Primary Cutaneous Anaplastic Large Cell Lymphoma with TRC- γδ Expression: A Case Series of Nine Patients with a Rare Immunophenotypic Variant. Anna Sarah Erem, Andrew L. Feldman, Werner Kempf, Christina Mitteldorf, Melissa Pulitzer, Carlos Torres Cabala, Stefano Pileri, Miguel Angel Piris, Alejandro A. Gru

Summary: Background: Primary cutaneous gamma-delta T-cell lymphoma (PC-GDTCL) is a rare, aggressive form of cutaneous T-cell lymphoma first acknowledged by the World Health Organization in 2008. The prognosis is poor, and differentiation of PC-GDTCL from overlapping entities is crucial, as their behavior and treatment vary. One of the key diagnostic immunophenotypic features of PC-GDTCL is the surface expression of TCR-gamma or delta (γδ) in the neoplastic cells. CD30 lymphoproliferative diseases are comparatively indolent and include primary cutaneous anaplastic large cell lymphoma (PC-ALCL) and lymphomatoid papulosis (LyP). However, they can rarely share immunophenotypic expression of TCR-γδ in addition to CD30. Design: We reviewed 9 cases of PC-ALCL with γδ phenotype identified through evaluation of internal and consultation files. At least two dermatopathologists with cutaneous lymphoma expertise independently verified each case, and clinicopathologic data were recorded. Results: The median patient age was 68 (range 38-95). Most cases presented as single lesions on upper extremities. All cases were ALK-, CD30 (>75% of tumor cells), and TCR-bF1 negative with at least 40% expression of TCR-γδ in the atypical cells. Pan T-cell antigens were expressed variably with CD2 (55% partial-positive and 45% negative), CD3 (67% partial-positive and 33% negative), and CD5 (37% partial-positive and 63% negative). Most cases showed CD4-/CD8- (67%), followed by four cases (33%) with partial expression of CD4 (CD4+/CD8-), while there were no cases with CD4-/CD8+ expression. Histopathologic features included intradermal infiltrates with large, atypical cells, frequent necrosis (44%), and inflammation (44%). Ulceration was present in 55% of cases. Epidermotropism (11%), angiotropism (11%), and angiocentricity (11%) were less common. DUSP22 rearrangement was present in two (2/8) cases. CD56 was negative in all cases where the marker was tested. Evaluation of TP63 rearrangement was not done. Conclusions: In this series, most cases of primary cutaneous anaplastic large cell lymphoma with diffuse expression of TCR-γδ lacked CD4 and CD8 expression, with residual expressing CD4+/CD8- T cell phenotype. Our case series identifies for the first time an unusual immunophenotypic variant of PC-ALCL (an indolent disorder) with the potential to be confused with primary cutaneous gamma-delta T-cell lymphomas, an often aggressive and lethal lymphoma subtype. This study emphasizes the importance of careful histopathological and clinical correlation in the diagnosis of cutaneous lymphoproliferative disorders.