Isolated Bone Marrow Involvement in Diffuse Large B Cell Lymphoma: A Report of Three Cases with Review of Morphological, Immunophenotypic and Cytogenetic Findings

Abstract

Diffuse large B cell lymphoma (DLBL) comprises a heterogenous entity characterized by the presence of large cells, exhibiting a mature B cell phenotype. The high proliferation rate and aggressive disease remain a therapeutic challenge, but the apparent biological diversity permits a risk-stratification model for prognostic grouping through the International Prognostic Index (IPI). Empirical to this approach is the consideration of cytogenetic data, offering an insight into the pathogenetic events which may underlie neoplastic clonal evolution and disease progression. We describe three cases of DLBL presenting with isolated marrow disease, a rare primary finding in this lymphoma. All three cases showed involvement of blood and bone marrow without evidence of splenic or lymph node involvement on imaging studies. Histological and immunophenotypic findings were similar in all three cases, outlining the phenotypic maturity of this disease. Cytogenetic analysis revealed complex karyotypes in the two cases examined. M-FISH (multicolour fluorescent in situ hybridization) performed on bone marrow from case 1 showed several cryptic translocations not evident on G-banding, including a novel translocation between 2p and 9p, and an unbalanced translocation between 14q and 11q. Cytogenetic analysis in case 2 showed abnormalities involving 7q, 9p at the site of the INK4a gene, and the bcl-2 locus, findings confirmed by M-FISH. These cases serve to highlight the biological and cytogenetic heterogenity of DLBL and emphasize the need for complementary investigations in the characterization of this entity.

Primary bone marrow lymphoma: A hematological emergency in adults with fever of unknown origin

“…PBML frequently manifests as HLH, with an extremely poor prognosis; however, it shows heterogeneous histology. Moreover, PBML can be identified as a special clinical phenotype in various study cohorts, including those considering cases of large cell lymphoma in the leukemic phase,6, 24 the Asian‐variant of intravascular large B‐cell lymphoma,22 or de novo CD5(+) DLBCL 25…”

“…However, several recently reported cases exhibited an uncommon NHL, without lymphadenopathy but only a primary tumor in the BM—primary bone marrow lymphoma (PBML) 1, 2, 3, 4, 5, 6…”

“…The current knowledge regarding PBML has mainly been derived from several clinicopathologic reports,1, 2, 3, 4, 5, 6 and most studies of PBML report two diagnostic criteria in common: pathological evidence of BM infiltration with NHL and the absence of any lymph‐node enlargement or tumor formation 1, 2, 3, 4. However, there are two major limitations to our current understanding of this condition.…”

Primary Isolated Bone Marrow Diffuse Large B-cell Lymphoma with Hemolytic Anemia as the First Manifestation

“…Non-Hodgkin's lymphoma restricted to the BM is extremely rare, with only 32 fully documented cases in the English-language literature, [1][2][3][4][5][6] of which 8 were IBMDLBL. 3,5,6) These patients consisted of four men and four women with an age range from 42 to 86 years.…”

“…Although bone marrow (BM) involvement in DLBL is relatively infrequent at presentation and is generally believed to represent systemic dissemination of disease, some cases may arise primarily in BM. [1][2][3][4][5][6] Primary BM involvement in NHL may be more frequent in cases of T-cell lymphoma, as only eight cases in 32 previous reports were DLBL in English literature. 3,5,6) But primary isolated BM DLBL was not reported in Korea.…”