Terry L. Barrett

Spindle Cell and Epithelioid Cell Nevi with Atypia and Metastasis (malignant Spitz Nevus)

We report on the clinical and pathologic features of 32 lesions diagnosed as malignant spindle cell and epithelioid cell nevus (S&E nevus). Because of the clinical or initial histopathologic diagnosis of malignant melanoma, six patients had lymph node dissection. Three of these patients also had an enlarged lymph node. In all six cases, metastatic spindle or epithelioid cells were found in at least one of the resected lymph nodes. Of the 30 patients with follow-up information, including all six patients with lymph node metastases, all are alive and well. No recurrences or further metastases have been found. On histopathologic reevaluation, all the lesions had features of S&E nevi. Study of these cases suggests that although some lesions with features of S&E nevi may involve local lymph nodes, widespread metastases do not result.

Hmb-45 Staining in Benign and Malignant Melanocytic Lesions: A Reflection of Cellular Activation

The antibody HMB-45 used as an immunohistochemical reagent has often been labeled as a marker for melanoma, even though some benign lesions have been noted to show positive staining reactions with this reagent. Biopsy specimens from 225 benign and malignant melanocytic lesions were examined after immunoperoxidase staining for S-100 protein and HMB-45. The lesions studied included common acquired nevi, spindle cell and epithelioid cell nevi (Spitz nevi), cellular blue nevi, deep penetrating nevi, congenital nevi, nevi from hormonally reactive areas (genital), malignant melanoma, and desmoplastic malignant melanoma. A positive reaction for HMB-45 was seen in the dermal component in a high percentage of each of these types of lesions except for the common acquired nevi and the desmoplastic malignant melanomas that were uniformly negative for HMB-45 in the dermal component. HMB-45 correlates with melanosome production and thus a melanocytic origin of HMB-45-positive cells. HMB-45 may correlate best with factors that stimulate melanocytic proliferation and production of melanosomes.

Nevi with site‐related atypia: a review of melanocytic nevi with atypical histologic features based on anatomic site

A subset of melanocytic nevi share features with melanoma and nevi with architectural disorder but are biologically inert and to date do not appear to portend an increased risk for the development of malignancy. These benign nevi with certain atypical histologic features cluster among specific anatomic sites and are thus designated nevi with site‐related atypia. We categorize these lesions into four main groups: acral, genital, special site and conjunctival, based on anatomy and relative prevalence of specific atypical histologic features. As the literature and our recognition of these lesions continue to grow, our understanding of their biology has not kept pace.

Distinction of benign sebaceous proliferations from sebaceous carcinomas by immunohistochemistry.

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.

Metastatic hidradenocarcinoma with demonstration of Her-2/neu gene amplification by fluorescence in situ hybridization: Potential treatment implications

Abstract:u2002 A 44‐year‐old man was referred for a right chest nodule of 3 months duration. A ‘benign’ nodule had been excised from this location 8 years prior. On examination, palpable nodes were noted in the right axilla. Radiographic studies were significant only for right axillary lymphadenopathy. Histologically, a nodular dermal proliferation composed of poorly differentiated epithelioid cells in nests and focally forming ducts with pseudopapillary architecture comprised the primary tumor. Features of a clear cell hidradenoma were noted focally. Immunohistochemical (IHC) analysis revealed reactivity for HMW cytokeratins, CK5 and CK7, p53, p63, CEA (focal), androgen receptor, EGFR, estrogen receptor (ER), MUC5AC, and strong/diffuse membranous staining for Her‐2/neu. Negative stains included villin, TTF‐1, CDX2, S‐100 protein, vimentin, gross cystic disease fluid protein 15 (GCDFP‐15), mammoglobulin, and MUC2. A wide local excision and axillary node dissection was performed. Metastatic tumor involved nine of 28 nodes. Interphase fluorescence in situ hybridization (FISH) demonstrated chromosomal amplification of the Her‐2/neu locus within the tumor and a nodal metastasis. The patient has completed adjuvant and radiotherapy, including trastuzumab, and is asymptomatic. We believe this to be the first demonstration of Her‐2/neu amplification in a malignant skin adnexal tumor. In analogy to breast carcinoma, these findings suggest the applicability of trastuzumab for patients with metastatic adnexal carcinomas demonstrating Her‐2/neu amplification.

Acral myxoinflammatory fibroblastic sarcoma: case series and immunohistochemical analysis.

Background:u2002 Acral myxoinflammatory fibroblastic sarcoma (AMFS) is a rare, low‐grade neoplasm most often occurring on the extremities of adults. It consists of mixed inflammatory infiltrates with nodules of epithelioid, spindled and bizarre‐appearing cells within a fibrosclerotic‐to‐myxoid stroma. AMFS frequently recurs, but only rarely metastasizes.

Papular eruption of human immunodeficiency virus disease : a review of the clinical, histologic and immunohistochemical findings in 48 cases

The papular eruption (PE) associated with human immunodeficiency virus infection, although described as a distinctive clinicopathologic entity, has shown a wide range of histologic findings ranging from eosinophilic folliculitis to granuloma annulare. We examined 48 cases of the PE in order to define the histologic spectrum of these lesions, and to correlate these findings with clinical presentations. The most distinctive clinical features are the frequency of these lesions in this population, the large number of lesions, pruritus, and the chronic nature of the lesions. His tologically, the distinctive features are the prominent perivascular factor XIIIa-positive dermal dendritic cells, atypigal vascular proliferation, and dermal fibrosis sometimes associated with diffuse necrobiotic changes.

Dermatofibrosarcoma protuberans and giant cell fibroblastoma exhibit CD99 positivity.

According to most authors, dermatofibrosarcoma protuberans (DFSP) and giant cell fibroblastoma (GCF) represent the adult and juvenile forms, respectively, of the same disease entity, as evidenced by similar morphology, an identical chromosomal translocation, and CD34 positivity. It has been shown that DFSP and nuchal‐type fibroma (NTF) (which is also CD34‐positive) are related lesions, and that there might possibly be a continuum between the two. In addition, NTF exhibits CD99 positivity. It was therefore, hypothesized that both DFSP and GCF would show similar immunopositivity for CD99. Archives of pathology at several institutions were searched for DFSP and GCF tissue blocks. A total of 29 DFSP and 5 GCF were analyzed by immunohistochemistry for expression of CD99. Twenty‐three of 29 DFSP (79%) and 2 of 5 GCP (40%) expressed CD99. Comparison of CD99 and CD34 showed that the non‐tumoral periphery of DFSP was less probable to be CD99 positive, but this finding was not statistically significant.

A Review of Tumor Suppressor Genes in Cutaneous Neoplasms With Emphasis on Cell Cycle Regulators

Cells normally have five options. These include renewal or proliferation, terminal differentiation, quiescence, senescence, and apoptosis. Many factors interact with cell cycle regulators to direct the cells toward these different options. Tumor suppressor genes play a pivotal role in this process. Alterations in these genes may limit the options that cells have and thus play a significant role in the multistep process of carcinogenesis. We will focus on tumor suppressor genes and especially tumor suppressor genes that interact directly with the cell cycle proteins.

New or unusual dermatopathology tumors: A review

As experience is acquired, there is a constant evolution in both terminology and understanding of various relatively newly described tumors in the realm of dermatopathology. Several mesenchymal tumors of the lower extremity have undergone various changes in nomenclature, molecular discoveries, and histologic grading. Examples include hemosiderotic fibrohistiocytic lipomatous lesion/pleomorphic hyalinizing angiectatic tumor; superficial acral fibromyxoma; and myxoinflammatory fibroblastic sarcoma. Primary cutaneous myoepithelioma is also a relatively newly described entity for which grading and classification continue to evolve. Finally, even our understanding of the classic granular cell tumor has expanded to include a non‐neural variant. This article reviews the current nomenclature, emerging concepts, and differential diagnosis of these evolving entities.