Mantle cell lymphoma successfully treated in a patient with multiple endocrine neoplasia type 2: a rare combination of two malignancies

Abstract

Sir, This case describes a 56-year-old Caucasian man with a newly diagnosed mantle cell lymphoma (MCL) and multiple endocrine neoplasia type 2 (MEN-2) diagnosed at the age of 20 years. His MEN-2 presented as a medullary thyroid carcinoma. The patient was previously treated with a thyroidectomy and repeated thorax and abdominal surgeries due to metastases, but he remained relapse-free for the last 10 years preceding lymphoma diagnosis. In 2005, he developed a generalized peripheral lymphadenopathy and was referred to hematologist for the lymphoma workup. At admission, the patient reported fatigue, weight loss, and night sweats. Laboratory investigations revealed the whole blood hemoglobin concentration (Hb) 143 g/l, white blood cell count (WBC) 9.25 9 10/l, platelet count (PLT) 364 9 10/l, and elevated serum concentration of lactate dehydrogenase (LDH). Histological and immunohistochemical examination of the cervical lymph node, bone marrow slides, and trephine biopsy sections has showed a MCL with a bone marrow involvement (stage IV B). Computed tomography (CT) imaging revealed abdominal lymphadenopathy, a few calcifications and multiple rounded nodules in the liver, and the normal spleen. A biopsy of the liver disclosed metastatic adenocarcinoma immunohistochemically positive for thyroid transcription factor-1 (TTF-1 marker). Because of the concomitant MEN-2, the patient has not been enrolled into ongoing Nordic Lymphoma Group (NLG) mantle cell lymphoma phase 2 protocol (NLG MCL-2) consisting of induction with maxi-CHOP-21 9 3 alternating with high-dose(HD)-cytarabine 9 2 with a consequent stem cell mobilization, in vivo stem cell purging, and autologous stem cells transplantation (autoSCT) [1]. Nevertheless, he received induction treatment with rituximab(R)-CHOP at 21-day intervals. The patient tolerated immunochemotherapy well and obtained an excellent clinical response with almost total regression of lymphadenopathy, confirmed by CT after 3 courses of R-CHOP-21. After 2 further R-CHOP courses, the patient has been qualified to auto-SCT. Stem cell mobilization with a HD-cyclophosphamide (2 g/m) and G-CSF allowed the collection of total 9.1 9 10 CD34? cells/kg body weight. Then the patient received myeloablative conditioning with BEAM (BCNU 300 mg/m, etoposide 200 mg/m, cytarabine 400 mg/m, melphalan 140 mg/m) and underwent auto-SCT. The post-transplantation period was complicated by grade 3 mucositis and FOU (fever of unknown origin) but otherwise uneventful. Several months after auto-SCT, the patient was able to come back to his work in a printing house. More than 5 years after allo-SCT, the patient still remains fully recovered and relapse-free from both MCL and MEN-2. Mantle cell lymphoma is a CD20-positive lymphoma and consist 5% of all non-Hodgkin lymphomas [2]. It is considered incurable with standard therapies (e.g., COP or CHOP) with a median survival time of approximately 3 years [1]. Multiple endocrine neoplasia type 2, occurring in 1:200,000 live births, is an autosomal dominant neuroendocrine neoplasia predisposition syndrome characterized by variable penetrance of medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism M. Machaczka (&) Division of Hematology, Department of Medicine at Huddinge, Karolinska Institute, and Hematology Center Karolinska, M54, Karolinska University Hospital Huddinge, Stockholm, Sweden e-mail: maciej.machaczka@ki.se