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.

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.

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.

Hypergammaglobulinemic purpura of Waldenström in children.

BACKGROUND: Hypergammaglobulinemic purpura of Waldenström (HGPW), a rare cutaneous eruption characterized by the triad of recurrent episodes of lower extremity petechiae, symptoms of stinging and burning, and lower extremity edema, is poorly described in children. Some children have been reported to follow a benign course, while others are eventually diagnosed with fulminant rheumatologic disease. OBJECTIVES: To determine the distinguishing features of HGPW including the spectrum of disease manifestations and clinical outcomes. METHODS: This is a multicenter, retrospective case series of six children with HGPW combined with a literature review of 45 previously published pediatric cases. RESULTS: Most children were eventually diagnosed with systemic disease (63%) or developed autoantibody accumulation suggestive of evolving disease (71%). The most common diagnoses were Sjogren's syndrome and systemic lupus erythematosus. The mean duration between onset of cutaneous eruption and diagnosis of systemic disease was 5.6 years, underscoring that HPGW patients often present with a rash that precedes the development of systemic symptoms. CONCLUSIONS: Diagnosis of HGPW should prompt initial screening for rheumatologic disease with long-term rheumatology follow-up, as the majority of patients present with evolving manifestations of systemic disease.

Palisaded Neutrophilic Granulomatous Dermatitis Leading to Diagnosis of Hodgkin Lymphoma: Report of Rare Case and Literature Review of Paraneoplastic Granulomatous Dermatitides.

Palisaded neutrophilic granulomatous dermatitis (PNGD) presents as skin-colored to erythematous papules symmetrically distributed on extensor extremities. Histologically, interstitial and/or palisaded granulomatous infiltrates are present with neutrophils and leukocytoclasis. Together with interstitial granulomatous dermatitis (IGD), PNGD is considered a reactive granulomatous dermatitis to a systemic trigger including connective tissue disease, infection, medication reaction, and less commonly malignancy. We present the second case of PNGD leading to diagnosis of Hodgkin lymphoma. A 47-year-old woman presented with a new asymptomatic eruption of erythematous, nonscaly papules and thin plaques with variable annular configuration, symmetrically distributed on extremities. Biopsies revealed mid-dermal focal degeneration of collagen and leukocytoclasis in association with a palisaded mixed inflammatory infiltrate of neutrophils, lymphocytes, and histiocytes, some forming small granulomas. She had associated fevers, night sweats, weight loss, arthralgias and malaise. Imaging revealed retroperitoneal adenopathy. Excisional lymph node biopsy led to diagnosis of Hodgkin lymphoma. Paraneoplastic PNGD is rare with only 9 reported cases. In all cases, PNGD presented concurrently or before presentation of clinical signs/symptoms of underlying neoplasm. We reviewed a total of 37 cases of paraneoplastic PNGD/IGD, summarizing clinical presentation, histology, associated neoplasm, and response of the skin lesions to treatment. The most commonly associated neoplasia is hematologic, with myelodysplastic syndrome (9 of the 37 cases or 24%) being the most frequent. Seven cases of solid tumor malignancies (prostate, esophageal, hypopharyngeal, breast, endometrial, and lung cancers) have been reported. Recognition of paraneoplastic PNGD/IGD may allow dermatopathologists, pathologists, and dermatologists to direct further workup that reveals underlying malignancy.

Treatment of Actinic Keratoses: A Randomized Split-Site Approach Comparison of Sequential 5-Fluorouracil and 5-Aminolevulinic Acid Photodynamic Therapy to 5-Aminolevulinic Acid Photodynamic Monotherapy.

BACKGROUND: Actinic keratoses (AKs) are skin lesions resulting from sun exposure and carry a risk of developing into squamous cell carcinoma. Current therapies for AK eradication include topical 5-fluorouracil (5-FU) and photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA). However, sequential therapy with 5-FU-ALA-PDT may offer improved outcome compared to ALA-PDT alone. OBJECTIVE: The purpose of this study is to compare the long-term efficacy of AK clearance by sequential therapy with 5-FU-ALA-PDT versus ALA-PDT alone. MATERIALS AND METHODS: This is a single center, randomized split-site approach study on equivalent anatomical and clinical sites. Seventeen patients were enrolled with one half of the site randomized to receive sequential 5-FU-ALA-PDT and the other side with ALA-PDT monotherapy. Total AKs were counted at baseline, 6 and 12 months. RESULTS: Median percentage reduction in AK number at 6 months for 5-FU-ALA-PDT versus ALA-PDT was 100% for 5-FU-ALA-PDT (N = 21) and 66.7% for ALA-PDT (N = 21), p = .001. Median percentage reduction in AK number at 12 months for 5-FU-ALA-PDT versus ALA-PDT was 100% for 5-FU-ALA-PDT (N = 22) and 82.6% for ALA-PDT (N = 22), p = .0002. CONCLUSION: Sequential therapy with 5-FU-ALA-PDT is more effective at AK clearance at 6 and 12 months compared to ALA-PDT monotherapy.