Case
Our patient was a 69-year-old man with mantle cell lymphoma (MCL) diagnosed 5 years prior and managed with active surveillance. He presented with a 20-pound weight loss over 4 weeks, although the patient was not sure of the exact timing. He had associated symptoms, which included anorexia, malaise, drenching night sweats, and subjective fevers. No interventions made his condition better or worse. He had hepatitis C infection treated with sofosbuvir/ledipasvir with a sustained virologic response when checked six months earlier. He did not use tobacco, alcohol, or intravenous drugs. He lived at home alone and had increasing difficulty with completing his activities of daily living due to weakness.
On physical exam, vital signs were temperature of 38.1°C, blood pressure 100/65 mm Hg, respirations of 26 breaths per minute, and heart rate of 110 beats per minute. He was a cachectic, pale, and ill-appearing male lying in bed. He had prominent bi-temporal wasting. There was bilateral anterior cervical lymphadenopathy with multiple lymph nodes measuring 2 cm. He had an unremarkable cardiovascular exam. He had mildly labored breathing, but his lungs were clear to auscultation bilaterally. The abdomen was soft with bowel sounds, and splenomegaly was noted.
Laboratory values were notable for a white blood cell count of 10,090 with 3.4% basophils (elevated). His hemoglobin was 13.2 mg/Dl, hematocrit was 39%, and platelet count was low at 48,000. He had elevated lactate dehydrogenase (16,849), uric acid (10.7 mg/dL), and creatinine (1mg/dL). The patient underwent a bone marrow biopsy with the following results: 50% abnormal lymphoid cells with immunohistochemistry positive for c-myc, bcl2, and cyclin D1 translations. Testing also revealed P53 mutations.
He was diagnosed with blastoid variant MCL and treated with bendamustine and rituximab. Unfortunately, he developed progressive multi-organ failure during his multi-week hospital course and passed away.
Discussion
Blastoid variant mantle cell lymphoma (MCL) is a very uncommon variant of non-Hodgkin lymphoma with an unclear incidence or prevalence. It is a subtype of MCL that arises from the naïve germinal center B cell and comprises 10-15% of MCLs.1 Among 183 patients, 152 patients had blastoid MCL, males comprised 75% of patients, and the median age was 65.4 Blastoid cells are always positive for BCL2 and sometimes express D1, as our patient’s histology did. Ki-67 index is an important prognostic factor more so than cytology, and the media Ki-67% was 70%.5 Currently, no described genetic alterations are unique to and differentiate blastoid MCL from classic MCL.5
Typically, MCLs are lymphoid cell proliferation with irregular nuclei and dispersed chromatin. Histopathology of recurrent MCLs often has these features and no mantle zone growth pattern, pleomorphism, or high mitotic activity.2 Blastoid MCL differs from standard MCL in that cells resemble lymphoblasts typically seen in lymphoma or leukemia with more dispersed chromatin and higher mitotic activity.5 Histopathologic confirmation is needed to establish the diagnosis.
Patients like ours can present with advanced disease, including splenomegaly, bone marrow involvement, and bulky lymphadenopathy. Blastoid MCL may spread extranodal to the gastrointestinal tract and Waldeyer ring.2 Gastrointestinal spread is associated with a more indolent disease course.5 Blastoid MCL has a higher rate of CNS involvement (28%) than classic MCL.5 Up to half of cases have “B” symptoms of fever, weight loss, and night sweats.3 High leukocyte count, mitotic activity, Ki-67 index, and peripheral spread are poor prognostic factors.1
Current treatment strategies recommend intensive chemotherapy, including cytarabine-based therapy, autologous stem cell transplant, and clinical trials. The dosing and frequency of treatments are different than that for classic MCL. Blastoid MCL is often refractory. Ibrutinib, lenalidomide, and temsirolimus can lead to short-term remission.5 In the future, targeted therapies like acalabrutinib, ibrutinib, venetoclax, and CD19 CAR-T therapies may improve outcomes.4
SGIM Forum clinicians should be aware that not all forms of mantle cell lymphoma are indolent. Many patients with mantle cell lymphoma are seen in GIM clinics, and thus, primary care clinicians should be aware of this form of mantle cell lymphoma. Patients with new weight loss and either lymphadenopathy or a history of mantle cell lymphoma should receive an evaluation for the aggressive subtype of this disease described in the case above.