A comparative immunohistochemical study of peritoneal and ovarian serous tumors, and mesotheliomas.

The distinction between serous neoplasms of the peritoneum in women and conventional mesothelioma can be difficult. In order to determine any significant immunohistochemical differences, formalin-fixed, paraffin-embedded sections of 10 peritoneal serous tumors (PST), 10 ovarian serous tumors (OST), and 10 epithelial mesotheliomas were evaluated with a panel of 10 antibodies directed against carcinoembryonic antigen (CEA: polyclonal, monoclonal), high molecular weight keratin (34 beta E12), low molecular weight keratin (35 beta H11), Leu-M1, TAG-72 (monoclonal antibody B72.3), human milk fat globulin (HMFG-2), vimentin, placental alkaline phosphatase (PLAP), and S-100 protein. The antibodies CEA, Leu-M1, and B72.3 had the most discriminatory value in differentiating serous tumors from mesothelioma. Eighty-five percent of PSTs and OSTs (17 of 20) were positive with CEA, Leu-M1, and/or B72.3. None of the mesotheliomas stained for CEA or Leu-M1; three mesotheliomas had very focal positivity with B72.3 (1% or less). Vimentin, PLAP, HMGF-2, keratin, and S-100 had no significant discriminatory value. Epithelial mucin was present in 80% of serous tumors, while the mesotheliomas lacked epithelial mucin. Leu-M1, CEA, and/or B72.3 positivity in a peritoneal tumor supports a diagnosis of serous tumor. However, since some PST do not stain for any of the three antibodies and the focal nature of positive reactions in some cases may be difficult to interpret, exclusion of mesotheliomas is enhanced by the use of mucin stains.

Prognostic significance of morphological parameters and flow cytometric DNA analysis in carcinoma of the breast.

The prognostic significance of conventional TNM staging remains the standard for determining prognosis in breast carcinoma. The presence (or absence) of axillary lymph node metastases remains the single most important parameter for predicting patient outcome. The presence of regional lymph node metastases implies that the primary tumor has the capacity for successfully completing the steps of the metastatic cascade. However, the absence of regional lymph node metastases does not ensure that distant or systemic seeding of tumor cells has not occurred, only that it is less likely. Staging data appear to be refined by addition of several standard morphological parameters. Although there is considerable overlap and interaction between these factors, as well as with staging data, there is strong evidence that grade, necrosis, inflammatory cell "immune response," and possibly pattern of invasion and intravascular tumor each independently supplement staging information. Some data appear to have independent significance only when applied to specific patient subsets, raising serious question as to their biologic importance. Nevertheless, morphological data are subjective and susceptible to observer variation and have less statistical power in predicting patient outcome than staging data. It was initially thought that DNA analysis of breast cancer by flow cytometry might supplant morphological data in assessing tumor behavior. The following conclusions can now be drawn: (1) there is no clear association between aneuploidy and SPF and stage; (2) aneuploid tumors are associated with higher SPF and shorter disease-free survival while diploid-range tumors generally have lower SPF and longer disease-free survival; (3) aneuploid DNA content is significantly associated with markers of decreased morphological (grade) and biochemical (ER status) differentiation. Determination of S-phase fraction by FCM appears to be a rapid and potentially easy method for obtaining kinetic information on individual breast tumors, although the technology for improving the accuracy of SPF measurements is still under development (e.g., tumor cell gating, debris subtraction). SPF appears to be comparable to other kinetic measurements, such as TLI, and shows many of the same associations with morphological and clinical data as ploidy. This is due to the close association of ploidy and SPF. Which of these parameters is more important for predicting patient outcome has not been clearly defined. Additional technological refinements for determining SPF may result in a more prominent prognostic role for this measurement. Three problems have limited our ability to draw specific conclusions about the biologic significance of tumor ploidy and SPF.(ABSTRACT TRUNCATED AT 400 WORDS)

Primary papillary serous neoplasia of the peritoneum: a clinicopathologic and ultrastructural study of eight cases.

The well-documented but rare primary papillary serous peritoneal tumors are difficult problems for the pathologist and the clinician. Because of their unusual location, these tumors are often classified as mesothelioma or advanced ovarian carcinoma. In this study, we report the clinicopathologic features of eight primary peritoneal serous papillary tumors and compare their histologic and ultrastructural features to 12 serous ovarian tumors and 16 epithelial mesotheliomas (two peritoneal and 14 pleural). The eight peritoneal serous papillary tumors occurred in women aged 19 to 75 years; two were serous tumors of low malignant potential (borderline) and six were serous carcinomas. The tumors were located in the mesosalpinx, left pelvis, omentum, and/or surface of the ovary. The two patients with borderline neoplasms had long disease-free survival (11 years and 20 years), while three of the four patients with carcinoma with more than 1 year of follow-up died of disease. The peritoneal serous papillary tumors were morphologically identical to serous ovarian tumors of equivalent grade. Well-differentiated papillary structures with distinct fibrovascular cores and one or several layers of columnar, crowded cells, dense overlapping nuclei with a long axis perpendicular to the surface of the papillary cores, and numerous psammoma bodies were features of the peritoneal and ovarian serous tumors. In contrast, the tubulo-alveolar, solid, or poorly defined papillary structures lined by well-spaced polygonal to cuboidal cells with abundant cytoplasm, absence of nuclear polarity, and infrequent psammoma bodies characterized the mesotheliomas. Epithelial mucin and carcinoembryonic antigen (CEA) immunoreactivity, when present, supported a diagnosis of serous tumor in these generally mucin-poor and CEA-negative neoplasms. Ultrastructurally, the cells of serous tumors had slender, straight microvilli of variable length interspersed with or without cilia, while the nonciliated cells of mesothelioma had long, exuberant, wavy microvilli. The morphologic and clinical features of the peritoneal papillary serous tumors are distinctive enough to warrant their separation from mesotheliomas.

Clinical characteristics distinguishing hereditary from sporadic medullary thyroid carcinoma. Treatment implications.

Distinctive differences between the hereditary and sporadic varieties of medullary thyroid carcinoma include the uniform bilaterality, consistent association of C cell hyperplasia, and the frequent association with other endocrine lesions as characteristics of the hereditary type. Total thyroidectomy is required for hereditary medullary thyroid carcinoma. Lateral cervical lymph node dissections do not appear necessary for the hereditary type when not palpable, detected only by family screening, and when biopsy of midjugular lymph nodes shows no evidence of metastasis. For palpable medullary thyroid carcinoma, the eradication of all cervical locations is unlikely to result in normal or undetectable levels of serum calcitonin postoperatively, even though such appears more likely for the sporadic variety.

The two-mutational-event theory in medullary thyroid cancer.

Comparisons are presented of the ages of onset of 20 cases of hereditary medullary carcinoma of the thyroid (MCT) and of 22 sporadic cases of this same type of cancer. These data are compatible with what might be expected by the two-mutational-event theory of the initiation of cancer postulated by Knudson. It had been previously postulated that C-cell hyperplasia of the thyroid was a premalignant change resulting from the first or genetic mutational event in the initiation of this type of cancer. The finding of C-cell hyperplasia in thyroid glands of each of the 10 patients with the hereditary condition and in none of the 10 sporadic patients is compatible with this theory. The C-cell hyperplasia is believed to be the expression of the genetic mutation, which requires a subsequent somatic mutation to transform the initially mutated cell into a cancer cell.

Multicellular origin of parathyroid "adenomas".

Most cases of primary hyperparathyroidism are associated with enlargement of a single gland (i.e., an "adenoma") or with chief-cell hyperplasia, but there is controversy about the relative frequency of each of these entities. It has even been postulated that adenomas do not arise spontaneously, bu- result from prolonged hyperplasia in response to unknown stimuli. We studied four parathyroid adenomas from three women with heterozygosity (GdB/GdA) for the X-chromosome-linked enzyme, glucose-6-phosphate dehydrogenase, to determine the number of cells from which the growths arise. Unicellular origin would be compatible with a rare oncogenic event, whereas multicellular origin might be seen with hyperplasia. Both B and A isoenzymes were found in each "adenoma" in proportions similar to those observed in normal tissues, indicating that the lesions have multicellular origin. Thus, parathyroid hyperplasia and adenomas, which at best are difficult to distinguish from one another pathologically, may also be similar biologically.