Diffuse Follicular Lymphoma Variant: An Unusual Case with Predominantly a Large B-Cell Lymphoma Component

Lessons From the Friday Unknowns

Histologic sections show a lymphoid infiltrate relatively well confined by fibrovascular stromal cells rather than a nodal capsule. The architecture is effaced by a large cell infiltrate with a poorly defined pattern.

In focal areas, the infiltrate has a vaguely nodular growth pattern and is composed of predominantly small to intermediate–sized lymphocytes with irregular nuclear contours, vesicular chromatin and scant to moderate amount of cytoplasm, and scattered large cells.

Scattered small, medium and large vessels show angiocentricity, where vessels are infiltrated mainly by small lymphocytes.

The neoplastic cells are positive for CD20, CD10 (subset), BCL6, CD23, and negative for BCL-2 and CD5. CD3 highlights small T cells. Ki-67 show a proliferation index of approximately 40–60% in most areas and ~90% in areas of confluent large cells.

Flow cytometry analysis was performed on a concurrent specimen, and detected an aberrant population of B cells (6.4% of the total event) that is positive for CD45, CD19, CD20, CD10, CD22, CD23, CD38, FMC 7 and BCL2, and negative for CD5 and CD11c.

Fluorescence in situ hybridization is positive for Del 1p and additional copy of IGH gene but is negative for IGH/BCL-2 gene rearrangement.

The histopathologic and immunophenotypic findings support the presence of follicular lymphoma grade 3A with areas of diffuse large B-cell lymphoma. The presence of Del 1p detected by FISH coupled with extensive expression of CD23 and absence of IGH-BCL2 is reminiscent of so-called diffuse variant of follicular lymphoma, which is usually described as a low grade lymphoma, presenting in the inguinal region as is the current case. According to current information, the lymphoma is localized and there is no evidence of systemic dissemination. Given the highly unusual scenario where this lymphoma is arising, as well as its unusual histopathologic features, it is very difficult to predict its behavior and close follow up is recommended in this case.

Diffuse follicular lymphoma variant is a novel variant mainly occurs in the inguinal region, forming larger tumours, but with little tendency to disseminate. It is characterized by a predominantly diffuse growth pattern with areas characterized by small follicles or so-called microfollicles.

Consistent absence of the t(14;18)(q32;q21) (IGH/BCL2) chromosomal translocation is noted in this variant, with weak to absent BCL2 staining. The neoplastic cells are usually CD10-positive, and in almost all cases express the CD23 antigen as well.

Although these cases cluster with typical FL by gene expression profiling, a recurrent genetic aberration, deletion in 1p36, is seen in most cases. However this alteration is not specific to this variant; the region at 1p36, which contains TNFRSF14, is also commonly affected in t(14;18) — positive FL.

Link to digital slides: Slides labeled case 4|https://bit.ly/3g0uQFX

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