LAUSR

A 28-year-old man presented with a history of persistent left groin swelling for 2 years, which has shown slow growth in recent 2 months. He denied any B symptoms including fever, night sweats, and weight loss. His complete blood count (CBC) was normal: white blood cell 7 200/uL, hemoglobin 14.7 g/dL, platelet 206 000/uL. His serum lactate dehydrogenase level (580 IU/L) was within the normal range (313-618 U/L). Positron emission tomography/computerized tomography (PET/CT) showed hypermetabolic nodal masses in left external iliac and inguinal nodal chains, the largest of which measuring 27 mm in size; no contralateral disease or disease above diaphragm. His Eastern Cooperative Oncology Group (ECOG) performance status was 1. Excisional biopsy of a groin mass revealed, at lower magnification, a lymph node with extensive necrosis (Image 1A, right lower corner). Focal viable areas showed diffuse neoplastic lymphoid cells with a “starry sky” appearance due to interspersed tingible body macrophages (Image 1A). At higher magnification, the neoplastic lymphoid cells were large in size, with pleomorphic nuclei, vesicular chromatin, distinct nucleoli, and moderately abundant cytoplasm (Image 1B). Some of them exhibited kidney-shaped nuclei (so-called hallmark cells; Image 1B, arrows). Numerous mitoses were noted. The neoplastic lymphoid cells were strongly and uniformly positive for CD30 (Image 1C), ALK1 (Image 1E), TIA1, CD43, CD45, MYC (80% of lymphoma cells were positive for MYC; Image 1F), and were negative for CD2, CD3 (Image 1D), CD4, CD7, CD8, CD56, CD15, CD20, and PAX5. The diagnosis of ALK+ anaplastic large cell lymphoma (ALCL) was established. Proliferation index by Ki67 was >95% in lymphoma cells. Fluorescence in situ hybridization (FISH) analysis demonstrated concurrent ALK (Image 1G) and MYC rearrangements (Image 1H). The nuclear and cytoplasmic staining pattern of ALK1 (Image 1E) suggested that the ALK rearrangement partner was NPM1. Additional FISH analysis showed negative results for rearrangements of IGH/ MYC (Image 1I) and immunoglobulin kappa (IGK, Image 1J) or lambda light chain (IGL, Image IK), suggesting that the MYC rearrangement partner was a non-IG gene. His bone marrow biopsy was negative for lymphoma. After being diagnosed with stage IIA ALCL, he was started on cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. After three cycles of CHOP, restaging PET/CT showed the lymph nodes had significantly decreased size, with residual fluorodeoxyglucose (FDG) avidity. After six cycles of CHOP, PET/CT showed no evidence of any FDG avid disease. He remained in complete remission and had no evidence of lymphoma at his last follow-up visit (58 months after initial diagnosis). Note, T-cell lymphomas often have increased MYC copy number, but very rarely carry MYC rearrangement. To date, only three cases of T cell lymphoma harboring MYC-rearrangement have been reported in the literature and all of them were children with ALK+ ALCL. All three pediatric patients had “double hit” ALCL (concurrent ALK and MYC rearrangements) and showed aggressive clinical courses: presentation with advanced stage, relapse and spread during chemotherapy, requiring intensive treatments such as multiple lines of chemotherapy and stem cell transplant. Two of them died in 6 months after diagnosis, including one who underwent stem cell transplant. Our patient is the first reported adult with “double hit” ALCL. In contrast to the reported pediatric patients with “double hit” ALCL, our patient had an indolent clinical course (> 2 years of slowly growing masses and stage IIA disease at diagnosis), complete response to CHOP chemotherapy, and durable remission (> 58 months), suggesting that the behavior of “double hit” ALCL may be different between adult vs pediatric patients. It would be important to consider this age-related difference when treating ALCL patients to avoid unnecessary aggressive treatment. Received: 12 July 2020 Revised: 15 August 2020 Accepted: 20 August 2020