GI Tract Pathology 2 PDF

Gastrointestinal Tract Pathology 2 Diogenis Batsoulis, M.D., M.Sc.  Case 3 A 54 year old Korean male presents to the clinic complaining of epigastric pain Upon taking a complete history, you learn he has lost over 10 kg over the last 2 month and has been vomiting after mea...

Gastrointestinal Tract Pathology 2 Diogenis Batsoulis, M.D., M.Sc.  Case 3 A 54 year old Korean male presents to the clinic complaining of epigastric pain Upon taking a complete history, you learn he has lost over 10 kg over the last 2 month and has been vomiting after meals The pain is not relieved by the use of over-the-counter antacids On physical examination, you note supraclavicular lymph node swelling You schedule the patient for upper endoscopy with biopsy  Gastric Adenocarcinoma Gastric cancer is almost always adenocarcinoma Risk Factors:  diet rich in nitrosamines  H.pylori  intestinal metaplasia (from chronic gastritis)  Gastric Adenocarcinoma Subclassified into 2 main types (Lauren classification):  Intestinal type  Diffuse type Gastric Adenocarcinoma-Intestinal Type Mass https://www.intechopen.com/books/gastric-carcinoma-new-insights-into-current-management/gastric-carcinoma-morphologic-classifications-and-molecular-changes Gastric Adenocarcinoma-Intestinal Type Ulcer https://en.wikipedia.org/wiki/Stomach_cancer#/media/File:Adenocarcinoma_of_the_stomach.jpg Gastric Adenocarcinoma-Intestinal Type Presence of Glands Image adapted, with permission, from https://eliph.klinikum.uni-heidelberg.de/allg/86/magenkarzinom  Gastric Adenocarcinoma Intestinal Type  more common; arises in areas of intestinal metaplasia  Commonly presents as a mass or ulcer Gastric adenocarcinoma Gastric adenocarcinoma with regression after chemotherapy Gastric Adenocarcinoma - Diffuse Type Signet ring cells: mucin pushes nuclei on the side!!! Image from www.pathpedia.c om Gastric Adenocarcinoma - Diffuse Type Signet ring cells: mucin pushes nuclei on the side!!! Gastric Adenocarcinoma - Diffuse Type Gastric Adenocarcinoma – Diffuse Type: Linitis Plastica Image from from Rubin R, Strayer D, et al., eds.: Rubin’s Pathology. Clinicopathologic Foundations of Medic ine, 6th ed. Baltimore, Lippincott Williams & Wilkins, 2012, figure13-28, p. 629.)  Gastric Adenocarcinoma Diffuse Type Characterized by signet ring cells that diffusely infiltrate the gastric wall Assosiated with desmoplasia (fibrous tissue around malignant cells) that results in thickening of stomach wall (linitis plastica) Risk factors undefined (not associated with H.pylori or nitrosamines)  Worse prognosis than Intestinal type Gastric Adenocarcinoma-Prognosis Staging: based on the TNM system Most important prognostic factor: depth of invasion!!! Early Gastric Carcinoma (confined to mucosa and/or submucosa) Surgically treated Early Gastric Carcinomas have 95% 5 year survival; overall it is only around 20% Gastric Adenocarcinoma-Prognosis Advanced Gastric Carcinoma (invades into the muscularis propria or extends more) Screening with endoscopy/biopsies, mostly in countries with high incidence of Gastric Carcinoma (Korea, Japan) Gastric Adenocarcinoma- HER2 Amplification HER2 Amplification in Gastric Adenocarcinoma Personalized Medicine Trastuzumab (Herceptin) for HER2 positive gastric cancers!!! This file is licensed under the Creative Commons Attribution-Share Alike 4.0 International license. Gastric Adenocarcinoma Spread Often asymptomatic until late in the course Spread to lymph nodes can involve the left supraclavicular node (Virchow's node) Distant metastases most commonly involve the liver Involvement of the ovaries (most commonly bilateral) by a metastatic carcinoma of GI (usually Gastric Adenocarcinoma of Diffuse type) is referred to as Krukenberg tumors Metastasis to Virchow’s Node https://casereports.bmj.com/content/2013/bcr-2013-200749  Krukenberg Tumors Bilateral Metastases to the Ovaries https://commons.wikimedia.org/wiki/File:Krukenberg_tumor_-1.jpg Tombs of the kings, Cyprus MALT Lymphoma https://www.webpathology.com/image.asp?case=201&n=6  Gastric Lymphoma Comprises approximately 5% of gastric cancers Most commonly MALT lymphona H.pylori involved in its pathogenesis Monoclonal; Effaced architecture; Diffuse pattern GI Tract Pathology Outline  Oral Cavity/Oropharynx  Esophagus  Stomach  Intestine  Case 4 A 23 year old female presents to the clinic complaining of a 4 week diarrhea She describes her stools as greasy, and foul-smelling On further questioning, she reveals that she has lost 4 kg over the past month even though her appetite has been greater than usual Physical examination reveals loss of muscle mass and marked pallor, and the abdominal examination is significant for hyperactive bowel sounds You order serum studies and come back positive of gluten autoantibodies Normal Histology for Comparison Image obtained, with permissionfrom http://library.med.utah.edu/. Copyright ©1994-2017 by Edward C. Klatt MD , Savannah, Georgia, USA. All rightsreserved worldwide  Celiac Disease Image adapted, with permission, from the Iowa Virtual Slidebox(http://www.mbfbioscience.com/iowavirtualslidebox )  Celiac Disease Immune-mediated damage of small bowel villi due to gluten exposure, present in wheat and grains Results in malabsorption (The chronic malabsorptive disorders most commonly encountered in the West are pancreatic insufficiency, celiac disease, and Crohn disease!!!)  Celiac Disease Diagnosis  serologic testing (anti- endomysial, tissue trasglutaminase, and gliadin antibodies) biopsy: loss of villi, intaepithelial lymphocytosis, increased lymphocytes/plasma cells in lamina propria (chronic inflammation) Symptoms resolve with gluten-free diet Celiac Disease  Case 5 A 25 year old woman presents to the clinic complaining of weight loss, intermittent bouts of diarrhea and RLQ pain not associated with meals Her mother has been diagnosed with IBD 10 years ago Your physical examination reveals a temperature of 37.8 C, and a terminal- ileum lesion Serum tests are notable for leukocytosis and increased CRP You order endoscopic examination with biopsy Inflammatory Bowel Disease (IBD) Image from: Robbins Basic Pathology, 9th Edition Inflammatory Bowel Disease (IBD) Chronic inflammation Unknown etiology; probably autoimmune and genetic causes Most commonly presents in young people in the West Subclassified as Crohn Disease and Ulcerative Colitis Diagnosis: endoscopy and biopsy  Crohn Disease Cobblestone Mucosa  Anywhere (mouth to anus)  Terminal ileum is the most common site  Patchy (Skip Lesions)  Transmural (full thickness)  Ulcers  Granulomatous inflammation can be present  Poor response to surgery  Increased risk of cancer Crohn Disease  Crohn Disease Granulomata are present is some cases Crohn Disease Transmural (full thickness) Inflammation and formation of Granulomas  Ulcerative Colitis  Colon only  Continuous  Superficial (mucosa/submucosa) Pseudopolyps  Ulcers  Good response to surgery  Increased risk of cancer Ulcerative Colitis Ulcerative Colitis Ulcerative Colitis Toxic megacolon  Case 6 A 13 year old girl presents to the emergency room with RLQ pain, nausea, and vomiting Just 12 hours earlier, she was experiencing vague, colicky periumbilical pain On physical examination, you find that the patient has a low-grade fever and localized tenderness in the RLQ when palpated Laboratory studies show leukocytosis You call the pediatric surgery team to prepare this patient for immediate surgery  Acute Appendicitis Image adapted, with permission, from http://aperio.duhs.duke.edu/Pathology_200/0054_Q%20Appendix.svs/view.apml  Acute Appendicitis Acute inflammation of the appendix; most common cause of acute abdomen Most commonly due to obstruction of the appendix by a fecalith Periumbilical pain, fever, and nausea; pain eventually localizes to right lower quadrant (McBurney's sign) Periappendiceal Abscess is a common complication Rupture results in Peritonitis  Case 7 A 65 year old man presents with abdominal pain in the LLQ of several days duration In the last hours, the pain has become worse. On physical examination, he has a temperature of 39 C, a palpable LLQ mass with tenderness, and bright red rectal hemorrhage Serum studies show leukocytosis You decide to start the patient on an antibiotic regimen to treat his current symptoms and you inform him that a high-fiber diet will be necessary Diverticular Disease Slide file from Hospital of Monfalcone (Italy); this file is licensed under the Creative Commons Attribution-Share Alike 3.0 Unported license  Diverticular Disease Mucosa and submucosa herniate through the discontinuous muscular layer Commonly seen in older adults; almost always multiple Most common location: sigmoid colon Associated with constipation, and low-fiber diet  Diverticular Disease Usually asymptomatic! Complications include:  Diverticulitis: due to obstructing fecal material; presents with appendicitis-like symptoms in the LLQ!!!  Perforation: due to the thin wall (look previous image) Meckel diverticulum  Case 8 A 55 year old man with a family history of colon cancer comes to the clinic for his annual colon cancer screening You perform a routine fecal occult blood test that results in a positive reading A colonoscopy is ordered during which several polyps are visualized and biopsied  Polyps Author: Emmanuelm at en.Wikipedia; this file is licensed under the Creative Commons Attribution 3.0 Unported license  Colonic Polyps Masses that protrude above the mucosal surface of the colon Polyps may also occur elsewhere in the GI tract (e.g.esophagus, stomach, small intestine)  Pedunculated: polyps with stalk  Sessile: polyps without stalk Polyps can be non-neoplastic and neoplastic Colonic Polyps: Non-malignant Hyperplastic  Most common type of polyp  Is there any malignant potential? Inflammatory IBD pseudopolyps  Colonic Polyps: Neoplastic Adenomas (or Adenomatous Polyps)  Due to neoplastic proliferation of glands  2nd most common type of colonic polyp  Most common adenomatous polyp: tubular adenoma  Adenoma Image adapted, with permission, from the Iowa Virtual Slidebox (http://www.mbfbioscience.com/iowavirtualslidebox )  Adenomas Usually asymptomatic but can result in rectal bleeding and iron deficiency anemia Benign, but with the additional presence of dysplasia!!! May progress to adenocarcinoma via the adenoma-carcinoma sequence The adenomas are the precursors to the majority of colon adenocarcinomas However, most adenomas do not progress to adenocarcinoma Adenoma with stalk  Villous Adenoma (formation of villi) Image adapted, with permission, from the Iowa Virtual Slidebox(http://www.mbfbioscience.com/iowavirtualslidebox )  Adenomas In colonoscopy, hyperplastic and adenomatous polyps differ most of the times. Often the polyps are removed and examined under the microscope.  Higher risk for progression from adenoma to carcinoma when:  larger size!  higher degree of dysplasia!  sessile growth (no stalk)! Familial Adenomatous Polyposis (FAP) Image obtained, with permission from http://library.med.utah.edu/. Copyright ©1994-2017 by Edward C. Klatt MD , Savannah, Georgia, USA. All rights reserved worldwide  Familiar Syndromes Familial Adenomatous Polyposis (FAP) Autosomal dominant disorder; characterized by many colonic adenomas due to inherited APC (Adenomatous Polyposis Coli) gene mutations  Colon and rectum are removed prophylactically; otherwise, almost all patients develop carcinoma by 40 years of age Hereditary nonpolyposis colorectal carcinoma (HNPCC)/ Lynch Syndrome  Due to inherited mutations in DNA mismatch repair genes  Colorectal Adenocarcinoma Colon cancer is almost always Adenocarcinoma! 3rd most common site of cancer and 2nd most common cause of cancer-related death (2018 US estimates); most common GI cancer Peak incidence is 60-70 years of age; predisposing factors include:  A low-fiber diet that is high in animal fat  Adenomatous polyps (adenomas)  Genetics  IBD  Colorectal Adenocarcinoma Colon cancer can grow as a: “napkin ring” lesion (presents as a “change in bowel habits” and can cause early obstruction); most commonly in distal colon polypoid mass (asymptomatic; however, it can present with iron deficiency anemia); most commonly in proximal colon  An older adult with iron deficiency anemia has colorectal carcinoma until proven otherwise!  Colorectal Adenoc a rc inoma Polypoid mass “napkin ring” lesion Adenocarcinoma Image from http://peir-vm.path.uab.edu/wsi.php?slide=IPLab7C olonC A Colon adenocarcinoma - T staging Colon adenocarcinoma Colon adenocarcinoma Colon adenocarcinoma pT3 Colon adenocarcinoma pT4a Colon adenocarcinoma venous invasion Metastatic Adenocarcinoma (Liver) http://virtualslides.med.umich.edu/M1%20Histopathology/037_40X.svs/view.apml Colon adenocarcinoma invasion of the spleen Colorectal Adenoarcinoma: Prognosis Grading: poorly-differentiated tumors (high-grade) are associated with worse prognosis Staging is more important; most important prognostic factors:  depth of invasion  presence of lymph node metastases Common distant metastatic sites (Stage IV cancer): liver (most common) and lungs  Colorectal Adenocarcinoma- Screening Occurs via fecal occult blood testing and colonoscopy Goal is to remove adenomas before carcinoma develops or to detect early cancers CEA is a serum tumor marker that is useful for assessing treatment response and detecting recurrence of colorectal cancer Vergina, Macedonia, Greece