Mixed neuronal-glial tumor of the digestive tract: distinctive entity from gastrointestinal stromal tumor?

A 53-year-old-woman presenting with pelvic discomfort was found to have a 9.5 cm tumor located in the wall of the ileon. Light microscopy showed that the tumor was made of fascicles of plump spindle cells and bizarre epithelioid cells. A cuff of lymphoid cells was also present at the tumor margin. The tumor cells strongly expressed tau protein, neuron-specific enolase, protein green product 9.5 and glial fibrillary acid protein (GFAP), but did not show positive immunostaining for S-100 protein, CD34 or CD117. The tumor showed unequivocal ultrastructural evidence of neural differentiation. Skeinoid fibers were scattered throughout the tumor. This is the first mixed neuronal-glial tumor of the digestive tract to be described in the literature. Such histological and immunohistochemical features could be misinterpreted as features of digestive schwannoma. We suggest that this tumor is distinct from gastrointestinal stromal tumors in lacking CD34 and CD117 expression.

Canine extracutaneous mast-cell tumours consisting of connective tissue mast cells.

Two cases of canine extracutaneous mast-cell tumours were encountered, originating from the mucosa of either the oral cavity or the small intestine. The dogs had no neoplasms in the skin. Immunohistochemical and ultrastructural studies demonstrated that the neoplastic cells had the features of connective tissue mast cells. It would seem, therefore, that at least some extracutaneous forms of the neoplasm originate from connective tissue mast cells. Heparin was a useful cytological marker to diagnose this type of mast-cell tumour.

Morphological-histochemical study of intestinal carcinoids and K-ras mutation analysis in appendiceal carcinoids.

Intestinal carcinoids are potentially malignant neoplasms. Their histogenesis and pathogenesis are currently uncertain. The morphological and histochemical characteristics of twenty intestinal carcinoids are studied. The primary sites of three mucin-producing tumors were examined by electron microscope. Furthermore 11 appendiceal carcinoids were analysed by the polymerase chain reaction (PCR) for the detection of ras and p53 point mutations. Microscopically all carcinoids were of mixed type. Focal mucin production was evident in three carcinoids that metastasised to regional lymph nodes. HID-Alcian blue staining proved that mucin in both primary and secondary foci did not belong to the sulphated group. The secretory granules and mucin droplets found in a single neoplastic cell suggest that carcinoids of the small intestine and some of the appendix arise from the endoderm. Neither ras nor p53 mutations were detected. It seems that ras oncogenes are probably not involved in the pathogenesis of appendiceal carcinoids.

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.

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.

Ileal lymphoma in swine.

Eleven cases of alimentary lymphoma affecting the ileum were observed among 26 cases of swine lymphoma detected by meat inspection in Kochi, Japan. The ileal lymphomas were located in the Peyer's patches, along with early involvement of regional lymph nodes, and showed a characteristic pattern of follicular invasion leading to diffuse growth. Following the National Cancer Institute Working Formulation, 10 neoplasms were classified as diffuse, large, noncleaved cell lymphomas and one neoplasm was a diffuse, mixed, small to large cell lymphoma. Both types of lymphoma featured numerous intermingled "starry sky" histiocytes. The lymphoma cells tended to infiltrate into the muscular layer of the ileum in an "Indian file" pattern. Two cases also showed transserosal metastasis into the abdomen and leukemic change. The lymphoma cells showed membrane positivity for alkaline phosphatase and diffuse cytoplasmic staining for acid phosphatase and non-specific esterase. Monoclonal intracytoplasmic immunoglobulins were demonstrated in nine neoplasms (IgM-lambda in seven, IgG-lambda in one, and IgG-kappa in one). In the areas of follicular invasion, an attenuated network of follicular dendritic cells was visualized via an antiserum against the beta subunit of S-100 protein. Ultrastructurally, strands of dilatated rough endoplasmic reticulum and scattered or clustered dense bodies were noted. When compared with feline and human alimentary lymphoma, including Burkitt's lymphoma, the present neoplasms possessed distinctive features, such as originating in Peyer's patches, transserosal metastasis, and predominantly large B cell type with IgM-lambda type immunoglobulin expression, although some features were similar.

Ultrastructural and immunocytochemical features of a case of neuroendocrine carcinoma developing in a prior ileostomy site.

A patient who developed a mixed neuroendocrine carcinoma and adenocarcinoma at the site of a previous long-standing ileostomy is reported. The neuroendocrine features are documented by both ultrastructural and immunocytochemical findings. Carcinoma arising in an ileostomy site is rare but has been recorded in patients with long-standing ileostomies after colectomy for chronic inflammatory bowel disease, as in this patient. Neuroendocrine carcinoma developing in this setting apparently has not been described before, however.

Gastrointestinal autonomic nerve tumor presenting as high-grade sarcoma. Case report and review of the literature.

Gastrointestinal autonomic nerve (GAN) tumors, also known as plexosarcomas, are a rare distinct subtype of the gastrointestinal stromal tumors. These tumors are usually histologically low-grade, epithelioid or spindle-cell neoplasms that can be distinguished from the other gastrointestinal stromal tumors on the basis of their unique ultrastructural features. A 66-year-old female presented with a histologically high-grade sarcoma of the small bowel. Ultrastructural studies showed features of a GAN tumor. The light microscopic and ultrastructural features are described. The tumor cells gave strong, diffuse staining for vimentin and synaptophysin, and weak focal staining for neuron-specific enolase and S100. While usually presenting as low-grade neoplasms on histologic examination, this case demonstrates that GAN tumors should be considered in the differential diagnosis of a histologically high-grade sarcoma of the gastrointestinal tract, especially when evidence of smooth muscle, peripheral nerve sheath, or neuroblastic origin is not forthcoming.

Multiple ileal carcinoids and appendiceal endocrine carcinoma in association with Meckel's diverticulum. A histochemical and immunohistochemical study.

An unusual case of multicentric ileal carcinoids and appendiceal endocrine carcinoma in association with Meckel's diverticulum was studied, with special attention given to the histogenesis of these neoplasms. A total of six ileal carcinoids, the largest of which was located in the wall of Meckel's diverticulum, were macroscopically and microscopically confirmed to be multicentric and revealed no visceral metastases. The histochemical and immunohistochemical profiles of the ileal carcinoids and the appendiceal carcinoma differed considerably: the former resembled subepithelial neuroendocrine cells and the latter resembled epithelial nonmucous cells and Paneth cells. The appendiceal carcinoma exhibited signs of endocrine differentiation, expressing somatostatin and vasoactive intestinal polypeptide, and secreted mucus. The tumor had metastasized to various organs. The carcinoids exhibited signs of neuroendocrine and glandular differentiation, expressing neuron-specific enolase, serotonin, chromogranin A, and endocrine granule constituent, and secreted little mucus. The data suggest different tumor cell origins or different grades of differentiation of the two types of intestinal endocrine cell tumor.

[The differentiation of tumor cells of the human large intestine during the acquisition of multiple drug resistance]. / Differentsirovka kletok opukholei tolstoi kishki cheloveka pri priobretenii mnozhestvennoi lekarstvennoi ustoichivosti.

By selection in the medium containing increasing actinomycin D concentrations two sublines with acquired multidrug resistance (MDR) caused by P-glycoprotein (P170) overproduction were isolated. The obtained cell lines as well as parent cells grow in vitro as morphologically organized aggregates, so-called organoids. Comparative electron microscopic study of sensitive and drug resistant organoids has shown that the development of MDR was accompanied by the enhancement of the tumour cell differentiation: the percentage of differentiated cells, the extent of their maturity, and the quantity of lumens were higher in MDR organoids than in parent cell line. The size of glandular structures in resistant organoids was also enlarged. Possible mechanisms of observed phenomenon are discussed.

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.

Electron microscopy of intestinal adenomatosis in the blue fox, Alopex lagopus.

Scanning electron microscopy of adenomatous intestinal tissue in the blue fox revealed an irregular surface topography of the colon with increased diameter of the crypt openings and prominent ridge formations between crypts. The ileum showed villous atrophy and fusion. Microvilli were short and irregular. Small ulcerations of intestinal mucosa were seen. Freeze-fracture revealed curved intracellular organisms in the altered epithelial cells. Transmission electron microscopy showed features associated with immaturity and high protein synthesis. Filamentous extensions from the basolateral plasma membrane of altered epithelial cells sometimes penetrated the basal lamina. The cytoplasm contained numerous polyribosomes, nuclei had many indentations and large and irregular nucleoli. Intracellular bacteria, with morphology corresponding to Campylobacter spp. were found in the apical epithelial cytoplasm. No host-cell-derived membrane was seen to surround the bacteria.

Inflammatory fibroid polyp of the small intestine: ultrastructural and immunohistochemical observations.

The ultrastructural and immunohistochemical features of a primary tumor of the ileum showing the classic histologic features of an inflammatory fibroid polyp (IFP) of the gastrointestinal tract are presented. Ultrastructurally the proliferating cells showed a combination of fibroblastic and histiocytic features, with abundant rough endoplasmic reticulum and active production of collagen in many of the cells and long, dendritic cytoplasmic projections with large cytoplasmic vacuoles containing remnants of phagocytosed cellular debris in others. Immunohistochemical studies showed strong cytoplasmic positivity in the proliferating cells with vimentin antibodies and scattered positivity with muramidase. Additional findings include the ultrastructural demonstration of oligocilia and occasional primitive intercellular junctions. The findings in this case suggest that IFP may represent a proliferation of primitive submucosal stromal cells exhibiting incomplete fibrohistiocytic differentiation.

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.

Dual carcinoid tumors of Meckel's diverticulum presenting as metastasis in an inguinal hernia sac: case report with literature review.

Neoplasms arising in Meckel's diverticulum or involving hernia sacs are rare. The authors present a unique case of two asymptomatic carcinoid tumors arising in a Meckel's diverticulum, which were discovered because of microscopic metastasis in a grossly unremarkable inguinal hernia sac. This article describes the clinical and morphologic features of this unusual case, reviews the topic of neoplasms involving hernia sacs and Meckel's diverticula, and includes a brief review of immunocytochemical findings in carcinoid tumors.

Application of Grimelius argyrophil staining to the study of tumour ultrastructure. II. Effects of resin embedding: Epon.

2 methods have so far been proposed for staining samples by the argyrophil technique of Grimelius for electron microscopy. Vassallo et al. (1971) used en bloc staining after fixation with a mixture of glutaraldehyde and formaldehyde, then Håkanson et al. (1971) stained sections from samples previously fixed by double formaldehyde/OsO4 treatment and embedding in resin. Another investigation that concerned glutaraldehyde fixation showed the effect of this fixative in sample staining (Soranzo and Roland 1987). The present experiments demonstrated that Epon intervenes directly in argyrophil staining of sections. With this resin, the staining process lasted longer than with paraffin embedding materials and offered no guarantee of positivity. Granules with a double structure and dense core displayed different locality of argyrophilia before and after embedding.