Cutaneous Manifestations of Castleman Disease: Histopathological Characteristics and Review of Literature

Abstract

Castleman disease (CD) is a poorly understood lymphoproliferative disorder characterized by enlarged lymph nodes. The spectrum of differential diagnoses is wide, and it is hard to differentiate from other diseases. Cutaneous involvement of CD is rare, and studies that describe cutaneous dermatopathology of CD are scarce. The aim of this study was to collect case reports of CD with cutaneous manifestations and identify potential relevant histopathological features. We found that cases of CD with cutaneous manifestations often exhibited dermal lymphoid follicles with follicle center infiltration of lymphocytes and plasma cells. These dermal follicles also had regressive or atrophic germinal centers and were penetrated by hyalinized vessels. Patients with CD also consistently exhibited perivascular and deep dermal inflammatory infiltrate, primarily composed of lymphocytes and plasma cells. We intend to raise awareness of this rare entity and provide more histopathological information regarding its dermatological manifestations.

Cutaneous reactive B‐cell lymphoid proliferations

“…There have been only several reported cases of skin involvement, often in the context of multicentric disease 127 . Cutaneous Castleman tends to present with multiple brown nodules or violaceous papules and plaques, with cases frequently encountered in patients of Asian descent 128 . Lesions histopathologically show dermal lymphoid follicles with CD20 and BCL‐2 expression 129 .…”

“…(C, H&E Â200) A well-formed germinal center is present. (D, H&E Â400) The atrophic mucosa shows numerous plasma cells in the infiltrate of Asian descent 128. Lesions histopathologically show dermal lymphoid follicles with CD20 and BCL-2 expression 129.…”

“…Histopathologically, lesions show hyperplastic cutaneous lymphoid follicles with polyclonal infiltrates, admixed plasma cells, and interfollicular sclerotic collagen. Vascular hyperplasia, endothelial enlargement, and peri-vascular hyalinized sclerosis are often seen among atrophic germinal centers with an expanded "onion-skinning" mantle zone 128,[131][132][133][134]. A "lollipop sign," consisting of radially expanded mantle zone lymphocytes and a central sclerotic blood vessel, can be an important histopathologic clue.…”

Chronic urticaria as a manifestation of multicentric Castleman disease treated with rituximab

“…6 Erythematous to brown papules, plaques and/or nodules with histopathology of dermal lymphoid follicles with infiltration of lymphocytes and plasma cells are considered as extra-nodal activity of MCD. 6 CU was related to MCD in a 36-year-old Japanese woman who had resolution of her systemic symptoms after anti-IL6 therapy with tocilizumab, but CU improved only after switching to anti-IL1 therapy with canakinumab. 9 In our patient, CU did not show histology features of MCD, and hence it does not represent extra-nodal activity of MCD.…”

“…3 CU has been related with autoinflammatory disorders such as Schnitzler syndrome and Gleich syndrome, 4,5 but the association with MCD only has been reported in other patient. 6 We report a case of CU that unravelled the presence of MCD after laboratory investigations.…”