[Establishment of a highly-metastatic model of human primary melanoma of the small intestine orthotopically transplanted in the small intestine of nude mice].

OBJECTIVE: To provide an useful animal model for exploring metastatic biology and anti-metastatic therapy of primary malignant melanoma of the small intestine. METHODS: A 49-year old male patient with malignant melanoma was treated by surgery, and the primary tumor in the small intestine and a metastatic tumor in the liver were removed. The diagnosis of malignant melanoma was confirmed by histopathology. Fresh melanoma tissue fragments taken from the primary intestinal tumor and hepatic metastatic tumor were orthotopically implanted into the mucosal layer of small intestine in nude mice, respectively. The tumor growth rate, invasion and metastasis of the transplanted tumors were observed. Light and electron microscopy, immunophenotype analysis, flow cytometry and karyotype analysis were carried out. RESULTS: Fragments of the primary and liver metastatic malignant melanoma were successfully implanted in nude mice. After continuous passages in nude mice, an highly-metastatic model of human primary malignant melanoma of the small intestine (from the primary lesion) in nude mice (termed HSIM-0602) and a liver metastatic model of human primary malignant melanoma of the small intestine (originally from the liver metastatic lesion) in nude mice (termed HSIM-0603) were successfully established. Histological examination of the transplanted tumors revealed a high-grade melanoma of the small intestine. Immunohistochemical stainings of S-100 protein and HMB45 were positive. Many scattered melanosomes and melanin complex were seen in the cytoplasm of tumor cells. Chromosomal modal number was between 55 and 59. DNA index (DI) was 1.59 - 1.71, representing a heteroploid. The HSIM-0602 and HSIM-0603 tumor models had been maintained for 21 and 23 passages in nude mice, respectively. 227 nude mice were used for transplantation. Both the growth rate after transplantation and resuscitation rate from liquid nitrogen cryopreservation were 100%. The HSIM-0602 model exhibited 84.8% lung metastasis, 65.7% liver metastasis and 63.8% lymph node metastasis. However, HSIM-0603 displayed 100% liver metastasis, 46.7% lung metastasis and 71.3% lymph node metastasis. The transplanted tumors actively and invasively grew in the small intestine of nude mice and showed hematogenous and lymphatic metastases. CONCLUSION: To our knowledge it is the first time that two strains of spontaneous highly-metastatic nude-mouse model of human primary malignant melanoma of the small intestine have been successfully established in our department. The models are very closely mimic the natural clinicopathologic course of primary small intestinal melanoma in humans and provide ideal animal models for the researches on metastasis biology and anti-metastatic experimental therapy of malignant melanoma of the small intestine.

Perivascular epithelioid cell tumor of the jejunum.

Certain HMB-45-positive epithelioid cell tumors have recently been categorized under a unified concept: perivascular epithelioid cell tumor (PEComa). In this report, we describe ajejunal PEComa arising in a 32-year-old woman without other tumors or stigmata of tuberous sclerosis. The tumor consisted of nests of epithelioid cells with clear to granular eosinophilic cytoplasm. The nests were separated by thin fibrovascular septa. The tumor cells were positive for HMB-45 and progesterone receptor, and negative for cytokeratin, epithelial membrane antigen, vimentin, desmin, alpha-smooth muscle actin and CD34. RT-PCR analysis failed to reveal fusion transcript ETW/ATF1, which is characteristic of clear cell sarcoma of the soft parts. She developed a recurrent tumor at the pelvic wall and the left ovary at 13 and 25 months after the first operation, respectively. Each tumor was resected surgically, and no additional therapy was performed. We think the tumor of this case is a malignant form of PEComa because of the clinical history of multiple recurrences and the size of the primary tumor. Our case underscores that to make a correct diagnosis, clinical information and immunohistochemical examination are essential.

Gastrointestinal autonomic nerve tumors (plexosarcomas). is A radiological diagnosis possible?

The gastrointestinal autonomic nerve (GAN) tumor, or plexosarcoma, is a very uncommon stromal tumor of the gastrointestinal tract and retroperitoneum. Distinction of GAN tumors from other stromal tumors is not possible based on imaging studies, and needs specific ultrastructural and inmunohistochemical techniques. There are some morphologic characteristics that the radiologist should know, so as to include these rare tumors in the differential diagnosis of an abdominal mass. We report two new cases: small bowel (jejunum-ileum) and stomach GAN tumors.

Jejunal stromal tumor with skeinoid fibers or myenteric plexoma: a case report.

Small intestinal stromal tumors with 'skeinoid fibers' are uncommon stromal tumors with an associated controversial histogenesis. Although their microscopic appearance is suggestive of a smooth muscle nature, they lack specific smooth muscle features, as evident by electron microscopy and immunohistochemistry. They also appear to lack features of neurogenic origin because they fall to react with neural/neuroendocrine markers such as S-100 protein, neuron-specific enolase and chromogranin. It is interesting, nonetheless, to note that the ultrastructural examination of these tumors may show structures reminiscent of neural differentiation, such as cytoplasmic projections, containing occasional membrane-bound, dense-core, neurosecretory-type granules, which mimick the long cytoplasmic processes seen in tumors of neural origin. Moreover, the association of these tumors with Von Recklinghausen's neurofibromatosis, as well as the presence of 'skeinoid fibers' in proven neurogenic spindle cell neoplasms such as gastrointestinal autonomic nerve tumors and schwannomas, suggests that these tumors might also be neurogenic in origin and enhances the diagnostic value of 'skeinoid fibers' as a possible ultrastructural marker of neural differentiation. Thus, light microscopic evaluation is clearly insufficient to accurately diagnose these tumors and to determine their histogenesis, electron microscopic and immunohistochemical studies being necessary. In this article the histogenesis of small intestinal stromal tumors with 'skeinoid fibers', regarding a jejunal neoplasm in a 63-year-old patient, is reviewed. The light microscopic, immunohistochemical and ultrastructural features are described and compared with findings usually seen in all those stromal tumors which may raise a differential diagnosis, such as smooth muscle stromal tumors, gastrointestinal autonomic nerve tumors, schwannomas, paragangliomas and fibrosarcomas.

Stromal tumors of the jejunum and ileum.

Gastrointestinal stromal tumors (GISTs), as currently defined, are mesenchymal tumors of the gastrointestinal tract composed of spindled and/or epithelioid stromal cells that are neither mature Schwann cells nor smooth muscle cells. Many studies have lumped GISTs from all gut sites, when in fact these tumors differ histologically by location. In this study, we evaluated a set of parameters by both univariate and multivariate analysis to determine which parameters correlated with metastases in 36 GISTs from the jejunum and ileum, exclusively. The parameters included organoid architecture, cellularity, mitotic counts, epithelioid cell shape, mucosal invasion, tumor size, skeinoid fibers, nuclear pleomorphism, ischemic necrosis, immunohistochemical differentiation, and proliferating cell nuclear antigen labeling. We evaluated these retrospectively without knowledge as to the metastatic outcome of the tumors. By univariate analysis, dense cellularity, mitotic counts, epithelioid cell shape, mucosal invasion, and size were statistically significant correlates with metastases. By multivariate analysis, only dense cellularity and mitotic counts were independent correlates with metastases. Whether these features are useful predictors of behavior remains to be tested.

Carcinoids of the small intestine: a statistical evaluation of 1102 cases collected from the literature.

A total of 1102 cases of jejunoileal carcinoids collected from 516 articles reported by over 35 countries or related areas were evaluated. Among these 1102 cases. 93 cases of Meckel's diverticular and 969 cases of remaining jejunoileal carcinoids could be effectively analyzed. Multiple clinicopathologic aspects were investigated including clinical manifestations, location, depth and size of the lesions related to metastases, immunohistochemistry, electron microscopy, carcinoid syndrome and serotonin activity. Jejunoileal carcinoids were characterized by a male preponderance with an age group older than that in the extraappendiceal gastrointestinal (GI) series. They also had a significantly aggressive malignant nature exhibiting a high metastasis rate particularly evident in small-size lesions with submucosal invasion. A high incidence of argentaffin cell type and carcinoid syndrome with high serotonin activity was also exhibited by jejunoileal carcinoids.

Sarcomatoid carcinoma of the small intestine.

A case of sarcomatoid carcinoma of the small intestine in a 76 year old Chinese woman is presented. The diagnosis was confirmed by light microscopic, immunohistochemical and ultrastructural findings. It is a rare neoplasm, with only 13 previous reported cases in the literature. Patients with the disease usually had a poor prognosis. The nomenclature, histological and immunohistochemical findings of these tumours were diverse. To our knowledge, this case is the first report of this disease entity in a Chinese patient, and has its distinctive features. The patient was the oldest one in literature with this disease, and had the shortest survival time after the presentation of symptoms.

Small intestinal stromal tumors with skeinoid fibers. Clinicopathological, immunohistochemical, and ultrastructural investigations.

Microscopic appearances of spindle cell tumors of the gastrointestinal tract are suggestive of smooth muscle origin; however, they usually lack specific muscle cell features by electron microscopy and immunohistochemistry, thus justifying their designation as stromal tumors. The present report describes nine cases of small intestinal stromal tumors with eosinophilic stromal globules composed of tangles of curved fibers with crossbands simulating an appearance of skeins, designated as skeinoid fibers. Patients' ages ranged from 28 to 87 years; and four were male. The tumors presented as well-delineated mural nodules ranging from 1.8 to 13 cm in size, causing intestinal obstruction or hemorrhage. Four were in the duodenum, three in the jejunum, and two unspecified. Microscopically, seven were benign; one, to the largest, was definitely malignant and metastasized to the liver. Another, the second largest (7.5 cm), showed moderate atypia with two mitoses per 10 high-power fields. The light microscopic appearance, including immunohistochemistry, were typical for small intestinal stromal tumors. Skeinoid fibers were strongly periodate-Schiff's procedure-positive and stained blue with the trichrome stain. They appeared as a few micra-sized specks to large globules reaching a few millimeters. Skeinoid fibers were also found in three neurogenic spindle cell tumors (an acoustic neuroma, a neurofibroma, and a plexosarcoma of the mesentery), suggesting that such fibers are possible ultrastructural markers for neurogenic tumors and thus small intestinal stromal tumors with skeinoid fibers are neurogenic in origin.

Dedifferentiated leiomyosarcoma of the intestinal tract: histological, ultrastructural and immunohistochemical examinations.

Six cases of dedifferentiated leiomyosarcoma of the small and large bowel are presented with histological, ultrastructural and immunohistochemical examination. One case arose in the jejunum, two in the ileum, and the other three in the large intestine. The tumours were submucosal in four cases with large areas of ulceration; two were polypoid. Four tumours showed typical leiomyosarcomatous appearance with dedifferentiated components and two were typical leiomyosarcomas at the primary site with differentiated components only in metastatic foci. By immunohistochemistry, typical leiomyosarcomatous areas showed a positive reaction for muscle-specific actin (MSA), MB1, MB2 and myosin. In contrast, desmin-positive cells were scattered throughout the tumour or were not present. Tumour cells in dedifferentiated components were positive for alpha-1-antitrypsin and alpha-1-antichymotrypsin in all cases but one; neuron specific enolase, MB1, MB2 and myosin were positive with variety. MSA was faintly positive in only a few tumour cells of two cases and desmin was not detected in any of the cases studied. Ultrastructurally, tumour cells in typical leiomyosarcomatous areas demonstrated evident smooth muscle features, although in dedifferentiated areas they lacked such features except in one case. Our results indicate that dedifferentiated elements may derive from ordinary leiomyosarcoma and loose muscle features due to dedifferentiation.

[An isolated intestinal form of infantile myofibromatosis]. / La forme intestinale isolée des myofibromatoses infantiles.

Infantile myofibromatosis is the most common form of fibromatosis in children. It can be solitary, mainly affecting the bone or soft tissues, or multicentric with the possibility of visceral involvement. Solitary forms of visceral localization are exceedingly rare. The authors report the observation of a newborn female infant, with solitary jejunal infantile myofibromatosis which after reviewing relevant litterature on the subject appears to be the sixth case of its kind. This form must be considered in the differential diagnosis of the neonatal intestinal obstruction.

Heterotopic gastric mucosa of the small intestine in laboratory beagle dogs.

Out of the 365 young laboratory beagle dogs which were used in 17 toxicity bioassays, 15 cases (4.1%) were diagnosed as having congenital heterotopic gastric mucosa of the small intestine. Its incidence in the male dogs (12 cases out of 187) was higher than in the female dogs (3 cases out of 178). Grossly, the lesions were seen as an ulcerous focus of the small intestine, 25 cm to 88 cm proximal to the ileocecal valve. All of the lesions were quite similar histologically and electron microscopically to the normal gastric mucosa, which are composed of the surface mucous cells, chief cells, parietal cells, mucous neck cells and basal granulated cells of the stomach. And consequently, they were considered to be that of a congenital heterotopic tissue in the small intestine. The only morphological characteristic of these lesions different from the regular gastric mucosa was an association with the tubular structure seen in the basal region of these mucosal layers. These cells were considered to be of mucous-secreting cell origin because of secreting type III mucous evident from paradoxical concanavalin A or periodic acid Schiff stains. They seemed to be protecting the surrounding intestinal mucosa from gastric acid.

Pleomorphic (giant cell) carcinoma of the intestine. An immunohistochemical and electron microscopic study.

Pleomorphic (giant cell) carcinomas have been described in the lungs, thyroid, pancreas, and gallbladder. Two pleomorphic carcinomas of the small bowel and two of the large bowel are presented. On light microscopic study, the carcinomas were solid, without squamous or glandular differentiation. The tumors were composed of the following three cell types: gemistocytic (giant) cells, smaller polygonal cells, and spindle cells, with identical immunohistochemical reactions. A panel of monoclonal and polyclonal antibodies was applied. All tumors were found to coexpress keratin and vimentin. A positive reaction for neuron-specific enolase (NSE) was found in three tumors and a positive reaction for chromogranin was found in one tumor. On electron microscopic study, intracytoplasmic whorls of intermediate filaments were seen in the perinuclear area. Dense core "neurosecretory" granules were rarely seen. Intestinal pleomorphic carcinomas are histologically identical to pulmonary giant cell carcinomas. The prognosis is poor due to early tumor spread, with only a few months of postoperative survival. The pleomorphic carcinomas have some of the differentiation characteristics of carcinoid tumors and are best regarded as poorly differentiated variants of neuroendocrine carcinomas.

[Familial occurrence of carcinoid of the small intestine]. / Vékonybél-carcinoid familiaris elöfordulása.

The case of a 41 year old woman has been reported, whose "flush" syndrome was caused by a carcinoid tumor originated from the jejunum. The patient's father had to be operated for intestinal carcinoid tumor several times. The occurrence of different forms of carcinoid tumors, especially in the gastrointestinal tract, has been discussed in connection with the diagnostic approaches and therapeutical possibilities. The authors considered the case interesting for publications, because carcinoid is a rather rare tumor, and one cannot find its familiar occurrence in the available literature.

Observations on the fine structure of interdigitating cell sarcoma.

In this histo-pathological follow-up study of a case of interdigitating cell sarcoma, intracytoplasmic membrane complexes were seen by electron microscopy within the neoplastic cells. These complexes might correspond to the eosinophilic inclusions seen in the tumour cells by light microscopy; they were not identified in the initial lymph node lesion. Recently, these structures have been found to be a variation of microtubuloreticular complexes. To our knowledge, they have not been previously described in interdigitating cell sarcoma. Their significance remains obscure.

Primary adenocarcinoma of the small intestine with emphasis on microvillous differentiation.

A detailed ultrastructural study was made of 12 primary adenocarcinomas of the small intestine. A comparative analysis of microvilli identified three characteristic features in various proportions on the apical tumor cell surface. These were; 1) "long rootlets," which are long intravillous filamentous cores penetrating into the cytoplasm and identical to those observed in colonic adenocarcinoma; 2) a regular arrangement of uniform microvilli similar to the brush border of normal intestinal epithelium; and 3) sparse rudimentary microvillous structures. Because of the rarity of adenocarcinoma in the small intestine no previous study defined these ultrastructural characteristics. The results of the present study suggest that the diverse ultrastructural findings may be related to different stages of tumor cell maturation and that the neoplastic state may increase the variation and range of microvillous differentiation regardless of capacity of mucin secretion by the tumor cells. For diagnostic purposes, brush borders as well as two other microvillous features may serve to identify adenocarcinoma of mucosal origin of the small intestine, if an ultrastructural study discloses these three features.

Jejunitis cystica profunda in a hamartomatous polyp. Report of a case.

A patient with a history of abdominal discomfort and rectal bleeding was discovered to have two hamartomatous polyps, one of the jejunum and one of the colon. The former was associated with mucinous cysts at its base. The findings were similar to those described for colitis cystica profunda. This case is a rare example of cystica profunda disease of the small bowel. Uniquely, it was associated with a hamartomatous polyp.

Pulmonary rhabdomyosarcoma with isolated small bowel metastasis. A report of a case with immunohistochemical and ultrastructural studies.

A unique case of pulmonary rhabdomyosarcoma with an isolated, symptomatic small bowel metastasis is presented. The tumor affected the middle lobe, and was treated with a right pneumonectomy. Eleven months after the operation, an isolated small bowel metastasis, which produced intestinal obstruction, was resected. The patient is currently alive, 11 months after operation. The myogenous nature of the tumor was confirmed by the immunohistochemical demonstration of myoglobin in the pulmonary and enteric lesion by the ultrastructural findings of poorly developed sarcomeres.