Azathioprine hypersensitivity syndrome: report of two cases with cutaneous manifestations.

Azathioprine is an immunosuppressant drug used in many dermatological and nondermatological pathologies. Azathioprine hypersensitivity syndrome (AHS) is a rare idiosyncratic reaction that is not related to dose or thiopurine methyltransferase activity. Up to half of cases of AHS can present with variable cutaneous manifestations besides fever, malaise and other systemic symptoms. It is important to be aware of AHS, as continuance or reintroduction of the drug can led to multiorgan failure and cardiovascular collapse.

SARS-CoV-2 Has Not Been Detected Directly by Electron Microscopy in the Endothelium of Chilblain Lesions: reply from authors.

We fully agree that the interpretation of electron microscopy findings can be challenging, even for experts. Differences between viral pathogens and normal subcellular organelles may be subtle, and some cellular components can masquerade as viruses. The size and shape of the particle shown in our paper fit with other descriptions of SARS-CoV-2, but there may be a bias in interpretation.

SARS-CoV-2 endothelial infection causes COVID-19 chilblains: histopathological, immunohistochemical and ultrastructural study of seven paediatric cases.

BACKGROUND: Chilblains ('COVID toes') are being seen with increasing frequency in children and young adults during the COVID-19 pandemic. Detailed histopathological descriptions of COVID-19 chilblains have not been reported, and causality of SARS-CoV-2 has not yet been established. OBJECTIVES: To describe the histopathological features of COVID-19 chilblains and to explore the presence of SARS-CoV-2 in the tissue. METHODS: We examined skin biopsies from seven paediatric patients presenting with chilblains during the COVID-19 pandemic. Immunohistochemistry for SARS-CoV-2 was performed in all cases and electron microscopy in one. RESULTS: Histopathology showed variable degrees of lymphocytic vasculitis ranging from endothelial swelling and endotheliitis to fibrinoid necrosis and thrombosis. Purpura, superficial and deep perivascular lymphocytic inflammation with perieccrine accentuation, oedema, and mild vacuolar interface damage were also seen. SARS-CoV-2 immunohistochemistry was positive in endothelial cells and epithelial cells of eccrine glands. Coronavirus particles were found in the cytoplasm of endothelial cells on electron microscopy. CONCLUSIONS: Although the clinical and histopathological features were similar to other forms of chilblains, the presence of viral particles in the endothelium and the histological evidence of vascular damage support a causal relation of the lesions with SARS-CoV-2. Endothelial damage induced by the virus could be the key mechanism in the pathogenesis of COVID-19 chilblains and perhaps also in a group of patients severely affected by COVID-19 presenting with features of microangiopathic damage. What is already known about this topic? Despite the high number of cases of chilblains seen during the COVID-19 pandemic, a definite causative role for SARS-CoV-2 has not yet been proven. Different pathogenetic hypotheses have been proposed, including coagulation anomalies, interferon release and external factors. What does this study add? The demonstration of SARS-CoV-2 in endothelial cells of skin biopsies by immunohistochemistry and electron microscopy confirms that these lesions are part of the spectrum of COVID-19. Virus-induced vascular damage and secondary ischaemia could explain the pathophysiology of COVID-19 chilblains. Our findings support the hypothesis that widespread endothelial infection by SARS-CoV-2 could have a pathogenetic role in the severe forms of COVID-19. Linked Comment: Wetter. Br J Dermatol 2020; 183:611.

Detection of human parvovirus B19 DNA in 22% of 1815 cutaneous biopsies of a wide variety of dermatological conditions suggests viral persistence after primary infection and casts doubts on its pathogenic significance.

BACKGROUND: 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.

Immunohistochemistry in dermatopathology: a review of the most commonly used antibodies (part II).

Dermatopathology includes a long list of disorders, some of which have very similar histopathology. Immunohistochemistry is an important auxiliary tool for diagnosis and differential diagnosis, and for predicting the outcome of many skin tumors. It is also the main technique for determining the origin of a tissue or the differentiation of neoplastic cells. In many cases, immunohistochemistry provides a more accurate diagnosis of the different processes that infiltrate the skin. This review examines the role of immunohistochemistry in studying the differentiation and biological behavior of the majority of tumors that can involve the skin. We review immunoperoxidase techniques, discuss the utility of the most commonly used antibodies, and highlight a number of diagnostic problems in which immunohistochemistry may be very useful. In each case, the goal is to reach a specific and definitive diagnosis. In the second part of our review, we examine the most useful and specific antibodies in the study of skin infections and of epithelial, muscular, lymphatic and hematologic, neural, neuroendocrine, and melanocytic neoplasms that affect the skin. Finally, we include a brief review of the immunohistochemical profile of skin metastases of malignant visceral tumors.

Immunohistochemistry in dermatopathology: a review of the most commonly used antibodies (part I).

Dermatopathology includes a long list of disorders, some of which have very similar histopathology. Immunohistochemistry is an important auxiliary tool for diagnosis and differential diagnosis, and for predicting the outcome of many skin tumors. It is also the main technique for determining the origin of a tissue or the differentiation of neoplastic cells. In many cases, immunohistochemistry provides a more accurate diagnosis of the different processes that infiltrate the skin. This review examines the role of immunohistochemistry in studying the differentiation and biological behavior of the majority of tumors that can involve the skin. We review the immunoperoxidase techniques, discuss the utility of the most commonly used antibodies, and highlight a number of diagnostic problems in which immunohistochemistry may be very useful. In each case, the goal is to reach a specific and definitive diagnosis. In the first part of this review, we examine the antibodies that determine the different cell-differentiation profiles of skin tumors.

Granulomas in Dermatopathology: Principal Diagnoses - Part 1. / Granulomas en dermatopatología: principales entidades. Parte I.

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

Granulomas in Dermatopathology: Principal Diagnoses - Part 2. / Granulomas en dermatopatología: principales entidades. Parte II.

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

Clinical and Histopathologic Characteristics of the Main Causes of Vascular Occusion - Part II: Coagulation Disorders, Emboli, and Other. / Dermatopatología de la oclusión intraluminal vascular: parteII (coagulopatías, émbolos y miscelánea).

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 partI of this review. In this second part, we look at additional causes of vascular occlusion.

Clinical and Histopathologic Characteristics of the Main Causes of Vascular Occlusion - Part I: Thrombi. / Dermatopatología de la oclusión intraluminal vascular: parte I (trombos).

Vascular occlusion has multiple, diverse clinical manifestations, some of which can have grave consequences for patients. The causes of vascular occlusion are also highly variable, ranging from thrombi triggered by the uncontrolled activation of coagulation mechanisms, on the one hand, to endothelial dysfunction or occlusion by material extrinsic to the coagulation system on the other. In a 2-part review, we look at the main causes of vascular occlusion and the key clinical and histopathologic findings. In this first part, we focus on vascular occlusion involving thrombi.

A unique dysembryonic neoplasm of the adrenal gland composed of nephrogenic rests in a child.

A primary neoplasm of the right adrenal gland in a 4-year-old boy was discovered after the patient developed bowel obstruction following an appendectomy. Until the histologic examination, the tumor was thought to be a neuroblastoma. However, the intra-adrenal tumor was composed of blastematous nodules, primitive tubules, and glomeruloid structures whose overall composition resembled a Wilms' tumor. Other than a single focus of mucinous glands, the tumor lacked the range of somatic tissue types of a teratoma. Approximately 50 cases of putative extrarenal Wilms' tumor have been reported. The retroperitoneum is one of the more common primary sites, yet our case is the first documented example of a neoplasm with features of a Wilms' tumor arising in the adrenal. Based on the embryologic and anatomic relationship between the adrenal gland and kidney, it is somewhat surprising that other instances of similar appearing tumors have not been described before the present case. Our patient was managed on a Wilms' tumor protocol and remains tumor free 15 months after surgery.

Intimal angiosarcoma of the aorta with tumour embolisation causing mesenteric ischaemia. Report of a case diagnosed using CD31 immunohistochemistry in an intestinal resection specimen.

Primary intimal angiosarcomas of the aorta (i.e. mostly intraluminal sarcomas with evidence of endothelial differentiation) are extraordinarily rare. We report a case in which the diagnosis was accurately made using immunohistochemistry in an intestinal resection specimen and confirmed during autopsy. The patient was a 64-year-old woman with mesenteric ischaemia and a "thrombus" in the abdominal aorta. Two segments of the ileum and the right colon were surgically removed. Histological examination showed multiple tumour emboli in small arteries of the submucosa, serosa and mesentery. The highly atypical cells comprising these emboli were positive immunohistochemically with antibodies to Ulex Europaeus, von Willebrand factor and CD31 and negative for CD34. During post-mortem examination, the intraaortic mass was located around the orifices of the coeliac and the superior mesenteric arteries, and gross tumour thrombi were found in the left renal and splenic arteries. This case emphasises the need for a wide panel of immunohistochemical antibodies when tumour emboli of unknown origin are under study.

Guidelines for processing and reporting of prostatic needle biopsies.

The reported detection rate of prostate cancer, lesions suspicious for cancer, and prostatic intraepithelial neoplasia (PIN) in needle biopsies is highly variable. In part, technical factors, including the quality of the biopsies, the tissue processing, and histopathological reporting, may account for these differences. It has been thought that standardisation of tissue processing might reduce the observed variations in detection rate. Consensus among the members of the pathology committee of the European Randomised study of Screening for Prostate Cancer (ERSPC) concerning the optimal methodology of tissue embedding resulting in guidelines for prostatic needle biopsy processing was reached. The adoption of an unequivocal and uniform way of reporting lesions encountered in prostatic needle biopsies is considered helpful for decision taking by the clinician. The definition of parameters for quality control of prostatic needle biopsy diagnostics will further facilitate clinical epidemiological multicentre studies of prostate cancer.

Sebaceous gland hyperplasia of the vulva: a case report.

A unique case of sebaceous gland hyperplasia presenting as polypoid lesions on the vulva of a 32-year-old white woman is reported. Sebaceous hyperplasia is a benign condition most frequently seen on the forehead of elderly patients. The reported case presented with three soft, nontender polypoid lesions located on mons veneris and right labium majus. Histological examination showed hyperplastic sebaceous lobules not associated with hair follicles. The extremely rare site of the lesion, the clinical and histopathological differential diagnosis, and a therapeutical approach are discussed.