Indolent mantle cell leukemia: a clinicopathological variant characterized by isolated lymphocytosis, interstitial bone marrow involvement, kappa light chain restriction, and good prognosis

Abstract

BackgroundCases of mantle cell lymphoma with indolent behavior have been reported, but are poorly identified by current clinical risk models. Early studies found peripheral blood involvement to be an adverse prognostic factor; however, cases of a seemingly indolent variant of mantle cell lymphoma, characterized by peripheral blood involvement and minimal nodal disease, have been incompletely described, particularly with regard to bone marrow findings. We report a series of leukemic phase mantle cell lymphomas with a non-progressive or slowly progressive course. Design and MethodsCases presenting with mantle cell lymphoma limited to the peripheral blood/bone marrow from 2000-2010 were identified. Diagnoses were established by morphology, flow cytometric analysis and requisite evidence of IGH-CCND1@ by fluorescence in-situ hybridization or t(11;14)(q13;q32) by cytogenetics. Patients with lymphadenopathy, splenomegaly and gastrointestinal symptomatology were excluded. ResultsPatients (n=8, median age 60.5 years) were asymptomatic with mild lymphocytosis (8.7¥10 9 /L; range, 4.5-14.2¥10 9 /L) and cytology typical of mantle cell lymphoma. Flow cytometric analysis showed that all expressed CD5, CD19, CD20, variable CD23, and a striking kappa immunoglobulin light chain restriction (7/8 cases). Bone marrow biopsy at diagnosis showed interstitial single or small lymphoid aggregates with similar patterns of CD20 and cyclin D1 immunostaining which were not readily discernable by hematoxylin and eosin stain. SOX11 was negative (4/5) or only weakly expressed (1/5). The median follow-up was 27 months (range, 5-109 months) and all patients, but one, are alive with no clinical evidence of disease. The prevalence of indolent mantle cell lymphoma presenting only with lymphocytosis, among all mantle cell lymphomas diagnosed during the same period, was 3%. ConclusionsLeukemic mantle cell lymphoma limited to blood and bone marrow is an indolent variant characterized by mild-moderate lymphocytosis, interstitial low-level bone marrow involvement, simple karyotype, kappa light chain expression, cyclin D1 expression with lack of SOX11, and slow or absent clinical progression. Some cases may represent a mantle cell lymphoma counterpart to chronic lymphocytic leukemia -phenotype monoclonal B-cell lymphocytosis. Recognition of this variant could inform treatment decisions and possibly avoid unnecessary treatment.

Plasma cell and terminal B-cell differentiation in mantle cell lymphoma mainly occur in the SOX11-negative subtype

“…[2][3][4][5][6] The potential implication of SOX11 in the aggressive behavior of mantle cell lymphoma was initially suggested when it was recognized as one of the genes highly expressed in tumors requiring treatment at diagnosis compared with cases with a very indolent clinical course. 7 The relationship between the absence of SOX11 expression and an indolent clinical behavior of these tumors has been confirmed in subsequent studies [8][9][10] but not in others. 11 However, most aggressive SOX11-negative mantle cell lymphoma carry also TP53 mutations and may, therefore, correspond to a transformed form of these tumors.…”

Validation of R‐MIPI and prognostic value of immunoglobulin light chain restriction in mantle cell lymphoma

“…The kappa group had an OS of 97 months (95% CI 51Á1-142Á8) and the lambda 25 months (95% CI 12Á5-37Á5) (Log Rank: P = 0Á045) (Fig 1). Surface light chain has not been previously studied as a prognostic factor, but is known that patients with indolent MCL have a predominance of kappa light chain restriction (Ondrejka et al, 2011); in fact 3 of the four patients with indolent disease in our study showed kappa LCR. When we excluded patients with indolent disease, the prognostic impact of LCR on OS remained (kappa: median 91 months, 95% CI 61Á62-120Á37; lambda: 20 months, 95% CI 7Á92-32Á07; Log Rank P = 0Á039).…”

Whole genome profiling and other high throughput technologies in lymphoid neoplasms—current contributions and future hopes

“…The use of this marker, together with other clinical (non-nodal presentation) and biological features (absence of genomic complexity and 17p/TP53 alterations), may be useful to recognize this particular subgroup of MCL. 51,52,71 Microarray studies in malignant lymphomas have provided new and robust prognostic information that improves the current prognostic indices mainly based on clinical criteria, such as the International Prognostic Index (IPI). Interestingly, the GEP-based prognostic models are different for each disease entity, suggesting that the behavior of each lymphoma is determined by different mechanisms.…”