Roles of trk family neurotrophin receptors in medullary thyroid carcinoma development and progression.

Although initiating mutations in the ret protooncogene have been found in familial and sporadic medullary thyroid carcinoma (MTC), the molecular events underlying subsequent tumor progression stages are unknown. We now report that changes in trk family neurotrophin receptor expression appear to be involved in both preneoplastic thyroid C cell hyperplasia and later tumor progression. Only a subset of normal C cells expresses trk family receptors, but, in C cell hyperplasia, the affected cells consistently express trkB, with variable expression of trkA and trkC. In later stages of gross MTC tumors, trkB expression was substantially reduced, while trkC expression was increased and often intense. In a cell culture model of MTC, exogenous trkB expression resulted in severely impaired tumorigenicity and was associated with 11-fold lower levels of the angiogenesis factor vascular endothelial growth factor. These results suggest that trk family receptor genes participate in MTC development and progression, and, in particular, that trkB may limit MTC tumor growth by inhibition of angiogenesis.

Epstein-Bar virus and progression of non-Hodgkin's lymphoma to Ki-1-positive, anaplastic large cell phenotype.

Epstein-Barr virus (EBV) has been implicated in the pathogenesis of a variety of lymphoproliferative disorders (LPDs) including endemic Burkitt's lymphoma, Hodgkin's disease (HD), HIV-associated non-Hodgkin's lymphomas (NHLs), and LPDs arising in immunosuppressed transplant patients. More recently, EBV has been associated with Ki-1-positive anaplastic large cell lymphoma (ALCL), a recently described NHL that shares with HD expression of the CD30 antigen Ki-1. Because EBV has been shown to induce Ki-1 expression in vitro, and ALCL has been diagnosed in patients with prior or concurrent HD or NHL, it has been proposed that EBV may mediate progression of a "primary" lymphoma to a "secondary" ALCL. We report a case in which an AIDS-associated, Ki-1-negative, large-cell immunoblastic lymphoma progressed to a Ki-1 positive ALCL. Analysis of the immunoglobulin heavy chain locus revealed a clonal relationship between these morphologically and immunophenotypically distinct tumors. Although EBV was absent from the original large-cell immunoblastic lymphoma as assessed by in situ hybridization for EBV-encoded small RNA1 (EBER1), polymerase chain reaction for EBNA-1, immunocytochemistry for latent membrane protein 1, and Southern blot hybridization for EBV terminal repeat sequences, all for techniques confirmed the presence of EBV in the secondary ALCL. Moreover, analysis of EBV terminal repeat sequences indicated that the ALCL resulted from expansion of a single EBV-infected clone. These data suggest that EBV may mediate progression of NHL to Ki-1-positive ALCL, and that in some instances, EBV may be involved in the later stages of clonal progression of NHL.

Is submission of remaining tissue necessary when incidental carcinoma of the prostate is found on transurethral resection?

We examined 151 entirely submitted transurethral resection of the prostate (TURP) specimens that showed incidental prostate cancer. Fifty-one (34%) showed > 15% involvement of the specimen by tumor; these were not reviewed because submission of more tissue would not convert these cases from stage T1b (> or = 5% of tumor) to stage T1a ( < 5% of tumor). Sixty-six cases (44%) that were totally submitted in < or = nine cassettes also were excluded because most laboratories would totally submit these specimens from the outset. The remaining 34 cases (22%) had < or = 15% tumor and required 10 or more cassettes for total submission. The first eight slides were reviewed and percentage of tumor involvement and grade was calculated. The remaining slides were then reviewed to see if the overall tumor percentage or grade changed. Because in one case the tumor grade was significantly increased in the remaining slides and of the infrequency with which more than eight cassettes needs to be submitted, we recommended submission of all remaining tissue in stage T1a lesions. There is no need to submit additional tissue in stage T1b lesions because the percentage will not decrease with greater sampling.