Gastrointestinal Tract Tumors PDF

THE GASTROINTESTINAL TRACT I: TUMOURS Esophageal anatomy and histology epithelio escamoso sin glandulas con capas Esophageal Tumors: adenocarcinoma adenocarcinoma : esophago con ulceras inflammacion...

THE GASTROINTESTINAL TRACT I: TUMOURS Esophageal anatomy and histology epithelio escamoso sin glandulas con capas Esophageal Tumors: adenocarcinoma adenocarcinoma : esophago con ulceras inflammacion no puede trar (la saliva) ▪ Most esophageal adenocarcinomas arise from Barrett Pathogenesis esophagus. ▪ Molecular studies suggest that the progression of Barrett ▪ Thus, increased rates of esophageal adenocarcinoma may esophagus to adenocarcinoma occurs over an extended be partly due to the increased incidence of obesity-related period through the stepwise acquisition of genetic and gastroesophageal reflux and Barrett esophagus. epigenetic changes (P53, P16) ▪ Additional risk factors include tobacco use and exposure to radiation. ▪ Esophageal adenocarcinoma occurs most frequently in Morphology Caucasians and shows a strong gender bias, being seven- ▪ Usually occurs in the distal third of the esophagus and fold more common in men. may invade the adjacent gastric cardia ▪ Microscopically, Barrett esophagus is frequently present adjacent to the tumor. ▪ Tumors most commonly produce mucin and form glands ,often with intestinal-type morphology; less frequently tumors are composed of diffusely infiltrative signet-ring cells (similar to those seen in diffuse gastric cancers). metastisa muy rapidamente  epithelio escamoso -> epithelio gladular epitelio escamoso = tiene la capa de ariba = sin la keratina = blanco metaplasia que se puede transformar en displasia y tumores muy pequeno tumor = puede tener metastasis anos de reflujo incontrolado asssociado con tabaco Esophageal tumours: Squamous Cell Carcinoma ▪ Affects males four times more frequently than females Morphology: ▪ Risk factors include alcohol and tobacco use (synergi), poverty, caustic esophageal injury, ▪ Half of squamous cell carcinomas occur in the middle third of the achalasia, tylosis, Plummer-Vinson syndrome, esophagus diets that are deficient in fruits or vegetables, ▪ Squamous cell carcinoma begins as an in situ lesion termed squamous and frequent consumption of very hot dysplasia beverages. ▪ Early lesions appear as small, gray-white, plaque-like thickenings. Over ▪ Esophageal squamous cell carcinoma is nearly months to years they grow into tumor masses that may be polypoid, or eight-fold more common in African Americans exophytic, and protrude into and obstruct the lumen. Other tumors are than Caucasians. either ulcerated or diffusely infiltrative lesions that spread within the esophageal wall and cause thickening, rigidity, and luminal narrowing. ▪ Most squamous cell carcinomas are moderately to well-differentiated Plummer-Vinson syndrome: ▪ The sites of lymph node metastases vary with tumor location: cancers in the upper third of the esophagus favor cervical lymph nodes; those in the middle third favor mediastinal, paratracheal, and tracheobronchial nodes; and those in the lower third spread to gastric and celiac nodes. principal riesgo adenocarcinoma = reflujo principal riesgo escamous cellulas carcinoa = alcohol Stomach: anatomy and histology tiene plies para maximar el Gastric Polyps proliferationes benignos hyperplasia Hyperplastic/inflamatory Polyps Usually develop in association with chronic gastritis, which initiates the injury that leads to reactive hyperplasia and polyp growth. Among individuals with H. pylori gastritis, polyps may regress after bacterial eradication. Morphology: - The majority of inflammatory or hyperplastic polyps are smaller than 1 cm in diameter and are frequently multiple - Ovoid in shape and have a smooth surface, though superficial erosions are common. - Microscopically, polyps have irregular, cystically dilated, and elongated foveolar glands The lamina propria is typically edematous with variable degrees of acute and chronic inflammation, and surface ulceration may be present.  Fundic Gland Polyps relacionados con el acid ▪ The prevalence of fundic gland polyps has increased markedly in recent years as a result of increasing use of proton pump inhibitor therapy. These drugs inhibit acid production, which leads to increased gastrin secretion and, in turn, oxyntic gland growth. ▪ Fundic gland polyps occur sporadically and in individuals with familial adenomatous polyposis (FAP). ▪ Morphology: - Fundic gland polyps occur in the gastric body and fundus and are well-circumscribed lesions with a smooth surface. - They may be single or multiple and are composed of cystically dilated, irregular glands lined by flattened parietal and chief cells. - Inflammation is typically absent or minimal glandulas dilatadas benignas crecimiento del epitelio Gastric Adenoma benigno pero lesion maligna ▪ Gastric adenomas represent up to 10% of all gastric polyps. ▪ Adenomas almost always occur on a background of chronic gastritis with atrophy and intestinal metaplasia. ▪ The risk of adenocarcinoma in gastric adenomas is related to the size of the lesion and is particularly increased in lesions greater than 2 cm in diameter. ▪ Morphology: glandulas differentes mas proliferativo - Gastric adenomas are usually solitary lesions less than 2 cm in diameter, most commonly located in the antrum. - The majority of adenomas are composed of intestinal-type columnar epithelium that exhibits varying degrees of dysplasia. - Dysplasia can be classified as low or high grade. - High-grade dysplasia is characterized by more severe cytologic atypia and irregular architecture, including glandular budding and gland-within- gland, or cribriform, structures. - Gastric adenomas are pre-malignant neoplastic lesions. crecimientos Gastric Adenocarcinoma ▪ Adenocarcinoma is the most common malignancy of the stomach, comprising more than 90% of all gastric cancers. ▪ Early symptoms of both types of gastric adenocarcinoma resemble those of chronic gastritis and peptic ulcer disease, including dyspepsia, dysphagia, and nausea. As a result, these tumors are often discovered at advanced stages, when symptoms such as weight loss, anorexia, early satiety (primarily in diffuse cancers), anemia, and hemorrhage trigger further diagnostic evaluation. ▪ Mass endoscopic screening programs have been successful in regions where the incidence is high, such as Japan, where 35% of newly detected cases are early gastric cancers, limited to the mucosa and submucosa. ▪ Metastases are often detected at time of diagnosis. Sites most commonly involved include the supraclavicular sentinel lymph node (Virchow node), periumbilical lymph nodes (Sister Mary Joseph nodule), the left axillary lymph node (Irish node), the ovary (Krukenberg tumor), or the pouch of Douglas (Blumer shelf). ▪ Gastric cancer is more common in lower socioeconomic groups and in individuals with multifocal mucosal atrophy and intestinal metaplasia. ▪ Gastric dysplasia and adenomas are recognizable precursor lesions associated with gastric adenocarcinoma ▪ Environmental and dietary factors contribute to the development of gastric cancers. Consistent with this conclusion, studies of migrants from high-risk to low-risk regions have shown that gastric cancer rates in second-generation immigrants are similar to those in their new country of residence. ▪ The cause of the overall reduction in gastric cancer is most closely linked to decreases in H. pylori prevalence. Another possible contributor is the decreased consumption of dietary carcinogens, such as N-nitroso compounds and benzo[a]pyrene, because of the reduced use of salt and smoking for food preservation and the widespread availability of food refrigeration. ▪ Although overall incidence of gastric adenocarcinoma is falling, cancer of the gastric cardia is on the rise. This is probably related to Barrett esophagus and may reflect the increasing incidence of chronic GERD and obesity. Consistent with this presumed common pathogenesis, distal esophageal adenocarcinomas and gastric cardia adenocarcinomas are similar in morphology, clinical behavior, and therapeutic response. Virchow node Sister Mary Joseph nodule Sister Mary Joseph’s nodule refers to a palpable nodule bulging into the umbilicus as result of a malignant cancer in the abdomen or pelvis. It is associated with multiple peritoneal metastases and usually indicates an advanced stage of disease with a poor prognosis. Most cases are metastatic adenocarcinoma malignancies. The most common primary sites are the gastrointestinal tract (Gastric, Colonic and Pancreas) that accounts for about a half of the underlying sources (52%) and gynecologic (ovarian and endometrial cancer, 28%). Krukenberg tumor Krukenberg tumor, refers to the "signet ring" subtype of metastatic tumor to the ovary. The colon and stomach are the most common primary tumors to result in ovarian metastases, followed by the breast, lung, and contralateral ovary. Pathogenesis.  Morphology Gastric tumors with a diffuse infiltrative growth pattern Gastric tumors with an intestinal morphology Diffuse gastric cancer is generally composed of discohesive cells, likely as a result of E-cadherin loss These cells do not form glands but instead have large Tend to form bulky tumors, exophytic mass or an mucin vacuoles that expand the cytoplasm and push the ulcerated tumor nucleus to the periphery, creating a signet-ring cell morphology Composed of glandular structures They permeate the mucosa and stomach wall individually or in small clusters, and may be mistaken for inflammatory cells, such as macrophages, at low Intestinal-type gastric cancer predominates in high- magnification. risk areas and develops from precursor lesions, including flat dysplasia and adenomas When there are large areas of infiltration, diffuse rugal flattening and a rigid, thickened wall may impart a leather bottle appearance termed linitis plastica. The remarkable decrease in gastric cancer incidence applies only to the intestinal type, which is most closely associated with atrophic gastritis and intestinal metaplasia Gastric tumors with an intestinal Gastric tumors with a diffuse morphology infiltrative growth pattern Lymphoma: Extranodal marginal zone B-cell lymphomas (lymphomas of mucosa-associated lymphoid tissue (MALT) Morphology ▪ Usually arise at sites of chronic inflammation. ▪ In the stomach, MALT is induced, typically as a result Histologically, gastric MALToma takes the form of a dense of chronic gastritis. lymphocytic infiltrate in the lamina propria ▪ H. pylori infection is the most common inducer in the neoplastic lymphocytes infiltrate the gastric glands focally to the stomach and, therefore, is found in association create diagnostic lymphoepithelial lesions with most cases of gastric MALToma May disseminate as discrete small nodules or infiltrate the wall ▪ As with other low-grade lymphomas, MALTomas can diffusely. transform into more aggressive tumors that are Like other tumors of mature B cells, MALTomas express the B- histologically identical to diffuse large B-cell cell markers CD19 and CD20 and are positive for CD43 in about lymphomas. 25% of cases, an unusual feature that can be diagnostically helpful. Gastrointestinal Stromal Tumor Morphology ▪ GI stromal tumor (GIST) is the most common mesenchymal ▪ Primary gastric GISTs can be quite large, as much as tumor of the abdomen 30 cm in diameter. ▪ More than half of these tumors occur in the stomach. ▪ They usually form a solitary, well-circumscribed, fleshy ▪ The term stromal reflects historical confusion about the origin of mass covered by ulcerated or intact mucosa. this tumor, which is now recognized to arise from the interstitial ▪ The cut surface shows a whorled appearance. cells of Cajal. ▪ Metastases may take the form of multiple serosal nodules throughout the peritoneal cavity or as one or ▪ Approximately 75% to 80% of all GISTs have oncogenic, gain-of- more nodules in the liver; spread outside of the function mutations in the receptor tyrosine kinase KIT. abdomen is uncommon, but can occur. Histology ▪ GISTs composed of thin elongated cells are classified as spindle cell type whereas tumors dominated by epithelial-appearing cells are termed epithelioid type; mixtures of the two patterns also occur. ▪ The most useful diagnostic marker is KIT, which is detectable in Cajal cells and 95% of gastric GISTs by immunohistochemical stains: CKIT/CD117 Colon: Anatomy Colon: histology Hyperplastic Polyps Colonic hyperplastic polyps are benign epithelial proliferations that are typically discovered in the sixth and seventh decades of life They are the most common colonic polyp Without malignant potential. Most commonly found in the left colon and are typically less than 5 mm in diameter They may occur singly but are more frequently multiple Histologically, hyperplastic polyps are composed of mature goblet and absorptive cells with a serrated surface architecture that is the morphologic hallmark of these lesions Serration is typically restricted to the upper third, or less, of the crypt. Sessile serrated adenomas ▪ More commonly found in the right colon ▪ Serrated architecture throughout the full length of the glands, including the crypt base, crypt dilation, and lateral growth ▪ Malignant potential : Serrated neoplastic precursor lesion of colorectal cancer ▪ May develop traditional cytologic dysplasia and progress to colorectal carcinoma with microsatellite instability Traditional serrated adenoma ▪ Serrated neoplastic precursor lesion for aggressive BRAF mutated microsatellite instability (MSI) stable subtype of colorectal carcinoma ▪ Characterized by prominent eosinophilic cytoplasm, elongated nuclei, tubulovillous (filiform) architecture ▪ More often found in the rectosigmoid colon Tubular adenoma ▪ Neoplastic colon polyp with at least low grade dysplasia ▪ Precursor to invasive adenocarcinoma ▪ Found more commonly in the left colon and rectum ▪ Morfology: 1 cm: may bleed, lead to iron deficiency anemia, obstruction; increased risk of progressing to carcinoma May be sessile or pedunculated Features concerning for high grade dysplasia or malignancy include size >1 cm, villous architecture and ulceration / friability Histology: Polypoid colonic mucosa covered with dysplastic epithelium comprised of hyperchromatic, elongated nuclei arranged in a pseudostratified manner Dysplasia could be low grade or high grade, with architectural (cribriforming, luminal necrosis) and cytologic changes (vesicular chromatin, nucleoli, loss of basal polarity). Intramucosal carcinoma occurs when dysplastic epithelial cells breach the basement membrane to invade the lamina propria or muscularis mucosae. Because functional lymphatic channels are absent in the colonic mucosa, intramucosal carcinomas have little or no metastatic potential and complete polypectomy is generally curative. Invasion beyond the muscularis mucosae, including into the submucosal stalk of a pedunculated polyp, constitutes invasive adenocarcinoma and carries a risk of spread to other sites. In such cases several factors, including the histologic grade of the invasive component, the presence of vascular or lymphatic invasion, and the distance of the invasive component from the margin of resection, must be considered in planning further therapy. Well documented "adenoma to carcinoma” sequence, that involves mutations in KRAS, TP53, APC and beta-catenin  Adenomatous Polyposis ▪ Familial adenomatous polyposis (FAP) is an autosomal dominant disorder in which patients develop numerous colorectal adenomas as teenagers. ▪ It is caused by mutations of the adenomatous polyposis coli, or APC, gene. ▪ Approximately 75% of cases are inherited, while the remaining appear to be caused by de novo mutations. ▪ At least 100 polyps are necessary for a diagnosis of classic FAP, but as many as several thousand may be present. ▪ Colorectal adenocarcinoma develops in 100% of untreated FAP patients, often before age 30 and nearly always by age 50. ▪ Prophylactic colectomy is the standard therapy for individuals carrying APC mutations. ▪ Colectomy prevents colorectal cancer, but patients remain at risk for neoplasia at other sites. Adenomas may develop elsewhere in the GI tract, particularly adjacent to the ampulla of Vater and in the stomach. Hereditary Non-Polyposis Colorectal Cancer Also known as Lynch syndrome Account for 2% to 4% of all colorectal cancers Was originally described based on familial clustering of cancers at several sites including the colorectum, endometrium, stomach, ovary, ureters, brain, small bowel, hepatobiliary tract, pancreas, and skin. Colon cancers in HNPCC patients tend to occur at younger ages than sporadic colon cancers and are often located in the right colon. HNPCC is caused by inherited mutations in genes that encode proteins responsible for the detection, excision, and repair of errors that occur during DNA replication. There are at least five such mismatch repair genes, but majority of patients with HNPCC have mutations in MSH2 or MLH1. Adenocarcinoma ▪ Adenocarcinoma of the colon is the most common malignancy of the GI tract and is a major cause of morbidity and mortality worldwide. ▪ The dietary factors most closely associated with increased rates of colorectal cancer are low intake of unabsorbable vegetable fiber and high intake of refined carbohydrates and fat. ▪ Reduced fiber content leads to decreased stool bulk and altered composition of the intestinal microbiota. This change may increase synthesis of potentially toxic oxidative by-products of bacterial metabolism, which would be expected to remain in contact with the colonic mucosa for longer periods of time as a result of reduced stool bulk. High fat intake also enhances hepatic synthesis of cholesterol and bile acids, which can be converted into carcinogens by intestinal bacteria. Pathogenesis. At least two genetic pathways have been described. Both pathways involve the stepwise accumulation of multiple mutations, but differ in the genes involved and the mechanisms by which mutations accumulate. Microsatellite instability pathway APC/β-catenin pathway ▪ Associated with defects in DNA mismatch repair and accumulation of mutations in microsatellite repeat regions of the genome ▪ In patients with DNA mismatch repair deficiency, ▪ Activated in the classic adenoma-carcinoma mutations accumulate in microsatellite repeats, a sequence condition referred to as microsatellite instability (MSI). ▪ The classic adenoma-carcinoma sequence, ▪ These molecular alterations are common in sessile accounts for up to 80% of sporadic colon serrated adenomas and cancers that arise from them. tumors and typically includes mutation of ▪ Carcinomas with microsatellite instability often have APC early in the neoplastic process. prominent mucinous differentiation and are frequently located in the right colon ▪ It is important to identify patients with HNPCC because of the implications for genetic counseling, the elevated risk of a second malignancy of the colon or other organs, and, in some settings, differences in prognosis and therapy. APC/ B-catenina pathway Morphology ▪ Tumors in the proximal colon often grow as polypoid, exophytic masses that extend along one wall of the large-caliber cecum and ascending colon; these tumors rarely cause obstruction. ▪ Carcinomas in the distal colon tend to be annular lesions that produce “napkin-ring” constrictions and luminal narrowing sometimes to the point of obstruction. ▪ Most tumors are composed of tall columnar cells that resemble dysplastic epithelium found in adenomas. ▪ The invasive component of these tumors elicits a strong stromal desmoplastic response, which is responsible for their characteristic firm consistency. Some poorly differentiated tumors form few glands. Others may produce abundant mucin that accumulates within the intestinal wall, and these are associated with poor prognosis. Although poorly differentiated and mucinous histologies are associated with poor prognosis, the two most important prognostic factors are depth of invasion and the presence of lymph node metastases. Invasion into the muscularis propria confers significantly reduced survival that is decreased further by the presence of lymph node metastases. Metastases may involve regional lymph nodes, lungs and bones, but as a result of portal drainage of the colon, the liver is the most common site of metastatic lesions Tumors of the Appendix ▪ The most common tumor of the appendix is the well- differentiated neuroendocrine (carcinoid) tumor. ▪ It is usually discovered incidentally at the time of surgery or examination of a resected appendix. ▪ This neoplasm, which is almost always benign, most frequently forms a solid bulbous swelling at the distal tip of the appendix, where it can reach 2 to 3 cm in diameter. ▪ Conventional adenomas or non–mucin-producing adenocarcinomas also occur in the appendix and may cause obstruction. ▪ Mucocele, a dilated appendix filled with mucin, may simply represent an obstructed appendix containing inspissated mucin or be a consequence of mucinous cystadenoma or mucinous cystadenocarcinoma. In the latter instance, invasion through the appendiceal wall can lead to intraperitoneal seeding and spread. In women the resulting peritoneal implants may be mistaken for mucinous ovarian tumors. In the most advanced cases the abdomen fills with tenacious, semisolid mucin, a condition called pseudomyxoma peritonei.. This disseminated intraperitoneal disease may be held in check for years by repeated debulking but, in most instances, follows an inexorably fatal course.