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Background
Metastatic tumors to the skin may occasionally be the first manifestation of a cancer. Unfortunately, when this occurs, the cancer is usually advanced. The incidence and type of metastases varies by age, sex, and tumor type.
Skin metastases was the initial presenting manifestation of the cancer in 0.8% of 7316 cancer patients.
See table below.
(J Am Acad Dermatol 1999;22:19)
Cancer Percentage % of tumors as initial sign of disease Lung 60 Renal Cell 53 Ovarian 40 Non-Hematopoietic Cutaneous Metastases In Children and Adolescents
(J Cutan Pathol 2000;27:485-492)
Cancer Cases n=34 Neuroblastoma 8 6 4 Rhabdomyosarcoma, alveolar 4 Osteosarcoma 2 Choriocarcinoma 2 Peripheral neuroepithelioma or Ewing's sarcoma 2 Malignant rhabdoid tumor 1 Paraganglioma 1 Nasopharyngeal carcinoma 1 Colon adenocarcinoma 1 Malignant melanoma 1 Sarcoma NOS 1 This last chart is taken from a thirty year study period at St. Jude Children's Research Hospital in Memphis, TN. A total of 34 cases of non-hematopoietic neoplasms were identified from 1971 cases (2% of total skin accessions). The study included both surgical and autopsy cases. These patients ranged in age from 1 month to 20 years (mean 9.8 years). Not surprisingly, the most common metastatic tumor is rhabdomyosarcoma, which is also the most common soft tissue sarcoma of childhood. In 53% of cases, the skin lesion was the presenting sign.
OUTLINE
Histopathological Features and Variants Special Stains/
Immunohistochemistry/
Electron MicroscopyDifferential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
HISTOLOGICAL AND CLINICAL VARIANTS CHARACTERIZATION GENERAL
Mask-like metastasis: report of 2 cases of 4 eyelid metastases and review of the literature.
Martorell-Calatayud A, Requena C, Díaz-Recuero JL, Haro R, Sarasa JL, Sanmartín O, Botella-Estrada R, Calderón MB, Barona CG, Requena L.Servicio de Dermatología, Fundación Instituto Valenciano de Oncología, Valencia, España.
Am J Dermatopathol. 2010 Feb;32(1):9-14. Abstract quote
Bilateral periorbital edema and swelling are frequent in clinical practice and are commonly attributed to orbital contact dermatitis due to different drugs and cosmetic products. However, when there is a background of a solid cancer, the possibility of eyelid metastasis should be also considered.
Metastases to the eyelids are rare, and in most cases, these lesions are unilateral. Because only a few cases of bilateral involvement have been reported in the literature, clinical and morphological data of this variant are under recognized.
We report the clinical and histopathological characteristics of 2 patients with 4 eyelid metastasis and review the previous cases reported in the literature.
Institute for Dermatopathology, Conshohocken, Pennsylvania 19428, USA.
Cutaneous metastases present themselves in a variety of clinical patterns and tend to be manifested as indurated papules/nodules/tumors. Some of those clinical expressions are unique for certain types of metastases.
This report describes an entirely different phenomenon of clinically incognito cutaneous metastases that were only apparent histopathologically as an incidental finding.Cutaneous metastasis: a clinical, pathological, and immunohistochemical appraisal.
Saeed S, Keehn CA, Morgan MB.
Department of Pathology, University of South Florida College of Medicine, Tampa, FL, USA.
J Cutan Pathol. 2004 Jul;31(6):419-30. Abstract quote
BACKGROUND: Cutaneous tumor metastasis may be the first manifestation of cancer, but more often is a harbinger of advanced disease that portends an ominous prognosis. All skin accessions over the past 10 years from a large Veterans Administration (VA) hospital were reviewed.
METHODS: Archived histories, glass slides, and the immunohistochemical battery (IHC), were assessed to determine diagnostic accuracy.
RESULTS: Of the 100,453 cases reviewed, there were a total of 77 cases (75 males and 2 females) of cutaneous metastasis from the lungs (28.6%), metastatic melanoma (18.2%), gastrointestinal tract (14.2%), genitourinary tract (10.4%), head and neck (9.1%), hematologic (5.2%), breast (5.2%), and miscellaneous (<2%). Metastasis represented the first indication of an internal malignancy in 7.8% of cases. The cutaneous sites of involvement included the head and neck (28%), the trunk (40%), the extremities (18%), and multiple sites (14%). The age range was 38-83 years, with a mean of 62 years. The average time interval between diagnosis of internal malignancy and cutaneous presentation was 33 months (range: <1 month-22 years), and the average survival following diagnosis was 7.5 months (range: <1 month-8 years). In a cohort of subjects, a truncated immunohistochemical battery consisting of CK-7, CK-20, and S-100 was consistent with the expected staining pattern of the primary source of cutaneous metastasis in 83.33% of the patients.
CONCLUSIONS: Excluding the potential for age and gender bias in this study conducted in a VA setting, cutaneous metastases represent an uncommon, deadly, and late-developing occurrence in many patients. Compared with previous studies, lung carcinoma remains the most common of the cutaneous metastases, with a relative rise in the incidence of metastatic melanoma. The immunohistochemical battery of CK-7, CK-20, and S-100 is a helpful adjunct in narrowing the differential diagnosis of the primary site of a large proportion of cutaneous metastases, particularly tumors with an epithelioid appearance such as carcinomas and melanomas.BREAST CANCER Breast carcinoma-histiocytoid variant Cancer 1973;31:793
Tendency to metastasize to eyelid
Epidermotropic metastases from breast carcinoma showing different clinical and histopathological features on the trunk and on the scalp in a single patient
Dimitrije Brasanac , Ivan Boricic and Vera Todorovic
J Cutan Pathol 2003;30:641-646 Abstract quote A 54-year-old female presented with the cutaneous metastases of the breast carcinoma that produced combination of pigmented zosteriform eruption on the trunk and eroded plaque on the scalp, 13 years after radical mastectomy.
Histologically, zosteriform lesions displayed prominent infiltration of the epidermis in nesting or linear pattern by neoplastic cells with focal formation of intraepidermal and subepidermal vesicles due to discohesion of tumor cells and dermal edema. Examination of scalp plaque revealed ulcerations and infiltration of the epidermis with scattered basal and suprabasal malignant cells in pagetoid fashion. Immunohistochemically, tumor cells were cytokeratin 7- and estrogen receptor-positive and cytokeratin 20 negative. HMB-45 and Melan-A-stained numerous dendritic melanocytes intermingled with intraepidermal and superficial dermal tumor cells in the trunk lesion, whereas on the scalp, only occasional melanocytes surrounding intraepidermal carcinomatous cells were identified.
Our case described, to our knowledge, so far unreported combination of individually rare, clinical and histological patterns of cutaneous metastases from breast carcinoma in a single patient.CHORIOCARCINOMA Testicular choriocarcinoma metastatic to the skin: an additional case and literature review.
Tinkle LL, Graham BS, Spillane TJ, Barr RJ.
University of California at Irvine, USA.
Cutis 2001 Feb;67(2):117-20 Abstract quote
Choriocarcinoma, a malignancy of trophoblastic cells, is characterized by the secretion of human chorionic gonadotropin (hCG). Choriocarcinoma primarily arises from the fetal (placental) trophoblasts in the setting of a molar pregnancy. Nongestational choriocarcinoma from the ovary or testis is much rarer. Testicular choriocarcinoma is a malignant tumor with great propensity for distant metastasis.
The primary sites of metastasis are the lungs, liver, and brain. Skin metastasis is very rare but portends a grave prognosis when diagnosed.
We present the case of a 24-year-old white male with a testicular mixed germ-cell tumor with skin metastases of choriocarcinoma.
ESOPHAGEAL CANCER Metastatic adenocarcinoma of the esophagus to the skin: new patterns of tumor recurrence and alternate treatments for palliation
Kathleen J. Smith1, John Williams1 and Henry Skelton2
1 Departments of Dermatology and Pathology, National Naval Medical Center, Bethesda, Maryland, USA, 2 Department of Pathology, University of Alabama, Birmingham, Alabama, USA
Journal of Cutaneous Pathology 2001; 28 (8), 425-431 Abstract quote
Background: Esophageal cancer, particularly adenocarcinoma of the esophagus (ACE), has been steadily increasing in incidence in the United States. In the past, patients usually died rapidly with locoregional disease that leads to inanition and aspiration. However, today when patients with ACE are treated successfully with induction chemotherapy and radiation therapy, followed by surgical excision, ACE usually does not recur locally, but presents with metatastic disease.
We present a 62-year-old white male with ACE, which was treated with induction chemotherapy and radiation therapy followed by surgical excision. After approximately 1 year with no evidence of locoregional recurrence, the patient presented with diffuse cutaneous metastatic disease.
Methods: In addition to routine staining immunohistochemical stains for CK(AE1/AE3), CK7, CK 20, EMA, a-smooth muscle (SM) actin, S-100 protein, CD34, P53, Bcl-2, c-erbB-2 were performed.
Results: The immunohistochemical profile was consistent with an esophageal origin showing positive staining with CK20 and CK7 as well as AE1/AE3 and EMA. In addition, there was marked nuclear expression of p53, as well as membrane expression of c-erb-B2; consistent with progression of the disease and poor response to further cytotoxic therapeutic regimes.
Conclusions: With new therapeutic protocols, we can expect to see more metastatic disease with recurrences of ACE. The histopathologic features and the immunohistochemical profile of the recurrent tumors may be helpful in determining alternate forms of therapy that either alone or in combination could be useful in palliation and delaying progression.
GLIOBLASTOMA MULTIFORME Cutaneous metastasis from an intracranial glioblastoma multiforme
Patricio Figueroa, MD
Jason R. Lupton, MD
Todd Remington, MD
Michael Olding, MD
Robert V. Jones, MD
Laligam N. Sekhar, MD
Virginia I. Sulica, MD
Washington, DC, and Fairfax, VirginiaJ Am Acad Dermatol 2002;46:297-300 Abstract quote
A 34-year-old white man with a history of an intracranial glioblastoma multiforme was treated with surgical excision and radiotherapy. Five months later, the patient had a rapidly growing scalp mass develop. This lesion was excised, and the histology revealed a tumor that was similar to the originally resected intracranial glioblastoma.
Immunohistochemistry for general neuroepithelial derivation (S-100 protein) and for glial fibrillary acidic protein (GFAP) was positive, whereas mesenchymal, epithelial, and neuronal markers were negative. This immunohistochemistry pattern was identical to the original tumor. Although metastasis of this tumor is not uncommon, metastasis to the skin has never been reported.
To our knowledge, this is the first reported case of cutaneous metastasis from glioblastoma in the world literature.
HEPATOCELLULAR CARCINOMA
Jean Kanitakis, MD, etal.
Hepatocyte paraffin 1 (Hep Par 1), a monoclonal antibody recognizing an antigen thought to be specific for hepatocyte mitochondria, is considered the most specific and sensitive marker of normal and neoplastic hepatocytes and has been used in diagnosing hepatocellular carcinomas. Recent data suggest that the specificity of Hep Par 1 for hepatic neoplasms is not absolute; nonhepatic neoplasms might express this marker.
We assessed the value of Hep Par 1 in the diagnosis of cutaneous metastases of visceral tumors by immunostaining 65 biopsy or excision specimens with Hep Par 1. Hepatocarcinomas (primary and metastatic to the skin) showed specific (coarse granular intracytoplasmic) immunoreactivity. A similar reactivity pattern was found in 5 of 10 metastases of bronchial adenocarcinoma. Nonspecific (weak, nongranular) cytoplasmic immunoreactivity was observed in 5 cases of nonhepatic skin metastases.
Hep Par 1 seems to be a sensitive marker of hepatocellular carcinomas metastatic to the skin, but its specificity is not absolute because it might be expressed in metastases of nonhepatic tumors, namely bronchial adenocarcinomas.
Hep Par 1 should be used with caution in the investigation of cutaneous metastases from an unknown primary site, preferably in conjunction with other markers of neoplastic hepatocytes.
Cutaneous metastasis of hepatocellular carcinoma diagnosed with hepatocyte paraffin (Hep Par 1) antibody immunohistochemistry
J. Kanitakis , A. S. Causeret, A. Claudy and J. Y. Scoazec
J Cutan Pathol 2003;30:637-640 Abstract quote
Cutaneous metastases from hepatocellular carcinomas are rare, and their diagnosis may be difficult on histological grounds.
We report a case of metastatic hepatocellular carcinoma to the skin that was confirmed immunohistochemically by the expression of a hepatomitochondria-specific antigen detectable on paraffin-embedded sections (Hep Par 1).LARYNGEAL CARCINOMA
Cutaneous metastasis of neuroendocrine carcinoma of the larynx: report of a case.
Ottinetti A, Colombo E, Dardano F, Migliora P, Picciotto F, Zaccagna A, Angeli G.
Department of Pathology, Department of Dermatology, Ospedale S. Andrea, Vercelli, and Operative Unit of Oncologic Dermatosurgery, Institute for Cancer Research and Treatment I.R.C.C., Candiolo (TO), Italy.
J Cutan Pathol. 2003 Sep;30(8):512-5 Abstract quote.
BACKGROUND: Cutaneous metastasis from neuroendocrine carcinomas of visceral origin is rarely described in indexed literature. The primary sites of origin include: lung (Wick et al., J Am Acad Dermatol 1985; 13: 134), larynx (Zambruno et al., Ann Dermatol Venereol 1989; 116: 855; Schmidt et al., J Laryngol Otol 1994; 108: 272; Guerzider et al., Ann Pathol 1991; 11 (4): 253), mediastinum (Yoshimasu et al., J Dermatol 2001; 28 (3): 168), uterus (Fogaca et al., J Cutan Pathol 1993; 20: 455), and thymus (Wick et al., J Am Acad Dermatol 1985; 13: 134).
METHODS: In this report, the authors present the clinical, histological, immunohistochemical, and ultrastructural characteristics of secondary skin localizations of a neuroendocrine laryngeal tumor that occurred in a 61-year-old man. The complete follow up of the case is described and a brief revision of the terminology and classification of neuroendocrine neoplasms of the larynx is discussed, since a significant relationship exists between the degree of differentiation and biological behavior.
RESULTS: On histological examination, the secondary cutaneous localization appeared to be more dedifferentiated compared to the primary tumor. The immunohistochemical patterns of reactivity were similar in both neoplasms, showing expression of neuroendocrine and epithelial markers.
CONCLUSIONS: An important issue of prognostic significance is to differentiate a cutaneous metastasis of a neuroendocrine carcinoma from the primary small cell-undifferentiated carcinoma of the skin (Merkel cell carcinoma).MESOTHELIOMA
- Pleural mesothelioma with cutaneous extension to chest wall scars.
Shieh S, Grassi M, Schwarz JK, Cheney RT.
Department of Dermatology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
J Cutan Pathol. 2004 Aug;31(7):497-501. Abstract quote
BACKGROUND: Cutaneous mesothelioma is rare but may occur following local surgical procedures for visceral mesothelioma or as a metastasis.
METHODS: A patient with pleural mesothelioma, who developed papules within chest wall scars, 14 and 15 months after pleural biopsy and thoracentesis, respectively, is reported.
RESULTS: Histopathology showed an epithelioid tumor forming tubulopapillary and glandular structures. The diagnosis of mesothelioma was confirmed with immunohistochemistry. Tumor cells stained characteristically for low-molecular-weight cytokeratins 5/6, calretinin, and vimentin and were negative for mucicarmine, carcinoembryonic antigen, thyroid transcription factor 1, prostate-specific antigen, gross cystic disease fluid protein, S-100, factor VIII, and CD31.
CONCLUSIONS: Histologically, mesothelioma may resemble a primary adnexal neoplasm, metastatic adenocarcinoma, or angiosarcoma. Immunohistochemistry can clarify the diagnosis. Clinicians should be aware of the varied presentations of mesothelioma, as cutaneous presentations are becoming increasingly common.PANCREATIC ADENOCARCINOMA
- Epidermotropically metastatic pancreatic adenocarcinoma.
Ambro CM, Humphreys TR, Lee JB.
From the Department of Cutaneous Dermatology and Cutaneous Biology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
Am J Dermatopathol. 2006 Feb;28(1):60-2 Abstract quote.
We describe an epidermotropically metastatic pancreatic mucinous ductal adenocarcinoma on the scalp.
Neoplastic glandular structures that varied in size and shape containing abundant mucin within the lumens and in the neoplastic cells were present within a seborrheic keratosis and adjacent normal epidermis.
Similar neoplastic glandular structures were present in the dermis, some within adnexal epithelium and lymphatic vessels.
The patient's history of pancreatic mucinous ductal adenocarcinoma and immunohistochemical staining pattern of carbohydrate antigen 19-9 (CA 19-9) confirmed the diagnosis.
RETE TESTIS ADENOCARCINOMA
- Cutaneous metastases from adenocarcinoma of the rete testis.
Rubegni P, Poggiali S, De Santi M, Marsili S, Bilenchi R, Miracco C, Fimiani M.
Department of Clinical Medicine and Immunological Sciences, Section of Dermatology, University of Siena, Italy.
J Cutan Pathol. 2006 Feb;33(2):181-4. Abstract quote
Adenocarcinoma of the rete testis (ACRT) is extremely rare and has only been the subject of sporadic case reports, in most of which the neoplasm manifested as a scrotal mass with diffuse enlargement of the testis. Only a few cases of scrotal infiltration by a contiguous ACRT have been described.
To our knowledge, none have reported distant skin metastases. We report a case of ACRT presenting with suprapubic skin metastases. The diagnosis was based on clinical and histopathological findings and supported by the results of immunohistochemical and ultrastructural studies.
We discuss the differential diagnosis to this rare entity, which include metastatic adenocarcinoma, serous tumor of the testis, and mesothelioma of the tunica vaginalis.SISTER MARY JOSEPH'S NODULE
Department of Dermatology, University of Maryland, Baltimore, MD, USA.
Sister Mary Joseph's nodule is referred to as metastatic lesion of the umbilicus. Most of the tumors are adenocarcinomas originating from gastroenteric and genital tracts. Only rarely were metastases from other locations reported.
We describe here an unusual case of a Sister Mary Joseph's nodule that was metastasized from prostate carcinoma 3 years after radiation therapy. The lesion was the first sign of metastatic disease, and the diagnosis was made on skin biopsy. The patient died of extensive metastases of prostate carcinoma 4 months later.
We report this case to extend the list of differential diagnosis for Sister Mary Joseph's nodule in male patients and emphasize the importance of Sister Mary Joseph's nodule as an ominous diagnostic sign.THYROID CANCER
- Cutaneous Metastases of Follicular Thyroid Carcinoma: A Report of Four Cases and a Review of the Literature.
Quinn TR, Duncan LM, Zembowicz A, Faquin WC.
From *Pathology Services, Inc., Cambridge, Massachusetts; daggerDepartment of Pathology, Massachusetts General Hospital, Boston, Massachusetts; and double daggerMassachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
Am J Dermatopathol. 2005 Aug;27(4):306-312. Abstract quote
Cutaneous metastasis of follicular carcinoma of the thyroid is very rare, and when it occurs, can exhibit a variety of histologic appearances. The 4 cases presented here were identified from the surgical pathology files of the James Homer Wright Laboratories of Pathology at the Massachusetts General Hospital (MGH).
The cases consisted of 4 patients, 3 men and 1 woman, aged 52 to 75 years, with cutaneous metastasis of follicular thyroid carcinoma. The tumors include a conventional follicular carcinoma, a follicular carcinoma with anaplastic transformation following initial metastasis, the first reported cutaneous metastases of a follicular carcinoma with oncocytic features (Hurthle cell carcinoma), and a follicular carcinoma with a prominent insular carcinoma component. All 4 tumors were widely invasive within the thyroid gland. Sites of dermal metastases included a post-thyroidectomy scar, scalp, and sacral skin.
Three metastases retained the morphologic and immunocytochemical features of the primary thyroid tumors. However, in one case there was high-grade transformation to anaplastic carcinoma following treatment of a sacral metastasis with accompanying loss of the characteristic immunophenotype of follicular thyroid carcinoma.
Awareness of the varied morphologies of metastatic follicular thyroid carcinoma to the skin may prompt immunohistochemical analysis and the request for a complete clinical history, ultimately preventing misdiagnosis.?Metastatic papillary carcinoma of the thyroid.
Mahalingam M, Bhawan J.
Quest Diagnostics Incorporated, Cambridge, MA 02139, USA.
J Cutan Pathol. 2004 Aug;31(7):509-12. Abstract quote
BACKGROUND: Cutaneous metastases from thyroid carcinomas, although uncommon, have been previously reported and are usually found in association with evidence of disseminated disease.
METHODS: We report a 75-year-old male who presented with a 4-cm reddish violaceous nodule on the left temple and a clinical history significant for papillary carcinoma of the thyroid.
RESULTS: Microscopic examination of a 4-mm punch biopsy revealed a poorly circumscribed neoplasm with focal epidermal connection and multiple cystic cavities and papillary projections.
CONCLUSIONS: This case report describes a solitary cutaneous lesion as the first evidence of disseminated neoplastic disease in a patient with no other clinical evidence of concurrent metastases. The histology of the lesion was unusual in that it mimicked a primary cutaneous neoplasm.UTERUS
Am J Dermatopathol. 2005 Oct;27(5):436-8. Abstract quote
Uterine papillary serous carcinoma (UPSC) is an uncommon highly malignant variant of endometrial adenocarcinoma that histologically and clinically resembles papillary serous carcinoma of the ovary.
This case demonstrates a very rare case of cutaneous metastasis of uterine papillary serous carcinoma. A 54-year-old Korean female developed multiple pruritic skin nodules on the pubic area 13 months later after diagnosis of uterine papillary serous carcinoma. A biopsy of the skin lesions showed papillary serous carcinoma, compatible with her primary tumor.
Without clinical history, it is difficult to distinguish other types of metastatic carcinoma to the skin and primary apocrine carcinoma of the skin from metastatic uterine papillary serous carcinoma.
Whereas uterine papillary serous carcinoma only rarely involves the skin, this entity should be included in the differential diagnosis of papillary adenocarcinoma in the skin.
SPECIAL STAINS AND IMMUNOHISTO-
CHEMISTRYCHARACTERIZATION
J Cutan Pathol. 2005 Sep;32(8):561-566. Abstract quote
Determining the primary origin of skin metastases might be a challenging issue for pathologists, especially when there is no primary history or when this history is unavailable. The poor specificity of morphological appreciation is challenging, emphasizing the need for ancillary studies.
We have retrieved 44 cases of skin metastases from our pathology files. Paraffin blocks were collected and homemade tissue arrays were made. We have tried to assess the primary origin based on morphological data alone, and then using 13 antibodies (cytokeratins (CK) 5/6, 7, 19, 20, thyroid transcription factor-1, carcinoembryonic antigen, PS100, tumor-associated glycoprotein 72, BerEP4, estrogen receptor (ER), progesterone receptor (PR), CD10, and E-cadherin). Most metastases in our series were from breast (13) and colorectal cancers (six) as they are the main clinical activity in our hospital.
Only 44% of cases were correctly assessed based on the sole morphology, emphasizing the need for ancillary studies. CK 20, ER, and PR were the most helpful markers to determine the primary origin of skin metastases by highlighting colorectal origin and mammary origin, respectively.
By far, clinical information and morphological evaluation are more reliable than the use of ancillary techniques, which have to be used in the absence of the former one and the poor differentiation of the latter ones.p63
Departments of Pathology, and Dermatology, University of Texas - M.D. Anderson Cancer Center, Houston, TX, USA.
p63, a recently identified homologue of the p53 gene, is mainly expressed by basal and myoepithelial cells in skin. Others and we have shown the value of p63 in distinguishing primary adnexal tumors from visceral adenocarcinomas metastatic to skin.
We now investigate the pattern of p63 expression in metastases from skin adnexal carcinomas and their cognate primaries and evaluate p63 expression in a larger case series of malignant cutaneous adnexal neoplasms.
Immunohistochemical analysis for p63 was performed on 13 metastases of adnexal carcinomas and their corresponding primary tumors. Twenty visceral metastatic adenocarcinomas to the skin and 7 primary mucinous carcinomas with cutaneous or visceral origin were compared. The majority (90.9%) of primary adnexal tumors strongly expressed p63 and their metastases labeled similar to their cognate primary tumors. With one exception, primary or metastatic mucinous carcinomas did not express p63. Metastases from two apocrine carcinomas lacked p63 expression. All other cutaneous metastases from internal adenocarcinomas were negative for p63.
Analysis of p63 expression may assist in the differential diagnosis of primary adnexal carcinomas versus metastatic visceral adenocarcinomas to the skin. Metastases from adnexal carcinomas generally retain p63 expression similar to their associated primary tumors.PODOPLANIN
- Liang H,
- Wu H,
- Giorgadze TA,
- Sariya D,
- Bellucci KS,
- Veerappan R,
- Liegl B,
- Acs G,
- Elenitsas R,
- Shukla S,
- Youngberg GA,
- Coogan PS,
- Pasha T,
- Zhang PJ,
- Xu X.
Departments of *Pathology and Laboratory Medicine parallelDermatology, University of Pennsylvania School of Medicine daggerFox Chase Cancer Center, Philadelphia, PA double daggerDepartment of Pathology, East Tennessee State University paragraph signJames H. Quillen, VAMC, Johnson City, TN section signInstitute of Pathology, Medical University of Graz, Graz, Austria.
Distinction of primary skin adnexal carcinomas from cutaneous metastasis of adenocarcinomas is challenging. In this study, we evaluated podoplanin immunoreactivity in a series of primary skin adnexal tumors and adenocarcinomas metastatic to skin using a D2-40 antibody. The initial test series were composed of a total of 93 cases including 32 primary skin adnexal carcinomas, 46 benign primary adnexal tumors, and 15 cutaneous metastatic adenocarcinomas.
We found that variable D2-40 reactivity was seen in all of the primary cutaneous carcinomas including sebaceous carcinomas (10/10), squamous cell carcinomas (10/10), porocarcinomas (4/4), trichilemmal carcinomas (4/4), skin adnexal carcinomas not otherwise specified (4/4), and in the majority of benign skin adnexal tumors. In contrast, no podoplanin immunoreactivity was seen in any of the 15 (0/15) cutaneous metastases. To confirm the initial findings and to further explore the utility of podoplanin reactivity in the distinction of these tumors, we also examined a test set of 35 unknown cases, including 21 adenocarcinomas metastatic to skin and 14 primary adnexal tumors, in a blinded fashion. In this test set of cases, podoplanin was negative in 22 cases and positive in 13 cases. Of the 22 podoplanin negative cases, 20 were proven to be metastatic adenocarcinoma. Of the 13 D2-40 positive cases, 12 were proven to be primary adnexal tumors.
Our results suggest that podoplanin can be a useful tool to distinguish primary skin adnexal carcinomas form adenocarcinomas metastatic to skin with high sensitivity (94.5%) and specificity (97.2%).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. Fourth Edition. Mosby 2001.
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