Systemic Mycoses by Novel Onygenalean Fungal Pathogens Emergomyces spp and Blastomyces percursus in Rwanda.

We report 2 cases of infection by fungi unprecedented in Rwanda. One patient with emergomycosis presented with disseminated disease and prominent cutaneous involvement and one patient with African blastomycosis had cutaneous and osseous disease. These cases illustrate the clinicopathologic and molecular traits of novel dimorphic onygenalean species in Rwanda.

Disseminated Mycobacterium avium Complex Infection Following CD3/CD20 Bispecific Antibody Therapy in a Patient With Follicular Lymphoma.

Infections remain a major concern following bispecific antibody therapy but are not well described in pivotal trials. We present the first well-documented case of a classic but rare opportunistic infection, disseminated Mycobacterium avium complex, in a patient receiving bispecific antibody therapy.

The Histopathology of Vacuoles, E1 Enzyme, X-Linked, Autoinflammatory, Somatic Syndrome: Report of 12 Skin Biopsies From 6 Patients.

ABSTRACT: We present the histopathology of 12 skin biopsies from 6 patients with vacuoles, enzyme E1, X-linked, autoinflammatory, somatic syndrome and review the literature. The age of these 6 men ranges from 62 to 83 years (median of 70 years). UBA1 mutation was documented in all 6 patients. Multiple organ systems were involved with constitutional symptoms noted in 4 of 6 patients (67%), cutaneous involvement in 6 of 6 patients (100%), hematologic abnormalities in 6 of 6 patients (100%), pulmonary involvement in 4 of 6 patients (67%), musculoskeletal abnormalities in 3 of 6 patients (50%), vascular thrombosis in 2 of 6 patients (33%), ocular involvement in 2 of 6 patients (33%), and gastrointestinal involvement in 5 of 6 patients (83%). Of the 6 presented patients, neutrophilic dermatosis was seen in 3 biopsies, histiocytoid neutrophilic dermatosis in 1 biopsy, neutrophilic dermatosis with vasculitis in 1 biopsy, neutrophilic and granulomatous dermatitis in 2 biopsies, septal panniculitis consistent with erythema nodosum in 2 biopsies, and nonspecific patterns in 3 biopsies. In summary, neutrophilic dermatosis, small-vessel vasculitis, and panniculitis are frequent histopathologic patterns noted in decreasing frequency in skin biopsies of the patients with vacuoles, enzyme E1, X-linked, autoinflammatory, somatic syndrome. However, the histopathologic findings can be diverse, nonspecific in some instances, and varied among different biopsies obtained from the same patient.

Erythrasma of the Vulva: An Invisible Dermatosis.

Erythrasma is a prevalent superficial bacterial infection typically caused by Corynebacteria species and preferentially affecting intertriginous sites including axillary, interdigital, and inguinal skin folds. However, erythrasma of the vulva is uncommon, with only 2 cases previously reported. Although erythrasma can be diagnosed clinically using Woods lamp examination, it may not always be considered in the differential diagnosis for patients presenting with persistent vulvar pruritus. We report 12 cases of vulvar erythrasma identified by histopathology, with a review of clinical and histologic features. The mean patient age was 60.1 yr and the mean patient BMI was 30.5. Five of 12 patients presented with pruritic rash. The time from symptom onset to diagnosis was 9 mo in 1 case, >18 mo in 4 cases, and unknown in the remaining cases. The characteristic histologic features were compact orthokeratosis and mild perivascular chronic inflammation. In all 12 cases, Periodic Acid-Schiff-diastase (PAS-D) staining highlighted intracorneal filamentous rods which were not readily appreciable on H&E. After the diagnosis of erythrasma, 4 patients were treated with topical lincomycin, of whom 3 had clinical improvement in symptoms. One patient was treated with topical macrolide antibiotic and also reported improvement in symptoms. Consideration of erythrasma on the differential for patients presenting with vulvar rash and pruritus may shorten the time to diagnosis and treatment, minimize patient discomfort, and reduce the scope and cost of diagnostic testing.

Epidermodysplasia verruciformis-associated eccrine neoplasm: a rare entity with distinctive clinical and histopathologic features.

Most tumors are caused by inherited or acquired genetic changes. However, a subset of tumors is driven by viral infection including Kaposi sarcoma, nasopharyngeal carcinoma, and others. Human papillomavirus (HPV) is an especially common cause of epithelial cancers and hyperplasias. Epidermodysplasia verruciformis (EDV) is a rare type of HPV infection with characteristic histopathologic features and a unique spectrum of HPV subtypes. We report here a distinctive form of EDV-associated eccrine neoplasia. Seven tumors from two patients were analyzed and show highly uniform features including multiple clustered clinical lesions, multifocal epidermal origin, eccrine differentiation with close association with the acrosyringium, an anastomosing growth pattern, and a bland monotonous poroid-to-basaloid cytomorphology. Clinical follow-up for one patient has been benign to date. These tumors show strong similarity to two previously reported cases, suggesting that this type of EDV-associated eccrine neoplasia may represent a rare but reproducible form of skin adnexal tumor with distinctive clinicopathologic features.

Generalized pustular psoriasis-like widespread eruption following COVID-19 infection in a patient with spondyloarthropathy on adalimumab.

Generalized pustular psoriasis (GPP) is a form of pustular psoriasis that is distinguished by recurring or persistent outbreaks of non-acral primary sterile pustules. These eruptions can occur with or without systemic inflammation. Various factors, such as medications, stress and viral infection, have been identified as potential triggers for GPP flares. While several cases have detailed GPP-like eruptions in the setting of coronavirus disease 2019 (COVID-19) infection, few have explored the interplay between infection and biologic use in the development of GPP. In this case, we detail the history and management of a 45-year-old male patient with a prior history of spondyloarthropathy managed on a tumour necrosis factor-α inhibitor and recent COVID-19 infection presenting with a new, spreading pustular rash.

A Novel Fusion Partner, SP100, Drives Nuclear Dot Localization of ALK in Epithelioid Fibrous Histiocytoma.

ABSTRACT: Epithelioid fibrous histiocytoma (EFH) is a distinctive benign cutaneous neoplasm composed of uniform epithelioid cells, often with binucleated cells. EFH are characterized by the presence of anaplastic lymphoma kinase ( ALK ) gene rearrangements with a variety of binding partners. These rearrangements result in the overexpression of ALK , which can be detected using immunohistochemistry. Cytoplasmic ALK expression is by far the most common pattern encountered. Here, we describe a case of EFH with a distinctive intranuclear dot-like ALK expression pattern. Subsequent next-generation DNA sequencing revealed a novel SP100::ALK gene fusion. Speckled protein-100 (SP100) is a constituent of nuclear dots, also known as promyelocytic leukemia bodies, which are still poorly understood membraneless subnuclear structures. Thus, this novel ALK fusion partner seems to explain this distinctive pattern of ALK localization. We examined ALK expression patterns in 11 other cases of EFH, but all showed typical cytoplasmic localization. This study expands the morphologic and molecular spectrum of EFH, provides a dramatic illustration of the ability of fusion partners to control protein localization, and implies that tumorigenic ALK signaling may occur at a variety of subcellular locations.

Teaching Infectious Disease Pathology and Taking it To Africa.

With the advent of increasing emerging infectious diseases, rising antibiotic resistance, and the growing number of immunocompromised patients, there is increasing demand for infectious disease (ID) pathology expertise and microbiology testing. Currently, ID pathology training and emerging molecular microbiology techniques (eg, metagenomic next-generation sequencing and whole genome sequencing) are not included in the most American Council of Graduate Medical Education medical microbiology fellowship curricula, and not surprisingly, many institutions lack anatomical pathologists with expertise in ID pathology and advanced molecular diagnostics. In this article, we describe the curriculum and structure of the Franz von Lichtenberg Fellowship in Infectious Disease and Molecular Microbiology at Brigham and Women's Hospital in Boston, MA. We emphasize the value of a training model that strives to integrate anatomical pathology, clinical pathology, and molecular pathology by providing examples in a case-based format and presenting selected metrics of the potential effect of such integrative ID pathology service and briefly describing opportunities and challenges of our global health efforts in Rwanda.

Deep-penetrating-nevus-like melanoma arising in patients with familial adenomatous polyposis syndrome.

Deep penetrating nevi (DPN) are uncommon but distinctive melanocytic neoplasms that show an epithelioid to spindle cell morphology, prominent pigmentation with melanophages, and a plexiform growth pattern. Molecularly, most DPN are thought to be characterized by dual activation of the mitogen-activated protein kinase and the wingless-related integration site (Wnt) pathways, the latter being most commonly driven by activating ß-catenin mutations. DPN-like melanomas are very rare but can be recognized through their overlapping morphologic and architectural features with DPN. Familial adenomatous polyposis (FAP) is a hereditary cancer predisposition syndrome associated with multiple tumor types including colorectal carcinoma and desmoid fibromatosis. Like DPN, FAP is also driven by activation of the Wnt pathway, most commonly through loss of function mutations in APC, which is a major negative regulator of ß-catenin. Here we report two cases of DPN-like melanoma arising in FAP patients. While the small number of cases precludes definitive establishment of an etiologic link between these entities, the shared molecular pathogenesis of DPN-like lesions and FAP suggests that FAP patients may be at increased risk for this rare subtype of melanoma.

Cutaneous Melanocytic Tumor With CRTC1::TRIM11 Translocation : An Emerging Entity Analyzed in a Series of 41 Cases.

Cutaneous melanocytic tumor with CRTC1::TRIM11 fusion (CMTCT) is a recently described dermally based neoplasm with melanocytic differentiation. It can easily be confused with clear cell sarcoma and metastatic melanoma. Our understanding of this lesion, including its potential for aggressive disease, has been limited by the small number of previously reported cases (13) and the limited clinical follow-up data. Here, we report a series of 41 CMTCT confirmed by molecular studies. We find that the lesion shows highly uniform and reproducible morphologic, immunohistochemical, and genetic features across a wide variety of anatomic locations and age groups. Among 22 cases with follow-up, 1 local recurrence and 1 nodal metastasis were identified. Our data support the classification of CMTCT as a unique nosologic entity and emphasize the importance of distinguishing this entity from its histologic mimics, especially clear cell sarcoma and metastatic melanoma, to guide therapy and establish accurate prognostic expectations.

Rigidoporus corticola Colonization and Invasive Fungal Disease in Immunocompromised Patients, United States.

We report 2 cases of Rigidoporus corticola (Oxyporus corticola) infection in humans in the United States. Clinical manifestations consisted of angioinvasive fungal sinusitis in 1 patient and pulmonary intracavitary fungus ball in the other patient. These cases illustrate previously undescribed clinicopathologic manifestations of infection by this filamentous basidiomycete in humans.

Vulvar Melanoma in association with germline MITF p.E318K variant.

Vulvar melanoma is a rare and aggressive cancer with a poor prognosis. The etiology of mucosal melanoma remains largely uncharacterized and no hereditary risk factors are established for this rare disease. While the germline variant MITF p.E318K confers an increased risk for cutaneous melanoma, this variant has not been associated with risk of non-cutaneous melanoma. Herein, we describe the presence of a germline MITF p.E318K pathogenic variant in a 47-year-old woman with vulvar melanoma and a family history of cutaneous melanoma in a first-degree relative. To our knowledge, this is the first reported case of MITF p.E318K in vulvar melanoma. This finding highlights the potential involvement of MITF p.E318K in risk assessment and clinical management of patients with vulvar melanoma. Further study of this observation is needed to inform appropriate identification of patients with non-cutaneous melanoma for MITF germline genomic evaluation and to potentially guide management for early detection of vulvar melanoma.

Proficiency at Tick Identification by Pathologists and Clinicians Is Poor.

OBJECTIVES: Prompt accurate identification of tick species is required for appropriate administration of single dose antimicrobial prophylaxis for Lyme disease in selected patients. To determine the proficiency of clinicians at tick identification in the northeastern United States where Lyme disease has its highest incidence, we undertook a survey. METHODS: We analyzed the results of a voluntary survey testing proficiency in identifying tick species using high-resolution photographs of ticks. RESULTS: Only 35% of ticks were correctly identified. Although 60% of respondents could identify a nonengorged adult blacklegged tick, only 34% could correctly identify a partially engorged blacklegged tick. Participants performed even worse at classifying brown dog, American dog, and Lone Star ticks. CONCLUSIONS: Proficiency of tick identification by pathologists and clinicians is poor.

Identification of Hard Ticks in the United States: A Practical Guide for Clinicians and Pathologists.

ABSTRACT: According to guidelines published by the Infectious Disease Society of America, Lyme disease prophylaxis is possible if a tick can be identified as Ixodes scapularis (nymphal or adult) within 72 hours of tick removal. However, a recent survey of medical practitioners indicates generally poor proficiency in tick identification. In this study, we provide a simple, practical guide to aid medical practitioners in identifying the most commonly encountered human biting ticks of North America.

Scedosporium and Lomentospora Infections Are Infrequent, Difficult to Diagnose by Histology, and Highly Virulent.

OBJECTIVE: To further characterize the histomorphology and clinicopathologic features of colonization and invasive disease by Scedosporium and Lomentospora. METHODS: We conducted a 20-year retrospective study. Patients with at least 1 histopathology specimen and concurrent culture were included. Clinical features, histopathology, microbiology, and outcomes were analyzed. RESULTS: Eighteen patients were identified, and all were immunocompromised. Eight patients had colonization, while 10 had invasive disease (pneumonia [n = 3], skin and soft-tissue infections [n = 3], disseminated disease [n = 4]). Scedosporium apiospermum was identified in 15 patients, Lomentospora prolificans in 2 patients, and Scedosporium ellipsoideum in 1 patient. Fungal elements were identified histologically in 11 patients. Granulomatous, suppurative, and necrotizing inflammation with irregular branching hyphae and characteristic microconidia were observed in 9 cases; conidiogenous cells were identified in 4 cases. Seven patients died of invasive disease despite therapy, and 3 recovered after treatment. No deaths were observed in patients with colonization. CONCLUSIONS: Scedosporium and Lomentospora are rare, virulent opportunistic fungal pathogens. Fungal morphology may overlap with other hyaline molds, but identification of obovoid conidia should allow a diagnosis of non-Aspergillus hyalohyphomycosis and consideration of Scedosporium and Lomentospora. Histopathologic correlation with culture and polymerase chain reaction is critical for diagnosis and treatment.

Occurrence of Helicobacter Pylori in Specimens of Chronic Gastritis and Gastric Adenocarcinoma Patients: A Retrospective Study at University Teaching Hospital, Kigali, Rwanda.

INTRODUCTION: Helicobacter pylori (H. pylori) infection is the major cause of gastroduodenal diseases in populations of different ages. We conducted aretrospective studyusing archived tissue samples to determine the prevalence of H. pylori infection among patients diagnosed with gastritis and gastric adenocarcinoma by histopathology cases in one hospital in Rwanda. MATERIALS AND METHODS: Cases of chronic gastritis and gastric adenocarcinoma histologically diagnosed in a tertiary hospital in Rwanda over the period of 2016-2018 were studied for the presence of H. pylori using immunohistochemistry. Diagnosis of positive cases considered immunoreactivity as well as bacterial morphology, including spiral, rod-shaped, angulated and coccoid forms. RESULTS: Three hundred and seven cases were included in this study; chronic gastritis and gastric adenocarcinoma representing 39% and 61%, respectively. The overall frequency of H. pylori infection was 77.5% (80% among chronic gastritis cases versus 76% among gastric adenocarcinoma cases). Prevalence of H. pylori infection in chronic gastritis and adenocarcinoma did not significantly associate with age and sex. CONCLUSION: The prevalence of H. pylori was high among chronic gastritis and gastric adenocarcinoma cases in Rwanda. Pathologists should investigate the presence of H. pylori in gastric biopsies. Our data shows immunohistochemistry method is feasible and adequate to facilitate detection of H. pylori, which may guide timely treatment.

Clinical Performance of Mycobacterial Immunohistochemistry in Anatomic Pathology Specimens.

OBJECTIVES: Diagnosis of mycobacterial infections poses significant challenges in anatomic pathology. We recently described the use of antimycobacteria immunohistochemistry (IHC) as a sensitive, efficient diagnostic tool and now report the clinical performance of this assay among general, noninfectious disease pathology-trained anatomic pathologists. METHODS: Over a 2-year period, all cases were retrospectively identified in which mycobacterial IHC was performed during routine diagnostic workup. RESULTS: From October 2017 to September 2019, mycobacterial IHC was evaluated for 267 cases, resulting in 58 (22%) positive stains. Compared with culture and molecular results, the sensitivity and specificity of IHC were 52% and 80%, respectively. IHC performed significantly better than acid-fast bacilli (AFB) staining (Ziehl-Neelsen) (P < .0001; sensitivity 21%, specificity 92%) but similarly to modified AFB staining (mAFB; Fite-Faraco) (P = .9; sensitivity 61%, specificity 84%). In cases with discordant IHC and mAFB staining, there were no differences in rates of culture or polymerase chain reaction-confirmed positivity. CONCLUSIONS: Mycobacterial IHC was well adopted with superior clinical performance to AFB and comparable performance to mAFB. These results support the use of IHC as an adjunctive tool in the diagnosis of mycobacterial infections and suggests its potential role as a rapid screening test for molecular testing.