Squamoid eccrine ductal carcinoma

Kutane und systemische Veränderungen mit Ähnlichkeiten zum Omenn‐Syndrom bei heterozygoter Mutation im RAG2‐Gen

Epigenetic Silencing of CDR1as Drives IGF2BP3-Mediated Melanoma Invasion and Metastasis.

Summary Metastasis is the primary cause of death of cancer patients. Dissecting mechanisms governing metastatic spread may uncover important tumor biology and/or yield promising therapeutic insights. Here, we investigated the role of circular RNAs (circRNA) in metastasis, using melanoma as a model aggressive tumor. We identified silencing of cerebellar degeneration-related 1 antisense (CDR1as), a regulator of miR-7, as a hallmark of melanoma progression. CDR1as depletion results from epigenetic silencing of LINC00632, its originating long non-coding RNA (lncRNA) and promotes invasion in vitro and metastasis in vivo through a miR-7-independent, IGF2BP3-mediated mechanism. Moreover, CDR1as le…

Answer to “Immunoexpression of p53 in cutaneous and subcutaneous leiomyosarcomas”

Fluorescent in situ hybridization (FISH): A useful diagnostic tool for childhood conjunctival melanoma

Introduction: Conjunctival melanoma is extremely rare in children and has low rates of resolution. Definitive histopathological diagnosis based exclusively on microscopic findings is sometimes difficult. Thus, early diagnosis and adequate treatment are essential to improve clinical outcomes. Clinical case: We present the first case in which the fluorescent in situ hybridization (FISH) diagnostic technique was applied to a 10-year-old boy initially suspected of having amelanotic nevi in his right eye. Based on the 65% of tumor cells with 11q13 (CCND1) copy number gain and 33% with 6p25 (RREB1) gain as measured by the FISH analysis, and on supporting histopathological findings, the diagnosis …

Identification of a 58-kilodalton cell surface fibrinogen-binding mannoprotein from Candida albicans.

Treatment of both yeast (blastoconidia) and hyphal (blastoconidia with germ tubes) cells of Candida albicans with beta-mercaptoethanol (beta ME) releases a complex array of cell wall-bound proteins and glycoproteins. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western immunoblotting with fibrinogen-anti-fibrinogen antibody allowed the identification of a 58-kDa mannoprotein (mp58) in both extracts which specifically interacts with human fibrinogen. Treatment of intact cells with low concentrations of beta-glucanase (Zymolyase 20T) for short periods or with beta ME abolished or significantly reduced binding of fibrinogen. A rabbit polyclonal antiserum was raised…

Two-year-old girl with tuberous xanthomas.

A 2-year-old girl was referred for evaluation because she had two nodular lesions located on both heels, and another elongated lesion in the intergluteal cleft. On physical examination, two yellow to orange well-defined nodules, suggestive of xanthomas, were bilaterally located on the Achilles tendon areas (figure 1A). Moreover, another yellowish, slightly raised lesion with band-like morphology was seen in the intergluteal cleft (figure 1B). There were no other anomalies on physical examination. Figure 1 (A) Tuberous xanthoma located on the left heel. (B) Planar xanthoma located in the intergluteal cleft. (C) Peripheral blood smear examination showing numerous red cells and two macrothromb…

Is It a Metastatic Disease: A Case Report and New Understanding of Rosai-Dorfman Disease?

Pleomorphic cutaneous Rosai-Dorfman disease.

we report three cases of pure cutaneous Rosai-Dorfman disease (RDD) showing prominent nuclear pleomorphism. This unusual finding confers a worrisome appearance to these lesions, challenging their recognition and creating difficulty in the differential diagnosis with malignant neoplasms. This article is protected by copyright. All rights reserved.

Expression of Peripheral Node Addressins by Plasmacytic Plaque of Children, APACHE, TRAPP, and Primary Cutaneous Angioplasmacellular Hyperplasia.

High-endothelial venules are a common feature of 3 types of cutaneous pseudolymphomas: pretibial lymphoplasmacytic plaque (PLP) of children, acral pseudolymphomatous angiokeratoma of children (APACHE), and T-cell rich angiomatoid polypoid pseudolymphoma (TRAPP). In addition, primary cutaneous angioplasmacellular hyperplasia (PCAH) overlaps with these other 3 conditions. We intend to study the expression of peripheral node addressins in PLP, APACHE, TRAPP, and PCAH. We studied 1 case of PLP, 2 cases of APACHE, 2 cases of TRAPP, and 2 cases of PCAH. Immunostainings for MECA-79 and WT-1 were obtained in all cases. All cases showed a dense lymphohistiocytic dermal inflammatory infiltrate with a…

Psammomatous malignant melanoma arising in an intradermal naevus

Psammomatous malignant melanoma arising in an intradermal naevus Aims: A wide variety of differentiation patterns may be found in malignant melanoma. Schwannian features are unusual, and mostly present in the desmoplastic variant. We report the first description of psammoma bodies in malignant melanoma. Methods and results: A malignant melanoma arose in an intradermal naevus of the scalp in a 51-year-old woman, displaying focal neural-like features in the form of rosette-like pseudo-meissnerian alveolar nests, as well as numerous psammoma bodies grouped in a few areas. Tumour cell immunostaining for S100, HMB45, NKI-C3, and vimentin was detected. In addition, both malignant and benign melan…

Verrucous Plaque With Unusually Large Candida Blastoconidia: A Unique Clinicopathological Presentation of Systemic Mucocutaneous Candidiasis.

Mucocutaneous candidiasis is a common infection affecting both immunocompetent and immunosuppressed individuals. Diversity in the clinical and histopathological presentation of mucocutaneous candidiasis is well known. However, the occurrence of cutaneous verrucous lesions and giant yeast-like structures has been rarely reported. In this article, we describe a case of disseminated mucocutaneous candidiasis in an immunosuppressed patient who presented as a verrucous plaque on the scrotum with giant Candida blastoconidia. This peculiar presentation expands the clinicopathological spectrum of mucocutaneous candidiasis and highlights the wide range of clinical manifestations and great morphologi…

Proteinuria persistente en mujer hipertensa infectada por el VIH

Clinical strains ofCandida albicansexpress the surface antigen glyceraldehyde 3-phosphate dehydrogenase in vitro and in infected tissues

We have previously described the presence of an enzymatically active form of glyceraldehyde 3-phosphate-dehydrogenase (GAPDH) in the cell surface of Candida albicans ATCC 26555 which is also a fibronectin and laminin binding protein. Immunohistochemical analysis of tissue sections from patients with disseminated candidiasis with a polyclonal antiserum to GAPDH from C. albicans (PAb anti-CA-GAPDH) revealed that the enzyme is expressed at the surface of fungal cells in infected tissues. The same PAb detected the presence of GAPDH species, with a molecular mass of approximately 33 kDa, in cell wall extracts obtained from clinical isolates of the fungus. These cell surface-bound GAPDH moieties …

Monoclonal antibody 3H8: A useful tool in the diagnosis of candidiasis

In a previous series of experiments six mAbs were obtained against cell wall extracts of Candida albicans ATCC 26555. After several studies only one of them, designated 3H8, has been used to produce a commercial kit for the rapid diagnosis of candidiasis, Bichro-latex albicans (Fomouze Diagnostics). The present study involved the generation and characterization of this mAb as an immunoglobulin G1 which recognizes mannoproteins of high molecular mass present in the C. albicans cell wall. ELISA assays showed that the presence of the epitope recognized by mAb 3H8 was similar in both yeast and mycelial cell walls of C. albicans, in contrast to the epitope for mAb 1B12, which is mainly expressed…

Keratoacanthoma Centrifugum Marginatum (KCM) after photodynamic therapy with good response to oral retinoids and topical 5‐fluorouracil

Keratoacanthoma centrifugum marginatum (KCM) is a rare variant of keratoacanthoma (KA), characterized by progressive peripheral growth, and usually devoid of deep invasion. Different systemic (oral retinoids) or topical treatments have been reported, but there is not a well-defined therapeutic protocol. We report the case of a KCM developing after photodynamic therapy (PDT) on the right leg of a 64-year-old woman. It was treated successfully with oral acitretin combined with topical 5-Fluorouracil + salicylic acid for 5 months. This is the first case of KCM developing after PDT and successfully treated with oral retinoid combined with topical treatment.

Asymptomatic erythematous hardened plaque on the scalp

Cutaneous sclerosing Pacinian-like perineurioma

Cutaneous sclerosing Pacinian-like perineurioma Aims: The term perineurioma has been used to designate a variety of clinically and histologically different proliferations of perineurial cells based on immunohistochemical and/or ultrastructural characterization. There are two different groups of neoplasms derived from perineurial cells: extraneural or soft tissue perineuriomas, and intraneural perineuriomas. Recently, a sclerosing variant of cutaneous perineurioma has been described. Methods and results: We report a case of a cutaneous form of perineurioma, combining features of the intraneural and sclerosing varieties, as well as showing a Pacinian pattern of growth. In order to assess the …

Uterine glomeruloid hemangioma in a patient without POEMS syndrome.

Cutaneous glomeruloid hemangioma is a hallmark of POEMS syndrome. These patients have elevated serum levels of vascular endothelial growth factor. The authors report an extracutaneous uterine glomeruloid hemangioma in an 82-year-old woman with a history of breast and endometrial carcinomas. Within the lumen of myometrial vessels, a lobular, glomeruloid proliferation of capillary-like CD31 and vascular endothelial growth factor receptor-1-positive endothelial cells was found. The capillary loops were lined by endothelial cells, most of them containing PAS-positive and immunoglobulin-positive eosinophilic hyaline globules (thanatosomes). This vascular proliferation was consistent with a glom…

Reply to "More evidence that genetic profiling will delineate the nosology and biologic potential of fibrohistiocytic tumors in the dermatofibrosarcoma protuberans spectrum".

Molecular cloning and characterization ofEchinostoma caproniheat shock protein-70 and differential expression in the parasite derived from low- and high-compatible hosts

SUMMARYWe cloned and expressedEchinostoma caproniHSP70 inEscherichia coli. This molecule presents an open reading frame (ORF) of 655 amino acids, and a theoretical molecular weight of 71 kDa.E. caproniHSP70 protein showed a high homology to other helminth molecules, major differences being located in the C-terminal region of the molecule, with a hydrophobic portion. Studies of protein and messenger RNA (mRNA) expression revealed a distinct pattern, depending on the host (low- or high-compatible). Specific polyclonal antisera raised against the recombinant protein expressed inEscherichia colidemonstrated its selective presence in excretory/secretory products (ESP) of adult parasites obtained…

Regresión completa de nevos melanocíticos: correlación clínica, dermatoscópica e histológica de una serie de 13 casos

Resumen Antecedentes y objetivos La regresion completa de neoplasias melanociticas, confirmada mediante estudio histologico, se ha descrito de forma excepcional en la literatura. En esos casos es muy complicado discernir si la lesion previa era maligna o benigna, y en ocasiones tan solo la presencia o ausencia de metastasis en el seguimiento posterior del paciente permite establecer dicha distincion. Metodos Se realizo un analisis descriptivo que incluyo los nevos melanociticos extirpados en nuestro Servicio de Dermatologia en un periodo de tres anos, en los que el estudio histologico demostro una regresion completa de los mismos. Se analizaron exclusivamente aquellas lesiones de las cuales…

Invasión de vasos linfáticos en nevos melanocíticos. Estudio clinicopatológico de ocho casos

Introduccion . La invasion de vasos linfaticos por melanocitos de nevos melanociticos es un hallazgo infrecuente. Por otro lado, la presencia de melanocitos en los ganglios linfaticos se detecta de forma casual en linfadenectomias regionales por carcinomas y melanomas. Metodos . Hemos estudiado 8 casos de nevos melanociticos cutaneos con invasion de vasos linfaticos, analizando sus caracteristicas clinicas e histologicas, asi como la inmunotincion para Ki-67. Resultados . Siete de los 8 casos correspondian a mujeres; cinco fueron diagnosticados como nevos congenitos, observandose en estos ultimos un crecimiento solido melanocitico intravascular con integridad de la superficie endotelial. En…

Pseudohyphal Regulation by the Transcription Factor Rfg1p in Candida albicans

ABSTRACT The opportunistic human fungal pathogen Candida albicans is a major cause of nosocomial infections. One of the fundamental features of C. albicans pathogenesis is the yeast-to-hypha transition. Hypha formation is controlled positively by transcription factors such as Efg1p and Cph1p, which are required for hyphal growth, and negatively by Tup1p, Rfg1p, and Nrg1p. Previous work by our group has shown that modulating NRG1 gene expression, hence altering morphology, is intimately linked to the capacity of C. albicans to cause disease. To further dissect these virulence mechanisms, we employed the same strategy to analyze the role of Rfg1p in filamentation and virulence. Studies using …

Echinostoma caproni: intestinal pathology in the golden hamster, a highly compatible host, and the Wistar rat, a less compatible host.

The histopathological changes induced by Echinostoma caproni (Trematoda: Echinostomatidae) in a high (golden hamster) and a low compatible host (rat) were compared at 15 and 30 days post-infection. Infection of rats was characterized by a progressive increase in erosion of villi and elevated numbers of goblet cells, which could be related to the early expulsion of the parasite in a host of low compatibility. In contrast to rats, the number of goblet cell in E. caproni-infected hamsters was low, but increased numbers of neutrophils and mesenteric inflammatory cells were observed. This indicated that local inflammatory responses in hamsters were greater than in rats. An immunohistochemical st…

Diagnostic value of CD34 immunostaining in desmoplastic trichilemmoma.

Desmoplastic trichilemmoma (DT) is a variant of trichilemmoma, characterized by a central prominent desmoplastic component which may simulate invasive carcinoma. We have studied the morphologic and immunohistochemical features of seven cases of DT. Immunohistochemistry was performed on paraffin sections using monoclonal antibodies to CD34 (QBEND/10), vimentin and GCDFP-15. CD34 was also tested in seven cases of basal cell carcinoma (BCC), three with outer root sheath differentiation and four with morphea-form features, and five squamous cell carcinomas. Histologically, features of conventional trichilemmoma were seen at the periphery of the seven lesions. In contrast, at the center, the epi…

Haemangioendothelioma: a current perspective

The density and type of MECA-79-positive high endothelial venules correlate with lymphocytic infiltration and tumour regression in primary cutaneous melanoma

Aims Tumour-infiltrating lymphocytes have prognostic value in malignant melanoma. High endothelial venules (HEVs) are specialized vessels present in lymph nodes and tertiary lymphoid organs. CCL19, CCL21 and CCR7 regulate lymphocyte migration through HEVs. The aim of our study was to correlate HEV density in cutaneous primary and metastatic malignant melanomas with clinicopathological parameters, and with CCL19, CCL21 and CCR7 mRNA expression. Methods and results High endothelial venule density was evaluated by immunohistochemistry with a specific antibody, MECA-79, and chemokine expression was evaluated by real-time PCR. MECA-79-positive vessels, covered by cuboidal (C-HEV) or flat (F-HEV)…

Validation of the Tetracycline Regulatable Gene Expression System for the Study of the Pathogenesis of Infectious Disease

Understanding the pathogenesis of infectious disease requires the examination and successful integration of parameters related to both microbial virulence and host responses. As a practical and powerful method to control microbial gene expression, including in vivo, the tetracycline-regulatable system has recently gained the favor of many investigative groups. However, some immunomodulatory effects of the tetracyclines, including doxycycline, could potentially limit its use to evaluate host responses during infection. Here we have used a well-established murine model of disseminated candidiasis, which is highly dependent on both the virulence displayed by the fungal cells and on the host im…

An attention-based weakly supervised framework for spitzoid melanocytic lesion diagnosis in whole slide images

[EN] Melanoma is an aggressive neoplasm responsible for the majority of deaths from skin cancer. Specifically, spitzoid melanocytic tumors are one of the most challenging melanocytic lesions due to their ambiguous morphological features. The gold standard for its diagnosis and prognosis is the analysis of skin biopsies. In this process, dermatopathologists visualize skin histology slides under a microscope, in a highly time-consuming and subjective task. In the last years, computer-aided diagnosis (CAD) systems have emerged as a promising tool that could support pathologists in daily clinical practice. Nevertheless, no automatic CAD systems have yet been proposed for the analysis of spitzoi…

Familial seborrhoeic keratosis associated with multiple 'pure reticulated acanthomas' and infundibulocystic basal cell carcinomas.

Background A variety of genodermatoses with multiple cutaneous tumors with germline genetic alterations such as Gorlin syndrome with PTCH1 gene mutations have been described. Other cutaneous syndromes have been associated with somatic gene mutations, such as FGFR3 in familial seborrhoeic keratosis. Objective We describe the clinical, dermoscopic, and histopathological features of multiple cutaneous lesions, mostly infundibulocystic basal cell carcinomas and pure reticulated acanthomas, present in a family affected by familial seborrhoeic keratosis. In addition, we tested for possible germline alterations in the FGFR3 and PTCH1 genes. Methods Ten members of one family were clinically examine…

Protocolo de diagnóstico histológico para muestras de pacientes con melanoma cutáneo. Documento de consenso de la SEAP y la AEDV para el Registro Nacional de Melanoma.

This article describes a proposed protocol for the histologic diagnosis of cutaneous melanoma developed for the National Cutaneous Melanoma Registry managed by the Spanish Academy of Dermatology and Venereology (AEDV). Following a review of the literature, 36 variables relating to primary tumors, sentinel lymph nodes, and lymph node dissection were evaluated using the modified Delphi method by a panel of 8 specialists (including 7 pathologists). Consensus was reached on the 30 variables that should be included in all pathology reports for cutaneous melanoma and submitted to the Melanoma Registry. This list can also serve as a model to guide routine reporting in pathology departments.

Clear Cell Syringoid Carcinoma

Syringoid carcinoma (syringoid "eccrine" carcinoma or eccrine epithelioma) is a rare cutaneous tumor with some controversy regarding its correct definition. It may also be difficult to differentiate from its benign counterpart (syringoma), other adnexal carcinomas, and cutaneous metastasis from adenocarcinomas. We present a case of a syringoid carcinoma of the clear cell variant complemented with an immunohistochemical and ultrastructural study, the latter revealing cytoplasmic accumulation of glycogen and presence of intercellular and intracellular lumina in clear tumor cells, as well as diverse hallmarks of malignancy (i.e., perineural invasion, tumor necrosis, and deep invasion). Clear t…

Leukocytoclastic vasculitis associated with sulfuric acid inhalation

Malignant proliferating trichilemmal tumours: an histopathological and immunohistochemical study of three cases with DNA ploidy and morphometric evaluation

Aims: Malignant proliferating trichilemmal tumours (MPTT) are rare neoplasms capable of tissue invasion and metastasis, the diagnosis of which is based essentially on histological features. In difficult cases, however, evaluation of additional parameters may be needed to diagnose malignancy. Methods and results We report three cases of MPTT in which, in addition to the histological features, we have determined the DNA ploidy, nuclear area and proliferative fraction. CD34 immunoreactivity has also been tested. Two cases were aneuploid, and one diploid with increased proliferating index. PCNA immunostaining labelled 40% and 80% of tumour cells in aneuploid tumours and 30% of the diploid neopl…

Melanocytic Hyperactivation Simulating an Acral Lentiginous Melanoma in a Patient With Parkinson Disease Treated by Levodopa

Expression levels of a filament-specific transcriptional regulator are sufficient to determine Candida albicans morphology and virulence

Candida albicans , the major human fungal pathogen, undergoes a reversible morphological transition from single yeast cells to pseudohyphal and hyphal filaments (elongated cells attached end-to-end). Because typical C. albicans infections contain a mixture of these morphologies it has, for many years, been difficult to assess the relative contribution of each form to virulence. In addition, the regulatory mechanisms that determine growth in pseudohyphal and hyphal morphologies are largely unknown. To address these questions we have generated a C. albicans strain that can be genetically manipulated to grow completely in the hyphal form under non-filament-inducing conditions in vitro. This w…

Immunoexpression of p53 in cutaneous and subcutaneous leiomyosarcomas.

The diagnosis of malignancy in cutaneous and subcutaneous smooth muscle tumors is based on subtle criteria. Therefore, any ancillary technique useful in this differential diagnosis is always welcome. In this report, we study the immunoexpression of p53 in 19 malignant smooth muscle tumors of the skin (15 cutaneous leiomyosarcomas, 2 subcutaneous leiomyosarcomas, and 2 cutaneous metastases of leiomyosarcoma), as well as in 1 leiomyoma with cellular atypia, therefore complementing a previous study on p53 immunoexpression in leiomyomas of the skin. The p53 staining was positive in 12 (63.16%) of 19 leiomyosarcomas. Percentages of immunostaining in the positive cases varied from 2% to 95%. Ten …

A heterozygous mutation in the RAG2 gene with cutaneous and systemic manifestations partially resembling Omenn syndrome

Subcutaneous panniculitis-like T-cell lymphoma, lupus erythematosus profundus, and overlapping cases: molecular characterization through the study of 208 genes

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic cutaneous lymphoma. Differential diagnosis with lupus erythematosus panniculitis (LEP) can be challenging and overlapping cases have been described. In this study, we investigate whether gene expression profiling may or not identify markers that can be used to improve our understanding of the disease and to make a precise differential diagnosis. SPTCL, LEP, and overlapping cases were analyzed using a customized NanoString platform including 208 genes related to T-cell differentiation, stromal signatures, oncogenes, and tumor suppressor genes. Gene expression unsupervised analysis of the samples differentiated SPTCL f…

Cutaneous dermal non-neural granular cell tumor is a granular cell dermal root sheath fibroma

Dermal non-neural granular cell tumor (NNGCT) was first described in 1991 as an S100-negative polypoid non-melanocytic tumor. Although originally introduced in the literature as a primary cutaneous tumor, it was later emphasized that such qualification could not be held until the line of differentiation was clarified. It was also demonstrated that not all cases were polypoid. In the current study we try to further characterize this entity by presenting 5 cases of NNGCT. As expected, not all of them were polypoid. The ages of the patients varied from 10 to 43 (mean age 22). They all were composed of S100-negative granular cells with variable atypia and mitotic figures. None of them recurred …

Extracellular Vesicles From the Helminth Fasciola hepatica Prevent DSS-Induced Acute Ulcerative Colitis in a T-Lymphocyte Independent Mode

The complexity of the pathogenesis of inflammatory bowel disease (ulcerative colitis and Crohn's disease) has led to the quest of empirically drug therapies, combining immunosuppressant agents, biological therapy and modulators of the microbiota. Helminth parasites have been proposed as an alternative treatment of these diseases based on the hygiene hypothesis, but ethical and medical problems arise. Recent reports have proved the utility of parasite materials, mainly excretory/secretory products as therapeutic agents. The identification of extracellular vesicles on those secreted products opens a new field of investigation, since they exert potent immunomodulating effects. To assess the ef…

In regard to “A tale of two clones: Caldesmon staining in the differentiation of cutaneous spindle-cell neoplasms”

Primary cutaneous biphasic sarcomatoid basal cell carcinoma with myoepithelial carcinoma differentiation: A new variant

Isolated cases of basal cell carcinoma (BCC) with partial myoepithelial component have been described. However, myoepithelial differentiation has not been described in sarcomatoid basal cell carcinomas, which usually show features resembling osteosarcoma, chondrosarcoma, or leiomyosarcoma. We report a case of an 87-year-old man with a forehead lesion that histologically showed a minor component of conventional nodular BCC in transition with a major biphasic sarcomatoid growth composed of invasive spindle-cell and epithelial-like components, the latter with a reticular pattern and scattered ductal structures. Both components showed cytological atypia and high mitotic rate (26/10HPF), with at…

Complete Regression of Melanocytic Nevi: Correlation Between Clinical, Dermoscopic, and Histopathologic Findings in 13 Patients

Background: The complete regression of melanocytic tumors, confirmed by histology, has rarely been reported in the literature. It is very difficult to determine the malignant or benign nature of a regressed tumor, and on occasions, the only indication of malignancy is the subsequent development of metastasis. Material and methods: We performed a descriptive study of melanocytic nevi that had undergone complete, histologically confirmed regression prior to excision in the dermatology department of our hospital over a period of 3 years. We included only lesions in which dermoscopy performed prior to regression showed features that suggested benignity. We assessed various clinical, dermoscopic…

Transcriptomic identification of miR-205 target genes potentially involved in metastasis and survival of cutaneous malignant melanoma

AbstractCutaneous melanoma is an aggressive neoplasm and is responsible for the majority of skin cancer deaths. Several miRNAs are involved in melanoma tumor progression. One of them is miR-205, the loss of which contributes to the development of melanoma metastasis. We evaluated whole-genome mRNA expression profiling associated with different miR-205 expression levels in melanoma cells. Differential expression analysis identified 243 differentially expressed transcripts including inositol polyphosphate 5′-phosphatase-like protein-1 (INPPL1) and BTB/POZ Domain-Containing Protein 3 (BTBD3). INPPL1 and BTBD3 were downregulated when melanoma cells expressed miR-205, indicating that these genes…

Pruriginous Lesions in a Young Girl: Challenge.

The Amount of Melanin Influences p16 Loss in Spitzoid Melanocytic Lesions: Correlation With CDKN2A Status by FISH and MLPA.

AIMS The risk assessment of spitzoid lesions is one of the most difficult challenges in dermatopathology practice. In this regard, the loss of p16 expression and the homozygous deletion of CDKN2A, have been pointed in the literature as reliable indicators of high risk. However, these findings are poorly reproducible, and the molecular bases underlying the loss of p16 expression remain unclear. We aimed to identify the underlying events causing loss of CDKN2A/p16 in spitzoid tumors. MATERIALS AND METHODS We evaluated the immunohistochemical expression of p16, and the presence of CDKN2A genetic alterations detected through fluorescence in situ hybridization (FISH) and multiplex ligation-depen…

Candida albicans adhesin Als3p is dispensable for virulence in the mouse model of disseminated candidiasis

The presence of specific proteins, including Ece1p, Hwp1p and Als3p, distinguishes theCandida albicanshyphal cell wall from that of yeast-form cells. These proteins are thought to be important for the ability ofC. albicanscells to adhere to living and non-living surfaces and for the cell-to-cell adhesion necessary for biofilm formation, and also to be pivotal in mediatingC. albicansinteractions with endothelial cells. Using anin vitroflow adhesion assay, we previously observed that yeast cells bind in greater numbers to human microvascular endothelial cells than do hyphal or pseudohyphal cells. This is consistent with previous observations that, in a murine model of disseminated candidiasis…

Desmoplastic primitive nonneural granular cell tumor of the skin.

Abstract Primitive nonneural granular cell tumor of the skin was first described by LeBoit et al in 1991 as "primitive polypoid granular cell tumor." Few cases have been reported to date, all being polypoid or deep well-delimited lesions and formed by large spindle or polygonal granular cells with moderate nuclear atypia and increased mitotic activity. This granular cell population does not have a Schwannian, myogenic, melanocytic, fibroblastic, histiocytic, or epithelial differentiation. We report a case that fully satisfies the criteria for primitive nonneural granular cell tumor of the skin and, in addition, shows an extensive desmoplastic stroma. This desmoplastic variant of primitive n…

Abstract PR04: Epigenetic silencing of CDR1as drives IGF2BP3-mediated melanoma invasion and metastasis

Abstract Metastasis is the primary cause of death of cancer patients. Dissecting mechanisms governing metastatic spread may uncover new biology and/or yield promising therapeutic insights. Here we investigated the role of circular RNAs (circRNAs), a class of noncoding RNAs lacking characterized functions, in metastasis, using melanoma as a model aggressive tumor. We analyzed RNA-seq of melanocytes and melanoma short-term cultures to characterize the landscape of circRNA in melanocytic cells. We observed silencing of Cerebellar Degeneration Related 1 (CDR1as), a neuronal-enriched circRNA and known regulator of the microRNA miR-7, in melanoma cell lines and short-term cultures compared to cul…

CCL27 Signaling in the Tumor Microenvironment

Chemokines are a group of small proteins which play an important role in leukocyte migration and invasion. They are also involved in the cellular proliferation and migration of tumor cells.Chemokine CCL27 (cutaneous T cell-attracting chemokine, CTACK) is mainly expressed by keratinocytes of the normal epidermis. It is well known that this chemokine plays an important role in several inflammatory diseases of the skin, such as atopic dermatitis, contact dermatitis, and psoriasis. Moreover, several studies have shown an association between CCL27 expression and a variety of neoplasms including skin cancer.In this chapter, we address the role of chemokine CCL27 in the tumor microenvironment in t…

New type of chimeric fusion product between theEWS andATF1 genes in clear cell sarcoma (malignant melanoma of soft parts)

We report a new case of clear cell sarcoma (CCS) harboring the t(12;22)(q13;q12). Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed the presence of a chimeric transcript between the EWS and ATF1 genes, both in primary and metastatic tissue. Sequencing studies disclosed an in-frame fusion between EWS gene codon 265 and ATF1 gene codon 110. This breakpoint has not been reported previously and indicates an important in vivo loss of EWS and ATF1 gene domains, which could be associated with the unusually aggressive behavior of this tumor. Genes Chromosomes Cancer 23:358–360, 1998. © 1998 Wiley-Liss, Inc.

Development and pathology of echinostoma caproni in experimentally infected mice

In the present article, several parasitological features of mice, each experimentally infected with 75 metacercariae of Echinostoma caproni (Trematoda: Echinostomatidae), were studied during the first 12 wk postinfection. Moreover, the early pathological responses also were analyzed and compared with data previously published on other host species of E. caproni to gain further insight into the factors determining worm rejection or establishment of chronic infections. The results obtained show that the pattern of E. caproni infection in mice is consistent with a highly compatible host–parasite system. This combination is characterized by a high worm establishment, high egg output, and long s…

Echinostoma caproni (Trematoda): differential in vivo cytokine responses in high and low compatible hosts.

In order to investigate the factors determining the expulsion of intestinal trematodes, we have analyzed the in vivo cytokine responses at several levels and the local responses against Echinostoma caproni (Trematoda) in two host species displaying different compatibility with the parasite. The response of the high compatible host (mice) is characterized by a mixed Th1/Th2 phenotype in the spleen, Peyer's patches and mesenteric lymph nodes. At the intestine, a marked Th1 response with a marked increase of IFN-γ together with elevated number of mucosal neutrophils and expression of induced nitric oxide synthase were observed. The responses in the host of low compatibility (rats) with the par…

Granulomas en dermatopatología: principales entidades. Parte I

This series of 2 articles on dermatopathologic diagnoses reviews conditions in which granulomas form. Part 1 clarifies concepts, discusses the presentation of different types of granulomas and giant cells, and considers a large variety of noninfectious diseases. Some granulomatous diseases have a metabolic origin, as in necrobiosis lipoidica. Others, such as granulomatous mycosis fungoides, are related to lymphomas. Still others, such as rosacea, are so common that dermatologists see them nearly daily in clinical practice.

Meningioma-like Tumor of the Skin Revisited: A Distinct CD34+ Dermal Tumor With an Expanded Histologic Spectrum.

The term meningioma-like tumor of the skin (MLTS) was coined in 1993 to designate a particular whorled spindle cell superficial cutaneous tumor. No additional confirmed cases of this entity have been reported to date. Some authors have speculated that these cases might be cellular neurothekeomas. In order to delineate the histologic spectrum and the immunophenotype of this unusual tumor, we studied 5 cases, 2 previously unreported and the 3 original cases. The immunohistochemical findings of case 5, however, were limited to those from the original study. Clinically, the tumor presented as a reddish papule, plaque, or nodule, located in the extremities or trunk. The patient often referred to…

Physiologic Expression of the Candida albicans Pescadillo Homolog Is Required for Virulence in a Murine Model of Hematogenously Disseminated Candidiasis

ABSTRACT Morphogenetic conversions contribute to the pathogenesis of Candida albicans invasive infections. Many studies to date have convincingly demonstrated a link between filamentation and virulence; however, relatively little is known regarding the role of the filament-to-yeast transition during the pathogenesis of invasive candidiasis. We previously identified the C. albicans pescadillo homolog ( PES1 ) as essential during yeast growth and growth of lateral yeast on hyphae but not during hyphal growth. Furthermore, we demonstrated that PES1 is required for virulence in vivo in a Galleria mellonella larva model of candidiasis. Here, we have used a regulatable tetO-PES1 / pes1 strain to …

Specific immunohistochemical identification of Candida albicans in paraffin-embedded tissue with a new monoclonal antibody (1B12).

In invasive candidiasis, the identification of Candida organisms in tissue samples or in normally sterile fluids is essential for an accurate diagnosis. Species identification is an important clue for the source of infection and in epidemiological studies. In this article, the authors have tested the value of a new monoclonal antibody (1B12) to detect C albicans in culture by immunofluorescence, and in tissue samples by immunohistochemistry. MAb 1B12 was found to specifically recognize C albicans , does not cross-react with other Candida species or other structurally similar fungi, and is very sensitive and specific in paraffin-embedded tissue, having no reactivity in normal human tissues o…

EngineeredControl of Cell Morphology In Vivo Reveals Distinct Roles for Yeast andFilamentous Forms of Candida albicans duringInfection

ABSTRACT It is widely assumed that the ability of Candida albicans to switch between different morphologies is required for pathogenesis. However, most virulence studies have used mutants that are permanently locked into either the yeast or filamentous forms which are avirulent but unsuitable for discerning the role of morphogenetic conversions at the various stages of the infectious process. We have constructed a strain in which this developmental transition can be externally modulated both in vitro and in vivo. This was achieved by placing one copy of the NRG1 gene (a negative regulator of filamentation) under the control of a tetracycline-regulatable promoter. This modified strain was th…

La diferenciación perineural en los tumores cutáneos

Liquen plano hipertrófico: importancia del seguimiento y de la correlación clinicopatológica

Spontaneous regression of multiple melanocytic nevi after melanoma: report of 3 cases.

Complete spontaneous regression of multiple melanocytic nevi after melanoma is an extremely rare phenomenon. We report 3 cases of patients with a history of melanoma that showed regression of almost all melanocytic nevi over time. One of the patients had 2 simultaneous primary cutaneous melanomas without metastasis. In the other 2 patients, regression of the melanocytic nevi was seen after the development of metastasis in lymph nodes. These patients had spontaneously developed an efficient immune response against melanocytes, and they would represent paradigmatic examples of the spontaneous immune responses in melanoma patients. Better understanding of the mechanisms involved in the complet…

Blueberry Muffin Baby Associated with Bone Demineralization Due to Congenital Transient Neonatal Hyperparathyroidism

Nonepithelial skin tumors with multinucleated giant cells

Recognition of the different types of multinucleated giant cells in neoplastic and pseudotumoral lesions of the skin may be helpful in the differential diagnosis of these tumors. In this review, we will analyze the different types of multinucleated giant cells that can be found in nonepithelial cutaneous tumors and, more importantly, the clinicopathological context in which they are found. Touton giant cells are typically present in juvenile xanthogranuloma, necrobiotic xanthogranuloma, and some subtypes of xanthomas. Giant cells with a ground glass appearance are typically present in the solitary reticulohistiocytoma and multicentric reticulohistiocytosis. Osteoclast-like cells are found i…

High CCL27 immunoreactivity in ‘supratumoral’ epidermis correlates with better prognosis in patients with cutaneous malignant melanoma

AimsIt has been proposed that the expression of chemokines and chemokine receptors by melanoma cells may have a role in tumour immune escape. Chemokine CCL27 is reported to be expressed specifically on the epidermal keratinocytes. The implication of CCL27 in cutaneous melanomas is currently unresolved. It has been suggested that CCL27 expression in melanomas can induce antitumoral immunity, and that CCL27 may suppress tumour growth probably due to the local lymphocyte recruitment.MethodsWe studied CCL27 chemokine expression in three different concentric epidermal areas covering the primary cutaneous melanoma in patients with a long clinical follow-up. Our study included 91 cases of primary …

Examination of the pathogenic potential of Candida albicans filamentous cells in an animal model of haematogenously disseminated candidiasis

The opportunistic fungal pathogen Candida albicans is an increasingly common threat to human health . Candida albicans grows in several morphologies and mutant strains locked in yeast or filamentous forms have attenuated virulence in the murine model of disseminated candidiasis. Thus, the ability to change shape is important for virulence. The transcriptional repressors Nrg1p and Tup1p are required for normal regulation of C. albicans morphology. Strains lacking either NRG1 or TUP1 are constitutively pseudohyphal under yeast growth conditions, and display attenuated virulence in the disseminated model. To dissect the relative importance of hyphae and pseudohyphae during an infection, we use…

Ovarian sex cord tumor with annular tubules in a woman with premature ovarian failure.

Abstract Objective: To report a case of premature ovarian failure (POF) associated with an ovarian sex cord tumor with annular tubules. Design: Case report. Setting: Reproductive endocrinology unit in a tertiary academic center. Patient(s): A 20-year-old woman with POF. Intervention(s): Biopsy of the rudimentary ovary by laparoscopy. Main Outcome Measure(s): Protocol for POF investigation and histological study of the ovarian sample. Result(s): An ovarian sex cord tumor with annular tubules was detected in the rudimentary right ovary. Conclusion(s): The rare ovarian sex cord tumor with annular tubules, which may be hormonally active, was detected in a case of POF.

Intracellular coexpression of CXC- and CC– chemokine receptors and their ligands in human melanoma cell lines and dynamic variations after xenotransplantation

Abstract Background Chemokines have been implicated in tumor progression and metastasis. In melanoma, chemokine receptors have been implicated in organ selective metastasis by regulating processes such as chemoattraction, adhesion and survival. Methods In this study we have analyzed, using flow cytometry, the systems formed by the chemokine receptors CXCR3, CXCR4, CXCR7, CCR7 and CCR10 and their ligands in thirteen human melanoma cell lines (five established from primary tumors and eight established from metastasis from different tissues). WM-115 and WM-266.4 melanoma cell lines (obtained from a primary and a metastatic melanoma respectively) were xenografted in nude mice and the tumors and…

Protocolo de diagnóstico histológico para muestras de pacientes con melanoma cutáneo. Documento de consenso de la SEAP y la AEDV para el Registro Nacional de Melanoma

Resumen: El presente texto es una propuesta de protocolo de diagnóstico histológico para el melanoma cutáneo realizada a instancias del Registro Nacional de Melanoma de la Academia Española de Dermatología y Venereología. Tras una búsqueda bibliográfica, un grupo de ocho panelistas (siete patólogos) decidieron entre 36 variables del tumor primario, el ganglio centinela y la linfadenectomía incluir un total de 30 variables mediante el método de Delphi modificado. Se han consensuado las variables que deberían contener un informe histológico de melanoma cutáneo para que puedan ser utilizadas en el Registro de Melanoma o servir de modelo para los distintos Servicios de Anatomía Patológica a la …

CXCR3 chemokine receptor immunoreactivity in primary cutaneous malignant melanoma: correlation with clinicopathological prognostic factors.

A role for CXCR3, the receptor for chemokines Mig, IP-10 and interferon-inducible T cell alpha-chemoattractant, in tumour cell migration during melanoma progression has been proposed.To analyse CXCR3 expression in primary cutaneous malignant melanomas and its comparison with clinicopathological and prognostic factors.A retrospective immunohistochemical study was carried out on formalin-fixed paraffin-wax-embedded sections from 82 patients with primary invasive cutaneous melanomas, with a monoclonal antibody to CXCR3 (clone 49801.111; RD Systems). Immunoreactivity was semiquantitatively evaluated: labelling intensity (0, absent; 1, weak; 2, moderate; 3, strong) multiplied by the percentage o…

UME6, a Novel Filament-specific Regulator ofCandida albicansHyphal Extension and Virulence

The specific ability of the major human fungal pathogen Candida albicans, as well as many other pathogenic fungi, to extend initial short filaments (germ tubes) into elongated hyphal filaments is important for a variety of virulence-related processes. However, the molecular mechanisms that control hyphal extension have remained poorly understood for many years. We report the identification of a novel C. albicans transcriptional regulator, UME6, which is induced in response to multiple host environmental cues and is specifically important for hyphal extension. Although capable of forming germ tubes, the ume6Δ/ume6Δ mutant exhibits a clear defect in hyphal extension both in vitro and during i…

h-caldesmon immunoreactivity in atypical fibroxanthoma: implications for the differential diagnosis.

Progressive depigmentation of a melanocytic lesion: a dermoscopic challenge for melanoma diagnosis.

Characterization of a Naturally Occurring Breast Cancer Subset Enriched in Epithelial-to-Mesenchymal Transition and Stem Cell Characteristics

Abstract Metaplastic breast cancers (MBC) are aggressive, chemoresistant tumors characterized by lineage plasticity. To advance understanding of their pathogenesis and relatedness to other breast cancer subtypes, 28 MBCs were compared with common breast cancers using comparative genomic hybridization, transcriptional profiling, and reverse-phase protein arrays and by sequencing for common breast cancer mutations. MBCs showed unique DNA copy number aberrations compared with common breast cancers. PIK3CA mutations were detected in 9 of 19 MBCs (47.4%) versus 80 of 232 hormone receptor–positive cancers (34.5%; P = 0.32), 17 of 75 HER-2–positive samples (22.7%; P = 0.04), 20 of 240 basal-like c…

Clinically atypical spitzoid lesions: semi-quantitative histologic index correlation with dermoscopic scores (ABCD rule, 7-point checklist and pattern analysis)

Background The distinction of Spitz and Reed nevi with atypical features from melanoma may be a difficult task. In these cases, the dermoscopic scores could bring variable results and not always correlate with the histologic diagnosis. Objective The aim of this study was to compare the histopathologic and dermoscopic findings in a cohort of clinically atypical Spitz and Reed nevi. Methods We retrospectively reviewed 19 cases of atypical Spitz and Reed nevi from our files. We constructed a new semi-quantitative histologic index (HI) based on the reproducible microscopic features, and correlated it with two dermoscopic scores: ABCD and 7-point checklist, as well as with the predominant dermos…

Dermatopatología de la oclusión intraluminal vascular: parte I (trombos)

Resumen: La patología vascular oclusiva es causante de diversas y variadas manifestaciones clínicas, algunas de las cuales son de catastróficas consecuencias para el paciente. Sin embargo, las causas de tal oclusión son muy variadas, extendiéndose desde trombos por acción descontrolada de los mecanismos de coagulación, hasta anomalías de los endotelios de los vasos u oclusión por materiales extrínsecos. En una serie de dos artículos hacemos una revisión de las principales causas de oclusión vascular, resumiendo sus manifestaciones clínicas principales y los hallazgos histopatológicos fundamentales. Esta primera parte corresponde a las oclusiones vasculares que cursan con trombos. Abstract: …

Granulomas en dermatopatología: principales entidades. Parte II

Part 2 of this series on granulomatous diseases focuses on skin biopsy findings. Whereas the first part treated noninfectious conditions (metabolic disorders and tumors, among other conditions), this part mainly deals with various types of infectious disease along with other conditions seen fairly often by clinical dermatologists.

Increased Goodpasture antigen-binding protein expression induces type IV collagen disorganization and deposit of immunoglobulin A in glomerular basement membrane

Increased expression of Goodpasture antigen-binding protein (GPBP), a protein that binds and phosphorylates basement membrane collagen, has been associated with immune complex-mediated pathogenesis. However, recent reports have questioned this biological function and proposed that GPBP serves as a cytosolic ceramide transporter (CERTL). Thus, the role of GPBP in vivo remains unknown. New Zealand White (NZW) mice are considered healthy animals although they convey a genetic predisposition for immune complex-mediated glomerulonephritis. Here we show that NZW mice developed age-dependent lupus-prone autoimmune response and immune complex-mediated glomerulonephritis characterized by elevated GP…

Inhibition of Filamentation Can Be Used To Treat Disseminated Candidiasis

ABSTRACT Candida albicans remains the leading causative agent of invasive fungal infection. Although the importance of filamentation in C. albicans pathogenesis has been extensively investigated, in vivo studies to date have been unable to dissect the role of this developmental process in the establishment of infection versus the development of active disease as characterized by damage to the host leading to mortality. To address this issue, we genetically engineered a C. albicans tet-NRG1 strain in which filamentation and virulence can be modulated both in vitro and in vivo simply by the presence or absence of doxycycline (DOX): this strain enabled us, in a prior study, to demonstrate that…

Pigmented desmoplastic trichilemmoma

Desmoplastic trichilemmoma (DT), the pseudomalignant variant of conventional trichilemmoma described by Hunt et al in 1990, displays a superficial lobular growth pattern of glycogen-rich cells with peripheral nuclear palisading surrounded by a thickened basement membrane. DT differs from its conventional counterpart by showing a central hyalinized area with epithelial cords and strands mimicking invasive carcinoma. We report a case that fully satisfies the criteria for DT and, in addition, shows an extensive melanocytic cell component and prominent melanin deposition. To our knowledge, a pigmented variant of DT has not been reported and should be recognized in order to appropriately face th…

Papel de las quimiocinas en la progresión del melanoma

Resumen Las metastasis son la principal causa de mortalidad en el melanoma. Las quimiocinas son citocinas quimiotacticas de bajo peso molecular que permiten la migracion celular, atrayendo a celulas que expresan sus receptores. Como algunas quimiocinas son abundantes en organos que son asiento comun de metastasis, y sus receptores son expresados por las celulas tumorales, se planteo la hipotesis de que un gradiente de estas quimiocinas facilitaria selectivamente las metastasis a esos organos. El hallazgo posterior de la produccion de estas quimiocinas por las propias celulas tumorales, y su efecto autocrino, obliga a modular esta hipotesis. Ademas, muchas quimiocinas tienen efectos contrapu…

Atrophic dermatofibrosarcoma protuberans with the fusion gene COL1A1-PDGFB

Molecular diagnosis of dermatofibrosarcoma protuberans: A comparison between reverse transcriptase-polymerase chain reaction and fluorescence in situ hybridization methodologies

Dermatofibrosarcoma protuberans (DFSP) is characterized by the presence of the t(17;22)(q22;q13) that leads to the fusion of the COL1A1 and PDGFB genes. This translocation can be detected by multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) or fluorescence in situ hybridization (FISH) techniques. We have evaluated the usefulness of a dual color dual fusion FISH probe strategy for COL1A1/PDGFB detection in a series of 103 archival DFSPs and compared the obtained results with RT-PCR analyses. FISH and RT-PCR were carried out on paraffin embedded tissue samples. Regarding the RT-PCR approach, all COL1A1 exons and exon 2 of PDGFB were evaluated. Sensitivity, specificity, positi…

Florid fibroplasia in melanocytic lesions. A retrospective study.

Microcystic pseudoglandular plexiform cutaneous neurofibroma

Glandular structures are well documented to appear in peripheral nerve sheath tumors. These epithelial elements are usually present in malignant peripheral nerve sheath tumors although a few cases of glandular benign peripheral nerve sheath tumors have also been described, most of them being schwannomas. A neurofibroma with glands is considered to be a rare type of divergent differentiation, but a neurofibroma containing gland-like or pseudoglandular structures have not, to our knowledge, been described. We report a 33-year-old patient with a well-demarcated dermal neoplasm, composed of neoplastic Schwann cells, perineurial-like cells and fibroblasts in a matrix with collagen fibers and myx…

Downregulation of intratumoral expression of miR-205, miR-200c and miR-125b in primary human cutaneous melanomas predicts shorter survival

AbstractWhile only 15–25 percent of melanoma patients develop distant metastasis and die, this disease is still responsible for the majority of skin cancer-related deaths. The availability of adjuvant therapies makes the selection of high-risk patients essential. We evaluated the intratumoral expression of ten miRNAs in primary melanomas in relation to its ability to predict melanoma survival. To this end, we correlated miRNA expression in 132 cryopreserved primary and metastatic tumors with clinicopathological factors and clinical outcome. We found sequential downregulation of intratumoral expression of miR-125b, miR-182, miR-200c and miR-205 over the full spectrum of melanoma progression.…

Hypertrophic Lichen Planus: Importance of Follow-Up and Clinicopathologic Correlation

Immunodetection of CD45 epitopes on the surface of Candida albicans cells in culture and infected human tissues.

Candida albicans is a leading cause of disseminated fungal infection in immunocompromised patients. Candida-host cell interactions are mediated at the cell surface. Since blood-group I epitopes have been detected on the surface of C albicans cells, we investigated whether CD45, the molecule that carries the I antigen on human lymphocytes, is present on the C albicans cell surface, in culture and in human tissue specimens of human candidiasis. By using monoclonal antibodies to CD45, CD45RO, and CD45RA, we found a strong immunoreactivity at the cell surface of blastoconidia bearing germ tubes but weak or no immunostaining of the germ tubes themselves. In human tissues, immunostaining of C alb…

Depressed indurated plaque with elastorrhexis as a distinctive lesion in Buschke‐Ollendorff syndrome

Buschke-Ollendorff syndrome (BOS) is a rare autosomal dominant genodermatosis caused by heterozygous mutations in LEMD3 and characterized by connective tissue nevi and sclerotic bone lesions known as osteopoikilosis. We report a family with three individuals affected by BOS, two of whom manifested clinical and histopathological peculiarities, presenting with a depressed indurated plaque as the main cutaneous manifestation instead of the classic connective tissue nevi. Notable elastorrhexis was present in both biopsies.

Histiocytosis with mixed cell populations

Langerhans cell histiocytosis (LCH) and juvenile xanthogranuloma (JXG) are thought to originate from a common stem cell precursor, with divergent differentiation under different microenvironmental conditions. We describe an exceptional case of multiple cutaneous lesions in a 10-year-old boy, in which the coexistence of both LCH and JXG cell populations is found in every single lesion. The presence of Birbeck granules and CD207 (langerin) immunostaining in the LCH component would argue against the diagnosis of indeterminate cell histiocytosis (ICH). This unique case gives additional support to the hypothesis of a potentially common histogenesis for LCH and JXG.

Use of a Genetically Engineered Strain To Evaluate the Pathogenic Potential of Yeast Cell and Filamentous Forms duringCandida albicansSystemic Infection in Immunodeficient Mice

ABSTRACTThe pathogenesis ofCandida albicanssystemic infection is complex and results from the balance between its intrinsic virulence attributes and the host immune responses. Morphogenetic transitions between yeast cell and filamentous forms are considered one of the main virulence attributes inC. albicans. We have examined the pathogenesis of a genetically engineeredC. albicansstrain in which morphogenetic conversions can be externally manipulated in immunodeficient mice; these included B-cell deficient, nude (T cell deficient), SCID (lacking both functional T and B cells), and DBA/2N (C5 deficient with impaired neutrophil activity) mice. We also tested mice severely immunosuppressed by c…

Graft Healing in ACL Reconstruction: Can We Enhance It in Clinical Practice?

The ACL-Deficient Knee: A Problem Solving Approach, focuses on problem analysis and problem solving, as well as analyzing the possibility of prevention. In each chapter, the biomechanics, anatomy, etc. that are relevant to the topic are reviewed. There are chapters where highly specialized surgical techniques are presented (v. gr. double bundle reconstruction or meniscal transplant), as well as developing areas such as ACL tears in children, where we are finding a growing number of injuries due to the increase of sports at early ages Surgical reconstruction of the anterior cruciate ligament (ACL) using tendon grafts is the current standard to treat the functionally ACL-deficient knee. The s…

Levetiracetam‐induced pediatric toxic epidermal necrolysis successfully treated with etanercept

Successful management of toxic epidermal necrolysis (TEN) with tumor necrosis factor-α inhibitors has been described in adults, but few cases have been reported in children. To date, only four pediatric cases of TEN treated with infliximab and one with etanercept have been published. We present the case of an 8-year-old boy diagnosed with TEN induced by levetiracetam, successfully treated with etanercept, systemic corticosteroids, and intravenous immunoglobulin.

Reply to “Primary cutaneous biphasic sarcomatoid basal cell carcinoma with myoepithelial carcinoma differentiation. Is it a new variant of sarcomatoid basal cell carcinoma or a collision tumor composed of a myoepithelial carcinoma and an incidental basal cell carcinoma?”

A pigmented and eroded lesion on the buttock.

CD99 Immunoreactivity in Atypical Fibroxanthoma

Atypical fibroxanthoma (AFX), a pleomorphic superficial cutaneous tumor of low-grade malignancy, shares many morphologic features with malignant melanoma (MM) and squamous cell carcinoma (SCC). Absence of S-100, keratin, and desmin immunoreactivity is the clue for this diagnosis. In a search for positive markers, we tested 26 cases of AFX with 2 antibodies: O13 (CD99) and protein gene product 9.5 (PGP9.5). We also included 10 cases of poorly differentiated SCC and 10 cases of MM in the study. In AFX, CD99 immunoreactivity was present in 19 cases (73%), whereas focal PGP9.5 immunoreactivity was found in only 9 cases (35%). None of the SCC cases showed CD99 immunostaining. No CD99 immunoreact…

Desmoplastic melanoma may mimic a cutaneous peripheral nerve sheath tumor: Report of 3 challenging cases

Desmoplastic melanoma (DM) and cutaneous malignant peripheral nerve sheath tumors (MPNST) reveal histological and immunohistochemical similarities, including S100 positivity and negative staining for conventional melanocytic markers. We present 3 cases of cutaneous S100-positive spindle cell tumors in elderly patients, in which first findings led to initial misdiagnoses as cutaneous MPNST and benign peripheral sheath nerve tumor (neurofibroma). The identification of adjacent atypical melanocytic hyperplasia in the overlying skin along with tumor cell proliferation, also in the superficial dermis, the neurotropic component and the absence of any relationship between the tumor and a major ner…

Folliculotropic Mycosis Fungoides With Flexural Eruptive Cysts and Comedones in a 14-Year-Old Boy

Mioepitelioma sincitial cutáneo doloroso: desde la clínica inespecífica al diagnóstico histopatológico

Pseudoxanthoma elasticum‐like syndrome with coagulation deficiency associated with carotid artery hypoplasia and a novel gamma‐glutamyl carboxylase gene mutation

Tissue invasiveness and non-acidic pH in human candidiasis correlate with "in vivo" expression by Candida albicans of the carbohydrate epitope recognised by new monoclonal antibody 1H4

Background: The morphogenetic conversion between yeast and hyphal growth forms appears to be crucial in the pathogenesis of invasive candidiasis, and can be regulated by environmental signals such as extracellular pH. Aims: To characterise the epitope recognised by monoclonal antibody 1H4, and to evaluate the expression of its corresponding epitope in Candida albicans cells under different conditions of pH and temperature, and “in vivo”, in tissue samples from patients with human candidiasis. Methods: Monoclonal antibody 1H4 was generated against the 58 kDa cell wall mannoprotein of C albicans (mp58), and was further characterised by immunoblot analysis, periodate treatment of the antigenic…

Actualización en el síndrome Birt-Hogg-Dubé

Resumen El sindrome de Birt-Hogg-Dube (SBHD) es una rara genodermatosis de herencia autosomica dominante caracterizada esencialmente por la presencia de fibrofoliculomas y/o tricodiscomas, quistes pulmonares, neumotorax espontaneos y canceres renales, siendo los tipos histologicos mas frecuentes las formas hibridas de oncocitoma y carcinoma cromofobo o formas puras de carcinoma cromofobo, oncocitico, de celulas claras o papilar. El gen implicado en este sindrome, FLCN, codifica la foliculina, que se expresa preferentemente a nivel cutaneo, renal y pulmonar. Este sindrome puede presentarse con una gran variabilidad clinica, y las lesiones cutaneas que son el signo de alarma para los dermatol…

Alteración renal en la infección por el virus de la inmunodeficiencia humana

Fundamento y objetivo Aunque la enfermedad renal se esta convirtiendo en un problema emergente en la poblacion infectada por el virus de la inmunodeficiencia humana (VIH), se tiene muy escasa informacion sobre su curso natural. El objetivo del presente estudio es analizar las lesiones renales en una serie de autopsias de pacientes con infeccion por el VIH en ausencia de tratamiento antirretroviral Pacientes y metodo Se han revisado retrospectivamente datos de las autopsias de 61 sujetos infectados por el VIH (edad media [DE], 36,9 [8,4] anos; un 58,6% eran adictos a drogas por via parenteral y el 84%, varones) fallecidos en nuestro hospital entre 1984 y 1997. Ningun paciente recibio tratami…

Biphasic dermatofibrosarcoma protuberans with a labyrinthine plexiform high‐grade fibrosarcomatous transformation

Several variants of dermatofibrosarcoma protuberans, a low-grade superficial sarcoma, are well recognized. The most prognostically important is the fibrosarcomatous variant. We report a case of biphasic dermatofibrosarcoma protuberans in which the high-grade component exhibited a previously undescribed plexiform pattern. A clinicopathological study complemented with immunohistochemical, ultrastructural, reverse transcription polymerase chain reaction and fluorescence in situ hybridization analyses of this unique case. Histopathologically, a conventional low-grade dermatofibrosarcoma protuberans was admixed with intratumoral high-grade areas showing a striking labyrinthine plexiform pattern …

Painful cutaneous lesions on the hand palm after Takotsubo cardiomyopathy and coronary angiography.

Circulating miRNA expression analysis reveals new potential biomarkers for human cutaneous melanoma staging.

Dermatopatología de la oclusión intraluminal vascular: parte II (coagulopatías, émbolos y miscelánea)

Resumen: La patología vascular oclusiva es causante de diversas y variadas manifestaciones clínicas, algunas de ellas con catastróficas consecuencias para el paciente. Dado que las causas de tal oclusión son muy variadas, hemos abordado en un artículo previo reciente en esta misma revista las causas trombóticas. En el presente artículo recopilamos diversas causas adicionales de oclusión intravascular. Abstract: Vascular occlusion has multiple, diverse clinical manifestations, some of which can have grave consequences for patients. It also has a wide variety of causes, including thrombi, which we recently addressed in part I of this review. In this second part, we look at additional causes o…

Cutaneous Lymphadenoma Is a Distinct Trichoblastoma-like Lymphoepithelial Tumor With Diffuse Androgen Receptor Immunoreactivity, Notch1 Ligand in Reed-Sternberg-like Cells, and Common EGFR Somatic Mutations.

The term "cutaneous lymphadenoma" was coined in this journal for an unusual lymphoepithelial cutaneous adnexal neoplasm, possibly with immature pilosebaceous differentiation. Some authors further proposed that cutaneous lymphadenoma was an adamantinoid trichoblastoma. However, although a hair follicle differentiation is widely accepted, the fact that this is a lymphoepithelial tumor is not appropriately explained by the trichoblastoma hypothesis. Our goal was to further clarify the phenotypic and genotypic features of cutaneous lymphadenoma in a series of 11 cases. Histologically, a lobular architecture surrounded by a dense fibrous stroma was present in all cases. The lobules were composed…

Telomeric length heterogeneity influences spontaneous regression of malignant melanoma

A proteomic-based approach for the identification ofCandida albicans protein components present in a subunit vaccine that protects against disseminated candidiasis

Candidiasis has become a prevalent infection in different types of immunocompromised patients. The cell wall of Candida albicans plays important functions during the host-fungus interactions. Cell wall (surface) proteins of C. albicans are major elicitors of host immune responses during candidiasis, and represent candidates for vaccine development. Groups of mice were vaccinated subcutaneously with a beta-mercaptoethanol (beta-ME) extract from C. albicans containing cell wall proteins. Vaccinated mice were then infected with a lethal dose of C. albicans. Increased survival and decreased fungal burden were observed in vaccinated mice as compared to a control group, and 75% of vaccinated mice…

Efficacy of a genetically engineered Candida albicans tet-NRG1 strain as an experimental live attenuated vaccine against hematogenously disseminated candidiasis.

ABSTRACT We report on the efficacy of the genetically engineered Candida albicans tet-NRG1 strain as an experimental live, attenuated vaccine against disseminated candidiasis in both immunocompetent and immunodeficient mice mostly dependent on T-cell immunity. This experimental vaccination model may represent an important tool to unravel the mechanisms of protective immunity during candidiasis.

Clinicopathological and immunohistochemical analysis of 20 cases of Merkel cell carcinoma in search of prognostic markers.

Aims:  To evaluate the clinicopathological and immunohistochemical characteristics of Merkel cell carcinoma (MCC) in an attempt to find new, potentially significant, prognostic markers. Methods and results:  Clinical data and follow-up, histopathological features (pattern, cell size, thickness, mitoses, vascular invasion, lymphocytic infiltration) and immunohistochemical detection [CK20, thyroid transcription factor (TTF-1), chromogranin A, synaptophysin, p53, Ki67, Fli-1, CD99, c-Kit] were evaluated in 20 cases of MCC. Fli-1 and CD99 were detected in 90% and 55% of cases, respectively. Tumour size > 30 mm, stage II, ‘absent’ lymphocytic infiltration, and the presence of > 50% of Ki67+ tumo…

A significant percentage of CD20-positive TILs correlates with poor prognosis in patients with primary cutaneous malignant melanoma

Descriptive Dermoscopic Study of Depigmentation in Melanocytic Nevi Without a Visible Halo

Background and objectives: There are few cases described in the literature in which depigmentation of melanocytic nevi occurs without the appearance of halos. The aim of this study was to analyze the correlation between clinical and dermoscopic findings and to assess the usefulness of dermoscopy to identify possible markers of complete regression in melanocytic lesions. Materials and methods: A prospective, observational, descriptive study of 77 melanocytic lesions in 52 patients was undertaken over a 5-year period. Melanocytic lesions from patients who underwent periodic follow-up in the digital dermoscopy unit were analyzed if they had exhibited partial or total, permanent depigmentation …

Dermatofibrosarcoma protuberans: a comprehensive review and update on diagnosis and management

Dermatofibrosarcoma protuberans (DFSP) is a rare superficial tumor characterized by high rates of local recurrence and low risk of metastasis. DFSP occurs most commonly on the trunk and proximal extremities, affects all races, and often develops between the second and fifth decade of life. The tumor grows slowly, typically over years. Histologically, several variants of DFSP have been described and should be well characterized to avoid misdiagnosis with other tumors. These include pigmented (Bednar tumor), myxoid, myoid, granular cell, sclerotic, atrophic DFSP, giant cell fibroblastoma, and DFSP with fibrosarcomatous areas. Of all these variants, only the DFSP with fibrosarcomatous areas is…

Role of Chemokines in Melanoma Progression

Metastasis is the main cause of death from melanoma. Chemokines are low molecular weight chemotactic cytokines that facilitate cellular migration. Thus, cells that express receptors for a given chemokine are attracted to the site of its production. As certain chemokines are found in abundance in organs that are common targets of metastasis and receptors for these chemokines are expressed by tumor cells, it was hypothesized that chemokine gradients might selectively facilitate metastasis to these organs. A later finding that these chemokines were produced by tumor cells, with evidence of autocrine effects, obliged the modification of that hypothesis. Many chemokines are also known to have op…

HMB-45 Immunostaining and Ultrastructure of Melanocytic Hyperplasia in Pigmented Basal Cell Carcinomas

The pigmented variant of basal cell carcinoma (PBCC) may be clinically misinterpreted as malignant melanoma. Histologically this variant is characterized by the presence of functional melanocytes distributed among epithelial tumor cells, particularly in superficial areas. Our finding of a case of PBCC with numerous atypical HMB-45-positive melanocytes prompted us to analyze the morphologic and immunohistochemical features of 20 consecutive cases of PBCC. Four additional cases with numerous large HMB-45-positive melanocytes, also present in the most invasive tumor nests, were found. Ultrastructural examination was performed in two selected cases. Large melanocytes with immature (stages I an…

Eritema en diana inducido por trametinib

Painful papule on the right arm of a woman.

Painful Cutaneous Syncytial Myoepithelioma: From Nonspecific Symptoms to Histopathologic Diagnosis

Estudio descriptivo dermatoscópico de los nevos melanocíticos con despigmentación sin halo clínico

Resumen Introduccion la despigmentacion de nevos melanociticos sin halo perilesional se ha descrito de forma excepcional en la literatura. Material y metodos estudio observacional, descriptivo y prospectivo de 77 lesiones melanociticas correspondientes a 52 pacientes, llevado a cabo durante un periodo de 5 anos. Se han analizado las lesiones melanociticas de pacientes revisados periodicamente en la unidad de dermatoscopia digital que habian sufrido una despigmentacion permanente, ya fuera total o parcial, pero sin presentar clinicamente un halo blanquecino alrededor de los mismos. El objetivo fue estudiar la correlacion entre los hallazgos clinicos y dermatoscopicos a estudio, y establecer …

Dermatofibrosarcoma protuberans: clinical, pathological, and genetic (COL1A1-PDGFB ) study with therapeutic implications.

Aims:  To analyse the presence of collagen type I alpha 1–platelet-derived growth factor beta (COL1A1–PDGFB) transcripts in 20 cases of dermatofibrosarcoma protuberans (DFSP) and to assess the relationship between COL1A1 breakpoints and clinical and histopathological variables. Methods and results:  Multiplex reverse transcriptase-polymerase chain reaction was carried out using frozen tissue. Our series contained 14 men and six women. Histologically, most cases were of conventional type (n = 9), followed by fibrosarcoma (n = 4), Bednar tumour (n = 2), sclerosing (n = 2), myoid (n = 1) and atrophic (n = 1) DFSP, and giant cell fibroblastoma (n = 1). Immunohistochemistry revealed CD34 express…

BRG1 and NRG1 form a novel feedback circuit regulating Candida albicans hypha formation and virulence

In the opportunistic fungal pathogen Candida albicans both cellular morphology and the capacity to cause disease are regulated by the transcriptional repressor Nrg1p. One of the genes repressed by Nrg1p is BRG1, which encodes a putative GATA family transcription factor. Deletion of both copies of this gene prevents hypha formation. We discovered that BRG1 over-expression is sufficient to overcome Nrg1p-mediated repression and drive the morphogenetic shift from yeast to hyphae even in the absence of environmental stimuli. We further observed that expression of BRG1 influences the stability of the NRG1 transcript, thus controlling filamentation through a feedback loop. Analysis of this phenom…

Expression of the fibrinogen binding mannoprotein and the laminin receptor of Candida albicans in vitro and in infected tissues.

We have previously reported a 37 kDa laminin-binding protein (p37) and a 58 kDa fibrinogen-binding mannoprotein (mp58) on the surface of Candida albicans. A few yeast cells expressed both functional receptors at the surface while germ tubes expressed a functional mp58 fibrinogen but not a functional p37 laminin receptor. These receptors were heterogeneously dispersed at the surface as shown by binding of rabbit antiserum to mp58 (PAb anti-mp58) and antiserum to the human high affinity laminin receptor. In this report we have used a dual fluorescence technique to determine if the two receptors colocalize, perhaps as part of a receptor complex. Fibrinogen was used as a probe for mp58 and poly…

Matrical carcinoma with prominent melanocytic hyperplasia (malignant melanocytic matricoma?) A report of two cases.

Melanocytic matricoma is a recently described lesion characterized by well-circumscribed nodules composed of matrical and supramatrical cells with clustered ghost cells, and admixed pigmented dendritic melanocytes, with no cyst formation or connection to the epidermis or pre-existing hair follicles. Although variable cytologic atypia and frequent mitoses in the epithelial component may be present, given the well-defined margins and absence of tumor recurrences, these lesions were initially considered benign neoplasms, and not matrical carcinoma. Theoretically, the detection of numerous melanocytes in matrical carcinoma should not be surprising, but is in fact a very unusual feature. A case …

Erythrophagocytic tumour cells in melanoma and squamous cell carcinoma of the skin

Aims: Erythrophagocytosis is a characteristic feature of tumour cells in malignant histiocytosis, some leukaemias, lymphomas, and also reactive histiocytes in the haemophagocytic syndrome associated with a variety of infections and neoplasms. It has also been found exceptionally in metastatic malignant epithelial cells in bone marrow and lymph nodes. We present two cases, a cutaneous malignant melanoma and an acantholytic squamous cell carcinoma, in which erythrophagocytosis by tumour cells was demonstrable by both light and electron microscopy. Methods and results: The melanocytic and squamous nature of these cells was supported by the immunohistochemical detection of HMB45, S100, and NKI-…

Birt–Hogg–Dubé Syndrome: An Update

Birt-Hogg-Dube syndrome is a rare autosomal dominant genodermatosis that is characterized by the presence of fibrofolliculomas and/or trichodiscomas, pulmonary cysts, spontaneous pneumothorax, and renal tumors. The most common histological types found in renal tumors from patients with the syndrome are oncocytoma-chromophobe carcinoma hybrids and pure forms of chromophobe carcinoma, oncocytic carcinoma, and clear cell or papillary cell carcinoma. The syndrome is linked to mutations in the FLCN gene, which encodes folliculin and is preferentially expressed in the skin, kidney, and lung. The syndrome can exhibit a high degree of clinical variability, and the skin lesions that are a warning si…