Serous surface carcinoma of the peritoneum: a clinicopathologic study of 22 cases.

Serous surface carcinoma (SSC) of the peritoneum is defined as a primary tumor histologically indistinguishable from serous carcinoma of the ovary, diffusely involving the peritoneal surface but sparing or only superficially invading the ovaries. In this study of 22 cases of SSC, it was found that the main clinical manifestations of SSC were abdominal pain and enlargement. In most cases, SSC evenly involved the entire mesothelial surface but rarely was predominant in or even limited to the pelvis. It frequently invaded the submesothelium, but deep invasion into abdominal and pelvic organs or local metastasis was rare, and distant metastasis was not seen at presentation. Microscopically, SSC was a high-grade tumor frequently showing high mitotic rate, psammomas bodies, and necrosis. The tumor was usually contiguous with hyperplastic mesothelium on either ovarian surface or other locations. Tumor cells in all cases except one showed cytoplasmic or surface neutral or acidic mucin or both. Tumor cells stained positive for keratin (100% of cases), epithelial membrane antigen (100%), Leu-M1 (45%), B72.3 (85%), vimentin (35%), and carcinoembryonic antigen (25%). Electron microscopic studies of six cases showed epithelial differentiation in each. Seven patients (32%) were alive with no clinical disease at 3 to 31 months, one patient (4%) was alive with extensive local disease at 24 months, 11 patients (50%) died almost exclusively of local recurrence at 1 to 70 months, and three patients (14%) died of operative complications. It is concluded that SSC arises from peritoneal mesothelium but has epithelial phenotype. It can be morphologically differentiated from other conditions with similar laparotomy findings, such as malignant mesothelioma, benign papillary mesothelioma, cystic mesothelioma, and benign or borderline peritoneal serous tumors. The prognosis of SSC is poor, and most patients die of uncontrollable local disease.

Localized fibrous tumor of the serosal cavities. Immunohistochemical, electron-microscopic, and flow-cytometric DNA study.

Localized fibrous tumor of the serosal cavities (localized fibrous mesothelioma) is a generally benign spindle cell neoplasm of uncertain histogenesis. Fourteen histologically similar primary tumors from different mesothelium-lined sites (11 pleural and 1 each in the pericardium, peritoneal cavity, and pouch of Douglas) and 2 recurrences of those tumors (pericardium and pouch of Douglas) were examined histopathologically and by flow cytometry to relate histologic features and DNA ploidy to biologic behavior (follow-up, 48-255 months among 13 patients). All 16 tumors (14 primaries and 2 recurrences) displayed diploid DNA pattern, and none of 13 patients died of disease (1 patient was lost to follow-up). To elucidate the histogenesis, seven primary tumors were examined for vimentin and keratin immunostaining and six primary tumors were assessed by electron microscopy. All cases exhibited spindle-fibroblastic cell proliferation with a prominent hemangiopericytic pattern. All cases so examined had positive results for vimentin and negative results for keratin. Ultrastructurally, the tumor cells showed mesenchymal-fibroblastic features. These results support a mesenchymal origin, most likely from submesothelial fibroblasts. Further, this neoplasm may recur but retain its basic histologic features, diploidy, and benign outcome.

Peritoneal malignant mesothelioma versus serous papillary adenocarcinoma. A histochemical and immunohistochemical comparison.

In order to evaluate adjunctive histologic methods for separating mesothelioma (MM) and serous adenocarcinoma (SC), we studied 28 and 46 respective cases histochemically and immunohistochemically. Ten serous adenocarcinomas arose primarily in extraovarian sites within the abdomen. Diagnoses in each case were established retrospectively by a combination of electron microscopy and clinicopathologic correlation. A panel of antibodies to cytokeratin (CK), epithelial membrane antigen (EMA), B72.3, placental alkaline phosphatase (PLAP), S-100 protein, carcinoembryonic antigen (CEA), Leu M1, CA-125, and amylase (AM) was applied to paraffin sections of each case. Serous carcinoma was reactive for neutral mucins whereas mesothelioma was not; however, only 50% of adenocarcinoma cases stained in this manner. Peritoneal mesothelioma showed reactivity for CK (28 of 28 cases), EMA (24 of 28 cases), AM (five of 28 cases), CA-125 (four of 28 cases), and S-100 protein (three of 28 cases), but lacked B72.3, PLAP, and CEA. Three mesotheliomas expressed Leu M1, but in an extremely focal distribution. Serous carcinoma reacted for CK (46 of 46 cases), EMA (46 of 46 cases), CA-125 (42 of 46 cases), S-100 protein (40 of 46 cases), Leu M1 (34 of 46 cases; with diffuse staining), B72.3 (33 of 46 cases), PLAP (29 of 46 cases), AM (15 of 46 cases), and CEA (six of 46 cases). Two profiles (S-100 + B72.3; S-100 + PLAP) were seen in 41 of 46 serous adenocarcinoma cases but were absent in all mesotheliomas. Hence, these combinations of determinants are effective in separating such neoplasms diagnostically. Moreover, diffuse reactivity for Leu M1, B72.3, PLAP, or CEA in papillary peritoneal neoplasms appears to exclude the possibility of mesothelioma; however, focal Leu M1 reactivity may indeed be seen in mesothelioma. Although CA-125 is a sensitive marker for serous carcinoma, it is not effective in distinguishing it from mesothelioma.

Pulmonary metastases in patients with low-grade endometrial stromal sarcoma. Clinicopathologic findings with immunohistochemical characterization.

Two cases of low-grade endometrial stromal sarcoma (ESS) presenting as cystic pulmonary metastases are reported. Both lung lesions were initially thought to represent examples of so-called mesenchymal cystic hamartoma. A diligent search of the past medical records in the first case revealed that a primary low-grade ESS of the uterus had been resected 27 years earlier. In the second case, a uterine tumor was seen by computed tomography scan and subsequent pathologic examination of the hysterectomy specimen established the presence of a low-grade ESS. Peritoneal metastases, present in both cases, also presented diagnostic problems until the uterine primaries were recognized. Immunoreactivity for desmin was detected in all primary and metastatic tumor sites examined. We conclude that ESS should be included among the desmin-positive spindle cell sarcomas and that metastatic ESS should be included in the differential diagnosis of "benign" mesenchymal cystic hamartoma of the lung.

Asbestos fibre content of lungs with mesotheliomas in Osaka, Japan: a preliminary report.

That crocidolite and amosite are both associated with the development of mesothelioma is now well established, but earlier studies have failed to find an excess of chrysotile in lungs with mesotheliomas as compared with the amounts in lungs of unaffected controls. In an attempt to clarify the importance of fibre type in tissue, an examination of a series of mesotheliomas is being undertaken in Osaka, Japan. A total of 23 mesotheliomas and 5 rejected cases reviewed by the Osaka Mesothelioma Panel were examined for the types of asbestos and semiquantitative fibre content by means of a transmission electron microscope equipped with energy-dispersive X-ray analyser. Asbestos fibres were detected in 19 of the 23 mesotheliomas (21 pleura, 1 pericardium, 1 peritoneum; 19 males, 4 females). Amphibole fibres were found in 13 cases. Five pleural and one peritoneal mesothelioma were found to have only chrysotile fibres. One female pleural mesothelioma with neighbourhood exposure had short chrysotile fibres. Among the 5 rejected cases, only one case with occupational exposure had both chrysotile and amosite fibres. A group of 17 controls were also examined and asbestos fibres were found in 5. Our data, while not definitive, suggest that mesotheliomas can be induced in humans, not only by crocidolite and amosite, but also by chrysotile, though possibly to a lesser extent.

Immunohistologic detection of estrogen and progesterone receptors in disseminated peritoneal leiomyomatosis.

Disseminated peritoneal leiomyomatosis (DPL) is a rare clinicopathologic entity typically observed in women during pregnancy or immediately postpartum. Immunohistologic examinations of frozen as well as paraffin sections in three cases of DPL confirmed the myocytic character of the lesion and substantiated the hormonal influence on growth and regression of DPL nodules by detection of estrogen and progesterone receptors in the tumor cells. Implications of functional aspects as well as the benign clinical and morphologic feature of DPL are discussed in order to avoid inappropriate therapeutic measures.

Improved radiolabeled monoclonal antibody uptake by lavage of intraperitoneal carcinomatosis in mice.

The effect of peritoneal lavage with saline on tumor and systemic uptake of intraperitoneally administered tumor-specific (131I-5G6.4) and nonspecific (125I-UPC-10) radiolabeled monoclonal antibodies was evaluated in a nude mouse model of human intraperitoneal ovarian carcinomatosis (IP3 model). Peritoneal lavage at 2 or 6 hr postintraperitoneal antibody injection significantly improves intraperitoneal tumor/nontumor uptake ratios of specific antibody apparently by limiting systemic exposure to antibody. This enhancement tends to be more dramatic if lavage is performed within 2 hr, rather than 6 hr, of intraperitoneal antibody administration, though both times result in significant improvements in target/background ratios over no lavage. Twenty-four-hour tumor/nontumor ratios for specific antibody 5G6.4 generally are 1.5-fourfold higher following lavage than those achieved in control animals, without decreasing absolute tumor uptake of specific radiolabeled antibody. By contrast, nonspecific antibody UPC-10 binding is lower in tumor and normal tissues following lavage, with no lavage-induced improvement in tumor/nontumor ratios seen. Peritoneal lavage is a simple method to allow for specific antibody binding to accessible intraperitoneal tumors yet to limit systemic exposure thus increasing the therapeutic margin. This method may have considerable applicability in the enhancement of intraperitoneal immunoconjugate delivery to intraperitoneal tumors.

Malignant peritoneal mesothelioma in childhood.

We present a case of diffuse malignant peritoneal mesothelioma, initially misdiagnosed as benign. Electron microscopy and immunocytochemistry proved helpful diagnostically. Using monoclonal antibodies against cytokeratin and vimentin, we compared neoplastic with normal and reactive mesothelia and we found coexpression of these two intermediate filaments in the reactive and neoplastic mesothelial but not in the normal mesothelia, supporting the suggestion that surface mesothelial cells are derived from multipotential submesothelial cells.

[Immunochemical identification of beta2-globulin in metastases of ovarian tumors]. / Immunokhimicheskaia identifikatsiia beta2-globulina v metastazakh ovarial'nykh opukholei.

Antisera were obtained upon immunization of rabbits with the extracts obtained from metastatic tissues of primary ovarian carcinoma into the omentum. Eight antigens were found, which were termed "ovarian-metastatic antigens" (OMA). OMA 1-7 showed cross-reactions with the antigens of one of the normal organs of the adult man: kidneys, spleen, brain. OMA-8 was not identified in the internal organ tissues of the adults and fetuses. Using immunodiffusion method, OMA-8 was revealed in the tissues of metastases of primary ovarian cancer into the omentum in 55% of cases (3-180 mg/l), in 50% of cases it was detected in primary ovarian carcinomas (3-50 mg/l) and in mature placenta (38-40 weeks) (6-12 mg/l). OMA-8 was detected in the chorion (8-20 weeks) and in the amniotic fluid at all periods at the maximum sensitivity of immunodiffusion method (1-2 mg/l). OMA-8 is a beta 2-globulin of protein nature with NW 35 kD, containing alpha- and beta-subunits with MW 18 and 19.5 kD. No carbohydrates, lipids and ferrum were determined in OMA-8. Its physico-chemical and antigenic properties differ from those of the described carcinoembryonic and placental proteins.

Benign cystic mesothelioma of the peritoneum: immunohistochemical and ultrastructural features in a child.

Benign cystic mesothelioma of the peritoneum is a well-defined but rare entity. A total of 35 instances have been reported, almost all in adults, the majority females. Cystic mesotheliomas have, until recently, been labeled cystic lymphangiomas or lymphohemangiomas. We report the case of a 14-year-old boy who, despite only subtotal resection of his abdominal mass, is well and recurrence free 9 months after surgery. The role of immunohistochemistry and electron microscopy in diagnosis is emphasized.

Intermediate filament proteins in asbestos-induced mesotheliomas of the rat.

Abdominal diffuse malignant mesotheliomas develop in rats administered asbestos by the intraperitoneal route. A latency period of 6 to 24 months precedes tumor development; the biological and morphological features of these tumors resemble mesotheliomas in humans. Using one- and two-dimensional gel electrophoresis and immunoblotting, rat mesotheliomas (n = 24) were shown to express two classes of intermediate filament (IF) proteins. The tumors contained both vimentin and at least one of six keratins (p40, Mr 40,000; Dm, Mr 50,000; p53, Mr 53,000; Bm, Mr 53,000; Cm, Mr 54,000; Am, Mr 54,000). Vimentin predominated in 15 of 16 tumors exhibiting either sarcomatous or mixed (epithelial and mesenchymal) appearance. One of eight mixed lesions and six of eight epithelial tumors had a complement of IF proteins in which cytokeratins predominated. A similar pattern has been reported in mesotheliomas in humans (Blobel et al., Am. J. Pathol. 121: 235, 1985). Epithelial tumors often contain comparable amounts of vimentin and low molecular weight cytokeratins, while vimentin is the most actively expressed IF protein in sarcomatous tumors. Thus, tumors induced by asbestos in the rat peritoneum express IF proteins in a manner that resembles human mesotheliomas, supporting the notion that these lesions are appropriate models of human mesothelioma.

Peritoneal mesothelial cell injury factors in rat cancerous ascites.

To elucidate the mechanism of the peritoneal dissemination of cancer, the influence of cancerous ascites on peritoneal mesothelial cells was studied by scanning electron microscopy and light microscopy. We inoculated normal Donryu rats with AH100B ascites hepatoma cells and studied the influence of the supernatant from cancerous ascites on the normal rat peritoneal surface by i.p. injection. The mesothelial cells were damaged and exfoliated markedly, which is supposed to be a profitable condition for cancer cells to proliferate on the peritoneal surface. Therefore, the presence of mesothelial cell injury factors was noted. Subsequently, we divided the supernatant from rat cancerous ascites into four fractions by gel filtration and revealed the distribution of mesothelial cell injury factors by studying the influence of each fraction on the normal rat peritoneal surface. Although Fraction I (fibrin fraction) and Fraction II (IgG fraction) made no changes on the peritoneal surface, Fraction III (albumin fraction) and Fraction IV provoked damages on the mesothelial cells. We found that the mesothelial cell injury factors are present in the albumin fraction and in the fraction containing low-molecular-weight substances.

Hyaluronic acid content of effusions as a diagnostic aid for malignant mesothelioma.

A high-performance liquid chromatographic technique, using a size exclusion column (TSK-5000PW), has been developed for the quantification of hyaluronic acid (HA) in pleural and peritoneal effusions. Sample preparation requires only a 100-fold dilution of the exudate with phosphate buffer prior to analysis. Chromatographic conditions are: 0.05 M phosphate buffer (pH, 5.0) mobile phase at a flow rate of 1.0 ml/min, ultraviolet absorbance detection at 200 nm. The method resolves HA from all other glycosaminoglycans. The presence of HA is confirmed by the removal of the HA peak (retention time, approx. 5.3 min) by incubation of a second sample aliquot with hyaluronidase. Effusions of 13 of 14 patients with confirmed malignant mesothelioma contained HA in the 0.3 to 11.1 mg/ml range. In only one case was no HA detected. None of the effusions from 56 control patients with various other primary tumors contained detectable HA, i.e., there were no false positives. An unidentified peak, not susceptible to hyaluronidase appeared in 11% (6 of 56) of the controls. A single mesothelioma case was correctly identified in a group of 10 coded samples. It is suggested that an effusion with an HA concentration greater than 0.25 mg/ml, confirmed by hyaluronidase susceptibility, is an indication of the presence of malignant mesothelioma. The test is simple and rapid, and it is recommended that any effusion of uncertain etiology be screened for the presence of HA.

Peritoneal endometriosis. Report of a case with cytologic, cytochemical and histopathologic study.

The cytologic and histochemical data in a case of extensive peritoneal endometriosis are presented. The presence of macrophages heavily laden with blue and dark pigment (as demonstrated by May-Grünwald-Giemsa, Perls and Fontana stains) and scattered non-neoplastic endometrial cells in hemorrhagic ascitic fluid indicated a diagnosis of peritoneal endometriosis. Metabolized hemoglobin material was related to both recent and older hemorrhages.

[Pseudomyxoma peritonei: a case with multiple metastases. Ultrastructural study and chemical analysis of the mucoid substance]. / Pseudomyxome péritonéal: un cas avec métastases multiples. Etude ultrastructurale et analyse chimique de la substance mucoïde.

A patient with spreading pseudomyxoma peritonei probably caused by a tumor of the appendix showing suggestive clinical features is presented. The long evolution was marked by the discovery of gelatinous substance in the stools and in the lumen of the gut, and the appearance of distant metastasis in the lungs, adrenal glands and lymph nodes. Histochemical studies showed that periodic Shiff acid and Alcian blue were fixed by the mucoid substance. The use of toluidin blue (pH 1) revealed metachromosia. Electron microscopy ascertained the presence of enterocytes and mucous cells and revealed a more obvious nuclear disorganisation than by histological microscopy. Biochemical study showed that the mucoid substance extracted from the pseudomyxoma was rich in carbohydrates and could be identified as a mucin on the basis of the composition of its monosaccarides and of the alkali-lability of its glycanprotein linkages. The mucin was weakly hydrolysed by trypsin in vitro but was deeply attacked by the same enzyme after desialylation. These results: a) confirm the possibility of observing spreading distant metastasis in the pseudomyxoma peritonei; b) underline the potential interest of electron microscopic study in case of wavering diagnosis; c) show that the mucoid substance belongs to the group of neutral sulfomucins; d) legitimate, in the future, a trial of palliative treatment by neuraminidase in such cases.

Estrogen and progesterone cytosol receptor concentration in endometriotic tissue and intrauterine endometrium.

Cytosol estrogen (ER) and progesterone (PR) receptors were assayed in peritoneal and ovarian endometriotic tissue from 20 patients. In 12 of the cases the intrauterine endometrium was assayed as well. The control material consisted of normal endometrium from 30 women. The receptor content of the endometriotic tissue was less than that of the endometrium of the same patient. In most cases no receptors could be detected (12/20 cases ER-, 7/9 cases PR-) irrespective of the phase of the menstrual cycle. The endometrial receptor concentrations were that same in patients with endometriosis as in the control group. There were no differences in binding characteristics of the receptors in the two tissue types. It is concluded that endometriotic tissue contains lower a concentration of cytoplasmic ER and PR than the normal endometrium.

Ultrastructure and steroid-binding studies in leiomyomatosis peritonealis disseminata.

Leiomyomatosis peritonealis disseminata (LPD) is characterized by the development of numerous leiomyomata throughout the peritoneal cavity which appear grossly malignant but histologically benign. The etiology of this disorder has been controversial. The tenth reported case of LPD is presented with ultrastructural evidence that these tumors arise from smooth muscle cells. The cytoplasmic estrogen and progesterone bindings by these tumors were ninefold and twofold greater than receptor concentrations in normal myometrium from the same patient. In addition to the steroid binding data, the strong association of this disorder with pregnancy or, as in this case, oral contraceptives suggests that the stimulus for neoplastic initiation and growth is hormonally related.