Sebaceus
Noriyuki Misago, M.D.; Hanako Kodera, M.D.; Yutaka Narisawa, M.D.
From the Division of Dermatology, Department of Internal Medicine, Saga Medical School, Saga, Japan.
Am J Dermatopathol 2001;23:456-462 Abstract quote
A 73-year-old woman had a linear yellowish plaque on the upper part of her right ear since birth. She presented because of the sudden growth of a nodule within the plaque. The plaque was waxy and yellowish, arching around the upper part of the ear. A reddish to yellowish large nodule was seen within the central part of the arc-shaped plaque; in addition, a small pigmented nodule, a small skin-colored nodule, and a few pigmented papules were observed in the anterior half of the arched plaque.
Histopathologic examination revealed the large nodule to be sebaceous carcinoma, the small pigmented nodule to be trichoblastoma, the small skin-colored nodule to be sebaceoma with the features of trichoblastoma, a few pigmented papules to be superficial trichoblastomas due to primitive follicular induction, and the linear yellowish plaque to be nevus sebaceus. Although our literature search revealed scanty reports of definite cases of sebaceous carcinoma in nevus sebaceus, the presented case demonstrated the occurrence of sebaceous carcinoma in nevus sebaceus.
Malignant neoplasms occurring in nevus sebaceous seem to be extremely rare, but care should be taken when a large nodule suddenly grows in a lesion of nevus sebaceus, especially in older adults. The presented case also suggested a close relation between trichoblastoma and sebaceoma. The cytokeratin staining pattern could not distinguish between sebaceous and follicular neoplasms in our case.
PATHOGENESIS CHARACTERIZATION MISMATCH REPAIR GENES
Loss of mismatch repair proteins in sebaceous gland tumors.Popnikolov NK, Gatalica Z, Colome-Grimmer MI, Sanchez RL.
Departments of Pathology and Dermatology, The University of Texas Medical Branch at Galveston, Texas, USA.
J Cutan Pathol 2003 Mar;30(3):178-84 Abstract quote BACKGROUND: Sebaceous gland neoplasms are rare tumors that are associated with visceral malignancies in patients with Muir-Torre syndrome (MTS). The majority of the MTS-associated tumors reveal mutations in DNA mismatch repair (MMR) genes (most often hMSH-2 and hMLH-1) and microsatellite instability. The sebaceous gland lesions in patients with MTS can often precede or occur concurrently with the visceral neoplasms. The early recognition of those lesions and their differentiation from sporadic sebaceous gland tumors are critical for proper patient management. Here we investigate the MMR gene expression in a variety of sebaceous gland tumors, with or without associated visceral malignancy.
METHODS: We studied the expressions of hMLH-1 and hMSH-2 in 10 consecutive sebaceous hyperplasias, 10 sebaceus nevi, 12 sebaceous adenomas, seven sebaceous carcinomas and the adjacent normal sebaceous glands using immunohistochemistry and paraffin-embedded sections.
RESULTS: The normal sebaceous glands and the glands of all the sebaceus nevi were positive for hMLH-1 and hMSH-2. Loss of hMSH-2 expression was found in 1/10 (10%) sebaceous hyperplasias, 3/12 (25.0%) sebaceous adenomas, and 2/7 (28.6%) sebaceous carcinomas. Loss of hMLH-1 expression was seen in 1/10 (10%) hyperplasias, 3/12 (25.0%) adenomas, and 1/7 (14.3%) carcinomas. No concurrent loss of both hMLH-1 and hMSH-2 was observed. Loss of MMR (either hMLH-1 or hMSH-2) was detected in 80% of the benign sebaceous lesions associated with malignancy. In comparison, only 23% of sebaceous lesions not associated with malignancy showed loss of MMR proteins. No loss of hMSH-2 protein was found in the visceral cancer in one patient with hMSH-2-negative sebaceous adenoma.
CONCLUSIONS: Our results confirm the previous reports of alterations of mismatch repair genes in the sebaceous neoplasms of patients with MTS. However, we showed that those changes also occur early at the stage of sebaceous hyperplasia, even in the absence of a visceral malignancy. This indicates the importance of the abnormal DNA mismatch repair in the progression of this disease.
Molecular Pathologic Analysis Enhances the Diagnosis and Management of Muir-Torre Syndrome and Gives Insight Into Its Underlying Molecular Pathogenesis
Melissa C. Southey, Ph.D.; Mary-Anne Young, R.N.; Jonathan Whitty, B.Sc.; Sharon Mifsud, B.App.Sc.; Michelle Keilar, B.App.Sc.; Leeanne Mead, M.Sc.; Lynne Trute, B.App.Sc.; Kristiina Aittomäki, M.D., Ph.D.; Sue-Anne McLachlan, M.D., M.Sc.; Henry Debinski, M.B., B.S.; Deon J. Venter, M.B., Ch.B., Ph.D.; Jane E. Armes, B.M., B.S., Ph.D.
From the Departments of Pathology (M.C.S., J.W., S.M., M.K., D.J.V., J.E.A.) and Research (M.C.S., L.M., L.T., D.J.V., J.E.A.), Victorian Breast Cancer Research Consortium (J.E.A.), and the Familial Cancer Centre (S.-A.M., H.D., K.A., M.-A.Y.), Peter MacCallum Cancer Institute, Melbourne, Victoria, Australia; and the Department of Pathology (M.C.S., D.J.V., J.E.A.), University of Melbourne, Parkville, Victoria, Australia.
Am J Surg Pathol 2001;25:936-941 Abstract quote
The Muir-Torre syndrome (MTS) is an autosomal dominantly inherited disorder, characterized by visceral malignancies and sebaceous skin lesions. In a subset of MTS families the disease is due to an underlying DNA mismatch-repair defect.
We have identified a MTS family whose spectrum of reported neoplasia included adenocarcinomas of numerous gastrointestinal sites, carcinomas of the endometrium, ovary and breast, papillary transitional cell carcinoma of the ureter, a range of cutaneous tumors, as well as keratoacanthomas.
All tumors were tested for microsatellite instability and immunohistochemically stained for expression of MLH1 and MSH2 proteins. All tumors were found to be microsatellite unstable and lacking in MSH2 protein expression. The subsequent mutation detection focused on hMSH2, and a germline mutation was identified (CAATAA, GlnSTOP, codon 337). This mutation was subsequently found in a family member with a single skin lesion only.
We propose that the combination of immunohistologic and microsatellite instability analysis can be exploited to screen individuals with characteristic skin lesions even before development of visceral tumors and to direct the subsequent germline mutation search. The profile of microsatellite instability and the genes rendered dysfunctional differed between tumor samples, suggesting that the molecular pathogenesis varied between lesions, despite a common germline mutation.
Muir-Torre phenotype has a frequency of DNA mismatch-repair-gene mutations similar to that in hereditary nonpolyposis colorectal cancer families defined by the Amsterdam criteria.
Kruse R, Rutten A, Lamberti C, Hosseiny-Malayeri HR, Wang Y, Ruelfs C, Jungck M, Mathiak M, Ruzicka T, Hartschuh W, Bisceglia M, Friedl W,
Propping P. Institute of Human Genetics, Friedrich-Wilhelms University, Bonn, Germany.
Am J Hum Genet 1998 Jul;63(1):63-70 Abstract quote
Muir-Torre syndrome (MTS) is an autosomal dominant disease defined by the coincidence of at least one sebaceous skin tumor and one internal malignancy. About half of MTS patients are affected by colorectal cancer. In a subgroup of MTS patients the disease has an underlying DNA mismatch-repair (MMR) defect and thus is allelic to hereditary nonpolyposis colorectal cancer (HNPCC).
The purpose of this study was to examine to what extent germ-line mutations in DNA MMR genes are the underlying cause of the MTS phenotype. We ascertained 16 MTS patients with sebaceous skin tumors and colorectal cancer, and we examined their skin and visceral tumors for microsatellite instability. All the patients exhibited high genomic instability in at least one tumor. The search for germ-line mutations in the hMSH2 and hMLH1 genes in 13 of the MTS patients revealed truncating mutations in 9 (69%): eight mutations in the hMSH2 gene and one in the hMLH1 gene. This is the first systematic search for germ-line mutations in patients ascertained on the basis of sebaceous skin tumors.
Our results indicate that (1) MTS patients exhibit significantly more mutations in the hMSH2 gene than in the hMLH1 gene; and (2) the subpopulation of MTS patients who are also affected by colorectal cancer, irrespective of family history and age at onset of tumors, may have a likelihood for an underlying DNA MMR defect similar to that for patients with a family history fulfilling the strict clinical criteria for HNPCC.
Microsatellite instability in benign skin lesions in hereditary non-polyposis colorectal cancer syndrome.
Swale VJ, Quinn AG, Wheeler JM, Beck NE, Dove-Edwin I, Thomas HJ, Bodmer WF, Bataille VA.
Academic Department of Dermatology, St Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK.
J Invest Dermatol 1999 Dec;113(6):901-5 Abstract quote
The coexistence of cutaneous and extra-cutaneous malignancies within one family could be explained by shared genetic mechanisms such as common tumor suppressor gene mutations or oncogene activation, as well as mutations in DNA repair genes. Hereditary non-polyposis colorectal cancer syndrome (HNPCC) and its variant Muir-Torre syndrome (MTS) are caused by germline DNA mismatch repair gene mutations. Colonic and endometrial tumors from HNPCC patients exhibit microsatellite instability (MSI), as do sebaceous lesions in MTS. We recruited individuals from cancer prone families to determine if MSI is found in benign and malignant skin lesions and to assess whether MSI in the skin is predictive of genomic instability with susceptibility to tumors characteristic of HNPCC.
One hundred and fifteen benign, dysplastic, and malignant skin lesions from 39 cancer prone families were analyzed. Thirteen benign skin lesions from three individuals belonging to two HNPCC pedigrees showed MSI. No mutations in hMSH2 and hMLH1 were found in two of the three individuals with RER + skin lesions. We found MSI in non-sebaceous non-dysplastic skin lesions in HNPCC pedigrees. MSI was not found in skin lesions within other family cancer syndromes.
These results have important clinical implications as the detection of MSI in prevalent readily accessible skin lesions could form the basis of noninvasive screening for HNPCC families. It may also be a valuable tool in the search for new mismatch repair genes.
RETINOID RECEPTORS
- Expression of retinoid receptors in sebaceous cell carcinoma.
Chakravarti N, El-Naggar AK, Lotan R, Anderson J, Diwan AH, Saadati HG, Diba R, Prieto VG, Esmaeli B.
Department of Head and Neck/Thoracic Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
J Cutan Pathol. 2006 Jan;33(1):10-7. Abstract quote
Purpose: The aim of this study is to investigate whether there are any abnormalities in the in vivo expression of retinoid acid receptors (RAR-alpha, RAR-beta and RAR-gamma) and retinoid X receptors (RXR-alpha, RXR-beta and RXR-gamma) in sebaceous cell carcinoma. Methods: Expression of retinoid receptors in paired specimens of cancerous tissues (n = 10) and adjacent normal tissues (n = 10) from 10 patients with sebaceous cell carcinoma was studied immunohistochemically by using anti-retinoid receptor antibodies.
Results: In eight of the 10 normal tissue samples, all six receptors were expressed. In the other two samples, all receptors were expressed except RAR-gamma (one sample) or RXR-gamma (two samples). Five tumours (50%) lacked RAR-alpha; RAR-alpha expression was lower in tumours than in normal tissues in eight of 10 cases. RAR-beta was expressed in the cytoplasm of nine of 10 tumours; RAR-beta expression was at least as high in tumours as in normal tissue in eight of 10 cases. Two tumours lacked RAR-gamma; three tumours had lower RAR-gamma expression than paired normal epithelium; four had the same RAR-gamma expression, and one had higher RAR-gamma expression. RXR-alpha expression was strong in all normal tissues and tumour samples. Ten tumours lacked RXR-beta and all 10 tumours lacked RXR-gamma expression.
Conclusions: Diminished RXR-beta and RXR-gamma expression might be related to the development of sebaceous cell carcinoma. Additional studies are required to establish whether the defects in RAR expression in sebaceous cell carcinoma might affect the potential response of this tumour to treatment with retinoids.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION CHILDHOOD
Sebaceous carcinoma in children.Omura NE, Collison DW, Perry AE, Myers LM.
Section of Dermatology and the Department of Pathology, Dartmouth-Hitchcock Medical Center.
J Am Acad Dermatol 2002 Dec;47(6):950-3 Abstract quote Sebaceous carcinoma is a rare malignant tumor derived from the epithelium of sebaceous glands. It potentially may develop from any sebaceous gland, but most commonly occurs in the periorbital area.
We report a case of sebaceous carcinoma in a 14-year-old girl who was first seen with an asymptomatic 2.5 x 2.3-cm firm, multilobulated cutaneous nodule on the anterior thorax, which had been present for 1 year. She was adopted, and no family history is available. A skin biopsy specimen revealed a poorly differentiated infiltrative carcinoma involving the dermis and subcutaneous fat and focally involving the epidermis. Tumor cells had sebaceous and squamous differentiation. A diagnosis of sebaceous carcinoma was made.
She was treated by surgical excision with a 2-cm margin. Further work-up showed no evidence of Muir-Torre syndrome.
EXTRAOCULAR Highly Aggressive Extraocular Sebaceous Carcinoma
C. Moreno, M.D.; W. K. Jacyk, M.D.; M. J. Judd, M.D.; L. Requena, M.D.
From the Departments of Pathology (C.M.) and Dermatology (L.R.), Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain; Dermatology (W.K.J.) and Anatomical Pathology (M.J.J.), University of Pretoria, Pretoria, Republic of South Africa.
Am J Dermatopathol 2001;23:450-455 Abstract quote
Extraocular sebaceous carcinoma is an uncommon neoplasm usually localized on the head and neck.
We report a case of sebaceous carcinoma of the axillary skin with a highly aggressive behavior. The patient was a 43-year-old black man who developed multiple cutaneous and lymph node metastases shortly after the excision of primary sebaceous carcinoma of the axillary skin. Many neoplastic aggregations were identified within the lumina of the dermal lymphatic vessels in the excised specimen of the primary neoplasm.
Although extraocular sebaceous carcinoma has been traditionally considered a less aggressive neoplasm than its ocular counterpart, a review of the literature and this case demonstrate that extraocular sebaceous carcinoma may also lead to disseminated metastatic disease.
NIPPLE
IUMC Clarian Pathology Laboratory 350 West 11th Street, Indianapolis, IN 46202, USA.
Sebaceous carcinoma (SC) is an uncommon neoplasm that usually presents as an ocular or extraocular cutaneous lesion of the head and neck.
We report a case of an 83-year-old woman with SC of the nipple.
To our knowledge, this is the first report of SC arising in the nipple.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL Hum Pathol 1982;13:113-122
- Histopathological review of sebaceous carcinoma of the eyelid.
Pereira PR, Odashiro AN, Rodrigues-Reyes AA, Correa ZM, de Souza Filho JP, Burnier MN Jr.
Department of Ophthalmology, Federal University of Sao Paulo, Sao Paulo, Brazil.
J Cutan Pathol. 2005 Aug;32(7):496-501. Abstract quote
Background: Sebaceous carcinoma of the eyelid can clinically mimic benign conditions, such as recurrent chalazion and inflammation and histopathologically squamous cell and basal cell carcinoma (BCC). This retrospective study was undertaken as an attempt to improve the characterization and consequently the diagnosis of these tumors.
Methods: Retrospective analysis was performed on eyelid specimens diagnosed as sebaceous carcinoma retrieved from Henry C. Witelson Ophthalmic Pathology Registry, Canada and Hospital Luis S. Bulnes Pathology Registry, Mexico. Two independent, masked pathologists reviewed the H&E microslides.
Results: Forty-four cases were retrieved, 31 from Canada and 13 from Mexico. Cytoplasmic vacuoles were observed in 48% of the cases. Eighty-four percent of the cases were classified as poorly differentiated lesions. Of these, 75% had features similar to squamous cell carcinoma (SqCC), some with dyskeratosis (30%) and 7% resembled BCC. Solid growth pattern was seen in 26.2% of the cases and lobular growth pattern in 26.2%. Superficial spread resembling Bowen-like disease was observed in 33% of the cases, pagetoid features in 33% and comedocarcinoma in 31.8%.
Conclusion: Sebaceous carcinoma presented as a poorly differentiated lesion in most cases of this series, which suggests a possibility of misdiagnosis because of its similarities to SqCC.VARIANTS APOCRINE CHANGES Sebaceous carcinoma with apocrine differentiation Am J Dermatopathol 2001;23:50-57
Low grade cancer associated with glandular structures showing evidence of decapitation secretion
CARCINOID PATTERN
- Carcinoid-Like Pattern in Sebaceous Neoplasms: Another Distinctive, Previously Unrecognized Pattern in Extraocular Sebaceous Carcinoma and Sebaceoma.
Kazakov DV, Kutzner H, Rutten A, Mukensnabl P, Michal M.
From *Sikl's Department of Pathology, Charles University, Medical Faculty
Hospital, Pilsen, Czech Republic; and dagger
Dermatohistopathologische Gemeinschaftspraxis, Friedrichshafen, Germany.
Am J Dermatopathol. 2005 Jun;27(3):195-203. Abstract quote
This report emphasizes a carcinoid-like pattern, a previously unrecognized feature in cutaneous sebaceous neoplasms.
We report 7 patients with sebaceous tumors in which neoplastic cells were arranged in a trabecular and ribbon-like pattern or formed rosettes/pseudorosettes. The cases included 6 men and 1 woman, with their ages at the diagnosis ranging from 43 to 87 years (median age, 59). All patients presented with a solitary lesion. Locations were the scalp (n = 6) and forearm (n = 1). The carcinoid-like arrangement of neoplastic cells was the sole pattern in 4 cases, and in 3 cases the so-called labyrinthine/sinusoidal and/or rippled patterns were seen in addition. Sebaceous differentiation in the form of mature sebocytes varied from almost none to approximately 10%.
Although the neoplasm appeared benign architecturally, the presence of cytologic atypia qualified 2 tumors as low-grade carcinomas. Four lesions represented sebaceomas, and in 1 case microscopic delineation between a carcinoma and sebaceoma was difficult. No neuroendocrine differentiation was demonstrated immunohistochemically, histochemically, and ultrastructurally. Electron microscopic examination performed in 1 case of carcinoma revealed lipid vacuoles in a minority of cells. There were no membrane-bound neuroendocrine granules. Rare cells contained peculiar large helioid inclusions.
We conclude that the carcinoid-like pattern is another distinctive pattern indicative of sebaceous neoplasms. This pattern seems to be closely related to the rippled and labyrinthine/sinusoidal patterns, as exemplified by our cases, in which these arrangements sometimes occurred simultaneously.CYSTIC Cystic sebaceous tumors as marker lesions for the Muir-Torre syndrome: a histopathologic and molecular genetic study.
Rutten A, Burgdorf W, Hugel H, Kutzner H, Hosseiny-Malayeri HR, Friedl W, Propping P, Kruse R.
Laboratory of Dermatohistopathology, University of Bonn, Germany.
Am J Dermatopathol 1999 Oct;21(5):405-13 Abstract quote
Cystic sebaceous tumors (CST) are well-circumscribed, large, deeply located dermal sebaceous proliferations with a cystic growth pattern.
We identified 12 CST in 8 of 19 patients with Muir-Torre syndrome (MTS). We interpret CST as a tumor spectrum with clearly benign cystic sebaceous adenomas at one end and proliferative atypical cystic sebaceous tumors at the other. When examining these proliferative atypical tumors on morphologic criteria alone, the possibility of an evolving cystic sebaceous carcinoma cannot be excluded. We have not observed recurrences or metastases, indicating that these lesions are not highly malignant carcinomas. In 10 of 12 cases of CST, we examined microsatellite instability (MSI). All 10 examined examples of CST from patients with MTS showed MSI characteristic for hereditary nonpolyposis colorectal cancer (HNPCC), which is caused by autosomal dominant inherited DNA mismatch repair (MMR) defects. Mutational analysis of the MMR genes hMSH2 and hMLH1 had revealed different germline mutations in the hMSH2 gene in three of six examined patients with MTS with CST. We then found four more CST in patients without a history of internal malignancy. All four CST exhibited MSI. By mutational analysis in one of these patients we identified a truncating germline mutation in the MMR gene hMLH1.
We conclude that CST is a marker for the mismatch repair-deficient subtype of MTS with a high risk for later internal malignancies. By recognizing CST, the histopathologist can suggest the great likelihood of MTS to the clinician.
INTRAEPITHELIAL
- Intraepithelial sebaceous carcinoma of the eyelid misdiagnosed as Bowen's disease.
Leibovitch I, Selva D, Huilgol S, Davis G, Dodd T, James CL.
Oculoplastic & Orbital Unit, Department of Ophthalmology and Visual Sciences, Royal Adelaide Hospital, University of Adelaide, Adelaide, South Australia, Australia.
J Cutan Pathol. 2006 Apr;33(4):303-8. Abstract quote
Background: Sebaceous carcinoma (SC) is well known for its ability to masquerade clinically and histologically as a variety of periocular conditions resulting in a delayed diagnosis. We present a series of periocular SC cases and discuss the difficulties in histopathological diagnosis when this tumor presents with a Bowenoid pattern of intraepithelial spread.
Methods: A retrospective case study of all patients with SC of the eyelid treated in our Hospital, from 1997 to 2004, was conducted.
Results: Eight patients were identified (four females and four males). Seven cases involved the upper eyelid. Initial clinical diagnoses included blepharitis (three cases), blepharoconjunctivitis (one case), cicatrizing conjunctivitis (one case), and lid lesions (two cases). Histopathologically, 87.5% of cases were misdiagnosed as Bowen's disease (BD) on the initial biopsy. Six of these cases showed no invasive disease on the initial biopsy and were eventually found to be invasive SC on subsequent excisions. In one case, the tumor was wholly in situ. Delay in diagnosis ranged from 0 to 56 months.
Conclusions: SC should always be considered in the histological differential diagnosis of any eyelid lesion which resembles BD, particularly if the upper eyelid is involved or if multivacuolated cytoplasmic clear cell changes are seen.
SPECIAL STAINS/
IMMUNOPEROXIDASE/
OTHERCHARACTERIZATION Special stains Fat stain positive for Oil Red O and Sudan Black B Immunoperoxidase Sebaceous cells are positive for EMA and CD15 ADIPOPHILIN
Adipophilin expression in sebaceous tumors and other cutaneous lesions with clear cell histology: an immunohistochemical study of 117 cases.
Ostler DA, Prieto VG, Reed JA, Deavers MT, Lazar AJ, Ivan D.Departments of Pathology and Dermatology, Baylor College of Medicine, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA.
Mod Pathol. 2010 Jan 29. Abstract quote
Adipophilin is a monoclonal antibody against a protein on the surface of intracellular lipid droplets, and it was recently shown to be expressed in sebocytes and sebaceous lesions.
This study examines adipophilin expression in various sebaceous lesions and other cutaneous tumors with a clear cell histology that may mimic sebaceous differentiation. A total of 117 cutaneous clear cell lesions including 16 sebaceous adenomas, 25 sebaceous carcinomas, 8 basal cell carcinomas, 12 squamous cell carcinomas, 6 xanthomas, 10 xanthelasmas, 10 xanthogranulomas, 4 balloon cell nevi, 5 trichilemmomas, 8 clear cell hidradenomas, and 13 metastatic renal cell carcinomas were examined using immunohistochemistry for the expression of adipophilin. Of these 117 lesions, 42 (36%) were from the periocular region.
Adipophilin was expressed in 16 of 16 (100%) sebaceous adenomas, 23 of 25 (92%) sebaceous carcinomas, 10 of 10 (100%) xanthelasmas, 9 of 10 (90%) xanthogranulomas, 6 of 6 (100%) xanthomas, and 9 of 13 (62.5%) metastatic renal cell carcinomas. The characteristic staining pattern differed between sebaceous and non-sebaceous tumors with the former showing a membranous vesicular pattern and the latter being more granular. Adipophilin expression was not seen in any of the other lesions with clear cell histology, basal cell carcinomas, or squamous cell carcinomas, including cases that had focal clear cell differentiation.
Adipophilin can be valuable in an immunohistochemical panel when evaluating cutaneous lesions with clear cell histology as it identifies intracytoplasmic lipid vesicles in sebaceous and xanthomatous lesions. In periocular lesions, it is effective in helping to exclude basal cell carcinoma and squamous cell carcinoma when sebaceous carcinoma is under consideration. Adipophilin expression is not as useful for the differential diagnosis that includes metastatic renal cell carcinoma, a rare but important, diagnostic differential. The pattern of adipophilin reactivity is important to observe as membranous vesicular staining is suggestive of intracellular lipids whereas granular cytoplasmic reactivity is not.
From the *Departments of Pathology and Dermatology, Stanford University Medical Center, Palo Alto, CA, USA, daggerDepartment of Hematopathology, Armed Forces Institute of Pathology, Washington, DC, USA, double daggerLaboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, section signDepartments of Dermatology and Pathology, University of Texas, Southwestern Medical Center, Dallas, TX, USA
Sebaceous lesions, including sebaceous hyperplasia, sebaceomas, and sebaceous adenomas and carcinomas, are histologically distinctive adnexal proliferations with a spectrum of biological behavior ranging from benign to frankly malignant. The histologic distinction between sebaceous adenomas and carcinomas may be challenging, especially in cases showing atypical features and in small or partial biopsies.
We studied multiple oncogenic and therapeutic related proteins by immunohistochemistry to identify differences in expression between benign and malignant sebaceous proliferations. A total of 27 cases, including 9 sebaceous adenomas, 4 sebaceomas, 8 sebaceous carcinomas, and 6 cases of sebaceous hyperplasia, were examined by immunohistochemistry, with antibodies directed against Ki-67 (MIB-1), bcl-2, p53, p21WAF1, p27Kip1, c-erbB-2 (Her-2/neu), CD117 (c-kit), cyclin D1, MDM2, CD99, MLH-1, and MSH-2. We found that sebaceous adenomas and sebaceomas stained like sebaceous hyperplasia did, whereas carcinomas had statistically significantly increased levels of p53 (50% versus 11%, respectively) and Ki-67 (30% versus 10%). The carcinomas also had significantly reduced levels of bcl-2 (7% versus 56%, respectively) and p21 (16% versus 34%) compared to the adenomas.
Thus, a combination of several of these markers may be diagnostically useful in challenging cases. In addition, we found little or no Her-2/neu and CD117 staining, indicating that immunotherapy with Herceptin or Gleevac would likely not be useful for sebaceous carcinomas. Moreover, these results show that sebaceous adenomas and carcinomas are distinct neoplasms and provide no support for the theory that all sebaceous adenomas are truly malignant.CYTOKERATIN
Department of Dermatology, Wayne State University School of Medicine, Detroit, MI, USA.
Background: Distinction between sebaceous tumors and basal cell carcinomas can often pose diagnostic problems. Recent work with the antibody to cytokeratin 19 (CK 19) has shown that this marker has high specificity for undifferentiated basaloid cells. Our aim was to evaluate the use of CK 19 staining patterns in differentiating between sebaceous tumors and basal cell carcinomas. The sebaceous tumors that were examined in this study included sebaceous adenomas, sebaceous epitheliomas (sebaceomas) and sebaceous carcinomas.
Methods: Thirty-seven cases including 5 sebaceous adenomas, 16 sebaceous epitheliomas, 6 sebaceous carcinomas and 14 basal cell carcinomas (7 being of the morpheaform type and 7 nodular basal cell carcinomas) were tested with a monoclonal mouse antibody to human CK 19.
Results: CK 19 was focally positive in 1/5 (20%) sebaceous adenomas, 8/16 (50%) of sebaceous epitheliomas and 1/6 (17%) of sebaceous carcinomas. Strongly positive expression of CK 19 was not seen in any of the sebaceous adenoma, sebaceous epithelioma or sebaceous carcinoma specimens. CK 19 was found to be strongly positive in 9/14 (64%) and focally positive in 2/14 (14%) of basal cell carcinomas.
Conclusion: CK 19 expression can be helpful in differentiating sebaceous tumors (including sebaceous adenomas, sebaceous epitheliomas and sebaceous carcinomas) from basal cell carcinomas and may be a useful adjunct when these entities are included in the differential diagnosis.PODOPLANIN
Recent research suggests that the D2-40 monoclonal antibody recognizes the 40,000 Da O-linked sialoglycoprotein podoplanin. Podoplanin not only is highly expressed in lymphatic endothelium but also in other cell types, including sebaceous carcinoma cells. Using the D2-40 antibody, our purpose was to evaluate expression of podoplanin in sebaceous glands of normal skin.
Twenty-four formalin-fixed, paraffin-embedded normal skin specimens (10 from scalp and 14 from cheeks) were immunostained using the D2-40 mouse monoclonal antibody.
Strong immunostaining with D2-40 antibody was observed at the periphery of sebaceous glands and in skin lymphatic endothelium of all specimens, demonstrating that podoplanin is expressed in sebaceous glands of normal skin.
DIFFERENTIAL DIAGNOSIS CHARACTERIZATION SEBACEOMA Am J Dermatopathol 1984;6:7-13
Benign neoplasm with sebaceous differentiation
Sebocytes at different stages of maturation (vacuolated and nonvacuolated cells) with different sizes and shapes and disposed as solitary units and in small clusters with irregularly distributed sebaceous duct-like structuresSome connection to the epidermis composed of small, monomorphous, strongly basophilic, germinative cells
Nevus sebaceus-associated type is similar to the classic type, although this type seems to more often consist of aggregations composed of larger, oval, pale-staining basaloid cells with distinct nucleoli similar to sebaceous germinative cells at the periphery of normal sebaceous lobules or germinative cells in some trichoblastomas
Seborrheic keratosis/verruca vulgaris type is characterized by dermal aggregations always connected to the epidermis with similar features to seborrheic keratosis/verruca vulgaris in both silhouette and cytology
From the *Department of Dermatology, University of Fukui, Fukui; daggerDivision of Plastic Surgery, Obihiro-Kousei General Hospital, Obihiro; and double daggerSapporo Institute for Dermatopathology, Sapporo, Japan.
A 68-year-old Japanese man presented with a nodule that had been present for 5 to 6 years on the right side of the back. Physical examination revealed a dome-shaped, 12 x 13-mm, dark red nodule. It was excised with a 2 to 3-mm margin. The patient remained free of disease during 77 months of follow-up.
Microscopic examination revealed a bulb-like tumor in the dermis, contiguous with the overlying epidermis. It was composed of small, monomorphous, cigar-shaped basaloid cells in linear, parallel rows, resembling the palisading of nuclei of Verocay bodies, and presenting a rippled-pattern. There were scattered cells showing sebaceous differentiation with vacuolated cytoplasm and scalloped nuclei. There were tiny, duct-like spaces. The tumor revealed characteristics of rippled-pattern sebaceoma.
The present case is the first reported rippled-pattern sebaceous neoplasm on the back. Many spindle cell tumors, such as basal cell carcinoma, pleomorphic adenoma, dermatofibrosarcoma protuberans, myofibroblastoma, and leiomyoblastoma, in addition to trichoblastoma and sebaceoma, can have a rippled-pattern.Sebaceoma arising in association with seborrheic keratosis.
Betti R, Inselvini E, Vergani R, Moneghini L, Crosti C.
Clinica Dermatologica IV, Universita degli Studi di Milano, Ospedale San Paolo, Milano, Italy.
Am J Dermatopathol 2001 Feb;23(1):58-61 Abstract quote
We report a case of a 60-year-old woman with a 4-year history of an asymptomatic plaque on her left cheek.
The lesion was composed of two distinct adjacent and continuous parts comprising a lateral yellowish flat portion and a medial reddish nodular portion. Histologic examination revealed that the plaque was composed of two different adjacent tumors. The lateral portion of the plaque had the aspect of a seborrheic keratosis (SK) with hyperkeratosis and acanthosis with irregular proliferation of apparently benign basaloid and squamous keratinocytes and small horn pseudocysts. The medial portion showed a dermal tumor made up of differently sized lobules composed of immature sebocytes mixed with single or clustered mature sebaceous cells. Sebaceous ductal differentiation was visible.
We made the diagnosis of SK associated with sebaceoma. The association of an SK with a benign neoplasm with sebaceous differentiation is rare. It may only be a coincidence, but a role for the preexisting SK cannot be ruled out.
Rippled-pattern Sebaceoma
Noriyuki Misago, M.D.; Yutaka Narisawa, M.D.
Division of Dermatology, Department of Internal Medicine, Saga Medical School, Saga, Japan.
Am J Dermatopathol 2001;23:437-443
A 71-year-old woman had a dome-shaped, slightly erythematous nodule on the anterior scalp. The nodule histopathologically revealed sebaceoma based on the silhouette and cytology. A notable and unique finding was often observed in the aggregations of sebaceoma; an arrangement of small, monomorphous, cigar-shaped basaloid cells in linear rows parallel to one another, resembling the palisading of nuclei of Verocay bodies, namely a rippled-pattern. Although we are not certain that sebaceoma can be clearly separated from trichoblastoma with sebaceous differentiation in all cases, in the present case, the absence of an abundant and densely fibrotic stroma, of follicular differentiation, and of a palisading border in the neoplastic aggregations as well as the presence of many vacuolated cells and tiny duct-like spaces favors the diagnosis of sebaceoma rather than trichoblastoma with sebaceous differentiation.
Based on the expression patterns of CKs as well as similar cytological features between germinative cells in our case and immature cells in the mantles of normal vellus follicles, we believe that rippled-pattern sebaceoma is composed of immature sebaceous germinative cells with some foci of advanced sebaceous differentiation (toward the sebaceous duct and sebaceous lobule).
Sebaceoma and related neoplasms with sebaceous differentiation: a clinicopathologic study of 30 cases.Misago N, Mihara I, Ansai S, Narisawa Y.
Division of Dermatology, Department of Internal Medicine (N.M., Y.N.), Saga Medical School, Saga; Mihara Clinic of Dermatology (I.M.), Tsuruoka; and the Department of Dermatology (S.A.), Akita University School of Medicine, Akita, Japan.
Am J Dermatopathol 2002 Aug;24(4):294-304 Abstract quote The classification of benign sebaceous neoplasms has been challenged both by the assertion that sebaceous adenomas are really carcinomas and by difficulties in drawing the boundaries between sebaceomas and other lesions.
We performed a clinicopathologic study of 30 cases of basaloid neoplasms with sebaceous differentiation, excluding cases of definite sebaceous carcinoma with severe nuclear atypia invading deep within the subcutaneous tissue and those of ocular sebaceous carcinoma. We tried to classify sebaceous neoplasms in six categories with defined histopathologic criteria. All the neoplasms were characterized by aggregations of basaloid cells admixed with sebocytes and sebaceous duct-like structures located in the dermis with or without connection to the epidermis. The categories were 1) sebaceoma (14 cases); 2) trichoblastoma with sebaceous differentiation (3 cases); 3) apocrine poroma with sebaceous differentiation (2 cases); 4) low-grade sebaceous carcinoma (6 cases); 5) sebaceous carcinoma (4 cases); and 6) basal cell carcinoma with sebaceous differentiation (1 case). The sebaceoma was further subclassified as classic type (12 cases) or verruca/seborrheic keratosis type (2 cases).
Although most sebaceomas can be distinguished from other lesions, there are problematic cases. We discuss the histopathologic diagnostic problems associated with sebaceoma and also argue in favor of the concept of sebaceous adenoma.
SEBACEOUS EPITHELIOMA Sebaceous epithelioma and adenoma Am J Dermatopathol 1999;21:405-413
J Cutan Pathol 1992;19:449-457There is increasing evidence that these tumors may actually represent low grade sebaceous carcinomas
PROGNOSIS CHARACTERIZATION
TREATMENT CHARACTERIZATION GENERAL 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
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