Retroviral inclusions in the enteric smooth muscle of a tumor-bearing young chicken.

A 15-cm segment of small intestine from a 7-wk-old broiler chicken presented for slaughter was encased by a firm, white mass. Other tissues were grossly unremarkable. Microscopically, the enteric serosa and peripheral muscularis of this segment of small intestine were replaced by a fibrosarcoma. Numerous linear, intracytoplasmic, eosinophilic inclusion bodies were present in smooth muscle cells of the muscularis of the small intestine, and a few similar inclusions were present in the muscularis of the proventriculus. In the heart, there were rare intracytoplasmic inclusions typical of viral matrix inclusions. Ultrastructurally, inclusion bodies in enteric smooth muscle were viral matrix inclusions, and virions resembling avian retroviruses were present in adjacent intercellular spaces. Polymerase chain reaction (PCR) of the deoxyribonucleic acid (DNA) extracted from tumor tissues indicated the presence of proviral DNA of subgroup J avian leukosis virus. This is the first description of the light microscopic appearance of these viral matrix inclusions in enteric smooth muscle.

Rat ileocecal immunocytoma. An ultrastructural study with special attention to the presence of viral particles.

Fifteen spontaneous immunocytomas originating in the ileocecal lymph nodes of Lou/C/Wsl rats were studied by means of electron microscopy. The histology was characteristic, the tumor being formed by an accumulation of large, rounded cells with slightly eccentric ovoid nuclei, large nucleoli, and finely condensed chromatin along the nuclear walls; the cytoplasma was rich in polyribosomes. The appearance of the rough endoplasmic reticulum was apparently the same whether or not the tumor was secretory. Its development varied from one cell to another, and in only a small proportion of cells did it attain any considerable volume. In all the tumors examined, we noted the presence of intracisternal A-particles. In its morphology, the rat immunocytoma resembled the plasmacytomas induced in mice, and it also resembled certain human tumors such as Burkitt's lymphoma.

Integrin alphavbeta3 promotes anchorage-dependent apoptosis in human intestinal carcinoma cells.

A population of cells surviving during prolonged incubation in suspension (anoikis-negative cells) were selected from the original anoikis-positive human intestinal carcinoma cell line Caco-2. Anoikis-negative cells are characterized by a strong transcriptional downregulation of the alphav-integrin chain as detected by FACS analysis, RT-PCR and Northern blotting. This finding suggested that alphav-integrin generates a signal stimulating apoptosis of Caco-2 cells upon their detachment from the extracellular matrix. Two lines of evidence supporting this suggestion were provided. First, activation of the alphavbeta3 integrin on Caco-2 cells by their treatment with an alphavbeta3-specific monoclonal antibody resulted in marked stimulation of anoikis. Second, treatment of Caco-2 cells with alphav-specific antisense oligonucleotide resulted in downregulation of the expression of alphav chain and in elevated resistance of these cells to anoikis. Thus, for the first time, our data prove that alphavbeta3 integrin can be an active transducer of apoptosis-stimulating signals generated in response to disruption of the cell-matrix contacts.

Intestinal perineuriomas: clinicopathologic definition of a new anatomic subset in a series of 10 cases.

Benign peripheral nerve sheath tumors are uncommon in the gastrointestinal tract, and perineuriomas have not previously been reported to occur at this anatomic location. In this study, we analyzed the clinicopathologic and immunohistochemical features of 10 perineuriomas arising in the intestine. Eight patients were female and 2 male (median age, 51 years; range, 35-72 years). Eight of the lesions were intramucosal perineuriomas presenting as small sessile polyps detected during colonoscopy; 6 of these 8 patients were asymptomatic and undergoing colorectal cancer screening. The remaining 2 cases were submucosal masses, one each located in the colon and jejunum. Of the mucosal polyps, six were located in the rectosigmoid or sigmoid colon and one each was detected in the descending colon and transverse colon. The polyps ranged from 0.2 to 0.6 cm (median, 0.4 cm) in greatest dimension. The colonic and jejunal masses measured 3 cm and 4.5 cm, respectively. Histologically, the intramucosal perineuriomas were composed of uniform bland spindle cells having ovoid to elongated nuclei and pale indistinct cytoplasm, with no cytologic atypia, pleomorphism, or mitotic activity. The lesions had a fine collagenous stroma, demonstrated irregular borders with the adjacent lamina propria, and entrapped colonic crypts. Five cases exhibited hyperplastic changes in the adjacent or entrapped epithelium. The colonic submucosal tumor was microscopically well circumscribed, whereas the jejunal perineurioma showed focal infiltration through the muscularis propria into the subserosa. The stroma was collagenous in the colonic tumor and predominantly myxoid in the jejunal tumor. The spindle cells in the submucosal perineuriomas demonstrated tapered nuclei and elongated bipolar cytoplasmic processes. All tumors except one were positive for epithelial membrane antigen (EMA); 4 of 10 expressed claudin-1 and 2 of 10 expressed CD34. All tumors were negative for S-100 protein, glial fibrillary acidic protein, neurofilament protein, smooth muscle actin, desmin, caldesmon, KIT, and pan-keratin. Electron microscopy was performed on the tumor lacking EMA expression, revealing typical features of perineurioma, namely, spindle cells with long bipolar cytoplasmic processes and prominent pinocytotic vesicles, surrounded by discontinuous basal lamina. Clinical follow-up was available for 4 patients (median, 34 months; range, 8-53 months). No tumor recurred. In summary, perineuriomas may arise in the intestine, most often as intramucosal lesions detected as colorectal polyps with distinctive histologic features including entrapment of colonic crypts. Distinguishing perineuriomas from other spindle cell neoplasms of the gastrointestinal tract can be facilitated by immunostaining for EMA and claudin-1.

Activation of proglucagon gene transcription by protein kinase-A in a novel mouse enteroendocrine cell line.

The gene encoding proglucagon is expressed predominantly in the pancreas and intestine. The physiological importance of glucagon secreted from the islets of Langerhans has engendered considerable interest in the molecular control of proglucagon gene transcription in the endocrine pancreas. In contrast, little is known about the molecular control of proglucagon gene expression in the intestine. The recent demonstration that glucagon-like peptide-1 (GLP-1) secreted from the intestine is a potent regulator of insulin secretion and glucose homeostasis has stimulated renewed interest in the factors that control GLP-1 synthesis in the intestinal L-cell. To develop a model for the analysis of intestinal proglucagon gene expression, we have targeted expression of a proglucagon gene-simian virus-40 large T-antigen fusion gene to enteroendocrine cells in transgenic mice. These mice develop intestinal tumors that were used to derive a novel cell line, designated GLUTag, that expresses the proglucagon gene and secretes immunoreactive GLP-1 in vitro. GLUTag cells demonstrate morphological characteristics of enteroendocrine cells by electron microscopy and are plurihormonal, as shown by immunocytochemistry and RNA analyses. GLUTag cells express the proglucagon and cholecystokinin genes, consistent with the pattern of lineage-specific enteroendocrine differentiation described for mouse intestine. Proglucagon gene expression was induced by activators of the protein kinase-A pathway, and a combination of messenger RNA half-life and nuclear run-on experiments demonstrated that the protein kinase-A-induction is mediated by an increase in proglucagon gene transcription. In contrast, activators of protein kinase-C stimulated secretion, but not biosynthesis of the PGDPs in GLUTag cell cultures. Analysis of proglucagon processing in GLUTag cells demonstrated the liberation of glucagon, oxyntomodulin, glicentin, and multiple forms of GLP-1. These observations provide evidence for the direct induction of proglucagon gene transcription by a cAMP-dependent pathway and suggest that the GLUTag cell line represents a useful model for the analysis of the molecular determinants of enteroendocrine gene expression.

A primary immunoblastic T malignant lymphoma of the small bowel, with azurophilic intracytoplasmic granules. A histologic, immunologic, and electron microscopy study.

We report an aggressive primary T-immunoblastic lymphoma of the small intestine without blood involvement or associated celiac disease. Grossly, the tumor was composed of multiple disseminated ulcerated, infiltrating, or protuberant nodular lesions. Immunologic investigation showed that lymphoma cells were of peripheral (post-thymic) T-cell origin and expressed the phenotype associated with cytotoxic-suppressor subset (Leu4/CD3+, Leu9/CD7+, Leu2/CD8+, Leu11/CD16+, Leu 7/NKcells+, FcIgG+, HLA-DR+, anti-Tac/CD25+, Ki-1/CD30-, Leu1/CD5-, Leu5/CD2-, Leu3/CD4-). A particular morphologic feature of this case is the presence of numerous azurophilic granules within the lymphoma cells, identified as lysosomes by cytochemical and ultrastructural studies. In view of recent immunologic evidence that normal cytotoxic/suppressor T-cells selectively reside within the epithelium of the normal bowel and some of them contain azurophilic granules, it could be suggested that our patient's lymphoma represents a malignant counterpart of these lymphocytes. Furthermore, the aggressive character of this T malignant lymphoma (T-ML) could be related to the expression of T-cell activation markers HLA-DR and Tac/CD25 and the proliferation-associated antigen Ki-67 on a high proportion of tumor cells.

Middle East lymphoma and alpha-chain disease. An immunohistochemical study.

An immunoperoxidase study of the small intestinal mucosa of three patients with alpha-chain disease showed heavy infiltration of the mucosa by plasma cells containing alpha-heavy chain and J-chain but no light chains. An additional band-like and nodular mucosal infiltrate was also present and consisted of cells showing no evidence of cytoplasmic immunoglobulin synthesis. The cells comprising this infiltrate invaded and destroyed intestinal crypts, and immunoperoxidase staining showed them to be sharply distinct from the alpha-chain-containing plasma cells. In two cases of Middle East lymphoma, immunohistochemistry revealed a normal plasma cell population in the lamina propria of the small intestine. These results show that alpha-chain disease can be diagnosed in routine paraffin sections which should permit clarification of its true incidence in Middle East lymphoma. The demonstration of sharp distinction between the two types of mucosal infiltrate in alpha-chain disease is in contrast to previous immunofluorescence results and enables more ready identification of mucosal changes that may be important in the management of the disease.

Nuclear localization of 111In after intravenous injection of [111In-DTPA-D-Phe1]-octreotide in patients with neuroendocrine tumors.

UNLABELLED: Treatment with tumor-targeting substances is currently being evaluated in clinical trials. For patients with neuroendocrine tumors expressing somatostatin receptors, the 111In-labeled somatostatin analog [diethylenetriaminepentaacetic acid (DTPA)-DPhe1]-octreotide has been used with promising results. To further investigate the clinical effect of the injected conjugate, we analyzed the cellular distribution of 111In by ultrastructural autoradiography. METHODS: Seven patients with somatostatin receptor-expressing midgut carcinoid tumors scheduled for abdominal surgery were investigated by somatostatin receptor scintigraphy. During operation, tumor tissue samples and samples of normal intestine were collected, fixed, and processed for electron microscopy. A thin layer of film emulsion was applied on sections and after the exposure film was developed. The cellular distribution of silver precipitations indicating the presence of isotope was evaluated. RESULTS: Cell surface receptor binding and internalization of [111In-DTPA-D-Phe1]-octreotide in the tumor cells was easily revealed by silver precipitations in the film. Multiple silver grains were seen at the plasma membrane, in the cytoplasmic area among secretory granules and vesicular compartments, and in the perinuclear area. Silver grains were also regularly located in the nucleus. For all patients, the silver precipitation patterns from 111In decay were identical in all examined cells from removed tumors, and in most cells 111In could be seen in the nucleus. The specificity of the silver reaction products is supported by the observation that enterocytes in intestinal tissue specimens from near the tumor did not show any silver grains and no background labeling was seen in the plastic. CONCLUSION: After internalization through the somatostatin receptor system, 111In is translocated to the perinuclear area and into the nucleus. Whether the nuclide is still conjugated to the intact somatostatin analog or to part of it cannot be evaluated in this study. Despite the short irradiation range of 111In, the nuclear localization can explain its clinical effectiveness. The results from this study suggest that [111In-DTPA-D-Phe1]-octreotide may act as a powerful tumor cell-targeting substance.

Differential expression of VIP/PACAP receptor genes in breast, intestinal, and pancreatic cell lines.

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are structurally-related neuropeptides that function as trophic factors in addition to their more classical roles as neurotransmitters. Binding and molecular cloning studies have shown that their actions are mediated by receptors encoded by at least three different genes. VIP binding has been demonstrated on many tumor types, and radiolabeled VIP has recently been used as a novel method to localize intestinal tumors in humans and their sites of metastasis. To determine the receptor subtype and level of gene expression, we screened breast, intestinal, and pancreatic, cell lines by Northern blot analysis. Breast lines expressed VIP/PACAP1 receptor mRNA levels comparable to intestinal lines, in agreement with the studies showing particularly high VIP binding in these tumors and their derived cell lines. Pancreatic cell lines expressed mRNA for several receptor types. This extends the potential utility of VIP and PACAP in the localization of tumors, and because VIP and PACAP may regulate the growth rate of some tumors by autocrine or other mechanisms, the identification of receptor subtypes on these lines sets the stage for studies in which the activity of these individual receptors in growth and other processes can be investigated.

Malignant fibrillo-caveolated cell carcinoma of the human intestinal tract.

The ultrastructural features of a peculiar midgut carcinoid, containing cytoplasmic filaments, fibrils, and caveolae, are presented. Because of the morphologic similarities between the tumor cells and the recently described intestinal caveolated cell, it is proposed that the cells of the reported carcinoid represent the malignant counterpart of this new type of cell. The name suggested for this variant of a tumor of the enterochromaffin group of intestinal endocrine cells is malignant fibrillocaveolated cell carcinoma.

Intestinal ganglioneuromatosis: mucosal and transmural types. A clinicopathologic and immunohistochemical study of six cases.

Six cases of intestinal ganglioneuromatosis (GN) included in this study reveal the occurrence of two morphologic patterns. Transmural GN was characterized by neural hyperplasia in all layers of the bowel wall with predominant involvement of the myenteric plexus. It was found in three patients affected by multiple endocrine neoplasia IIb. Mucosal GN, having predominant involvement of the mucosa without concomitant hyperplasia of the myenteric plexus, was associated with von Recklinghausen's disease, adenocarcinoma of the colon, and multiple adenomas with megacolon in one case each. Clinicopathologic correlations and review of the literature suggest that mucosal GN might represent a distinct entity with a lower morbidity rate than the transmural variant. Immunohistochemical stains reveal considerable heterogeneity. S-100 protein, neuron-specific enolase, and synapto-physin immunostaining followed the distribution of the nervous hyperplasia in the different intestinal layers as identified morphologically and allowed precise determination of the proliferating cells. Increased reactivity for vasoactive intestinal polypeptide, opioid peptides leu-enkephalin and met-enkephalin, and substance P was present in all cases with transmural involvement; mucosal GN showed normal reactivity for opioid peptides and focal increased staining for substance P (one case) and vasoactive intestinal polypeptide (two cases) in the lamina propria. Mild increased immunoreactivity for tyrosine hydroxylase was present in the myenteric plexus of four out of four cases. Histochemical determination of acetylcholinesterase, performed in one case of transmural type, demonstrated hyperplasia of parasympathetic fibers and neurons. Electron microscopic study of another case suggested the presence of several neurotransmitters. These results indicate that the physiopathology of GN is related to a complex hyperplasia of several peptidergic, cholinergic, and probably adrenergic nerve fibers instead of a selective overgrowth of one type of nerve fiber.

Well-differentiated endocrine tumours of the middle ear and of the hindgut have immunocytochemical and ultrastructural features in common.

The immunocytochemical analysis of two cases of well-differentiated endocrine tumours (carcinoids) of the middle ear revealed predominant cell populations producing pancreatic polypeptide (PP)-related peptides, glucagon-related peptides, and serotonin (the latter only in one case). In consecutive sections PP- and glucagon-related immunoreactivities mainly colocalized in the same tumour cells. Ultrastructurally tumour cells were characterized by medium-sized to large granules of moderate to high density, on which PP and glicentin were localized by the immunogold technique. No amphicrine cells were found. These features are consistent with those of similar tumours in the rectal mucosa that are mainly composed of L cells coexpressing both PP-related and glucagon-related peptides. Additional tumour antigens of hindgut type detected immunohistochemically were prostatic acid phosphatase and CAR-5 mucin. Expression of the CAR-5 antigen was also found in samples of normal middle ear mucosa, in which endocrine cells have not been identified. In case 1 peritumoral mucosal invaginations showed a proliferation of endocrine cells identical immunophenotypically to tumour cells, possibly representing a precursor lesion. It is concluded that well-differentiated endocrine tumours of the middle ear are a distinct pathological entity characterized by multiple hormone production, typically involving three classes of hormones (pancreatic polypeptide-related peptides, glucagon-related peptides, and serotonin) of the hindgut endocrine system.

Comparative ultrastructural study of cytotoxic granules in nasal natural killer cell lymphoma, intestinal T-cell lymphoma, and anaplastic large cell lymphoma.

Comparative immunohistochemical and ultrastructural studies were performed on five nasal natural killer (NK) cell lymphoma cases, two intestinal T-cell lymphoma cases, and eight anaplastic large cell lymphoma (ALCL) cases to clarify morphological differences in cytotoxic granules among these cytotoxic lymphomas. Nasal NK-cell lymphomas and intestinal T-cell lymphomas had fine azurophilic granules and displayed dot-like immunostaining of granzyme B- and T-cell intracellular antigen 1 (TIA-1), predominantly in the central area of the cytoplasm. Ultrastructurally, these NK-cell lymphomas and intestinal T-cell lymphomas had two types of cytotoxic granules, type-I granules (dense core granules) and type-II granules (multivesicular bodies), which have been demonstrated in normal large granular lymphocytes in peripheral blood. However, ALCLs did not have azurophilic granules, and only type-II cytotoxic granules were found ultrastructurally, even though they showed similar dot-like immunostained patterns of granzyme B and TIA-1, as seen in NK-cell lymphomas and intestinal T-cell lymphomas. Immunoelectron microscopy revealed that TIA-1 was primarily located at the periphery of the cytoplasmic granules in the NK-cell lymphoma and ALCL cases. These findings suggest that malignant lymphomas with a cytotoxic phenotype can be divided into two types, (azurophilic granule)+, (type-I granule)+, (type-II granule)+ lymphomas and (azurophilic granule)-, (type-I granule)-, (type-II granule)+ lymphomas.

Pancreastatin-like immunoreactivity in human carcinoid disease.

Pancreastatin-like immunoreactivity has been demonstrated in human carcinoid tumors by immunohistochemistry and radioimmunoassay, employing antisera raised to a synthetic C-terminal fragment of porcine pancreastatin. Immunohistochemistry revealed intense immunoreactivity in all tumors. By radioimmunoassay, high concentrations of pancreastatin-like immunoreactivity were measured in carcinoid tumors arising from the fore-gut (mean +/- S.D. and range: 369 +/- 955 and 9.4-3670 pmol g-1, respectively, n = 14), mid-gut (mean +/- S.D. and range: 1354 +/- 1538 and 337-3978 pmol g-1, respectively, n = 5) and in metastases associated with mid-gut tumors (mean +/- S.D. and range: 684 +/- 739 and 31-2255 pmol g-1, respectively, n = 7), compared to corresponding normal tissues (less than 1.4 pmol g-1). Individuals with hepatic metastases and carcinoid syndrome had elevated circulating levels of pancreastatin-like immunoreactivity (mean +/- S.D. and range: 770 +/- 1249 and 42-4120 pmol l-1; n = 12), significantly above the normal, fasting range (mean +/- S.D. and range: 14.9 +/- 7.5 and 4-37.5 pmol l-1, respectively, n = 42). However, patients with non-metastatic carcinoid tumors (n = 4), who had been clinically cured after primary tumor resection, had plasma levels within the normal range. Chromatographic analysis of extracts of primary lung and ileal tumors, hepatic metastases from ileal tumors and plasma from individuals with carcinoid syndrome revealed molecular heterogeneity of pancreastatin-like immunoreactivity.

Pleomorphic carcinoma of the small bowel. The limitations of immunohistochemical specificity.

We report 3 cases of poorly differentiated tumors of the small bowel with histological, immunohistochemical, and ultrastructural studies. The patients were male, aged 45, 57, and 63. In all 3 cases, histological features of spindle cell, epithelioid cell and giant cell areas favoured a diagnosis of carcinoma, although a malignant stromal tumor could not be firmly excluded. Immunohistochemistry demonstrated in the 3 cases a strong expression of both "epithelial" (cytokeratin) and "stromal" (vimentin) markers; one tumor expressed the epithelial membrane antigen, and another one desmin. Electron microscopy showed no specific features in one case. The case positive for desmin demonstrated intracytoplasmic lumina, allowing the diagnosis of carcinoma. In spite of a non-specific immunohistochemical pattern, we finally considered these 3 tumors as of epithelial origin, corresponding to the rare and recently described pleomorphic carcinoma of the small bowel. This report emphasizes the difficult diagnosis of some poorly differentiated tumors, particularly in the gastro-intestinal tract. Such problems had until recently been resolved by ultrastructural and mostly by immunohistochemical studies. However, an increasing number of reports, together with our 3 cases, show unexpected reactivity of tumors with theoretically specific immunoreactions, such as those directed against intermediate filaments. Coexpression of intermediate filaments could be due to cross reactivity of molecules bearing common epitopes, or to the presence of different filaments in the same cell type; recent immunoblotting studies favour this latter hypothesis.

Malignant mesenchymoma of the small intestine.

We present the clinical and pathologic features of a malignant mesenchymoma of the small intestine. Light and electron microscopic studies of the sarcoma revealed multiple patterns of differentiation, including fibrosarcoma, leiomyosarcoma, chondrosarcoma, and osteosarcoma. A recurrence had the morphologic nature of a mesenchymal chondrosarcoma. Clinically, the neoplasm was not detected by barium contrast radiography, but it was readily defined by sonography and computed tomography. Despite aggressive surgery and chemotherapy, the patient died 15 months after the diagnosis was made.

Gastric heterotopia in the ileum causing hemorrhage.

Two cases of infants with heterotopic gastric mucosa in the ileum causing hemorrhage and massive bleeding per rectum are presented. Preoperative Technetium 99 m scanning was valuable as a means to the diagnosis. Successful operative treatment was achieved by segmental resection with end to end anastomosis.

Intestinal schwannoma in a rhesus monkey.

An intestinal schwannoma (neurilemmoma) was found in an aged female rhesus monkey culled from a research colony. The neoplasm was characterized principally by palisades of spindle-shaped cells (Antoni type A) surrounded by thick argyrophilic fibres, while plump cells with areas of vacuolation (Antoni type B) were observed to a lesser extent. Thick hyalinized perivascular cuffs were prominent and multifocal thromboses were present in cavernous vascular channels. Electron microscopic examination of the intercellular matrix between Antoni type A cells revealed long-spacing (100 to 120 nm) collagen fibrils. Although the mass had expanded beyond the confines of the muscularis externa, the cytological features of the neoplasm appeared benign.

Gastrointestinal autonomic nerve tumor (plexosarcoma): report of a case with fine needle aspiration biopsy and histologic, immunocytochemical and ultrastructural study.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) encompass a large group of mesenchymal neoplasms that display common cytologic spindle-shaped morphology on light microscopy. Immunocytochemical and ultrastructural studies can demonstrate several patterns of differentiation. CASE: A 70-year-old male presented with two intraabdominal small bowel masses. The cytopathologic features of a fine needle aspiration biopsy (FNAB) included plump spindle cells in densely populated aggregates or in a fasciculated pattern, without significant pleomorphism. An epithelioid component in a lobular arrangement with abundant, eosinophilic cytoplasm was also noted. The nuclei were vesicular, with a very evident, eosinophilic nucleolus and finely distributed chromatin. Groups of loosely cohesive cells with slender, dendritic-like cytoplasm were evident. Immunocytochemical study of the embedded, fine needle aspirated fragments of the neoplasm demonstrated immunoreactivity for vimentin and neuron-specific enolase. Cytokeratin immunoreactivity or muscular, vascular, neuroendocrine or nerve sheath differentiation failed to be demonstrated. The cytologic and immunocytochemical findings correlated well with the histologic features of the neoplasm. The morphologic diagnosis was confirmed by ultrastructural study. CONCLUSION: FNAB and immunocytochemistry can be valuable in making the correct diagnosis between gastrointestinal stromal tumors.

[Intestinal ganglioneuromatosis: histochemical, histoenzymological and ultrastructural study of a case]. / La ganglioneuromatose intestinale: étude histochimique, histo-enzymologique et ultrastructurale d'une observation.

Report of a child with disseminated ganglioneuromatosis of the gut. The complexity of the intestinal nervous system malformation is proved by histochemical, histoenzymological and ultrastructural studies. The malformation is characterized by: hyperplasia and hypertrophy of enteric plexus and nerves bundles in the meso, high acetylcholinesterase activity, aplasia of the sympathetic innervation with the exception of perivascular plexus, qualitative and likely quantitative integrity of the endocrine digestive system. These data are compared with similar observations in the literature.