Ágnes Lacza

Pulmonary enteric adenocarcinoma indistinguishable morphologically and immunohistologically from metastatic colorectal carcinoma

Adenocarcinoma is the most common and heterogeneous type of lung cancer. Pulmonary enteric adenocarcinoma (PEAC) is a recently described, extremely rare primary pulmonary adenocarcinoma variant, which has a histological morphology and immunohistochemical phenotype similar to metastatic colorectal carcinoma (MCC). It was described originally in 1991 by Tsao et al. as a primary pulmonary adenocarcinoma with enteric differentiation. In 2005, Inamura et al. reported a series of seven cases, and in 2008 Meada et al. described a case as pulmonary intestinal-type adenocarcinoma. Currently, there have only been 17 reported cases. PEAC was classified as a rare variant of invasive adenocarcinoma by the International Association for the Study of Lung Cancer/American Thoracic Respiratory Society in 2011. Here we describe a PEAC that developed in the postoperative scar of a 65-year-old male with a history of segmental resection and adjuvant radiotherapy for squamous cell carcinoma (SCC). Together, retrospective comparative analysis of tumour samples from the first and second surgical interventions and the autopsy findings suggest that the subsequent adenocarcinoma was PEAC rather than metastatic adenocarcinoma. The tumour was indistinguishable from MCC by histology, immunohistochemistry and EGFR/K-RAS mutation analysis.

Pheno- and Genotypic Features of Epstein-Barr Virus Associated B-Cell Lymphoproliferations in Peripheral T-Cell Lymphomas

Among the 300 peripheral T-cell lymphomas (PTCL) searched for EBV positive non-resting B-cells by EBER in situ hybridization 12 have been identified with various forms of EBV-driven B-cell proliferation. This could be categorized into three major forms. i. In the first form scattered immature, mononuclear B-cells of immuno-, centroblastic type with CD20+. CD30+ CD45+, LMP1+ phenotype, reactive appearance and polyclonal immunoglobulin heavy chains gene rearrangement (IgH-R) were admixed to the PTCL cells. ii. The second form mimicked diffuse large B-cell lymphoma as homogenous sheets, largely demarcated from the PTCL, of mononuclear, immature B-cell of CD20+, CD30+, CD45+, LMP1+, EBNA-2+ phenotype but with lack of monoclonal IgH-R were present. iii. In the third form scattered Hodgkin-Reed-Sternberg (HRS) type of cells were noticed which exhibited the CD15+/−, CD20−/+, CD30+, CD45−, LMP1+, EBNA-2- phenotype and in 50% showed clonal IgH gene rearrangement in whole tissue DNA extract. The IgH associated transcription factors’ (OCT2, BOB.1/OBF.1, PU.1) expression patterns in these cells corresponded to those of HRS cells in cHL. Based on analysis of 65 PTCLs, we have identified in the positive cases a highly significant increase of EBV+ small, reactive, resting B-cell compartment (75.9 / 100 HPF in PTCL vs. 1.5 / 100 HPF in control lymph nodes) likely to be due to the decreased immune surveillance. This progressive accumulation of EBV+ by-stander B-cell population in PTCLs might be the source of various B-cell proliferations, which in any form represent major diagnostic pitfalls and require a careful differential diagnostic procedure.

Increased incidence of monoclonal B-cell infiltrate in chronic myeloproliferative disorders

A total of 106 trephine biopsy specimens with clinical, laboratory and pathology findings corresponding to chronic myeloproliferative disorders (CMPD) were analyzed to reveal the nature of the lymphoid infiltrate in the bone marrow. Histological investigation in 31 chronic myeloid leukemia (CML), 29 CMPDs not otherwise specified (CMPD-NOS), 28 essential thrombocytosis (ET), 15 polycythemia vera (PV) and three chronic eosinophilic leukemia/hypereosinophilic syndrome (CEL/HES) exhibited in 32% various amounts of lymphocytic infiltrate of sparsely to moderately diffuse or nodular types in the bone marrow, but the reactive or coinciding lymphomatous nature could not be revealed by histology alone in the majority of cases. PCR analysis of the immunoglobulin heavy chain (IgH) gene rearrangement was successfully performed in 81 out of the 106 DNA specimens extracted from formol–paraffin blocks. Out of the 81 samples with good-quality DNA, 18 gave a single or double discrete amplification band(s), which was reproducible only in four specimens. Sequencing finally proved monoclonal B-cell population of both pre- and postfollicular origin in all four samples (5%), one CML and three CMPD-NOS. Detailed clinical and pathological investigations indicated overt B-cell malignant lymphoma with clonal relationship to the CMPD in two out of these four patients. We conclude that detailed molecular analysis of IgH gene rearrangement in bone marrow samples of CMPD patients is needed to identify the true monoclonal B-cell infiltration, which—even without overt malignant lymphoma—may occur in this group of disorders.

Detection of early precursors of t(12;21) positive pediatric acute lymphoblastic leukemia during follow-up†

DNA‐, RNA‐, and cell‐based methods provide different biologic information for determining the presence of minimal residual disease (MRD). We monitored the responses of patients with pediatric acute lymphoblastic leukemia (pALL) using DNA markers, TEL/AML1 expression, and scanning fluorescence microscopy (SFM). Using SFM, 36% of patients exhibited 1.5–3.1 log and 2.9–4.2 log higher MRD levels compared with those based on DNA and RNA markers, respectively. CD10+ ancestor cells with germline antigen receptors, but silent TEL/AML1 expression, may reside in the lymphoid stem cell compartment of treated t(12;21)‐positive patients and might act as a potential source of cells for late relapses. Pediatr Blood Cancer 2010; 54:158–160.

Prognosztikai faktorok komplex vizsgálata krónikus lymphocytás leukémiában

INTRODUCTION Many new prognostic factors established in recent years in chronic lymphocytic leukemia. May help predicting survival. AIMS The goal of the present study was to determine the frequency and the correlation of these novel prognostic factors in samples of 419 leukemia patients. METHODS The mutation status of the IgH gene was evaluated in 160 cases. RESULTS In 62% of cases, non-mutated IgH gene was found, the heavy chain family usage was different in mutated and non-mutated cases. The CD38 expression demonstrated 78% concordance with the mutation status, the ZAP-70 expression failed to show any correlation. Cytogenetic abnormalities were seen in 76% of cases, the most frequent were del(13q) (57%), trisomy 12 (15%), del(11q) (12%) and del(17p) (6%). 95% of cases with del(11q) harbored non-mutated, 74% of cases with del(13q) as the sole anomaly demonstrated mutated IgH genes. CONCLUSIONS The parameters analysed are not independent of each other, utilization of them in the clinical routine needs careful planning.

Complex analysis of prognostic factors in chronic lymphocytic leukemia

INTRODUCTION Many new prognostic factors established in recent years in chronic lymphocytic leukemia. May help predicting survival. AIMS The goal of the present study was to determine the frequency and the correlation of these novel prognostic factors in samples of 419 leukemia patients. METHODS The mutation status of the IgH gene was evaluated in 160 cases. RESULTS In 62% of cases, non-mutated IgH gene was found, the heavy chain family usage was different in mutated and non-mutated cases. The CD38 expression demonstrated 78% concordance with the mutation status, the ZAP-70 expression failed to show any correlation. Cytogenetic abnormalities were seen in 76% of cases, the most frequent were del(13q) (57%), trisomy 12 (15%), del(11q) (12%) and del(17p) (6%). 95% of cases with del(11q) harbored non-mutated, 74% of cases with del(13q) as the sole anomaly demonstrated mutated IgH genes. CONCLUSIONS The parameters analysed are not independent of each other, utilization of them in the clinical routine needs careful planning.

Prognosztikai faktorok komplex vizsgálata krónikus lymphocytás leukémiában@@@Complex analysis of prognostic factors in chronic lymphocytic leukemia

INTRODUCTION Many new prognostic factors established in recent years in chronic lymphocytic leukemia. May help predicting survival. AIMS The goal of the present study was to determine the frequency and the correlation of these novel prognostic factors in samples of 419 leukemia patients. METHODS The mutation status of the IgH gene was evaluated in 160 cases. RESULTS In 62% of cases, non-mutated IgH gene was found, the heavy chain family usage was different in mutated and non-mutated cases. The CD38 expression demonstrated 78% concordance with the mutation status, the ZAP-70 expression failed to show any correlation. Cytogenetic abnormalities were seen in 76% of cases, the most frequent were del(13q) (57%), trisomy 12 (15%), del(11q) (12%) and del(17p) (6%). 95% of cases with del(11q) harbored non-mutated, 74% of cases with del(13q) as the sole anomaly demonstrated mutated IgH genes. CONCLUSIONS The parameters analysed are not independent of each other, utilization of them in the clinical routine needs careful planning.