Objective The glands of the stomach body and antral mucosa contain a complex compendium of cell lineages. In lower mammals, the distribution of oxyntic glands and antral glands define the anatomical regions within the stomach. We examined in detail the distribution of the full range of cell lineages within the human stomach. Design We determined the distribution of gastric gland cell lineages with specific immunocytochemical markers in entire stomach specimens from three non-obese organ donors. Results The anatomical body and antrum of the human stomach were defined by the presence of ghrelin and gastrin cells, respectively. Concentrations of somatostatin cells were observed in the proximal stomach. Parietal cells were seen in all glands of the body of stomach as well as in over 50% of antral glands. MIST1-expressing chief cells were predominantly observed in the body, although individual glands of the antrum also showed MIST1-expressing chief cells. While classically-described antral glands were observed with gastrin cells and deep antral mucous cells without any parietal cells, we also observed a substantial population of mixed-type glands containing both parietal cells and G cells throughout the antrum. Conclusions Enteroendocrine cells show distinct patterns of localization in the human stomach. The existence of antral glands with mixed cell lineages indicates that human antral glands may be functionally chimeric with glands assembled from multiple distinct stem cell populations.
OBJECTIVE-Ménétrier's disease (MD) is a rare hypertrophic gastropathy characterised by giant rugal folds, hypochlorhydria, protein loss and a classic constellation of symptoms -nausea, vomiting, abdominal pain and peripheral oedema. It is considered a clinical diagnosis that, at times, may be difficult to establish. We propose firm diagnostic criteria for MD by delineating the clinicopathological features that best differentiate MD from its mimics. DESIGN-Forty-eight patients referred to Vanderbilt University Medical Center for consideration of enrolment in a clinical trial to treat MD patients with cetuximab were evaluated for a definitive diagnosis by assessment of clinical presentation, pertinent laboratory values and histopathological features.RESULTS-MD was confirmed in 25/48 (52%) of the patients. We designated the remaining 23 patients as mimics of MD; the most common diagnoses among the MD mimics were gastric polyps or polyposis syndromes (13/23, 57%). Gastric slides were available from 40 of 48 cases for detailed histological analysis (22/25 MD cases and 18/23 non-MD cases). Foveolar hyperplasia, glandular tortuosity and dilatation, and a marked reduction in parietal cell number were present in all 22 MD cases; lamina propria smooth muscle hyperplasia and oedema characterised most cases (18/22 and 19/22, respectively); more than half had prominent eosinophils (11/22) and/or plasma cells (12/22) in the lamina propria. The clinical presentation of MD patients was characterised by significantly younger age at onset, male predominance and increased vomiting compared to non-MD, and lower prevalence of anaemia compared to non-MD with polyps; there was trend towards increased frequency of peripheral oedema in MD versus non-MD.CONCLUSIONS-MD is most accurately diagnosed by clinicohistopathological analysis including esophagogastroduodenoscopy with gastric pH, appropriate laboratory tests (complete blood count, serum albumin, serum gastrin, H. pylori and cytomegalovirus serology) and full thickness mucosal biopsy of the involved gastric mucosa.Corresponding Author: Robert Coffey, robert.coffey@vanderbilt.edu, Tel: 615-343-6228, Fax: 615-343-1591 however, each has yielded inconsistent benefits, and none have been evaluated in a clinical trial. [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] The only definitive treatment is total gastrectomy. A recently published clinical trial from our group reported that MD patients treated with cetuximab, a monoclonal antibody to the epidermal growth factor receptor (EGFR), showed significant clinical and biochemical improvement in all 7 patients that completed the one-month trial with subsequent histological reversion to normal or near normal in 4 of these patients. [27][28][29] The pathogenesis of MD is related to increased EGFR signalling in the stomach. In vitro, administration of transforming growth factor-α (TGF-α), one of seven mammalian EGFR ligands, stimulates gastric epithelial growth, inhibits acid production and increases mucin levels...
Nodular lymphocyte Hodgkin lymphoma (NLPHL) is a rare disease for which the optimal therapy is unknown. We hypothesized that rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) could decrease rates of relapse and transformation. We retrospectively reviewed patients with NLPHL diagnosed between 1995 and 2015 confirmed by central pathologic review. Fifty-nine had sufficient treatment and follow-up data for analysis. We described progression-free survival (PFS), overall survival (OS), and histologic transformation according to treatment strategy and explored prognostic factors for PFS and OS. The median age at diagnosis was 41 years; 75% were male, and 61% had a typical growth pattern. Twenty-seven patients were treated with R-CHOP with an overall response rate of 100% (complete responses 89%). The median follow-up was 6.7 years, and the estimated 5- and 10-year PFS rates for patients treated with R-CHOP were 88.5% (95% confidence interval [CI], 68.4% to 96.1%) and 59.3 (95% CI, 25.3% to 89.1%), respectively. Excluding patients with histologic transformation at diagnosis, the 5-year cumulative incidence of histologic transformation was 2% (95% CI, 87% to 100%). No patient treated with R-CHOP experienced transformation. A high-risk score from the German Hodgkin Study Group was adversely prognostic for OS ( = .036), whereas male sex and splenic involvement were adversely prognostic for PFS ( = .006 and .002, respectively) but not OS. Our data support a potential role for R-CHOP in patients with NLPHL. Larger prospective trials are needed to define the optimal chemotherapy regimen.
To describe extreme hyperprolactinemia originating from a pituitary adenoma in the wall of an ovarian dermoid. This is a description of an unusual case and a review of ectopic prolactin production. Ectopic production of prolactin is a rare condition that has been reported in isolated organ system pathology including ovaries. An ovarian dermoid is a benign neoplasm that has the potential for active unregulated endocrine function. Hyperprolactinemia can result from functioning lactotrophs found in ovarian dermoids and can lead to clinical sequelae. Definitive treatment of the condition requires surgical removal of the functioning endocrine tissue. Extreme hyperprolactinemia caused by a pituitary tumor located within a dermoid has not been reported before. We present a case of profound hyperprolactinemia originating from a pituitary adenoma found in the wall of an ovarian dermoid and give a broad overview of the condition and literature. Ectopic prolactin production should always be considered in symptomatic patients found to have elevated serum levels and no findings on brain imaging.
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