Glioma-Associated Oncogene-1 Expression in Basal Cell Carcinoma and Its Histologic Mimics.

ABSTRACT: Basal cell carcinoma (BCC) is the most common skin cancer, and it has numerous histologic mimics with variable prognoses and treatments. Although some immunohistochemical stains can be used for the differential diagnosis of BCC, variability and overlap in results can complicate their interpretation. Immunohistochemical staining for glioma-associated oncogene-1 (Gli-1) was performed on 26 nodular BCCs, 22 infiltrative BCCs, 9 basaloid squamous cell carcinomas, 12 desmoplastic trichoepitheliomas, 19 Merkel cell carcinomas, 11 sebaceous carcinomas, 10 cylindromas, 14 spiradenomas, 12 adenoid cystic carcinomas (AdCC), and 1 solitary trichoepithelioma. Strength of staining was scored as 0, 1+, 2+, or 3+, and distribution of staining was categorized as diffuse, multifocal, or focal. Strong, diffuse Gli-1 expression was seen in all tumors with basal epidermal-type differentiation, including BCC, trichoepithelioma, and basaloid squamous cell carcinoma. All examples of Merkel cell carcinoma were negative for cytoplasmic expression. Seven out of 11 sebaceous carcinomas were negative for Gli-1, and the remaining 4 showed 1+ expression. Cylindroma, spiradenoma, and AdCC, each an adnexal skin tumor, showed the most variable staining, but with cylindroma and spiradenoma demonstrating comparable labeling patterns. Overall, although Gli-1 may not distinguish between basal epidermal-type tumors, it may have a role in separating that group from lesions with adnexal differentiation, particularly sebaceous carcinoma, but also cylindroma, spiradenoma, and AdCC. Any cytoplasmic staining seems to exclude the diagnosis of Merkel cell carcinoma.

Eccrine spiradenoma of the nipple: Case report, differential diagnosis and literature review.

Eccrine spiradenoma is a rare lesion originating from eccrine sweat glands, with only few cases reported in breast tissue: we here describe for the first time, an eccrine spiradenoma arising in the nipple. An 84 year-old woman with a lesion enlarging her right nipple, showing ulcerations and eczema-like changes of the covering skin, was admitted to our hospital. Surgical excision of the central quadrant with nipple-areola complex was performed, followed by histopathological evaluation which revealed an adenoma with predominantly basaloid epithelial cells. The lesion was composed of tightly packed small and large groups of cells, arranged in diffuse alveolar/pseudorosette formations. The small cells expressed p63 and calponin, while a positive expression of CK7 and CD117 was detected in large cells. After careful and detailed examination, excluding various similar entities, a diagnosis of eccrine spiradenoma has been rendered. Although extremely rare, eccrine spiradenoma should be taken into account in the differential diagnosis of subcutaneous primary breast tumors.

Perineural growth of benign cutaneous sweat gland tumors: a hitherto unrecognized phenomenon unassociated with malignancy.

BACKGROUND: Cutaneous intraneural reactive epithelial proliferations mimicking malignancy include epithelial sheath neuroma, re-excision perineural invasion and reactive neuroepithelial aggregates. Nevertheless, intraneural growth of benign sweat gland tumors has not been reported before. AIMS: To report a predominantly intraneural proliferation of morphologically bland sweat gland tumors, describe their clinicopathological features and correlate them with survival. RESULTS: We analyzed a spiradenoma and a hidradenoma with a prominent intraneural growth, occurring on the back of the 19-year-old woman and on the arm of the 53-year-old woman. Both lesions presented as a painful and slightly raised papule. After complete excision, an uneventful clinical course was observed during the follow-up period of 52 and 54 months. Pathologically, the most striking feature was an almost exclusive intraneural growth within the peripheral nerves of the deep dermis and subcutis. CONCLUSION: We report for the first time the predominantly intraneural growth of benign sweat gland tumors. Although their histogenesis is unknown, perineural displacement due to previous surgery or trauma, as well as development from intraneural embryological epithelial remnants remains possibilities. Long-term follow-up of our patients suggests that intraneural growth of otherwise bland sweat gland tumors does not signify malignancy. Complete excision appears to be sufficient treatment procedure.

Hidradenoma papilliferum of the vulva in association with an anogenital mammary-like gland.

Hidradenoma papilliferum (HP) is a benign adnexal neoplasm which preferentially develops in the anogenital region of women. Although the origin of HP was previously thought to be an apocrine sweat gland, recent studies have suggested that it may derive from the anogenital mammary-like gland (MLG). In this paper, we present a 43-year-old Japanese woman with hidradenoma papilliferum of the vulva. The lesion developed 7 years prior to her visit, and clinically appeared as a skin-colored cystic nodule. Histopathological examination revealed that the neoplasm was formed by the tubular structures consisting of two types of pleomorphic cells, columnar cells in the luminal layer and cuboidal cells in the basal layer. Further, the surgical specimen contained a wide, divergent, lobular ductal structure located in the vicinity of the neoplastic lesion, which was consistent with MLG.

Papillary hidradenoma of the eyelid margin: clinical and immunohistochemical observations further supporting an apocrine rather than an eccrine origin.

A 46-year-old woman was evaluated for a "recurring papilloma" of the left medial upper eyelid margin. Beneath the papillary lesion medial to the punctum was a 5-mm diameter cutaneous mass thought to be cystic. After excisional biopsy, histopathologic analysis documented the presence of an epidermal keratinizing squamous papilloma surmounting a circumscribed dermal papillary hidradenoma composed of deeply eosinophilic columnar cells. Additionally, there was intraductal proliferation of tumor extending toward a subclinical poral opening through the epidermis. Immunohistochemistry proved the apocrine nature of the benign, non-cystic lesion by virtue of its nuclear androgen receptor and cytoplasmic gross-cystic disease fluid protein-15 positivity, along with its smooth muscle actin-positive myoepithelial layer. This and prior cases establish that apocrine tumors, both benign and malignant, are strictly localized at or near the eyelid margin where only apocrine glands are found. These tumors are more often papillary than solid adenomas, and most exceptionally can be malignant. We review the differential diagnosis of simulating eccrine eyelid tumors. We recommend wide local excision for benign lesions, in view of possible intraductal extension that can be eccentric to the main tumor and the miniscule potential for malignant transformation.

Pseudocarcinomatous hyperplasia associated with hidradenoma papilliferum.

Cutaneous pseudocarcinomatous hyperplasia is a benign proliferation that can be associated with many nontumoral and tumoral conditions. In the literature, squamous proliferations of different types have been associated with several types of adnexal adenomas. However, we found no reported case of association of hidradenoma papilliferum with pseudocarcinomatous hyperplasia. We had the opportunity of studying this type of an association in a 38-year-old man. The hidradenoma was located deep in the corion of the biopsy and the uppermost squamous epithelium showed a pseudocarcinomatous hyperplasia that focally contacted with the hidradenoma. No atypia was noted in the squamous proliferation. E-cadherin was diffusely expressed by the squamous nests, whereas p53 and Ki-67 were restricted to the basal layer. Cyclin D-1 was expressed in the parabasal layer. Immunohistochemistry of the squamous proliferation was negative for human papillomavirus.

Cutaneous myoepithelioma arising within hidradenoma of the scalp.

A 62-year-old man presented with a 2-year history of a 2-cm cystic mass involving his occiput. There had been recent enlargement, and the clinical impression was that of a pilar cyst. Histopathological sections showed a partially dermal solid and cystic proliferation. The tumor contained areas of glandular differentiation with cuboidal to columnar cells lining luminal and cystic spaces. A concurrent spindle cell proliferation was seen interspersed between glands and also formed broad, cellular sheets of cells. The stroma was sclerotic and without chondroid or myxoid elements. Immunohistochemistry showed that the spindled cells expressed S100 protein, cytokeratin and smooth muscle myosin. The immunohistochemical profile and the relationship with ductal elements supported myoepithelial differentiation. The proliferation warranted the diagnosis of myoepithelioma arising from a hidradenoma, which to our knowledge has not been previously described. In addition to discussing this case, we provide a brief review of epithelial-myoepithelial neoplasms encountered in the skin.

Epidermal growth factor receptor gene status by fluorescence in situ hybridization in malignant, atypical, and benign hidradenomas.

BACKGROUND: Epidermal growth factor receptor (EGFR) protein overexpression and gene amplification are important prognostic factors in various tumors and EGFR inhibitors are now available as promising chemotherapeutic agents. There is little information in the literature regarding the EGFR protein and gene status in hidradenocarcinomas which has an aggressive biologic course characterized by repeated local recurrences and systemic metastasis. We have previously reported EGFR protein overexpression in malignant, atypical, and benign hidradenomas and would like to further evaluate their gene status by fluorescence in situ hybridization. METHODS: Fluorescence in situ hybridization by 2-color probe Vysis LSI EGFR SpectrumOrange/CEP 7 SpectrumGreen Probe (Abbott Molecular) and EGFR immunostain (H11, Dakocytomation) were performed in 15 malignant, 15 atypical, and 7 benign hidradenomas. RESULTS: High polysomy and low trisomy was noted in 1 and 4 hidradenocarcinoma, respectively; however, EGFR overexpression was seen only in 1 low trisomy case. Disomy is noted in the remaining 29 cases (9 hidradenocarcinomas, 15 atypical hidradenomas, and 5 benign hidradenomas). EGFR overexpression was seen in 3/12 (25%) malignant hidradenomas, 7/15 (47%) atypical hidradenomas, and 3/5 (60%) benign hidradenomas; none of these cases demonstrated EGFR gene amplification. CONCLUSIONS: Polysomy/trisomy is more frequently seen in hidradenocarcinoma than atypical and benign hidradenomas. The role of EGFR inhibitor therapy in hidradenocarcinoma cases with protein overexpression remains unclear. Lack of correlation between the protein expression and polysomy/gene amplification suggests that molecular mechanisms other than gene amplification play a role in EGFR overexpression in malignant, atypical, and benign hidradenomas.

From hidroacanthoma simplex to poroid hidradenoma: clinicopathologic and immunohistochemic study of poroid neoplasms and reappraisal of their histogenesis.

BACKGROUND: Poroid neoplasms comprise classic poroma (P), hidroacanthoma simplex (HS), dermal duct tumor (DDT), and poroid hidradenoma (PH). The 3 latter are rarely reported. Poroid cells in P have recently been identified as keratinocytes of the lowermost acrosyringium and the sweat duct ridge. OBJECTIVES: To investigate a large cohort of poroid neoplasms to better define the clinical and pathologic aspects of HS, DDT, and PH. To analyze the expression of discriminatory keratins in all 4 poroid neoplasms. METHODS: 202 P, 11 HS, 17 DDT, 31 PH, and 5 composite tumors were examined under light microscopy, and 11, 9, 10, 15, and 2, respectively, by immunohistochemistry using anti-keratin antibodies, in particular, anti-K77, specific for luminal cells of the eccrine dermal sweat duct, and Ki-67 antibody. RESULTS: HS appeared later in life (66.6 years old) than P, DDT, and PH. Whereas P, DDT, and PH displayed unspecific clinical aspects, HS had most frequently the aspect of a large seborrheic keratosis with well-defined borders. HS, DDT, and PH were absent on palms and soles, but were found on the trunk, the lower limbs, and the upper limbs. Similar pathologic features were observed in all tumors, that is, a majority of poroid cells expressing K14, islands of K10-positive and K77-negative large cells. K77 expression was limited to luminal cells of intact ductal structures within the tumors. CONCLUSIONS: Our data demonstrate the common histogenesis of the 4 poroid neoplasms, which seem to derive from the basal keratinocytes of the sweat duct ridge and the lower acrosyringium. The variable length of the sweat duct ridge may account for the variety of poroid neoplasms, according to the site of tumor induction along this structure.

Giant clear cell hidradenoma of the knee.

Hidradenomas, also referred to as nodular hidradenomas or clear cell hidradenomas (CCH), are benign cutaneous eccrine tumors usually 2-3 cm in dimension. Hidradenomas are relatively common; however, giant forms are rare. We report a case of an 8.0 x 6.0 x 3.0 cm clear cell hidradenoma of the left knee in a 43-year-old man. The tumor was mobile, located above the patellar tendon and was without bony involvement on imaging studies. Grossly, the resected tumor was unencapsulated and tan, with a solid and cystic cut surface showing papillary excrescences on the cyst wall. Microscopically, the tumor cells showed an infiltrative growth pattern at the periphery, however, the tumor cytology was bland and no necrosis or mitoses were identified. The overlying dermis contained hemosiderin pigment deposition and infiltration with eosinophils. Immunohistochemically, tumor cells were positive for cytokeratin, CAM5.2, p53, carcino-embryonic antigen (CEA) and epithelial membrane antigen (EMA), and negative for CD10 and Ki-67. The cytological features of hidradenomas can present diagnostic challenges, as other 'clear cell' tumors such as metastatic renal cell carcinoma should be considered. Immunohistochemical studies and differential diagnoses are discussed.

A single lesion showing features of pigmented eccrine poroma and poroid hidradenoma.

Poroid hidradenoma (PH) is a variant of poroma. This entity was defined by Abenoza and Ackerman in 1990. This neoplasm shows architectural characteristics of hidradenoma (tumor cells confined entirely within the dermis in both solid and cystic components) and cytologic characteristics of poroid neoplasm (poroid and cuticular cells, the latter showing ductal differentiation). We herein document a case of single poroid lesion with the features of both eccrine poroma and PH. The patient was a 55-year-old woman with a pigmented nodular lesion on her upper back for 7 years. The histopathologic features of the lesion were consistent with those of eccrine poroma and PH. Unlike most eccrine poromas, this case was pigmented, clinically and microscopically.

A malignant eccrine poroma in a pregnant woman: case report and review of the literature.

Malignant eccrine poroma is a rare cutaneous neoplasm that originates from the intraepidermal portion of the eccrine gland. It affects mainly elderly people while its occurrence in younger adults is extremely rare. We present the first reported case of a malignant eccrine poroma in a pregnant woman, with emphasis on its pathologic and immunohistochemical features. Early diagnosis and treatment of eccrine neoplasms are of crucial importance when pregnancy coexists, because of their tendency to aggravate under the influence of gestation-related changes.

Sarcomatoid eccrine porocarcinoma: report of two cases and a review of the literature.

Eccrine porocarcinoma is an uncommon sweat gland malignancy. To the best of our knowledge, there has been no report in the English literature of porocarcinoma with predominantly undifferentiated sarcomatous change. We present two cases of sarcomatoid eccrine porocarcinoma associated with a benign poroma. Case 1 pertained to an 82-year-old woman with an ulcerated chest wall tumor, and Case 2 was that of a 74-year-old woman who presented with an ulcerated plaque in the lower leg. Case 1 showed an unusual pseudo-angiosarcomatous morphology with spindle cells dissecting through collagen bundles and forming vascular like channels. Case 2 revealed high-grade malignant spindle cells with focal evidence of ductal differentiation. In both the cases, benign poromatous elements were histologically evident. Immunohistochemistry performed showed pancytokeratin positivity in spindle cells of both lesions. Epithelial membrane antigen and carcino-embryonic antigen positivity in the malignant ductal elements and focal smooth muscle actin staining of the spindle cells were demonstrated in Case 2. A brief review of relevant literature is presented.

Keratin profiles may differ between intraepidermal and intradermal invasive eccrine porocarcinoma.

We report two cases of eccrine porocarcinoma (EPC), one of intrepidermal EPC (IEEPC) and one of intradermal invasive EPC (IDEPC) in an immunohistochemical study of cytokeratins (CK) using nine different anti-keratin antibodies against CK1, 7, 8, 10, 14, 16, 17, 18 and 19. IEEPC expressed terminal differentiated CK1 and CK10. In contrast, IDEPC expressed simple-epithelial keratins such as CK7, 8, 18 and 19. Keratin expression of IEEPC preserves the immunophenotypes of normal epidermis. IDEPC, however, expresses poorly differentiated keratin. These results suggest that the keratin profiles of EPC are correlated with the invasive degree and reflect the clinical prognosis of EPC.

Expression of CD10 in basal cell carcinoma.

We investigated the expression of CD10 by an immunohistochemical method in 51 basal cell carcinomas (BCCs), eight pilomatricomas, five trichoblastomas, two trichofolliculomas, three sebaceomas, five sebaceous carcinomas, ten syringomas, two spiradenomas, ten poromas, four porocarcinomas, one eccrine duct carcinoma (not otherwise specified, NOS), six mixed tumors of apocrine origin, and nine squamous cell carcinomas (SCCs). We detected strong expression of CD10 in tumor cells of BCC (86%), and found that the smaller the number of positive tumor cells, the larger the number of positive stromal cells, in particular in sclerosing BCCs. Spearman's rank correlation test revealed a significant negative correlation in BCCs between the expression of CD10 in tumor cells and that in stromal cells (P = 0.001). In all pilomatricomas (100%) and in four trichoblastomas (80%), strong expression was also detected in tumor cells. There was no detectable expression in trichofolliculomas. One sebaceoma (33%) and two sebaceous carcinomas (40%) expressed CD10 in a similar fashion to BCCs. All tumors of eccrine gland origin, including syringoma, spiradenoma, poroma, porocarcinoma, and eccrine duct carcinoma (NOS), did not express CD10. Five mixed tumors (83%) were immunopositive. In SCC, CD10 was overexpressed only in the stromal cells. These findings support the hypothesis that BCC is derived from the folliculo-sebaceous apocrine unit, especially having the same origin as trichoblastoma and pilomatricoma. CD10 might be an indicator of tumor invasiveness if it is expressed in stromal cells, while it might be a marker of follicular differentiation if it is expressed in the actual tumor cells of cutaneous epithelial neoplasms.

Eccrine porocarcinoma with Bowenoid changes: epithelial membrane antigen is not a useful marker for malignant tumours arising from eccrine gland structures.

A case of eccrine porocarcinoma with Bowenoid changes is reported. We compared the results of immunohistochemical staining for epithelial membrane antigen in the present case with results in Bowen's disease to determine whether the presence of epithelial membrane antigen (EMA) enabled us to differentiate between Bowen's disease and eccrine porocarcinoma with Bowenoid changes. Histologically, the present tumour was characterized by atypical clear cells with Bowenoid changes as well as uniform small cells and intradermal nests with ductal structures. The membrane and cytoplasm of uniform small cells and ductal luminal surfaces were positive for EMA. However, the atypical cells with Bowenoid changes were negative for this. In contrast, tumour cells in Bowen's disease were positive for EMA. Although EMA is known to be a useful marker for some benign tumours derived from eccrine ducts, we found it difficult to distinguish eccrine porocarcinoma with Bowenoid changes from Bowen's disease using immunohistochemical staining for EMA.