AbstractDistinguishing cellular follicular adenomas (FA) from minimally invasive follicular carcinomas (FC) continues to plague even experienced thyroid pathologists. DNA ploidy analysis has been promoted as a means of making this differentiation; however, the finding of DNA aneuploidy in FA has caused concern that they may demonstrate potential for malignant behavior or should even be reclassified as low‐grade noninvasive cancers. In histologically‐proven FC, nuclear DNA content has been claimed to have predictive power equivalent to that of all other prognostic factors combined. The aims of the present study, therefore, were to define the DNA ploidy characteristics of FA and FC, to assess the diagnostic potential of cell‐cycle parameters, and, in FC, to investigate the prognostic role of such measurements.We measured DNA content of 124 tumors (60 FA, 64 FC). DNA pattern was normal (diploid) in 75% of FA and 45% of FC, tetraploid/polyploid (T/P) in 13% of FA and 25% of FC, and aneuploid in 12% of FA and 30% of FC. FC was histologically verified in 39% of DNA normal, 67% of T/P, and 73% of aneuploid tumors. DNA index, S‐phase, G2M, and S‐phase plus G2M were analyzed and were not helpful in differentiating between FA and FC. No patient with FA developed tumor recurrence. In FC (excluding the Hürthle cell variant), no significant differences were found among the 3 DNA ploidy groups with respect to either cancer death or tumor recurrence; however, combining the Hürthle cell variant of follicular carcinomas with pure follicular carcinomas, the presence of distant metastases, DNA aneuploidy, and patient age were the only independently significant prognostic variables. Based on these data, while not valuable for determining the presence of malignancy, DNA ploidy determination is of major prognostic value in follicular carcinomas (including the Hürthle cell variant).
Flow cytometric DNA measurements in benign and malignant Hürthle cell tumors of the thyroid
AbstractThe prediction of outcome in the rare Hürthle cell tumor of the thyroid continues to present a problem to surgeons and pathologists. To better clarify the distinctions between benign and malignant tumors, we have measured DNA content by flow cytometry on isolated cell nuclei derived from archival paraffin‐embedded tissue blocks of 125 Hürthle cell tumors operated from 1943 to 1985 at the Mayo Clinic, Rochester, Minnesota, U.S.A. Nuclear DNA ploidy patterns were divided into 3 groups. A DNA normal (diploid) pattern was found in 55% of 75 Hürthle cell adenomas and in 26% of 50 Hürthle cell cancers; a DNA tetraploid/polyploid pattern was found in 11% of benign, and 14% of malignant tumors. An abnormal DNA stemline was detected in 34% of benign and 60% of malignant tumors. Hürthle cell cancer was the histologic diagnosis in 24% of the DNA normal, 47% of the DNA tetraploid/polyploid, and 54% of the DNA aneuploid tumors. None of the patients with adenomas developed tumor recurrence. However, 20% of the euploid and 40% of the aneuploid tumors developed local or distant recurrences. Survival to thyroid cancer death was significantly correlated with DNA ploidy status (p=0.02) but did not correlate with either tumor size or histologic grade. To date, deaths from thyroid cancer have been confined to patients whose tumors were DNA aneuploid. We would conclude that determination of DNA ploidy status may not aid the surgical pathologist in the diagnosis of Hürthle cell cancer. However, when a patient's Hürthle cell cancer is DNA aneuploid, there is significant risk of death from thyroid cancer.