Advanced Hemepath Flashcards
17 y.o. F presents with a neck mass. Biopsy shown here. Cells are BCL6 positive, but negative for t(8;14), MYC, BCL2, and BCL6 rearrangement. What is the diagnosis?
Burkitt-like lymphoma with 11q aberration
Looks like Burkitt’s, smells like Burkitt’s, but classical rearrangements are negative.
It is a GC-derived, CD10+ tumor that is genetically closer related to High grade BCL/DLBCL than Burkitt’s, but presents with a starry sky pattern and BCL6 positivity.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717587/
Splenectomy is commonly preformed in most hereditary X-cytoses due to sequestration, however it is contraindicated in which diseases due to increased risk of thromboembolism?
Xerocytosis and stomatocytosis
Diffuse splenic red pulp small B-cell lymphoma
Mature splenic B cell lymphoma characterized by diffuse infiltration of the splenic red pulp with small, monomorphous B lymphocytes.
Bone marrow sinusoids and peripheral blood are often also involved, often by lymphocytes with a villous morphology (shown here). It is one of the few lymphomas which can do this, but it is in the largest subgroup (small B cell intrasinusoidal lymphomas).
Indolent, but curable, with 93% survival at 5 years. Importantly, it is often resistant to chemotherapies which are effective for HCL, HCLv, and splenic MZL/splenic LWCVL. Often treated first with splenectomy, second line may be chemo or rituximab.
IHC: CD20+, DBA-44+, CD79a+
Flow: IgM alone/IgG alone/IgM+IgD/IgM+IgG, CD20+, CD22+, CD11c moderate, CD103 faint, CD5 neg, CD23 neg, CD25 neg, CD123 neg
Molecular: Del7(q), partial trisomy 3q, trisomy 18, del17(p), CCND3 mutations. Mutations in NOTCH, MAPK21, and TP53 are associated with progression.
Splenic B cell lymphoma/leukemia with prominent nucleoli (formerly Hairy cell leukemia variant)
Morphologically and immunophenotypically similar, but biologically distinct lymphoma, to hairy cell leukemia. While classical HCL is driven by BRAFV600E (95% of cases), HCLv is negative for BRAF alterations.
Morphologically, characterized by intermediate size cells with blastic or convoluted nuclei, prominent nucleoli and circumferential shaggy contours. Convoluted and blastoid morphologic variants also exist.
Unlike cHCL, HCLv is NOT associated with marrow reticulin fibrosis. One of the intrasinusoidal lymphomas of the bone marrow, spleen, and liver, but also often involves the red pulp diffusely and has a circulating leukemic component.
Immunophenotype: CD11c +, CD19/20/22 +, DBA-44 +, Monotypic IgG +, CD25 neg, CD123 neg, TRAP weak-to-neg, annexin A1 neg, BRAFV600E neg
Molecular: Recurrent MAP2K1 muts, KMT2C, CCND3, or U2AF1 in a subset, large number of DNA copy alterations, most commonly chromosome 5 gains and chromosome 7q or 17q losses.
Differentiating the splenic villoid lymphocytic neoplasms
IHC for CD25, CD103, CD123
BRAFV600E (if pos, HCL)
HCL: CD25+, CD103+, CD123+
HCLv: CD25 neg, CD103 variable, CD123 neg
SDRP-SBCL: CD25 neg, CD103 neg, CD123 neg
SMZL/SLWCVL: CD25 +, CD103 variable, CD123 neg
Follicular lymphoma - duodenal type
Lymphoma with similar histologic, immunophenotypic, and molecular features (IGH-BCL2) to follicular lymphoma - but arising within the duodenum and with an indolent course. Only ~10% of patients progress to nodal disease.
Typically detected at a low stage as polypoid lesions, usually multifocal.
Treatment may be a watch and wait approach, or localized radiation +/- chemo or rituximab.
If a polyp comes back from an endoscopic biopsy with a weird looking follicle, consider throwing on a BCL-2 to screen for this neoplasm.
What is the non-classical Hodgkin lymphoma?
Nodular lymphocyte predominant
Characterized by popcorn cells surrounded by a rosette of T cells.
Follicular neoplasia in-situ
Some percentage of B cells will acquire the IGH-BCL2 translocation during BCR rearrangement. These cells then go on into the bloodstream as naive B cells and may colonize a germinal center, replacing it with a clonal population which carries the translocation.
FNIS is identified in 2-3% of excised lymph nodes if stained with BCL2, but only about 2-3% of FNIS will go on to become follicular lymphoma.
FNIS is also characterized by CREBBP, TNFRSF14, and EZH2 mutations, and a low frequency of KMT2D mutations (as opposed to the KTM2D negative duodenal FL).
Mantle cell neoplasia in-situ
As with FNIS, some percentage of B cells will acquire the IGH-CCND1 translocation during BCR rearrangement. These cells then go on into the bloodstream as naive B cells and may colonize the mantle zone of a lymphoid follicle, replacing it with a clonal population which carries the translocation.
This population may rarely be identified on H&E as irregular invagination of the marginal zone into the germinal center of a reactive-appearing lymph node.
Staining for cyclin D1 reveals diffusely positive mantle zone cells in involved follicles, as well as scattered positive cells within the GC and the background interfollicular space.
As with FNIS, only <10% of MCNIS will go on to progress to a mantle cell lymphoma.
Mantle cell neoplasia progression
Follicular neoplasia progression
