Search

A large percentage of patients with HIV/AIDS will develop dermatological complications. Consequently, all practising clinicians and pathologists in regions with a high prevalence of HIV/AIDS must be familiar with the diverse cutaneous manifestations of the disease. This paper highlights the fact that biopsy material in this clinical context may occasionally reveal more than one pathological process. The potential spectrum includes two or more infections in a single skin biopsy (e.g., herpes simplex and cytomegalovirus infection), neoplastic lesions containing infective organisms (Kaposi sarcoma (KS) and cryptococcosis), dermatoses in association with neoplastic lesions (e.g., KS and interface dermatitis), or more than one dermatosis in a given specimen (e.g., papulopruritic eruption and nodular prurigo). Rare biopsies may even demonstrate triple pathology. The importance of careful examination of skin biopsies in this clinical context is emphasised. Failure to recognise an undiagnosed concomitant opportunistic infective pathogen could have potentially disastrous consequences for the patient.

Background: Kaposi sarcoma (KS) is a low-grade angioproliferative neoplasm derived from lymphatic endothelium. Lesions progress from early patch stage into plaques that ultimately form tumor nodules. Several histological variants of KS have been described. The aim of this study is to describe 5 new histopathologic variants of cutaneous KS. Method: Skin biopsy material submitted to a South African dermatopathology practice diagnostic of KS was reviewed. Formalin-fixed, paraffin-embedded tissue was routinely processed and stained with hematoxylin and eosin. Confirmatory immunohistochemical stains included CD31 and latent nuclear antigen-1 (human herpesvirus 8). Results: All biopsies were procured from HIV-positive patients with a clinical diagnosis of cutaneous KS tumor. Five distinct histologic KS variants, not previously well characterized in the literature, were identified including glomeruloid KS, telangiectatic KS, ecchymotic KS, KS with myoid nodules, and pigmented KS. Tumor cells in all of these variants were immunoreactive for CD31 and latent nuclear antigen-1. Conclusions: These unique cases highlight the ability of KS to exhibit variable histomorphology. Their clinical significance requires further study. Dermatopathologists should be aware of these newly described variants to avoid the potential for their misdiagnosis.

Summary Exogenous (cosmetic) ochronosis is caused by the long term use of skin-lightening creams containing hydroquinone. Three cases of systemic sarcoidosis with cutaneous sarcoidal granulomas, which developed on ochronotic skin were last described by Jacyk in 1995. Dogliotti and Leibowitz previously reported cases of granulomatous ochronosis with sarcoid-like histological changes but with no associated systemic sarcoidosis. We report two additional cases of cutaneous sarcoidal granulomas, which developed on a background of cosmetic ochronosis in patients recently diagnosed with systemic sarcoidosis.

The authors present a series of 24 malignant neoplasms arising in preexisting benign spiradenoma (20), cylindroma (2), and spiradenocylindroma (2). Nineteen patients (12 females, 7 males; age range, 41 to 92 y) had a solitary neoplasm (size range, 2.2 to 17.5 cm; median 4 cm), whereas the remaining 5 (4 females, 1 male; age range, 66 to 72 y) manifested clinical features of Brooke-Spiegler syndrome (BSS), an autosomal dominantly inherited disease characterized by widespread, small, benign neoplasms on which background larger malignant lesions appeared. Microscopically, all cases showed the residuum of a preexisting benign neoplasm. The malignant components of the lesions were variable and could be classified into 4 main patterns, occurring alone or in combination: 1) salivary gland type basal cell adenocarcinoma-like pattern, low-grade (BCAC-LG); 2) salivary gland type basal cell adenocarcinoma-like pattern, high-grade (BCAC-HG); 3) invasive adenocarcinoma, not otherwise specified (IAC-NOS); and 4) sarcomatoid (metaplastic) carcinoma. In 1 case of IAC-NOS, an in situ adenocarcinoma was also found, presumed to have evolved from an adjacent adenomatous and atypical adenomatous component. Cases harboring a sarcomatoid carcinoma featured a malignant epithelial component composed of varying combinations of BCAC-HG, BCAC-LG, IAC-NOS, or squamous cell carcinoma, whereas the sarcomatoid component appeared as either a pleomorphic or spindle-cell sarcoma. Additionally, in 2 cases there were foci of heterologous chondrosarcomatous differentiation and in 1 case there was rhabomyosarcomatous differentiation. Of the 21 patients with available follow-up (range, 3 mo-15 y; average 4.8 y; median 3.5 y), 10 were without evidence of disease, 1 was alive with metastatic disease, 1 was alive with BSS, 3 developed local recurrences, 4 had died of disease, and 2 were dead of other causes. The histologic pattern of the malignant neoplasm correlated to some extent with the clinical course. BCAC-LG neoplasms showed a less aggressive course, with local recurrences but no distant metastases, whereas the BCAC-HG neoplasms typically followed a highly aggressive course resulting in the death 3 of 6 patients with BCAC-HG. Patients with sarcomatoid carcinoma had a relatively good survival. Molecular genetic investigations revealed no mutations in the CYLD gene in the 4 sporadic cases investigated. One patient with BSS revealed a novel missense germline mutation in exon 14 (c. 1961T>A, p. V654E), whereas a living descendant of another deceased patient demonstrated a recurrent nonsense germline mutation in exon 20 (c. 2806C>T, p. R936X). Given the morphologic diversity and complexity of the neoplasms in question, we propose using a more specific terminology with the precise description of the neoplasm components, rather than generic and less informative terms such as "spiradenocarcinoma" or "carcinoma ex cylindroma."

Aim:To determine if human papillomaviruses (HPVs) play a role in the histogenesis of adenosarcomas of the uterine cervix.Methods:Nine archival cases of primary cervical adenosarcoma were studied. The HPV status of the nine histologically proven tumours was investigated by non-isotopic in situ hybridisation (NISH) and PCR. NISH was performed using digoxigenin labelled probes to HPV types 6, 11, 16, 18, 31 and 33. PCR used GP5+/GP6+ primers to the HPV L1 gene.Results:Neither the benign epithelial components nor the malignant stromal components of the 9 neoplasms harboured nuclear NISH signals for the HPV types investigated. Amplimers of the HPV L1 gene were not detected by PCR in any of the tumours studied.Conclusion:HPVs do not appear to play an aetiological role in cervical adenosarcomas. This suggests that a different histogenetic pathway for this rare tumour type must exist.

Lymphoepithelial carcinoma (LEC) is a rare category of malignant neoplasms that share morphologic features with undifferentiated nasopharyngeal carcinoma, which can be regarded as the prototype Epstein-Barr virus (EBV)–positive epithelial neoplasm. A similar association with EBV is emerging for LEC of the oral cavity, which appears to be strongly influenced by the ethnic origin of the patient. A rare case of primary LEC of the lower lip in a 73-year-old Caucasian man is described. The tumor showed a striking microscopic resemblance to undifferentiated nasopharyngeal carcinoma (lymphoepithelioma) with features of a syncytial growth pattern, large undifferentiated tumor cells with vesicular nuclei, prominent eosinophilic nucleoli, and a dense intratumoral lymphocytic infiltrate. There was, however, no evidence of EBV infection of the tumor cells by immunohistochemistry and polymerase chain reaction, suggesting that EBV probably does not play a role in the pathogenesis of LEC of the lip in Caucasian patients.

A systematic analysis of the entire spectrum of various forms of differentiation and metaplastic epiphenomena in cutaneous apocrine mixed tumor (AMT) has never been performed.The purpose of our study was to study a large number of cutaneous mixed tumors so as to fully characterize the entire spectrum of differentiations and metaplastic changes that may occur in the epithelial, myoepithelial, and stromal components of AMT.This article reports a light-microscopic study of 244 cases of cutaneous AMT, complemented by a literature review.All types of differentiation along the lines of the folliculosebaceous-apocrine unit can be seen in AMT. The spectrum of metaplastic changes in the epithelial components includes squamous metaplasia, mucinous metaplasia, oxyphilic metaplasia, clear cell change, columnar metaplasia, hobnail metaplasia, and cytoplasmic vacuolization. The following changes in the myoepithelial component were documented: clear cell change, hyaline cells, plasmacytoid cells, spindling, and collagenous spherulosis. Stromal alterations included chondroid metaplasia, osseous metaplasia, and adipose metaplasia.This study utilizes tissue specimens that mainly came as consultations; therefore some inherent selection bias exists.AMT displays a wide range of differentiation and metaplastic changes in its epithelial, myoepithelial, and stromal components. These phenomena are not mutually exclusive. When unduly prominent, they may present diagnostic pitfalls. Our findings corroborate those of previous publications, stressing the remarkable diversity of differentiation and metaplasias that may be found in cutaneous AMT. We propose that the most appropriate name for these lesions is "mixed tumor of the folliculosebaceous-apocrine complex."

Mutations in beta-catenin are present in benign pilomatrixomas. beta-catenin is a downstream effector in the WNT-signalling pathway, acting as a signal for differentiation and proliferation. Mutations in CTNNB1, the gene encoding beta-catenin, are present in a wide variety of benign and malignant neoplasms. We examined beta-catenin in a series of pilomatrix carcinomas (15 cases) by using immunohistochemistry and DNA sequencing of exon 3 from CTNNB1, and compared these to a series of benign pilomatrixomas (13 cases). All 11 pilomatrix carcinomas available for examination showed nuclear localization of beta-catenin and mutations in exon 3 similar to those demonstrated in benign pilomatrixomas. Two of 11 pilomatrix carcinomas showed significant nuclear accumulation of p53, whereas this was absent in all 13 benign pilomatrixomas. Expression of nuclear cyclin D1 was similar in both benign pilomatrixomas and pilomatrix carcinomas. Clinical follow-up from the 15 malignant cases reported in this study and by others indicates that wide excision offers superior control of local recurrence, compared to simple excision. Immunohistochemical and molecular analysis of beta-catenin reveals that both pilomatrix carcinomas and benign pilomatrixomas harbour mutations in beta-catenin. This implies a common initial pathogenesis and is compatible with the proposition that pilomatrix carcinomas may at least on occasion arise from their benign counterparts.

Ganglioneuroblastic differentiation in malignant melanomas is an exceedingly rare event. Although there has been a single report of this occurrence in a metastatic melanoma, divergent ganglioneuroblastic differentiation has not been documented previously in a primary cutaneous lesion of melanoma. The present report describes an unusual case of invasive melanoma arising on the lower leg of a 61-year-old woman. The 16.9-mm thick tumor showed extensive ganglioneuroblastic differentiation, which was confirmed both immunohistochemically and ultrastructurally. Although the prognostic significance of this observation remains uncertain, the unique case reaffirms the potential morphologic diversity of melanomas and suggests a shared histogenetic origin from a common neural crest derivative.

Rosai-Dorfman disease (RDD) is a rare but distinctive clinicopathologic entity of unknown etiology affecting lymph nodes as well as extranodal sites. Although cutaneous involvement in RDD is common, purely cutaneous disease is rare and not well documented. We report 22 patients with cutaneous and superficial subcutaneous RDD. The lesions presented as papules and nodules, often with discoloration (9/22) and frequent multifocality (13/22), without predilection for a specific site of the body. Age distribution was wide and ranged from 15 to 68 years, with a median of 43.5 years. Of the 17 patients for whom information on racial background was available, 7 were Asian, 8 were white, and 2 were black, with a marked female predominance (2:1). The lesions resolved in 6 of 13 patients for whom follow-up data were available, regardless of the treatment given. Lesions persisted or recurred in 7 patients. Histologically, the lesions are invariably characterized by a proliferation of polygonal S100-positive histiocytes showing emperipolesis and a mixed inflammatory infiltrate. This study characterizes the histologic spectrum of cutaneous RDD in regard to variation in the numbers of typical S100-positive histiocytes and emperipolesis, variation in the quality and quantity of the inflammatory response, and the degree of stromal fibrosis, which resulted in a strikingly storiform growth pattern in six lesions and a lobulated pattern in two lesions. Whereas the clinical as well as histologic appearance of the cutaneous and subcutaneous lesions in the purely extranodal forms of RDD is indistinguishable from that of systemic RDD, this study emphasizes that purely cutaneous RDD is a distinct clinical entity in regard to its epidemiology and remains localized to the skin even with long-term follow-up. Patients with purely cutaneous RDD are of an older age at onset of disease (median = 43.5 years), with a reversed male/female ratio. There are no significant systemic extracutaneous or serologic manifestations. Whereas systemic RDD is commonly seen in blacks and only rarely reported in Orientals, the majority of the patients in this series with purely cutaneous RDD are Asians and whites.

"Basaloid carcinoma" of the uterine cervix is a neglected and underrecognized entity that is not included in the current World Health Organization's classification of cervical neoplasms. Historically, this term has been used synonymously with adenoid basal carcinoma (ABC). In recent years, however, it has become evident that a broad spectrum of basaloid cervical neoplasms exist. At one end of the spectrum are low-grade lesions, such as ABC; at the opposite end of the spectrum there are aggressive tumors, including adenoid cystic carcinoma, large cell neuroendocrine carcinoma, and basaloid squamous carcinoma. The purpose of this review is to revisit the concept of basaloid tumors of the cervix, to define their morphologic spectrum, and to address potential pitfalls in the differential diagnosis. To avoid confusion, use of the term "basaloid squamous cell carcinoma" is recommended when diagnosing a cervical tumor with histologic features of "basaloid carcinoma," as seen in other anatomic sites. A proposed classification of basaloid tumors of the uterine cervix is also presented.

Five previous cases of extrarenal Wilms tumor (EWT) occurring in the uterus have been reported. The oldest patient was 22 years. We report a case of uterine EWT occurring in a 42-year-old woman. Histologically, there was typical triphasic differentiation, including epithelial, blastemal, and mesenchymal elements. The important differential diagnosis in this age group, the malignant mixed mullerian tumor, is excluded by the absence of glomeruloid structures and primitive tubules. The exact histogenesis of EWT is unknown but most likely relates to the presence of nephrogenic rests occurring in the female genital tract.

Carcinosarcomas (malignant Mullerian mixed tumors [MMMTs]) of the uterine cervix are rare neoplasms. This report describes the morphology, immunohistochemical profiles, and human papillomavirus (HPV) status of eight cervical MMMTs. Patients' ages ranged from 32 to 93 years (mean, 61 years). Seven cases showed in situ squamous cell carcinoma (SCC). The invasive epithelial component (EC) was composed of combined adenoid basal carcinoma, basaloid SCC, and adenoid cystic carcinoma (ACC) in two cases. Keratinizing SCC, large cell nonkeratinizing SCC, undifferentiated carcinoma, and basaloid SCC predominated in the remaining tumors, one of which had admixed ACC. The sarcomatous component (SC) was homologous and spindled with admixed myxoid areas in three lesions. The ECs and SCs in six MMMTs showed dual immunostaining with epithelial membrane antigen and the pan-keratin marker, MNF116. The SC was vimentin-positive in seven cases. Five tumors had a vimentin-positive EC. The SC was positive for muscle specific actin and/or smooth muscle actin in seven lesions, of which four were desmin-positive. Polymerase chain reaction (PCR) using GP5+/GP6+ L1 consensus primers detected HPV DNA in all eight cases. Nonisotopic in situ hybridization with digoxigenin-labeled probes to HPV types 6, 11, 16, 18, 31 and 33 demonstrated integrated HPV 16 in three cases, not only in the EC, but also in nuclei of the SC. This is the first study to implicate HPV in the evolution of cervical MMMTs. The above observations lend support to a metaplastic theory of histogenesis.

A 52-year-old woman underwent a hysterectomy for a large tumor of the uterine cervix that was shown to be a xanthomatous leiomyosarcoma (LMS) by histologic examination, the first example of this tumor in this site. Two previous similar tumors have been reported in the uterine corpus.

This review provides a comprehensive overview of the broad clinicopathologic spectrum of cutaneous Kaposi sarcoma (KS) lesions. Variants discussed include: usual KS lesions associated with disease progression (i.e. patch, plaque and nodular stage); morphologic subtypes alluded to in the older literature such as anaplastic and telangiectatic KS, as well as several lymphedematous variants; and numerous recently described variants including hyperkeratotic, keloidal, micronodular, pyogenic granuloma-like, ecchymotic, and intravascular KS. Involuting lesions as a result of treatment related regression are also presented.