Pathologies of Stomach PDF

PATHOLOGIES OF STOMACH Özge Ertener, MD SBM 302 Learning Objectives List the non-neoplastic diseases of stomach List the neoplastic diseases of stomach Define the clinical and morphological features of gastric polyps Define the clinical and histopathological features of gastric adenocarcinoma and MA...

PATHOLOGIES OF STOMACH Özge Ertener, MD SBM 302 Learning Objectives List the non-neoplastic diseases of stomach List the neoplastic diseases of stomach Define the clinical and morphological features of gastric polyps Define the clinical and histopathological features of gastric adenocarcinoma and MALT lymphoma Explain the origin and main features of the rare tumors of the stomach 2 Pathologies of Stomach Gastritis Acute Gastritis Chronic Gastritis Autoimmune Gastritis Peptic Ulcer Disease Hypertrophic Gastropathies Zollinger-Ellison Syndrome Gastric Polyps Hyperplastic Polyps Fundic Gland Polyps Gastric Adenoma (Adenomatous polyps) Gastric Adenocarcinoma Gastric Lymphoma Other tumors of stomach 3 Anatomy of Stomach 4 Histology of Stomach *At the esophagogastric junction, stratified squamous epithelium (SSE) lining the esophagus is abruptly replaced by simple columnar epithelium (SCE) of the stomach. *Also seen here are the mucous esophageal cardiac glands (ECG) beneath the lamina propria (LP) and muscularis mucosae (MM). Citation: Digestive Tract, Mescher AL. Junqueira’s Basic Histology: Text and Atlas, 15e; 2018. Available at: https://accessmedicine.mhmedical.com/ViewLarge.aspx?figid=190283332&gbosContainerID=0&gbosid=0&groupID=0 Accessed: February 12, 2020 Copyright © 2020 McGraw-Hill Education. All rights reserved 5 Histology of Stomach A low-magnification micrograph of the stomach wall at the fundus shows the relative thickness of the four major layers: the mucosa (M), the submucosa (SM), the muscularis externa (ME), and the serosa (S). Two rugae (folds) cut transversely and consisting of mucosa and submucosa are included. The mucosa is packed with branched tubular glands penetrating the full thickness of the lamina propria so that this sublayer cannot be distinguished at this magnification. The muscularis mucosae (arrows), immediately beneath the basal ends of the gastric glands, is shown. The submucosa is largely loose connective tissue, with blood vessels (V) and lymphatics. (X12; H&E) (Reproduced, with permission, from Berman I. Color Atlas of Basic Histology. 3rd ed. New York, NY: McGraw-Hill; 2003). Citation: Digestive Tract, Mescher AL. Junqueira’s Basic Histology: Text and Atlas, 15e; 2018. Available at: https://accessmedicine.mhmedical.com/content.aspx?bookid=2430&sectionid=190283267 Accessed: February 12, 2020 Copyright © 2020 McGraw-Hill Education. All rights reserved Wall of the stomach with rugae. 6 Gastric Polyps Hyperplastic Polyps Gastric Adenoma Fundic Gland Polyps 7 Gastric Polyps General Features Usually found incidentally on upper gastrointestinal endoscopy performed for an unrelated indication Rarely symptomatic The diagnosis and appropriate management of gastric polyps are important (WHY?) Hyperplastic polyps and gastric adenomas are relatively more common as compared with fundic gland polyps (recent studies?) https://www.uptodate.com/contents/gastric-polyps/print 8 The management of gastric polyps and surveillance are specific to the underlying presentation, pathology, and malignant potential. 9 Gastric Polyps Clinical Manifestations Fundic gland polyps Hyperplastic polyps Gastric adenomas Usually asymptomatic Usually asymptomatic Usually asymptomatic If symptomatic: Rare cases cause obstruction symptoms of nausea, vomiting, or epigastric pain If symptomatic: GI bleeding (Bleeding is usually occult but occasionally evident) In rare cases, intermittent obstruction may occur when pedunculated polyps in the antrum prolapse into or through the pylorus If symptomatic: GI bleeding (Bleeding is usually occult but occasionally evident) Obstruction (rarely) https://www.uptodate.com/contents/gastric-polyps/print 10 Fundic Gland Polyps General Features Located at the gastric body and fundus Related with chronic acid suppression* Can be sporadic Can be associated with familial adenomatous polyposis (FAP) Dysplasia / cancer may occur in FAP-associated fundic gland polyps Sporadic fundic gland polyps carry no cancer risk 11 Fundic Gland Polyps Macroscopic Examination: Well-circumscribed lesions with a smooth surface Single or multiple Microscopic Examination: Composed of cystically dilated, irregular glands lined by flattened parietal and chief cells Inflammation is typically absent or minimal 12 Hyperplastic Polyps «Inflammatory polyp» «Regenerative polyp» Most common in 50 and 60 years of age Etiopathology: Chronic inflammation drives the development «develop in association with chronic gastritis» H. pylori infection Usually < 1 cm Risk of carcinoma is related to dysplasia Risk of dysplasia: Polyps larger than 1.5 cm are risky 13 Hyperplastic Polyps Microscopic Examination Irregular, cystically dilated glands Edematous lamina propria with acute and chronic inflammation Surface ulceration (may be present) Thick walled blood vessels 14 Hyperplastic Polyps https://www.cghjournal.org/article/S1542-3565(13)00455-2/pdf 15 Gastric Adenoma (Adenomatous Polyps) 50- 60 years of age Males > females Often flat or sessile Mostly located in the antrum Pre-malignant neoplastic lesions Increased risk of adenocarcinoma in large gastric adenomas (mostly > 2 cm) Associated with autoimmune gastritis, intestinal metaplasia, familial adenomatous polyposis Carcinoma may be present in up to 30% of gastric adenomas 16 Gastric Adenoma Microscopic Examination Polypoid projections of dysplastic epithelium with pseudostratification, nuclear abnormalities, mitotic figures overlying cystically dilated glands Varying degrees of dysplasia 17 Due to the increased risk of malignancy associated with these polyps, recommendations include complete removal of the adenoma, with further examination of the entire gastric mucosa for abnormalities, all of which should be biopsied. Additionally, endoscopic follow-up is required after resection at 6 months (for incompletely resected polyps or high-grade dysplasia) or 1 year (for all other polyps) Operative resection should be considered for gastric adenomas that are not amenable to endoscopic resection https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992058/pdf/GH-09-640.pdf 18 19 Gastric Tumors Gastric Adenocarcinoma Carcinoid tumors MALToma GIST SCC Adenosquamous carcinoma Undifferentiated Carcinoma 21 Gastric Cancer (GC) Features More common in men than in women More common at 60s - 80s More common in Hispanic Americans, African Americans, Native Americans, and Asian/Pacific Islanders than it is in non-Hispanic whites More common in Japan, China, Southern and Eastern Europe, and South and Central America 22 Gastric Cancer (GC) Risk Factors Environmental factors High-salted diet, smoked foods, salted-fish, pickled vegetables Cigarettes smoking Family history of gastric cancer Inherited cancer syndromes Host genetic alterations H. pylori infection Adenomatous polyp 23 Gastric Cancer (GC) Molecular Features The incidence of GC has shown a dramatic decrease in recent years due to H. pylori eradication The overall survival is still quite poor due to its silent nature, late clinical presentation, and genetic heterogeneity Molecular classifications of GC have been provided to reveal the genomic landscape of GC The Cancer Genome Atlas (TCGA) classification is a milestone for the molecular characterization of GC Clinical translation of these molecular findings will provide novel strategies for early GC detection and promote precision therapies for GC patients 24 Comprehensive molecular characterization of gastric adenocarcinoma The Cancer Genome Atlas Research Network, Nature volume 513, pages202–209 (2014) 25 Gastric Cancer Pathogenesis Gastric cancer (GC) results from a multistep process that is influenced by Helicobacter pylori infection, genetic susceptibility of the host, as well as of other environmental factors. GC results from the accumulation of numerous genetic and epigenetic alterations in oncogenes and tumor suppressor genes, leading to dysregulation of multiple signaling pathways, which disrupt the cell cycle and the balance between cell proliferation and cell death. For this special issue, we have selected to review last year's advances related to three main topics: the cell of origin that initiates malignant growth in GC, the mechanisms of direct genotoxicity induced by H. pylori infection, and the role of aberrantly expressed long noncoding RNAs in GC transformation. The understanding of the molecular basis of GC development is of utmost importance for the identification of novel targets for GC prevention and treatment. https://onlinelibrary.wiley.com/doi/epdf/10.1111/hel.12338 26 Gastric Adenocarcinoma 90% of Gastric cancers Developes from the glands of the most superficial layer or the mucosa They are classified according to their location and gross and histologic morphology Mostly involve the gastric antrum; the lesser curvature is involved more often than the greater curvature Gastric dysplasia and adenomas are precursor lesions 27 The 2019 WHO classification of tumours of the digestive system «5th ed.» The 2010 WHO classification of tumours of the digestive system «4th ed.» https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003895/pdf/HIS-76-182.pdf Gastric Adenocarcinoma Terminology Separated morphologically into 2 (Lauren classification): Intestinal type: tends to form bulky masses Diffuse type (linitis plastica): infiltrates the wall diffusely, thickens it, and is typically composed of signet ring cells Early carcinoma (definitions): 1. The carcinoma that is limited to mucosa and/or submucosa (lymph nodes may or may not be involved) 2. Invasive gastric cancer that invades no more deeply than the submucosa, irrespective of lymph node metastasis 29 Gastric Adenocarcinoma «Intestinal type» 30 Gastric adenocarcinoma «Diffuse type» (Linitis plastica) 31 KRUKENBERG TUMOR 32 Gastric Adenocarcinoma Clinical Manifestations Early symptoms of both types of gastric adenocarcinoma (intestinal/diffuse) resemble those of chronic gastritis and peptic ulcer disease: Dyspepsia Dysphagia Nausea When these tumors are discovered; mostly they are at advanced stages, and present with the symptoms like: Weight loss Anorexia Early satiety (primarily in diffuse cancers) Anemia Hemorrhage 33 Gastric Adenocarcinoma Prognostic Factors & Treatment Prognostic indicators in gastric cancer: The depth of invasion The extent of nodal and distant metastases at the time of diagnosis Local invasion into the duodenum, pancreas, and retroperitoneum First choice of treatment is surgery: With surgical resection, the 5-year survival rate of early gastric cancer can exceed 90%, even if lymph node metastases are present Alternative /additional treatments: Chemotherapy Radiation therapy Palliative care 34 https://www.cap.org/protocols-and-guidelines/cancer-reporting-tools/cancer-protocol-templates 35 https://www.cap.org/protocols-and-guidelines/cancer-reporting-tools/cancer-protocol-templates 36 Gastric Lymphoma «MALT lymphoma» «MALToma» Extranodal lymphomas are mostly located in the GI tract, especially in the stomach Gastric lymphomas are mostly secondary (only 5% primary) Primary gastric lymphomas are: mostly: Extranodal Marginal B zone Lymphoma followed by: Diffuse Large B cell Lymphoma (second) In the stomach, MALToma is induced, typically as a result of chronic gastritis H. pylori infection is the most common cause H. pylori eradication results in durable remissions with low rates of recurrence in most MALToma patients 37 MALToma Clinical Manifestations Dyspepsia Epigastric pain Hematemesis Melaena Weight loss ***Gastric MALTomas and H. pylori gastritis often coexist and have overlapping clinical symptoms and endoscopic appearances 38 On endoscopy MALTomas present with: polypoid mass ulcerative infiltration hypertrophic thick folds 39 MALToma Microscopic Examination: Diffuse / follicular Dense, monotonous population of atypical lymphoid cells Residual germinal centers Lymphoepithelial lesions 40 41 42