Purpose: Patients with papillary thyroid carcinoma often have two or more distinct papillary tumors at thyroidectomy. Whether these multifocal papillary lesions are clonally related or whether they arise independently is unknown as previous studies have shown conflicting results. Molecular analysis of microsatellite alterations and X-chromosome inactivation status in separate tumors from the same patient can be used to define the genetic relationships among the multiple coexisting tumors. Experimental Design: We examined 64 separate tumors from 22 female patients who underwent thyroidectomy for thyroid carcinoma. All patients had multiple and separate papillary carcinomas (range, two to six). Genomic DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-capture microdissection. Loss of heterozygosity assays for three microsatellite polymorphic markers for putative tumor suppressor genes on chromosomes 3p25 (D3S1597), 9p21 (D9S161), and 18p11.22-p11 (D18S53) were done. In addition, X-chromosome inactivation analysis was done on the tumors from all patients. Results:Twenty of 22 (91%) cases showed allelic loss in one or more of the papillary lesions in at least one of the three polymorphic markers analyzed. Concordant allelic loss patterns between coexisting papillary tumors were seen in 20 of 23 (87%) cases. A concordant pattern of nonrandom X-chromosome inactivation in the multiple coexisting papillary lesions was seen in all informative cases. Conclusion: Our data suggest that the multifocal tumors in patients with papillary thyroid carcinoma often arise from the same clone. Thus, intrathryoid metastasis may play an important role in the spread of papillary thyroid carcinoma, a finding that has important therapeutic, diagnostic, and prognostic implications.Papillary thyroid carcinoma is the most common malignancy of the adult thyroid with an average of 20,000 new cases occurring each year. These tumors often present as thyroid nodules or as lymphadenopathy due to metastases (1, 2). Papillary thyroid carcinoma is frequently seen in the setting of Hashimoto's thyroiditis and is more frequently multifocal than any other well-characterized type of thyroid carcinoma. Often, there is a primary tumor that is >1 cm and additional microscopic foci measuring <1 cm (3, 4). Multifocal tumors have been associated with an increased risk of lymph node and distant metastases, suggesting multifocal papillary thyroid cancer may necessitate a unique treatment approach (5).Previous genetic studies have shown follicular thyroid carcinomas to display more extensive loss of heterozygosity and increased chromosomal instability than papillary carcinomas, which may be responsible for the more indolent course and better prognosis of papillary lesions (6 -8). The RET, NTRK1, RAS, and BRAF genes have been shown to participate in the pathogenesis of papillary thyroid carcinoma (9 -18). Subsequent clonality studies have yielded variable results, with independent clonal origin of multifocal papi...
A case of basosquamous or so-called transitional cloacogenic carcinoma of the sigmoid colon, which arose above the pelvic brim at the peritoneal reflection, is reported. We were not able to find a report of this histologic type of tumor arising this far from the pectinate line of the anus, which is the most common primary site of this neoplasm. Possibilities as to the histogenesis of this tumor at this site are stated. The neoplasm also produced parathyroid hormone (PTH) and also possibly adrenal corticotrophic hormone (ACTH), which had not been previously reported for this specific neoplasm.
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