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Acral cutaneous metastasis from internal malignancy is rare, and the pathogenesis is not completely understood. We present the case of a 54-year-old black woman with a history of breast cancer diagnosed 2 years prior who developed multiple cutaneous metastases to acral sites involving the palmar and plantar surfaces of the hands and feet. This case represents an unusual metastatic pattern of breast carcinoma that arose after treatment with bevacizumab, an angiogenesis inhibitor that binds vascular endothelial growth factor A. We propose that bevacizumab-induced vascular changes localized to acral skin may have contributed to the metastatic pattern seen in our patient.

A 48-year-old Hispanic man presented with a nodule on the right cheek. The lesion had started as a papule 4 months previously that had slowly enlarged and then plateaued at its present size. The nodule was asymptomatic, and the patient denied bleeding, draining, or preceding trauma. Review of systems was negative for fevers, weight loss, night sweats, lymphadenopathy, or other skin findings. Past medical history was significant only for type 2 diabetes mellitus, hyperlipidemia, and hypertension.

Background: STAT3 drives development of Th17 cells and cytokine production by Th2 and Th17 cells, which contribute to asthma. Alternative asthma treatments are needed, especially for the Th17 phenotype. We sought to determine whether C188-9, a small-molecule STAT3 inhibitor, can block Th2 and Th17 cell expansion and cytokine production to prevent house dust mite (HDM)-induced airway inflammation and remodeling., Methods: Three groups of C57BL/6 mice were treated intranasally (IN) and intraperitoneally (IP) daily for 3 weeks with the following: (i) vehicle 1 IN and vehicle 2 IP, (ii) HDM IN and vehicle 2 IP, or (iii) HDM IN and C188-9 IP. Sections of lung were stained with Alcian Blue/PAS and examined microscopically. Total (t) STAT3, STAT3 phosphorylated on Y705 (pSTAT3), IL-17, IL-13, IL-5, and IL-4 levels were measured in lung protein extracts and serum using Luminex beads. Frequencies of Th2-type and Th17-type lymphocytes were assessed in lungs and bronchoalveolar lavage fluid (BALF) by multiparametric flow cytometry., Results: HDM inhalation markedly increased airway goblet cell numbers and thickness of the epithelium and subepithelial smooth muscle layer, which was accompanied in the whole lung by increased pSTAT3, IL-4, IL-5, IL-13, and IL-17, and % CD4 + T cells that produce IL-5, IL-13, and IL-17. HDM inhalation also increased serum IL-4 and IL-17 levels and increased BALF % CD4 + T cells that produce IL-5 and IL-13. Remarkably, treatment with C188-9 normalized each endpoint., Conclusion: HDM-induced airway inflammation, remodeling, and Th2/Th17-type cell accumulation involve STAT3 activation that can be prevented by C188-9 treatment., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Finasteride and dutasteride, both 5-alpha reductase inhibitors, are considered first-line treatment for androgenetic hair loss in men and used increasingly in women. In each case, patients are expected to take the medications indefinitely despite the lack of research regarding long-term adverse effects. Concerns regarding the adverse effects of these medications has led the United States National Institutes of Health to add a link for post-finasteride syndrome to its Genetic and Rare Disease Information Center. Herein, the authors report the results of a literature search reviewing adverse events of 5-alpha reductase inhibitors as they relate to prostate cancer, psychological effects, sexual health, and use in women. Several large studies found no increase in incidence of prostate cancer, a possible increase of high-grade cancer when detected, and no change in survival rate with 5-alpha reductase inhibitor use. Currently, there is no direct link between 5-alpha reductase inhibitor use and depression; however, several small studies have led to depression being listed as a side effect on the medication packaging. Sexual effects including erectile dysfunction and decreased libido and ejaculate were reported in as many as 3.4 to 15.8 percent of men. To date, there are very few studies evaluating 5-alpha reductase inhibitor use in women. Risks include birth defects in male fetuses if used in pregnancy, decreased libido, headache, gastrointestinal discomfort, and isolated reports of changes in menstruation, acne, and dizziness. Overall, 5-alpha reductase inhibitors were well-tolerated in both men and women, but not without risk, highlighting the importance of patient education prior to treatment.

Alopecias represent a heterogeneous group of disorders with different etiologies, presentations, and treatment options. The evaluation of the hair loss patient includes a comprehensive clinical history and physical examination; appropriate laboratory testing; and if indicated, a scalp biopsy. Treatment methods vary depending on the type of alopecia, and include watchful waiting, topical and systemic formulations, surgery, and treatment of any underlying or associated conditions. Referral to a dermatologist is helpful in diagnostically challenging and difficult to treat cases. Alopecia can cause emotional, mental, and social distress to patients. Early diagnosis and timely institution of appropriate treatment are helpful and comforting to those affected by this disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Inflammatory dermatoses are frequently encountered by the allergist, and histologic evaluation achieved through skin biopsy can be of tremendous value clinically. There is no substitute for a thorough history and physical exam; however, the skin biopsy is a simple, in-office procedure with little risk of complication that can provide invaluable information when a diagnosis is uncertain. Histopathologically, many inflammatory eruptions can look similar or overlap, but information provided by the dermatopathologist can help the clinician render or refine the clinical diagnosis and guide management. This review will discuss descriptive elements contained in the pathology report to provide a framework that can be used by the allergist to comfortably and confidently diagnose inflammatory dermatologic conditions.

Angiolymphoid hyperplasia with eosinophilia (ALHE), also named epithelioid hemangioma (EH), is an inflamed vascular tumefaction of uncertain pathogenesis, characterized by proliferation of histiocytoid endothelial cells with prominent lymphocytic and eosinophilic infiltration. Although considered a benign condition, it may recur in up to one-third of cases in the absence of complete surgical excision. The pathogenesis of ALHE/EH is still controversial. However, reaction to trauma and arteriovenous shunting are considered relevant. Histologically, ALHE/EH may be differentiated from other vascular neoplasms by its several unique characteristics including prominent proliferation of plump endothelial cells, and accompanying eosinophilic and lymphocytic inflammation, often with formation of lymphoid follicles. Surgery is the mainstay of treatment and various other treatment strategies have been used with varying results.

Background: Angiosarcoma (AS) is a rare soft tissue sarcoma showing endothelial differentiation as indicated by morphology and expression of CD31 (blood), D2-40 (lymphatic), factor VIII, and CD34 (both). We sought to examine the pattern of immunohistochemical markers of differentiation in AS and correlate these with outcome., Design: An AS tissue microarray (n = 70 specimens) was constructed for immunohistochemical analysis of CD31, CD34, factor VIII, D2-40, and pan-cytokeratin. Samples on this array were linked to clinicopathologic and outcome data for these patients. Univariate analyses were used to explore disease-specific survival (DSS) factors., Results: Nine metastatic, 23 localized, and 4 recurrent cases were included. Information about the tissue status (ie, primary or metastasis) was unavailable in 4 patients. Primary sites for the tumor included bone (n = 1), breast parenchyma (n = 11), breast skin (n = 4), heart (n = 5), skin (n = 8), soft tissue (n = 7), and unknown (n = 3). Three patients presented with multifocal disease (primary sites in these patients included breast, skin, and soft tissue). Metastatic sites included lung, bone, lymph nodes, brain, liver, and parotid. Of the 40 cases, 8 (20%) showed a pure or predominant epithelioid histology. Of the biomarkers evaluated by tissue microarray, 92% of tumors expressed at least one endothelial marker (factor VIII = 83%, CD31 = 80%, CD34 = 63%, and D2-40 = 43%) with 88% expressing 2 or more markers. Eighty-eight percent of tumors expressing D2-40 coexpressed CD31, an unusual combination in normal vessels. No endothelial marker clearly associated with disease-specific survival. Fifty percent (4/8) of epithelioid cases and 9% (3/32) of nonepithelioid cases showed keratin expression., Conclusions: Unusual patterns and loss of endothelial markers are common in AS, suggesting use of multiple markers in challenging cases and perhaps indicating important biologic characteristics.

Trichotillomania (TTM) is an impulse disorder in which patients chronically pull out hair resulting in noticeable hair loss. TTM is reported to affect as much as 4% of the population with the highest incidence in childhood and adolescence. The diagnostic criteria for TTM is likely to be revised in the planned fifth edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-V) to remove the requirement that the patient has "tension" followed by "relief" or "gratification" after hair pulling. First-line therapy is cognitive behavioral therapy, with strongest support for the subtype habit reversal training. Among pharmacologic therapy, clomipramine has been most effective in clinical trials. However, selective serotonin reuptake inhibitors are most commonly prescribed despite the lack of data supporting their efficacy. This article reviews the clinical features and treatment options for TTM to enhance knowledge and clinical management of TTM.

New World cutaneous leishmaniasis (CL) is considered in the differential diagnosis for patients with nonhealing ulcers and a history of travel to high-risk areas. For patients at risk for progression to mucocutaneous leishmaniasis, first-line treatment in the United States entails the use of sodium stibogluconate (SSG), which is obtained from the Centers for Disease Control and Prevention (CDC) under an investigational drug protocol. We report 2 cases of New World CL in travelers to endemic areas who were diagnosed and treated with SSG. These cases demonstrate the logistics of coordinating with the CDC to definitively diagnose New World CL and initiate the necessary treatment.

An otherwise healthy 45-year-old man with a 3-year history of poorly controlled psoriasis (no arthritis) was treated with etanercept 50-mg subcutaneous injections twice weekly for 3 months and then once weekly. Alternative treatment options were either unavailable (long commute for phototherapy) or contraindicated (history of alcohol abuse). The patient initially tolerated etanercept well with significant clinical improvement and had an uneventful course; however, approximately 18 months after initiating therapy, he abruptly developed dusky, indurated, and tender plaques on his abdomen and thighs at the sites of etanercept injections (Figure 1). There was also diffuse woody induration involving his flanks and back where injections had not been performed. His only recent prior exposure to an injectable medication was rabies vaccination in his arm 1 year earlier. The patient denied any systemic symptoms. Upon noting these findings, etanercept was immediately discontinued. Biopsy of an indurated plaque on his right lower abdomen revealed a superficial and deep perivascular lymphoplasmacytic inflammatory infiltrate in a background of thickened and hyalinized collagen fibers with notable loss of perieccrine fat (Figure 2). These features were most consistent with the inflammatory stage of morphea. Further work-up revealed a negative antinuclear antibody, anti-double-stranded DNA, anti-Scl-70, and anti-centromere. Borrelia titers were not obtained. The differential diagnosis included scleredema and scleromyxedema; serum and urine protein electrophoresis were within normal limits. The sites were treated with intralesional corticosteroids. During the next 3 months, there was minimal progression of disease although the plaques of morphea had not yet resolved.

Recent studies have proposed that MART-1 may falsely stain clusters of intraepidermal nonmelanocytic cells in lichenoid dermatitides. This may become an issue especially in isolated lesions of lichen planus-like keratosis (LPLK), a condition also known as benign lichenoid keratosis, and one that is often mistaken clinically for a malignant cutaneous neoplasm. LPLKs are known to exhibit basal epidermal pseudonests, mimicking a regressing melanocytic lesion histologically, and often may prompt the pathologist to obtain a MART-1 stain. If MART-1 is falsely positive, it may seal an incorrect diagnosis. To determine whether or not pseudonests in LPLK decorated with MART-1, we reviewed 70 cases from our institution, stained them with MART-1 (Thermo Fisher-Lab Vision, Ab3 clone, 1:400 dilution, heat-induced epitope retrieval with 0.02M citrate buffer at pH 6.0), and evaluated them for the presence or absence of staining within pseudonests. Four cases demonstrated an occasional MART-1-positive junctional nest. In these cases, microphthalmia transcription factor was also positive, confirming a true melanocytic origin. None of the other cases showed a MART-1 pattern that would have been suspicious for a melanocytic lesion. We propose that this discrepancy between our study and prior ones may be explained by differences in staining protocols or by a very low incidence of non-specific staining. Our study suggests that MART-1 is a useful marker in differentiating melanocytic nests from pseudonests in LPLK.

Adult Still disease is an inflammatory arthritis classically associated with daily spiking fevers, evanescent rash, organomegaly, lymphadenopathy, and laboratory anomalies. The typical cutaneous lesions are thin pink papules in a morbilliform distribution, of short duration. Histologically, these lesions are characterized by a superficial perivascular and interstitial mixed dermatitis with lymphocytes and variable neutrophils. A variant clinical presentation is increasingly recognized, which demonstrates persistent hyperpigmented plaques, often with a rippled or linear appearance. The histologic findings consist of upper epidermal dyskeratotic keratinocytes, increased dermal mucin, and a superficial perivascular infiltrate of lymphocytes and possibly neutrophils or eosinophils. We encountered 2 patients who presented with the characteristic rash of adult Still disease, both of whom progressed to develop the pigmented cutaneous plaques. We propose that this variant clinical and histologic appearance is the outcome of persistent disease activity.

Sclerosing spindle cell rhabdomyosarcoma (SSRMS) is a newly recognized entity in adults. The authors report a new case of SSRMS in a 31-year-old woman who presented with a large right leg mass. Biopsy revealed a malignant spindle cell neoplasm with focal sclerotic areas. A diagnosis of monophasic synovial sarcoma was favored initially. The tumor cells in the resection specimen were positive for myosin, myogenin, and MyoD1. Fluorescence in situ hybridization performed on the resection specimen showed no evidence of SYT gene rearrangement in the neoplastic cells, ruling out monophasic synovial sarcoma. A diagnosis of SSRMS was established. The patient succumbed to widely metastatic disease 16 months after initial diagnosis. This case highlights the utility of skeletal muscle markers and cytogenetic testing in distinguishing SSRMS from its mimic, monophasic synovial sarcoma. It is hoped that this case will expand the literature on adult SSRMS and help clinicians and pathologists better understand this newly described entity.

The association between house dust mites (HDMs) and atopic dermatitis (AD) has long been a contested issue in both dermatology and allergy/immunology. As AD continues to burden millions of individuals and even whole societies, the commercial availability of a HDM allergen mix for epicutaneous testing has revived efforts to identify a definitive link between HDMs and AD. Conclusive evidence of a role for HDMs in the pathogenesis of AD would justify patch testing with mite allergens and would further the use of allergen-specific immunotherapy in the management of such patients; an absence of involvement would refocus our investigative efforts on other conspirators. We present a thorough review of the dissenting scientific evidence and expert opinions on this controversial topic. The association of HDMs with AD has remained elusive, and additional investigation is necessary to resolve this vexing riddle.

Distinctive dermal clear cell mesenchymal neoplasm (DDCCMN) is a newly described entity characterized by a dermal proliferation of neoplastic cells with clear to reticulated cytoplasm and vesicular nuclei. Atypical features in the form of nuclear pleomorphism and mitoses may be found. The histogenesis of these neoplastic clear cells is not currently known but they are thought to be mesenchymal in origin. Immunohistochemically, they stain positively for NKI-C3 and negatively for melanocytic, epithelial and lymphoid markers. All five cases originally reported by Lazar and Fletcher occurred in the lower extremities. We report herein a case of DDCCMN with atypical features arising in the scalp.

Melanoma has a propensity to mimic the morphologic appearances of a wide variety of epithelial and soft tissue neoplasms. Although rarely encountered, these unusual morphologic variants of melanoma are often treacherous and may be difficult and challenging to diagnose. Thus, recognition of these variants is of paramount importance in the evaluation of any kind of epithelial or soft tissue neoplasm. Rhabdoid melanoma is one such example of these melanoma variants. Very few cases of rhabdoid melanoma have been reported, most of which were found in metastatic lesions. We wish to expand this rather sparse body of literature by reporting a case of metastatic rhabdoid melanoma arising subcutaneously in the right thigh of a 64-year-old man with a remote history of primary toe melanoma. Moreover, we present a comparative review of the clinical, histologic, immunohistochemical and ultrastructural features of previously reported cases. We found significant heterogeneity in the extent of rhabdoid change, expression of melanocytic and non-melanocytic markers and ultrastructural filamentous patterns in the cases we reviewed. It is our hope that this case report and literature review will help pathologists in the evaluation of neoplasms with rhabdoid morphology.

A number of C-type lectins on antigen-presenting cells play an important role in regulating innate immunity. Previously, we identified the mouse C-type lectins (dectin-1, and dectin-2) and human DECTIN-1. To identify human DECTIN-2, we employed degenerative polymerase chain reaction-based cDNA cloning using RNA from human Langerhans cell (LC)-like dendritic cells (DCs). This process yielded a cDNA encoding a C-type lectin with 66.5% amino acid sequence homology to mouse dectin-2, the same gene reported by Kanazawa et al. (J Invest Dermatol 2004: 122: 1522-1524) using the disparate approach of analyzing coding sequences in chromosome 12. Similar to their findings, we found gene expression in lung, spleen, and lymph node. Among resting leukocytes, it was expressed at highest levels by CD14+ monocytes, at lower levels by CD19+ B cells, and not at all by CD4+ T cells. Activation of CD19+ B cells with pokeweed mitogen down-regulated gene expression, whereas expression in CD4+ T cells was induced by Con A. Among our novel findings are an alternatively spliced transcript lacking exon 2, expression in bone marrow and tonsil, expression in CD8+ T cells that is abrogated following activation with phytohemagglutinin, restricted expression to CD1a+ LC within epidermis, and preferential expression by plasmacytoid (rather than myeloid) DC. Finally, we found that treatment with interleukin-4 (IL-4), IL-10, or UVB down regulated gene expression in CD14+ monocytes, whereas granulocyte-macrophage colony-stimulating factor, transforming growth factor-beta1, or tumor necrosis factor-alpha treatment up-regulated it. Our findings may form the basis for understanding the function of human DECTIN-2 in innate immunity.