Expression of TdT in Merkel cell carcinoma and small cell lung carcinoma.

Merkel cell carcinoma (MCC) is an uncommon tumor with indistinct clinical features. The differential diagnosis includes small cell lung carcinoma (SCLC). We characterized the expression of terminal deoxynucleotidyl transferase (TdT) and a panel of immunohistochemical markers in 40 MCC, 30 SCLC, and 6 pulmonary carcinoid tumor (PCT) cases. We used antibodies against TdT, thyroid transcription factor (TTF)-1, cytokeratins (CKs) 7 and 20, chromogranin, and synaptophysin. Immunostaining was recorded semiquantitatively. Of 40 MCC cases, 28 (70%) were positive for TdT, showing, on average, more than 25% of tumor cells reactive with moderate nuclear staining intensity. TTF-1 (1 [3%]), CK7 (2 [5%]), CK20 (35 [88%]), chromogranin (29 [73%]), and synaptophysin (39 [98%]) were expressed in the MCCs. Of the 5 CK20- MCC cases, 4 were positive for TdT. SCLC showed expression of TTF-1 (23/30 [77%]), CK7 (22/30 [73%]), chromogranin (16/30 [53%]), and synaptophysin (22 [73%]) and no CK20 (0%) expression. Of 30 SCLC cases, 2 (7%) were positive for TdT. TdT may be beneficial in rare cases of CK20- MCC and may assist in distinguishing between MCC and SCLC. There is significant immunohistochemical variability and overlap between these 2 tumors.

Breast metastasis by medullary thyroid carcinoma detected by FDG positron emission tomography.

Medullary thyroid carcinoma (MTC) is an uncommon thyroid cancer comprising 5% to 8% of thyroid neoplasms. In contrast to common thyroid tumors, this tumor originates from the calcitonin-producing C cells. Regional metastases to cervical lymph nodes occur early in the disease, whereas distant metastasis occurs late. Common metastatic sites include the liver, bone, brain, and adrenal medulla. We present a case of MTC metastatic to the breast. We report on this case for the following reasons: (1) metastasis to the breast is an extremely rare occurrence and could be easily confused clinically and pathologically with a primary breast neoplasm and (2) this is the first reported case of detection of breast metastasis by an MTC using FDG ((18)F-fluoro-2-deoxy-D-glucose) positron emission tomography with an accompanying histologic description.

Functional oncocytic adrenocortical carcinoma.

We present a case of oncocytic adrenocortical carcinoma in a 25-year-old man who presented with persistent hypertension, hypokalemia, and a large right adrenal mass. Clinical workup revealed increased serum aldosterone level, suppressed serum ACTH level and high 24-h urine cortisol. Histologically the tumor showed several features of malignancy and electron microscopy confirmed oncocytic differentiation. This case is reported as the first case of an aldosterone and cortisol-producing malignancy with an oncocytic phenotype.

Comparative study of the expression of p53, Ki67, E-cadherin and MMP-1 in verrucous hyperplasia and verrucous carcinoma of the oral cavity.

CONTEXT: Oral verrucous carcinoma (OVC) and oral verrucous hyperplasia (OVH) may be clinically and histologically similar. Problems separating these lesions are compounded by poorly oriented tissue sections and biopsies failing to demonstrate lesional margins. OBJECTIVE: To distinguish OVC from OVH utilizing an immunohistochemical panel (p53, matrix metalloproteinase-1, E-cadherin, Ki67) shown to be useful in differentiating pseudoepitheliomatous hyperplasia from oral squamous cell carcinoma of the head and neck. MATERIALS: Twenty-eight cases of OVH and thirty-two cases of OVC studied. Diagnoses were confirmed by two pathologists. Formalin-fixed, paraffin-embedded archival material was used for immunohistochemistry (avidin-biotin immunoperoxidase technique). RESULTS: More diffuse nuclear staining of p53 and Ki67 was detected in the OVC cases compared to the OVH cases (P < 0.001). There was statistically significant increased staining within adjacent stromal cells for matrix metalloproteinase-1 (P < .05) in the OVC cases. E-cadherin demonstrated diffuse membranous staining in both groups. CONCLUSION: Ki67, p53, and MMP-1 demonstrated significant staining trends. Although a properly oriented hematoxylin-eosin-stained section including normal marginal tissue is considered to be the gold standard for differentiation of OVH and OVC, this immunohistochemistry panel may serve as a useful diagnostic adjunct in difficult cases.

The meanings of markers: ancillary techniques in diagnosis of thyroid neoplasia.

This review article primarily discusses immunohistochemical markers used to aid the diagnosis of thyroid neoplasia. The review concentrates on high molecular weight cytokeratins, cytokertain 19, HBME-1, and galectin-3. Diagnostic uses of proliferation markers such as p27(kip1) and Ki-67 are discussed along with the oncogene ret in relation to papillary carcinomas and PAX8-peroxisome proliferator-activated receptor gamma1 in relation to follicular carcinoma. The diagnostic use of retinoblastoma tumor suppressor gene product is also discussed. The sensitivities and specificities as well as the pitfalls of these techniques are reviewed. On the basis of the literature, the most highly recommended of these markers to aid in diagnosis are HBME-1 and galectin-3.

Colocalization of pancreatic polypeptide and insulin in secretory granules of a pancreatic endocrine neoplasm.

A 45-year-old woman presented with clinical symptoms of hypoglycemia of 4 months duration. Laboratory testing confirmed hyperinsulinemia; mild hypercalcemia and hypergastrine-mia were also documented. At the time of operation, 3 pancreatic endocrine neoplasms were found, and a diagnosis of multiple endocrine neoplasia type I was made. Immunohistochem-istry and immunoelectron microscopy showed all the tumors to be plurihormonal, each containing three or more of the following: insulin, glucagon, somatostatin, pancreatic polypep-tide, gastrin, and serotonin. Electron microscopy of 2 tumors revealed numerous atypical granules. In 1 tumor, pancreatic polypeptide and insulin were colocalized in secretory granules by dual-staining immunoelectron microscopy. To our knowledge, this combination of hormones has not been described previously in pancreatic endocrine neoplasms and suggests that such neoplasms, like mature pancreatic endocrine cells, may originate from pluripotential common precursor cells.

Immunohistochemical localization of metal binding proteins in thyroid tissues and tumors.

Positive immunohistochemical staining for three metal binding proteins, ceruloplasmin, lactoferrin, and transferrin, has been suggested to be a reliable diagnostic marker of malignant but not benign thyroid neoplasms. We tested this hypothesis on a series of 9 nodular hyperplasias, 17 follicular adenomas, 54 papillary carcinomas, 20 follicular carcinomas, and 3 anaplastic carcinomas of thyroid using formalin-fixed paraffin-embedded tissues. We found focal staining for ceruloplasmin and lactoferrin in approximately 25% of follicular adenomas examined; focal ceruloplasmin positivity was also seen in nonneoplastic tissues surrounding thyroid neoplasms. No staining for these markers was found in malignant neoplasms or hyperplasias. Transferrin was found in 55% of papillary carcinomas, but more follicular adenomas (20%) than follicular carcinomas (11%) were positive using this antiserum. These findings show that immunostaining for these antigens is not a reliable method to distinguish benign from malignant thyroid lesions of follicular cell origin.