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August 2004

Editors:
Michael Cibull, MD, professor of pathology and laboratory medicine and director of surgical pathology, University of Kentucky Medical Center, Lexington
Subodh Lele, MD assistant professor of pathology and laboratory medicine, University of Kentucky Medical Center
Melissa Kesler, MD, hematopathology fellow, University of Texas Southwestern Medical Center at Dallas

Follicular thyroid carcinoma: histology and prognosis
EBV-positive gastric adenocarcinomas: a distinct clinical entity

Follicular thyroid carcinoma: histology and prognosis

Follicular thyroid carcinoma is the second most common thyroid malignancy, surpassed only by papillary thyroid carcinoma. The authors studied the clinical course of 132 patients with follicular thyroid carcinoma (FTC) to determine whether there was a direct relation between the histologic degree of invasion, tumor recurrence, and patient survival. The 132 patients in the study population underwent 182 thyroid carcinoma-related operations, and their mean followup was 7.5 years (median, six years; range, zero to 39 years). The following criteria were used to define malignant follicular neoplasms: minimally invasive, tumor invasion through the entire thickness of the tumor capsule; moderately invasive, tumor with angioinvasion, with or without capsular invasion; and widely invasive, broad area or areas of transcapsular invasion of thyroid and extrathyroidal tissue. Forty-five of 119 patients (37.8 percent) presented with minimally invasive FTC (capsular invasion only), 50 patients (42 percent) presented with moderately invasive FTC (angioinvasion with or without capsular invasion), and 24 patients (20 percent) presented with widely invasive FTC. At presentation, 12 patients (nine percent) had distant metastases and eight patients (six percent) had lymph node metastases. Excluding 12 patients who presented with distant metastases, 21 patients (16 percent) developed recurrent metastases six months after initial treatment. Among 45 patients with capsular invasion only, six patients (13 percent) developed recurrent or persistent disease, and five patients (11 percent) died. Of the 50 patients who had angioinvasion with or without capsular invasion, 10 patients (20 percent) developed recurrent or persistent disease and seven patients (14 percent) died. Patients who had angioinvasion with or without capsular invasion had a less favorable prognosis compared with patients who had capsular invasion only (P<0.0001). Among patients who had widely invasive FTC, nine of 24 patients (38 percent) developed recurrent disease and eight patients (33 percent) died. Seven of the other 24 patients (29 percent) had persistent disease and died. The overall death rate for patients with widely invasive FTC was 62 percent. Patients with persistent disease had a poorer prognosis than patients who had recurrent disease (P<0.0001). Twenty-eight patients (21 percent) in the group died of FTC. In this retrospective investigation, the authors demonstrated that patients with minimally invasive FTC (capsular invasion only) had a slightly better survival rate at five years (98 percent) than patients who had angioinvasion with or without capsular invasion (80 percent) and had better survival compared with patients who had widely invasive FTC (38 percent). Other, but not all, reports in the literature support the findings that FTC with angioinvasion is more aggressive than FTC with only capsular invasion, yet it is less aggressive than widely invasive FTC. The authors concluded that FTC no longer should be classified only as minimally or widely invasive. Instead, they recommend classifying FTC as minimally, moderately, or widely invasive, because prognosis varies according to these groupings.

D'Avanzo A, Treseler P, Ituarte PH, et al. Follicular thyroid carcinoma: histology and prognosis. Cancer. 2004;100:1123- 1129.

Reprints: Dr. Orlo H. Clark, Dept. of Surgery, University of California-San Francisco/Mt. Zion Medical Center, 1600 Divisadero St., No. C347, San Francisco, CA 94143-1674; clarko@surgery.ucsf.edu

EBV-positive gastric adenocarcinomas: a distinct clinical entity

Epstein-Barr virus is detected in a substantial subgroup of gastric adenocarcinomas worldwide. The authors previously reported that these Epstein-Barr virus (EBV)-positive gastric carcinomas carry distinct genomic aberrations. In the present study, the authors analyzed a large cohort of EBV-positive and EBV-negative gastric adenocarcinomas for their clinicopathologic features to determine whether they constitute a different clinical entity. Using a validated polymerase chain reaction/enzyme immunoassay-based prescreening method combined with EBER1/2-RNA in situ hybridization, EBV was detected in the tumor cells of 7.2 percent (n=41) of the gastric carcinomas from the Dutch D1D2 trial (n=566; mean followup, nine years). EBV status was correlated with clinicopathologic features collected for the Dutch D1D2 trial. EBV-positive gastric carcinomas occurred significantly more frequently in males (P<.0001) and in younger patients (P=.012). Most were of the intestinal type according to the Laurén classification (P=.047) or tubular according to the WHO classification (P=.006) and located in the proximal part of the stomach (P<.0001). A significantly lower tumor-node-metastasis system-stage (P=.026) was observed in the patients with EBV-carrying carcinomas, which was solely explained by less lymph node involvement (P=.034) in these cases. In addition, a better prognosis, as reflected by a longer disease-free period (P=.04) and significantly better cancer-related survival (P=.02), was observed for these patients, which could be explained by less lymph node involvement, less residual disease, and younger patient age. The authors concluded that EBV-carrying gastric adenocarcinomas are a distinct entity of carcinomas, characterized not only by unique genomic aberrations, but also by distinct clinicopathologic features associated with significantly better prognosis.

Van Beek J, zur Hausen A, Kranenbarg EK, et al. EBV-positive gastric adenocarcinomas: a distinct clinicopathologic entity with a low frequency of lymph node involvement. J Clin Oncol. 2004;22(4): 664-670.

Reprints: Dr. Elisabeth Bloemena, Dept. of Pathology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, Netherlands; e.bloemena@vumc.nl