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Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis. We observe genome-wide significant association with FFA at four genomic loci: 2p22.2, 6p21.1, 8q24.22 and 15q2.1. Within the 6p21.1 locus, fine-mapping indicates that the association is driven by the HLA-B*07:02 allele. At 2p22.1, we implicate a putative causal missense variant in CYP1B1, encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlights overrepresentation of transcripts encoding components of innate and adaptive immune response pathways. These findings provide insight into disease pathogenesis and characterise FFA as a genetically predisposed immuno-inflammatory disorder driven by HLA-B*07:02., Frontal fibrosing alopecia (FFA) features lichenoid cutaneous inflammation and scarring hair loss. Here, Tziotzios et al. identify four genetic loci associated with FFA by GWAS followed by Bayesian fine-mapping, co-localisation and HLA imputation which highlights HLA-B*07:02 as a risk factor.

Background Folliculitis decalvans (FD) is a rare neutrophilic cicatricial alopecia that poses a therapeutic challenge. Objectives To describe the therapeutic response in a large number of cases of FD with long-term follow-up and analyze potential prognostic factors associated with severity of form and with a better therapeutic response. Methods This multicenter prospective study included patients with FD who had a minimum of 5 years of follow-up. Severity was assessed by the maximum diameter of the cicatricial area. Therapeutic response was evaluated according to stabilization of the size of the cicatricial areas and the improvement in clinical symptoms. Results A total of 60 patients (37 men [61.7%] and 23 women [38.3%]) with a mean age of 40 years were included. Earlier age of onset (P = .01) was statistically associated with severity of form. Treatment with rifampicin and clindamycin, tetracyclines, and intralesional steroids was the most effective. No statistically significant prognostic factors predicting a better therapeutic response were found. Limitations Because FD is a rare disease, the main limitation was the sample size. Conclusions An earlier age of onset was associated with the severe form of the disease. The proposed specific therapeutic protocol can be a very useful tool in clinical dermatologic practice.

Background Frontal fibrosing alopecia (FFA) is a chronic cicatricial alopecia with an increasing incidence and unknown aetiology. Aim To identify possible environmental and hormonal factors related to FFA. Methods We conducted a multicentre case-control study paired by sex and age, and recruited 664 women (335 cases and 329 controls) and 106 men (20 cases and 86 controls). Study subjects completed an exhaustive questionnaire enquiring about pharmacological, environmental, hormonal, social, job exposure, lifestyle, drugs and diet factors to which they were exposed at least 5 years prior to the onset of the disease. Results For women, there was a statistical association between alopecia and history of pregnancy (OR = 1.6; 95% CI 1.06-2.41), use of facial sunscreen (OR = 1.6; 95% CI 1.06-2.41) and hormone replacement therapy (HRT) (OR = 1.76; 95% CI 1.11-2.8) or raloxifene (no controls exposed therefore OR was not calculated), exposure to alkylphenolic compounds (OR = 1.48; 95% CI 1.05-2.08), and presence of rosacea (OR = 1.91; 95% CI 1.07-3.39), lichen planus pigmentosus (LPP) (OR = 5.14; 95% CI 1.11-23.6) or hypothyroidism (OR = 1.73; 95% CI 1.11-2.69). For men, there was a statistical association between alopecia and use of facial sunscreens (OR = 11.6; 95% CI 1.7-80.9) or antiageing creams (OR = 1.84; 95% CI 1.04-3.23). Conclusions FFA seems to be associated with hormonal exposure (pregnancy, HRT and raloxifene), comorbidities (hypothyroidism, LPP and rosacea) and environmental factors (facial sunscreens, antiageing creams and occupational exposure). Further research is required to analyse the exact mechanism in which these environmental factors participate in the development of this alopecia.

Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma. The clinical course of the disease is typically characterized by progression from a nonspecific phase of erythematous macules to the appearance of plaques and ultimately, in some patients, tumors. However, numerous clinical and histopathologic variants of MF with specific therapeutic and prognostic implications have been described in recent decades. Clarification of the differential diagnosis can be frustrated by the wide range of clinical manifestations and histopathologic patterns of cutaneous infiltration, particularly in the early phases of the disease. In this paper, we review the main clinical, histopathologic, and immunohistochemical characteristics of the variants of MF described in the literature in order to facilitate early diagnosis of the disease.

Resumen La micosis fungoide (MF) es el linfoma primario cutaneo de celulas T mas frecuente. La evolucion clinica clasica de la enfermedad se caracteriza por la progresion desde una fase inespecifica de maculas eritematosas a la aparicion de placas y, finalmente, tumores en algunos pacientes. Sin embargo, a lo largo de las ultimas decadas se han descrito numerosas variantes de MF, tanto desde el punto de vista clinico como histopatologico, con implicaciones terapeuticas y pronosticas especificas. El diagnostico diferencial se ve dificultado asi ante el amplio abanico de manifestaciones clinicas y patrones histopatologicos de infiltracion cutanea, especialmente en fases precoces de la enfermedad. Este articulo revisa las principales caracteristicas clinicas, histopatologicas e inmunohistoquimicas que definen las distintas variantes de MF descritas en la literatura con el objetivo de facilitar el diagnostico temprano de MF.

Elastosis perforans serpiginosa (EPS) is a rare skin disorder characterized by transepidermal elimination of abnormal elastic fibres. We present a new case of D-penicillamine (DPA)-induced EPS, and describe the clinical, dermoscopic, histopathological and direct immunofluorescence (DIF) findings. A 33-year-old woman receiving treatment with DPA presented with annular skin lesions. Digital dermoscopy of the lesions showed a central area of pink and yellowish discolouration with keratotic papules in the periphery, surrounded by a white halo, disposed in a way that resembled the islands of an archipelago. Other lesions showed a white to yellow central colouration and 'chrysalides' surrounding the keratotic plugs. Linear and granular deposits of IgG attached to the abnormal elastic fibres were seen with DIF. Dermoscopy can be helpful in the diagnosis of EPS. Moreover, DIF findings in skin biopsies of this case support the immune-mediated pathogenesis of EPS.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft-tissue tumor characterized by a relatively high risk for local recurrence and low risk for metastasis. Many histopathologic variants of DFSP have been described, including the fibrosarcomatous and myoid variants, which may obscure the diagnosis in some cases, especially when arising in unusual locations. Of all the variants described so far, the only one with prognostic relevance is the FS-DFSP variant, which implies tumor progression and a higher possibility for metastasis. The authors report a case of a giant DFSP, located on the vulvar area, which histopathologically showed areas of fibrosarcomatous and myoid differentiation, and discuss the importance of the myoid variant in regards of the debated histogenesis of DFSP.

A large list of foreign substances may penetrate the skin and induce a foreign body granulomatous reaction. These particles can enter the skin by voluntary reasons or be caused by accidental inclusion of external substances secondary to cutaneous trauma. In these cases, foreign body granulomas are formed around such disparate substances as starch, cactus bristles, wood splinters, suture material, pencil lead, artificial hair, or insect mouthparts. The purpose of this article is to update dermatologists, pathologists, and other physicians on the most recent etiopathogenesis, clinical presentations, systemic associations, evaluation, and evidence-based management concerning foreign body granulomatous reactions of skin.

Amyloid is characterized by its fibrillary ultrastructure, and more than 20 proteins have been described to date as possible precursors. Among them, insulin and enfuvirtide represent the only medications described as amyloidogenic substances. We describe two diabetic patients, who were undergoing long-standing subcutaneous insulin treatment, who developed subcutaneous nodules at the sites of insulin injections. Histopathologic examination showed the presence of eosinophilic and amorphous masses in deep dermis, which stained positive with Congo red, amyloid P substance and anti-human insulin antibody. Whether the type of injected insulin played a role or not in the pathogenesis of the process is still uncertain, because all described patients used both fast-acting and slow-acting insulins at the same injection sites. Our second case showed nodular insulin-derived amyloid tumors only at the sites where exclusively fast-acting insulin was injected, which supports the notion that fast-acting insulin may also be the cause of this disorder. Insulin-derived nodular amyloidosis is probably underdiagnosed because of the small body of literature in comparison with the prevalence of insulin dependent diabetic patients. This underdiagnosis probably is because of its clinical similarity with the lesions of lipohypertrophy at the sites of insulin injections, which is rarely biopsied.

Merkel cell carcinoma (MCC) has been reported in association with other types of cutaneous neoplasms within the same lesion, including squamous cell carcinoma, Bowen's disease, actinic keratosis, follicular cysts, trichoblastoma and lentigo maligna, among others. However, the association of MCC and sweat gland tumors has never been described in the literature. We report two unique cases of MCC that developed within cutaneous poromas. A 56-year-old male (Patient 1) and an 81-year-old female (Patient 2) presented with nodules on the upper arm and lower back, respectively. Histopathologic study of both cases revealed a tumor in the dermis composed of poroid and cuticular cells intermingled with a proliferation of small round cells that showed characteristic histopathological and immunohistochemical features of MCC. In both cases, the two neoplasms were tightly admixed and distinct, suggesting that the MCC could have developed within a previously existing poroma. No morphological features of transition between the two tumors were seen. Neoplastic cells of MCC expressed immunoreactivity for chromogranin, synaptophysin, neuron-specific enolase, CAM 5.2 and cytokeratin 20, the last two markers showing the characteristic paranuclear dot-like pattern. In contrast, the poroma cells only expressed cytokeratin MNF116. Metastatic deposits were not identified in the regional lymph nodes or distantly.

Resumen El diagnostico de las enfermedades del cabello y del cuero cabelludo se basa, en la mayoria de las ocasiones, en el reconocimiento de signos clinicos; sin embargo, dichos signos no siempre son caracteristicos y, en ocasiones, tenemos que recurrir a tecnicas mas invasivas como la realizacion de una biopsia. En este articulo se revisa de forma detallada las principales formas de alopecia desde un punto de vista histopatologico, y para ello se utiliza la clasificacion tradicional de las alopecias que las divide en 2 grandes grupos: las alopecias cicatriciales y las no cicatriciales. Las alopecias cicatriciales son aquellas en las cuales el foliculo piloso es sustituido por tejido fibroso cicatricial, causando una perdida permanente del cabello. En las alopecias no cicatriciales el foliculo permanece intacto y puede retomar su actividad cuando cesa el estimulo desencadenante. La primera parte de este articulo revisa las principales formas de alopecia no cicatricial desde un punto de vista histopatologico. Dado que una buena correlacion clinico-patologica es fundamental para realizar el correcto diagnostico histopatologico de las alopecias, en este articulo se incluye tambien una breve descripcion de las caracteristicas clinicas de las principales formas de alopecia.

The diagnosis of disorders of the hair and scalp can generally be made on clinical grounds, but clinical signs are not always diagnostic and in some cases more invasive techniques, such as a biopsy, may be necessary. This 2-part article is a detailed review of the histologic features of the main types of alopecia based on the traditional classification of these disorders into 2 major groups: scarring and nonscarring alopecias. Scarring alopecias are disorders in which the hair follicle is replaced by fibrous scar tissue, a process that leads to permanent hair loss. In nonscarring alopecias, the follicles are preserved and hair growth can resume when the cause of the problem is eliminated. In the first part of this review, we describe the histologic features of the main forms of nonscarring alopecia. Since a close clinical-pathological correlation is essential for making a correct histologic diagnosis of alopecia, we also include a brief description of the clinical features of the principal forms of this disorder.

Background Folliculitis decalvans (FD) is a rare neutrophilic scarring alopecia that represents a therapeutic challengefor dermatologists.Objective To describe the epidemiology, comorbidities, clinical presentation, diagnostic !ndings and therapeuticoptions in a large series of patients with FD.Methods This retrospective multicentre review includes patients diagnosed with FD based on clinical and histopatho-logic !ndings. The clinical severity was determined by the maximum diameter of the largest alopecic patch (slight

Background To our knowledge, there are no large multicenter studies concerning frontal fibrosing alopecia (FFA) that could give clues about its pathogenesis and best treatment. Objective We sought to describe the epidemiology, comorbidities, clinical presentation, diagnostic findings, and therapeutic choices in a large series of patients with FFA. Methods This retrospective multicenter study included patients given the diagnosis of FFA. Clinical severity was classified based on the recession of the frontotemporal hairline. Results In all, 355 patients (343 women [49 premenopausal] and 12 men) with a mean age of 61 years (range 23-86) were included. Early menopause was detected in 49 patients (14%), whereas 46 (13%) had undergone hysterectomy. Severe FFA was observed in 131 patients (37%). Independent factors associated with severe FFA after multivariate analysis were: eyelash loss, facial papules, and body hair involvement. Eyebrow loss as the initial clinical presentation was associated with mild forms. Antiandrogens such as finasteride and dutasteride were used in 111 patients (31%), with improvement in 52 (47%) and stabilization in 59 (53%). Limitations The retrospective design is a limitation. Conclusions Eyelash loss, facial papules, and body hair involvement were associated with severe FFA. Antiandrogens were the most useful treatment.

Drug-induced lupus erythematosus (DILE) is a less severe variant of systemic lupus erythematosus (SLE) that generally resolves within weeks or months after the withdrawal of the implicated drug. DILE is unusual during childhood, with the most frequent age of presentation being at 50-70 years of age. Among different drugs, most commonly procainamide and hydralazine have been implicated as a cause of DILE. However carbamazepine (CBZ) is considered a low-risk drug and very few cases have been reported in children. We describe the case of CBZ-induced SLE in a 9-year-old girl following 3 years of CBZ therapy. This case report shows that drug-induced SLE is an important side-effect to be considered, even after long-term treatment with CBZ, and also during childhood.

Background Bevacizumab is a recombinant, humanized monoclonal antibody against vascular endothelial growth factor (VEGF) that inhibits angiogenesis. Bevacizumab is typically well tolerated; its major side effects include hypertension, proteinuria, bleeding, gastrointestinal perforation, and arterial thrombotic events, among others. Cutaneous side effects associated with the use of bevacizumab are rare and involve mainly itching and exfoliative dermatitis. Nonspecific skin rash and acneiform eruptions have recently been described in patients following infusion of bevacizumab. Methods Findings in a 52-year-old patient with stage IV lung cancer with brain metastasis, who developed severe, acute, and persistent acne after intravenous (IV) infusion of bevacizumab, are examined. Results The cutaneous eruption was classified as true acne rather than as an acneiform eruption because all cutaneous lesions of acne, namely comedones, inflammatory papules, and pustules, were present. Conclusions To the authors’ knowledge, this is the first report of an association between acne and IV administration of bevacizumab.

Background Polymorphous light eruption (PLE) is the most common form of idiopathic photodermatosis. Several morphologic variants of PLE have been described, including a localized form of PLE primarily affecting the helices of the ears. To our knowledge, the presence of lesions on the elbows as the unique manifestation of PLE has not yet been reported. We have studied 9 patients presenting with a recurrent eruption on the elbows, with clinical and histopathologic features indistinguishable from PLE, occurring during springtime. Recently, a peculiar eruption of the elbows, with similar clinical features to our patients, has been proposed as a manifestation of cutaneous lupus erythematosus. Objective We sought to describe the clinical, histopathological, and immunohistochemical features of this peculiar eruption of the elbows. Methods Nine patients presenting a recurrent spring eruption on the elbows, collected from April 1989 to June 2012, were retrospectively analyzed. We studied their clinical and histopathological features, and the immunophenotype of the infiltrate. Results Five patients were men and 4 were women. The mean age was 44.7 years. The lesions consisted of pruriginous, erythematous-edematous papules and plaques, located on both elbows. The eruption appeared during the spring or early summer and recurred seasonally. No associated symptoms were present and the eruption regressed spontaneously or with topical corticosteroids after 7 to 15 days. Histopathologically, the lesions showed typical features of PLE, with variable degree of edema in the papillary dermis, and a papillary and reticular dermal perivascular infiltrate mostly composed of small lymphocytes. Immunohistochemical studies demonstrated strong immunoreactivity for CD2, CD4, and CD8, revealing the infiltrate was composed predominantly of T lymphocytes, with a predominance of T-helper over T-cytotoxic lymphocytes. Immunostaining for CD123 was negative, highlighting the absence of plasmacytoid dendritic cells. Other T- and B-cell markers, including CD30, PD-1, CXCL13, FoxP3, CD79a, and CD56 were also negative. Limitations Retrospective case series design is a limitation. Phototests were not performed. Results of antinuclear antibodies were only available in 1 patient. Conclusions We believe this recurrent eruption of the elbows represents a distinctive and localized variant of PLE rather than a peculiar manifestation of cutaneous lupus erythematosus and suggest the term "spring and summer eruption of the elbows" for this peculiar condition. The mechanism of this localization on the elbows, with sparing of other photoexposed areas, remains unknown.

Primary cutaneous signet-ring cell carcinoma is a rare and aggressive neoplasm which diffusely involves dermis and subcutis of the eyelid or axillae. Neoplastic cells show a signet-ring cell or histiocytoid morphology in variable number, and can be found intermingled among collagen bundles, sparing the epidermis. This neoplasm typically appears in the eyelids of elderly men, in the form of a painless infiltration and swelling but with no other specific clinical feature, and frequently causes diagnostic retardation and worse prognosis. Frequent involvement of both eyelids of the same eye has given it the name of monocle tumor. Only 29 cases have been described in English literature to date, of which 7 developed metastases, mainly on regional lymph nodes. The authors present a case of involvement of contralateral eyelid, which has only been described previously in 2 cases. The immunohistochemical profile of the involvement in the contralateral eye, and the absence of other metastasis, suggest that it is locally spread from the initial lesion. However the possibility of being a second primary tumor or metastasis cannot be readily ruled out.

Frontal fibrosing alopecia (FFA) is an increasingly common acquired primary scarring alopecia, first described by Kossard in 1994. Clinically it is characterized by frontotemporal hairline recession, frequently accompanied by eyebrow loss. FFA was initially thought to have a hormonal origin as it was first described in postmenopausal women and premenopausal women with a history of hysterectomy or early menopause. This origin, however, has been questioned in recent years due to the publication of cases in men and premenopausal women. Although FFA has a highly characteristic clincal pattern, it is histologically similar to lichen planopilaris, and is currently believed to be a clinical variant of this condition. No clinical trials to date have investigated the efficacy of treatments for FFA. Numerous drugs, however, have been assessed in observational studies, and the best results to date have been reported for 5-αreductase inhibitors and intralesional corticosteroids, followed by antimalarials and calcineurin inhibitors. In this article, we review the latest data on the etiology, pathogenesis, clinical presentation, diagnosis, and treatment of FFA.

Post-transplant lymphoproliferative disorder (PTLD) is a lymphoid proliferation that develops as a complication of solid organ or bone marrow transplants. PTLD limited to the skin is very rare. Plasmacytoma-like PTLD is an uncommon variant of monomorphic PTLD. Its presentation in the skin is extraordinary with very few cases reported in the literature. We report a new case of plasmacytoma-like PTLD presenting as multiple skin nodules on the leg of a 74-year-old kidney transplant recipient. Histopathologic and immunohistochemical examination of one nodule revealed atypical plasmacytoid and plasmablastic cells that showed kappa light chain restriction and stained positive for CD138. Staging investigations excluded extracutaneous manifestations of the disease. This case is unusual for several reasons including involvement limited to the skin, plasmacytoid phenotype of the tumor, presentation 18 years following transplantation and Epstein-Barr virus negativity.

Immunohistochemistry (IHC) is now one of the main adjunctive methods to conventionally stained sections in histopathology. This is mainly related to the fact that it is a relatively simple, fast, and inexpensive method. Due to technical advances, there has been a significant increase in the number of diagnostic immunohistochemical markers available for pathologists and dermatopathologists in recent years. The sensitivity and specificity of certain antibodies, their staining pattern (nuclear, cytoplasmic, or membranous), and background artifact must be considered in their interpretation. In addition, evaluation must be done in relation to internal control. IHC, however, is only a tool to be used appropriately in the context of clinical and histopathologic correlation; unreasonable use can be misleading and financially cost ineffective. In this review, we highlight the main available immunohistochemical markers that have been used for diagnosis of neoplasms with eccrine and apocrine differentiation. Although the diagnosis of neoplasms showing secretory apocrine differentiation is straightforward, specific markers for histopathologic differential diagnosis between eccrine and apocrine ductal neoplasms are still missing. In any case, numerous markers are now available to assist the dermatopathologist in the diagnosis of these neoplasms, supporting true ductal differentiation and helping in the distinction between primary and metastatic adenocarcinomas in the skin.

Drug-induced lupus erythematosus (DILE) is a less severe variant of systemic lupus erythematosus (SLE) that generally resolves within weeks or months after the withdrawal of the implicated drug. DILE is unusual during childhood, with the most frequent age of presentation being at 50-70 years of age. Among different drugs, most commonly procainamide and hydralazine have been implicated as a cause of DILE. However carbamazepine (CBZ) is considered a low-risk drug and very few cases have been reported in children. We describe the case of CBZ-induced SLE in a 9-year-old girl following 3 years of CBZ therapy. This case report shows that drug-induced SLE is an important side-effect to be considered, even after long-term treatment with CBZ, and also during childhood.

Molluscum contagiosum (MC) is the commonest human poxvirus infection. Follicular induction has rarely been observed in the epidermis surrounding lesions of MC. A virus-induced localized proliferation of germinative/stem cells of the folliculosebaceous-apocrine unit has been suggested as the underlying cause, however few reports of this peculiar phenomenon exist in the literature and the mechanisms involved in this proliferation require further study.We prospectively collected MC cases showing multifocal areas of primitive follicular induction involving the adjacent undersurface epidermis. Immunohistochemical expression of BerEP4, PHLDA1 and cytokeratin 20 (CK20) was evaluated in the basaloid germs surrounding the lesions. For PHLDA1, we used epidermal melanocytes as a positive internal control. For BerEP4, we employed a basal cell carcinoma (BCC) and for CK20, colon as positive external controls. An incubation without the primary antibody functioned as an external negative control.All the cases studied showed an intense positive staining of the basaloid buds with BerEP4 and weaker stain for PHLDA1. CK20 showed the presence of scattered Merkel cells within the induced epidermal basaloid proliferations favoring their reactive origin.The pathogenetic mechanisms behind the development of these microscopic features and the link between follicular induction and poxvirus infection are explored. Awareness of this unusual phenomenon by dermatopathologists will be helpful in avoiding a misdiagnosis of a superficial BCC in such cases.BerEP4 and PHLDA1 were consistently expressed in the areas of primitive follicular induction surrounding lesions of MC. CK 20 stained the Merkel cells present in the basaloid buds. All these findings support the reactive origin of this phenomenon, which we believe is most probably viral-induced.

Although rising incidence rates of cutaneous melanoma have been observed during the last 4 decades in white populations worldwide, the sebocyte-like cell variant has been described only twice in the literature to date. In our case, a 64-year-old man presented for evaluation of a changing pigmented lesion on the left upper back. Excision of the lesion revealed an invasive melanoma with a Breslow depth of 3.3 mm. Microscopic sections showed a predominantly dermal-based tumor composed of sheets and nests of enlarged epithelioid melanocytes, most of which showed an uncommon phenotype with multivacuolated cytoplasms and scalloped nuclei, features that gave them a strong resemblance to mature sebocytes. The lesional cells expressed S100 protein, Melan-A, and p16, whereas adipophilin was positive only within the sebocyte-like component of the neoplasm and showed focal nonspecific staining. The patient's sentinel lymph node biopsy was positive for micrometastases, although a subsequent position emission tomography scan was unremarkable. Sebocyte-like melanocytes are a rare distinctive type of melanocytes that can be found mostly in benign but also in malignant melanocytic lesions. They usually present focally within the lesions and, therefore, do not represent a diagnostic problem in nevus or primary cutaneous melanoma. However, when sebocyte-like melanocytes are the main cellular component of a melanocytic lesion or when they are found in the context of metastatic melanoma, they may create a potential diagnostic pitfall; for this reason, awareness of this cell type is important.

The identification of pathogens is of vital importance for the adequate treatment of infections. During the past 2 decades, the approach to histopathologic diagnosis has been dramatically transformed by immunohistochemistry (IHC) specifically in the diagnosis and classification of tumors and more recently in the diagnosis of infectious diseases in tissue samples. The main goals of this article were to: (1) identify by IHC the cutaneous structures where bacterial pathogens are expressed in the course of infection, (2) identify the specific cells in which bacterial pathogens are expressed in positive cases, and (3) describe the pattern of distribution of the bacterial antigens within these cells (nuclear, cytoplasmatic, or membranous). This article is an up-to-date overview of the potential uses and limitations of IHC in the histopathologic diagnosis of cutaneous bacterial infections. In conclusion, IHC is especially useful in the identification of microorganisms that are present in low numbers, stain poorly, are fastidious to grow, culture is not possible, or exhibit an atypical morphology.

Amyloid is characterized by its fibrillary ultrastructure, and more than 20 proteins have been described to date as possible precursors. Among them, insulin and enfuvirtide represent the only medications described as amyloidogenic substances. We describe two diabetic patients, who were undergoing long-standing subcutaneous insulin treatment, who developed subcutaneous nodules at the sites of insulin injections. Histopathologic examination showed the presence of eosinophilic and amorphous masses in deep dermis, which stained positive with Congo red, amyloid P substance and anti-human insulin antibody. Whether the type of injected insulin played a role or not in the pathogenesis of the process is still uncertain, because all described patients used both fast-acting and slow-acting insulins at the same injection sites. Our second case showed nodular insulin-derived amyloid tumors only at the sites where exclusively fast-acting insulin was injected, which supports the notion that fast-acting insulin may also be the cause of this disorder. Insulin-derived nodular amyloidosis is probably underdiagnosed because of the small body of literature in comparison with the prevalence of insulin dependent diabetic patients. This underdiagnosis probably is because of its clinical similarity with the lesions of lipohypertrophy at the sites of insulin injections, which is rarely biopsied.

Cutaneous viral infections are of increasing clinical importance, particularly in patients who are immunocompromised.The use of immunohistochemistry (IHC) in the diagnosis of cutaneous infections provides a rapid morphological diagnosis and can be applied to confirm the diagnosis of specific viral infections that may be difficult to diagnose with certainty using routine microscopy alone, thus facilitating clinical decisions in patient care.Several immunostains for specific viruses that have been useful in dermatopathology are reviewed. Emphasis is placed on new stains and novel uses of existing stains.This article is an up-to-date overview of the potential uses and limitations of IHC in the histopathologic diagnosis of cutaneous viral infections by herpesviruses and papillomaviruses.Whereas specific monoclonal antibodies effectively distinguish infections by herpes simplex virus-1, herpes simplex virus-2, varicella zoster virus, Epstein-Barr virus, and cytomegalovirus, IHC does not distinguish between the 120 antigenically distinct strains of human papillomavirus.IHC may assist dermatopathologists to appropriately diagnose viral infections caused by herpesviruses and papillomaviruses.

Superficial acral fibromyxoma (SAF) is a recently recognized myxoid tumor that usually occurs on the fingers and toes of middle-aged adults. We report the case of a 53-year-old man with a SAF on the first left toe that had been slowly growing for 2 years. Hispathologically, the lesion was nonencapsulated and was composed of stellate and spindle cells, arranged in a myxoid matrix. No atypia or mitotic figures were found. Neoplastic cells showed positive staining for CD34 and negative staining for epithelial membrane antigen, actin, desmin, keratins, S-100 protein, and HMB45. Main differential diagnoses of SAF include benign and malignant myxoid and spindle cells tumors, such as myxoid fibrous histiocytoma, superficial angiomyxoma, myxoid neurofibroma, myxoid dermatofibrosarcoma protuberans, and low-grade fibromyxoid sarcoma.

Giant congenital melanocytic nevi (GCMNs) represent a distress to patients for 2 reasons: one is disfigurement, and the other is the increased risk of developing secondary melanocytic tumors, such as benign proliferative nodules (BPNs) and malig- nant melanoma (MM). BPN present as a rapid growth nodule arising within a congenital melanocytic nevus (CMN) that often ulcerates, occurs in children younger than 2 years of age. BPNs arising within a CMN are exceedingly rare after childhood, and very few cases have been described in adults. Despite the worrisome clinical and histologic findings of BPN, most laboratory investigations seem to support their benignity. The distinction between MM and BPN is extremely important, but the histopathology of BPN of GCMN can be a challenge to differentiate from MM. In the recent years, molecular tests that investigate DNA copy number alterations such as fluores- cence in situ hybridization and comparative genomic hybridization have shown promise to help guide the diagnosis of ambiguous melanocytic proliferations arising within CMNs. We report the case of a 22-year-old woman with a nodule arising in a GCMN and with an axillary mass suggesting a nodal metastasis of melanoma, and discuss the unusual clinical, histopathologic, and molecular findings that make this case particularly interesting.

The diagnosis of disorders of the hair and scalp can generally be made on clinical grounds, but clinical signs are not always diagnostic and in some cases more invasive techniques, such as a biopsy, may be necessary. This 2-part article is a detailed review of the histologic features of the main types of alopecia based on the traditional classification of these disorders into 2 major groups: scarring and nonscarring alopecias. Scarring alopecias are disorders in which the hair follicle is replaced by fibrous scar tissue, a process that leads to permanent hair loss. In nonscarring alopecias, the follicles are preserved and hair growth can resume when the cause of the problem is eliminated. In the second part of this review, we describe the histologic features of the main forms of scarring alopecia. Since a close clinical-pathological correlation is essential for making a correct histopathologic diagnosis of alopecia, we also include a brief description of the clinical features of the principal forms of this disorder.