Absence of cyclin D1 protein expression in splenic marginal zone lymphoma.

Splenic marginal zone lymphoma (SMZL) is a recently recognized primary splenic lymphoma. SMZL can be associated with peripheral lymphocytosis, in which some cells have a villous morphology (splenic lymphoma with villous lymphocytes [SLVL]). Several recent studies suggested involvement of the bcl-1 locus and/or the cyclin D1 gene, located on chromosome 11q, in SMZL/SLVL. Translocation t (11;14) is associated with rearrangement of the bcl-1 locus and overexpression of the cyclin D1 gene. Both the translocation and cyclin D1 protein expression are characteristic of mantle cell lymphoma (MCL) and are rare in other lymphoid neoplasms; thus, their detection is useful in the diagnosis of MCL. Because the differential diagnosis of low-grade lymphoma in the spleen can be difficult, it is important to assess the frequency of cyclin D1 expression in SMZL to determine its usefulness in differential diagnosis from MCL. We analyzed the expression of cyclin D1 nuclear protein in paraffin sections using an immunoperoxidase technique in 17 cases diagnosed as SMZL. In eight cases, the presence of cyclin D1 mRNA was also assessed by Northern blot analysis. None of the 17 cases of typical SMZL showed expression of cyclin D1 mRNA or protein. In contrast, four cases used as controls showed either expression of cyclin D1 protein or mRNA or both. We conclude that assessment of cyclin D1 protein expression can be useful in distinguishing SMZL from MCL involving the spleen.

Sertoli cell tumors of the testis, not otherwise specified: a clinicopathologic analysis of 60 cases.

Sixty Sertoli cell tumors of the testis, excluding large cell calcifying and sclerosing subtypes, are described. Patient age ranged from 15 to 80 years (mean, 45 years). The initial manifestation was usually a testicular mass; in 14 cases it had been enlarging slowly for a period of up to 14 years (mean 3.7 years). Only five patients had testicular pain. Four patients had metastatic disease at the time of presentation. All the tumors were unilateral and ranged from 0.3 cm to 15 cm (mean 3.6 cm). They were typically well circumscribed. Sectioning usually disclosed firm, tan-gray, white, or yellow tissue with areas of hemorrhage and a minor cystic component in approximately one third. Microscopic evaluation usually revealed diffuse sheets or large, nodular aggregates of tumor cells, within which solid or hollow, sometimes dilated, tubules and, less often, cords were usually at least focally identifiable. A relatively acellular, often vascular, fibrous to hyalinized stroma was frequently conspicuous. The tumor cells typically had moderate amounts of pale to lightly eosinophilic cytoplasm, but 10 tumors had cells with abundant eosinophilic cytoplasm. Large cytoplasmic vacuoles were prominent in 26 tumors. Nuclear atypicality was absent or mild in 54 cases, moderate in 4 cases, and marked in 2 cases. Mitotic rate ranged from less than 1 to 21 per 10 high power fields, with 50 tumors having no or only rare mitoses. Vascular space invasion was present in 11 cases and was prominent in 8. Follow-up of more than five years (average 8.4 years), or until evidence of metastasis was seen, was available for 16 patients. Nine were alive and well with no evidence of disease. Four were alive with disease and three died of disease. The pathologic features that best correlated with a clinically malignant course were as follows: a tumor diameter of 5.0 cm or greater, necrosis, moderate to severe nuclear atypia, vascular invasion and a mitotic rate of more than 5 mitoses per 10 high power fields. Only one of nine benign tumors for which follow-up data of 5 years or more were available had more than one of these features, whereas five of seven malignant tumors had at least three.

Stage IB and IIA cervical cancer with negative lymph nodes: the role of adjuvant radiotherapy after radical hysterectomy.

The records of 171 patients with lymph node-negative stage IB and IIA cervical cancer primarily treated with radical hysterectomy and pelvic lymphadenectomy from 1974 to 1992 were retrospectively reviewed to identify poor prognostic factors and evaluate the role of adjuvant pelvic radiotherapy. One hundred sixteen patients (68%) were treated with radical hysterectomy alone (RH) and 55 patients (32%) received adjuvant radiotherapy (RH + RT). Factors predictive of recurrence for the entire group of patients included lymph-vascular space invasion (LVSI) (P = 0.003) and grade 3 histology (P = 0.04). Patients receiving RH + RT were older and more likely to have outer third cervical wall invasion, LVSI, positive margins, > or =2 cm pathologic tumor size, and >4 cm clinical tumor size (all P < 0.05). Overall, 28 patients (16%) developed recurrent disease with no difference between RH and RH + RT groups. After controlling for confounding variables, patients with LVSI who received RH + RT were less likely to develop disease recurrence than patients receiving RH alone (P = 0.04). LVSI is an important prognostic variable in lymph node-negative stage IB and IIA cervical cancer. Although adjuvant pelvic radiotherapy may decrease the risk of recurrence in patients with LVSI, the majority of patients with negative lymph nodes may be treated with radical surgery alone.

Characterization of a xenograft model of human ovarian carcinoma which produces intraperitoneal carcinomatosis and metastases in mice.

A new xenograft model for human epithelial ovarian carcinoma, with extensive intraperitoneal (i.p.) carcinomatosis as the predominant disease manifestation, is described. Cells from the established NIH:OVCAR-5 cell line were injected i.p. into 6- to 8-week-old Swiss nude mice. Comparative analyses between cells cultured in vitro and tumor cells derived ex vivo were performed to assess histologic features, immunohistochemical cell markers, hormonal receptor expression, adhesion to extracellular matrix molecules and chromosomal constitution. Macroscopically, the extent of tumor development appeared to be site-dependent and tumor cell survival was dose-dependent. Advanced disease was characterized by extensive solid tumor burden and ascites with parenchymal invasion, lymphatic metastases and vascular dissemination. Individual tumor nodules exhibited developing neovasculature characterized by the absence of mature basement membrane. Despite some histologic loss of cellular differentiation in advanced disease, antigenic expression was preserved, distinguishing these cells as epithelial in origin. Karyotyping of tumor cells demonstrated multiple numeric and structural chromosomal abnormalities. Serum and ascites CA 125 levels were consistently elevated only in tumor-bearing mice. This new murine model closely resembles the aggressive disease process of human epithelial ovarian carcinoma, in which the efficacy of i.p. and systemic therapeutic modalities can be investigated.

CD8-positive B-cell chronic lymphocytic leukemia. A report of two cases.

Most B-cell chronic lymphocytic leukemias and a small normal subset of B lymphocytes express the T-cell-associated CD5 antigen; expression of other T-cell antigens has been reported only rarely. The authors report two cases of typical B-cell chronic lymphocytic leukemia, seen during 1 year, in which two-color flow cytometric analysis documented expression of the T-cell-associated CD8 antigen by the monoclonal B cells. Genotypic studies showing immunoglobulin but not T-cell-receptor gene rearrangements confirmed the B-cell origin of the neoplastic cells. The true frequency of the CD8-positive B-cell chronic lymphocytic leukemia, any clinical implications, and the possibility of a normal subset of CD5-positive CD8-positive B cells remain to be determined.

Intestinal ischemia secondary to thromboangiitis obliterans.

A 38-year-old woman presented with a 10-month history of postprandial abdominal pain and weight loss. She smoked two packs of cigarettes a day, but her history did not indicate diabetes mellitus, hyperlipidemia, or hypercoagulability. A lateral aortogram documented complete occlusion of all three mesenteric arteries but showed no evidence of atherosclerosis, arteritis, or medial fibroplasia. Two retrograde aortomesenteric grafts, one to the superior mesenteric artery and another to the meandering mesenteric artery, utilizing the greater saphenous vein were placed. Pathologic examination of the inferior mesenteric artery demonstrated changes that were considered diagnostic of thromboangiitis obliterans. We found only 10 confirmed cases of thromboangiitis obliterans involving the mesenteric vessels in the English language literature. The present case appears to be the first involving a woman and the only one in which the main trunk of all three mesenteric vessels was involved.