Intralymphatic Cutaneous Anaplastic Large Cell Lymphoma/Lymphomatoid Papulosis Expanding the Spectrum of CD30-positive Lymphoproliferative Disorders

Intravascular large B-cell lymphomas and EBV+ NK/T-cell lymphomas commonly follow an aggressive clinical course. We recently reported an entirely intravascular anaplastic large cell lymphoma (ALCL) in the skin with a surprisingly indolent clinical course; interestingly, this lymphoma involved the lymphatic rather than the blood vasculature. We hypothesized that intravascular skin-limited ALCL is distinct from aggressive systemic intravascular lymphomas in its intralymphatic localization and clinical course. We now describe 18 cases of cutaneous intravascular large cell lymphoproliferations from 4 institutions. All 12 intravascular large T-cell lesions were intralymphatic; the majority (9) were CD30(+) T-cell lymphoproliferative disorders (TLPDs), 5 further classified as intravascular ALK(-) ALCL. One ALK(+) ALCL and 2 benign microscopic intravascular T-cell proliferations were also intralymphatic. A single case of otherwise typical cutaneous follicle center lymphoma contained intralymphatic centroblasts. The clinical and pathologic characteristics of the CD30(+) TLPDs were similar to those of their extravascular counterparts, including extralymphatic dermal involvement in a subset, DUSP22-IRF4 translocations in half of tested ALK(-) ALCLs, and associated mycosis fungoides in 1; most were skin-limited at baseline and remained so at relapse. All 5 cases of intravascular large B-cell lymphoma involved the blood vasculature and behaved in a clinically aggressive manner; the ALK(+) ALCL, although intralymphatic, was systemic and clinically aggressive. We propose that cutaneous ALK(-) ALCL and related CD30(+) ALK(-) TLPDs involving the lymphatics are part of an expanding spectrum of CD30(+) TLPDs. The identification of intralymphatic as distinct from blood vascular localization may provide critical prognostic and therapeutic information.