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Published on: November 26, 2018
Mutational Profile and Pathological Features of a Case of Interleukin-10 and RGS1-Positive Spindle Cell Variant
Joaquim Carreras1, Yara Yukie Kikuti1, Masashi Miyaoka1
1Department of Pathology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Kanagawa, Japan.
Insights
This study details a rare spindle cell variant of diffuse large B-cell lymphoma (DLBCL) in a 74-year-old male. The case highlights unique mutations and immune microenvironment features, leading to a complete response with R-CHOP therapy.
Area of Science:
- Hematology
- Oncology
- Pathology
Background:
- Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma.
- Rare morphological variants of DLBCL present diagnostic challenges.
- Spindle cell morphology in DLBCL is uncommon and requires thorough characterization.
Observation:
- A 74-year-old male presented with enlarged supraclavicular lymph node.
- Histopathology revealed a proliferation of spindle-shaped cells.
- Immunohistochemistry excluded melanoma, carcinoma, and sarcoma.
Findings:
- The lymphoma was classified as germinal center B-cell-like (GCB) subtype.
- Genetic analysis identified mutations in ACTB, ARID1B, DUSP2, DTX1, HLA-B, PTEN, and TNFRSF14.
- LymphGen 1.0 predicted an ST2 subtype.
- The immune microenvironment showed M2-like macrophages and PD-L1 expression.
- Poor prognostic markers HLA-DP-DR, IL-10, and RGS1 were expressed by lymphoma cells.
Implications:
- This case expands the understanding of DLBCL heterogeneity.
- The identified mutations may offer therapeutic targets.
- Characterizing the immune microenvironment is crucial for DLBCL prognosis.
- The patient achieved a complete response to R-CHOP therapy, suggesting treatment efficacy for this rare variant.
Abstract:
Diffuse large B-cell lymphoma with spindle cell morphology is a rare variant. We present the case of a 74-year-old male who initially presented with a right supraclavicular (lymph) node enlargement. Histological analysis showed a proliferation of spindle-shaped cells with narrow cytoplasms. An immunohistochemical panel was used to exclude other tumors, such as melanoma, carcinoma, and sarcoma. The lymphoma was characterized by a cell-of-origin subtype of germinal center B-cell-like (GCB) based on Hans' classifier (CD10-negative, BCL6-positive, and MUM1-negative); EBER negativity, and the absence of BCL2, BCL6, and MYC rearrangements. Mutational profiling using a custom panel of 168 genes associated with aggressive B-cell lymphomas confirmed mutations in ACTB, ARID1B, DUSP2, DTX1, HLA-B, PTEN, and TNFRSF14. Based on the LymphGen 1.0 classification tool, this case had an ST2 subtype prediction. The immune microenvironment was characterized by moderate infiltration of M2-like tumor-associated macrophages (TMAs) with positivity of CD163, CSF1R, CD85A (LILRB3), and PD-L1; moderate PD-1 positive T cells, and low FOXP3 regulatory T lymphocytes (Tregs). Immunohistochemical expression of PTX3 and TNFRSF14 was absent. Interestingly, the lymphoma cells were positive for HLA-DP-DR, IL-10, and RGS1, which are markers associated with poor prognosis in DLBCL. The patient was treated with R-CHOP therapy, and achieved a metabolically complete response.
