Skip to Main content Skip to Navigation
Journal articles

Contiguous follicular lymphoma and follicular lymphoma in situ harboring N-glycosylated sites

Abstract : Follicular lymphoma in situ (FLIS) is composed of a clonal B-cell population harboring the typical t(14;18) hallmark of follicular lymphoma (FL), forming unconventional BCL2 Bright CD10 + cell foci in an otherwise normal reactive lymph node (LN). The diagnosis of FLIS is made on the fortuitous discovery of unconventional BCL2 Bright CD10 + cell foci. 1 Several studies recently demonstrated that FLIS are already advanced precursors in follicular lymphomagene-sis, but not necessarily committed to malignant transformation. 2,3 However, the relationship between FLIS and FL still remains unclear, as only a minority (<5%) of FLIS patients eventually develop FL. This is in line with the usually indolent progression of the disease, and the genomic instability observed in FLIS cells, which can engage FL precursor cells either in an evolutionary malignant process, or to an evolutionary dead end. 4 We report the case of a 35-year old male patient who presented with a cervical adenopathy. Histological examination of the excised LN displayed an altered architecture suggestive of FL, consisting of high number of monomorphic large follicles, uniformly spread in the cortical and medullary areas. Most follicles contained a predominant population of small cleaved cells with scant macrophages and mitoses. The mantle zone was reduced or absent. However, in a minor cortical area, a few follicles showed features mimicking residual classical germ cells (GC), including a smaller size, higher cell polymorphism, and a preserved mantle zone (Figure 1A). The BCL2 immunostaining (clone 100) was negative in follicles displaying a typical FL pattern. In contrast, follicles located in the pseudo-residual area were BCL2bright, i.e. more strongly stained than the surrounding mantle zone and reactive T cells (Figure 1B). Most follicles were only slightly positive for Ki67 (Online Supplementary Figure S1A). Both BCL2 – and BCL2 + follicles were CD10 positive (Online Supplementary Figure S1B) and contained a BCL2/JH break-point evidenced by fluorescence in situ hybridization (FISH) (Figure 1C). Taken together these results suggested the diagnosis of simultaneous occurrence of BCL2 – FL (grade I/II) and of BCL2 + FLIS in the same LN. We decided to further analyze those two lesions independently, and performed macrodissection in order to proceed with individual molecular analyses when required. Sanger sequenc-ing revealed that both FLIS and FL shared the same BCL2/JH sequence at the t(14;18)+ breakpoint, and thus originated from the same clone (Figure 1D). We tested two other anti-BCL2 antibodies (E17, SP66) directed against other epitopes, but the staining remained BCL2-in the FL area of the LN, similar to the anti-BCL2 antibody (clone 100) staining (Figure 1E and F). We thus sequenced exons 1 to 3 of the BCL2 gene (B-cell CLL/lym-phoma 2, NG_009361.1). Punctual mutations, resulting in amino acid substitutions, were found in the FL component (Online Supplementary Table S1), and were indeed located in the targeted aa41 to aa54 epitope of clone 100 (mutations
Document type :
Journal articles
Complete list of metadatas

Cited literature [15 references]  Display  Hide  Download

https://hal-amu.archives-ouvertes.fr/hal-01216319
Contributor : Administrateur Hal Amu <>
Submitted on : Friday, October 16, 2015 - 9:45:26 AM
Last modification on : Wednesday, January 29, 2020 - 11:10:04 AM
Long-term archiving on: : Monday, January 18, 2016 - 5:59:02 AM

File

ptpmcrender.pdf
Publisher files allowed on an open archive

Identifiers

  • HAL Id : hal-01216319, version 1

Collections

Citation

Emilie Mamessier, Charlotte Drevet, Florence Broussais-Guillaumot, Marie-Laure Mollichella, Sylvain Garciaz, et al.. Contiguous follicular lymphoma and follicular lymphoma in situ harboring N-glycosylated sites. Haematologica, Ferrata Storti Foundation, 2015, 100, pp.E155-E157. ⟨hal-01216319⟩

Share

Metrics

Record views

268

Files downloads

276