Rhabdomyosarcoma of the duodenum: report of a case.

This report presents a case of primary pleomorphic rhabdomyosarcoma arising in the duodenum. A 63-year-old male with persistent melena was referred for a solid tumor in his right upper abdomen detected using ultrasonography. Gastrofiberscopy revealed a protrusion in the upper part of the duodenum, with a large ulcer on the top of it. Enhanced computed tomography showed that the tumor extended to the pancreas. Pancreaticoduodenectomy was performed, despite the absence of malignant cells in the biopsy specimen, with a preoperative diagnosis of duodenal cancer. The tumor consisted of multiple cell types, and immunohistochemical staining was positive for desmin, HHF-35 and alpha smooth muscle actin. Electron microscopy revealed primitive Z-band structures in the tumor. The final diagnosis was pleomorphic rhabdomyosarcoma of the duodenum. This is the first report of primary rhabdomyosarcoma occurring in the duodenum, confirmed by immunohistochemical staining and electron microscopy.

Bombesin receptors in a human duodenal tumor cell line: binding properties and function.

The bombesin family of peptides elicit numerous biological responses in the gut, including stimulation of cell proliferation, and have been implicated as growth factors in a variety of gastrointestinal tumors. Even though these peptides and their receptors are distributed throughout the gastrointestinal tract, there are few cell lines available as model systems to study bombesin action in gastrointestinal cells. In this study, we have characterized functional bombesin receptors in a human duodenal cancer cell line, HuTu-80. The binding of [125I-Tyr4]bombesin to intact cells at 4 degrees C reached equilibrium by 6 h. Scatchard analysis of [125I-Tyr4]bombesin binding showed that HuTu-80 cells contained a single class of high affinity binding sites (5900 +/- 1960/cell; Kd = 80 +/- 20 pM). [125I-Tyr4]bombesin binding was inhibited by bombesin receptor agonists and antagonists with the following order of potencies: gastrin-releasing peptide (GRP) = GRP-(14-27) = bombesin > [DPhe6]bombesin(6-13)ethylamide > [Leu13 psi-(CH2NH)Leu14]bombesin > neuromedin B. Photoaffinity cross-linking studies, in which N-5-azido-2-nitrobenzoyloxysuccinimide was used to covalently couple [125I]GRP(14-27) to cells at 4 degrees C, resulted in the specific labeling of a broad band with an apparent molecular mass of 66,000 daltons. Consistent with the presence of high affinity receptors, bombesin increased the formation of inositol phosphates in HuTu-80 cells in a dose-dependent manner (concentration eliciting half-maximal effect, 290 +/- 70 pM). However, under conditions where both insulin and serum increased [3H]thymidine incorporation into DNA, 10 nM bombesin had no effect either alone or in the presence of insulin. Bombesin also had no effect on colony formation by HuTu-80 cells in soft agar. Furthermore, the bombesin receptor antagonist, [Leu13 psi(CH2NH)Leu14]bombesin, did not inhibit [3H]thymidine incorporation or clonal growth either in the absence or in the presence of serum. Together, these results show that HuTu-80 cells contain high affinity bombesin receptors of the GRP subtype. These receptors are functionally coupled to second messenger production but do not stimulate cell proliferation.

Gangliocytic paraganglioma.

Six cases of upper intestinal gangliocytic paraganglioma, five in the duodenum and one in the jejunum, are reported. Three histologic patterns, each comparable to patterns in paraganglioma, ganglioneuroma, or carcinoid-islet cell tumor, are mixed in varying proportions. The complex histologic patterns encountered within these tumors reflect the differentiation of pluripotent cells. Although the parent cell is not identified in this study, gangliocytic paragangliomas may arise from cells which normally reside in the mucosal crypts and are presumably derived from cells originating in the neural crest. Three of the six tumors contain stromal amyloid. In one case, studied by electron microscopy, dense-cored cytoplasmic vesicles almost fill some of the tumor cells. Gangliocytic paragangliomas share the features of stromal amyloid and dense-cored vesicles with other neurocrine tumors.

Psammomatous somatostatinomas of the duodenum.

The presence of psammoma bodies in carcinoid tumors of the gastrointestinal tract is a rare occurrence; it has also been reported to be associated with features of somatostatin production by the tumor cells. The morphologic features of three such tumors arising in the duodenum were studied by a combination of histochemical, immunocytochemical, and ultrastructural techniques in an effort to delineate their secretory profile and further subclassify them. All tumors showed a mixed architectural pattern with prominent areas of glandular differentiation. The psammoma bodies were almost exclusively located within the glandular lumina. In each instance, the majority of tumor cells showed histochemical and immunocytochemical features of somatostatin-containing cells, and one tumor studied ultrastructurally showed numerous large- and small-sized intracytoplasmic secretory granules, both of which contained somatostatin. In contrast to other endocrine tumors of the duodenum that frequently have a multihormonal secretory profile, psammomatous duodenal carcinoids are associated with the exclusive presence of somatostatin within tumor cells. While many more of such examples of this uncommon tumor need to be systematically investigated for their immunocytochemical and ultrastructural characteristics, duodenal somatostatinomas need to be included in the differential diagnosis of psammomatous tumors.

Duodenal carcinoids in patients with and without neurofibromatosis. A comparative study.

Nine duodenal carcinoids from patients with von Recklinghausen's neurofibromatosis (VRNF) were investigated for their morphologic, immunocytochemical, and ultrastructural characteristics, and were compared with seven similar tumors from patients without VRNF. Strong similarities were found between tumors in each group. Irrespective of their association with VRNF, duodenal carcinoids arose in adults and usually produced jaundice, upper intestinal bleeding, or obstruction. Tumors larger than 2.0 cm had already metastasized when first detected. All tumors showed a mixed architectural pattern; five tumors associated with VRNF were of the psammomatous type, as opposed to two of those without VRNF. While no tumors showed argentaffinity, stray argyrophil cells were present only in the three tumors not associated with VRNF. All of the tumors showed immunocytochemical evidence of somatostatinomas, and only one VRNF-associated tumor showed immunoreactivity for an additional regulatory substance, as opposed to three of those not associated with VRNF. Thus, while VRNF-associated duodenal carcinoids are not otherwise distinctive, they tend to be pure somatostatinomas (eight of nine cases), whereas similar tumors unassociated with VRNF are frequently multihormonal (three of seven cases). While many more duodenal carcinoids need to be investigated systematically for their immunocytochemical profile, detection of a pure somatostatinoma in the duodenum should alert one to the possibility of coexistent VRNF.

Duodenal gangliocytic paraganglioma. An immunohistochemical and ultrastructural study and a hypothesis concerning its origin.

We report the immunohistochemical and ultrastructural features of three duodenal gangliocytic paragangliomas and compare them with duodenal carcinoid, extra-adrenal paraganglioma, pheochromocytoma, and ganglioneuroma. The gangliocytic paraganglioma is characterized by polygonal or columnar epithelial cells, ganglion cells, and spindle cells. The epithelial cells stained for neurofilament, neuron-specific enolase, pancreatic polypeptide, and somatostatin in three cases; leu-enkephalin, molluskan cardioexcitatory peptide, and vasoactive intestinal peptide in two; and glucagon and insulin in one case each. The ganglion cells were positive for leu-enkephalin, neurofilament, neuron-specific enolase, pancreatic polypeptide, and somatostatin in three cases, and glucagon in one. The spindle cells stained for neurofilament, neuron-specific enolase, and S-100 protein. Although there was some overlap in immunoreactivity between the gangliocytic paraganglioma and the other tumors examined, our data indicate that the gangliocytic paraganglioma is a distinctive lesion. We propose that it is a hyperplastic or neoplastic proliferation of 1) endodermally derived epithelial cells originating from the ventral primordium of the pancreas, 2) neuroectodermal ganglion cells, and 3) neuroectodermal spindle cells (Schwann cells).

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.

Duodenal somatostatin-containing tumor with psammoma bodies.

A duodenal tumor was found in a 68-year-old woman undergoing routine cholecystectomy for chronic cholecystitis associated with cholelithiasis. Microscopically, the tumor contained glandular structures and psammoma bodies. Electron microscopic examination demonstrated numerous intracytoplasmic neurosecretory granules consistent with endocrine D cells. Immunoperoxidase staining for somatostatin was positive in the tumor cells. The tumor appeared to be different from the somatostatinomas reported in the literature in that it was nonfunctional, located in the duodenum, and associated with psammoma bodies.

Adenocarcinoid tumor of the periampullary region: a novel duodenal neoplasm presenting as biliary tract obstruction.

An adenocarcinoid tumor of the duodenum, similar to those arising in the appendix, is reported. The tumor presented as a periampullary mass causing pancreaticobiliary obstruction. The microscopic features were typical of adenocarcinoid with diffuse infiltration of mucosa, submucosa, and smooth muscle by tubuloglandular structures lined by enteroendocrine and goblet cells. Signet ring cells were also present. It is desirable to distinguish adenocarcinoids from adenocarcinomas and typical carcinoids in this setting as, by analogy with appendiceal tumors, adenocarcinoids may be expected to have an intermediate prognosis.

Duodenal gangliocytic paraganglioma. Clinicopathologic and immunocytochemical study of 11 cases.

The clinicopathologic features of 11 cases (8 in men) of duodenal gangliocytic paraganglioma are presented. The patients averaged 56 years of age; none showed evidence of phakomatosis. Ten tumors occurred in the second portion of the duodenum, and one arose in the third portion. All tumors were polypoid, and half presented with gastrointestinal bleeding. The neoplasms were composed of paraganglioma and carcinoid-like elements, neurons, and Schwann as well as sustentacular cells. All tumors behaved in a benign fashion after local resection or snare polypectomy; long-term follow-up (1-25 years; mean, 8.3 years) showed no recurrence in any case. Immunocytochemical examination demonstrated the presence of somatostatin, serotonin, and human pancreatic polypeptide within endocrine cells and neurons.

Paraganglioneuroma of the duodenum: an evolutionary hybrid?

On light microscopy the neural component of a hybrid neural and endocrine duodenal tumour was characterised by ganglion cells and the endocrine component by epithelioid cells which were both argentaffin and argyrophil. Spindle-shaped cells of indeterminant lineage were also present. Electron microscopy revealed 'pale' and 'dark' cells, the former corresponding to the epithelioid cells and containing many membrane-bound neurosecretory granules, the latter probably corresponding to the spindle cells and containing large numbers of neurofilaments. Occasional cells contained both neurofilaments and secretory granules arranged in a consistent pattern in the cytoplasm. These composite cells may have represented an incompletely differentiated precursor of both the neural and endocrine elements of the tumour.

Cytogenetically detected clonal heterogeneity in a duodenal adenocarcinoma.

A primary duodenal adenocarcinoma, a tumor type for which no previous chromosome data existed, was cytogenetically analyzed after short-term culture. The main tumor mass was localized in the pancreatic head, but the histopathologic examination revealed its duodenal origin. A total of six abnormal, karyotypically unrelated, clones were identified. The largest exhibited clonal evolution and consisted of two subclones with massively rearranged karyotypes in the hypodiploid and hypotetraploid range. Chromosome imbalances brought about by these complex changes were gain of 1q, losses of chromosomes 6 and 9, and total or partial losses of 1p, 3p, 3q, 9p, 10p, 17p, 17q, 18q, 20p, and 20q. The remaining five smaller clones had 1-2 numerical or balanced structural chromosome aberrations. The present study thus revealed yet another epithelial tumor type characterized by karyotypically unrelated clones. For this as for other tumors, the pathogenetic significance of such cytogenetic polyclonality remains uncertain.

Exocrine pancreatic insufficiency and pancreatic fibrosis due to duodenal somatostatinoma in a patient with neurofibromatosis.

A case of duodenal somatostatinoma is described in a patient with Von Recklinghausen neurofibromatosis. The patient presented with exocrine pancreatic insufficiency, probably due to distal obstruction of the pancreatic duct by the tumor. Preoperative evaluation with calcium-pentagastrin and tolbutamide stimulation tests were nondiagnostic. At laparotomy, local excision of the tumor was performed. Pathological findings were compatible with duodenal somatostatinoma, causing pancreatic fibrosis. Somatostatin extracted from the tumor coeluted with the somatostatin-14 standard on high performance liquid chromatography (HPLC).

Glycocalyceal bodies and microvillous core rootlets: their value in tumor typing.

An ultrastructural study of the cell surface of lumen-forming tumors was carried out to determine the distribution of two morphologic markers seen in relation to the microvilli. These are membrane-bound glycocalyceal bodies and microvillous filament cores that penetrate the underlying cytoplasm as rootlets. They were found (especially when in combination) to be valuable in identifying tumors of what is referred to as intestinal-type epithelium, and could be seen in cases in which brush borders were absent. They have been demonstrated in intestinal-type carcinomas of the stomach and gallbladder, in adenocarcinomas of the small and large intestines and pancreatic ducts, in mucin-forming bronchiolar carcinomas, and in certain mucinous ovarian and endocervical tumors. Other tumors, whether mucin-producing or not, have been found to consistently lack these structures.

Epithelioid leiomyosarcoma of the small intestine with oncocytic change.

We describe a 53-year-old woman who was found to have a large, ulcerated duodenal mass that on histologic examination was determined to be an epithelioid leiomyosarcoma and on ultrastructural studies contained a prominent component of cells with oncocytic change. To our knowledge, the findings in this case are unique, and on review of the literature, no similar cases of oncocytic change in smooth-muscle neoplasms of the gastrointestinal tract were found.

Primary duodenal small-cell neuroendocrine carcinoma with production of vasoactive intestinal polypeptide.

A primary duodenal small-cell neuroendocrine carcinoma was found in an elderly man who presented with upper abdominal pain. Although metastatic small-cell carcinoma was documented by liver biopsy, the primary lesion was not identified until postmortem examination. The latter tumor, which ulcerated the duodenal mucosa, was composed of small ovoid cells with sparse cytoplasm and granular chromatin. Electron microscopy revealed cytoplasmic dense-core granules. Immunocytochemical study demonstrated the presence of neuron-specific enolase, Leu 7 antigen, chromogranin, epithelial membrane antigen, and vasoactive intestinal polypeptide within tumor cells. However, there was no evidence of a clinical endocrinopathy. This case emphasizes the need to include the duodenum as a possible primary site when metastatic small-cell neuroendocrine carcinoma is seen in the absence of apparent pulmonary disease.

Duodenal somatostatinoma with psammoma bodies.

A duodenal somatostatinoma was found incidentally in a 60-year-old woman undergoing cholecystectomy. Microscopically, the tumor had a glandular architecture with abundant psammoma bodies. Electron microscopy revealed tumor cells resembling D-cells of the pancreatic islets. Immunohistochemically, there was staining for neuron-specific enolase, chromogranin, and diffuse cytoplasmic positivity for somatostatin only. By immunoelectron microscopy, somatostatin was identified predominantly in lucent membrane-bound secretory granules. X-ray-dispersive microanalysis showed the psammoma bodies contained calcium apatite crystals. This case is compared with other reported cases with a description of cellular localization of somatostatin and development of psammomatous calcification.

Endocrine cells in adenocarcinomas and their prestages in the glandular stomach and duodenum of rats after MNNG administration. Histochemical, electron microscopical and radioimmunological studies.

Tumours of the glandular stomach and upper small intestine were induced in rats by oral administration of MNNG. In most cases the lesions were identified histologically as adenocarcinomas and their prestages, such as polypeous and downward growing adenomatous hyperplasias. Out of 48 adenomatous hyperplasias and adenocarcinomas of the stomach and 24 well differentiated adenocarcinomas of the small intestine, we observed argyrophilic cells in nearly the half of the cases. Endocrine cells were also identified by electron microscopy. The frequency of endocrine cells was reduced with decreasing degree of tissue differentiation. In poorly differentiated carcinomas, including signet ring cell carcinomas, no argyrophilic cells were found. Out of 10 adenomatous hyperplasias and tumours of the stomach investigated immunohistochemically, 5 cases showed gastrin producing cells. Most of these animals were radioimmunologically characterized by strongly elevated serum gastrin levels. Derivation and potential relevance of the endocrine cells in tumours are discussed.