Primary Cutaneous Anaplastic Large Cell Lymphoma with Locoregional Lymph Node Involvement: Challenges in Diagnosis and Clinical Management.

Primary cutaneous anaplastic large cell lymphoma (PC-ALCL) belongs to the group of primary cutaneous CD30-positive lymphoproliferative disorders. Its diagnosis requires a multidisciplinary approach, integrating clinical, histopathological, and immunohistochemical findings. Although extracutaneous spread is uncommon in PC-ALCL, locoregional lymph node involvement may occur and can pose significant diagnostic challenges, particularly in distinguishing PC-ALCL from systemic ALCL with secondary skin involvement. PC-ALCL has predilection for the head and neck area, whereas systemic ALCL tend to show more disseminated disease. ALK1 might help in the differential between ALK-positive systemic ALCL and ALK-negative systemic ALCL, but other molecular studies such as DUSP22 and TP63 rearrangement do not aid in the differential diagnosis between PC-ALCL and ALK-negative systemic ALCL. Here, we add 2 new cases of PC-ALCL with nodal disease to the 8 cases previously reported, including one during pregnancy. Both cases presented with a solitary lesion and ipsilateral axillary lymph node involvement. Histological and immunophenotypic features were consistent across skin and lymph node biopsies and supported the diagnosis of primary cutaneous origin and were managed with brentuximab vedotin-based chemotherapy, with favorable clinical responses. We emphasize the importance of thorough clinical staging and histopathological correlation to establish the correct diagnosis and the optimal treatment for cases like ours.