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Chin Med J (Taipei) 1997;59:265-8.
Departments of 1Pediatrics, 2Pediatric Surgery, and 3Pathology, Veterans General Hospital-Taipei, Taipei, Taiwan, R.O.C.
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.
[Chin Med J (Taipei) 1997;59:265-8.]
Keywords: hamartoma, mesenchymoma, mesothelioma, primitive cystic hepatic neoplasm
Received: June 12, 1996.
Accepted: January 24, 1997.
Address reprint requests to: Dr. Hsueh-Ping Shing, Department of Pediatrics, Veterans General Hospital-Taipei. No. 201, Sec. 2, Shih-Pai Rd, Taipei, Taiwan, R.O.C.
Mesothelioma is an uncommon adult-type neoplasm with rare occurrences in the first two decades of life; childhood malignant mesothelioma has been considered in the past to be a curiosity. In adults, mesothelioma have a peak incidence in the sixth to seventh decades, often following severe exposure, or prolonged, low-dose exposure to asbestos. The available evidence does not appear to support a causal relationship between malignant mesothelioma and asbestos, radiation in utero. Diffuse malignant mesothelioma in childhood is a particularly aggressive tumor, with a median survival of patients of 8 to 12 months. However, such localized malignant hepatic cysts with mesothelial differentiation may exhibit an indolent biologic behavior similar to that of low-grade neoplasia or well-differentiated papillary mesothelioma in adults.
A 3-year-old boy was admitted with an abdominal mass and a six months history of progressive painless abdominal distension. There was no history of any other illness preceding the onset of distension. His appetite, weight gain, bowel and urinary habits were normal. However, his abdomen had hardened and become distended as well in half a month. There was no history of asbestos exposure, and no evidence of environmental exposure to asbestos was found on inspection of his home. There was no history of prenatal exposure to radiation or to drugs. There was no history of other cancers or major illnesses in his family. On examination, the child had a large abdominal mass which measured 10 x 10 cm over upper abdomen by palpation. It was firm, non-tender and had a smooth surface; the rest of the physical examination was unremarkable. Laboratory workup showed a hemoglobin level of 10.5 g/dl, a hematocrit of 30.5 %, and a platelet count of 217,000/cumm. The leukocyte count was 11,300/cumm with a normal differential cell count. The reticulocyte count was 1.5%, and the red cells were hypochromic and microcytic in appearance. Serum electrolytes were normal, and creatinine was 0.5 mg/dl with a BUN of 7 mg/dl. Total serum protein was 7.6 g/dl, albumin 4.5 g/dl, globulin 3.0 g/dl, and bilirubin 0.3 mg/ dl, and the liver transaminases were normal. Alkaline phosphatase and lactate dehydrogenase were mildly elevated. Prothrombin time and partial thromboplastin time were within the normal range. The urine had a specific gravity of 1.025, PH 5.0, trace proteins, and no glucose; 2 to 5 white blood cells were present per high power field in the urinary sediment. Serum alpha-fetoprotein and HCG were not elevated.
Ultrasonography of the abdomen showed huge, multiple loculated cysts spread over the whole abdominal cavity, from the diaphragm to the pelvis measuring about 15 x 15 x 19 cm in size (Figure 1). Computed tomography of the abdomen confirmed these findings but showed some solid parts over the periphery of the mass (Figure 2). The cystic mass may have arisen from the anterior superior border of the right lobe of the liver. Magnetic resonance imaging could not determine its origin because the mass was too large. The preoperative diagnosis was omental cysts or cystic lymphangioma.
During laparotomy, a huge multilocular cystic neoplasm covered with liver capsules and arising from the anterior superior border of the right lobe was found. The inferior portion of the cystic mass had a soft tissue component, and clear fluid was found inside the mass. The cystic tumor also involved gall bladder fossa. There was no evidence of abnormality of any other organ, and the cysts appeared almost completely avascular. The operative approach was based on suspected benign hepatic cysts; the cystic neoplasm was totally removed, with partial resection of the liver. The biopsy sample from the tumor of the liver had two distinct histological patterns by light microscopy. The multiple cysts lined by cuboidal cells were separated by fibrotic liver parenchyma. Tumor cell emboli were noted in lymphatic vessels. In the other solid area, a papillary arrangement and solid sheets of tumor cells were noted. Mitotic activity was high. The non-tumorous part of the liver showed portal fibrosis and bile duct hamartoma. (No mesenchymal component such as bone, cartilage, or muscle was present in the neoplasm) (Figure 3). Histochemistry showed that the tumor cells were positively stained by Alcian blue, and there was more weakly stained by Alcian blue with hyaluronidase. Immunohistochemistry of the tumor cells was positive for cytokeratin and vimentin, but negative for CEA, AFP, HCG and Factor 8. The picture of the tumor was compatible with that seen in malignant epithelial neoplasm consistent with primitive cystic hepatic neoplasm with mesothelial differentiation.
After discharge, the patient were followed up regularly at our OPD for two months. However, tumor recurrence with jaundice, ascites and hepatomegaly gradually developed. The case was then transferred to National Taiwan University Hospital for help, and the patient responded excellently to chemotherapy with a regimen of VP-16, Endoxan, Cisplatin and Adriamycin. Till now, he receives chemotherapy by schedule, our restricted basis, and radiological image shows of gradual tumor mass regression.
Mesotheliomas are tumors of mesodermal origin which arise from the lining of the pleural, pericardial or peritoneal cavities. In the peritoneal cavity, both benign and malignant variants have developed in the reflection of the peritoneum over the genital tracts, involving the epididymis and tunica vaginalis propria in men, and the posterior aspect of the uterus and Fallopian tubes in women. Mesothelioma is an uncommon, adult-type neoplasm with rare occurrence in the first two decades of life. Approximately two cases of mesotheliomas per million per year are diagnosed in the general population of the United States, and only 2-5% of this total are discovered in children and adolescents [1,2]. The majority of mesotheliomas in childhood, like their adult counterparts, originate in the pleura; less frequent sites are the peritoneum, including the tunica vaginalis and the pericardium [3-5]. Only 13 confirmed malignant mesotheliomas have been observed in more than 42,000 cancer-related deaths in the children [6]. The role of asbestos in the etiology of mesothelioma was first convincingly documented by Wagnet, et al. in 1960 [7]. In adults, mesotheliomas often occur following severe exposure, or prolonged, low-dose exposure to asbestos. In a review of published cases, only 4 of the 80 children with a previous diagnosis of malignant mesothelioma had a history of exposure to known risk factors: two had a history of exposure to asbestos, two had received radiation therapy. Therefore, mesotheliomas in children may represent a different entity from mesothelioma in adults [8].
Localized forms of malignant mesotheliomas are rare, localized fibrous types have been described in the pleura and liver; cystic mesotheliomas may develop elsewhere in the peritoneal cavity. But experience with these adult cases suggests a high potential for recurrence but no progression to malignancy.
The diagnosis may be perplexing because of its rarity and its pathologic similarities to other papillary or spindle cell neoplasm's in the pediatric age group. The differential diagnosis includes reactive mesothelial hyperplasia, other papillary neoplasms of Mullerian or germ cell derivation, and spindle cell or sarcomatoid neoplasm. The distinction of malignant mesotheliomas from other tumors is based on well documented light microscopic, histochemical, immunohistochemical and ultrastructural features.
The histology of malignant mesothelioma is divided into three types: epithelial, sarcomatoid and mixed [9]. The epithelial type is most common and, in turn, is divided into four subtypes: papillary, tubulopapillary, cord-like and sheet-like. The results of the histochemical stain were characterized by the presence of periodic acid-schiff stain (PAS) positive diastase-sensible, and alcian-positive hyaluronidase sensible intracellular and extracellular material. Immunohistochemistry was immunoreactive for a combination of low molecular weight keratin and epithelial membrane antigen (EMA), in addition to vimentin, but sometimes expressed CA-125, B72.3, S-100 protein and Leu-M1; placental alkaline phosphates (PCAP), factor-8, and carcinoembryonic antigen (CEA) were not present. Ultrastructural analysis demonstrated features characteristic of mesothelial cells, including microvilli, numerous desmosomes, abundant tonofilament and the absence of glandular differentiation or cilia. The malignant nature of the tumor is supported by demonstration of DNA aneuploidy by flow cytometry. Diffuse malignant mesotheliomas in childhood are particularly aggressive tumors, and they are difficult to treat. However, localized malignant mesothelioma may be similar to that of low-grade neoplasia or well differentiated papillary mesothelioma in adults. At the present time, there appears to be no satisfactory therapy for diffuse malignant mesotheliomas. The median survival rate of patients is 8 to 12 months [10]. Partial or complete surgical resection has been reported to increase the length of survival [11]. The role of radiotherapy remains unclear despite its use in the few reported long-term survivors of the tumors. These has been an occasional occurrence of a complete response, but more frequently partial responses and chemotherapy have been observed using combinations of chemotherapy include doxorubicin (Adriamycin) [12,13]. This drug appears to be the most effective available agent against mesotheliomas.
The authors thank the laboratory of Pathology, the National Cancer Institute and the Armed Forces Institute of Pathology in Maryland of U.S.A for pathology consultation.
Copyright: 1997, Chinese Medical Association (Taipei)