The spectrum of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma: a description of 10 cases.

B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, is a diagnostic provisional category in the World Health Organization (WHO) 2008 classification of lymphomas. This category was designed as a measure to accommodate borderline cases that cannot be reliably classified into a single distinct disease entity after all available morphological, immunophenotypical and molecular studies have been performed. Typically, these cases share features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, or include characteristics of both lymphomas. The rarity of such cases poses a tremendous challenge to both pathologists and oncologists because its differential diagnosis has direct implications for management strategies. In this study, we present 10 cases of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma and have organized the criteria described by the WHO into four patterns along with detailed clinical, morphological and immunophenotypic characterization and outcome data. Our findings show a male preponderance, median age of 37 years and a mediastinal presentation in 80% of cases. All cases expressed at least two markers associated with B-cell lineage and good response to combination chemotherapy currently employed for non-Hodgkin lymphomas.

Prognostic impact of MUM1 expression by immunohistochemistry on primary mediastinal large B-cell lymphoma.

Diffuse large B-cell lymphoma can be classified into two prognostically distinct subgroups with germinal center B-cell-like (CG) and activated B-cell-like (post-CG) characteristics, based on CD10, BCL-6, and MUM1 expression. We performed a retrospective analysis of the clinical variables of 37 patients with primary mediastinal large B-cell lymphoma and the expression of BCL-6 and MUM1 in 22 patients with available tissue. The median age was 30 years, and 70% of the patients were female. BCL-6 and MUM1 were expressed in 64% and 45% of cases, respectively. Five-year overall survival (OS) and disease-free survival (DFS) were 47% and 81%, respectively. In univariate analysis, complete response (p = 0.0001), radiation therapy (p = 0.01), International Prognostic Index (p = 0.001), and MUM1 expression (p = 0.002) correlated with OS. For this group of patients with homogeneous clinical characteristics, response to initial chemotherapy and MUM1 expression were associated with prognosis.

Cell cycle characteristics and Epstein-Barr virus are differentially associated with aggressive and non-aggressive subsets of Hodgkin lymphoma in pediatric patients.

We investigated the correlation of tumor characteristics with clinico-biological markers of aggressive disease, evaluated by Ann Arbor stage, risk group, B-symptoms, number of involved anatomic areas, mediastinal mass, nodular sclerosis (NS) grade, and risk, in pediatric Hodgkin lymphoma (HL). Leukopenia and extranodal disease influenced event-free survival (p = 0.032 and p = 0.041). In multivariate analysis, extranodal disease was associated with high number of tumor-infiltrating eosinophils (p = 0.035) and Ki67 < 50% (p = 0.024); B-symptoms with Ki67 > or =75% (p = 0.027) and high LDH levels (p = 0.001); and mediastinal mass with leukopenia (p = 0.048), NS grade II (p = 0.025), and high-risk (p = 0.046). Furthermore, low stages correlated with Ki67 > or =50% (p = 0.005) and Epstein-Barr virus (EBV) (p = 0.065). Low-risk NS was associated with EBV (p = 0.014). Hierarchical cluster analysis identified two clusters, one composed of high-risk patients and cell cycle and apoptosis features, and the other including low-risk patients, EBV, and low-risk NS. Our results show the association of biological markers with disease aggressiveness in pediatric HL.

T-cell leukemia 1 expression in nodal Epstein-Barr virus-negative diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma.

The physiologic expression of the product of the proto-oncogene TCL1 (T-cell leukemia 1) is primarily restricted to early embryonic cells. In nonneoplastic B cells, the expression of TCL1 is determined by the differentiation step with silencing at the germinal center stage. TCL1 protein is overexpressed in a wide variety of human diseases. It has been shown that TCL1 is a powerful B-cell oncogene, which has been implicated in the pathogenesis of various types of mature B-cell lymphomas. There is no comparative information in the literature addressing the expression of TCL1 in pediatric and adult nodal diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma. We studied 55 cases of adult and pediatric diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma to analyze the phenotypic profile of these lymphomas, including TCL1 expression, and its relationship with clinical outcome in different age groups. The cases were analyzed by immunohistochemistry for the expression of TCL1, CD10, BCL-2, BCL-6, and MUM1. We also evaluated c-MYC translocation by fluorescence in situ hybridization. TCL1 was observed in 11 cases, 5 pediatric and 6 adult cases, all but one diffuse large B-cell lymphoma. Pediatric cases showed a significant association between TCL1 expression, high proliferative index, and presence of c-MYC translocation. TCL1 positivity was predominantly found in germinal center phenotype diffuse large B-cell lymphoma. Overall survival was worse in adult TCL1-positive cases than pediatric ones. Primary mediastinal large B-cell lymphomas infrequently expressed TCL1 in both age groups.

Myxopapillary ependymoma of the posterior mediastinum.

A left paravertebral mass discovered incidentally on routine examination in a 39-year-old woman is described. Computerized tomography studies revealed a 7 x 6 cm, well circumscribed, noncalcified soft tissue mass with lobular borders abutting the left inferior pulmonary vein and descending aorta. It was not possible to determine the exact anatomic location of the mass based on the imaging studies as both peripheral lung tumors and posterior mediastinal lesions may exhibit the imaging findings described here. At thoracotomy, the mass was seen to be well circumscribed, focally attached to the pleura but without involvement of lung parenchyma, and situated in the left posterior mediastinum. On histological examination, the lesion showed the classical features of myxopapillary ependymoma. Immunohistochemical studies confirmed this impression by demonstrating strong positivity of the tumor cells for S-100 protein, glial fibrillary acidic protein, and CD99 and negative staining with other differentiation markers. A review of the literature with a discussion of the histologic and radiologic differential diagnosis of these lesions is presented.

Unusual cases of hyperparathyroidism.

The history, physical and radiologic findings, treatment and pathology in five unusual cases of hyperparathyroidism is presented. The hyperparathyroidism was caused by a large (113 grams) mediastinal adenoma in the first patient, who is alive 25 years after surgery. A parathyroid carcinoma with compression of the esophagus was documented in the second patient. This patient is alive and normocalcemic 23 years after surgical treatment. A third patient with hyperplasia returned with hypercalcemia 20 years postsurgery requiring reoperation. A fourth patient with advanced bone findings was found to have a parathyroid adenoma. The fifth case is a patient with tertiary hyperparathyroidism secondary to hypophosphatemic rickets.

Unusual cases of hyperparathyroidism

The history, physical and radiologic findings, treatment and pathology in five unusual cases of hyperparathyroidism is presented. The hyperparathyroidism was caused by a large (113 grams) mediastinal adenoma in the first patient, who is alive 25 years after surgery. A parathyroid carcinoma with compression of the esophagus was documented in the second patient. This patient is alive and normocalcemic 23 years after surgical treatment. A third patient with hyperplasia returned with hypercalcemia 20 years postsurgery requiring reoperation. A fourth patient with advanced bone findings was found to have a parathyroid adenoma. The fifth case is a patient with tertiary hyperparathyroidism secondary to hypophosphatemic rickets