Anaplastic Lymphoma Kinase (ALK)-Positive Diffuse Large B-Cell Lymphoma Presenting with CNS Involvement: A Case Report

Anaplastic lymphoma kinase (ALK)- positive large B-cell lymphoma is a rare form of large B-cell lymphoma originally described in 1997¹ . Since its initial description, approximately fifty cases have been reported in the literature, none of which describe extranodal involvement of the CNS as we will present below.

The patient is a 30 year old previously healthy male who presented with visual changes described as decreased acuity and headaches. Papilledema was present on exam, but exam was otherwise negative. Imaging showed an enhancing mass posterior to the Torcula Herophili. With the working diagnosis of meningioma, the lesion was embolized and then debulked. Final pathology, however, revealed an ALK-positive large B-cell lymphoma with cytoplasmic granular ALK staining. Immunohistochemistry was positive for CD 138, CD 45, CD 38, CD 4, MUM1, epithelial membrane antigen (EMA) and monoclonal IgA lambda, and negative for CD 20, CD30, CD 3, and CD 8. FISH revealed ALK rearrangement (likely with clathrin, but pending at time of abstract) and c-MYC amplification, but not translocation. Serum immunoglobulins were normal. PET/CT showed skeletal metastasis but no additional visceral disease.

ALK-positive large cell lymphomas described previously show immunoblastic/plasmablastic-like phenotypes (CD138+, CD 45+, CD 20-, and cytoplasmic IgA expression), but are CD30-negative and have uniform EMA expression and ALK translocations, as did our patient. The majority of ALK-positive DLBCL exhibit an ALK translocation with the long arm of the clathrin gene to form t(2;17)(p23;q23)² .

ALK-positive large cell tumors typically present nodally, but cases have been reported extranodally in the nasopharynx, tongue, bone, soft tissue, and stomach. There is a 3:1 male predominance and a poor overall prognosis with a median survival of 12.2 months, with isolated cases having longer survival. Most patients were treated with CHOP-based regimens with or without radiation therapy² ,³ . The need for more intense or biologically directed therapy in these cases, including early intensification with or without autologous stem cell rescue is recognized. Gambacorti-Passerini and Poglinani recently described lymphoma sensitivity with crizotinib, an anaplastic lymphoma tyrosine kinase inhibitor, in relapsed anaplastic large cell lymphoma after standard treatment with promising results. Investigation into the use of crizotinib in ALK-positive large cell lymphomas as salvage therapy is potentially warranted⁴ .

This case presents an interesting treatment dilemma given the ALK mutation, c-myc amplification, and CNS disease. Crizotinib is likely not a salvage option for this patient given unclear CNS availability and the possibility of this tumor being motivated by c-myc as well as ALK.

No relevant conflicts of interest to declare.