Diffuse Large B-Cell Lymphoma

Authors:
Lincey Alexida, BS, MBA
Saint James School of Medicine, Anguilla

Pranav Patel, MD
Palos Heights, Illinois

Citation:
Alexida L, Patel P. Diffuse large B-cell lymphoma. Consultant. 2017;57(8):506-507.

A 60-year-old woman presented with a persistent dry cough, extreme fatigue, and a decrease in appetite following a diagnosis of streptococcal pharyngitis and tonsillitis 3 weeks prior. The patient had a past medical history of type 2 diabetes, hypertension, hypothyroidism, anxiety, depression, and hyperlipidemia. She also had a past surgical history of right total knee arthroplasty, partial hysterectomy, and cholecystectomy.

Physical examination. A review of systems and physical examination showed that she had unintentionally lost 9 kg in the 3 weeks since her last visit. She also had increased paleness and decreased exercise tolerance. An exudative lesion was seen on the right tonsil during oral examination. Findings of a manual examination of her neck and pelvis were negative for peripheral lymphadenopathy. She returned home pending blood test results.

Diagnostic tests. Results of laboratory investigations revealed anemia, with a ferritin level of 1607 ng/mL (reference range, 11-307 ng/mL), a low transferrin level, a low iron level, and a hemoglobin of 8.6 g/dL (13.6 g/dL 2 months previously). Accordingly, the patient was asked to return to the office.

Physical examination at the return visit showed an additional 4.5-kg weight loss for a total loss of 13.6 kg in less than 1 month. Her signs and symptoms had remained the same from the last visit, except that now an approximately 3-cm right cervical lymph node was palpable on manual examination. This finding prompted a referral for a complete workup.

Abdominal ultrasonography revealed splenomegaly and multiple masses in the retroperitoneum suggesting enlarged lymph nodes. Results of computed tomography (CT) scanning of the abdomen and pelvis with and without contrast showed extensive bilateral para-aortic, paracaval, mesenteric, and less-pronounced iliac chain adenopathy with splenomegaly (Figures 1 and 2). The largest lymphadenopathy focus measured 7 cm across the right mid to lower abdomen. Contrast-enhanced CT of the neck showed multiple enlarged lymph nodes in the neck, the mediastinum, and the left axillary and subpectoral regions. Several of the lymph nodes demonstrated central necrosis.

Figure 1. Axial CT image showing extensive lymphadenopathy in the lower abdomen.

Figure 2. Coronal CT image showing para-aortic, mesenteric, and iliac chain lymphadenopathy.

The pathology report of a biopsy of the right level II deep cervical lymph node uncovered the final diagnosis of diffuse large B-cell lymphoma (DLBCL), nongerminal center B-cell–like subtype. Immunochemistry analysis findings showed that the lymphoma was 10% to 20% positive for the B-cell CLL/lymphoma 6 gene (BCL6), approximately 30% positive for the myelocytomatosis oncogene (MYC), 60% to 70% positive for the marker of proliferation Ki-67 gene (MKI67), and diffusely positive for the B-cell CLL/lymphoma 2 gene (BCL2) and the melanoma-associated antigen (mutated) 1 gene (MUM1). Flow cytometric immunophenotypic analysis of the lymph node specimen revealed a λ light chain–restricted B-cell population that was CD20⁺, CD5^–, and CD10^–.

Discussion. DLBCL is one of the most common subtypes of non-Hodgkin lymphoma (NHL). NHL is a malignancy of the lymphoid tissue, and it accounts for more than 60% of adult cases of lymphoma.¹ DLBCL is a rapidly progressive tumor that is aggressive in its presentation. Gene expression profiling has led to the discovery of many molecular subtypes, with the top 2 being germinal center B-cell (GCB) and activated B-cell.² However, most oncologists simply classify DLBCL into 2 subclasses, GCB or non-GCB.

DLBCL displayed a 100% 1-year fatality rate in a group of newly diagnosed patients who rejected medical intervention.³ Nevertheless, DLBCL has proven to be curable in more than 60% of patients who are treated with the combination therapy R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).⁴ A small population (< 5%) of DLBCL patients have the presence of 2 simultaneous oncogenic mutations (eg, MYC and BCL2) rather than only one. Referred to as double-hit lymphoma (DHL), it has the worst prognosis and is less responsive to R-CHOP.² Because DHL is a rare subtype of DLBCL, an insufficient number of studies have evaluated alternative treatment options outside of R-CHOP.

Among the numerous management approaches to DLBCL, the top 3 are chemotherapy, radiotherapy, and comprehensive treatment. The prognosis for DLBCL is related to the patient’s age, the stage of disease, the presence of B symptoms (ie, fever, night sweats, weight loss), the serum lactate dehydrogenase (LDH) level, the pathological type, and treatment choices.^3,5 The prognosis is favorable for patients who are younger than 60 years, have a low stage (I or II), have an absence of B symptoms, and have a normal serum LDH level.³ While the success rate of the comprehensive treatment option for DLBCL has improved, particularly with the use of R-CHOP,^3,6 due to the nature of this tumor, the rate of recurrence or failure to achieve complete remission approaches one-third of patients with DLBCL.⁶

Outcome of the case. The patient received a diagnosis of stage III DLBCL, IPI (International Prognostic Index) 2, based on stage, age, and normal LDH level. She was not considered to have DHL, because she had only approximately 30% MYC positivity in addition to being diffusely positive for BCL2. Nevertheless, being 30% positive for a concurrent mutation with MYC is rare and is a consideration in determining the number of chemoimmunotherapy cycles a patient receives.

She is being treated with 6 cycles of R-CHOP, with cycles added if they become necessary. She also has scheduled visits with her primary care physician for routine blood tests to monitor her prednisone level and to avoid therapy toxicity.

References:

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3. Jiang JN, Sun XH. The prognosis factors research on the 172 non-Hodgkin lymphoma cases. Biomed Res (Aligarh). 2016;27(2):336-344.
4. Johnson NA, Slack GW, Savage KJ, et al. Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2012;​30(28):3452-3459.
5. Zhou Z, Sehn LH, Rademaker AW, et al. An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era. Blood. 2014;123(6):837-842.
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