Thymidylate synthase (TS) catalyses the conversion of deoxy-uridylate to deoxy-thymidylate and is essential for DNA synthesis. The human TS gene promoter is polymorphic, having either double or triple tandem repeats of a 28-bp sequence. Here we determined the significance of this polymorphism in humans and its prediction for clinical outcome of patients with metastatic colorectal cancer treated with 5-fluorouracil. The TS mRNA level was analyzed using RT-PCR. Individuals homozygous for the triple repeat variant (L/L) had 3.6 times higher TS mRNA levels compared to those homozygous for the double repeat variant (S/S) in tumor tissue (P = 0.004). We tested 50 patients with disseminated colorectal cancer who received 5-FU treatment to determine whether this TS polymorphism will predict clinical outcome. We found individuals with S/S genotype had a response rate of 50% (4/

Human herpesvirus-8 (HHV8)-positive effusion-based lymphomas have been termed primary effusion lymphoma (PEL) in the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Kaposi sarcoma herpesvirus (KSHV)/ HHV8-negative effusion-based lymphomas (KSHV/HHV8-negative EBLs) resembling PELs have been reported in the literature and in many cases have been (mis)classified as PEL-like lymphomas. Herein, we present a series of cases and a review of KSHV/HHV8-negative EBLs. This lymphoma, although cytomorphologically resembling PEL, is a distinct entity with characteristic clinical and pathologic features. Patients are older, generally human immunodeficiency virus negative and not immunosuppressed, frequently hepatitis C positive compared with the population baseline, and often have an underlying medical condition leading to fluid overload. The lymphoma cells express pan-B-cell antigens in 86.7%, and CD20 is expressed in 71.1% of the cases. The lymphoma is often of germinal center B or mixed germinal center B/activated B-cell signature with the Hans classifier, and Epstein-Barr virus is positive in nearly 30% of cases. Rare T-cell lymphomas were also reported. Clinical outcomes and response to therapy, including isolated aspiration, are relatively favorable compared with cases of PEL. We suggest that HHV8-negative effusion-based lymphoma is a distinct entity associated with fluid overload states.

Follicular dendritic cell sarcoma is an uncommon neoplastic proliferation of spindled to ovoid cells with morphologic and immunophenotypic features similar to normal follicular dendritic cells. While most follicular dendritic cell sarcomas arise from lymph nodes, at least one-third occur in extranodal sites. A broad differential diagnosis can be developed--as this tumor has morphologic features similar to other tumors, hence creating a diagnostic pitfall--but its immunophenotypic profile is quite specific and is diagnostically crucial. Herein, we review the pathogenesis; histologic morphology; and immunohistochemical, electron microscopy, and clinical features, including treatment and prognosis, of follicular dendritic cell sarcomas. We will briefly describe the role of molecular studies including utility of BRAF mutations in diagnosing this tumor.

The majority of patients with systemic mastocytosis with associated clonal, hematological non-mast cell lineage disease (SM-AHNMD) have a myeloid stem cell malignancy including myelodysplastic syndromes (MDS), myelodysplastic/myeloproliferative disorders, acute myeloid leukemia (AML), or chronic myeloproliferative disease. The clinicopathologic features of SM-AHNMD have not been fully characterized. We describe seven cases of this entity: 3 with MDS, 3 with AML, and 1 with chronic myelomonocytic leukemia. In the majority of cases, SM was diagnosed concurrently with the myeloid malignancy and aberrant mast cell morphology was observed. The commonly described c-kit enzymatic site mutation Asp816Val was detected only in 2 cases, while 3 patients carried the Asp816His mutation. Among the 3 cases with AML, 2 patients carried the translocation t(8;21). On the basis of our results and other reported cases, there appears to be a specific association between SM and AML with t(8;21). Concurrent occurrence of SM may define a subset of patients with de novo AML and other myeloid malignancies who have an adverse prognosis. As clinically effective tyrosine kinase inhibitors that inhibit enzymatic-type c-kit mutations are being developed, detection of mast cell proliferation associated with myeloid malignancy may have important therapeutic implications. Am. J. Hematol. 73:12-17, 2003.