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.

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.

Brooke-Spiegler syndrome: report of a case of multiple cylindromas and trichoepitheliomas.

We report a case of Brooke-Spiegler syndrome, a rare autosomal dominant disorder caused by mutations of the cylindromatosis gene (CYLD) tumor suppressor gene resulting in multiple cylindromas and trichoepitheliomas. Treatment of these patients can involve surgical excision, laser therapy, or topical applications of aspirin derivatives.

Metastatic myoepithelial carcinoma in a child.

Cutaneous myoepithelial tumors are rare entities, with few reported malignant variants in the literature. The majority of these tumors are reported in the head and neck region of the adult population, with few examples in the literature arising in young patients. We present a case of myoepithelial carcinoma in a 13-year-old girl, with documented metastatic disease. Reproducible predictors of malignant behavior have yet to be clarified.

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.

Lymph node biopsy results for desmoplastic malignant melanoma.

Desmoplastic malignant melanoma (DMM) is a rare variant of melanoma with distinct histopathologic and clinical features. Compared with other melanomas, the desmoplastic variant demonstrates a greater frequency of local recurrence and a proclivity for tracking along nerves, but it poses a lower risk of distant metastases. Elective lymph node dissection and sentinel lymph node biopsy (SLNB) are commonly used tools for determining prognosis in thick melanomas. The role of these procedures for DMM remains unclear. This study was designed to characterize DMM and determine the frequency of histologically positive lymph nodes in patients with DMM. This retrospective chart review included patients with DMM treated by Johns Hopkins Hospital (JHH) physicians between 1998 and 2003. Among the 28 patients included in the study, 18 patients had biopsies performed on lymph nodes (15 SLNBs and 3 radical neck dissections). One patient had a sentinel lymph node with histology positive for DMM. All others had negative results from histology and S100 stains. This study suggests that the frequency of positive SLNBs in DMM may be substantially lower than that of other melanomas.

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

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.

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.

Inflammatory dermatoses of the vulva.

Inflammatory, non-neoplastic epidermal alterations of the vulva can be correctly diagnosed using classification schemes applied to skin elsewhere on the body. A wide range of inflammatory disorders may occur on the vulva, and they may have a similar clinical presentation to HPV lesions. However, HPV is incurable and often is treated surgically. Accordingly, as inflammatory dermatoses commonly occur on the vulva and are often curable with topical therapy, an awareness of these entities and an ability to distinguish them from HPV are imperative.

Absence of V599E BRAF mutations in desmoplastic melanomas.

BACKGROUND: Desmoplastic melanoma is an uncommon variant of cutaneous melanoma that mimics soft tissue sarcoma both clinically and morphologically. An activating point mutation of the BRAF oncogene has been identified in a high proportion of conventional cutaneous melanomas, but its frequency in the desmoplastic subtype is not known. METHODS: The authors tested 12 desmoplastic melanoma specimens for the thymine (T)-->adenine (A) missense mutation at nucleotide 1796 of the BRAF gene using a newly developed assay that employs a novel primer extension method. They also tested 57 vertical growth phase cutaneous nondesmoplastic melanoma specimens. RESULTS: The 1796 T-->A mutation was detected in 23 of the 57 conventional cutaneous melanoma specimens but in none of the 12 desmoplastic melanoma specimens (40% vs. 0%; P=0.0006, Fisher exact 2-tailed test). CONCLUSIONS: The relative importance of BRAF mutational activation in melanocytic tumorigenesis clearly was not the same across the various subtypes of melanoma, even for melanomas of cutaneous origin that are associated with sun exposure. In contrast to conventional cutaneous melanomas, the desmoplastic variant frequently did not harbor an activating mutation of BRAF. Accordingly, patients with melanomas should not be collectively regarded as a uniform group as new therapeutic strategies are developed that target specific genetic alterations.

Collagenolytic (necrobiotic) granulomas: part II--the 'red' granulomas.

A collagenolytic or necrobiotic non-infectious granuloma is one in which a granulomatous infiltrate develops around a central area of altered collagen and elastic fibers. The altered fibers lose their distinct boundaries and exhibit new staining patterns, becoming either more basophilic or eosinophilic. Within the area of altered collagen, there may be deposition of acellular substances such as mucin (blue) or fibrin (red), or there may be neutrophils with nuclear dust (blue), eosinophils (red), or flame figures (red). These color distinctions can be used as a simple algorithm for the diagnosis of collagenolytic granulomas, i.e. 'blue' granulomas vs. 'red' granulomas. Eight diagnoses are included within these two groupings, which are discussed in this two-part article. In the previously published first part, the clinical presentation, pathogenesis and histologic features of the 'blue' collagenolytic granulomas were discussed. These are the lesions of granuloma annulare, Wegener's granulomatosis, and rheumatoid vasculitis. In this second half of the series, the 'red' collagenolytic granulomas are discussed; these are the lesions of necrobiosis lipoidica, necrobiotic xanthogranuloma, rheumatoid nodules, Churg-Strauss syndrome, and eosinophilic cellulitis (Well's Syndrome).

Collagenolytic (necrobiotic) granulomas: part 1--the "blue" granulomas.

A collagenolytic or necrobiotic non-infectious granuloma is one in which a granulomatous infiltrate develops around a central area of altered collagen and elastic fibers. The altered fibers lose their distinct boundaries and exhibit new staining patterns, becoming either more basophilic or eosinophilic. Within the area of altered collagen, there may be deposition of acellular substances such as mucin (blue) or fibrin (red), or there may be neutrophils with nuclear dust (blue), eosinophils (red), or flame figures (red). These color distinctions can be used as a simple algorithm for the diagnosis of collagenolytic granulomas, i.e. "blue" granulomas vs. "red" granulomas. Eight diagnoses are included within these two groupings, which are discussed in this two-part article. In this first part, the clinical presentation, pathogenesis, and histologic features of the "blue" collagenolytic granulomas are discussed. These are the lesions of granuloma annulare, Wegener's granulomatosis, and rheumatoid vasculitis. In the subsequent half of this two-part series, the "red" collagenolytic granulomas will be discussed; these are the lesions of necrobiosis lipoidica, necrobiotic xanthogranuloma, rheumatoid nodules, Churg-Strauss syndrome, and eosinophilic cellulitis (Well's syndrome).

An unusual case of calciphylaxis.

BACKGROUND: Cutaneous calciphylaxis is a rare disorder that occurs most frequently in patients with end-stage renal disease (ESRD), those on hemodialysis, and renal transplant recipients. It is frequently associated with hyperparathyroidism and a markedly elevated calcium-phosphate product, and it carries a high mortality rate. The usual clinical presentation is of painful, stellate necrosis of the thighs or buttocks, often in the setting of livedo reticularis. Death usually results from septicemia. OBJECTIVE: This report documents an unusual case of recurrent, self-limiting calciphylaxis in the setting of a patient with ESRD and discusses the clinical and pathologic features of this potentially very fatal disorder. METHODS AND RESULTS: A 52-year-old woman presented with a greater than one-year history of relapsing and remitting, exquisitely painful, necrotic, numular plaques on the abdomen, breast, and arm. This patient had a markedly elevated calcium-phosphate product and parathyroid hormone level. The diagnosis of calciphylaxis was made by wedge biopsy of the most recent plaque, revealing calcification of medium-sized subcutaneous vessels and lobular capillaries with associated epidermal necrosis. CONCLUSIONS: This case demonstrates an unusual clinical variant of calciphylaxis that presented without the characteristic stellate necrosis or livedo reticularis that normally marks this condition and spontaneous resolution without incurring septicemia. Regardless of morphology, calciphylaxis should be considered in the differential diagnosis of painful, necrotic lesions occurring in the setting of ESRD.

Basaloid follicular hamartoma with trichoblastomatous proliferations.

BACKGROUND: Basaloid follicular hamartomas (BFH) are rare, benign, adnexal lesions with diverse clinical presentations. Previous studies documented BFHs with fibroepithelioma of Pinkus-like proliferations, or proliferations that resemble trichoepitheliomas. OBJECTIVE: We report on a patient with linear, unilateral BFH and extensive trichoblastomatous proliferations involving the right arm, torso, and leg. An 18-year-old female presented with multiple, hyperkeratotic, linear nodules and plaques limited to her right side from the shoulder to the leg. The lesions had existed since birth and gradually increased over time. RESULTS: The lesions contained hyperpigmented, exophytic nodules with acanthosis, pseudoepitheliomatous hyperplasia, focally associated with hyperkeratosis, and squamous eddies. Some areas contained trichoepithelioma-like proliferations, or large nodules of basaloid cells with numerous cystic spaces, marked hyperpigmentation, and melanophages. The diagnosis was linear, unilateral BFH with an unusual trichoblastomatous component. CONCLUSION: While trichoblastomatous proliferations could occur in a BFH, to our knowledge this finding has not been reported.