Stomach Neoplasms and Gastric Polyps

• Stomach neoplasms encompass various benign and malignant growths in the stomach.

Gastric Polyps

• Polyps are masses projecting above the surrounding mucosa level.
• Development is due to epithelial or stromal cell changes such as hyperplasia, inflammation, ectopia, or neoplasia.
• The stomach can host various types of polyps, with hyperplastic and inflammatory polyps, fundic gland polyps, and adenomas being primary examples.

Inflammatory and Hyperplastic Polyps

• These represent opposite inflammatory spectrum ends, distinction based on inflammation degree.
• These commonly affect individuals aged 50-60 years old, typically arising from underlying chronic gastritis that causes polyp growth.
• Regression may occur following bacterial eradication when associated with H. pylori gastritis.
• Dysplasia development is linked to size; polyps exceeding 1.5 cm pose a greater risk.

Fundic Gland Polyps

• Such polyps can occur sporadically or in individuals with familial adenomatous polyposis (FAP).
• Polyps linked to FAP might show dysplasia without progressing to malignancy.
• Sporadic lesion incidence rose with proton pump inhibitors that likely increased gastrin secretion and glandular hyperplasia.
• These fundic gland polyps usually appear asymptomatic, often found by chance.
• Well-defined in the gastric body and fundus, these polyps often consist of many cystically dilated irregular glands with flattened parietal and chief cells.

Gastric Adenoma

• Adenoma incidence aligns with gastric adenocarcinoma incidence increasing with age, varying across populations.
• Predominantly affects individuals aged 50-60, with a higher prevalence in males.
• Development commonly arises amidst chronic gastritis with atrophy and intestinal metaplasia.
• All gastrointestinal adenomas display epithelial dysplasia, which can be classified as low or high grade.
• Adenocarcinoma risk development relates to lesion size; lesions over 2 cm have elevated risk.
• The malignant potential surpasses colon counterpart malignancies, with carcinoma potentially present in up to 30% of gastric adenomas.

Gastric Adenocarcinoma

• Adenocarcinoma is the most prevalent form of gastric cancer, accounting for over 90% of cases.
• Initial symptoms mirror chronic gastritis including dyspepsia, dysphagia, and nausea.
• Diagnosis often occurs at advanced stages after weight loss, anorexia, bowel changes, anemia, or hemorrhage.
• Gastric cancer incidence varies by geographic region.

Pathogenesis of Gastric Cancers

• Cancers are genetically diverse, with common molecular alterations (mutations).
• Most gastric cancers aren't hereditary.
• Germline CDH1 mutations are linked to familial cases, mainly the diffuse type.
• Patients with FAP with germline APC gene mutations face a higher intestinal-type gastric cancer risk.
• Sporadic intestinal-type gastric cancer displays several genetic abnormalities.
• Chronic gastritis from H. Pylori infections encourages cancer development and progression stemming from diverse genetic changes.
• This infection induced chronic gastritis increases proinflammatory proteins like interleukin-1β (IL-1β) and tumor necrosis factor (TNF).
• Production of these cytokines raises the risk of chronic gastritis-associated gastric cancer with coexisting H. Pylori infection.
• EBV is linked to 10% of gastric adenocarcinomas, though its specific role remains unclear, infection may precede neoplastic transformation.
• EBV-positive tumors are morphologically proximal with diffuse structure and lymphocytic infiltrate.

Morphology of Gastric Adenocarcinomas

• Adenocarcinomas are classified by location in the stomach, alongside gross and histologic features.
• Lauren classification splits tumors into their intestinal and diffuse correlating to different molecular alteration patterns.
• Intestinal types are large and glandular, similar to esophageal and colonic adenocarcinomas.
• These grow along cohesive fronts forming exophytic or ulcerated tumors, often contain apical mucin vacuoles, and abundant mucin may be present in gland lumina.
• Diffuse cancers display infiltrative patterns with discohesive cells featuring large mucin vacuoles displacing nuclei forming signet ring cells that permeate the mucosa and stomach either individually or as small clusters.
• A mass is hard to appreciate in diffuse cancers and evokes desmoplastic reactions stiffening the stomach wall causing widespread rugal flattening creating a "leather bottle" appearance termed linitis plastica.

Clinical Features

• Intestinal-type cancer is dominant in high-risk zones, stemming from dysplasia and adenoma precursor lesions.
• The average presentation is at 55, with a 2:1 male-to-female ratio.
• Diffuse cancer shows relatively uniform incidence across areas without known precursor lesions, affecting males and females similar rates.
• Invasion depth and nodal/distant metastasis remain vital prognostic factors.
• Local invasion into the duodenum, pancreas, and retroperitoneum is also characteristic.

Lymphoma

• They often occur in the GI tract, notably in the stomach, most commonly extranodal marginal zone B-cell lymphomas.
• Lymphomas in the gut are called MALTomas and diffuse large B-cell lymphoma is the second most common primary lymphoma in the gut.

Neuroendocrine (Carcinoid) Tumors

• These arise from neuroendocrine organs and neuroendocrine-differentiated GI epithelia.
• Such gastric tumors might be connected to endocrine cell hyperplasia, chronic atrophic gastritis, and Zollinger-Ellison syndrome.
• Known as “carcinoid” due to slower growth than carcinomas.
• WHO's system classifies these as low or intermediate, termed neuroendocrine carcinomas as high-grade tumors, closely resemble small cell lung carcinoma, commonly exist in the jejunum within the GI tract.
• They appear as intramural/submucosal masses creating polypoid lesions, elicit intense the desmoplastic reactions potentially causing kinking/obstruction.
• Display yellow or tan appearance and exhibit a fine, granular cytoplasm with a round-to-oval stippled nucleus.
• Incidence peaks in the sixth decade, appear at any age, symptoms depend on hormones produced
• The carcinoid syndrome is caused by vasoactive substances secreted by the tumor—cutaneous flushing, sweating, bronchospasm, colicky abdominal pain, diarrhea.
• Confined intestinal tumors’ substances are metabolized to inactive forms by the liver- a effect similar to oral drugs known as the "first pass" effect.
• The carcinoid syndrome strongly connects to metastatic disease.

Gastrointestinal Stromal Tumor (GIST)

• GIST is the most common mesenchymal abdominal tumor mostly arising in the stomach, wide varieties of mesenchymal neoplasms e.g. leiomyomas, leiomyosarcomas, schwannomas, and glomus tumors can arise.
• Nearly all GISTs arise from the pacemaker cells of Cajal embedded within the muscular GI tract tissue.
• Pacemaker and tumor cells express c-kit oncogene (CD117) promoting cell proliferation.
• About 80% of GISTs have a gain-of-function mutation to c-kit and about 10% are activating with mutation of PDGFR.
• Gastric GISTs tend to nonaggressive fashion oppose to what is to be expected with small large bowel.
• Primar GISTs produce solitary, circumscribed, fleshy, submucosal masses and metasastases produce serosal small nodules or large nodules with rare liver occurrences .
• GIST cells can be composed of spindle or epithelioid cells.
• KIT is the most effective marker.
• Incidence peaks in the sixth decade, more frequent in males.
• Smaller GISTs could be discovered with mass effects on mucus, intestinal construction, etc.
• Prognosis with tumor size correlates mitotic rate indexes and locations - gastric less aggressive - with recurrence and metasistis are rare, GISTS diameter measures less than 5 cm, active mitosis larger than 10 cm are common.

Adenomas in Small and Large Intestine

• Colonic adenomas are the most common neoplastic polyps and the precursors to the majority of colorectal adenocarcinomas.
• Neoplastic mass lesions in the GI tract cause polyps including adenocarcinomas, neuroendocrine tumors, stromal tumors, lymphomas, or even metastatic cancers distant from the sites.
• Recommended to undergo surveillance beginning around age 40 after the polyps are the precursors to colorectal adenocarcinoma.
• The prevalence of colorectal adenomas match to that of colorectal adenocarcinoma, with its distributions showing consistency, regardless, it must be emphasized that not majority of tumors lead to adenocarcinomas.

Villous and Serrated Lesions

• Villous adenomas harbor cancers more frequently than tubular adenomas and overlap histologically with hyperplastic polyps yet commonly found in the right colon. Despite malignant potential, these polps lack typical cytologic features of dysplasia
• Serrated architecture is found throughout the full length of glands differentiated from hyperplastic polyps - crypt base, serrated lesions, lateral crypt growth, commonly referred to as serrated adenomas.

Intramucosal Carcinoma

• It occurs when dysplastic epithelial cells breach the basement membrane to invade the lamina propria that might lead to musculariis mucosae but not through it.
• Functional channels in the colonic mucosa are missing intramucosal carcinomas are given slight metastatic potential.

Familial Adenomatous Polyposis (FAP)

• FAP is an autosomal dominant disorder with numerous colorectal adenomas as teenagers.
• 100% of untreated patients will develop colorectal adenocarcinoma and often prior to age 30, or age 50.
• APC somatic mutations are often inheritable with at least 100 polyp diagnosis is necessary APC mutations have manifestations along with FAP such as Gardner’s Sydrome, or Turcot Syndrome.
• Patients without loss of APC have MUTYH (also referred to as MYH) which also is known to be the the excision repair base gene autosomal recessive disorder is defined as MAP characterized with 100 fewer polyps with later age appearances.

Hereditary Non- Polyposis Colorectal Cancer (HNPCC) - Lynch Syndrome

• Caused by inherited mutations in mismatch repair genes which encode the proteins that detect for DNA errors during the replication and account for 2-4% of all colorectal cancers.
• Colon cancers typically occur in younger ages than sporadic ones.
• HNPCC patients' mutations are often from in MSH2 or MLH1 which lose through mutation or deficiencies accumulate defects in short sequences leading to microsatellites due to mutation with expansion known as MSI

Adenocarcinoma of the colon

• Common Gl malignancy, is a cause with mobility, and mortality wide
• Adenocarcinomas are typically responsible for 10% rates of cancer relating to Colorectal incidence peaks of age range from 60-70 though may increase before - 40 data increases, diets low in low absorbable veggie fiber or high rates or intake refined carbs and fats increase with risks.
• Aspirin intake and other NSAIDS can be effective protectors.

Tumors of the Appendix

• Differentiated neuroendocrine (carcinoid) is noted in resections that might be discovered during surgery.
• Mucinous Tumors -grade, High AMPN.

Tumors of the Anal Canal

• Carcinomas can be caused through squamous or glandular patterns with capitulating or epithelial upper or lower infections from HPV (high and low).

Morphology and Malabsorption

• It can be characterized through fat defects, fat - solute vitamins, electrolytes, proteins and soluble vitamins with hallmark having fat and high concentrations of stool fat, large, greasie etc .. and may lead to diarrhea, abdominal pain and weight loss, anorexia.
• Inadequate vitamins and minerals lead to anemia (B-12 or folate), and Vitamin 12 deficiency.
• Absorption defects often causes by Celiac, immune gluten-barley, or genetic factor which contributes to genetic polymorphisms.

Celiac Disease

• It is known as celac spure
• Gliadin is alcohol- solute, gluten fraction causes the digestive enzymes, Luminal, brush- border to be small, peptide, amino - acid, 33- - gliadin which are hard digested by gastric, pancreatic and proteases as with factors all individuals have the class 11 HIA, DQ or DQ8.
• Additional genetic factors increase the immune and epithelia's, thyroids, and lgA and infections by a 6–24—month-old infant are likely for diarrhea, celiac or malabsorption which also is known to a genetic one.

Infections and Deficiences

• The Environmental Enteric can can cause dysfunction and malnutrition.
• Lactase - lactose is not absorbed when breaking glucose leading to intolerance, Histology is often unremarkable, causes diarrhea ( congenital lack of Lactase ).
• Autoimmune disorders in children ( rare for Autoimmune) , intraepith. Cells and can not lead to ABeta or CysticFibrosis or Pancreas.

Acute Gastritis

• Gastritis is often caused through mucosal injury.
• When neutrophils are present, these lesions are associated with acute responses and regeneration is rare.
• H. pylori may often be the culprit but not only,
• Factors - NSAIDS that block prostaglandins, alcohols, Bile, Mucus secretion issues, Blood flow, transport, capacity.
• Aches and Nausea often associated.

Pathogenesis and Stress

• Acidic Lumen ph < 1 - it might cause damage but allows the mucin that is produced from epithelia also promotes for fluids that remove protons
• Uremic patients will have issues - it comes due to the inhibition of bicarbonate
• Chemicals will need damage.
• Stress in patients ( major/ extensive trauma ) have symptoms, which - stress can be ulcers due to low pressure shock.
• Causes include from local ISCHEMIA or direct stimulation
• Erosions, with bleeding or normal surrounding tissue, and perforation that must be taken in surgical means can all lead to tissue damage or bleeding.

Bacteria and Autoimmune

• Chronic typically related with helicobacter and might cause bile acid reflux

• Often related infection from Hp often increases the acids.

• Virulence or flagella in ureases cause adhesion to the fovealar cells .

• H. Pylori are not in Intestinal.

• Autoimmune gastritis and atrophic are often from Vit - B issues, gastric secretions and are associated with reduced output levels.

Complications

• Causes in the three is from Ulcer , Metaplasia, or, Dysplasia
• Caused by the high pH increasing carcinogens and allows the cells to start spreading to cancer.
• Metaplasia is when there may be the pre sence of Goblet cells it should be mentioned for possible rates of getting glandulo cellula
• High risk when the intestines has metaplasia in it which cause carcinogens and permits overgrowth in H. pylori. Can also decrease if the organism decreases

Dysplasia

• Can start having free epithelium from radicals damage or stimulate over time it accumulates as carcinoma
• Histologic can make as dysplasia.
• It is the deviation in size, shape, orrientation chromatin hyperchromasia and expansion