Friedrichshafen, Germany
Friedrichshafen, Germany

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Llamas-Velasco M.,Hospital Infanta Cristina | Perez-Gonzalez Y.C.,Hospital Infanta Cristina | Kutzner H.,Dermatopathologie Friedrichshafen
Journal of the American Academy of Dermatology | Year: 2014

The dermatologic hallmark of a recently described BAP1-associated cancer susceptibility syndrome is a dome-shaped nevus with distinct clinicopathological features, first delineated by Wiesner and colleagues. Here we describe the leading histopathological criteria of Wiesner nevus. Wiesner nevus is composed of various nevomelanocytic populations all showing different degrees of atypia ranging from hyperchromatic nevus cell-like to large atypical epithelioid cells. Immunohistochemically, Wiesner nevus is BAP1 negative and VE1 positive. © 2013 by the American Academy of Dermatology, Inc.


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.


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.


Kempf W.,Kempf und Pfaltz Histologische Diagnostik | Kempf W.,University of Zürich | Kazakov D.V.,Charles University | Scharer L.,Dermatopathologie Friedrichshafen | And 6 more authors.
American Journal of Surgical Pathology | Year: 2013

Lymphomatoid papulosis (LyP) belongs to the spectrum of primary cutaneous CD30-positive lymphoproliferative disorders. Clinically, LyP is characterized by a variable number of self-healing papulo-nodular lesions, with the typical waxing and waning course. Histologically, 4 types (A, B, C, and D) have been delineated. Angioinvasive growth and large ulcers are rare findings in LyP and simulate aggressive lymphoma. We retrospectively analyzed the clinicopathologic and molecular features of angioinvasive LyP in a series of 16 patients. This new form of LyP is characterized by oligolesional papules that rapidly ulcerate and evolve into large necrotic eschar-like lesions with a diameter of 1 to 4 cm and an angiocentric and angiodestructive infiltrate of small-sized to medium-sized atypical lymphocytes expressing CD30 and frequently CD8. As in other forms of LyP, the lesions underwent spontaneous regression after a few weeks. Recurrences were common, but the prognosis was excellent with no extracutaneous spread or disease-related deaths. Complete remission occurred in 9 of 16 patients (56%). This LyP variant should be distinguished from aggressive forms of angiocentric and angiodestructive and cytotoxic T-cell lymphomas. We propose the term LyP type E for this clinically and histologically unusual variant. Copyright © 2012 by Lippincott Williams &Wilkins.


Martin B.,St Thomas Hospital | Poblet E.,University of Murcia | Rios J.J.,Hospital Virgen Of La Macarena | Kazakov D.,Charles University | And 3 more authors.
Histopathology | Year: 2013

Aims: To report on 15 cases of Merkel cell carcinoma (MCC) with divergent differentiation, to characterize its clinicopathological spectrum and its relationship with Merkel cell polyomavirus (MCV). Methods and results: Fifteen patients with a mean age of 81 years were included. Follow-up was available for 13 cases (range 12 days to 6 years; median 6 months). Recurrence, metastasis and mortality rates were 15.4%, 53.8% and 61.5%, respectively. All tumours showed the typical histological and immunohistochemical features of MCC, with at least one additional divergent component. Eight cases had a single aberrant component (squamous in six cases, follicular in one case, and porocarcinoma in one case), six cases had two aberrant components (squamous and sarcomatous in three cases, glandular and squamous in two cases, and sarcomatous and neuroblastic in one case), and one case had three aberrant components (glandular, squamous, and sarcomatous). All cases had dysplastic changes in the overlying epithelium, and four of 15 showed epidermotropism. PCR analysis for Merkel cell polyomavirus (MCV) gave negative results in all 12 cases tested. Conclusions: Merkel cell carcinoma with divergent differentiation is a highly aggressive tumour that might be difficult to recognize, owing to its wide histological variability. Negativity for MCV suggests that the virus is not implicated in the development of this subtype of MCC. © 2012 Blackwell Publishing Ltd.


Llamas-Velasco M.,Hospital Universitario Of La Princesa | Paredes B.E.,Dermatopathologie Friedrichshafen
Actas Dermo-Sifiliograficas | Year: 2012

In this article, we review some of the artifacts commonly observed in biopsies and the methods used to prevent their appearance. We describe the basic techniques for taking biopsies of melanocytic lesions, bullous diseases, and from special areas such as the scalp and nail region. We also provide a brief summary of the role of skin biopsy in the diagnosis of neurological diseases and prenatal diagnosis. The aim of this guide is to improve the diagnostic yield of biopsies and to highlight the importance of a correct clinical-histological correlation; we therefore provide clues to the interpretation of the dermatopathology report. © 2011 Elsevier España, S.L. y AEDV. Todos los derechos reservados.


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.


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.


Sellheyer K.,Cleveland Clinic | Nelson P.,Nelson Dermatopathology Associates | Kutzner H.,Dermatopathologie Friedrichshafen
British Journal of Dermatology | Year: 2012

Background Fibroepithelioma of Pinkus (FEP) has long been viewed as a subtype of basal cell carcinoma (BCC). Recently, however, the proposal has been made that FEP represents a fenestrated trichoblastoma/trichoepithelioma. One of the main arguments is the presence of Merkel cells in FEP, which typically do not occur in BCC. Objectives As the new stem cell marker, PHLDA1 (TDAG51), labels trichoepithelioma but not BCC, our aim was to characterize its staining pattern in FEP. Because adnexal tumours have been viewed as recapitulating embryogenesis, we also examined PHLDA1 immunoreactivity in the skin of human embryos and fetuses. Methods We studied immunohistochemically PHLDA1 staining in 31 FEPs, 14 BCCs and 16 trichoepitheliomas and compared this with its staining pattern in embryonic skin and with the distribution of Merkel cells. Results In FEP, PHLDA1 labels the anastomosing network of thin cellular strands but not the basaloid nubbins. During embryogenesis, PHLDA1 stains the basal cell layer of the epidermis, as long as adnexal structures develop. Immunoreactivity for PHLDA1 correlates positively with the presence of Merkel cells. Conclusions We propose that the thin anastomosing network of PHLDA1-positive cells represents a type of epidermal hyperplasia specific to FEP. The multifocal BCCs that are PHLDA1-negative develop from this network which becomes incorporated into the tumour. Viewing the anastomosing network as a tumour-specific form of epidermal hyperplasia explains the hitherto enigmatic presence of Merkel cells in FEP. © 2011 British Association of Dermatologists.

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