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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.

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.

[Background]: Acantholytic cutaneous squamous cell carcinomas (aCSCCs) have been classically considered as a high-risk variant of CSCC. However, more recent studies show that aCSCC does not confer more aggressiveness. This study aims to establish whether the prognosis of the aCSCC is worse than that of the non-acantholytic (naCSCC) or not. [Methods]: Retrospective case-control study with 50 aCSCCs and 50 naCSCCs. For each aCSCC, an naCSCC with similar high-risk features to the aCSCC but with no acantholysis was selected. Prognosis between both groups was compared. [Results]: The mean age was 86 years (SD 9.61). Sixty-one patients were men. Thirty-nine CSCCs were located in high-risk head and neck areas. Twenty CSCCs exhibited a poor degree of differentiation, and 36 showed an infiltrative growth pattern. The tumor diameter was 18.71 mm (interquartile range, IQR 35), and the tumor thickness was 6.72 mm (IQR 15.50). Twelve CSCCs exhibited perineural infiltration, and eight CSCCs exhibited invasion beyond the subcutaneous fat. Positive margins after excision of the tumor in 22 aCSCCs vs eight naCSCCs (P, Instituto de Salud Carlos III, Grant/Award Number: PI18/000587

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 of vascular occlusion.

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.

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 hora de elaborar sus propios informes de forma rutinaria. Abstract: 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.

Reticular telangiectatic erythema is a benign dermatosis which has been described on patients with pacemakers, implantable devices or materials inserted in their body. Etiology of this entity hasn't been clarified since the first description in 1981 but it is suggested that physical or mechanical factors have to be involved. We present the second case of bilateral reticular telangiectatic erythema by breast implants described in the literature.

Atypical fibroxanthoma is a rare mesenchymal skin tumor of intermediate malignancy that typically occurs on sun-damaged skin of elderly patients. Histologically, it is composed of pleomorphic cells with hyperchromatic nuclei and abundant cytoplasm, commonly arranged in a spindle cell pattern. Different histologic variants have been described during the past years. We present a case of atypical fibroxanthoma containing a dense inflammatory infiltrate, which in conjunction with the existence of immunoblast-like and Reed-Sternberg-like neoplastic cells could be misinterpreted as a lymphoid neoplasm. Immunohistochemical studies revealed strong positivity of tumor cells for CD10 and negativity for cytokeratins, p63, p40, S100, SOX10, ERG, actin, desmin, B and T-cell markers, BCL6, CD15, and CD30. The inflammatory infiltrate contained a mixed reactive T- and B-cell population with negative T-cell receptor and immunoglobulin heavy rearrangements. We discuss the differential diagnosis of this entity in which clinical, immunohistochemical, and molecular features are essential to avoid the diagnosis of a lymphoproliferative disease.

The novel coronavirus disease (COVID-19) is a rapidly spreading pandemic, secondary to severe acute respiratory syndrome coronavirus 2. The severity and the little knowledge that we have of the disease have made us focus mostly on the respiratory symptoms. As we bend the curve, other findings reported in association with COVID-19 become of importance for specialists to recognize. We describe the spectrum of clinicopathologic lesions in the skin that can be the only symptom or the first manifestation of COVID-19 and demonstrate the origin of the virus. We collected 25 patients with skin lesions in this context. We recognized 5 types of cutaneous manifestations including acute acroischemic or chilblain-like lesions (11), purpura palpable (2), exanthemas (9), urticarial eruptions (1), and other lesions (2) that might appear with more unspecific pictures. Chilblain-like lesions were the most common form of presentation, which tend to appear as self-healing, erythematous-necrotic plaques mostly on the feet, in young patients with no systemic symptoms associated. Importantly, we visualized viral particles with electron microscopy in 5 of 13 cases analyzed. In this study, we seek to draw a picture of the spectrum of clinicopathologic lesions that may appear in the skin in the context of COVID-19. Although apparently skin lesions are not correlated with disease severity, it may help in some cases to recognize and control the spread of the infection sooner.

Background The introduction of immune checkpoint inhibitors (ICI) has improved the survival outcomes of patients with advanced melanoma. To date, only a few studies have evaluated the immunohistochemical (IHC) expression of PD-1 and CTLA-4 in tumor-infiltrating lymphocytes (TILs) as predictive markers of response to ICI, most of them in the context of clinical trials. Moreover, the predictive value of PD-L1 in melanoma cells in the response to immunotherapy is unclear. The aim of our study was to assess the IHC expression of PD-L1, PD-1, and CTLA-4 in samples of patients with advanced melanoma and to establish their prognostic value as predictors of ICI response in a university hospital. Methods The expression of PD-L1, PD-1, and CTLA-4 was evaluated in pretreatment tumor samples in a series of 35 patients, 21 patients treated with nivolumab and 14 patients with ipilimumab in monotherapy. Results In the nivolumab group, 4 tumors (19%) were positive for PD-L1 and all of them showed a partial response to the treatment. However, 4 patients whose tumors did not express PD-L1 also responded to nivolumab. PD-1 expression was not associated with better progression-free survival (PFS). In the ipilimumab group, 5 patients (35.7%) showed expression of CTLA-4. Positive cases showed a better PFS; however, one negative case responded to ipilimumab. Conclusions Nivolumab produces a better response compared with ipilimumab in patients with melanoma. The IHC expression of PD-L1 and CTLA-4 are associated with a higher response rate to nivolumab and ipilimumab, respectively, and better PFS, but the existence of responder patients with negative expression suggests that they are not adequate biomarkers to select candidate patients for ICI in the clinical practice.

To the Editor: Perineural invasion (PNI) is rare and usually incidental in cutaneous squamous cell carcinoma (SCC), with an incidence of 2.5% to 14%.1 Incidental PNI is associated with poor prognosis in cutaneous SCC,2 and some evidence suggests its outcome differs, depending on the PNI pattern. We evaluated patterns of incidental PNI, using a multicenter retrospective cohort of 140 cutaneous SCCs with incidental PNI to determine the influence of nerve involvement on cutaneous SCC prognosis., Dr Canueto is partially supported ~ by grants PI18/000587 (Instituto de Salud Carlos III, cofinanced by Fondo Europeo de Desarrollo Regional) and GRS 1835/A/18 (Gerencia Regional de Salud de Castilla y Leon).

Dermatofibroma (DF) represents one of the most common mesenchymal proliferations of the skin. Their recurrence rate, even when incompletely excised, is very low, whereas the atypical, aneurysmal, and cellular variants have recurrence rates of up to 20% each. Extraordinary rare malignant lesions with metastases to lymph nodes and/or lung have been described. We report a 64-year-old woman with a long history (years) of a skin lesion on her right arm that became painful during the last months. Histologically, it consisted of a conventional cellular DF in which perineural invasion was present. Subsequently, the lesion showed a clinically aggressive course with recurrences, sarcomatous transformation, and pulmonary metastases. Given that no predictive morphological features have been identified to separate classical benign DF from rare metastasizing forms, perineural invasion in an otherwise conventional DF could be a histopathologic clue for an adverse prognosis and should provoke a closer clinical follow-up., info:eu-repo/semantics/published

Crystalglobulinemia is an extremely rare pathology that is associated in most cases with plasma cell dyscrasia, mainly multiple myeloma. In most cases, it may be the manifestation of incipient gammopathy or it manifests shortly after diagnosis. We report a patient with ischemic lesions of thrombotic origin in lower limbs. Subsequently, renal involvement occurs, in view of this involvement, it is suspected that the patient may have an associated vasculitis. After performing the biopsy and with the subsequent diagnosis of monoclonal gammopathy of uncertain significance, the diagnosis is made. We review the most recent bibliography of patients who have been diagnosed with crystalglobulinemia associated with plasma dyscrasia focusing in those with thrombotic vasculopathy or acute renal failure. In our case, in addition to being associated with monoclonal gammopathy of undetermined significance that is less frequent, the debut of the symptoms is years before the detection of the monoclonal peak. This could speak of patients with a low peak of monoclonal component (not detected by immunoelectrophoresis) who could have kidney and vascular damage.

Graft-versus-host disease (GVHD) is one of the most common and serious complications of hematopoietic stem-cell transplantation that mainly affects the skin, gastrointestinal tract, and liver. Hepatic GVHD is associated with high morbidity and mortality, and its diagnosis can be especially challenging because of nonspecific clinical signs and symptoms. It must be suspected in patients with elevated liver enzymes and cholestasis, especially in those with a history of preceding skin rash and diarrhea. We describe 3 patients with cutaneous and hepatic GVHD that presented with severe hypercholesterolemia and hypertriglyceridemia, and no xanthomatous macular lesions, in which cutaneous biopsies revealed the presence of xanthomatous dermal histiocytes. We propose that the presence of these xanthomatous cells in skin biopsies from patients with cutaneous GVHD could be a dermatopathological clue for the diagnosis of hepatic GVHD.

BackgroundPanniculitis occurring in dermatomyositis is uncommon, with only a few cases described in the literature, most of them as case reports. ObjectiveThis report describes the clinicopathological and immunohistochemical findings in a series of 18 patients with panniculitis associated with dermatomyositis. MethodsIn each patient, we collected the clinical data of the cutaneous lesions as well as the characteristic clinical and laboratory findings. A series of histopathologic findings was recorded in the biopsy of each patient. A panel of antibodies was used in some cases to investigate the immunophenotype of the infiltrate. Data of treatment and follow-up were also collected. ResultsOf the 18 patients, 13 were female and 5 were male, ranging in age from 13 to 74 years (median, 46.4 years). In addition to panniculitis, all patients presented pathognomonic cutaneous findings of DM and reported proximal muscle weakness prior to the diagnosis of panniculitis. Muscle biopsy was performed in 17 patients and MRI in one, all with the diagnosis of inflammatory myopathy. None of the patients presented any associated neoplasia. Panniculitis lesions were located in the upper or lower limbs. Histopathology showed a mostly lobular panniculitis with lymphocytes as the main component of the infiltrate. Most cases showed also numerous plasma cells and lymphocytes surrounding necrotic adipocytes (rimming) were frequently seen. Lymphocytic vasculitis and abundant mucin interstitially deposited between collagen bundles of the dermis were also frequent findings. Late-stage lesions showed hyaline necrosis of the fat lobule and calcification. Immunohistochemistry demonstrated that most lymphocytes of the infiltrate were T-helper lymphocytes, with some B lymphocytes in the lymphoid aggregates and small clusters of CD-123-positive plasmacytoid dendritic cells in the involved fat lobule. ConclusionPanniculitis in dermatomyositis is rare. Histopathologic findings of panniculitis dermatomyositis are identical to those of lupus panniculitis. Therefore, the final diagnosis requires clinic-pathologic correlation. Linked article: This article is commented on by A. Kuhn, pp. 1231-1232 in this issue. To view this article visit

The identification of B-Raf proto-oncongene ( BRAF ) mutation and the emergence of targeted therapy marked a turning point in the treatment of melanoma. The study of mutation status concordance between primary tumors and metastases in this cancer has major treatment implications as it facilitates the selection of candidates for targeted therapy. This review analyzes the evidence on the level of mutation status concordance between primary tumors and different types of metastases in cutaneous melanoma and provides an overview of the advantages and disadvantages of the various methods used to detect BRAF mutations.

Allogeneic hematopoietic stem-cell transplantation and solid-organ transplantation are associated with an increased risk of secondary neoplasms. Indeterminate cell histiocytosis (ICH) is a rare disease composed of so-called indeterminate cells, an alleged cutaneous dendritic cell subset displaying histological and some ultrastructural and immunophenotypic features of Langerhans cells but lacking Birbeck granules. We report a case of cutaneous ICH occurring after allogeneic hematopoietic stem-cell transplantation for a myelodysplastic syndrome in a 56-year-old man. Microsatellite analysis demonstrated that the neoplastic cells were derived from the donor's hematopoietic system. This case broadens the spectrum of complications after stem-cell transplantation and demonstrates that cutaneous ICH in the setting of myelodysplastic syndromes may have a nonrelated origin to dysplastic myeloid cells.

We review the most characteristic clinical and histopathologic findings of the cutaneous manifestations of the occlusive nonvasculitic vasculopathic disorders. Clinically, most of these conditions are characterized by retiform purpura. Histopathologic findings consist of occlusion of the vessel lumina with no vasculitis. Different disorders may produce nonvasculitic occlusive vasculopathy in cutaneous blood and lymphatic vessels, including embolization due to cholesterol and oxalate emboli, cutaneous intravascular metastasis from visceral malignancies, atrial myxomas, intravascular angiosarcoma, intralymphatic histiocytosis, intravascular lymphomas, endocarditis, crystal globulin vasculopathy, hypereosinophilic syndrome, and foreign material. Other times, the occlusive disorder is due to platelet pugging, including heparin necrosis, thrombocytosis secondary to myeloproliferative disorders, paroxysmal nocturnal hemoglobinuria, and thrombotic thrombocytopenic purpura. Occlusive vasculopathy may also appear in cold-related gelling agglutination, like that occurring in cryofibrinogenemia, cryoglobulinemia, cold agglutinin syndrome, and crystalglobulinemia. Microorganisms may also occlude the vessels lumina and this is especially frequent in ecthyma gangrenosum, opportunistic fungi as aspergillosis or fusariosis, Lucio phenomenon of lepromatous leprosy and disseminated strongyloidiasis. Systemic coagulopathies due to defects of C and S proteins, coumarin/warfarin-induced skin necrosis, disseminated intravascular coagulation, and antiphospholipid antibody/lupus anticoagulant syndrome may also result in occlusive nonvasculitic vasculopathy. Finally, vascular coagulopathies such as Sneddon syndrome, livedoid vasculopathy, and atrophic papulosis may also cause occlusion of the vessels of the dermis and/or subcutis. Histopathologic study of occlusive vasculopathic lesions is the first step to achieve an accurate diagnosis, and they should be correlated with clinical history, physical examination, and laboratory findings to reach a final diagnosis.

The occurrence of Pacinian corpuscles associated to lymph nodes is an anatomical rarity and very scarce information exists in this regard. Here we examined immunohistochemically four Pacinian corpuscles found in the close vicinity of the hiliar blood vessels of lymph nodes (2 cervical, 1 axillary, and 1 inguinal) during routine surgical pathology. Pacinian corpuscles were normally arranged and displayed a pattern of protein distribution as follows: the axon was positive for neurofilament proteins and neuron specific enolase, the inner core cells showed intense S100 protein and vimentin immunostaining while they were negative for glial fibrillary acidic protein, type IV collagen and glucose transporter 1; vimentin, type IV collagen, and glucose transporter 1 were also observed also in the outer-core and the capsule. These results are in agreement with those reported for cutaneous Pacinian corpuscles, demonstrating that the immunohistochemical profile of these corpuscles is independent of its anatomical localization. The possible functional significance of Pacinian corpuscles in lymph nodes is discussed. Anat Rec, 300:2233-2238, 2017. © 2017 Wiley Periodicals, Inc.

Degos disease (DD) or papulosis atrophicans maligna, is an extremely infrequent thrombotic microangiopathy of unknown etiology(1). Clinically, it is characterized by small erythematous papules with an atrophic center that may simulate a simple scar and distinct histopathological feature that is not always present. Due to the rarity of this entity, diagnosis may go unnoticed with the first onset of cutaneous lesions. Therefore, high clinical suspicion and adequate clinicopathological correlation are required to establish an early diagnosis and consequently treatment. This article is protected by copyright. All rights reserved.

Therapies targeting the BRAF oncogene have improved the overall and disease-free survival of patients with advanced melanomas. An unresolved issue in clinical practice is the existence (or not) of BRAF-mutated and BRAF-nonmutated tumors in individual patients (intrapatient BRAF mutation heterogeneity), which may serve as a mechanism of resistance to BRAF inhibitors or lead to diagnostic problems. Different research groups have reported differing results after analyzing the BRAF mutation statuses of multiple melanoma tumors. Herein, we present a brief revision of the literature on this controversial topic and propose a theory to justify the divergence of the results found in the literature.

[Background]: Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans after basal cell carcinoma, and its incidence is dramatically rising. CSCC is rarely problematic, but given its high frequency, the absolute number of complicated cases is also high. It is necessary to identify molecular markers in order to recognize those CSCCs with poor prognosis. There is controversy concerning the role of epidermal growth factor receptor (EGFR) as a marker of prognosis in CSCC. In addition, EGFR-targeted therapies have emerged in recent years and a better understanding of the role of EGFR in CSCC may be of help for some patients in predicting prognosis and guiding curative management. [Objectives]: To evaluate the role of EGFR as a prognostic factor in CSCC. [Methods]: We evaluated clinical and histopathological features, including events of poor clinical evolution, in a series of 94 cases of CSCC. We also analysed EGFR expression by immunohistochemistry, fluorescent in situ hybridization and quantitative polymerase chain reaction. [Results]: We detected EGFR in 85 cases (90%), with overexpression in 33 cases (35%), and aberrant EGFR expression in the cytoplasm in 50 cases (53%). EGFR overexpression in the primary tumours was associated with lymph node progression, tumour–nodes–metastasis stage progression and proliferation (Ki-67 staining) in CSCC. EGFR overexpression and poor grade of differentiation were the strongest independent variables defining lymph node metastasis and progression in CSCC in a logistic regression model. [Conclusions]: We demonstrate that EGFR overexpression has prognostic implications associated with lymph node metastasis and progression in CSCC., J.P.‐L. was partially supported by FEDER and MICINN (PLE2009‐119, SAF2014‐56989‐R), Instituto de Salud Carlos III (PI07/0057, PI10/00328, PIE14/00066), Junta de Castilla y León (SAN673/SA26/08, SAN126/SA66/09, SA078A09, CSI034U13, BIO/SA31/15), IBSAL (IBY15/00003), the ‘Eugenio Rodríguez Pascual’, the ‘Fundación Inbiomed’ (Instituto Oncológico Obra Social de la Caja Guipozcoa‐San Sebastian, Kutxa) and the ‘Fundación Sandra Ibarra de Solidaridad frente al Cáncer’. C.R.‐C. is funded by Q3718001E (2009‐2010) and GRS 612/A/11 (2011‐2012) and ‘the Fundación Eugenio Rodríguez Pascual’. A.C.‐M. was supported by FIS (PI07/0057) and MICINN (PLE2009‐119).

Indeterminate dendritic cell tumor (IDCT) is a rare disease composed of so-called indeterminate cells, a dendritic cell subset displaying histological and some ultrastructural and immunophenotypic features of Langerhans cells, but lacking Birbeck granules. We report a case of cutaneous IDCT occurring in a patient with chronic myelomonocytic leukemia (CMML) successfully treated with UV-A phototherapy. Next-generation sequencing studies of the CMML demonstrated mutations in TET2, ASXL1, and ZRS2 genes, also detected in the IDCT, demonstrating a clonal relationship between both tumors and confirming IDCT as a specific subtype in the spectrum of CMML-related cutaneous lesions.

Background Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans and can be both locally invasive and metastatic at distant sites. While research efforts have been made to predict poor outcome of CSCC, there is a lack of knowledge regarding molecular markers. PODOPLANIN has been associated with poor outcome in several types of cancer including CSCC, but this is controversial and only a few studies have evaluated the prognostic implications of Podoplanin in the development of this tumor. Methods We evaluated Podoplanin expression in a series of 94 CSCCs, and searched for associations between Podoplanin expression and histopathological characteristics and with events of poor clinical evolution of the disease. Results Podoplanin expression was observed in 48.9% of the cases and the expression was considered moderate to intense in 19 of the cases. Moderate/intense Podoplanin was associated with infiltrative growth pattern, desmoplasia, and lymphovascular invasion, and with a higher risk of nodal progression and with short disease-free survival, specifically with a short latency to nodal progression. Conclusions This paper provides evidence supporting the implication of Podoplanin expression as a marker of bad prognosis of CSCC.

Key Clinical Message Primary cutaneous plasmacytoma should be in the differential diagnosis in case of solitary or multiple erythematous–violaceous nodules or papules. The diagnosis relies on clinical, histological, and immunochemical findings, without underlying evidence of multiple myeloma. Treatment should be individualized, and agents such as bortezomib or lenalidomide have shown to be effective.

Fibroblastic connective tissue nevus (FCTN) is a rare, benign, dermal mesenchymal hamartoma that affects children. We report a 15-year-old boy with a congenital FCTN and describe the clinical, dermatoscopic, and histopathologic features.

Cutaneous collagenous vasculopathy is a rare clinicopathological entity, first described in 2000. Cutaneous collagenous vasculopathy has been considered a form of microangiopathy of superficial dermal vessels and produce lesions that appear as telangiectasia. We present a patient with histopathologic features of cutaneous collagenous vasculopathy and scattered erythematous papules on the trunk with a striking dermatoscopic finding. We propose the term of 'cutaneous papular collagenous vasculopathy' as a new clinical manifestation of this disease.

The era of targeted therapy has introduced a new therapeutic perspective for melanoma patients. Treatment with BRAFV600 inhibitors has improved overall and disease-free survival in metastatic melanoma patients whose tumors harbor BRAFV600 mutations. Although the BRAFV600E mutation appears to have a critical role in tumor initiation, its expression during tumor progression remains controversial. In fact, various authors claim that BRAFV600E heterogeneity is evident in melanoma tumors. Herein, we investigated the pattern of BRAFV600E expression in matched primary and metastatic samples from 140 patients. Using a combination of real-time PCR and immunohistochemical analyses, we demonstrated that BRAFV600E expression is homogeneous in melanoma tumors and hypothesized that the heterogeneity described by others might be attributable to technical issues when molecular methods are used. We also demonstrated the high efficiency of the anti-BRAFV600E VE1 antibody for the detection of BRAFV600E mutations in melanoma tumors.

Pagetoid dyskeratosis (PD) is an incidental pathologic finding that appears in several skin conditions. In an attempt to better understand PD and its incidence in dermatopathology, the authors have analyzed all skin biopsies performed over the period of 1 year in our Department of Dermatology and examined their clinical and dermatopathological variables. The criteria used for a keratinocyte to be considered a PD cell were: (1) a size larger than normal, (2) the presence of pycnotic nucleus, (3) a clear halo surrounding the nucleus, and (4) a pale eosinophilic cytoplasm. A total of 3565 biopsies were analyzed, PD cells being found in 80 cases (2.24%). Melanocytic nevi were the commonest skin lesions in which PD was observed, followed by soft fibromas, angiofibromas, and acrochordons. Most lesions were located on the head, neck, and trunk. Most cases displayed fewer than 15 PD cells per field. PD cells were normally located in the mid epidermis (frequently in clusters). The biopsies usually revealed indirect signs of rubbing, although PD cells were also found in places where rubbing was unlikely. Here, the authors report the largest series of PD analyzed to date, expanding our understanding of this striking pathological observation.

Importance Histiocytoid Sweet syndrome is a rare histopathologic variant of Sweet syndrome. The nature of the histiocytoid infiltrate has generated considerable controversy in the literature. Objective The main goal of this study was to conduct a comprehensive overview of the immunohistochemical phenotype of the infiltrate in histiocytoid Sweet syndrome. We also analyze whether this variant of Sweet syndrome is more frequently associated with hematologic malignancies than classic Sweet syndrome. Design This is a retrospective case series study of the clinicopathologic, immunohistochemical, and molecular features of 33 patients with a clinicopathologic diagnosis of histiocytoid Sweet syndrome was conducted in the dermatology departments of 5 university hospitals and a private laboratory of dermatopathology. Main Outcome and Measures The clinical, histopathological, immunohistochemical, and follow-up features of 33 patients with histiocytoid Sweet syndrome were analyzed. In some cases, cytogenetic studies of the dermal infiltrate were also performed. We compare our findings with those of the literature. Results The dermal infiltrate from the 33 study patients (20 female; median age, 49 years; age range, 5-93 years; and 13 male; median age, 42 years; age range, 4-76 years) was mainly composed of myeloperoxidase-positive immature myelomonocytic cells with histiocytoid morphology. No cytogenetic anomalies were found in the infiltrate except in 1 case in which neoplastic cells of chronic myelogenous leukemia were intermingled with the cells of histiocytoid Sweet syndrome. Authentic histiocytes were also found in most cases, with a mature immunoprofile, but they appeared to be a minor component of the infiltrate. Histiocytoid Sweet syndrome was not more frequently related with hematologic malignancies than classic neutrophilic Sweet syndrome. Conclusions and Relevance The dermal infiltrate of cutaneous lesions of histiocytoid Sweet syndrome is composed mostly of immature cells of myeloid lineage. This infiltrate should not be interpreted as leukemia cutis.

SummaryBackground Human parvovirus B19 (B19V) has been associated with a number of dermatological and systemic conditions, including myocarditis and autoimmune syndromes. Objectives To determine the frequency of B19V DNA detection in a large dermatopathology practice, and to characterize the histopathological patterns involved. Methods We selected for polymerase chain reaction (PCR) detection of B19V a total of 1815 skin biopsies pertaining to entities allegedly related to B19V, as well as cases suspected clinically of representing paraviral exanthemas. Immunohistochemical detection of B19V viral protein 2 (VP2) was performed in 92 PCR-positive cases. Results B19V DNA was found by PCR in 402 out of 1825 biopsy specimens (22%). VP2 protein was identified by immunohistochemistry in only three instances of papular purpuric ‘gloves-and-socks’ syndrome. Conclusions As the virus has the capacity to persist in different tissues (including the skin) for long periods, it could represent merely an innocent bystander, so no pathogenetic significance can be inferred from the PCR positivity for B19V in the vast majority of dermatological conditions studied.

Follicular mucinosis coexisting with lymphoproliferative disorders has been thoroughly debated. However, it has been rarely reported in association with inflammatory disorders.Thirteen cases have been retrieved, and those with cutaneous lymphoma or alopecia mucinosa were excluded.Follicular mucinosis was found in the setting of squamous cell carcinoma, seborrheic keratosis, simple prurigo, acne vulgaris, dextrometorphan-induced phototoxicity, polymorphous light eruption (2 cases), insect bite (2 cases), tick bite, discoid lupus erythematosus, drug-related vasculitis, and demodecidosis. Unexpectedly, our observations revealed a preponderating accumulation of mucin related to photo-exposed areas, sun-associated dermatoses, and histopathologic solar elastosis. The amount of mucin filling the follicles apparently correlated with the intensity of perifollicular inflammatory infiltrate, which was present in all cases. The concurrence of dermal interstitial mucin was found in 7 cases (54%).The concurrence of interstitial dermal mucinosis or the potential role of both ultraviolet radiation and the perifollicular inflammatory infiltrates in its pathogenesis deserves further investigations. Precise recognition and understanding of this distinctive, reactive histological pattern may prevent our patients from unnecessary diagnostic and therapeutic strategies.

BACKGROUND Metastatic dissemination is the most frequent cause of death in patients with sporadic colorectal cancer (sCRC). It is believed that the metastatic process is related at least in part to a specific background of genetic alterations accumulated in cells from primary tumors, and the ability to detect such alterations is critical for the identification of patients with sCRC who are at risk of developing metastases. METHODS The authors used high-resolution, 500-K single nucleotide polymorphism arrays to identify copy number alteration profiles present at diagnosis in primary tumors from patients with metastatic (n = 23) versus nonmetastatic (n = 26) sCRC. RESULTS The results revealed a characteristic pattern of copy number alterations in metastatic sCRC tumors that involved losses of 23 regions at chromosomes 1p, 17p, and 18q, together with gains of 35 regions at chromosomes 7 and 13q. CONCLUSIONS In line with expectations, the copy number profile investigated involved multiple genes that were associated previously with sCRC (ie, SMAD2) and/or the metastatic process (ie, podocalyxin-like [PODXL]), and it also was associated with a poorer outcome. Cancer 2014;120:1948–1959. © 2014 American Cancer Society.

Papular epidermal nevus with "skyline" basal cell layer is a variant of keratinocytic nevus that usually occurs sporadically but may affect different family members. We report on the fourth family with papular epidermal nevus with "skyline" basal cell layer affecting a 3-month-old girl and her father.

Scleromyxedema (SM) is a rare primary cutaneous inflammatory mucinosis characterised by papular mucinosis, monoclonal gammopathy and extracutaneous involvement. Most therapeutic options have failed in SM but high-dose therapy followed by autologous peripheral blood stem cell transplantation (APBSCT) appears to be highly effective, although SM normally relapses. We report the case of a 29-yr-old patient with severe SM who achieved stringent complete response with Bortezomib plus Dexamethasone after an early relapse subsequent to a high-dose melphalan regimen followed APBSCT. It is of particular note that dermatological lesions responded to both therapies before M-component modifications, suggesting that SM is independent of M-component characteristics. However, treatment should be directed towards the underlying plasma cell malignancy with typical anti-myeloma agents.

Resumen Se describe el caso de una mujer de 24 anos de edad con una tumoracion subcutanea localizada en la region pubiana inferior izquierda cuyo estudio histopatologico mostro una mama ectopica. Las lesiones tumorales vulvares son poco frecuentes y la presencia de tejido mamario ectopico a nivel vulvar es extremadamente rara. El motivo de consulta en estos casos suele ser el aumento de tamano fluctuante en relacion con cambios hormonales, generalmente secundarios al embarazo o la lactancia, o con alteraciones tumorales asociadas. El caso que se presenta mostraba un crecimiento progresivo sin aparente causa hormonal o neoplasica subyacente, se trataba por tanto de una mama ectopica con clinica de tumoracion subcutanea.

We describe a 24-year-old woman with a subcutaneous swelling in the left inferior pubic region. Histology revealed ectopic breast tissue. Vulvar tumors are uncommon and the presence of ectopic breast tissue in this region is extremely rare. In these cases, patients usually consult for a mass that varies in size with hormonal changes, typically during pregnancy or breast-feeding, or that has associated neoplastic changes. In our patient, the mass had grown progressively with no identifiable underlying hormonal association or neoplasm. We therefore classified it as ectopic breast tissue presenting as a subcutaneous mass.

Striated muscle hamartoma (SMH) is a rare, congenital or acquired, benign tumor that predominantly affects children. Therapeutic management has classically been surgical intervention. We present a pediatric case of a facial plaque-type SMH with spontaneous regression that highlights the importance of clinical observation for a conservative approach.

Dermatofibromas (DFs) are common benign fibrohistiocytic lesions, mostly affecting young adults. Many types of DF have been described, depending on architectural, cellular, and stromal peculiarities. Recently, a peculiar type of benign cutaneous tumor showing hemosiderotic DF-like stroma and apocrine glands has been described. We report 2 additional cases of DF without hemosiderotic changes showing entrapped apocrine glandular structures. We speculate about the origin of the glandular component and propose the term adenodermatofibroma for this type of lesions.

Follicular mucinosis (FM) is an uncommon reaction pattern in which the accumulation of mucin in the follicular epithelium is the main pathologic finding. FM may be idiopathic (primary follicular mucinosis [PFM]), in association with mycosis fungoides or cutaneous T-cell lymphoma, or in association with other neoplastic and inflammatory conditions. Herein we report a case of PFM with identical T-cell clone rearrangement at anatomically distinct sites, supporting the idea that some authors have proposed, that FM may represent a low-grade lymphoproliferative disease related to mycoses fungoides with favorable prognosis.

Meningiomas are cytogenetically heterogeneous tumors in which chromosome gains and losses frequently occur. Based on the intertumoral cytogenetic heterogeneity of meningiomas, hypothetical models of clonal evolution have been proposed in these tumors which have never been confirmed at the intratumoral cell level. The aim of this study was to establish the intratumoral patterns of clonal evolution associated with chromosomal instability in individual patients as a way to establish tumor progression pathways in meningiomas and their relationship with tumor histopathology and behavior. A total of 125 meningioma patients were analyzed at diagnosis. In all cases, multicolor interphase fluorescence in situ hybridization (iFISH) studies were performed on fresh tumor samples for the detection of quantitative abnormalities for 11 different chromosomes. In addition, overall tumor cell DNA content was measured in parallel by flow cytometry. iFISH studies were also performed in parallel on tissue sections in a subset of 30 patients. FISH studies showed that 56 (45%) of the 125 cases analyzed had a single tumor cell clone, all these cases corresponding to histologically benign grade I tumors. In the remaining cases (55%) more than one tumor cell clone was identified: two in 45 cases (36%), three in 19 (15%), and four or more clones in five cases (4%). Overall, flow cytometric analysis of cell DNA contents showed the presence of DNA aneuploidy in 44 of these cases (35%), 30% corresponding to DNA hyperdiploid and 5% to hypodiploid cases; from the DNA aneuploid cases, 35 (28%) showed two clones and 9 (7%) had three or more clones. A high degree of correlation (r ≥ 0.89; P

Resumen Introduccion Con el uso de la mamografia cada vez se diagnostican mas lesiones no palpables de la mama. Hasta ahora, el metodo de extirpacion era mediante la colocacion de un arpon guiado por mamografia. Describimos una tecnica de utilizacion de la ecografia intraoperatoria para guiar la extirpacion de la lesiones no palpables de la mama, y tambien para mejorar la obtencion de margenes negativos en la cirugia del cancer de mama. Metodos Se utilizo la ecografia intraoperatoria para guiar la extirpacion de las lesiones mamarias no palpables detectadas en la mamografia y que se podian visualizar en la ecografia, y las lesiones palpables con un diagnostico o sospecha de cancer para la obtencion de margenes negativos en la cirugia del cancer de mama. Resultados Un total de 34 pacientes fueron incluidas en el estudio. En todas las pacientes se extirparon las lesiones guiado por ecografia. En 20 pacientes la lesion fue benigna y en 14 pacientes fue diagnosticada de cancer de mama. Se obtuvieron margenes en 13 de las 14 pacientes. La evaluacion de los margenes fue correcta, al comparar la patologia con la ecografia en 13 pacientes (92,8%). Conclusiones La ecografia intraoperatoria de mama es un metodo alternativo a la localizacion con arpon de las lesiones no palpables de la mama, evitando las desventajas de esta tecnica. Asimismo, puede utilizarse para mejorar la obtencion de margenes negativos en la cirugia inicial del cancer de mama.