BACKGROUND: B‐cell lymphoma, Unclassifiable with features intermediate between diffuse large B‐cell lymphoma (DLBCL) and Burkitt lymphoma, for convenience referred to here as unclassifiable B‐cell lymphoma, is a category in the 2008 World Health Organization system used for a group of histologically aggressive neoplasms that are difficult to classify definitively. Currently, there is no established standard therapy for these neoplasms.METHODS: The authors assessed MYC status and correlated it with treatment response and outcome in a group of 52 patients with unclassifiable B‐cell lymphoma treated with either a standard DLBCL regimen (R‐CHOP [rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone‐related therapy]) or more intensive regimens, such as R‐hyper‐CVAD (rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high‐dose methotrexate and cytarabine). The regimens were selected by the treating clinicians based on the overall clinical and pathological findings.RESULTS: Thirty (58%) unclassifiable B‐cell lymphomas had MYC abnormalities (MYC⁺) including 27 with rearrangement, 2 with amplification, and 1 with both. The MYC⁺ and MYC⁻ groups were similar in their age distribution and International Prognostic Index scores. Progression‐free survival of patients with MYC⁺ unclassifiable B‐cell lymphoma treated initially with R‐CHOP was significantly worse than patients treated with R‐hyper‐CVAD (P = .0358). In contrast, for the MYC⁻ unclassifiable B‐cell lymphoma group, some patients responded to R‐CHOP, and others were refractory to R‐hyper‐CVAD.CONCLUSIONS: MYC aberrations are common in unclassifiable B‐cell lymphoma. The presence of MYC aberrations identifies a patient subset that requires more aggressive therapy than R‐CHOP. In contrast, MYC⁻ unclassifiable B‐cell lymphoma patients responded variably to either R‐CHOP or aggressive therapy, and the latter showed no survival advantage. Cancer 2011;. © 2011 American Cancer Society.

Waldenstrom macroglobulinemia (WM) is a clinicopathologic syndrome in which a B-cell neoplasm involving the bone marrow, usually lymphoplasmacytic lymphoma (LPL), is associated with immunoglobulin M paraprotein in the serum. Extramedullary involvement occurs in a subset of patients and is infrequently examined histologically. The files of M.D. Anderson Cancer Center were searched for patients with WM who underwent biopsy of one or more extramedullary sites during the course of disease. Each biopsy specimen was classified using the criteria of the World Health Organization classification. The study group consisted of 44 patients (26 men and 18 women), with a total of 51 specimens obtained from lymph nodes (n = 36), soft tissue (n = 4), spleen (n = 3), skin (n = 2), lung (n = 2), tonsils (n = 1), colon (n = 1), liver (n = 1), and gallbladder (n = 1). Lymphoplasmacytic lymphoma was the most common histologic type, in 40 (78%) samples. This category was morphologically heterogeneous and was further subclassified as lymphoplasmacytic (n = 21), lymphoplasmacytoid (n = 18), and polymorphous (n = 1). Four of these LPL cases morphologically resembled marginal zone B-cell lymphoma. Four additional samples were involved by diffuse large B-cell lymphoma, probably transformed from LPL. Three more samples were involved by LPL with unusual features: two were CD5-positive and one was a composite tumor with classical Hodgkin's disease. Other categories of lymphoma in this group of patients with WM included small lymphocytic lymphoma/chronic lymphocytic leukemia (n = 2), mantle cell lymphoma (n = 1), and follicular lymphoma (n = 1). Waldenstrom macroglobulinemia is most commonly associated with LPL but can rarely occur with other types of B-cell lymphoma. Lymphoplasmacytic lymphoma in patients with WM is morphologically heterogeneous and can be indistinguishable from marginal zone B-cell lymphoma. CD5+ B-cell lymphomas with features otherwise typical of LPL are rare, and we think these tumors are part of the spectrum of LPL.

Acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2) is a rare type of leukemia recently added to the World Health Organization (WHO) classification scheme. In this study, we analyzed the clinicopathologic and cytogenetic features of 30 cases of de novo acute myeloid leukemia with inv(3)/t(3;3). The median patient age was 53 years (range, 27–77 years). The platelet count was variable (range, 21–597 × 10⁹/l, median: 128 × 10⁹/l), and two (6.7%) patients presented with thrombocytosis (>450 × 10⁹/l). Morphologically, these neoplasms showed a spectrum of findings. Myelomonocytic differentiation was most common in 11 (37%) cases. Morphological evidence of dysplasia was observed in at least one lineage in 23 of 25 (92%) cases in which maturing elements could be assessed. In all, 5 (17%) patients had isolated inv(3) or t(3;3) and 25 (83%) patients had additional cytogenetic abnormalities, most often monosomy 7 (40%). Eleven (37%) patients had a complex karyotype (≥3 additional abnormalities). FLT3 gene mutation by internal tandem duplication was identified in 2 of 23 (9%) cases assessed. No clinical, pathological, or cytogenetic features independent of inv(3) or t(3;3) correlated with a worse outcome. However, patients treated with allogeneic stem cell transplantation (n=11) had a significantly better survival than did those treated with chemotherapy alone (n=17) (13.8 vs 8.0 months, P=0.041). We conclude that de novo acute myeloid leukemia associated with inv(3)/t(3;3) is an aggressive type of leukemia regardless of morphological or karyotypic findings, supporting the inclusion of this disease as a specific entity defined by inv(3)/t(3;3) in the WHO classification. Allogeneic stem cell transplantation seems to improve outcome in patients with this disease.