Previously Unrecognized Variant of FL Described


Follicular large cleaved cell lymphoma is frequently misclassified, according to researchers.

Follicular large cleaved-cell lymphoma (FLC) represents a previously unrecognized variant of follicular lymphoma (FL) with distinctive pathologic features and implications for treatment decision-making, according to authors of a case series published in Human Pathology.

“The correct diagnosis of FLC is important for accurate prognostication and may be important in the selection of therapy for these patients,” reported Patricia Aoun, MD, MPH, of the City of Hope National Medical Center in Duarte, California, and coauthors. “FLC is a variant of follicular lymphoma which should be recognized in future lymphoma classifications,” the authors wrote.

The World Health Organization (WHO) classification system for lymphoma recommends categorizing FL cases into three grades (FL1-3) that reflect the average number of centroblasts in the neoplastic follicles. However, that classification system does not recognize a form of FL characterized by a predominance of large cleaved cells (centrocytes) with too few centroblasts to meet the WHO FL3 criteria, the authors noted. 

“Because FLC is not included in the WHO classification, the entity is not well-described in the current literature, and the diagnosis can be challenging for pathologists,” they emphasized, noting that pathologists are frequently puzzled by the presence of numerous large cells, which the WHO classification system categorizes as low-grade disease. 

Using the Nebraska Lymphoma Study Group registry, the authors found 72 patients diagnosed between 1983 and 2010, whose FL they classified as FLC. Another 593 FL cases from the same period were retrieved for comparison.

Fifty-seven percent of the FLC cases were initially diagnosed as FLs, but the remainder were initially sent for pathological consultation without definitive diagnosis. The authors reported that, of the 41 cases originally recognized as FL, 46% were classified at low-grade disease (WHO FL1, 12%; FL2, 34%; FL3, 49%). 

Pathologists frequently recognize the high-grade nature of FLC cases based on the nuclear size, proliferation and chromatin pattern, but these cases do not meet the criteria of WHO FL3.

“However, nearly half [46%] of our cases were diagnosed as low-grade FL, which could affect the treatment and prognosis of these patients,” the authors emphasized. 

The pathologic features of FLC “include pale follicles with follicular or interfollicular fibrosis and a predominance of large cleaved cells with high proliferation,” the authors reported.

“Cytologically, the cells are predominantly large cleaved cells with moderately coarse to fine chromatin, absent or inconspicuous nucleoli, and small to moderate amounts of pale cytoplasm,” they wrote. “The t(14;18) [translocation] was present in 83% of the cases, and a high proportion expressed BCL2 (84%), BCL6 (100%), and CD10 (88%), and had high Ki67 proliferation (81%).” 

The average nuclear diameter of the large cleaved cells was roughly twice that of small lymphocytes, the authors noted.

Clinically, FLC is similar to other FL subtypes, with “excellent” survival outcomes among patients who are treated with anthracycline-based chemotherapy plus rituximab.

Recent Videos
The approval for epcoritamab in patients with R/R follicular lymphoma was supported by encouraging efficacy findings from the phase 1/2 EPCORE NHL-1 trial.
A phase 1/2 trial assessed the use of menin inhibitor DSP-5336 in patients with acute leukemia overexpressing HOXA9 and MEIS1.
A pooled analysis trial assessed the impact of acalabrutinib in patients with chronic lymphocytic leukemia across treatment lines.
This series features 2 KOLs.
This series features 2 KOLs.
relapsed or refractory mantle cell lymphoma, glofitamab, Obinutuzumab, phase 1/2 study, NCT03075696, Tycel J. Phillips, MD
This series features 2 KOLs.
This series features 2 KOLs.
Future meetings may address how immunotherapy, bispecific agents, and CAR T-cell therapies can further impact the AML treatment paradigm.