Clinicopathologic Characteristics and Outcome of Diffuse Large B-Cell Lymphomas Presenting With an Associated Low-Grade Component at Diagnosis

Ghesquières, Hervé; Berger, Françoise; Felman, Pascale; Callet‐Bauchu, Evelyne; Bryon, Paul‐André; Traverse-Gléhen, Alexandra; Thiéblemont, Catherine; Baseggio, Lucile; Michallet, Anne‐Sophie; Coiffier, Bertrand; Salles, Gilles

doi:10.1200/jco.2006.07.5671

Cited by 62 publications

(45 citation statements)

References 32 publications

(4 reference statements)

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“…9 Consistent with this notion, our study documents that: i) 25% of HCV-positive DLBCL harbor a minor area of the diagnostic biopsy composed of small to medium sized monocytoid B cells consistent with an MZL; ii) SMZL-associated NOTCH pathway mutations are significantly enriched in HCV-positive DLBCL harboring both low-and high-grade components; and iii) HCV-positive DLBCL harboring NOTCH pathway mutations are characterized by worse survival in exploratory univariate and multivariate analyses, with an expected survival superimposable on that of transformed DLBCL from other indolent B-cell tumors. 31,32 Overall, these data further support the notion that a subgroup of DLBCL arising in subjects carrying HCV infection represent the transformation of a previous, clinically unrecognized indolent MZL.…”

Section: Discussionsupporting

confidence: 67%

The NOTCH pathway is recurrently mutated in diffuse large B-cell lymphoma associated with hepatitis C virus infection

et al. 2014

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Section: Discussionsupporting

confidence: 67%

The NOTCH pathway is recurrently mutated in diffuse large B-cell lymphoma associated with hepatitis C virus infection

et al. 2014

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“…(10) The better outcomes for patients in our present study (5-year PFS rate, 55% and 5-year OS rate, 79%) might be partly associated with the younger median age (56 years) and relative frequency of cases with a low ⁄ low-intermediate International Prognostic Index. In addition, most of these patients received rituximab-containing treatment, although the benefit of rituximab was not proved in the current study.…”

Section: Discussionmentioning

confidence: 55%

“…Overall survival (OS) and freedom-from-progression rates at 5 years were 57% and 33%, respectively. (10) In recent years, several analyses of genetic alterations that appear to affect the risk for FL transformation have been reported, including activation of cMYC, (6,11) inactivation of TP53, (12,13) and inactivation of p16 INK4a . (14,15) However, few histopathological and immunohistochemical analyses of transformed FL have been performed.…”

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confidence: 99%

Clinicopathological prognostic indicators in 107 patients with diffuse large B‐cell lymphoma transformed from follicular lymphoma

et al. 2013

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Follicular lymphoma (FL) frequently transforms into diffuse large B-cell lymphoma (DLBCL). To clarify the associated clinicopathological prognostic parameters, we examined the correlation of 11 histopathological parameters with progression-free survival (PFS) and overall survival (OS) in 107 consecutive patients who had DLBCL with pre-existing (asynchronous) or synchronous FL. The patients comprised 58 men and 49 women with a median age of 56 years. For DLBCL, the complete response rate was 81%, overall response rate was 88%, and 5-year PFS and OS rates were 55% and 79%, respectively. Immunohistochemical analysis of the DLBCL component revealed the following positivity rates: CD10, 64%; Bcl-2, 83%; Bcl-6, 88%; MUM1, 42%; GCB, 82%; cMyc index 80%, 17%; and Ki-67 index 90%, 19%. IGH/BCL2 fusion was positive in 57% of DLBCL cases. In univariate analyses, asynchronous FL and DLBCL (24%, P = 0.021), 100% proportion of DLBCL (29%, P = 0.004), Bcl-2 positivity (P = 0.04), and high Ki-67 index (P = 0.003) were significantly correlated with shorter PFS. Asynchronous FL and DLBCL (P = 0.003), 100% proportion of DLBCL (P = 0.001), and high Ki-67 index (P = 0.004) were significantly correlated with shorter OS. In a multivariate analysis, asynchronous FL and DLBCL (P = 0.035) and 100% proportion of DLBCL (P = 0.016) were significantly correlated with shorter OS. Thus, asynchronism and 100% proportion of DLBCL, that is, FL relapsed as pure DLBCL, or FL and DLBCL at different sites, were significant predictors of unfavorable outcome of patients with DLBCL transformed from FL. (Cancer Sci 2013; 104: 952-957) F ollicular lymphoma (FL) is one of the most common subtypes of non-Hodgkin lymphoma in the Western world, accounting for 22% of all cases worldwide.(1) The risk of FL transformation was reported to be approximately 20% at 8 years.(2,3) Transformation to diffuse large B-cell lymphoma (DLBCL) is observed frequently, with cells most commonly resembling centroblasts, (4) but occasionally resembling anaplastic large cells with CD30 expression.(5) In rare cases, transformation to Burkitt or Burkitt-like lymphoma (6) or precursor B-lymphoblastic lymphoma ⁄ acute lymphoid leukemia has been noted.(7) Composite FL and Hodgkin lymphoma have been suggested to represent two morphologic manifestations of the same tumor clones. (8,9) Transformation to DLBCL is frequently associated with a rapidly progressive clinical course and death from a tumor that is refractory to treatment.(3) Ghesqui eres et al. analyzed 60 DLBCLs transformed from low-grade B-cell lymphoma and reported that complete remission with multidrug chemotherapy regimens was achieved in 60% of the patients, but 48% of them relapsed. Overall survival (OS) and freedom-from-progression rates at 5 years were 57% and 33%, respectively. (10) In recent years, several analyses of genetic alterations that appear to affect the risk for FL transformation have been reported, including activation of cMYC, (6,11) inactivation of TP53, (12,13) and inactivation of p16 INK4a . (14,15) Ho...

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“…Both conclude that response to treatment and survival does not differ between patients with marrow involved by low-grade lymphoma and patients with no marrow disease. A clinical study 30 examined the natural history of patients, who at first diagnosis of DLBCL had evidence, on lymph node biopsy, of coexisting or transformed MZL, FL, or small cell lymphoma. These patients were older and most had disseminated disease with .1 extranodal site at staging.…”

Section: Bone Marrow Staging Of Dlbcl By Pet-ct 63mentioning

confidence: 99%

PET-CT staging of DLBCL accurately identifies and provides new insight into the clinical significance of bone marrow involvement

Khan

Barrington

Mikhaeel

et al. 2013

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Clinicopathologic Characteristics and Outcome of Diffuse Large B-Cell Lymphomas Presenting With an Associated Low-Grade Component at Diagnosis

Abstract: Compared to de novo DLBCL, transformed NHL at diagnosis have similar overall survival but lower complete response to initial treatment and higher risk of indolent relapses.

Cited by 62 publications

References 32 publications

The NOTCH pathway is recurrently mutated in diffuse large B-cell lymphoma associated with hepatitis C virus infection

The NOTCH pathway is recurrently mutated in diffuse large B-cell lymphoma associated with hepatitis C virus infection

Clinicopathological prognostic indicators in 107 patients with diffuse large B‐cell lymphoma transformed from follicular lymphoma

PET-CT staging of DLBCL accurately identifies and provides new insight into the clinical significance of bone marrow involvement

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