title: ALK-positive diffuse large B-cell lymphoma: two more cases and a brief literature review.
abstract: Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL) is a rare, recently defined tumor distinct in many aspects from ALK-positive anaplastic large cell lymphoma (ALCL). We present two additional cases of ALK+DLBCL recently diagnosed in our department and a review of literature. A 48-year old man presented with a large upper neck mass growing slowly over 18 months. Histologically the tumor was diagnosed as an ALK-positive diffuse large B-cell lymphoma. with plasmablastic features. Large, frequently intrasinusoidal tumor cells expressed CD138, EMA, weakly IgA and kappa, but were negative for other B-cell markers, T-cell markers and CD30. The ALK staining was cytoplasmic with the increased intensity in the Golgi area. At the diagnosis the patient manifested with the stage IIIB. Three courses of CHOP resulted in partial and only transient remission. The patient died of massive bleeding from his decomposing tumor 3 months after the diagnosis. A 49-year old man complaining of abdominal pain revealed abdominal lymphadenomegaly and a gastric infiltrate, involving the deep portions of the gastric wall. The tumor showed immunoblastic/anaplastic morphology, with some Reed-Sternberg-like cells positive for ALK. ALK immunostaining was cytoplasmic, weak in a routine immunostain, enhanced with double (proteinase + pressure cooker) antigen retrieval. FISH was consistent with the t(2;5)/nucleophosmin(NPM)-ALK rearrangement. The tumor demonstrated similar "null" B/T phenotype with positivity for IgA, lambda, EMA and LCA. The patient (stage IVB) currently undergoes chemotherapy. ALK-positive DLBCL affects mostly middle-aged men, shows generally poor but stage-dependent prognosis (at least 60% mortality rate), presents typically as a lymph node-based disseminated disease, and very rarely involves the bone marrow. Genetic studies showed that the majority of ALK+DLBCL cases are characterized by the clathrin (CLTC)-ALK fusion and in a few cases the NPM-ALK rearrangement has been found.
authors.affiliation: Department of Pathomorphology, Collegium Medicum, Jagiellonian University, Kraków. mprudzki@cyf-kr.edu.pl
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Rudzki
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Rucińska
authors.forename: Wojciech
authors.initials: W
authors.lastname: Jurczak
authors.forename: Aleksander B
authors.initials: AB
authors.lastname: Skotnicki
authors.forename: Magdalena
authors.initials: M
authors.lastname: Maramorosz-Kurianowicz
authors.forename: Andrzej
authors.initials: A
authors.lastname: Mruk
authors.forename: Krystyna
authors.initials: K
authors.lastname: Piróg
authors.forename: Graźyna
authors.initials: G
authors.lastname: Utych
authors.forename: Piotr
authors.initials: P
authors.lastname: Bodzioch
authors.forename: Maria
authors.initials: M
authors.lastname: Srebro-Stariczyk
authors.forename: Iwona
authors.initials: I
authors.lastname: Włodarska
authors.forename: Jerzy
authors.initials: J
authors.lastname: Stachura
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000378:metabolism; D003520:Cyclophosphamide / Q000008:administration & dosage; D004273:DNA, Neoplasm / Q000032:analysis; D004317:Doxorubicin / Q000008:administration & dosage; D017809:Fatal Outcome; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008198:Lymph Nodes / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011241:Prednisone / Q000008:administration & dosage; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D011241:Prednisone