Summary Approximately 30% of patients with follicular lymphoma (FL) transform to a more aggressive malignancy, most commonly diffuse large B cell lymphoma. Rarely, FL transformation results in ...clinical findings, histology, and immunophenotype reminiscent of B-lymphoblastic leukemia/lymphoma. We report the largest series to date with detailed analysis of 7 such patients. Lymphoblastic transformation occurred on average 2 years after initial diagnosis of FL. Five patients had prior intensive chemotherapy. Two patients developed mature high-grade lymphoma, followed by the lymphoblastic transformation. FL had BCL2 gene rearrangement in 4 of 5 cases. High-grade transformation was accompanied by MYC gene rearrangement (5 of 5). Transformation was characterized by expression of TdT, loss of Bcl6, variable loss of immunoglobulin light chain, and persistence of Pax-5, Bcl2, and CD10. Whole-exome sequencing in 1 case revealed presence of several actionable mutations ( CD79B , CCND3 , CDK12 ). FL, aggressive mature B cell lymphoma, and lymphoblastic transformation were clonally related in 6 evaluable cases. After transformation, survival ranged from 1 to 14 months. Four patients died of disease, 2 were in remission after stem cell transplant, and 1 was alive with disease.
Mammary myofibroblastoma is a benign spindle cell tumor that can show variable morphologic patterns and lines of differentiation. Myofibroblastoma belongs to a family of CD34-positive tumors with ...similar morphology that show a deletion of 13q14, which includes RB1 and FOXO1A genes. A subset of these tumors demonstrates distinct smooth muscle differentiation which can be confused with other smooth muscle tumors of the breast, itself constituting a rarified morphological subgroup. We aimed to characterize 4 cases of the leiomyomatous variant of myofibroblastoma arising in the breast by clinicopathological, immunohistochemical, and molecular means. All 4 examples arose in women aged 41–62 years (median, 46.5 years). Tumors ranged in size from 1.7 to 2.5 cm (median, 2.2 cm). Morphologically, all tumors were characterized by bundles of smooth muscle cells with elongated cigar-shaped nuclei and eosinophilic cytoplasm. All four tumors showed diffuse positive staining with desmin, caldesmon, smooth muscle actin (SMA), estrogen receptor (ER), and Bcl-2. CD34 staining was diffusely positive in two cases, weak and patchy in one case, and was negative in one case. Two of four (50%) tumors showed deletion of RB1 by fluorescence in situ hybridization (FISH). Loss of Rb staining was seen in one tumor with RB1 deletion by FISH, while intact Rb staining was observed in one non-deleted case studied. In conclusion, this rare variant of myofibroblastoma is a distinct subgroup of tumors among an already uncommon category of (smooth muscle) breast tumors. Some reported examples of “parenchymal leiomyoma” may represent the leiomyomatous variant of myofibroblastoma.
Summary The current World Health Organization classification considers myelodysplastic syndrome with isolated del(5q) a distinct entity owing to its characteristic clinical and pathologic features. ...Recently, several studies have examined survival, leukemic transformation, and various prognostic factors in these patients. However, there is a lack of detailed comparative pathologic analysis of myelodysplastic syndrome cases in which del(5q) is present in association with additional cytogenetic abnormalities. We studied 26 cases of myelodysplastic syndrome at initial diagnosis with 5q − alone, 5q − plus 1 additional abnormality, and 5q − as part of a complex karyotype. Four of 17 patients had evidence of JAK2 V617F mutation. In contrast to cases of myelodysplastic syndrome with isolated 5q−, patients with additional abnormalities had normal mean corpuscular volume and decreased platelet counts ( P < .001). Based on bone marrow examination, they were significantly more likely to have increased cellularity, trilineage dysplasia, lower proportion of small hypolobated megakaryocytes, higher number of blasts, and fibrosis. The presence of these morphologic features can be used to distinguish these more aggressive cases from those with myelodysplastic syndrome with isolated 5q − and a more benign clinical course.
Summary Cytogenetic abnormalities in B-cell posttransplant lymphoproliferative disorders (PTLD) have not been well characterized. We thus performed cytogenetic analysis of 28 cases of B-cell PTLD, 1 ...infectious mononucleosis (IM)–like lesion, 9 polymorphic PTLD, 17 monomorphic PTLD, and 1 classical Hodgkin lymphoma (HL), and correlated the karyotypic findings with the phenotype, Epstein-Barr virus infection status, and clinical outcome. Karyotypes of 19 cases of posttransplant florid follicular hyperplasia (FFH) were also analyzed. Informative karyotypes were obtained in 20 (71.4%) of 28 PTLDs and 18 (94.7%) of 19 FFHs. Clonal karyotypic abnormalities were detected in 13 (65%) of 20 PTLDs, including 9 (75%) of 12 monomorphic PTLDs, 2 (33.3%) of 6 polymorphic PTLDs, 1 IM-like lesion, and 1 HL, and 2 (11.1%) of 18 FFHs. Recurrent chromosome breaks at 1q11-21 (n = 6, including 1 FFH), 14q32 (n = 3, including 1 FFH), 16p13 (n = 3), 11q23-24 (n = 2), and 8q24 ( c-MYC ) (n = 2); gains of chromosome 7 (n = 4), X (n = 3), 2 (n = 3), 12 (n = 2); and loss of chromosome 22 (n = 2, including 1 IM-like lesion) were identified. The presence of cytogenetic abnormalities did not correlate with PTLD phenotype, Epstein-Barr virus infection, or clinical outcome. We describe novel karyotypic aberrations in PTLD and report clonal cytogenetic abnormalities in posttransplant FFH and an IM-like lesion for the first time. Our findings provide validation of the current World Health Organization classification of PTLD and also suggest incorporation of FFH as the earliest recognizable precursor of PTLD.
PDF