Brief report: detection of high-molecular-weight cytokeratins in neoplastic and non-neoplastic thyroid tumors using microwave antigen retrieval.

Previous studies have demonstrated the utility of immunohistochemical staining for high-molecular-weight cytokeratins in the distinction of papillary carcinoma from other neoplasms of the thyroid, however, this technique was reliable only when applied to frozen tissues. Our objective in this study was to evaluate the use of this antibody in diagnostic thyroid pathology using paraffin-embedded materials with microwave antigen retrieval. We studied 89 thyroid tumors including 45 papillary carcinomas, 28 nodular hyperplasias, 10 follicular adenomas, and 6 follicular carcinomas. Moderate-to-strong diffuse staining was confined to papillary carcinoma, whereas follicular neoplasms and hyperplastic nodules were either negative or showed focal staining. These results confirm the utility of high-molecular-weight cytokeratins immunostaining in diagnostic thyroid pathology, and obviate the need for frozen material to apply this method. As paraffin-embedded tissues are more readily available, we recommend the use of high-molecular-weight cytokeratins with microwave antigen retrieval in cases in which it is difficult to distinguish papillary carcinoma from other thyroid tumors.

Papillary Hürthle cell carcinoma with lymphocytic stroma. "Warthin-like tumor" of the thyroid.

We report 13 cases of a peculiar thyroid tumor of follicular epithelial differentiation with distinctly papillary architecture, oxyphilic cytology, and lymphocytic infiltrates in papillary stalks. The majority of these tumors arose in glands with chronic lymphocytic thyroiditis. The combination of oxyphilic cells and lymphocytic stroma gives these tumors a startling resemblance to papillary cystadenoma lymphomatosum, or "Warthin's tumor" of the salivary gland. Twelve tumors occurred in women (age range: 26-66 years, mean 44 years). Two tumors were in the isthmus, six in the right lobe, and four in the left lobe. The only man, 34 years old, had multiple bilateral tumor nodules. The lesions ranged from 0.3 cm to 3.5 cm in maximum dimension. The largest lesion, in a 58-year-old woman, infiltrated skeletal muscle. Three other patients had lymph node metastases, while the nine remaining tumors were confined to the thyroid. Follow-up in these cases suggests that although the histological appearance of these neoplasms is unusual, they behave as typical papillary carcinomas. The striking lymphocytic infiltration and oxyphilic metaplasia in these tumors as well as the association with chronic lymphocytic thyroiditis suggest that as yet undefined immunological mechanisms may play a role in the pathogenesis of this disorder.

Clonality of thyroid nodules in sporadic goiter.

Clonality studies have suggested that neoplasms are monoclonal and hyperplasias are polyclonal. To investigate this question in thyroid, we analyzed the clonality of 26 morphologically characterized hyperplastic nodules from 19 patients with sporadic goiters. For comparison we studied six thyroid carcinomas. We used the highly informative M27 beta probe that maps to the X-chromosome DXS255 locus (X cen-p11.22). Material was obtained from 52 nodules; tissue from nine nodules was rejected because of contamination with normal elements, five patients (eight nodules) were homozygous at Pst I sites in nonnodular thyroid tissue, and three nodules were excluded for technical reasons. Methylation patterns after Hpa II digestion confirmed polyclonality in all nontumorous thyroids of informative patients. Seven hyperplastic nodules were polyclonal, and 18 were monoclonal; one showed loss of heterozygosity. One nodule exhibited aberrant methylation. Multiple nodules were obtained from four patients; in three, all were monoclonal with activation of the same allele. Three papillary carcinomas were monoclonal; two exhibited aberrant methylation. One follicular carcinoma showed loss of heterozygosity. Our data indicate that morphologically indistinguishable hyperplastic thyroid nodules may be monoclonal or polyclonal. These findings suggest that variable molecular mechanisms are involved in the pathogenesis of nodules in sporadic goiter. Future studies will need to explore the biological significance of nodules of variable clonal origin.

Malignant lymphoma presenting with an elevated serum CA-125 level.

An 80-year-old woman presented with fevers, night sweats, and weight loss. Her serum CA-125 level was markedly elevated (380 U/mL; normal < 35 U/ml). At post-mortem examination, the patient had widespread intermediate-grade malignant lymphoma with extensive infiltration of the greater omentum and pelvic peritoneum. Immunohistochemistry for CA-125 documented intense staining in the reactive mesothelial cells of the peritoneum; the tumor cells were not immunoreactive. CA-125 is a glycoprotein recognized by a monoclonal antibody raised against an ovarian-cancer cell line. Elevated levels have been reported rarely in patients with malignant lymphoma, and the pathophysiology of this finding has not been understood. Our data support the hypothesis that elevated CA-125 levels may reflect production by reactive mesothelium in patients with benign or malignant diseases involving the peritoneum, including malignant lymphoma. The clinical application of this marker, therefore, is broader than the recognized monitoring of patients with ovarian carcinoma.

A metastasizing composite carcinoma of the thyroid with distinct medullary and papillary components.

Thyroid tumors with differentiation of both parafollicular and follicular epithelial cells are rare. The majority of those reported have been composed of a single cell population with combined features of the two cell types. We describe a 48-year-old man with a thyroid tumor composed of two discrete cell populations: thyroglobulin-positive papillary carcinoma intermixed with calcitonin-containing medullary carcinoma. The tumor metastasized to regional lymph nodes and maintained this composite differentiation. We propose that such tumors with two discrete intermingled cell populations be called composite thyroid carcinomas, as opposed to mixed thyroid tumors, which describes tumors with a single cell population that exhibits features of two cell types. Dual differentiation in thyroid neoplasms has been interpreted as indicative of a common stem cell origin. In this case, the presence of two mature, highly differentiated elements may suggest a proliferative response of two distinct cell populations to a common tumorigenic stimulus.

Intrathyroidal lymphoepithelial cysts of probable branchial origin.

Lymphoepithelial cysts with histological features characteristic of branchial cleft cysts have been reported to occur rarely in the thyroid gland. To our knowledge only six cases of this lesion have been reported. Since these reports brought this entity to our attention, we have noted that intrathyroidal lymphoepithelial cysts are not rare lesions. We report six further cases; four were incidental histological findings, and two lesions were clinically detected masses. Each of the cysts had a squamous epithelial lining with abundant underlying lymphoid tissue, including lymphoid aggregates with large reactive germinal centers. All cases were associated with chronic lymphocytic thyroiditis. Because of the histological resemblance to branchial cleft cysts, it is postulated that these lymphoepithelial cysts are branchial in origin. The histogenesis of branchial cleft cysts is unknown; however, the ultimobranchial body, originating from branchial pouches four and/or five, contributes to the embryological development of the thyroid. Branchial cleft derivatives, such as thymus and parathyroid, develop in close association with the thyroid and may be found within the thyroid gland. These branchial cleft-like cysts also may arise from branchial cleft derivatives, and their enlargement may be related to the immunological mechanisms associated with autoimmune thyroiditis.