842 results on '"Kutzner H"'
Search Results
302. TTF-1 and PAX5 Are Frequently Expressed in Combined Merkel Cell Carcinoma.
- Author
-
Czapiewski P, Majewska H, Kutzner H, Kazakov D, Renkielska A, and Biernat W
- Subjects
- Aged, Aged, 80 and over, Carcinoma in Situ pathology, Carcinoma, Basal Cell pathology, Carcinoma, Merkel Cell pathology, Carcinoma, Squamous Cell pathology, Cell Differentiation, Europe, Female, Humans, Immunohistochemistry, Male, Neoplasms, Complex and Mixed pathology, Predictive Value of Tests, Skin Neoplasms pathology, Thyroid Nuclear Factor 1, Biomarkers, Tumor analysis, Carcinoma in Situ chemistry, Carcinoma, Basal Cell chemistry, Carcinoma, Merkel Cell chemistry, Carcinoma, Squamous Cell chemistry, Neoplasms, Complex and Mixed chemistry, Nuclear Proteins analysis, PAX5 Transcription Factor analysis, Skin Neoplasms chemistry, Transcription Factors analysis
- Abstract
Thyroid transcription factor-1 (TTF-1) is a marker of tumors of pulmonary and thyroid origin, and its expression practically excludes diagnosis of Merkel cell carcinoma (MCC). However, TTF-1 expression in combined MCC was recently reported. PAX5 is a marker of B-cell origin that is also expressed in most classical MCC cases; however, its expression was not described in combined MCC. The authors decided to evaluate the expression of both these markers in a group of 5 combined MCCs (2 with invasive squamous cell carcinoma, 2 with squamous cell carcinoma in situ, and 1 with basal cell carcinoma). Expression of TTF-1 was found in 4 of 5 cases; in 3 cases, the marker was shown in the MCC component (weakly in 2 cases and strongly in 1 case), whereas the non-MCC component presented TTF-1 expression in 2 cases. A weak-to-moderate immunoreactivity for PAX5 was identified in all cases of the MCC component but in none of the non-MCC component. The results show that the expression of TTF-1 is a frequent finding in combined MCC and can be present in the neuroendocrine component, which differs from the conventional MCC. In contrast, PAX5 expression pattern is similar to that of the classical MCC.
- Published
- 2016
- Full Text
- View/download PDF
303. Spitz Tumors: Comparison of Histological Features in Relationship to Immunohistochemical Staining for ALK and NTRK1.
- Author
-
Kiuru M, Jungbluth A, Kutzner H, Wiesner T, and Busam KJ
- Subjects
- Adolescent, Adult, Anaplastic Lymphoma Kinase, Child, Child, Preschool, Female, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Male, Melanocytes pathology, Middle Aged, Nevus, Epithelioid and Spindle Cell pathology, Receptor Protein-Tyrosine Kinases analysis, Receptor, trkA analysis, Skin Neoplasms pathology, Young Adult, Biomarkers, Tumor analysis, Nevus, Epithelioid and Spindle Cell diagnosis, Receptor Protein-Tyrosine Kinases biosynthesis, Receptor, trkA biosynthesis, Skin Neoplasms diagnosis
- Abstract
Spitz tumors are a group of melanocytic neoplasms with distinct morphological features that tend to affect young individuals. Distinguishing benign from malignant Spitz tumors can be challenging, but cytogenetic and molecular tests have contributed to improvements in diagnostic accuracy. Spitz tumors harbor diverse genetic alterations, including mutations in HRAS, loss of BAP1, or kinase fusions in ROS1, NTRK1, ALK, BRAF, and RET genes. Limited data exist on the correlation between histopathological features and kinase fusions. Here, we describe the histopathological features of 105 Spitz tumors (Spitz nevi and atypical Spitz tumors), comparing lesions according to their immunoreactivity for ALK or NTRK1. Intersecting fascicular growth of fusiform melanocytes was seen in all but one ALK-positive tumor (27 of 28 or 96.4%), whereas it was infrequent in NTRK1-positive tumors (5 of 20 or 25.0%) and tumors negative for both ALK and NTRK1 (96.4% vs 25.0% vs 8.7%, P < .0027). There was a trend toward ALK-positive tumors being amelanotic compared with NTRK1-positive tumors and combined ALK-/NTRK1-negative tumors (89.3% vs 45% vs 47.4%, respectively, P = .1023) and lacking epithelioid cell morphology (0% vs 45.0% vs 41%, respectively, P = .6985). In conclusion, this study confirms that although not specific, the growth pattern of intersecting fascicles of amelanotic fusiform melanocytes is strongly associated with ALK expression., (© The Author(s) 2016.)
- Published
- 2016
- Full Text
- View/download PDF
304. Melanocytic Hyperplasia in the Epidermis Overlying Trichoblastomas in 100 Randomly Selected Cases.
- Author
-
Al Omoush TM, Michal M, Konstantinova AM, Michal M, Kutzner H, and Kazakov DV
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Female, Humans, Hyperplasia pathology, Male, Middle Aged, Young Adult, Epidermis pathology, Hair Diseases pathology, Melanocytes pathology, Neoplasms, Adnexal and Skin Appendage pathology
- Abstract
One hundred cases of trichoblastomas (large nodular, small nodular, cribriform, lymphadenoma, and columnar) were randomly selected and studied for the presence of melanocytic hyperplasia in the epidermis overlying the tumors, which was defined as foci of increased melanocytes in the basal layer of the epidermis (more than 1 per 4 basal keratinocytes). Focal melanocytic hyperplasia was detected in a total of 22 cases of trichoblastoma (22%), and this phenomenon was most frequently seen in columnar trichoblastoma (7 cases), followed by large nodular trichoblastoma (5 cases). The mechanism of epidermal melanocytic hyperplasia overlying trichoblastoma is unclear. Ultraviolet may be a contributing factor, as focal melanocytic hyperplasia was also detected in one-third of cases in the epidermis overlying uninvolved skin, usually associated with solar elastosis. This is further corroborated by the occurrence of the lesions predominantly on the face. Melanocytic hyperplasia overlying trichoblastoma appears to have no impact on the clinical appearance of the lesion and is recognized only microscopically. In an adequate biopsy specimen containing at least part of trichoblastoma, it should not cause any diagnostic problems.
- Published
- 2016
- Full Text
- View/download PDF
305. Hemangioma with dabskoid features: a rare histopathologic variant of acquired hemangioma.
- Author
-
Llamas-Velasco M, Angulo J, Durán R, Fraitag S, Kutzner H, and Requena L
- Subjects
- Adolescent, Child, Female, Humans, Male, Transcriptional Regulator ERG metabolism, Biomarkers, Tumor metabolism, Endothelial Cells metabolism, Endothelial Cells pathology, Hemangioma metabolism, Hemangioma pathology, Platelet Endothelial Cell Adhesion Molecule-1 metabolism, Skin Neoplasms metabolism, Skin Neoplasms pathology
- Abstract
Dabska tumor, also known as papillary intralymphatic angioendothelioma (PILA), is a locally aggressive hemangiendothelioma characterized by intravascular papillary proliferations of atypical endothelial cells. Besides PILA, papillary tufts lined by hobnail endothelial cells have been rarely described in vascular proliferations. We report two cases of acquired hemangiomas, which focally showed this finding. We present a 15-year-old male and a 7-year-old girl with erythematous nodules. Both lesions were composed of capillary lobules intermingled with large sinusoidal spaces lined with a single layer of flat endothelial cells, which focally developed intravascular papillary proliferations lined by plump hyperchromatic endothelial cells and a central connective tissue core. Both types of cells were positive with CD31 and ERG and negative for Lyve-1, Prox-1 and podoplanin. Wilm's tumor 1 marker was strongly positive in the capillary hemangioma areas while negative in the intravascular tufts. Both lesions recurred after the first excision but we did not observe further recurrence or evidence of metastasis in the follow-up. In summary, our cases expand the histopathologic findings that may be seen in conventional acquired capillary hemangiomas. The focal presence of dabskoid tufts within an otherwise conventional capillary hemangioma should be not misinterpreted as evidence of malignancy., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2016
- Full Text
- View/download PDF
306. Genomic aberrations in spitzoid melanocytic tumours and their implications for diagnosis, prognosis and therapy.
- Author
-
Wiesner T, Kutzner H, Cerroni L, Mihm MC Jr, Busam KJ, and Murali R
- Subjects
- Animals, Genomics, Humans, Melanoma diagnosis, Melanoma therapy, Mutation, Nevus, Epithelioid and Spindle Cell diagnosis, Nevus, Epithelioid and Spindle Cell therapy, Nevus, Pigmented diagnosis, Nevus, Pigmented therapy, Phosphotransferases genetics, Prognosis, Proto-Oncogene Proteins genetics, Recombination, Genetic, Skin pathology, Skin Neoplasms diagnosis, Skin Neoplasms therapy, Tumor Suppressor Proteins genetics, Ubiquitin Thiolesterase genetics, Chromosome Aberrations, Melanoma genetics, Nevus, Epithelioid and Spindle Cell genetics, Nevus, Pigmented genetics, Skin Neoplasms genetics
- Abstract
Histopathological evaluation of melanocytic tumours usually allows reliable distinction of benign melanocytic naevi from melanoma. More difficult is the histopathological classification of Spitz tumours, a heterogeneous group of tumours composed of large epithelioid or spindle-shaped melanocytes. Spitz tumours are biologically distinct from conventional melanocytic naevi and melanoma, as exemplified by their distinct patterns of genetic aberrations. Whereas common acquired naevi and melanoma often harbour BRAF mutations, NRAS mutations, or inactivation of NF1, Spitz tumours show HRAS mutations, inactivation of BAP1 (often combined with BRAF mutations), or genomic rearrangements involving the kinases ALK, ROS1, NTRK1, BRAF, RET, and MET. In Spitz naevi, which lack significant histological atypia, all of these mitogenic driver aberrations trigger rapid cell proliferation, but after an initial growth phase, various tumour suppressive mechanisms stably block further growth. In some tumours, additional genomic aberrations may abrogate various tumour suppressive mechanisms, such as cell-cycle arrest, telomere shortening, or DNA damage response. The melanocytes then start to grow in a less organised fashion and may spread to regional lymph nodes, and are termed atypical Spitz tumours. Upon acquisition of even more aberrations, which often activate additional oncogenic pathways or alter cell differentiation, the neoplastic cells become entirely malignant and may colonise and take over distant organs (spitzoid melanoma). The sequential acquisition of genomic aberrations suggests that Spitz tumours represent a continuous biological spectrum, rather than a dichotomy of benign versus malignant, and that tumours with ambiguous histological features (atypical Spitz tumours) might be best classified as low-grade melanocytic tumours. The number of genetic aberrations usually correlates with the degree of histological atypia and explains why existing ancillary genetic techniques, such as array comparative genomic hybridisation (CGH) or fluorescence in situ hybridisation (FISH), are usually capable of accurately classifying histologically benign and malignant Spitz tumours, but are not very helpful in the diagnosis of ambiguous melanocytic lesions. Nevertheless, we expect that progress in our understanding of tumour progression will refine the classification of spitzoid melanocytic tumours in the near future. By integrating clinical, pathological, and genetic criteria, distinct tumour subsets will be defined within the heterogeneous group of Spitz tumours, which will eventually lead to improvements in diagnosis, prognosis and therapy., (Copyright © 2015 The Royal College of Pathologists of Australasia. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
307. Immunohistochemistry in Dermatopathology: A Retrospective Study of the Most Frequently Used Antibodies.
- Author
-
Fuertes L, Santonja C, Kutzner H, and Requena L
- Subjects
- Antibody Specificity, Biomarkers, Tumor analysis, Biomarkers, Tumor immunology, Biopsy, Cell Differentiation, Cell Proliferation, Dermatitis immunology, Dermatitis metabolism, Dermatitis pathology, Dermatology standards, Diagnosis, Differential, Humans, Immunohistochemistry standards, Pathology standards, Predictive Value of Tests, Reproducibility of Results, Retrospective Studies, Skin chemistry, Skin pathology, Skin Neoplasms chemistry, Skin Neoplasms immunology, Skin Neoplasms pathology, Antibodies immunology, Dermatitis diagnosis, Dermatology methods, Immunohistochemistry methods, Pathology methods, Skin immunology, Skin Neoplasms diagnosis
- Abstract
Immunohistochemistry (IHC) is an ancillary technique to improve diagnostic accuracy and prognosis in histopathology of both inflammatory and neoplastic cutaneous disorders. However, only a few studies address specifically the set of antibodies available for inflammatory or neoplastic skin diseases. In this study, we analyzed the IHC studies performed for inflammatory and neoplastic skin disorders in cutaneous biopsies taken in our department during 1 year. From a total of 8579 skin biopsies performed throughout the year 2011 in our department, IHC studies were performed in 283 cutaneous biopsies. The total number of different antibodies used in the IHC studies of those 283 skin biopsies was 129. These antibodies were used in 1421 studies, with a mean of 5 cases per antibody studied. The proliferative marker MIB-1 was the single antibody with the highest number of studies, with a total of 119 (8.3% of all IHC studies performed), followed by 113 of CD3 (7.9% of total IHC studies) and 108 of Melan-A (7.6% of total IHC studies). Other hematopoietic differentiation markers, such as CD20, CD4, and CD8, and other melanocytic markers, such as S-100 protein, Melan-A, and HMB-45, were all investigated with a frequency greater than 50 studies each. The 2 most frequent categories were melanocytic neoplasms, which represented 25% of all specimens studied by IHC, and the proliferations of lymphohematopoietic nature, which were 20% of all studied samples and represented by far the highest number of IHC stains per case to reach a final diagnosis. Both previous categories together accounted for 45% of all diagnoses in which IHC was performed. We compare our results with the only similar study previously published in the literature. The gold standard panel of antibodies that should be available in everyday practice in dermatopathology to arrive at a specific diagnosis in each cutaneous inflammatory disease or neoplastic process involving the skin is still a matter of discussion.
- Published
- 2016
- Full Text
- View/download PDF
308. Atypical Spitz Tumor Arising on a Congenital Linear Plaque-Type Blue Nevus: A Case Report With a Review of the Literature on Plaque-Type Blue Nevus.
- Author
-
Rongioletti F, Guadagno A, Campisi C, Cabiddu F, Kutzner H, Parodi A, and Fiocca R
- Subjects
- Female, Humans, Middle Aged, Nevus, Blue congenital, Cell Transformation, Neoplastic pathology, Nevus, Blue pathology, Nevus, Epithelioid and Spindle Cell pathology, Skin Neoplasms pathology
- Abstract
The plaque-type blue nevus (PTBN) is a rare variant of blue nevus, of which only a few reports are described. A nodular growth within a preexistent PTBN should always alert to the possibility of malignant transformation. The authors report the first case of an atypical Spitz tumor arising on a congenital linear PTBN in a 60-year-old woman. The diagnosis of "atypical Spitz tumor" is here used to describe a microscopic "gray zone" in which it is not possible to differentiate with adequate certainty between a Spitz nevus and a spitzoid melanoma. This report adds to and summarizes the small body of literature describing PTBN and discusses diagnostic and clinical implications.
- Published
- 2015
- Full Text
- View/download PDF
309. Sebocyte-like cell primary cutaneous melanoma: a rare cytologic variant of malignant melanoma.
- Author
-
Molina-Ruiz AM, Ortiz-Reina S, Carranza C, Kutzner H, and Requena L
- Subjects
- Humans, Male, Middle Aged, Melanocytes pathology, Melanoma pathology, Skin Neoplasms pathology
- Abstract
Although rising incidence rates of cutaneous melanoma have been observed during the last 4 decades in white populations worldwide, the sebocyte-like cell variant has been described only twice in the literature to date. In our case, a 64-year-old man presented for evaluation of a changing pigmented lesion on the left upper back. Excision of the lesion revealed an invasive melanoma with a Breslow depth of 3.3 mm. Microscopic sections showed a predominantly dermal-based tumor composed of sheets and nests of enlarged epithelioid melanocytes, most of which showed an uncommon phenotype with multivacuolated cytoplasms and scalloped nuclei, features that gave them a strong resemblance to mature sebocytes. The lesional cells expressed S100 protein, Melan-A, and p16, whereas adipophilin was positive only within the sebocyte-like component of the neoplasm and showed focal nonspecific staining. The patient's sentinel lymph node biopsy was positive for micrometastases, although a subsequent position emission tomography scan was unremarkable. Sebocyte-like melanocytes are a rare distinctive type of melanocytes that can be found mostly in benign but also in malignant melanocytic lesions. They usually present focally within the lesions and, therefore, do not represent a diagnostic problem in nevus or primary cutaneous melanoma. However, when sebocyte-like melanocytes are the main cellular component of a melanocytic lesion or when they are found in the context of metastatic melanoma, they may create a potential diagnostic pitfall; for this reason, awareness of this cell type is important.
- Published
- 2015
- Full Text
- View/download PDF
310. Circumscribed cicatricial alopecia due to localized sarcoidal granulomas and single-organ granulomatous arteritis: a case report and systematic review of sarcoidal vasculitis.
- Author
-
Yazdani Abyaneh MA, Raghu P, Kircher K, Kutzner H, Kortz A, and Carlson JA
- Subjects
- Acyclovir administration & dosage, Acyclovir analogs & derivatives, Adult, Aged, Alopecia Areata metabolism, Antibodies, Monoclonal, Murine-Derived metabolism, Antiviral Agents administration & dosage, Biopsy, Cytokines metabolism, Female, Glucocorticoids administration & dosage, Granuloma drug therapy, Humans, Lymphocytes pathology, Male, Middle Aged, Prednisone administration & dosage, Sarcoidosis drug therapy, Scalp metabolism, Skin Diseases drug therapy, Skin Diseases metabolism, Valacyclovir, Valine administration & dosage, Valine analogs & derivatives, Vasculitis drug therapy, Vasculitis, Central Nervous System metabolism, Alopecia Areata pathology, Granuloma pathology, Sarcoidosis pathology, Scalp pathology, Skin Diseases pathology, Vasculitis pathology, Vasculitis, Central Nervous System pathology
- Abstract
Vasculitis associated with sarcoid granulomas is an uncommon phenomenon. A 72-year-old female presented with an expanding region of circumscribed alopecia and scalp atrophy of 2 months duration. Biopsy showed non-caseating granulomas, dermal thinning, loss of follicles, fibrosis and muscular vessels disrupted by mixed lymphocyte, macrophage and giant-cell infiltrates. Affected vessels had loss and fragmentation of the elastic lamina, fibrous replacement of their walls and luminal stenosis (endarteritis obliterans). Dermal and vascular advential intralymphatic granulomas and lymphangiectases were found by D2-40 expression, suggesting lymphatic obstruction and poor antigen clearance. No evidence of a post-zoster eruption, systemic sarcoidosis or systemic giant-cell arteritis was found. Two years later, prednisone had halted - but not reversed - progression of her alopecia. Review of the literature showed two types of vasculitis associated with sarcoid granulomas: (i) acute, self-limited leukocytoclastic vasculitis and (ii) chronic granulomatous vasculitis (GV). Persistence of non-degradable material or antigen contributes to the pathogenesis of granulomatous inflammation. In this case, lymphatic obstruction probably impeded clearance of nonimmunologic and/or immunologic stimuli permitting and sustaining the development of sarcoid granulomas and sarcoid GV, ultimately causing scarring alopecia and cutaneous atrophy., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2015
- Full Text
- View/download PDF
311. Lymphocytic Arteritis in Epstein-Barr Virus Vulvar Ulceration (Lipschütz Disease): A Report of 7 Cases.
- Author
-
Barrett MM, Sangüeza M, Werner B, Kutzner H, and Carlson JA
- Subjects
- Adolescent, Adult, Child, Female, Herpesvirus 4, Human, Humans, Immunohistochemistry, In Situ Hybridization, Middle Aged, Polymerase Chain Reaction, Ulcer pathology, Young Adult, Arteritis virology, Epstein-Barr Virus Infections complications, Ulcer virology, Vulvar Diseases pathology, Vulvar Diseases virology
- Abstract
Epstein-Barr virus (EBV) infection can rarely present as painful genital ulcers, mostly in young female adolescents. Typically diagnosed by clinical findings, EBV vulvar ulceration (EBVVU) is rarely biopsied. Herein, the authors report the histopathology in 8 biopsies from 7 EBVVU patients, all serologically confirmed for acute (4/7) or reactivated-chronic (3/7) EBV infection. The 7 women all presented with 1 or more painful, punched-out vulvar ulcers. Only patients with acute EBV infection showed other clinical findings: fever and/or atypical lymphocytosis affected 75% (3/4); lymphadenopathy in 50%; and malaise/fatigue, dysuria and/or hepatomegaly in 25%. All reactivated-chronic EBVVU had a solitary ulcer, and 2 had history of a similar episode of vulvar ulceration (aphthosis). Histopathologically, lymphocytic arteritis was identified in 88% (7/8); a submucosal scar was found in the eighth specimen. Other histopathologies included venulitis (62%), endarteritis obliterans (38%), thrombosis (25%), neutrophilic sebaceous adenitis (25%), and mucosal lymphoid hyperplasia (12%). Dense angiocentric CD3 CD4 T-cell lymphocyte-predominant infiltrates were found, regionally or diffusely. In 2 specimens, neutrophils compromised half of the infiltrate. Minor components of CD8, CD20, and CD30 lymphocytes, CD123 plasmacytoid monocytes, CD68 macrophages, and plasma cells were present. Small-vessel endothelium and smooth muscle adjacent to the ulcers faintly expressed cytoplasmic EBV latent membrane protein-1 (LMP1). In situ hybridization for early EBV mRNA (EBER) identified rare solitary or scattered clustered positive lymphocytes in 38%. Polymerase chain reaction for EBV DNA was positive in one EBER positive biopsy. EBV infection has been documented in muscular vessel vasculitis. Based on the aforementioned, EBVVU appears to be the consequence of localized lymphocytic arteritis.
- Published
- 2015
- Full Text
- View/download PDF
312. BAP1-deficient and VE1-negative atypical Spitz tumor.
- Author
-
Requena C, Sanz V, Nagore E, García-Casado Z, Rubio L, Guillén C, and Kutzner H
- Subjects
- Adult, Biomarkers, Tumor metabolism, Female, Humans, Melanoma diagnosis, Melanoma genetics, Melanoma pathology, Mutation, Nevus, Epithelioid and Spindle Cell genetics, Nevus, Epithelioid and Spindle Cell metabolism, Nevus, Epithelioid and Spindle Cell pathology, Proto-Oncogene Proteins B-raf metabolism, Skin Neoplasms genetics, Skin Neoplasms metabolism, Skin Neoplasms pathology, Tumor Suppressor Proteins metabolism, Ubiquitin Thiolesterase metabolism, Nevus, Epithelioid and Spindle Cell diagnosis, Proto-Oncogene Proteins B-raf genetics, Tumor Suppressor Proteins deficiency, Ubiquitin Thiolesterase deficiency
- Abstract
Atypical Spitz tumor with loss of BAP1 or Wiesner nevus is a peculiar variant of intradermal spitzoid melanocytic neoplasm composed of epithelioid melanocytes with a sheet-like growth pattern, abundant infiltrating lymphocytes and rare or absent mitotic activity. This subset of atypical spitzoid tumors is characterized by the BRAF(V600E) mutation and loss of BAP1 expression. Recognition of these lesions is important because they can be a marker for a hereditary BAP1-associated cancer syndrome. We present an unusual case of sporadic Wiesner nevus that had typical histopathologic features and a BAP1 but not a BRAF mutation. The biological significance of Wiesner nevus is controversial, and little is known about prognosis, particularly in atypical cases like this one., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2015
- Full Text
- View/download PDF
313. Subungual Acral Fibromyxoma Involving the Bone: A Mimicker of Malignancy.
- Author
-
Carranza C, Molina-Ruiz AM, Pérez de la Fuente T, Kutzner H, Requena L, and Santonja C
- Subjects
- Diagnosis, Differential, Fibroma chemistry, Fibroma surgery, Humans, Male, Middle Aged, Neoplasm Invasiveness, Skin Neoplasms chemistry, Skin Neoplasms surgery, Toes, Fibroma pathology, Skin Neoplasms pathology, Toe Phalanges pathology
- Abstract
Superficial acral fibromyxoma (SAF) is a recently recognized myxoid tumor that usually occurs on the fingers and toes of middle-aged adults. We report the case of a 53-year-old man with a SAF on the first left toe that had been slowly growing for 2 years. Hispathologically, the lesion was nonencapsulated and was composed of stellate and spindle cells, arranged in a myxoid matrix. No atypia or mitotic figures were found. Neoplastic cells showed positive staining for CD34 and negative staining for epithelial membrane antigen, actin, desmin, keratins, S-100 protein, and HMB45. Main differential diagnoses of SAF include benign and malignant myxoid and spindle cells tumors, such as myxoid fibrous histiocytoma, superficial angiomyxoma, myxoid neurofibroma, myxoid dermatofibrosarcoma protuberans, and low-grade fibromyxoid sarcoma.
- Published
- 2015
- Full Text
- View/download PDF
314. Two cases of intralymphatic histiocytosis following hip replacement.
- Author
-
Bidier M, Hamsch C, Kutzner H, Enk A, and Hassel JC
- Subjects
- Aged, Diagnosis, Differential, Humans, Male, Middle Aged, Arthroplasty, Replacement, Hip adverse effects, Hip Prosthesis adverse effects, Histiocytosis pathology, Lymph Nodes pathology, Skin Diseases pathology
- Published
- 2015
- Full Text
- View/download PDF
315. Histologic and Immunohistochemical Features of the Skin Lesions in CANDLE Syndrome.
- Author
-
Torrelo A, Colmenero I, Requena L, Paller AS, Ramot Y, Richard Lee CC, Vera A, Zlotogorski A, Goldbach-Mansky R, and Kutzner H
- Subjects
- Antigens, CD analysis, Antigens, Differentiation, Myelomonocytic analysis, Chronic Disease, Dendritic Cells chemistry, Dendritic Cells pathology, Eosinophils pathology, Fever metabolism, Fever pathology, Histiocytes chemistry, Histiocytes pathology, Humans, Immunohistochemistry, Interleukin-3 Receptor alpha Subunit analysis, Lipodystrophy metabolism, Lymphocytes pathology, Macrophages chemistry, Macrophages pathology, Myeloid Cells chemistry, Myeloid Cells pathology, Peroxidase analysis, Receptors, Cell Surface analysis, Syndrome, Lipodystrophy pathology, Neutrophils, Skin Diseases metabolism, Skin Diseases pathology
- Abstract
Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome is a newly characterized autoinflammatory disorder, caused by mutations in PSMB8. It is characterized by early-onset fevers, accompanied by a widespread, violaceous, and often annular cutaneous eruption. Although the exact pathogenesis of this syndrome is still obscure, it is postulated that the inflammatory disease manifestations stem from excess secretion of interferons. Based on preliminary blood cytokine and gene expression studies, the signature seems to come mostly from type I interferons, which are proposed to lead to the recruitment of immature myeloid cells into the dermis and subcutis. In this study, we systematically analyzed skin biopsies from 6 patients with CANDLE syndrome by routine histopathology and immunohistochemistry methods. Skin lesions showed the presence of extensive mixed dermal and subcutaneous inflammatory infiltrate, composed of mononuclear cells, atypical myeloid cells, neutrophils, eosinophils, and some mature lymphocytes. Positive LEDER and myeloperoxidase staining supported the presence of myeloid cells. Positive CD68/PMG1 and CD163 staining confirmed the existence of histiocytes and monocytic macrophages in the inflammatory infiltrate. CD123 staining was positive, demonstrating the presence of plasmacytoid dendritic cells. Uncovering the unique histopathological and immunohistochemical features of CANDLE syndrome provides tools for rapid and specific diagnosis of this disorder and further insight into the pathogenesis of this severe life-threatening condition.
- Published
- 2015
- Full Text
- View/download PDF
316. Cutaneous borreliosis associated with T cell-predominant infiltrates: a diagnostic challenge.
- Author
-
Kempf W, Kazakov DV, Hübscher E, Gugerli O, Gerbig AW, Schmid R, Palmedo G, and Kutzner H
- Subjects
- Acrodermatitis etiology, Adult, Aged, Animals, Borrelia burgdorferi isolation & purification, DNA, Bacterial isolation & purification, Diagnosis, Differential, Erythema etiology, Female, Fibrosis, Histiocytes pathology, Humans, Leukemia, Lymphocytic, Chronic, B-Cell complications, Lyme Disease complications, Lyme Disease immunology, Lyme Disease pathology, Lyme Disease transmission, Lymphoma, T-Cell, Cutaneous diagnosis, Male, Middle Aged, Pseudolymphoma immunology, Pseudolymphoma pathology, Receptors, Antigen, T-Cell, gamma-delta genetics, Retrospective Studies, Skin immunology, Skin microbiology, Skin Diseases, Bacterial immunology, Skin Diseases, Bacterial pathology, Tick Bites complications, Tick Bites microbiology, Tick Bites pathology, Lyme Disease diagnosis, Pseudolymphoma diagnosis, Skin pathology, Skin Diseases, Bacterial diagnosis, T-Lymphocytes pathology
- Abstract
Background: With the exception of erythema migrans, Borrelia infection of the skin manifests much more commonly with B cell-rich infiltrates. T cell-rich lesions have rarely been described., Objective: We report a series of 6 patients with cutaneous borreliosis presenting with T cell-predominant skin infiltrates., Methods: We studied the clinicopathologic and molecular features of 6 patients with T cell-rich skin infiltrates., Results: Half of the patients had erythematous patchy, partly annular lesions, and the other patients had features of acrodermatitis chronica atrophicans. Histopathology revealed a dense, band-like or diffuse dermal infiltrate. Apart from small, well differentiated lymphocytes, there were medium-sized lymphocytes with slight nuclear atypia and focal epidermotropism. An interstitial histiocytic component was found in 4 cases, including histiocytic pseudorosettes. Fibrosis was present in all cases but varied in severity and distribution. In 5 patients, borrelia DNA was detected in lesional tissue using polymerase chain reaction studies. No monoclonal rearrangement of T-cell receptor gamma genes was found., Limitations: This retrospective study was limited by the small number of patients., Conclusion: In addition to unusual clinical presentation, cutaneous borreliosis can histopathologically manifest with a T cell-rich infiltrate mimicking cutaneous T-cell lymphoma. Awareness of this clinicopathologic constellation is important to prevent underrecognition of this rare and unusual presentation representing a Borrelia-associated T-cell pseudolymphoma., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
317. Primary cutaneous malignant granular cell tumor: an immunohistochemical study and review of the literature.
- Author
-
Pérez-González YC, Pagura L, Llamas-Velasco M, Cortes-Lambea L, Kutzner H, and Requena L
- Subjects
- Female, Granular Cell Tumor immunology, Granular Cell Tumor secondary, Granular Cell Tumor surgery, Humans, Lymph Node Excision, Lymphatic Metastasis, Middle Aged, Neoplasm Recurrence, Local, Predictive Value of Tests, Reoperation, Skin Neoplasms immunology, Skin Neoplasms pathology, Skin Neoplasms surgery, Time Factors, Treatment Outcome, Biomarkers, Tumor analysis, Granular Cell Tumor chemistry, Immunohistochemistry, Immunophenotyping methods, Skin Neoplasms chemistry
- Abstract
Granular cell tumors (GCTs) are uncommon soft tissue tumors characterized by cytoplasmic granular appearance of the neoplastic cells. Malignant granular cell tumors (MGCTs) comprise less than 2% of GCTs and are mostly found in the subcutaneous soft tissues of the lower extremities, especially the thighs. Very few cases have been reported in the skin. The uncommon occurrence of cutaneous MGCTs and their histopathologic similarities with their benign counterpart make difficult the diagnosis of this particular malignancy. We describe a primary cutaneous MGCT that presented as a left posterior chest wall mass in a 51-year-old woman. Local excision was performed for the primary tumor, which was first interpreted as an atypical GCT, but 3 months later a left axillary mass appeared, and subsequent axillary lymph node dissection demonstrated metastatic disease in 4 of 12 excised lymph nodes. We report the immunophenotype of this primary cutaneous MGCT, which was studied with an ample panel of antibodies and compare our results with those of the few previously reported cases in the skin and subcutaneous soft tissues.
- Published
- 2015
- Full Text
- View/download PDF
318. Immunohistochemistry in the diagnosis of cutaneous bacterial infections.
- Author
-
Molina-Ruiz AM, Cerroni L, Kutzner H, and Requena L
- Subjects
- Humans, Immunohistochemistry methods, Skin Diseases, Bacterial diagnosis, Skin Diseases, Bacterial microbiology
- Abstract
The identification of pathogens is of vital importance for the adequate treatment of infections. During the past 2 decades, the approach to histopathologic diagnosis has been dramatically transformed by immunohistochemistry (IHC) specifically in the diagnosis and classification of tumors and more recently in the diagnosis of infectious diseases in tissue samples. The main goals of this article were to: (1) identify by IHC the cutaneous structures where bacterial pathogens are expressed in the course of infection, (2) identify the specific cells in which bacterial pathogens are expressed in positive cases, and (3) describe the pattern of distribution of the bacterial antigens within these cells (nuclear, cytoplasmatic, or membranous). This article is an up-to-date overview of the potential uses and limitations of IHC in the histopathologic diagnosis of cutaneous bacterial infections. In conclusion, IHC is especially useful in the identification of microorganisms that are present in low numbers, stain poorly, are fastidious to grow, culture is not possible, or exhibit an atypical morphology.
- Published
- 2015
- Full Text
- View/download PDF
319. [Morphological and genetic aspects of Spitz tumors].
- Author
-
Wiesner T and Kutzner H
- Subjects
- Chromosome Aberrations, Diagnosis, Differential, Humans, Melanoma genetics, Melanoma pathology, Skin pathology, Nevus, Epithelioid and Spindle Cell genetics, Nevus, Epithelioid and Spindle Cell pathology, Skin Neoplasms genetics, Skin Neoplasms pathology
- Abstract
Background: Spitzoid melanocytic neoplasms (i.e. Spitz nevi, atypical Spitz tumors and spitzoid melanoma) are a clinical, histopathological and molecular genetic heterogeneous group of melanocytic skin tumors., Objectives: Correlation of the histological features of spitzoid neoplasms with molecular genetic aberrations., Material and Methods: A review and summary of the scientific literature., Results: Several histopathological and molecular genetic distinct subtypes of spitzoid lesions have been defined. Epithelioid Spitz tumors commonly show a loss of the BAP1 gene and BRAF mutations and are associated with a hereditary tumor predisposition syndrome. Desmoplastic Spitz tumors frequently harbor HRAS mutations and gains of the chromosome arm 11p. Plexiform Spitz tumors often display ALK translocations. The morphology of Spitz tumors with ROS1, NTRK1, RET and BRAF fusion genes seems to be unspecific and is currently not well characterized., Conclusion: Morphological features offer valuable clues to the underlying genetic aberrations in spitzoid neoplasms. Genetic aberrations can be found in the entire biological spectrum of spitzoid neoplasms (i.e. Spitz nevi, atypical Spitz tumors and spitzoid melanoma) and are, therefore, probably not useful for distinguishing benign from malignant tumors; however, genetic aberrations represent important targets for therapeutic interventions and offer investigational treatment options for patients with metastatic disease. The appearance of multiple epithelioid melanocytic tumors with BAP1 loss indicates a hereditary tumor syndrome and warrants genetic counseling and preventive screening of affected individuals.
- Published
- 2015
- Full Text
- View/download PDF
320. Immunohistochemistry in the diagnosis of cutaneous viral infections- part II: cutaneous viral infections by parvoviruses, poxviruses, paramyxoviridae, picornaviridae, retroviruses and filoviruses.
- Author
-
Molina-Ruiz AM, Santonja C, Rütten A, Cerroni L, Kutzner H, and Requena L
- Subjects
- Antibodies, Monoclonal, Biomarkers analysis, Biopsy, Filoviridae Infections immunology, Filoviridae Infections pathology, Filoviridae Infections virology, Humans, Paramyxoviridae Infections immunology, Paramyxoviridae Infections pathology, Paramyxoviridae Infections virology, Parvoviridae Infections immunology, Parvoviridae Infections pathology, Parvoviridae Infections virology, Picornaviridae Infections immunology, Picornaviridae Infections pathology, Picornaviridae Infections virology, Poxviridae Infections immunology, Poxviridae Infections pathology, Poxviridae Infections virology, Predictive Value of Tests, Retroviridae Infections immunology, Retroviridae Infections pathology, Retroviridae Infections virology, Skin pathology, Skin virology, Skin Diseases, Viral immunology, Skin Diseases, Viral pathology, Skin Diseases, Viral virology, Antigens, Viral immunology, Filoviridae Infections diagnosis, Immunohistochemistry, Paramyxoviridae Infections diagnosis, Parvoviridae Infections diagnosis, Picornaviridae Infections diagnosis, Poxviridae Infections diagnosis, Retroviridae Infections diagnosis, Skin immunology, Skin Diseases, Viral diagnosis
- Abstract
Background: Cutaneous viral infections are increasing in recent years, particularly in immunocompromised patients., Objective: Immunohistochemistry (IHC) provides a rapid and helpful tool that can be applied to confirm the diagnosis of specific viral infections that may be difficult to diagnose with certainty using routine microscopy alone., Methods: Several immunostains that are useful in histopathology have been reviewed and tested in cutaneous samples of viral infections. Emphasis is placed on new stains and novel uses of existing stains., Results: This article is an up-to-date overview of the potential uses of IHC in the histopathologic diagnosis of cutaneous viral infections by parvoviruses, polyomaviruses, poxviruses, paramyxoviridae, picornaviridae, retroviruses, and filoviruses., Limitations: Specific monoclonal antibodies are commercially available only for some members of these virus families., Conclusions: IHC may assist dermatopathologists to appropriately diagnose viral infections by parvoviruses, polyomaviruses, poxviruses, paramyxoviridae, picornaviridae, retroviruses, and filoviruses.
- Published
- 2015
- Full Text
- View/download PDF
321. Subcutaneous nodules with sporotrichoid spread in the forearm of a patient with rheumatoid arthritis.
- Author
-
de Vasconcelos P, Soares-Almeida L, Filipe P, and Kutzner H
- Subjects
- Forearm, Humans, Male, Middle Aged, Arthritis, Rheumatoid complications, Mycobacterium Infections, Nontuberculous complications, Mycobacterium Infections, Nontuberculous diagnosis, Mycobacterium chelonae, Skin Diseases, Bacterial complications, Skin Diseases, Bacterial diagnosis
- Published
- 2015
322. Immunohistochemistry in the diagnosis of cutaneous viral infections--part I. Cutaneous viral infections by herpesviruses and papillomaviruses.
- Author
-
Molina-Ruiz AM, Santonja C, Rütten A, Cerroni L, Kutzner H, and Requena L
- Subjects
- Biomarkers analysis, Biopsy, Herpesviridae Infections immunology, Herpesviridae Infections pathology, Herpesviridae Infections virology, Humans, Papillomavirus Infections immunology, Papillomavirus Infections pathology, Papillomavirus Infections virology, Predictive Value of Tests, Skin pathology, Skin virology, Skin Diseases, Viral immunology, Skin Diseases, Viral pathology, Skin Diseases, Viral virology, Antibodies, Monoclonal, Antigens, Viral analysis, Herpesviridae Infections diagnosis, Immunohistochemistry, Papillomavirus Infections diagnosis, Skin immunology, Skin Diseases, Viral diagnosis
- Abstract
Background: Cutaneous viral infections are of increasing clinical importance, particularly in patients who are immunocompromised., Objective: The use of immunohistochemistry (IHC) in the diagnosis of cutaneous infections provides a rapid morphological diagnosis and can be applied to confirm the diagnosis of specific viral infections that may be difficult to diagnose with certainty using routine microscopy alone, thus facilitating clinical decisions in patient care., Methods: Several immunostains for specific viruses that have been useful in dermatopathology are reviewed. Emphasis is placed on new stains and novel uses of existing stains., Results: This article is an up-to-date overview of the potential uses and limitations of IHC in the histopathologic diagnosis of cutaneous viral infections by herpesviruses and papillomaviruses., Limitations: Whereas specific monoclonal antibodies effectively distinguish infections by herpes simplex virus-1, herpes simplex virus-2, varicella zoster virus, Epstein-Barr virus, and cytomegalovirus, IHC does not distinguish between the 120 antigenically distinct strains of human papillomavirus., Conclusions: IHC may assist dermatopathologists to appropriately diagnose viral infections caused by herpesviruses and papillomaviruses.
- Published
- 2015
- Full Text
- View/download PDF
323. An immunohistochemical study of angiokeratomas of children.
- Author
-
Trindade F, Torrelo A, Kutzner H, Requena L, Tellechea Ó, and Colmenero I
- Subjects
- Adolescent, Angiokeratoma pathology, Child, Humans, Immunohistochemistry, Retrospective Studies, Skin Neoplasms pathology, Angiokeratoma classification, Biomarkers, Tumor analysis, Lymphatic Vessels abnormalities, Skin Neoplasms classification
- Abstract
Background: Angiokeratomas are vascular anomalies in which the clinical, histological, and immunohistochemical characteristics are insufficient to determine whether the lesion is a vascular neoplasm or vascular malformation, and their exact origin is also uncertain. To further clarify the nosology of angiokeratomas, we studied 14 cases., Objective: To analyze immunohistochemical characteristics of angiokeratomas to gain further insight into its histogenesis., Methods: We carried out a retrospective review of the histopathology files. Immunohistochemical expression for Wilms tumor 1 (WT1), GLUT1, D2-40, podoplanin, Prox1, and ERG1 was performed in 14 cases., Results: None of the lesions showed cytoplasmic immunoreactivity for WT1. GLUT1 resulted to be negative in 13 cases. All 14 cases in our series showed some expression with at least 1 lymphatic marker. In 12 cases, the positivity was diffuse and strong for ERG1., Conclusions: Angiokeratomas are complex lesions with difficult classification. Angiokeratomas are best considered vascular malformations in children, according to the WT1-negative stain. The lymphatic component of angiokeratoma is demonstrated by positivity and/or focal expression for lymphatic markers (podoplanin and Prox1); however, a blood capillary component within the malformation cannot be excluded.
- Published
- 2014
- Full Text
- View/download PDF
324. Sweet syndrome-like neutrophilic infiltrate as initial presentation of acute myelogenous leukemia.
- Author
-
Travassos AR, Soares-de-Almeida L, Kutzner H, Guerra L, Alves do Carmo J, Filipe P, and Marques MS
- Subjects
- Female, Fusion Proteins, bcr-abl genetics, Humans, Leukemia, Myeloid, Acute genetics, Middle Aged, Neutrophil Infiltration, Sweet Syndrome genetics, Leukemia, Myeloid, Acute pathology, Sweet Syndrome pathology
- Abstract
Sweet syndrome (SS) is a neutrophilic dermatosis that may be associated with malignancies, especially hematological. We describe the case of a 53-year-old woman with a clinical presentation suggestive of SS, accompanied by pancytopenia and a hypercellular marrow with signs of myelodysplasia. The histopathological findings were characterized as an SS-like cutaneous neutrophilic infiltrate with atypical myeloid cells, myeloperoxidase, and BCR-ABL+, which were absent in peripheral blood and bone marrow aspirate. The patient was treated with systemic corticosteroids with resolution of symptoms and relapse 3 months later when we tried drug withdrawal. Eight months later, the patient was admitted to hematology for a mature acute myelogenous leukemia with an FLT3 mutation. The patient successfully underwent medullar allotransplant and is now asymptomatic (5-month follow-up). This case describes a patient with an acute myelogenous leukemia presenting initially with heralding SS-like cutaneous neutrophilic infiltrate with atypical BCR-ABL+ myeloid cells, as a form of aleukemia cutis. Early recognition of this so-called aleukemic leukemia cutis may allow clinicians to intervene earlier, initiating effective treatment.
- Published
- 2014
- Full Text
- View/download PDF
325. Analysis of the lymphatic vessel architecture of atypical fibroxanthoma and pleomorphic dermal sarcoma.
- Author
-
Zschoche C, Hamsch C, Kutzner H, Mentzel T, Werchau S, Enk A, Hartschuh W, Hadaschik E, and Toberer F
- Subjects
- Biopsy, Needle, Diagnosis, Differential, Female, Fibroma diagnosis, Humans, Immunohistochemistry, Male, Sarcoma diagnosis, Skin Neoplasms diagnosis, Xanthomatosis diagnosis, Fibroma pathology, Lymphatic Vessels pathology, Sarcoma pathology, Skin Neoplasms pathology, Xanthomatosis pathology
- Published
- 2014
- Full Text
- View/download PDF
326. Self-healing juvenile cutaneous mucinosis: challenging diagnosis and management.
- Author
-
Kofler H, Lipsker D, Maurer H, Burgdorf W, Requena L, Torrelo A, Zelger B, Kutzner H, and Müller H
- Subjects
- Child, Preschool, Diagnosis, Differential, Humans, Male, Remission, Spontaneous, Dermatologic Agents therapeutic use, Facial Dermatoses drug therapy, Facial Dermatoses pathology, Immunosuppressive Agents therapeutic use, Mucinoses drug therapy, Mucinoses pathology
- Published
- 2014
- Full Text
- View/download PDF
327. Role of BRAFV600E in the first preclinical model of multifocal infiltrating myopericytoma development and microenvironment.
- Author
-
Sadow PM, Priolo C, Nanni S, Karreth FA, Duquette M, Martinelli R, Husain A, Clohessy J, Kutzner H, Mentzel T, Carman CV, Farsetti A, Henske EP, Palescandolo E, Macconaill LE, Chung S, Fadda G, Lombardi CP, De Angelis AM, Durante O, Parker JA, Pontecorvi A, Dvorak HF, Fletcher C, Pandolfi PP, Lawler J, and Nucera C
- Subjects
- Cell Line, Tumor, Cell Proliferation, Genotype, Glutamic Acid, Hemangiopericytoma genetics, Humans, Mass Spectrometry, Neoplasm Recurrence, Local genetics, Thyroid Neoplasms genetics, Valine, Vemurafenib, Xenograft Model Antitumor Assays, Angiogenesis Inhibitors pharmacology, Biomarkers, Tumor genetics, Hemangiopericytoma pathology, Indoles pharmacology, Mutation, Pericytes pathology, Proto-Oncogene Proteins B-raf genetics, Sulfonamides pharmacology, Thyroid Neoplasms pathology
- Abstract
Myopericytoma (MPC) is a rare tumor with perivascular proliferation of pluripotent stem-cell-like pericytes. Although indolent, MPC may be locally aggressive with recurrent disease. The pathogenesis and diagnostic biomarkers of MPC are poorly understood. We discovered that 15% of benign MPCs (thyroid, skin; 3 of 20 samples) harbored BRAF(WT/V600E); 33.3% (1 of 3 samples) of BRAF(WT/V600E)-MPCs were multifocal/infiltrative/recurrent. Patient-MPC and primary MPC cells harbored BRAF(WT/V600E), were clonal and expressed pericytic-differentiation biomarkers crucial for its microenvironment. BRAF(WT/V600E)-positive thyroid MPC primary cells triggered in vitro (8.8-fold increase) and in vivo (3.6-fold increase) angiogenesis. Anti-BRAF(V600E) therapy with vemurafenib disrupted angiogenic and metabolic properties (~3-fold decrease) with down-regulation (~2.2-fold decrease) of some extracellular-matrix (ECM) factors and ECM-associated long non-coding RNA (LincRNA) expression, with no effects in BRAF(WT)-pericytes. Vemurafenib also inhibited (~3-fold decrease) cell viability in vitro and in BRAF(WT/V600E)-positive thyroid MPC patient-derived xenograft (PDX) mice (n = 5 mice per group). We established the first BRAF(WT/V600E)-dependent thyroid MPC cell culture. Our findings identify BRAF(WT/V600E) as a novel genetic aberration in MPC pathogenesis and MPC-associated biomarkers and imply that anti-BRAF(V600E) agents may be useful adjuvant therapy in BRAF(WT/V600E)-MPC patients. Patients with BRAF(WT/V600E)-MPC should be closely followed because of the risk for multifocality/recurrence., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2014
- Full Text
- View/download PDF
328. Clinical and pathologic findings of Spitz nevi and atypical Spitz tumors with ALK fusions.
- Author
-
Busam KJ, Kutzner H, Cerroni L, and Wiesner T
- Subjects
- Adolescent, Adult, Anaplastic Lymphoma Kinase, Biomarkers, Tumor analysis, Biopsy, Child, Child, Preschool, DNA Copy Number Variations, Dynactin Complex, Female, Gene Dosage, Gene Rearrangement, Genetic Predisposition to Disease, Humans, In Situ Hybridization, Fluorescence, Lymphatic Metastasis, Male, Microtubule-Associated Proteins genetics, Nevus, Epithelioid and Spindle Cell enzymology, Nevus, Epithelioid and Spindle Cell pathology, Phenotype, Polymerase Chain Reaction, Receptor Protein-Tyrosine Kinases analysis, Skin Neoplasms enzymology, Skin Neoplasms pathology, Tropomyosin genetics, Young Adult, Biomarkers, Tumor genetics, Gene Fusion, Nevus, Epithelioid and Spindle Cell genetics, Receptor Protein-Tyrosine Kinases genetics, Skin Neoplasms genetics
- Abstract
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.
- Published
- 2014
- Full Text
- View/download PDF
329. Hypopigmented macules secondary to imatinib for the treatment of chronic myeloid leukemia: a histopathologic and immunohistochemical study.
- Author
-
Llamas-Velasco M, Fraga J, Kutzner H, Steegmann JL, García-Diez A, and Requena L
- Subjects
- Adult, Aged, Female, Humans, Imatinib Mesylate, Immunohistochemistry, Male, Melanins analysis, Melanins biosynthesis, Melanocytes pathology, Middle Aged, Skin Pigmentation drug effects, Antineoplastic Agents adverse effects, Benzamides adverse effects, Hypopigmentation chemically induced, Hypopigmentation pathology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Piperazines adverse effects, Pyrimidines adverse effects
- Abstract
Background: A few series addressing the cutaneous side effects related to imatinib in the skin have been published, but only one described scarce histopathologic information in seven patients., Objective: To characterize these lesions and compare the number of melanocytes between hypopigmented lesions and normal appearing skin., Methods: We retrieved clinical data of the patients and performed 24 skin biopsies (13 from hypopigmented skin and 11 from normal-appearing skin) within a cohort of 41 patients with chronic myeloid leukemia treated with imatinib. We classified the biopsies into three patterns., Results: About 45% of patients presented with periocular hypopigmentation. Perifollicular fibrosis was observed in hypopigmented skin biopsies (76.9%) and in normal-appearing skin (45.5%). Epidermal melanin, as determined with Masson-Fontana staining, and melanocyte number, as evaluated with MiTF, Melan A and c-kit immunostains, were lower in hypopigmented skin., Conclusions: Histopathologic study of hypopigmented macules demonstrates the presence of melanin with a statistically significant decrease in the number of melanocytes. Therefore, these findings differ from vitiligo, as melanocytes are present. Three histopathological patterns may be found, namely (a) perifollicular fibrosis, (b) lichen planopilaris-like and (c) apparently normal skin. One of the most striking histopathologic finding consisted of the presence of perifollicular fibrosis in both hypopigmented lesions and apparently normal skin., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2014
- Full Text
- View/download PDF
330. Histopathologic clues for the diagnosis of Wiesner nevus.
- Author
-
Llamas-Velasco M, Pérez-Gónzalez YC, Requena L, and Kutzner H
- Subjects
- Biopsy, Needle, Diagnosis, Differential, Genetic Predisposition to Disease, Germ-Line Mutation, Humans, Immunohistochemistry, Mutation, Nevus, Epithelioid and Spindle Cell chemistry, Nevus, Epithelioid and Spindle Cell diagnosis, Nevus, Pigmented chemistry, Nevus, Pigmented diagnosis, Proto-Oncogene Mas, Skin Neoplasms chemistry, Skin Neoplasms diagnosis, Biomarkers, Tumor analysis, Nevus, Epithelioid and Spindle Cell pathology, Nevus, Pigmented pathology, Skin Neoplasms pathology, Tumor Suppressor Proteins analysis, Ubiquitin Thiolesterase analysis
- Abstract
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., (Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
331. Desmoplastic melanoma: expression of epithelial-mesenchymal transition-related proteins.
- Author
-
Garrido MC, Requena L, Kutzner H, Ortiz P, Pérez-Gómez B, and Rodriguez-Peralto JL
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Immunohistochemistry, Male, Melanoma pathology, Middle Aged, Skin Neoplasms pathology, Tissue Array Analysis, Young Adult, Melanoma, Cutaneous Malignant, Biomarkers, Tumor analysis, Epithelial-Mesenchymal Transition, Melanoma metabolism, Skin Neoplasms metabolism
- Abstract
Desmoplastic melanoma (DM) is a rare variant of melanoma. Most frequently, it seems as clinically ambiguous and histologically characterized by a poorly demarcated neoplasm composed of a proliferation of spindle melanocytes dispersed in a prominent collagenous stroma. It often represents a diagnostic challenge, delaying its detection. We analyzed the expression profile of 29 (28 "pure" and 1 "combined") DM. These data were compared with a series of 62 primary vertical growth phase nondesmoplastic melanomas (NDMs) using a set of proteins including melanocytic markers (S-100 protein and melan-A) and epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin, SPARC, WT1, and PKCα). The S-100 protein confirmed the melanocytic origin of the DM (positive in 96%). The significant positive expression of N-cadherin, SPARC, and WT1 in DM (61%, 82%, and 71%) compared with NDM (28%, 43%, and 47%; P < 0.05) and a lower expression of E-cadherin in DM (14%) compared with NDM (61%) support specific adhesive and migratory properties of DM tumor cells. The study was carried out with tissue microarrays that partly limited the study of the tumor sections. This study demonstrates, for the first time, a prominent expression of epithelial-mesenchymal transition-related proteins in DMs and tries to be one more step in refining its knowledge and leading to a better understanding of its biological and clinical behaviors.
- Published
- 2014
- Full Text
- View/download PDF
332. Eruptive dermal clear cell desmo-plastic mesenchymal tumors with perivascular myoid differentiation in a young boy. A clinical, histopathologic, immunohistochemical and electron microscopy study of 17 lesions.
- Author
-
Tomasini C, Metze D, Osella-Abate S, Novelli M, and Kutzner H
- Subjects
- Actins, Antigens, CD metabolism, Antigens, Differentiation, Myelomonocytic metabolism, CD13 Antigens metabolism, Child, Follow-Up Studies, Humans, Immunohistochemistry, Male, Microscopy, Electron, Transmission, Neoplasm Proteins metabolism, Apoptosis, Cell Differentiation, Lysosomes metabolism, Lysosomes ultrastructure, Myeloid Cells metabolism, Myeloid Cells ultrastructure, Skin Neoplasms metabolism, Skin Neoplasms ultrastructure
- Abstract
Clear cell tumors of the skin are observed in a wide variety of benign and malignant conditions with different histogenesis, sharing the presence of cells with abundant clear cytoplasm. Herein, we report the clinicopathologic features of a healthy young patient affected by asymptomatic, eruptive and disseminated, benign clear cell dermal tumors since early infancy. Neither family history nor genetic testing and counseling provided further useful information. The lesions were mostly confined to the face and lower left extremity with pink teleangiectatic papules and small nodules. Over a 4-year period, a total of 16 different cutaneous lesions were biopsied and histopathologic and immunohistochemical studies carried out; an additional lesion was also removed for electron microscopy examination. Histopathology evidenced multiple perivascular growths of spindle to oval and round cells intermingled with clear/granular cells throughout the dermis, with prominent desmoplasia and numerous capillary-like vessels with focal hemangiopericytoma-like features. Immunohistochemical neoplastic cells were uniformly positive for h-caldesmon and focally smooth muscle α-actin and CD13 indicating myoid differentiation whereas the consistent diffuse cytoplasmic staining for lysosome antigen, such as CD68PG-M1 and NKI/C3 along with the ultrastructural findings supported the view of a lysosome-mediated apoptotic process. The differential diagnosis with other clear cell cutaneous neoplasms is discussed., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2014
- Full Text
- View/download PDF
333. Cutaneous deposits.
- Author
-
Molina-Ruiz AM, Cerroni L, Kutzner H, and Requena L
- Subjects
- Humans, Skin Diseases pathology
- Abstract
: The cutaneous deposition disorders are a group of unrelated conditions characterized by the accumulation of either endogenous or exogenous substances within the skin. These cutaneous deposits are substances that are not normal constituents of the skin and are laid down usually in the dermis, but also in the subcutis, in a variety of different circumstances. There are 5 broad categories of cutaneous deposits. The first group includes calcium salts, bone, and cartilage. The second category includes the hyaline deposits that may be seen in the dermis in several metabolic disorders, such as amyloidosis, gout, porphyria, and lipoid proteinosis. The third category includes various pigments, heavy metals, and complex drug pigments. The fourth category, cutaneous implants, includes substances that are inserted into the skin for cosmetic purposes. The fifth category includes miscellaneous substances, such as oxalate crystals and fiberglass. In this article, the authors review the clinicopathologic characteristics of cutaneous deposition diseases, classify the different types of cutaneous deposits, and identify all the histopathologic features that may assist in diagnosing the origin of a cutaneous deposit.
- Published
- 2014
- Full Text
- View/download PDF
334. Kinase fusions are frequent in Spitz tumours and spitzoid melanomas.
- Author
-
Wiesner T, He J, Yelensky R, Esteve-Puig R, Botton T, Yeh I, Lipson D, Otto G, Brennan K, Murali R, Garrido M, Miller VA, Ross JS, Berger MF, Sparatta A, Palmedo G, Cerroni L, Busam KJ, Kutzner H, Cronin MT, Stephens PJ, and Bastian BC
- Subjects
- Base Sequence, DNA Mutational Analysis, Genome, Human, Humans, Melanoma pathology, Molecular Sequence Data, Nevus, Epithelioid and Spindle Cell pathology, Reproducibility of Results, Skin Neoplasms pathology, Xenograft Model Antitumor Assays, Melanoma metabolism, Nevus, Epithelioid and Spindle Cell metabolism, Oncogene Proteins, Fusion metabolism, Protein Kinases metabolism, Skin Neoplasms metabolism
- Abstract
Spitzoid neoplasms are a group of melanocytic tumours with distinctive histopathological features. They include benign tumours (Spitz naevi), malignant tumours (spitzoid melanomas) and tumours with borderline histopathological features and uncertain clinical outcome (atypical Spitz tumours). Their genetic underpinnings are poorly understood, and alterations in common melanoma-associated oncogenes are typically absent. Here we show that spitzoid neoplasms harbour kinase fusions of ROS1 (17%), NTRK1 (16%), ALK (10%), BRAF (5%) and RET (3%) in a mutually exclusive pattern. The chimeric proteins are constitutively active, stimulate oncogenic signalling pathways, are tumourigenic and are found in the entire biologic spectrum of spitzoid neoplasms, including 55% of Spitz naevi, 56% of atypical Spitz tumours and 39% of spitzoid melanomas. Kinase inhibitors suppress the oncogenic signalling of the fusion proteins in vitro. In summary, kinase fusions account for the majority of oncogenic aberrations in spitzoid neoplasms and may serve as therapeutic targets for metastatic spitzoid melanomas.
- Published
- 2014
- Full Text
- View/download PDF
335. In response.
- Author
-
Kempf W, Kazakov DV, Cipolat C, Kutzner H, Roncador G, and Tomasini D
- Subjects
- Female, Humans, Biomarkers, Tumor analysis, CD4 Antigens analysis, CD8 Antigens analysis, Mycosis Fungoides immunology, Programmed Cell Death 1 Receptor analysis, Skin Neoplasms immunology, T-Lymphocytes, Helper-Inducer immunology
- Published
- 2014
- Full Text
- View/download PDF
336. Aberrant Promoter Hypermethylation of RASSF Family Members in Merkel Cell Carcinoma.
- Author
-
Richter AM, Haag T, Walesch S, Herrmann-Trost P, Marsch WC, Kutzner H, Helmbold P, and Dammann RH
- Abstract
Merkel cell carcinoma (MCC) is one of the most aggressive cancers of the skin. RASSFs are a family of tumor suppressors that are frequently inactivated by promoter hypermethylation in various cancers. We studied CpG island promoter hypermethylation in MCC of RASSF2, RASSF5A, RASSF5C and RASSF10 by combined bisulfite restriction analysis (COBRA) in MCC samples and control tissue. We found RASSF2 to be methylated in three out of 43 (7%), RASSF5A in 17 out of 39 (44%, but also 43% in normal tissue), RASSF5C in two out of 26 (8%) and RASSF10 in 19 out of 84 (23%) of the cancer samples. No correlation between the methylation status of the analyzed RASSFs or between RASSF methylation and MCC characteristics (primary versus metastatic, Merkel cell polyoma virus infection, age, sex) was found. Our results show that RASSF2, RASSF5C and RASSF10 are aberrantly hypermethylated in MCC to a varying degree and this might contribute to Merkel cell carcinogenesis.
- Published
- 2013
- Full Text
- View/download PDF
337. Cutaneous Alternariosis Caused by Alternaria infectoria: Three Cases in Kidney Transplant Patients.
- Author
-
Lopes L, Borges-Costa J, Soares-Almeida L, Filipe P, Neves F, Santana A, Guerra J, and Kutzner H
- Abstract
The genus Alternaria has more than 80 species. Alternaria alternata and Alternaria infectoria are the most frequent species associated with infections in humans. Their clinical importance lies in the growing number of cases reported in immunocompromised patients. Herein, we report three cases of kidney-transplanted patients with different clinical presentations of cutaneous alternariosis and we discuss the treatment options.
- Published
- 2013
- Full Text
- View/download PDF
338. Trichoblastomelanoma.
- Author
-
Juárez A, Díaz JL, Schaerer L, Kutzner H, and Requena L
- Subjects
- Humans, Male, Middle Aged, Hair Diseases pathology, Melanoma pathology, Neoplasms, Complex and Mixed pathology, Skin Neoplasms pathology
- Abstract
We present a 48-year-old man with a 1-year history of nodular lesion on the chest. On clinical examination, the tumor was ulcerated and had a translucent appearance with an erythematous halo. Histopathologic examination revealed a nodular lesion that comprised the upper half of the dermis and ulcerated the epidermis. The neoplasm was composed of 2 intermingled components: nests of atypical melanocytes and basaloid epithelial cells. Immunohistochemical stains confirmed 2 immunophenotypically distinct components. The melanocytic component expressed the usual melanocyte markers S100 protein, HMB45, Melan A, and MiTF1, whereas the second population of epithelial neoplastic cells expressed pan-cytokeratin-MNF116, Ber-Ep4, cytokeratin 14, beta-catenin, and pleckstrin homology-like domain, family A, member 1 positivity. On the basis of these immunohistochemical findings, a diagnosis of trichoblastomelanoma was established. Biphasic cutaneous neoplasms composed of melanocytes and epithelial cells are extremely rare, and to the best of our knowledge, this is the first description in the literature of a combination of trichoblastoma and melanoma in the same neoplasm.
- Published
- 2013
- Full Text
- View/download PDF
339. Sinonasal mucosal melanoma: Molecular profile and therapeutic implications from a series of 32 cases.
- Author
-
Turri-Zanoni M, Medicina D, Lombardi D, Ungari M, Balzarini P, Rossini C, Pellegrini W, Battaglia P, Capella C, Castelnuovo P, Palmedo G, Facchetti F, Kutzner H, Nicolai P, and Vermi W
- Subjects
- Adult, Aged, Aged, 80 and over, Cohort Studies, Cyclin D1 physiology, DNA-Binding Proteins physiology, Female, Genes, myb physiology, Genes, p16 physiology, Genes, ras physiology, Humans, Male, Melanoma pathology, Middle Aged, Mutation physiology, PTEN Phosphohydrolase physiology, Paranasal Sinus Neoplasms pathology, Proto-Oncogene Proteins B-raf physiology, Proto-Oncogene Proteins c-kit physiology, Transcription Factors physiology, Melanoma genetics, Melanoma therapy, Nasal Mucosa, Paranasal Sinus Neoplasms genetics, Paranasal Sinus Neoplasms therapy
- Abstract
Background: Primary sinonasal mucosal melanomas are aggressive tumors with a poor clinical control by current treatments, raising the urgent need of novel strategies., Methods: By fluorescence in situ hybridization (FISH), direct sequencing, and immunohistochemistry, we investigate the spectrum of molecular abnormalities in a cohort of 32 cases of primary sinonasal mucosal melanomas., Results: We found that all primary sinonasal mucosal melanomas lack BRAF V600E mutation; in addition, they are characterized by somatic mutations of NRAS (22%) and KIT (12.5%), together with amplification of RREB1 (100%) and loss of MYB (76%). The large majority of cases showed KIT protein expression (96.9%). Among tumor suppressor genes, primary sinonasal mucosal melanomas showed loss of PTEN (48.1%) and p16/INK4a (55.2%). All tested cases showed expression of pAkt and pErk, suggesting a combined activation of PI3K/Akt and RAS-mitogen-activated protein kinase (MAPK) pathways., Conclusions: This molecular fingerprint strongly argues against the clinical efficacy of BRAF-inhibitors, but could candidate primary sinonasal mucosal melanomas to therapeutic strategies targeting RAS and KIT mutations or inhibiting PI3K-Akt-mTOR pathway., (Copyright © 2012 Wiley Periodicals, Inc.)
- Published
- 2013
- Full Text
- View/download PDF
340. Cutaneous adenodermatofibroma: report of 2 cases.
- Author
-
Santos-Briz A, Llamas-Velasco M, Arango L, Yuste M, Paredes BE, and Kutzner H
- Subjects
- Adult, Apocrine Glands pathology, Biomarkers, Tumor analysis, Biopsy, Dilatation, Pathologic, Female, Histiocytoma, Benign Fibrous chemistry, Humans, Immunohistochemistry, Male, Skin Neoplasms chemistry, Stromal Cells pathology, Histiocytoma, Benign Fibrous pathology, Skin Neoplasms pathology
- Abstract
Dermatofibromas (DFs) are common benign fibrohistiocytic lesions, mostly affecting young adults. Many types of DF have been described, depending on architectural, cellular, and stromal peculiarities. Recently, a peculiar type of benign cutaneous tumor showing hemosiderotic DF-like stroma and apocrine glands has been described. We report 2 additional cases of DF without hemosiderotic changes showing entrapped apocrine glandular structures. We speculate about the origin of the glandular component and propose the term adenodermatofibroma for this type of lesions.
- Published
- 2013
- Full Text
- View/download PDF
341. Cutaneous PEComa does not harbour TFE3 gene fusions: immunohistochemical and molecular study of 17 cases.
- Author
-
Llamas-Velasco M, Mentzel T, Requena L, Palmedo G, Kasten R, and Kutzner H
- Subjects
- Adult, Aged, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors metabolism, Epithelioid Cells metabolism, Epithelioid Cells pathology, Female, Humans, In Situ Hybridization, Fluorescence, Male, Middle Aged, Perivascular Epithelioid Cell Neoplasms metabolism, SOXE Transcription Factors genetics, SOXE Transcription Factors metabolism, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors genetics, Gene Fusion, Perivascular Epithelioid Cell Neoplasms genetics, Perivascular Epithelioid Cell Neoplasms pathology
- Abstract
Aims: The family of perivascular epithelioid cell tumours (PEComas) comprises a related group of mesenchymal tumours of uncertain origin that show both smooth muscle and melanocytic differentiation markers. TFE3 nuclear immunoreactivity may be viewed as a supporting marker, as it has been found in a subset of visceral PEComas. We immunohistochemically analysed 17 cases of primary cutaneous PEComas for TFE3, and five of them also for SOX-10, and also analysed them by FISH for TFE3 rearrangement., Methods and Results: PEComas presented as skin-coloured tumours, in 12 women and five men, with a median age of 49.5 years. Tumours showed either a mixed clear cell-epithelioid cell pattern or a monomorphous clear cell pattern. None of the primary cutaneous PEComas showed detectable TFE3 or SOX-10 positivity. FISH assay for TFE3 rearrangement yielded negative results in all of the tested tumours., Conclusions: Cutaneous PEComas are mostly composed of clear cells, and, unlike a subset of visceral and deep-seated PEComas, cutaneous PEComas consistently lack TFE3 expression. Owing to the lack of SOX-10 expression, a neural crest origin could not be shown., (© 2013 John Wiley & Sons Ltd.)
- Published
- 2013
- Full Text
- View/download PDF
342. Brief S1 guidelines--Cutaneous angiosarcoma and Kaposi sarcoma.
- Author
-
Vogt T, Brockmeyer N, Kutzner H, and Schöfer H
- Subjects
- Dermatology trends, Germany, Humans, Medical Oncology standards, Medical Oncology trends, Dermatology standards, Hemangiosarcoma diagnosis, Hemangiosarcoma therapy, Practice Guidelines as Topic, Sarcoma, Kaposi diagnosis, Sarcoma, Kaposi therapy, Skin Neoplasms diagnosis, Skin Neoplasms therapy
- Published
- 2013
- Full Text
- View/download PDF
343. A benign cutaneous plexiform hybrid tumor of perineurioma and cellular neurothekeoma.
- Author
-
Requena L, Sitthinamsuwan P, Fried I, Kaddu S, Schirren CG, Schärer L, Hantschke M, Cerroni L, McCalmont TH, and Kutzner H
- Subjects
- Adult, Aged, Biomarkers, Tumor analysis, Female, Humans, Immunohistochemistry, Lip Neoplasms metabolism, Male, Middle Aged, Neoplasms, Complex and Mixed metabolism, Nerve Sheath Neoplasms metabolism, Neurothekeoma metabolism, Lip Neoplasms pathology, Neoplasms, Complex and Mixed pathology, Nerve Sheath Neoplasms pathology, Neurothekeoma pathology
- Abstract
There are several recent reports describing hybrid peripheral nerve sheath tumors showing a biphasic component of neoplastic cells. These combinations include a mixture of neurofibroma and schwannoma, schwannoma and perineurioma, neurofibroma and perineurioma, and perineurioma and granular cell tumor. A case of a triphasic combination of neurofibroma, schwannoma, and perineurioma has also been described. We describe the clinicopathologic and immunohistochemical characteristics of 9 cases of a benign cutaneous plexiform nerve sheath tumor located on the lips and exhibiting hybrid features of perineurioma and cellular neurothekeoma. Clinically, lesions were solitary dome-shaped papules located on the lips. Histopathologically, the neoplasms consisted of well-circumscribed but uncapsulated dermal nodules with a plexiform pattern. They were composed of nests or rounded aggregations of neoplastic cells embedded in a slightly myxoid stroma. Within the aggregates, cells were distributed in a storiform and lamellar pattern. Immunohistochemically, most neoplastic cells expressed strong immunoreactivity for S100A6, MiTF, NKI/C3, PGP9.5, EMA, and NSE, whereas variable, focal, and weaker positivity for CD34, claudin-1, and Glut-1 was seen in some cases. On the basis of these findings, we believe that this neoplasm is a distinctive benign cutaneous plexiform nerve sheath tumor with histopathologic and immunohistochemical hybrid features of perineurioma and cellular neurothekeoma.
- Published
- 2013
- Full Text
- View/download PDF
344. Molecular diagnostics in infectious skin diseases.
- Author
-
Kempf W, Flaig MJ, and Kutzner H
- Subjects
- Genetic Testing methods, Humans, Polymorphism, Single Nucleotide genetics, Biomarkers, Tumor genetics, DNA Mutational Analysis methods, Molecular Diagnostic Techniques methods, Skin Diseases, Infectious genetics, Skin Diseases, Infectious microbiology
- Published
- 2013
- Full Text
- View/download PDF
345. Basaloid tumors in nevus sebaceus revisited: the follicular stem cell marker PHLDA1 (TDAG51) indicates that most are basal cell carcinomas and not trichoblastomas.
- Author
-
Sellheyer K, Cribier B, Nelson P, Kutzner H, and Rütten A
- Subjects
- Biomarkers, Tumor metabolism, Carcinoma, Basal Cell metabolism, Cell Count, Hair Diseases metabolism, Hair Follicle pathology, Humans, Immunohistochemistry, Neoplasms, Adnexal and Skin Appendage metabolism, Nevus, Sebaceous of Jadassohn metabolism, Skin Neoplasms metabolism, Carcinoma, Basal Cell diagnosis, Hair Diseases diagnosis, Neoplasms, Adnexal and Skin Appendage diagnosis, Nevus, Sebaceous of Jadassohn diagnosis, Skin Neoplasms diagnosis, Transcription Factors metabolism
- Abstract
Background: Until the 1990s, basal cell carcinoma (BCC) was viewed as the most common epithelial neoplasm developing in association with nevus sebaceus (NS). Currently, trichoblastoma is thought of as the most prevalent basaloid neoplasm in NS. The follicular stem cell marker pleckstrin homology-like domain, family A, member 1 (PHLDA1) also known as T-cell death-associated gene 51 (TDAG51) labels trichoepithelioma (TE) but not BCC. Therefore, we explored its usefulness in basaloid neoplasms developing in NS., Methods: We studied immunohistochemically PHLDA1 in 10 nodular BCCs, 11 TEs, 11 trichoblastomas and 25 NS with basaloid tumors. Additionally, we examined the expression of BCC marker BerEP4 and the distribution of Merkel cells that function as surrogate markers for benign follicular neoplasms., Results: Nineteen of the 25 basaloid tumors in NS were PHLDA1-negative comparable to BCC arising de novo and six tumors were PHLDA1-positive comparable to solitary trichoblastomas and TEs. Fewer Merkel cells were seen in BCCs associated with NS when compared with trichoblastoma. BerEP4 did not discriminate between the neoplasms., Conclusions: We raise concern that the unquestioned assessment that basaloid tumors developing in association with NS represent mostly trichoblastomas and not BCC may not be true. This influences clinical care, as it is paramount in the decision of whether to excise these lesions or not., (Copyright © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)
- Published
- 2013
- Full Text
- View/download PDF
346. Molecular biology methods to improve diagnosis and prognosis of melanocytic tumors.
- Author
-
Wiesner T, Fried I, Cerroni L, and Kutzner H
- Subjects
- Female, Genetic Testing methods, Humans, Polymorphism, Single Nucleotide genetics, Biomarkers, Tumor genetics, DNA Mutational Analysis methods, Melanoma diagnosis, Melanoma genetics, Molecular Diagnostic Techniques methods, Skin Neoplasms diagnosis, Skin Neoplasms genetics
- Published
- 2013
- Full Text
- View/download PDF
347. Follicular lymphomatoid papulosis revisited: a study of 11 cases, with new histopathological findings.
- Author
-
Kempf W, Kazakov DV, Baumgartner HP, and Kutzner H
- Subjects
- Adolescent, Adult, Aged, Biopsy, Child, Dermatitis pathology, Female, Humans, Lymphocytes pathology, Male, Middle Aged, Retrospective Studies, Young Adult, Hair Follicle pathology, Lymphomatoid Papulosis pathology, Mucinosis, Follicular pathology, Skin Neoplasms pathology
- Abstract
Background: Follicular lymphomatoid papulosis (LyP) describes a variant of LyP with perifollicular infiltrates and some degree of folliculotropism of CD30(+) atypical lymphocytes. So far, only a few cases of follicular LyP have been described., Objective: Our goal was to study the clinicopathologic features of follicular LyP in a series of 11 cases (9 male, 2 female; age range 7-78 years, mean age 50 years)., Methods: In all, 113 cases of LyP were reviewed to select cases showing follicular involvement. Histology was correlated with the clinical data to exclude cases of CD30(+) anaplastic large-cell lymphoma or folliculotropic mycosis fungoides., Results: Six cases were classified as type C and 4 as type A, whereas the remaining case manifested epidermotropism of small lymphocytes in a background of a typical type A lesion (overlapping type A/B). Perifollicular infiltrates of CD30(+) atypical lymphoid cells were seen in all 11 cases, with infiltration of the follicular epithelium in 8 cases. Hyperplasia of the follicular epithelium was observed in 4 cases; ruptured hair follicles, in 3 cases; and follicular mucinosis, in 2 cases. In addition to hair follicle infiltration, atypical cells were recognized within sebaceous glands in 2 lesions. New findings were presence of numerous intrafollicular neutrophils in 2 patients, who clinically had pustules in addition to papules. Other histopathological features encountered included perieccrine infiltration (n = 5), focal subcutaneous involvement (n = 4), granulomatous inflammation (n = 3), epidermal hyperplasia (n = 2), and 1 each of infiltration of muscle bundles, numerous eosinophils in the infiltrate, and angiocentricity., Limitations: This was a retrospective study., Conclusions: Follicular LyP is a variant of LyP with involvement of hair follicles, mostly in the form of perifollicular infiltrate with variable degree of folliculotropism. Other changes including hyperplasia of the follicular epithelium, rupture of hair follicle, and follicular mucinosis are less common. Rarely, intrafollicular pustules can be seen in the follicular epithelium; such lesions manifest clinically as pustules., (Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
348. Molecular pathology diagnostics in cutaneous mesenchymal tumors.
- Author
-
Kutzner H, Requena L, Palmedo G, and Mentzel T
- Subjects
- Genetic Testing methods, Humans, Polymorphism, Single Nucleotide genetics, Biomarkers, Tumor genetics, DNA Mutational Analysis methods, Molecular Diagnostic Techniques methods, Sarcoma diagnosis, Sarcoma genetics, Skin Neoplasms diagnosis, Skin Neoplasms genetics
- Published
- 2013
- Full Text
- View/download PDF
349. The immunohistochemical differential diagnosis of microcystic adnexal carcinoma, desmoplastic trichoepithelioma and morpheaform basal cell carcinoma using BerEP4 and stem cell markers.
- Author
-
Sellheyer K, Nelson P, Kutzner H, and Patel RM
- Subjects
- Carcinoma, Basal Cell metabolism, Diagnosis, Differential, Humans, Immunohistochemistry methods, Neoplasms, Adnexal and Skin Appendage metabolism, Skin Neoplasms metabolism, Stem Cells metabolism, Stem Cells pathology, Transcription Factors metabolism, Biomarkers, Tumor metabolism, Carcinoma, Basal Cell diagnosis, Neoplasms, Adnexal and Skin Appendage diagnosis, Skin Neoplasms diagnosis
- Abstract
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.)
- Published
- 2013
- Full Text
- View/download PDF
350. Cutaneous epithelioid sarcomalike (pseudomyogenic) hemangioendothelioma: a little-known low-grade cutaneous vascular neoplasm.
- Author
-
Requena L, Santonja C, Martinez-Amo JL, Saus C, and Kutzner H
- Subjects
- Adult, Biomarkers, Tumor metabolism, Female, Hemangioendothelioma, Epithelioid metabolism, Hemangioendothelioma, Epithelioid surgery, Humans, Immunohistochemistry, Keratins metabolism, Male, Skin metabolism, Skin Neoplasms metabolism, Skin Neoplasms surgery, Young Adult, Hemangioendothelioma, Epithelioid pathology, Skin pathology, Skin Neoplasms pathology
- Abstract
Importance: Epithelioid sarcomalike (pseudomyogenic) hemangioendothelioma (ES-H) is a recently described and little-known vascular neoplasm that frequently presents with dermatologic lesions. Histopathologic characterization includes sheets or fascicles of plump, spindled and epithelioid, rhabdomyoblastlike neoplastic cells involving the dermis and often extending to subcutaneous tissue. Immunohistochemical analysis reveals neoplastic cells that show a constant immunophenotype characterized by immunoreactivity for cytokeratins and endothelial markers., Observations: We described the clinical, histopathologic, and immunohistochemical features of 2 cases of cutaneous ES-H. Clinical examination revealed multifocal lesions that consisted of erythematous nodules on the leg and foot in case 1 and small perioral papules in case 2. Neoplastic cells had a rhabdomyoblastic appearance, with large nuclei and ample eosinophilic cytoplasm. Immunohistochemical analysis revealed expression of cytokeratin AE1/AE3, CD31, ERG, and FLI-1, with focal and weak positivity for CAM 5.2 and smooth muscle actin. The nuclei of neoplastic cells showed intact expression of INI-1. This immunoprofile, especially the ERG positivity, demonstrated the endothelial nature of proliferating cells., Conclusions: We recommend adding the low-grade neoplasm ES-H to the large list of cutaneous vascular proliferations. Dermatologists should be aware of this low-grade cutaneous vascular tumor.
- Published
- 2013
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.