Histopathologic Analysis of Chronic Cutaneous Graft-Versus-Host Disease.

ABSTRACT: Chronic graft-versus-host disease (cGVHD) is the leading cause of morbidity and nonrelapse mortality after allogeneic hematopoietic cell transplantation. Skin biopsy of cGVHD is recommended when clinical features are not diagnostic, yet the histopathologic features of skin cGVHD are not well described. The objective of this study is to describe the histopathologic features of skin cGVHD in epidermal, sclerotic, and combination cGVHD. Of 49 patients with skin cGVHD, 30 of 49 (61.2%) were male, and mean age was 55 years (SD 11.1). Clinically, 33 of 49 (67.3%) had epidermal cGVHD (E-cGVHD), 1 of 49 (2.1%) had sclerotic cGVHD (S-cGVHD), and 15 of 49 (30.6%) had combination disease. The 49 patients corresponded to 83 unique pathologic specimens with 67 of 83 (80.7%) taken from E-cGVHD, and 16 of 83 (19.3%) from S-cGVHD lesions. Nearly all biopsy specimens from E-cGVHD showed minimal features of active GVHD, including apoptosis in the epidermal basal layer (n = 63, 94.0%), vacuolar change (n = 62, 92.5%), and lymphocyte satellitosis (n = 57, 85.1%). The predominant histologic pattern of E-cGVHD was lichen planus/interface dermatitis (n = 31, 47.0%). S-cGVHD specimens also showed minimal features of active GVHD with apoptosis of the epidermal basal layer (n = 11, 68.8%) and vacuolar change (n = 8, 50.0%). In addition, S-cGVHD showed sclerosis of the papillary and reticular dermis and subcutaneous septae (n = 8, 50.0%; n = 11, 68.8%; n = 5, 31.2%, respectively). The predominant histologic pattern of S-cGVHD was lichen sclerosus/morphea-like pattern (n = 10, 62.5%). Although minimal pathologic features of active GVHD are common, the majority of cGVHD biopsies share features with the inflammatory skin diseases that they clinically resemble. Complete histologic reporting is recommended with implications for disease endotyping and personalized therapy.

Nivolumab-induced localized genital bullous pemphigoid in a 60-year-old male.

A 60-year-old man with metastatic renal cell carcinoma presented with a 6-month history of a pruritic, exquisitely painful genital eruption appearing 3 months after initiation of nivolumab. Examination demonstrated a poorly defined, lichenified scrotal plaque studded with erosions, yellow crust, and tense vesicles. There was no other lesion on the body or mucosae. Histopathology revealed a subepidermal blister with a mixed lymphocytic, neutrophilic, and eosinophilic infiltrate. Direct immunofluorescence of perilesional skin demonstrated subclinical blister and linear/fibrillary patchy IgG and IgA along the dermoepidermal junction. Bullous pemphigoid (BP) serologies revealed normal IgG BP230 antibodies and minimally elevated IgG BP180 antibodies. Indirect immunofluorescence revealed positive IgG at the basement membrane ("epidermal pattern") in human split skin and monkey esophagus substrates; no IgA antibodies were detected. The patient was diagnosed with nivolumab-induced localized genital BP (LGBP). BP is a reported adverse effect of immune checkpoint inhibitors including nivolumab; however, cases are typically generalized. LGBP is a rare BP variant typically presenting in children and females; there are few reports of LGBP in adult males. We report a novel case of nivolumab-induced LGBP with unique histopathologic and clinical challenges. LGBP should be considered in patients on immune checkpoint inhibitor therapy with bullous genital eruptions.