Proliferative activity and p53 expression in adenoid cystic carcinoma of the breast.

Adenoid cystic carcinoma is a rare type of invasive breast carcinoma that has a good prognosis. We studied a series of four cases of adenoid cystic carcinoma in which we correlated the clinical and pathological features. The pathological features examined included light microscopy; electron microscopy; immunohistochemistry using antibodies to keratin, vimentin, S100 protein, actin, estrogen and progesterone receptors, and proliferation marker MiB-1, and p53 suppressor protein; image cytometric analysis for measurement of DNA ploidy; and molecular analysis using polymerase chain reaction single strand conformation polymorphism to assess point mutation of the p53 gene. All of the cases had a low nuclear grade, were negative for estrogen and progesterone receptors, and were DNA diploid. Three of the cases showed no evidence of metastases and had small primary tumors with low proliferative activity and absence of p53 protein expression. In contrast, one of the cases showed axillary lymph node metastases and in this case the primary tumor was large with a higher proliferative activity and expression of p53 protein, suggesting that these factors might play a role in the biological behavior of adenoid cystic carcinoma.

Concurrent medullary and papillary carcinomas of thyroid with lymph node metastases. A collision phenomenon.

The simultaneous occurrence of two distinct neoplasms derived from different cells of origin is a recognized, albeit rare, entity. In the thyroid, such lesions could consist of medullary carcinoma composed of parafollicular C cells and well-differentiated carcinoma showing follicular epithelial cell differentiation. We report a patient whose thyroid contained calcitonin-immunoreactive medullary carcinoma and thyroglobulin-positive papillary carcinoma, clearly separated from each other. The tumors metastasized to regional lymph nodes, where they formed foci of composite medullary and papillary carcinoma, with each component maintaining a distinct immunophenotypic profile. The composite metastases are best regarded as collision tumors, as each primary neoplasm exhibited only one line of differentiation. Given the high incidence of papillary carcinoma, the occurrence of the two tumors may be a coincidence. Alternatively, a common tumorigenic stimulus triggering neoplastic transformation of both parafollicular C cells and follicular epithelial cells is a plausible explanation for such a phenomenon.

Drug-related pigmentation of the thyroid associated with papillary carcinoma.

Black pigmentation of the thyroid attributed to minocycline hydrochloride is known, but to our knowledge, pigmentation associated with antidepressants has not been reported. We studied four patients with papillary carcinoma associated with thyroid pigmentation; two had received minocycline therapy, and two had received long-term treatment with antidepressants. The thyroids of patients who had been treated with minocycline were black, with pigment primarily in nontumorous tissue. The thyroids associated with antidepressant therapy were dark red, with pigment in both tumorous and nontumorous tissue. All four cases were positive for periodic acid-Schiff, periodic acid-Schiff with diastase predigestion, and Schmorl's stains and negative for Prussian blue; the results differed from those found with Fontana's technique. Minocycline-related pigmentation appears to imply a role for the iodide peroxidase system in the accumulation of pigment, whereas pigmentation attributed to intake of antidepressants appears to result from lysosomal accumulation of the drug itself.

Pathobiology of salivary glands. IV. Histogenetic concepts and cycling cells in human parotid and submandibular glands cultured in floating collagen gels.

Localization of cells with proliferative capacity in human major salivary glands lacks extensive study. Minced fragments of human parotid (n = 3) and submandibular (n = 3) glands embedded in a floating collagen gel matrix and cultured for up to 28 days allowed maintenance of the three-dimensional relationship of the various cell types in these glands. Immunocytochemistry and electron microscopy of a time-dependent series of cultured gland fragments showed gradual cytologic modification of acinar cells so that acini became duct-like but also established that even after 28 days of culture certain cellular features allowed continued identification of acinar cells. Serial section immunostaining for amylase, cytokeratins, and proliferating cell nuclear antigen (a specific marker for cycling cells) revealed that acinar, intercalated duct, and excretory duct (both basal and luminal) cells are all capable of entering the cell cycle. At day 5 of culture, the number of cycling cells increased 16-fold in the parotid gland and 9-fold in the submandibular gland over that in the respective in situ gland. In this in vitro system, which perhaps simulates regenerative processes in human salivary glands, none of the samples showed cycling cells localized only to segments of intercalated duct or the basal cells of excretory duct as suggested by current histogenetic concepts.

Expression of proliferation-associated nuclear antigen in human malignancies.

40 specimens consisting of 27 carcinomas, 9 lymphomas, 2 thymomas, 1 sarcoma and 1 neurinoma were studied by immunoperoxidase technique to demonstrate a cell proliferation-associated antigen defined by proliferating cells (PC) antibody. Though PC antibody expression did not seem to correlate well with histologic grading of carcinomas, positivity to this was consistently more intense in carcinomas than in normal epithelia. Correlation with histologic grading of lymphomas was more significant: the high grade types, e.g. ATL, exhibited greater positivity than intermediate grade types, e.g. diffuse medium lymphoma and certainly much more than low grade types, e.g. follicular lymphomas. These data were compared to another proliferation-associated antigen, the transferrin receptor.

Tissue polypeptide antigen--a marker antigen differentiating cholangiolar tumors from other hepatic tumors.

Twenty-two cases of primary hepatic tumors consisting of 11 hepatocellular carcinomas, 6 cholangiocarcinomas, 3 mixed hepatocellular and cholangiocellular carcinomas, and 2 biliary cystadenocarcinomas together with 8 cases of metastatic adenocarcinoma from various sites were studied by immunoperoxidase technic to demonstrate tissue polypeptide antigen. All of the tumors presumably derived from the epithelial lining of the bile duct, including cholangiocarcinoma, cholangiocarcinomatous portion of the mixed hepatocellular and cholangiocellular carcinoma, and biliary cystadenocarcinoma showed strong positive reaction. The hepatocellular carcinoma and the metastatic adenocarcinoma exhibited negative to weakly positive reactions. These results indicate that TPA can be of use in differentiating bile duct carcinomas from hepatocellular carcinoma and, to a lesser extent, from hepatic metastases of various adenocarcinomas.

Expression of transferrin receptor on human carcinomas--an immunohistological study.

Thirty specimens taken from 25 adenocarcinomas, 1 squamous cell carcinoma, 2 anaplastic carcinomas and 2 malignant lymphomas were studied for the presence of transferrin receptor (TR). Immunoperoxidase technique was used and OKT9, an anti-transferrin receptor monoclonal antibody, was introduced. The tissue localization of carcino-embryonic antigen (CEA) and epithelial membrane antigen (EMA) were also studied. Of these, 5 cases were strongly stained for TR, 17 moderately and 6 weakly stained. TR was demonstrated on the basal site while luminal preference was evident with CEA and EMA. This polarity was observed in the well- to moderately-differentiated adenocarcinomas and in the well-differentiated squamous cell carcinoma but not in the poorly-differentiated and anaplastic variants. Putatively normal epithelium registered very weak positivity though the polarity was still maintained.