Follicular lymphoma: 2020 update on diagnosis and management

Abstract

Disease overview: Follicular lymphoma (FL) is generally an indolent B cell lymphoproliferative disorder of transformed follicular center B cells. Follicular lymphoma is characterized by diffuse lymphadenopathy, bone marrow involvement, and splenomegaly. Extranodal involvement is less common. Cytopenias are relatively common but constitutional symptoms of fever, night sweats, and weight loss are uncommon in the absence of transformation to diffuse large B cell lymphoma. Diagnosis:The diagnosis is based on histology from a biopsy of a lymph node or other affected tissue. Incisional biopsy is preferred over needle biopsies in order to give adequate tissue to assign grade and assess for transformation. Immunohistochemical staining is positive in virtually all cases for cell surface CD19, CD20, CD10 and monoclonal immunoglobulin, as well as cytoplasmic expression of bcl-2 protein.The overwhelming majority of cases have the characteristic t(14;18) translocation involving the IgH/bcl-2 genes.Risk stratification: The Follicular Lymphoma International Prognostic Index (FLIPI) uses five independent predictors of inferior survival: age > 60 years, hemoglobin <12 g/dL, serum LDH > normal, Ann Arbor stage III/IV, number of involved nodal areas >4. The presence of 0-1, 2, and ≥ 3 adverse factors defines low, intermediate, and high-risk disease. There are other clinical prognostic models but the FLIPI remains the most common. Other factors such as time to relapse of less than 2 years from chemoimmunotherapy and specific gene mutations may also be useful for prognosis.Regardless of the prognostic model used, modern therapies have demonstrably improved prognosis.Risk-adapted therapy: Observation continues to be appropriate for asymptomatic patients with low bulk disease and no cytopenias. There is no overall survival advantage for early treatment with either chemotherapy or single agent rituximab. For patients needing therapy, most patients are treated with chemoimmunotherapy, which has improved response rates, duration of response and overall survival (OS).Randomized studies have shown additional benefit for maintenance rituximab.Lenalidomide was non-inferior to chemoimmunotherapy in a randomized front-line study and, when combined with rituximab, was superior to rituximab alone in relapsed FL. Kinase inhibitors, other immunotherapies, and stem cell transplantation (SCT) are also considered for recurrent disease.

Occult follicular lymphoma in a swollen regional lymph node of gastric schwannoma

“…Malignant lymphoma, including FL, is usually noticed by the appearance of B symptoms and/or cervical, axillary, or inguinal swollen lymph nodes [14]. After the imaging test, malignant lymphoma is diagnosed by the excisional biopsy of a cervical, axillary, mesenteric, inguinal, mediastinal, or para-aortic swollen lymph node.…”

“…The patient received no initial therapy for FL. FL is the most common indolent B-cell non-Hodgkin's lymphoma, most of which are diagnosed in an advanced stage (Ann Arbor stage III/IV) [14,16]. Limited stage (Ann Arbor I/II) FL is relatively uncommon; therefore, high-quality evidence for the treatment of limited stage FL is lacking [16].…”

“…Previous reports in the United States showed that the initial therapy given for stage I patients was as follows: rituximab plus chemotherapy, 28%; radiation therapy, 27%; observation, 17%; systemic therapy plus radiation therapy, 13%; rituximab monotherapy, 12%; and other, 3% [17]. Selected limited stage patients, such as asymptomatic and low-tumor burden patients, can be candidates for the strategy of a watchful waiting approach [9,14]. This is consistent with our present case.…”

Drug Resistance in Non-Hodgkin Lymphomas

“…Implementation of rituximab into CHOP (hence, R-CHOP) revolutionized the therapy of CD20+ B-NHL and soon, it was used not only as part of a front-line immunochemotherapy regimen, but also as a maintenance monotherapy in particular lymphoma subtypes [13][14][15][16]. Up to the present, R-CHOP remains the first-line standard of care for newly diagnosed patients with three most common types of B-NHL, diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and marginal zone lymphoma (MZL) [17]. Despite great expectations and many attempts to introduce other mAbs targeting other antigens than CD20, rituximab and the next-generation anti-CD20 mAbs ofatumumab and obinutuzumab have remained, so far, the only naked therapeutic monoclonal antibodies approved for the therapy of B-NHL [9].…”

Diagnosis of Hodgkin Lymphoma from Cell Block: A Reliable and Helpful Tool in “Selected” Diagnostic Practice

“…According to the current World Health Organization (WHO) classification, an integrated diagnostic system based on morphological pattern recognition, immunophenotyping and molecular analyses is recommended in clinical practice to establish a correct diagnosis, provide prognostic information and choose the most appropriate and effective therapy [ 1 , 2 ]. Surgical biopsy is considered the gold standard for the diagnosis of lymphoma [ 3 ], for it evaluates the architectural pattern of growth, establishing the grading, as for follicular lymphoma [ 4 ], and identifies possible areas that may progress into more aggressive forms [ 5 ]. However, for selected patients unsuitable for surgical procedures presenting extra-nodal or deep-seated lesions (such as intrathoracic, intra-abdominal, or other anatomical sites where the lesions are impalpable or not easily accessible by superficial biopsy and for which radiological guidance is required for appropriate sampling) or with recurrent lymphoma and/or poor performance status, ultrasound-guided fine needle aspiration (US-FNA) and endobronchial ultrasound-guided fine needle aspiration (EBUS-FNA) may be considered as alternative techniques to obtain diagnostic samples [ 6 , 7 ].…”