Richard B. Marshall

Malignant mixed müllerian tumors an ultrastructural and immunohistochemical analysis with histogenetic considerations

In the female genital tract, malignant mixed müllerian tumors (MMTs) are uncommon neoplasms of uncertain histogenesis. We have examined 11 MMTs by both electron microscopy (EM) and immunoperoxidase techniques (IPX). Eight were of endometrial, two were of ovarian, and one of tubal origins. The IPX analysis included monoclonal antibodies to keratin (k) and vimentin (v) and a polyclonal antibody to myoglobin. Carcinomatous elements were always keratin positive (K+) and were focally positive for vimentin in six tumors. Homologous stromal sarcoma cells were vimentin positive (V+) and in three tumors were focally K+. Ultrastructurally, the epithelial cells were not highly differentiated and the sarcomatous elements generally resembled normal proliferative‐phase stromal cells. The epithelial and stromal elements were separated by a thin basal lamina that only rarely and focally had discontinuities. No transitional cellular forms were identified. A definite positive myoglobin reaction was seen in two of the four neoplasms in which rhabdomyoblasts were identified by light microscopy. Myofilaments were identified by electron microscope in three neoplasms.

Endometrial adenocarcinoma: A multiparameter clinicopathologic analysis including the DNA profile and the sex steroid hormone receptors

With endometrial adenocarcinoma, several factors, such as stage and histologic grade, are well recognized as having prognostic significance. Other variables, e.g., nuclear grade, probably are also important clinically. A preliminary investigation of the prognostic value of the ploidy, cell cycle kinetics, and sex steroid receptor contents of these tumors has been conducted and compared with more conventional prognostic factors such as stage, grades, and depth of invasion. As analyzed by flow cytometry, the proliferative activities of the carcinomas were significantly associated with prognosis. Tumors with lower levels of proliferative activity were related to improved survivals. Two thirds of the carcinomas were diploid; ploidy did not carry prognostic weight in the series. Both the estrogen and progesterone receptor status were related to survival. Patients whose tumors were positive for these receptors had a better prognosis than did those in which the receptors were not present in significant quantities.

Sclerosing Encapsulating Peritonitis: Report of a Case With Small Bowel Obstruction Managed by Long-Term Home Parenteral Hyperalimentation, and a Review of the Literature

Sclerosing peritonitis has recently emerged as a complication of peritoneal dialysis associated with a high morbidity and mortality. These patients experience the characteristic syndrome of nausea, vomiting, abdominal pain, partial small bowel obstruction, and impaired ultrafiltration. A pathologic finding is the replacement of mesothelial cells with a thick layer of nondistensible fibroconnective tissue. We report here a 58-year-old white woman who developed peritoneal sclerosis after 4 years of peritoneal dialysis, including 3 years of continuous ambulatory peritoneal dialysis. Risk factors included peritoneal exposure to low concentrations of formaldehyde and a 1-week exposure to long-dwell acetate dialysate. Laparotomy for partial small bowel obstruction with resection of the involved segment was complicated by enterocutaneous fistulae, which improved only on cessation of oral intake and treatment with home parenteral nutrition. We have reviewed the literature to find 20 cases of sclerosing peritonitis in patients on peritoneal dialysis. A 78% mortality rate is reported in cases that had surgical intervention. We conclude that the use of long-term parenteral nutrition with cessation of oral intake may be necessary in the management of sclerosing encapsulating peritonitis.

The vascular component in meningiomas associated with severe cerebral edema.

Cerebral edema is usually a complication of the later growth stages of intracranial neoplasms. Three patients with small meningiomas presented with unusually several cerebral edema out of proportion to the size of tumors. All three tumors exhibited benign meningothelial components, the formation of pseudopsammoma bodies, and striking vascular mural proliferation of small dark cells. In two tumors ultrastructural examination of these cells showed features of pericytes. The vascular pericytic component in these tumors may grow more actively than the meningothelial component and thus may cause the production of severe cerebral edema. The clinical, radiological, operative, and light and electron microscopic findings are presented, and the relationship to angioblastic meningiomas is discussed.

Relationship of flow cytometry results to clinical and steroid receptor status in human breast cancer

SummaryFlow cytometry (FC), estrogen receptor (ER), and progesterone receptor (PR) analyses were performed on 226 breast cancers. The presence of steroid receptors was inversely proportional to proliferative index and percent aneuploidy. Within the two ER (+ and −) groups, the presence of PR did not add significantly to the comparison. The mean proliferative index for the diploid tumors was 17.5±6.8 compared to 27.8±9.8 for aneuploid tumors (p<.001). The degree of aneuploidy, or DNA index, was not related to cell cycle kinetics or steroid receptor status. In 163 tissues analyzed for percent tumor present, a correlation between the relative number of aneuploid cells and percent tumor in the histologic review was observed. A study of the diploid tumors indicated greater than 75% had at least 10% tumor cells by histologic review. Since with FC one can observe at least 10% aneuploid cells in a tumor sample, it is our opinion that the percent aneuploidy in this study is not artifactually low due to sampling error. There was no significant relationship between nodal status or number of positive nodes and proliferative index, aneuploidy, or steroid receptor status. Metastatic tumors had a higher mean proliferative index, but this was not statistically significant. There was a relationship between age and proliferative index but not between age and ploidy status. In a small group of patients there was a trend for proliferative index and percent aneuploidy to be higher in the poorly differentiated and larger tumors when compared to the well differentiated and smaller tumors.

Paraganglioma of the thyroid gland.

A case of a paraganglioma located within the thyroid gland is reported, and the light- and electron-microscopic features are described. Review of the literature reveals only one other case of intrathyroidal paraganglioma, which was associated with bilateral carotid body tumors. Regarding the present case, no similar tumors have been noted elsewhere. The findings support the view that the thyroid gland should be included among the unusual sites at which primary paragangliomas may occur.

Multiple Primary Malignant Tumors (MPMT): Study of 68 Autopsy Cases (1963–1980)

Review of 8428 autopsies (1870 for known cancer) showed that 68 patients had had multiple primary malignant tumors (MPMT). Those 68 cases represented 0.8 per cent of all autopsies done, 3.6 per cent of all cancer autopsies. Diagnosis of MPMT was made only at autopsy in 24 cases (35.3 per cent). Thirty‐six patients were male, 32 female. Their average age was 64 ±usmn;2.3 years. Cancers were “synchronous” (diagnosed within a six‐month period) in 15 patients, “metachronous” (diagnosed at greater than six‐month intervals) in 49, and “combined” in four. Metastatic foci were seen in 53 patients. Fifty‐nine patients had two primary malignant tumors (PMTs); seven had three PMTs; one had four PMTs; and one had five PMTs, for a total of 148 tumors. Over half (53.1 per cent) of the second PMTs occurred within five years of the first PMTs. First PMTs were most common in the hematopoietic system and the cervix; second PMTs were most common in the lungs and the hematopoietic system. Second PMTs were less well differentiated than index PMTs. Forty‐four deaths had not been directly tumor‐related. Nineteen patients with metachronous MPMT lived more than ten years. Of 23 patients with one pulmonary PMT, 22 died within two years. Concomitant findings of pulmonary artery embolism, gallstone(s), thyroid or prostatic hyperplasia, and benign tumor were common in these patients. It is hoped that accumulation of data from this and other series of MPMT will provide insight into the clinicopathologic characteristics, the causes, and the interrelationships of these lesions that constitute primarily a disease of the elderly.

Correlation of female sex steroid hormone receptors with histologic and ultrastructural differentiation in adenocarcinoma of the endometrium

A series of 43 patients with endometrial adenocarcinoma were evaluated in order to investigate the relationships of the estrogen receptor (ER) and the progesterone receptor (PR) with the histologic and nuclear grades and the ultrastructural differentiation of these tumors. Twenty‐six neoplasms were positive (10 fmole/mg protein) for both receptors, 1 was positive for the ER only, 9 were ER−PR+, and 7 were ER−PR−. Twenty carcinomas were histologic Grade I, 12 Grade II, and 11 Grade III. Distribution of nuclear grade was 11 Grade I, 18 Grade II, and 14 Grade III. Both histologic and nuclear grades were found to be significantly related to the presence or absence of both the ER and the PR. Several cytoplasmic structures (cilia, primary lysosomes, intracytoplasmic lumens) were highly specific but of low sensitivity for predicting the receptor status of these tumors. To a limited extent, ultrastructural markers were associated with histologic differentiation.

Carcinoma of the Parathyroid

We report on eight cases of parathyroid carcinoma seen at the Bowman Gray School of Medicine, Winston-Salem, NC, since 1969. Diagnosis of a parathyroid disorder was made on the basis of elevated serum calcium levels and associated disorders such as renal calculi, peptic ulcer disease, pancreatitis, and demineralization of bone. Six of the involved glands were on the left side. In seven patients, the disease was localized to the gland or adjacent structures; one patient had cervical lymph node invasion. Except for the last patient, in whom radical neck dissection and wide excision was done, local excision with adequate margins was the only procedure done. The patient with metastases died of his disease four years later. One patient died of myocardial infarction two years later, but had been normocalcemic in the interval between operation and death, and one patient is hypercalcemic and has had two local recurrences within a 3 1/2 year period. The other five patients are alive and well. The routine use of automated serum level determinations of all hospitalized patients has led to early detection of this malignancy, while it is still a stage I lesion in many instances. On the basis of this material, we conclude that radical neck dissection can no longer be advocated as a routine measure in the treatment of parathyroid carcinoma.

The significance of nuclear diameter in the biologic behavior of thyroid carcinomas: A retrospective study of 127 cases

The relationship between nuclear diameter and biologic behavior was studied in 127 cases of thyroid carcinoma. Using a sonic digitizer coupled to a minicomputer, nuclear diameters of 200 randomly selected cancer cells from each case (hematoxylineosin-stained paraffin sections) projected at X 400 magnification were traced and averaged. A total of 25,400 measurements were made. The nuclear diameters varied from 4.7 to 13.1 micron. By analysis of variance, the nuclear diameters were significantly different (p = 0.0007) among the four types of thyroid cancers, being largest in the undifferentiated cancers (8.7 +/- 0.8 micron) and smallest in the medullary cancers (6.6 +/- 0.1 micron). Nuclear diameter was also significantly correlated with degree of tumor differentiation (p = 0.002), maximal tumor diameter (p = 0.03), mitotic rate (p = 0.002), and 5-year survival (p less than 0.05) for all types of tumors. The correlation between nuclear diameter and disease stage was significant only for undifferentiated cancers (p = 0.04). No significant correlations were seen between nuclear diameter and duration of disease, sex, or age of the patient.