Jerzy Lasota

Molecular pathological analysis of testicular diffuse large cell lymphomas.

The molecular pathology of 20 lymphomas, which presented as testicular masses in patients with no evidence of previous lymphoma, was analyzed. These lymphomas occurred in men with a median age of 69 years (range, 37 to 87 years). Nine of the 14 patients with follow-up died of lymphoma (median survival, 12 months). All cases were diffuse large B-cell lymphomas that were positive for CD20 and commonly showed plasmacytoid differentiation (10 of 20 cases). Three cases were Burkitts-like large cell lymphomas. Infiltration by lymphoma in the seminiferous tubules was seen in most cases. All lymphomas were negative for human herpesvirus 8 and Epstein-Barr virus by 35 cycles of polymerase chain reaction (PCR), suggesting that these viruses are not involved in the pathogenesis of primary testicular diffuse large B-cell lymphomas (DLBCL). PCR-based studies for t(14;18) and t(11;14) translocations, commonly seen in follicular and mantle-cell lymphomas, were negative in all cases. Nucleotide sequences of the V-D- and J segments of the immunoglobulin heavy chain gene (IgH) rearrangements obtained in 12 cases after PCR amplification were analyzed and compared with known germlines. The frequency of VH-family use in testicular DLBCL was similar to that reported for normal peripheral blood lymphocytes and follicular lymphomas. This contrasts with the previously published findings of preferential use of the VH3- or VH4-family by nodal DLBCL. Comparison with the published germlines showed a low similarity index in most of the cases, suggesting the presence of extensive somatic mutations. Ongoing mutation, as indicated by intraclonal variation in IgH sequence, was observed in all sequenced cases, suggesting direct antigen stimulation, which represents another difference between primary testicular and nodal DLBCL. Our results suggest that testicular lymphomas represent a subset of DLBCL that differs from their nodal counterparts in several respects. Their histological and molecular features show some similarities to those seen in marginal zone (MALT) lymphomas.

Protocol for the examination of specimens from patients with gastrointestinal stromal tumor.

The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical specimen examinations. The College regards the reporting elements in the “Surgical Pathology Cancer Case Summary (Checklist)” portion of the protocols as essential elements of the pathology report. However, the manner in which these elements are reported is at the discretion of each specific pathologist, taking into account clinician preferences, institutional policies, and individual practice. The College developed these protocols as an educational tool to assist pathologists in the useful reporting of relevant information. It did not issue the protocols for use in litigation, reimbursement, or other contexts. Nevertheless, the College recognizes that the protocols might be used by hospitals, attorneys, payers, and others. Indeed, effective January 1, 2004, the Commission on Cancer of the American College of Surgeons mandated the use of the checklist elements of the protocols as part of its Cancer Program Standards for Approved Cancer Programs. Therefore, it becomes even more important for pathologists to familiarize themselves with these documents. At the same time, the College cautions that use of the protocols other than for their intended educational purpose may involve additional considerations that are beyond the scope of these documents.

Recurrent anaplastic ependymoma with an abnormal karyotype and c-myc proto-oncogene overexpression

Cytogenetic analysis on a supratentorial, recurrent, anaplastic ependymoma from a 29-year-old female disclosed the presence of an abnormal clone with the karyotype 46,XX,der(8)t(8;11)(q24;p11),−11,add(?)t(?;11) (?;q13). By the Northern hybridization assay and immunohistochemical staining, tumor cells revealed overexpression of c-myc proto-oncogene, although no evidence of amplification or structural rearrangement of this gene was found.

Chromosomal localization of four human zinc finger cDNAs

AbstractcDNA clones encoding zinc finger motifs were isolated by screening human placenta and T-cell (Peer) cDNA libraries with zinc finger (ZNF) consensus sequences. Unique cDNA clones were mapped in the human genome by rodent-human somatic cell hybrid analysis and in some cases in situ chromosomal hybridization. ZNF 80 mapped to 3p12-3qter, ZNF 7 was previously mapped to 8q24 and is here shown by in situ hybridization and use of appropriate hybrids to map telomeric to the MYC locus. ZNF 79 mapped to 9q34 centromeric to the ABL gene and between a constitutional chromosomal translocation on the centromeric side and the CML specific ABL translocation on the telomeric side. ZNF77 mapped to 19p while ZNF 78L1 (pT3) mapped to 19q. Chromosome 19 carries many ZNF loci and other genes with zinc finger encoding motifs; the pT3 clone additionally detected a locus designated ZNF 78L2, which mapped to chromosome region 1p, most likely in the region 1p32 where the MYCL and JUN loci map.

Histopathological and genotypic characterization of metastatic colorectal carcinoma with PD‐L1 (CD274)‐expression. Possible roles of tumour micro environmental factors for CD274 expression

Aberrant PD‐L1 (CD274) expression has been described in different types of tumour and linked to tumour aggressiveness and a poor prognosis. In primary colorectal carcinomas (CRCs), CD274 expression was reported to be associated with mismatch repair (MMR)‐deficiency, BRAF mutation, and “stem‐like” immunophenotype defined by down‐regulation of homeobox protein CDX2 and membranous expression of activated leukocyte cell adhesion molecule (ALCAM). However, the immunophenotype and genotype of CD274‐positive metastatic CRC have not been extensively analysed. In this study, 189 CRC metastases were evaluated immunohistochemically for CD274, MMR proteins, CDX2, and ALCAM expression. Immunostaining for CD4, CD8, and FOXP3 was also performed to characterize tumour‐associated immune cells. In addition, 34 arbitrarily selected lesions were genotyped using Sanger‐ and next‐generation sequencing. Univariate analyses showed no clear association between CD274 expression and clinicopathological parameters including MMR‐deficiency or “stem‐like” immunophenotype after adjustment for multiple testing. Comparison of the clinicopathological profiles of CD274‐positive primary and metastatic tumours revealed in the latter younger age of occurrence (60.9 ± 13.3 versus 72.6 ± 13.1 years, p = 0.001), cytoplasm‐dominant CD274 expression (p < 0.001), infrequent MMR‐deficiency (p < 0.001), and common KRAS mutations (54%, p < 0.001). In five cultured colon cancer cell lines, CD274 was expressed and modulated after exogenous exposure to IFNγ and TGF‐β1. Thus, CD274 regulation mechanisms might include tumour micro environmental factors. Based on significantly different characteristics in CD274‐positive metastatic and primary CRCs, evaluation of metastases should also be considered when planning immune checkpoint inhibitor therapy.

Translocation 11;14 in newly diagnosed chronic myelogenous leukemia.

In patients with chronic myelogenous leukemia (CML), the Philadelphia chromosome may be associated with a number of other cytogenetic lesions. However, t(11;14)(q13;q32), found mainly in B-cell lymphoproliferative disorders, has not been previously reported in Ph-positive CML. We describe a patient with hematologically typical chronic phase CML in whom both cytogenetic lesions were found at diagnosis.