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Localized and diffuse mesotheliomas of the genital tract and peritoneum in women. A clinicopathologic study of nineteen true mesothelial neoplasms, other than adenomatoid tumors, multicystic mesotheliomas, and localized fibrous tumors.

Peritoneal mesotheliomas are rare in women, compared to serous epithelial neoplasms with which they are often confused. We evaluated the clinicopathologic features of 19 true mesothelial neoplasms affecting the genital tract or peritoneum of women (other than adenomatoid tumors, benign multicystic mesotheliomas, and localized fibrous tumors) to characterize their clinicopathologic features and to determine their clinical behavior. Six tumors were localized to one anatomic site at presentation, and 13 involved more than one anatomic site. The six localized tumors were solitary, small (0.8-2.0 cm), polypoid or nodular lesions, five of which were incidental findings. All had a predominantly tubulopapillary pattern, either pure or mixed with adenomatoid-like or small solid foci. Nuclear grade ranged from 0 to 2. Mitotic figures (MF) were absent in two tumors. The mitosis count in the other four tumors was < 1 MF/10 high-power microscopic fields (HPF) (average method) and ranged from 1 to 3 MF/10 HPF (highest count method). Five patients were alive without recurrence after postoperative intervals ranging from 19 months to 9 years (median, 5 years); one patient died of metastatic gastric carcinoma at 14 months. Thirteen tumors involved more than one anatomic site and were classified as diffuse mesothelioma. Typically, these tumors were symptomatic and accompanied by ascites. The tumors had either a plaque-like or endophytic configuration. Eleven were purely epithelial mesotheliomas, and two had a minor sarcomatoid component. Tubulopapillary patterns were present in 10 tumors, usually admixed with focal adenomatoid-like or solid patterns, and three had a purely solid pattern. All 13 tumors had grade 3 nuclei. The mitosis count ranged from < 1 to 2 MF/10 HPF (average count method) with a range of 1-4 MF/10 HPF by the highest count method. Immunohistochemically, 13/13 tumors stained for cytokeratin (AE1/AE3). None were immunoreactive for polyclonal carcinoembryonic antigen (CEA), Leu-M1, or B72.3. One diffuse mesothelioma stained focally for Ber-EP4, and electron microscopy confirmed the mesothelial nature of this tumor. Nine patients died of tumor after postoperative intervals ranging from 1 month to 6 years. Eleven patients had received postoperative adjuvant intraperitoneal or systemic chemotherapy. One patient died with increased abdominal girth 8 years after operation and one course of intraperitoneal chemotherapy, though the role of mesothelioma in her death was uncertain. One patient was alive with diffuse tumor and persistent ascites 25 months after six courses of intraperitoneal chemotherapy. One patient was alive without evidence of disease 4 months after two courses of systemic chemotherapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenomatoid Tumor↗

Malignant epithelial neoplasm consistent with primitive cystic hepatic neoplasm with mesothelial differentiation: a case report.

Mesothelioma are primary tumors of the celiomic cavity and are seen more often in adults than in children: only an estimated 2-5% of all cases present within the first two decades of life. To best knowledge of the reviewing world literature reported to date, no more than 80 proved cases of this tumor have occurred in children. One-third of mesothelioma originate in the peritoneum and two-thirds arise in the pleural cavity. Mesothelioma of the liver are extremely rare; a review of the English literature shows only three adult cases that have been reported as fibrous mesothelioma of the liver; experience with these cases suggests a high potential for recurrence, but no progression to malignancy. Cystic mesothelioma occur mainly in adults and are considered to be benign and curable. We describe a case of malignant epithelial neoplasm consistent with primitive cystic hepatic neoplasm with mesothelial differentiation arising in a 3-year-old boy, a condition which has never before been reported in childhood. Malignant primitive cystic mesothelioma is possible that some cases of intraabdominal mesenchymoma or hamartoma with malignant differentiation may have been misdiagnosed in the past; future cases should be fully evaluated, to establish the true incidence of mesothelioma disease in children.

Child, Preschool↗

Immunoperoxidase localization of secretory component in reactive mesothelium and mesotheliomas.

Immunoperoxidase localization of the secretory component (SC) of immunoglobulin (Ig) A was undertaken on paraffin-embedded tissue to investigate its usefulness in differentiating epithelial from mesothelial neoplasms. Epithelial cells, but not mesothelial cells, have been previously reported to contain SC, which may be involved in the intraepithelial transport of secretory IgA. In this study we report, for the first time, focal but unequivocal staining for SC in reactive mesothelium and mesotheliomas (10/16). Reactivity was not associated with any histologic subtype of malignant mesothelioma although staining was usually seen in the "epithelial" type. The significance in terms of possible mesothelial secretory IgA transport is discussed.

Epithelium↗

Differential diagnosis between mesothelioma and adenocarcinoma: a multimodal approach based on ultrastructure and immunocytochemistry.

Most compensations for asbestos-related deaths secondary to cancer center around mesothelioma and bronchogenic carcinoma. The differential diagnosis between mesothelioma and adenocarcinoma is a common and troublesome one, necessitating the correlation between clinical history, radiographic findings, and pathologic examination of tissues and cells. We describe a multimodal approach based on the use of routine and special stains, immunocytochemistry, and electron microscopy for distinguishing between mesothelioma and adenocarcinoma. Once a malignant diagnosis is arrived at by careful pathological examination, the tumor is classified as mesothelioma if mesothelial cells are identified as the constituent cells of the neoplasm. Mesothelial cells are recognized by (1) their main ultrastructural features: slender and elongated microvilli, abundant intermediate filaments, and lacking secretory granules; and (2) their characteristic immunocytochemical reactivity: positivity for cytokeratin, EMA, and vimentin, and negativity for carcinoembryonic antigen (CEA), B72-3, Leu-M1, and other gland-cell markers. A variety of methods have been attempted in an effort to distinguish between reactive and malignant mesothelial cells. In practice, however, such distinction depends more on experience and expertise than in any fool-proof ancillary tests. A number of these tests are discussed along with the illustration of classical and unusual examples of mesothelioma and other pleural tumors.

Adenocarcinoma↗

Mesothelial and related neoplasms in children and adolescents: a clinicopathologic and immunohistochemical analysis of eight cases.

Mesothelioma is a neoplasm that occurs infrequently in childhood; only an estimated 2-5% of all cases present in the first two decades of life. The diagnosis may be perplexing because of its rarity and its pathologic similarities to other papillary or spindle cell neoplasms in the pediatric age group. We have studied eight cases of mesothelial or submesothelial-derived neoplasms of pleural (four cases) and peritoneal (four cases) origin in patients 4 to 17 years of age at diagnosis. Microscopically, six were epithelial, with papillary, tubuloglandular, and solid patterns. Two tumors were predominantly fibrous appearing, one a localized pleural fibroma and the other a diffuse pleural sarcomatoid mesothelioma. All of the tumors were immunoreactive for vimentin, and all except the pleural fibroma stained for either cytokeratin, epithelial membrane antigen, or both. None reacted with antibodies to carcinoembryonic antigen, placental alkaline phosphatase, or Leu-M1. At last follow-up, three patients were dead of tumor, three were alive and well, and two had been recently diagnosed and were undergoing treatment. These results indicate that the immunohistochemical profile delineated for mesothelioma in adults is equally applicable to mesothelial neoplasms in younger patients and is useful in establishing a diagnosis. The prognosis for malignant mesothelioma in childhood appears to be as unfavorable as the adult counterpart, with the possible exceptions of certain clinicopathologic subtypes.

Adolescent↗

Mesotheliomas: a light- and electron-microscopical study concerning histogenetic relationships between the epithelial and the mesenchymal variants.

Mesotheliomas have variable histological patterns which may suggest a predominance of epithelial cells, a predominance of mesenchymal cells, or a mixture of epithelial and mesenchymal cells. An adenomatoid tumor of the testis, a fibrous mesothelioma, and an epithelial mesothelioma were studied by light and electron microscopy to search for evidence of a histogenetic link between the various cell types. Each neoplasm was composed of poorly differentiated spindle-shaped cells and variably differentiated cells having epithelial, mesenchymal, and combined epithelial and mesenchymal features. The differentiated neoplastic cells exhibited a spectrum of cytodifferentiation with typical mesothelial cells at one end, typical fibroblasts at the other end, and transitional forms in between. These observations are presented in detail as morphological evidence for a direct histogenetic relationship between the epithelial-appearing cells and the mesenchymal-appearing cells of human mesothelial neoplasms.

Adult↗

[Occupation related thoracic tumors].

It is estimated that about 4% of cancer mortality is attributed to occupational risk factors. Due to long latency periods it is often difficult to establish causal relationships. Thoracal cancer accounts for about 88% of all compensated occupational cancers in Germany. Most important exposures and diseases are asbestos-related lung cancer, asbestos-related malignant mesothelioma and radiation induced lung cancer (by Radon and its decay products). Lung cancer caused by nickel compounds, hexavalent chromium, arsenic and its compounds, coke oven gases and polycyclic aromatic hydrocarbons are rare. Silica-dust induced lung cancer can be compensated as occupational disease if a silicosis is present. In Germany every physician is obliged to notify a suspected occupational cancer as well as other occupational diseases.

Asbestosis↗

Diffuse intra-abdominal clear cell myomelanocytic tumor: report of an unusual presentation of "PEComatosis" simulating peritoneal mesothelioma.

We report a case of diffuse myomelanocytic tumor of the peritoneum that simulates, clinically and instrumentally, a malignant mesothelioma. The patient was a 70-year-old woman with a history of ancient hysterectomy for fibroids, who presented with abdominal discomfort. Exploratory laparotomy revealed diffuse encasing of the peritonealized organs by a thin, fleshy, gray-white tissue rind. Scattered tumor masses were present as well. A dominant lesion measuring 6 cm in larger size was resected from the pelvis. Histological examination revealed a tumor composed of epithelioid and spindle cells, exhibiting either a clear or slightly eosinophilic cytoplasm and a mild to moderate nuclear pleomorphism. Focal areas of necrosis could be documented. Immunohistochemically, tumor cells were positive for HMB45, melan-A, and smooth muscle actin, but negative for other antibodies, including epithelial markers, desmin, and S100 protein. We believe that this case represents an example of myomelanocytic tumor of uncertain biologic potential, a member of the recently devised perivascular epithelioid cell tumors (PEComa), with an unusual presentation simulating a diffuse mesothelial neoplasm. The origin of this particular lesion is briefly discussed in light of the recent literature published on the subject.

Abdominal Neoplasms↗

Pathology of malignant mesothelioma.

The diagnosis of malignant mesothelioma can pose several problems to the surgical pathologist. First, the morphological appearances of the tumour are known to be diverse with mimicry of a range of both reactive and neoplastic conditions. Second, due to the relative inaccessibility of the serosa, biopsy material is often scanty and fragmentary, producing a plethora of interpretive ambiguities. Third, adjunct techniques such as mucin histochemistry and immunohistochemistry, whilst useful in excluding malignant mesothelioma have little role in confirming the diagnosis. The accurate diagnosis of diffuse malignant mesothelioma is important for two reasons: (1) In relation to prognosis as it has an almost invariable fatal outcome, which contrasts with the other mesothelial neoplasms such as the benign adenomatoid tumour and the borderline malignant tumours, namely the well-differentiated papillary mesothelioma and multicystic mesothelioma; (2) In relation to occupational-related compensation claims following asbestos exposure. This review summarizes the aetiology of asbestos-induced neoplasia, possible mechanisms of tumour development and highlights potential diagnostic pitfalls.

Asbestos↗

Synchronous diffuse malignant mesothelioma and carcinomas in asbestos-exposed individuals.

AIMS: The development of synchronous diffuse malignant mesothelioma and carcinoma in individuals exposed to asbestos is rare. We report nine cases and discuss the medico-legal implications. METHODS AND RESULTS: Five hundred patients seeking compensation for asbestos-related diffuse malignant mesothelioma were reviewed with access to post-mortem data. The study group comprised cases in which a second (non-mesothelial) neoplasm was identified. The study group comprised eight males, one female, mean age 68 years (range 60-75). All individuals gave a history of asbestos exposure. Synchronous malignant mesothelioma with carcinoma was identified in 9/500 (1.8%). Eight malignant mesotheliomas were pleural, one was primary peritoneal in origin. By morphological subtyping there were four epithelioid, three biphasic and two sarcomatoid mesotheliomas. In 6/9 (67%) the second tumour was a primary bronchogenic carcinoma (three adenocarcinomas, two squamous cell carcinomas and one small-cell carcinoma). In 3/9 (33%) the second tumour was a non-bronchogenic carcinoma (colonic, pancreatic and breast ductal adenocarcinoma). No other neoplasms were identified in the cohort of malignant mesotheliomas studied. Five persons had pathological evidence of asbestosis (four had bronchogenic carcinomas, one colorectal adenocarcinoma). Two persons with non-bronchogenic carcinomas had identifiable asbestos bodies but no interstitial fibrosis. In two cases the second neoplasms (primary bronchogenic squamous cell and small-cell carcinomas) were associated with diffuse interstitial fibrosis but no asbestos bodies were seen on light microscopy. In each case transmission electron microscopic mineral analysis revealed an asbestos fibre burden within the background population range for control subjects and well below that seen in cases of established asbestosis. These cases were considered to represent cryptogenic fibrosing alveolitis in subjects with a history of asbestos exposure. CONCLUSIONS: Synchronous malignant mesothelioma with carcinomas in asbestos-exposed workers is rare and identified in 1.8% of 500 malignant mesotheliomas in this series. In most cases the carcinoma represents a primary bronchogenic neoplasm. Primary lung carcinomas are recognized to be asbestos related only when occurring in association with asbestosis. In this series this combination (bronchogenic carcinoma and asbestosis) was seen in four (0.8%) cases. In post-mortem cases for possible malignant mesothelioma it is important to identify any other neoplasia and determine whether it is related to asbestos. Their presence impact upon anticipated life expectancy and in the presence of malignant mesothelioma will affect the compensation settlement.

Adenocarcinoma↗

[Epididymal adenomatoid tumors. 2 new cases].

OBJECTIVE: To review the different aspects of epididymal tumors, with special reference to adenomatoid tumor of the epididymis (mesothelial neoplasm). Two such cases are reported herein. METHODS: Two cases of adenomatoid tumor of the epididymis are described. The clinical features, diagnosis and treatment are discussed, within the context of the algorithm recently presented by Pellicé and co-workers. RESULTS/CONCLUSION: Most of the epididymal tumors are benign and treatment using a scrotal approach will suffice. However, inguinotomy should be performed when the benign nature of the tumor cannot be established unequivocally.

Adult↗

Selected other problematic testicular and paratesticular lesions: rete testis neoplasms and pseudotumors, mesothelial lesions and secondary tumors.

The proximity and, in some instances, communication between several structures in the testis and paratestis (rete testis, epididymis, mesothelium, vestigial epithelium and paratesticular soft tissue) result in a plethora of interesting tumors and tumor-like lesions that together pose a formidable diagnostic challenge both because of their morphologic overlap and rarity. The occasional spread of tumors primarily at other sites to this region adds to the potential problem encountered. This review provides an overview of the pathology of nonmesenchymal paratesticular neoplasms and pseudotumors with a focus on the approach to tubulopapillary neoplasms for which diagnostic considerations may include carcinoma of the rete testis, malignant mesothelioma, ovarian-type epithelial tumors, epididymal carcinoma and metastatic carcinomas. The cornerstone of accurate characterization of these lesions is still a comprehensive, traditional clinicopathologic approach, clinical history (of another primary), gross examination (location) and routine light microscopy, but judicious incorporation of contemporary immunohistochemical markers may aid or in some instances be crucial in resolving the problems encountered.

Adenocarcinoma↗

Primitive cystic hepatic neoplasm of infancy with mesothelial differentiation: report of a case.

A malignant cystic neoplasm in the liver of a 6-month-old girl is reported. The neoplasm has unique clinical and morphological features, and despite ultrastructural and immunohistochemical studies, the tumor could not be clearly classified as any known primary hepatic neoplasm of infancy. A differentiated cystic component of the neoplasm had features of cystic peritoneal mesothelioma. Alpha-1-antitrypsin and alpha-fetoprotein were demonstrated in solid, anaplastic portions of the recurrent tumor by immunohistochemistry. The neoplasm recurred after surgical resection and proved fatal 11 months following diagnosis, despite multiple courses of chemotherapy.

Female↗

Tumour spread in serosal cavities: what have we learned? Montebello Conference--PSC, Lillehammer, Norway, June 18-22, 2004.

During the Montebello Conference on malignant serosal tumours at Lillehammer, Norway, in June 2004, a group of 30 international experts addressed the biologic and genetic aspects of malignant tumours affecting serosal cavities in the human body. Three neoplasms were mainly dealt with: mesotheliomas arising locally, ovarian carcinomas developing in close proximity to the serosa, and breast tumours in which the spread came from some distance. New, important data on the tumour microenvironment and the process of carcinogenesis with progression and acquisition of invasive properties shed new lights on the mechanisms, including proliferative properties, alterations of signal transduction pathways, and tissue remodelling by proteolytic enzymes in the metastasizing cells. Several of these markers have considerable diagnostic and clinical interest. In addition, new aspects of morphologic and immunocytochemical characteristics of the cells as well as genetic markers may soon become powerful tools for practical use. The molecular fingerprint of the individual tumours may also give guidelines for chemotherapy as well as biologic therapies, including induction of apoptosis. The easy accessibility of tumours from serosal fluids and possibilities for specific discrimination of the neoplastic cells from admixed leukocytes and other cells are promising avenues for cytodiagnostics.

Breast Neoplasms↗

Fine-needle aspiration cytology of recurrent and metastatic mixed mesodermal tumors.

We report the cytological and clinical findings of 16 fine-needle aspirates (FNAs) performed on recurrent (n = 6) and metastatic (n = 10) mixed mesodermal tumors (MMMTs). The median interval between the primary diagnosis and FNA was 16 mo. Primary sites were the endometrium (n = 11), the ovary (n = 3), the cervix (n = 1), and pelvic soft tissue (n = 1). Primary tumors showed carcinoma with homologous mesenchymal components in 13 cases and focal heterologous elements in three (two chondrosarcomas and one rhabdomyosarcoma). The FNAs showed carcinoma in all 16 cases, with adenocarcinoma differentiation in three. Mesenchymal elements were identified in aspirates of three recurrent and two metastatic lesions. They were all homologous. aspirates. We conclude that mesenchymal components in FNAs of MMMTs are less likely to be seen in metastatic lesions, and that heterologous mesenchymal components are rarely seen in these aspirates even in recurrent disease. These findings confirm that the epithelial component is responsible for the malignant behaviour of MMMTs, and suggest that these lesions may need to be classified as sarcomatoid carcinomas rather than true carcinosarcomas.

Adenocarcinoma↗

Peritoneal carcinomatosis: role of (18)F-FDG PET.

UNLABELLED: Peritoneal carcinomatosis can be difficult to diagnose, as CT is insensitive, with peritoneal biopsy and lavage often subject to problems of sampling error. The aim of our study was to evaluate the role of (18)F-FDG PET in detecting peritoneal carcinomatosis in patients with stomach, ovarian, and adrenal cancer and mesothelioma and to compare the results with CT scans in the same patient group. Our secondary aim was to identify characteristic patterns of abdominal (18)F-FDG uptake in biopsy-proven peritoneal disease and to correlate these patterns with available histologic and anatomic findings after surgery and structural imaging. METHODS: The medical records of 88 patients with stomach (n = 48), ovarian (n = 13), and adrenal cancer (n = 6) and mesothelioma (n = 21) were reviewed for the presence of peritoneal tumor on (18)F-FDG PET and CT scans. The results were correlated with either contemporaneous peritoneal biopsy or ascitic aspirate or with radiographic or clinical follow-up if histology was negative or unavailable. Of 24 patients with suspected peritoneal tumor, 17 had biopsy-proven findings of peritoneal disease. RESULTS: Of the 24 patients with suspected peritoneal tumor, (18)F-FDG PET was positive in 14 patients, with 1 of these scans being false-positive, CT was positive in 10 patients, and either PET or CT was positive in 18 patients. This yielded sensitivities of 57% (13/23), 42% (10/23), and 78% (18/23), with uniformly high positive predictive values of 93% (13/14), 100% (10/10), and 95% (18/19), respectively. We identified 2 distinctly abnormal scintigraphic patterns of focal and uniform (18)F-FDG uptake corresponding to nodular and diffuse peritoneal disease on pathologic examination. CONCLUSION: (18)F-FDG PET adds to conventional imaging in the staging of peritoneal carcinomatosis. It is also a useful diagnostic tool when peritoneal biopsy is either unavailable or inappropriate. We have identified 2 distinct scintigraphic patterns that appear to predict the presence of either nodular or diffuse peritoneal pathology.

Adrenal Gland Neoplasms↗

The spectrum of mesenchymal skin neoplasms reflected by the new WHO classification.

Mesenchymal tumors are a heterogeneous group of tumors often arising in the skin and soft tissue. The tumors have been reclassified by the WHO in 2002. Benign mesenchymal tumors are about a hundred times more frequent than malignant mesenchymal tumors. Clinically, mesenchymal tumors often present as skin-colored nodes. Overall, elderly persons are more affected than younger individuals. The etiology is often unknown, sometimes there is an association with insults such as radiation, scars, or lymphedematous or venous stasis. Whereas some years ago a wide excision with a margin of 3-5 cm was performed for malignant variants, today micrographic surgery is preferred, as it can avoid mutilating procedures. Early detection and removal is critical since mesenchymal skin tumors often cannot be cured by radiation or chemotherapy.

Humans↗