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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. Lewin MR, Montgomery EA, Barrett TL. New or unusual dermatopathology tumors: a review.

Keywords: Cryptococcus; histopathologic pitfall; morphologic mimicker; neutrophilic dermatosis; Sweet's syndrome

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.

Progressive mucinous histiocytosis is a rare, benign, non-Langerhans' cell histiocytosis limited to the skin. Ten cases – all women – in four families and one sporadic case have been described in the literature. The disorder usually begins in childhood and progresses slowly. We report two sporadic cases of adult-onset progressive mucinous histiocytosis in unrelated African-American women, aged 48 and 55 years, respectively, who developed red-brown and flesh-coloured, asymptomatic papules on the face, the arms and the legs without truncal, mucosal or visceral involvement. The lesions showed no spontaneous regression. Both patients lacked associated systemic symptoms, including polyuria, polydipsia or seizures. There was no underlying hyperlipidaemia, paraproteinaemia or lymphoproliferative disease. No family history of similar lesions could be identified. Light microscopy revealed dermal proliferation of spindle-shaped histiocytes with abundant mucin deposition. Electron microscopy demonstrated a high number of myelin figures or zebra bodies in the cytoplasm of histiocytes. On immunohistochemistry, positive staining with macrophage markers – CD68, HAM56 and lysozyme – and factor XIIIa, a transglutaminase present in dermal dendrocytes, and negative staining with Langerhans' cell markers – CD1a and S100 – and CD34, a marker present in dermal dendritic cells derived from uncommitted mesenchymal cells, were observed.

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).

Two unusual acquired polypoid skin lesions exhibited prominent histological atypia, but were biologically benign. Both patients were elderly females. The lesions clinically mimicked fibroepithelial polyp or nevus lipomatosus. Both had been present for about 20 years. One lesion was located on the back, the other on the posterior thigh. Each lesion exhibited dilated, hyalinized vessels in the dermis with focal fibrin deposits, myxoid stroma, and a population of bizarre, pleomorphic spindle to stellate cells, some of which were multinucleated. Occasional atypical mitoses were present. One lesion had abundant admixed fat. Immunohistochemical staining was strongly positive only for vimentin. The lesions share features with degenerating angiofibroma and vaginal pseudosarcomatous polyp. As in these lesions, the atypia is most probably reactive and degenerative.

Majocchi's granuloma (nodular granulomatous perifolliculitis) is a well recognized but uncommon infection of dermal and subcutaneous tissue by fungal organisms (dermatophytes) usually limited to the superficial epidermis. The organism usually associated with Majocchi's granuloma is Trichophyton rubrum; however, other dermatophytes including T. mentagrophytes (variety granulosum), T. epilans, T. violaceum, M. audouinii, M. gypseum, M. ferrugineum, and M. canis may be the causative agent. A review of 17 cases revealed not only the variety of possible organisms but also a marked variation from the usual hyphal forms. The morphologic variations including yeast forms, bizarre hyphae, mucinous coatings, and the Splendore-Hoeppeli phenomenon may be factors which allow the dermatophytes to persist and grow in an abnormal location. Also, there is evidence that Majocchi's granuloma may occur in two distinct groups of patients.

A 59-year-old man presented with a 6-year history of a 2-cm tender nodule on his left lateral elbow. Excisional biopsy led to the diagnosis of angioleiomyoma. However, unlike typical angioleiomyoma which demonstrate extravascular extension, this lesion demonstrated purely intravascular growth.

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.

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.

Background: 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. Materials and methods: A retrospective analysis of all cases of AMFS seen in the past 4 years from the Stanford University Laboratory of Surgical Pathology and collaborating institutions was performed. We sought to better characterize the clinicopathologic characteristics of this rare tumor. Immunohistochemical stains, including CD34, epithelial membrane antigen (EMA), epidermal growth factor receptor (EGFR), CD117, CD163, Ki67 and p53, were also performed. Results: Eighteen cases were analyzed, and clinical information was available on 13 of them. The mean age at diagnosis was 48 years old, 10/13 (77%) occurred on the distal extremities and diameter of the lesions ranged from 1.0 to 10.0 cm. Treatment included wide local or radical excision and local recurrences were not reported. Many of the lesions were multinodular. Histologic characteristics included the presence of fibrosclerotic and myxoid stroma, sheets of spindled to round epithelioid cells, Reed-Sternberg or virocyte-like cells, lipoblast-like cells and rare mitotic figures. In most cases, CD34, EGFR and CD163 were diffusely positive. EMA and CD117 were weakly positive in some cases. Ki67 labeled < 10% of cells, and staining with P53 was variable. Conclusions: Because AMFS may be mistaken for lymphoma, infection or tumors with higher metastatic potential, correct diagnosis is important to avoid unnecessary procedures and allow for proper clinical management. EGFR positivity suggests possible therapeutic use in aggressive cases.

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.

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.

Ossifying fibromyxoid tumor of soft parts is a recently described, rare but morphologically distinctive tumor of soft tissue, including subcutaneous soft tissue. We report a case of ossifying fibromyxoid tumor of soft parts which occurred in the subcutaneous tissue of a 68-year-old male, and review the clinical, histologic, and immunohistologic features of this tumor. Ossifying fibromyxoid tumor of soft parts tends to occur in the subcutaneous tissue and have been reported from the head and neck, upper and lower extremities, and trunk. Immunohistologic studies have supported a neural origin. While considered benign, local recurrence after excision is common and these tumors should be excised with clear margins to prevent recurrence.

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).

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).

We report a case of a palisaded angioleiomyoma, a histopathologic variant of angioleiomyoma with prominent Verocay body formation.A healthy 31-year-old male requested removal of a subcutaneous nodule on the back of his head. The striking Verocay-like body formation of this tumor led to an initial frozen section diagnosis of neurilemoma. On hematoxylin and eosin staining, areas consistent with an angioleiomyoma were found as well. Immunohistochemistry gave positive reactions for actin and desmin, but was negative for S-100.To our knowledge this morphologic pattern in an angioleiomyoma has not been previously described. Palisaded angioleiomyoma should be added to the ever-expanding list of tumors that demonstrate nuclear palisades.

A 65-year-old woman presented with multiple subungal lesions for the past forty years. These were associated with increasing pain with growth, relieved only by destruction. They were treated as subungal warts by electrocautery and surgical excision. A biopsy of one lesion was interpreted as squamous cell carcinoma with subsequent partial amputation of the affected digit. She continued to develop painful subungal growths involving all her fingers, requiring repeated surgeries. On physical examination, subungal tumors associated with hyperkeratosis and erythema of the nail bed were found on the right thumb and ring finger. Subungal hyperkeratosis involved all other fingers. On histological examination, there was marked dyskeratosis with features of subungal keratoacanthoma or squamous cell carcinoma. This patient has a history of incontinentia pigmenti (IP) since childhood and she has three daughters with IP. We report a case of painful subungal dyskeratotic tumors in IP, considered as keratoacanthomas by some, as they grow rapidly and may demonstrate spontaneous resolution, albeit rarely. The distinguishing features of subungal tumor in IP are its occurrence in young women with multiple lesions and signs of IP, and its tendency to erupt persistently over a course of several years.

Background: Sebaceous tumors are adnexal tumors with usually low-gradebehavior. The distinction between sebaceous adenomas and carcinomas, especially on small biopsies from sensitive sites (i.e., ocular), may bedifficult. We compared the expression of various oncogenic andprognostic markers by immunohistochemistry in order to distinguishbenign from malignant sebaceous tumors.Design: 10 sebaceous adenomas, 10 sebaceous carcinomas, and 5 cases ofsebaceous hyperplasia, were studied with antibodies directed againstKi-67 (mib-1), bcl-2, p53, p21, p27, c-erb2 (Her-2/neu), CD117 (c-kit), cyclin D1, MDM2, and CD99 (mic2).Results: We found that sebaceous carcinomas differed from sebaceousadenomas by having increased staining for p53 (50% vs 11%) and mib-1(average 1.8+ vs. 1.0+), and significantly reduced levels of bcl-2 (7%vs 62%) and p21 (16% vs 34%).The other markers did not differ significantly, although there was atrend towards more Her-2/neu staining in the carcinomas. No cases showedany c-kit staining.Conclusions: We have shown that several markers, including mib-1, p53, p21, and bcl-2, are expressed at significantly different levels insebaceous carcinomas versus adenomas, and may be of use indiagnostically challenging cases. Whether or not any of these markerswill prove useful in predicting prognosis remains controversial.

Sclerotic fibroma is an uncommon benign neoplasm of the skin which may occur sporadically in a solitary form or as multiple lesions as a component of Cowden’s disease. Sclerotic fibromas have a distinctive histologic appearance characterized by well-circumscribed, hypocellular dermal nodules of thick, hyalinized collagen bundles arranged in a whorled or storiform pattern with prominent clefts. We present the case of a 52-year-old HIV-positive, African-American female who presented with multiple firm flesh-colored nodules of several year duration on bilateral lower extremities. Biopsies of the lesions demonstrated characteristic features of sclerotic fibroma. Detailed physical examination and extensive systemic work-up failed to reveal evidence of Cowden’s disease. To our knowledge, multiple sclerotic fibromas have not been reported in the absence of Cowden’s disease, and this is the first reported case of multiple sclerotic fibromas occurring in an HIV-positive patient without evidence of Cowden’s disease.

Progressive mucinous histiocytosis is a rare, benign, non-Langerhans cell histiocytosis limited to the skin. A total of ten cases, all women, in four families, and one sporadic case have been described in the English literature. The disorder usually begins in childhood and progresses slowly. We report two sporadic cases of adult-onset progressive mucinous histiocytosis in unrelated African American women, age 48 and 55 years old respectively, who developed red-brown and flesh-colored, asymptomatic papules on the face, arms and legs without truncal, mucosal or visceral involvement. The lesions show no spontaneous regression. Both patients lack associated systemic symptoms including polyuria, polydipsia or seizures. There is no underlying hyperlipidemia, paraproteinemia or lymphoproliferative disease. No family history of similar lesions can be identified. Light microscopy reveals dermal proliferation of spindle-shaped histiocytes with abundant mucin deposition. Electron microscopy demonstrates a high number of myelin-figures or zebra bodies in the cytoplasm of histiocytes. On immunohistochemistry, positive staining with macrophage markers CD68, HAM56 and lysozyme, and Factor XIIIa, a transglutaminase present in dermal dendrocytes, and negative staining with Langerhans cell markers CD1a and S100, and CD34, a marker present in dermal dendritic cells derived from uncommitted mesenchymal cells, are observed.