S-100 protein expressing spindle cells in spindle cell lipoma: a diagnostic pitfall.

Spindle cell lipoma represents a distinct clinicopathological entity and is related to cellular angiofibroma and mammary-type myofibroblastoma. Spindle cell lipomas are composed of mature lipogenic cells and a variable number of CD34-positive spindle cells that show loss of retinoblastoma protein expression. Spindle cell lipomas occasionally express S-100 protein. We studied one case of purely dermal spindle cell lipoma and four cases of classical subcutaneous spindle cell lipoma arising in one female and four male patients (age ranged from 55 to 69 years). The neoplasms arose on the nose, the chin, the neck, the forehead and retroauricular, and all lesions had been marginally or incompletely excised. The studied cases showed classical histological and immunohistochemical features of spindle cell lipoma and, in addition, strong expression of S-100 protein by spindle-shaped tumour cells. S-100-expression in spindle cell lipoma may cause problems in the differential diagnosis with neural and melanocytic neoplasms and emphasizes the plasticity of the spindle cells in spindle cell lipoma.

Fumarate hydratase immunohistochemical staining may help to identify patients with multiple cutaneous and uterine leiomyomatosis (MCUL) and hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome.

AIMS: Multiple cutaneous and uterine leiomyomatosis (MCUL) also named as hereditary leiomyomatosis and renal cancer syndrome (HLRCC) is an autosomal dominant disorder caused by heterozygotic germline mutations in fumarate hydratase (FH) with incomplete penetrance and clinically challenging to diagnose. To test immunohistochemistry for FH as a potential marker for the detection of FH-deficiency. METHODS AND RESULTS: We have tested 42 smooth muscle neoplasms, 13 lesions of patients with suspicious or confirmed HLRCC, 20 sporadic piloleiomyomas, two angioleiomyomas and 7 leiomyosarcomas. FH staining grades from 1 to 3. Ten of the 13 lesions from the patients with HLRCC syndrome showed negative FH staining. Most sporadic piloleiomyomas presented grade 3 FH staining although five cases presented grade 1 FH staining. Sensitivity of FH staining in our series is 83.3% but specificity is 75%. CONCLUSIONS: This staining could indicate a high risk of HLRCC in most of the confirmed cases but it could also suggest the presence of a syndrome in up to 25% of sporadic cases. HLRCC syndrome should be rule out in FH negative piloleiomyomas after complete anamnesis if multiple lesions or positive familiar history is found.

Resolving lesions in human cutaneous leishmaniasis predominantly harbour chemokine receptor CXCR3-positive T helper 1/T cytotoxic type 1 cells.

BACKGROUND: Cutaneous leishmaniasis (CL) is an epidemic disease affecting millions of individuals worldwide. Treatment options have several side-effects and a vaccine does not exist at present. OBJECTIVES: To translate information about protection against CL from mice to man, we studied the local immune response in CL skin biopsies and correlated these findings with clinical information. METHODS: The frequency of inflammatory cells was determined in skin biopsies of 20 patients diagnosed with CL using immunohistochemistry. In addition, the nature of the resulting adaptive immune response was assessed by (double) immunostaining against CD4 and chemokine receptors CXCR3 (T helper 1, Th1)/CCR4 (Th2). RESULTS: All lesions contained CD4+ and CD8+ T cells, B cells and CD68+ macrophages. CD1a+ epidermal Langerhans cells were absent above the centre of the lesions, but normally distributed in the surrounding tissue. Mast cell and CD56+ natural killer cell numbers were not affected. Interestingly, CCR4+ Th2 cells were not detected in any of the 20 samples. In contrast, the number of infiltrating CXCR3+ cells was high and the majority of these were CD4+ or CD8+ indicating that they represent interferon-gamma-producing Th1/T cytotoxic type 1 (Tc1) cells. Finally, these findings did not correlate with clinical information about the country where the infection was acquired, or age or sex of the patients. However, lesions that had already persisted for more than 6 months contained fewer CXCR3+ CD4 and CD8 T cells than those that had persisted for less than 6 months. CONCLUSIONS: Our data on the inflammatory infiltrate of human CL lesions underline the relevance of findings obtained in experimental models. Both Th1 and Tc1 cells appear to be critical for healing in CL in mouse and man.

Clear-cell dermal duct tumour: another distinctive, previously underrecognized cutaneous adnexal neoplasm.

AIMS: To describe 13 examples of clear cell dermal duct tumour, a neoplasm previously underrecognized in the literature. METHODS AND RESULTS: Thirteen examples of a neoplasm that we have named clear-cell dermal duct tumour were studied histopathologically and immunohistochemically. Histopathologically, all lesions consisted of mostly dermal neoplasms mainly composed of multiple solid aggregations of clear cells involving the dermis. Although the neoplasms were mostly solid, ductal structures were identified in all cases. Immunohistochemically, neoplastic cells were immunoreactive for MNF116 and AE1/AE3 cytokeratins, but not for CAM5.2 or cytokeratin 7. Epithelial membrane antigen, carcinoembryonic antigen and glial cystic disease fibrillary protein 15 decorated the ductal structures, but neoplastic cells were negative. In contrast to some other clear cell neoplasms of the skin, which may be associated with diabetes mellitus, none of our cases of clear cell dermal duct tumour developed in a diabetic patient. CONCLUSIONS: We consider these neoplasms to be clear cell dermal duct tumours for the following reasons: (i) the neoplasms were mostly composed of multiple solid aggregations of epithelial clear cells; (ii) neoplastic aggregations mostly involved the dermis; (iii) in some cases, neoplastic aggregations of conventional poroid cells were intermingled with the aggregations of clear cells; (iv) ductal structures were identified within some neoplastic aggregations; (iv) small areas of necrosis en masse were seen in some neoplastic aggregations; and (v) the stroma of the neoplasm was scant.

[Hypopigmented melanocytic tumors with spindle cells. A review]. / Hypopigmentierte spindelzellige melanozytäre Tumoren : Eine Ubersicht.

Hypopigmented and achromatic melanocytic tumors with spindle cells represent a diagnostic challenge. Spindle cell nevi resemble neural tumors. Desmoplastic nevi imitate dermatofibromas. Hypopigmented and amelanotic blue nevi are variants of the common and cell-rich blue nevus with an enhanced difficulty to make a correct diagnosis due to the lack of pigment. All of the above benign melanocytic tumors with proliferations of hypopigmented spindle cells can more or less show aspects of desmoplastic melanoma. The differential diagnosis of these entities demands a combination of clinical and histological parameters as well as supporting immunostaining. Regarding desmoplastic melanoma, diagnoses frequently made are benign spindle cell neoplasms, scar or unspecific inflammatory condition. As the histological aspects can be so misleading, attention is necessary in order to make the correct diagnosis. Particular care must be taken to rule out desmoplastic melanoma in the case of spindle cell proliferations, a cicatricial or inflammatory process in the classical settings of face, volar skin, or mucous membranes. The spindle cell melanoma must be distinguished from other types of malignant spindle cell neoplasms, which can involve the skin. The differential diagnosis with such tumors is entrusted mainly to immunostaining.

[Extrafacial granuloma eosinophilicum]. / Extrafaziales Granuloma eosinophilicum.

Three patients with a rare extrafacial granuloma eosinophilicum are presented. Lesions were localized on the scalp, the upper back or the upper arm. Only one patient had a typical facial granuloma eosinophilicum at the same time. Diagnosis was established by histopathology. The histopathological findings vary with the age of the lesion. Early lesions are characterized by a vasculitis with many eosinophils separated by a Grenz zone from epidermis and follicular structures. With time the inflammation changes and hyalin fibrosis takes place.

Cutaneous clear cell myomelanocytic tumour: a new member of the growing family of perivascular epithelioid cell tumours (PEComas). Clinicopathological and immunohistochemical analysis of seven cases.

AIMS: To analyse seven cases of cutaneous myomelanocytic tumour histologically and immunohistochemically. Perivascular epithelioid cell tumours (so-called PEComas) are rare and recently delineated neoplasms occurring in the lung, kidney, pancreas, uterus, falciform ligament, vulva, heart, prostate and soft tissues. PEComas are characterized by a perivascular location of neoplastic cells showing a broad spectrum of epithelioid and spindled cells with clear, and granular pale eosinophilic cytoplasm, and a variable expression of melanocytic and muscle markers, whereas S100 protein and cytokeratins are usually absent. METHODS AND RESULTS: We report seven cases of cutaneous myomelanocytic tumour arising on the lower (six cases) and upper (one case) extremities of female adults (age range 30-66 years). In all cases an ill-defined dermal lesion with extension into subcutaneous tissue was noted. The neoplasms contained numerous blood vessels with a lace-like pattern and slightly thickened vessel walls, and were composed of perivascular epithelioid cells containing clear or focally granular pale eosinophilic cytoplasm and round vesicular nuclei with small, sometimes slightly enlarged nucleoli. Increased proliferative activity and tumour necrosis were not seen. Immunohistochemically, tumour cells stained positively for HMB-45, microphthalmia transcription factor, and NKIC3 in all cases, whereas perivascular expression of alpha-smooth muscle actin and focal positivity for desmin were noted in one case each only. Two out of four cases tested stained focally positive for calponin. No expression of S100 protein and pancytokeratin was present. Despite incomplete/marginal excision in three cases none of the neoplasms has recurred locally so far. CONCLUSIONS: With the presented series of cutaneous myomelanocytic tumours the clinicopathological spectrum of PEComas is expanded.