Different clonal origin of bilateral papillary thyroid carcinoma, with a review of the literature |
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Authors: | Kuhn Elisabetta Teller Linda Piana Simonetta Rosai Juan Merino Maria J |
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Institution: | (1) Centro Consulenze Anatomia Patologica Oncologica, Centro Diagnostico Italiano, Milan, Italy;(2) Translational Surgical Pathology Section, Laboratory of Pathology, NCI/NIH, Bethesda, MD, USA;(3) Pathology Unit-IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy;(4) Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA |
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Abstract: | Papillary thyroid carcinoma (PTC) often presents with two or more anatomically separate foci. A long-standing argument is
whether this multifocality is the result of multiple independent tumors (“multicentricity”) or of intrathyroidal spread originating from a single tumor mass, presumably through permeation of intrathyroidal lymph vessels. We reexamined this issue
with a clonality assay and compared our results with those in the literature. A total of 27 nodules from 11 female patients
with bilateral PTC treated with total thyroidectomy were investigated for clonality using the HUMARA assay. Eight of 11 cases
were informative (72.7 %). All but one of tumor foci showed a monoclonal population. The outlier sample gave a value indicative
of balanced X-inactivation in one nodule. The monoclonality was concordant in three patients, discordant in three, and mixed
in two (with both concordant and discordant results). Interestingly, in both of the latter cases (composed of over two samples
per case), the contralateral nodules were discordant. Moreover, all four ipsilateral nodules were concordant. The results
of our study suggest that some cases of multifocal PTC are the result of true multicentricity, whereas others are the consequence
of intrathyroid spread by an originally single tumor mass. These conclusions support those made in the past years on the basis
of morphologic considerations. Specifically, the incidental finding of two or more microscopic foci of PTC widely separate
from each other was felt to favor multicentricity, whereas the finding of multiple ipsilateral foci of PTC within vascular
spaces, often accompanied by multiple lymph node metastases, suggested intrathyroid spread; the most striking manifestation
of this phenomenon being seen in the diffuse sclerosing variant of PTC. |
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