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Friedrichshafen, Germany

Gaitanis G.,University of Ioannina | Magiatis P.,National and Kapodistrian University of Athens | Hantschke M.,Dermatopathologie Friedrichshafen | Bassukas I.D.,University of Ioannina | Velegraki A.,National and Kapodistrian University of Athens
Clinical Microbiology Reviews | Year: 2012

In the last 15 years, the genus Malassezia has been a topic of intense basic research on taxonomy, physiology, biochemistry, ecology, immunology, and metabolomics. Currently, the genus encompasses 14 species. The 1996 revision of the genus resulted in seven accepted taxa: M. furfur, M. pachydermatis, M. sympodialis, M. globosa, M. obtusa, M. restricta, and M. slooffiae. In the last decade, seven new taxa isolated from healthy and lesional human and animal skin have been accepted: M. dermatis, M. japonica, M. yamatoensis, M. nana, M. caprae, M. equina, and M. cuniculi. However, forthcoming multidisciplinary research is expected to show the etiopathological relationships between these new species and skin diseases. Hitherto, basic and clinical research has established etiological links between Malassezia yeasts, pityriasis versicolor, and sepsis of neonates and immunocompromised individuals. Their role in aggravating seborrheic dermatitis, dandruff, folliculitis, and onychomycosis, though often supported by histopathological evidence and favorable antifungal therapeutic outcomes, remains under investigation. A close association between skin and Malassezia IgE binding allergens in atopic eczema has been shown, while laboratory data support a role in psoriasis exacerbations. Finally, metabolomic research resulted in the proposal of a hypothesis on the contribution of Malassezia-synthesized aryl hydrocarbon receptor (AhR) ligands to basal cell carcinoma through UV radiation-induced carcinogenesis. © 2012, American Society for Microbiology. All Rights Reserved.

Requena L.,Autonomous University of Madrid | Kutzner H.,Dermatopathologie Friedrichshafen
Seminars in Diagnostic Pathology | Year: 2013

Hemangioendothelioma is the term used to name those vascular neoplasms that show a borderline biological behavior, intermediate between entirely benign hemangiomas and highly malignant angiosarcomas. Although originally spindle cell hemangioendothelioma was proposed as a specific clinicopathologic variant of hemangioendothelioma, currently, it is considered as an entirely benign lesion, and thus, the name spindle cell hemangioma seems to be the most accurate for this lesion. Authentic hemangioendotheliomas involving the skin and soft tissues include papillary intralymphatic angioendothelioma (also known as Dabska tumor), retiform hemangioendothelioma, kaposiform hemangioendothelioma, epithelioid hemangioendothelioma, pseudomyogenic hemangioendothelioma (also known as epithelioid sarcoma-like hemangioendothelioma), and composite hemangioendothelioma. Each of these neoplasms exhibit characteristic histopathologic features. The most characteristic finding of papillary intralymphatic hemangioendothelioma consists of papillary tufts, with a central hyaline core lined by hobnail-like endothelial cells protruding into the lumina. Retiform hemangioendothelioma is an infiltrative neoplasm composed of elongated arborizing vessels, arranged in an anastomosing pattern that resembles that of the rete testis, and lined by a single layer of hobnail-like endothelial cells that protrude within the narrow lumina. Kaposiform hemangioendothelioma is composed of several solid poorly circumscribed nodules, and each nodule is composed of a mixture of small capillaries and solid lobules of endothelial cells arranged in a glomeruloid pattern. A frequent finding consists of the presence of areas of lymphangiomatosis adjacent to the solid nodules. Epithelioid hemangioendothelioma is composed of cords, strands, and solid aggregates of round, oval, and polygonal cells, with abundant pale eosinophilic cytoplasm, vesicular nuclei, and inconspicuous nucleoli, embedded in a fibromyxoid or sclerotic stroma. Many neoplastic cells exhibit prominent cytoplasmic vacuolization as an expression of primitive vascular differentiation. Pseudomyogenic hemangioendothelioma is a poorly circumscribed, fascicular lesion with infiltrative borders composed of round or oval neoplastic cells, with vesicular nuclei and inconspicuous nucleoli, and ample homogeneous eosinophilic cytoplasm, giving thema rhabdomyoblastic appearance. Finally, composite hemangioendothelioma is the term used to name locally aggressive vascular neoplasms of low-grade malignancy showing varying combinations of benign, lowgrade malignant, and high-grade malignant vascular components. From the immunohistochemical point of view, proliferating cells of all hemangioendotheliomas express a lymphatic endothelial cell immunophenotype. Most hemangioendotheliomas are low-grade vascular neoplasms, with a tendency to recur locally and a low metastatic potential, mostly to regional lymph nodes. Epithelioid hemangioendothelioma, especially large lesions and those located in deep soft tissues, seems to have a more aggressive biological behavior. © 2013 Elsevier Inc.

Busam K.J.,Sloan Kettering Cancer Center | Kutzner H.,Dermatopathologie Friedrichshafen | Cerroni L.,Medical University of Graz | Wiesner T.,Sloan Kettering Cancer Center | Wiesner T.,Medical University of Graz
American Journal of Surgical Pathology | Year: 2014

Spitz tumors represent a group of melanocytic neoplasms that typically affect young individuals. Microscopically, the lesions are composed of cytologically distinct spindle and epithelioid melanocytes, with a range in the architectural display or the cells, their nuclear features, and secondary epidermal or stromal changes. Recently, kinase fusions have been documented in a subset of Spitz tumors, but there is limited information on the clinical and pathologic features associated with those lesions. Here, we report a series of 17 patients (9 male, 8 female) with spitzoid neoplasms showing ALK fusions (5 Spitz nevi and 12 atypical Spitz tumors). The patients' ages ranged from 2 years to 35 years (mean=17 y; median=16 y). Most lesions were located on the lower extremities and presented clinically as polypoid nodules. All tumors were compound melanocytic proliferations with a predominant intradermal growth. Tumor thickness ranged from 1.1 to 6 mm (mean=2.9 mm; median=2.5 mm). The most characteristic histopathologic feature of the tumors (seen in all but 2 lesions) was a plexiform dermal growth of intersecting fascicles of fusiform melanocytes. All but 2 tumors were amelanotic. All tumors were strongly immunoreactive for ALK. The ALK rearrangements were confirmed in all cases by fluorescence in situ hybridization (FISH), and the fusion partner was determined by quantitative polymerase chain reaction as TPM3 (tropomyosin 3) in 11 cases and DCTN1 (dynactin 1) in 6 cases. None of the 8 tumors that were analyzed by FISH for copy number changes of 6p, 6q, 9p, or 11q met criteria for melanoma. Two patients underwent a sentinel lymph node biopsy, and in both cases melanocyte nests were found in the subcapsular sinus of the node. Array comparative genomic hybridization of these 2 tumors revealed no chromosomal gains or losses. In conclusion, our study revealed that Spitz nevi/tumors with ALK rearrangement show a characteristic plexiform morphology and that ALK immunohistochemistry and FISH enable the accurate identification of this morphologic and genetic distinct subset of spitzoid neoplasms. Copyright © 2014 by Lippincott Williams & Wilkins.

Requena L.,Autonomous University of Madrid | Cerroni L.,Medical University of Graz | Kutzner H.,Dermatopathologie Friedrichshafen
Dermatologic Clinics | Year: 2012

A large number of foreign substances may penetrate the skin for both voluntary and involuntary reasons. The voluntary group includes the particulate materials used in tattoos and cosmetic fillers, whereas the involuntary group is almost always caused by accidental inclusion of external substances secondary to cutaneous trauma. This article focuses on the histopathologic findings seen in cutaneous reactions to exogenous agents, with special emphasis on the microscopic morphology of the external particles in recognizing specifically the involved substance (something that is becoming increasingly important in the event of litigation). © 2012 Elsevier Inc.

Sellheyer K.,Cleveland Clinic | Nelson P.,Nelson Dermatopathology Associates | Kutzner H.,Dermatopathologie Friedrichshafen | Patel R.M.,University of Michigan
Journal of Cutaneous Pathology | Year: 2013

Background Microcystic adnexal carcinoma (MAC), desmoplastic trichoepithelioma (DTE) and morpheaform basal cell carcinoma (BCC) frequently impose a considerable differential diagnostic challenge and immunohistochemistry is often used as a differentiating diagnostic adjunct. Methods Using standard immunohistochemical techniques, we examined 21 examples of DTE, 17 examples of morpheaform BCC and 10 examples of MAC for the expression of BerEP4, a marker of epithelial cells, and of three stem cell markers, pleckstrin homology-like domain, family A, member 1 (PHLDA1) [T cell death-associated gene 51 (TDAG51)], cytokeratin 15 (CK15) and cytokeratin (CK19). Results All but one MAC was negative for BerEP4 and all morpheaform BCC expressed BerEP4. Sixteen out of 21 DTE were immunoreactive for BerEP4. All 21 DTE were PHLDA1 positive and all 17 morpheaform BCC were PHLDA1 negative. MAC showed a mixed staining pattern for PHLDA1. CK15 was expressed in 20/21 DTE, whereas the majority of cases of MAC and morpheaform BCC were CK15 negative. CK19 stained more MAC than DTE and morpheaform BCC. Conclusions BerEP4 differentiates between MAC and morpheaform BCC but not between MAC and DTE whereas PHLDA1 differentiates between DTE and morpheaform BCC but shows variable staining in MAC. CK15 and CK19 are helpful adjuncts in the differential diagnosis of sclerosing adnexal neoplasms but are second in line to BerEP4 and PHLDA1. We propose an algorithm for the immunohistochemical work-up of sclerosing adnexal neoplasms. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

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