Rubella virus-associated necrotizing neutrophilic granuloma in a patient with common variable immunodeficiency.

Patients with inborn errors of immunity (IEI) may develop granulomas in multiple organ systems including the skin. Vaccine strain rubella virus (RuV), part of the live attenuated measles, mumps, and rubella (MMR) vaccine, has been identified within these granulomas. RuV is typically found in macrophages; however, recently neutrophils have been identified as a novel cell type infected. Here, we present a case of RuV-associated cutaneous granuloma with RuV localized to neutrophils. A 46-year-old female with common variable immunodeficiency presented with verrucous papules and crusted plaques from the right knee to the distal shin of 20 years duration, associated with prior physical trauma. Biopsy specimen showed palisaded granulomas surrounding central necrosis with scattered aggregates of neutrophils. Vaccine-derived RuV was detected by molecular sequencing in lesional skin. Fluorescent immunohistochemistry with CD206, myeloperoxidase (MPO), and RV capsid (RVC) antibodies demonstrated that RuV localized to neutrophils but not macrophages. The clinical presentation, cutaneous findings, and likely presence of RVC-positive granulocytes in bone marrow provide potential support to the evolving hypothesis of persistent RuV within neutrophils contributing to chronic granulomatous inflammation in a milieu of immune dysregulation.

Zosteriform cutaneous metastases from urothelial carcinoma: Report of a rare case and literature review.

Zosteriform cutaneous metastases from urothelial carcinoma are rare. Here, we report a 50-year-old male with urothelial carcinoma who presented with multiple tender, erythematous papulonodules in an L1-L3 distribution approximately 6 years after primary tumor diagnosis. He had no history of prior herpes zoster infection. Histopathology showed lobules and small nests of atypical epithelioid cells positive for GATA3, CK20, CK7, and p40 throughout the dermis and within lymphatic vessels highlighted by D2-40, consistent with cutaneous metastases from urothelial carcinoma. No perineural invasion or viral cytopathic change was present. The patient died approximately 8 months after diagnosis of cutaneous metastases. Since its first report in 1986, there have been only six cases of zosteriform cutaneous metastases from urothelial carcinoma. We review the prior literature including hypotheses of the pathogenesis of zosteriform cutaneous metastases, which remain incompletely understood.

Concomitant nivolumab-associated Grover disease and bullous pemphigoid in a patient with metastatic renal cell carcinoma.

Immune checkpoint inhibitor (ICI)-induced bullous pemphigoid (BP) and Grover disease (GD) are uncommon, and concomitant GD and BP is rarer still. We report a third case of concomitant BP and GD associated with nivolumab with emphasis on the clinical, histopathologic and immunofluorescence findings as well as differential diagnoses. A 73-year-old male with metastatic renal cell carcinoma on nivolumab developed erythematous scaly papules on the trunk with biopsy showing suprabasal acantholysis with dyskeratosis, consistent with GD. Subsequently, he developed widespread lesions on arms, legs, trunk, and scrotum with new vesiculobullae and urticarial lesions. Biopsy of a vesicle showed subepidermal blister with numerous eosinophils and neutrophils, and immunofluorescence and serological studies were supportive of BP. He continued to have clinically apparent GD that was confirmed on repeat biopsy. The patient was diagnosed with concomitant GD and BP induced by nivolumab and successfully treated with dupilumab. The relationship between ICI-induced GD and BP is not well understood; it has been suggested that T-cell activation against the BP180 antigen expressed on surface of tumor cells may predispose susceptible individuals to BP. Subsequent ICI-induced GD may create keratinocyte injury needed to expose additional proteins to reactivated and autoreactive T-cells, leading to autoimmunity. An important differential diagnosis is bullous GD, which can be distinguished by negative immunofluorescence and serological studies.

Clinical, pathologic, and molecular analyses of superficial low-grade fibromyxoid sarcoma in two young patients: A rare and deceptive mimic of benignancy.

Low-grade fibromyxoid sarcoma (LGFMS) is a histopathologically deceptive soft tissue neoplasm with bland cytology, which is typically encountered in deep soft tissue of adults. We report two cases of superficial LGFMS in young patients (16 and 21 years old, respectively), which were difficult to diagnose on histopathologic and clinical findings alone. LGFMS commonly mimics benign neoplasms such as cellular neurothekeoma, fibromatosis, neurofibroma, and perineurioma. Malignancies included in the differential diagnosis are soft tissue neoplasms such as dermatofibrosarcoma protuberans and myxofibrosarcoma. A high degree of reported variation in pattern and cellularity among LGFMS further complicates the diagnosis. Careful examination and appropriate immunohistochemistry panels including MUC4 are essential for narrowing the differential diagnosis. Molecular studies for possible FUS translocation can confirm the diagnosis of LGFMS. Sufficient sampling and workup of these lesions are critical, especially in younger patients. Young age and superficial presentation can easily sway dermatopathologists/dermatologists toward an incorrect diagnosis of benignancy.

Updates on the Pathology and Management of Nail Unit Tumors and Dermatoses.

Nail unit pathology is indispensable to reach an accurate diagnosis of nail tumors as well as inflammatory disorders. This review article provides an update from the most recently published studies on the pathology and management of nail unit tumors and inflammatory disorders. Recent findings of nail clipping histopathology are described first, followed by discussing recent data on the diagnosis and surgical management of several types of nail unit tumors, ending with discussing the recent discoveries in selected nail unit inflammatory disorders.