Cutaneous lymphomatoid granulomatosis - Correlation of clinical and biologic features

Lymphomatoid granulomatosis (LYG) is a rare angiocentric and angiodestructi ve Epstein-Barr virus-associated B-cell lymphoproliferative disorder (EBV-B LPD), varying widely from an indolent process to an aggressive large cell l ymphoma. The skin is the extrapulmonary organ most commonly involved in LYG . We studied 32 skin lesions from 20 patients with known pulmonary LYG, usi ng immunohistochemistry, in situ hybridization for EBV, and polymerase chai n reaction for the presence of antigen receptor gene rearrangements (IgH an d TCR) to better define both the clinicopathologic spectrum and pathogenesi s of the cutaneous lesions. We describe two distinct patterns of cutaneous involvement. Multiple erythematous dermal papules and/or subcutaneous nodul es, with or without ulceration, were present in 17 patients (85%). These le sions demonstrate a marked angiocentric lymphohistiocytic infiltrate, compo sed predominantly of CD4-positive T-cells, with a high propensity for invol ving the subcutaneous tissues, and exhibiting angiodestruction, necrosis, a nd cytologic atypia. EBV-positive B-cells were detected in the nodules from five patients', clonal immunoglobulin heavy chain gene (IgH) rearrangement s were detected by polymerase chain reaction in two patients. Multiple indu rated, erythematous to white plaques were present in three patients (15%). The plaque lesions were negative for EBV and clonal IgH gene rearrangements in all cases studied. The clinical course of overall disease was variable, ranging from spontaneous regression without treatment (1 of 13; 7%), resol ution with chemo/immunomodulatory therapy (8 of 13, 62%), and progression ( 4 of 13; 31%). The clinical and histopathologic features of cutaneous LYG a re extremely diverse. However, the majority (85%) of the cutaneous lesions mirrors to some extent LYG in the lung, although EBV+ cells are less freque ntly identified. This subset of cases shows the histopathologic triad of an giodestruction with associated necrosis, panniculitis, and in some cases at ypical lymphoid cells. The commonality of the histologic features in this g roup suggests a common pathophysiologic basis, possibly mediated by cytokin es and chemokines induced by EBV. A small percentage of the lesions (15%) p resented as indurated and atrophic plaques, and EBV was not identified in t he small number of cases studied. The relationship of the plaque-like lesio ns to LYG remains uncertain. Whereas some cases of LYG regress spontaneousl y, most require therapy.