GI Cancers + Tumors – Flashcards
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Associate following tumor markers with their cancer: CEA + Chromogranin + CA-19-9 alpha-fetoprotein
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CEA + =* indicator of metastatic disease to liver from stomach, pancreas, or colon* Chromogranin + = neuroendocrine tumor; most common in *small intestine* CA-19-9 = indicator of *pancreatic adenocarcinoma* Alpha-fetoprotein = indicator of *hepatocellular carcinoma* (liver)
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Squamous Cell Carcinoma of the Oral Cavity
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malignant neoplasm of squamous cells lining oral mucosa; most common location is floor of the mouth risk factors: *tobacco and alcohol* usage, *HPV infection* precursor lesions include *oral leukoplakia* and *erythroplakia* diagnosis: biopsy
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What is an odontogenic tumor?
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tumors that arise from tooth forming tissues! 2 most common: odontoma (most common) ameloblastoma
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Odontoma
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most common type of ondotogenic tumor; arise from eptihelium but shows extensive deposits of enamel and dentim probably hamartomas (disorganized tissue that is in the right organ) treatment: cured by local excision
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Ameloblastoma
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rare, benign tumor of odontogenic eptithelium commonly cystic, slow growing, and locally invasive but has an indolent course (not bad) more often affects lower jaw
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Tumors found in salivary glands (benign and malignant) are most likely to be in which gland?
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parotid gland (the largest of the major salivary glands)
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Pleomorphic Adenoma of Salivary Gland
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*most common tumor of salivary gland (most commonly found in parotid*); *benign* tumor composed of *stromal (ex: cartilage) and epithelial tissue* cause: unknown; radiation exposure increases risk symptoms: mobile (hasnt invaded local tissue), painless (hasnt invaded facial nerve which runs thru parotid), circumscribed (distinct from surrounding tissue) at angle of the jaw high rate of recurrence bc tumor has irregular margins (often leads to incomplete resection by surgeon) histology: encapsulated structure that presents as a rounded-well demarcated mass; cut surface is gray-white with myxoid and blue translucent areas of chondroid (cartilage-like); Hallmark histologic feature is great heterogeneity. treatment: surgical removal RARELY may transform into carcinoma, which presents with signs of facial nerve palsy
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Warthin Tumor of Salivary Gland (Papillary Cystadenoma Lymphomatosum)
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*benign cystic tumor with lymph-node like stroma; 2nd most common tumor of salivary gland, almost exclusively found in parotid* incidence: more common in males; usually in 5th-7th decade of life cause: *smoking* (smokers have 8x risk of non smokers) histology: round to oval encapsulated masses; usually superficial in parotid gland; cystic tumor with abundant lymphocytes and germinal centers; hallmark features is spaces are lined by double layer of neoplastic epithelial cells resting on a dense lymphoid stroma, the columnar cells have abundant, finely granular eosiniophilic cytoplasm
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Mucoepidermoid Carcinoma
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malignant tumor composed of mucinous and squamous cells; most common malignant tumor of salivary gland (most often in parotid) symptoms: facial nerve palsy (common involves facial nerve (invades the nerve) cause: associated with 11;19 q21p13 chromosome translocation that creates a fusion gene composed of portions of MECT1 and MAML2 genes histology: production of mucin with squamous cells; circumscribed but lack well defined capsules (unlike benign tumors); pale and gray white on transection; hallmark feature is hybrid cell types with squamous features, with small to large mucus filled vacuoles, best seen when highlighted with mucin stain prognosis: depend on grade of neoplasm; low grade recur in 15% of cases but rarely metastasize, high grade tumors are more invasive
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Adenoid Cystic Carcinoma
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slow growing, but relentless, unpredictible and stubbornly recurrent tumor with tendency to invade perineural spaces very rare tumor, 50% found in minor salivary glands particularly in palate, but among major most likely in parotid and submandibular gross features: small, poorly encpasulated infiltrative with gray pink lesions histology: small cells with dark, compact nuclei and scant cytoplasm, cells disposed in tubular, solid or cribiform patterns; space between tumor cells often filled with hyaline material prognosis: 50% or more disseminate and neoplasms arising in minor glands have poorer prognosis
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Esophageal tumors: what are two most common types? What is most common in USA and which is most common in the world? What do most look like on gross exam (regardless of histology)
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*Squamous Cell Carcinoma (SCC)* - malignant proliferation of squamous cells; *most common worldwide* - way to remember is that the rest of the world smokes more than USA *Adenocarcinoma* - malignant proliferation of glands; *most common in USA* *Regardless of histology, 60% of tumors are polypoid or exophytic on gross examination*.
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Divide esophagus into upper, middle, and lower thirds. Describe each, and tell where lymph node drainage (and thus cancer spread) would be according to location.
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*Upper 1/3* - muscular ring of *skeletal* muscle with no voluntary control; spread to *cervical* nodes *Middle 1/3* - spread to mediastinal or trachceobronchal nodes *Lower 1/3* - lower esophageal sphincter with smooth msucle; spread to celiac and gastric nodes
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What is normal epithelial lining of esophagus?
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*nonkeratinized stratified squamous epithelium*
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Squamous Cell Carcinoma of Esophagus: what is it? What are risk factors? What lymph nodes does it spread to? What are symptoms?
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*malignant proliferation of nonkeratinized stratified squamous cells of esophageal epithelium* most common worldwide risk factors: *smoking, alcohol, achalasia* (lower esophageal sphincter wont open), *Chagas disease*, *esophageal web*, esophageal injury, *hot liquids, diverticula, lye, HPV infection* location: *upper 2/3* (spread to *cervical* lymph nodes) symptoms: *progressive dysphagia* (difficulty swallowing, first solids then liquids), *hoarseness* (recurrent laryngeal nerve involvement), *cough* (tracheal involvement), *weight loss* poor prognosis
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Adenocarcinoma of Esophagus: what is it? What are risk factors? What lymph nodes does it spread to?
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*malignant proliferation of glands of esophagus; most common in USA* risk factors: *chronic GERD (Barrett Esophagus), Obesity* location: *lower 1/3 (celiac/gastric nodes)* symptoms: *progressive dysphagia, pain, hematemesis*(vomiting of blood), and *weight loss*
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Barrett Esophagus
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*specialized intestinal metaplasia* *nonkeratinized stratified squamous epithelium* ---metaplasia--> *nonciliated columnar epithelium with goblet cells* cause: *chronic reflux esophagitis (GERD)* remember, goblet cells should normally only be in small and large intestine (NEVER in esophagus or stomach) Associated with increased risk of *esophageal adenocarcinoma*
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Where is most common site of stomach cancer? What type is most common? What are other types?
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most common type: *adenocarcinoma* (malignant proliferation of surface epithelial cells) location: *antrum* (bottom of stomach by pyloric sphincter) other types of gastric cancer: malignant stromal tumor, lymphoma, carcinoid tumor
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What are two types of gastric adenocarcinoma? Which is more common and where in the stomach are they?
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*Intestinal* (most common; affects antrum at lesser curvature) *Diffuse* (less common; affects entire stomach)
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Which type of gastric adenocarcinoma is associated with smoked foods, H. pylori, tobacco, achlorhydria, and chronic gastritis? Which type is more common in males?
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intestinal gastric adenocarcinoma; more common in males diffuse type even for males and females
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Compare appearance of intestinal and diffuse gastric adenocarcinoma
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intestinal = ulcer with raised margins; polypoid, elevated, moderately differentiated, expansile growth, intestinal metaplasia (goblet cells, nonciliated columnar epithelial cells; papillary structures) diffuse = linitis plastica (thick, rubbery stomach) and signet ring cells (nucleus pushed to side bc of mucus); poorly differentiated, ulcerated, fungating, infiltrative growth
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Virchow Node
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metastasis to left superclavicular node; seen with gastric adenocarcinoma
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Sister Mary Joseph Nodule
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metastasis to periumbelical node (seen in intestinal type)
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Kruckenberg Tumor
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bilateral metastasis to ovaries with signet ring cells (seen in diffuse type)
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Where besides lymph nodes do gastric adenocarcinomas like to metastasize? What are symptoms of gastric adenocarcinoma?
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liver and lungs symptoms present late and include weight loss, early satiety, acanthosis nigricans or leser Trelat sign
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Acanthosis Nigricans
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dark, velvety discoloration in body folds, espeically axillary region; can occur in obesity, diabetes, or be a sign of GI cancer
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Leser- Trélat Sign
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explosive onset of many subhorreic keratoses (warty, age spots); may be a sign of GI cancer
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Upper GI Neuroendocrine Tumor (Carcinoid Tumor): what is it? What is carcinoid syndrome? What must you have to have carcinoid symptoms?
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big hypervascular and red tumors that secrete serotonin; can be in stomach, esophagus (rarely) or duodenum Organoid arrangements of the tumor cells ; relatively uniform nuclei with "salt and pepper chromatin pattern" the stomach ones are type I II and III NET (neuroendocrine tumors) carcinoid syndrome - high serotonin; abdominal pain, flushing (red), peripheral edema, hypotension, cyanosis, wheezing, palpation, diarrhea; check 5-HIAA or 5-HT levels MUST have liver replaced with metastasis to have carcinoid symptoms
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Zollinger Ellison Syndrome
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*malignant gastrin secreting tumor (gastrinoma)* symptoms: *multiple peptic ulcers with negative H pylori* serum: high gastrin levels so high acid in stomach
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Pancreatic Adenocarcinoma
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adenocarcinoma arising from panceratic ducts; most often occurs in *head of pancreas* most commonly seen in elderly (70 years); major risk factors are *smoking and chronic pancreatitis* clinical features: unfortunately presents very late in disease -epigastric abdominal pain and weight loss -*obstructive jaundice with pale stools (fatty) and palpable gallbladder* -*secondary diabetes mellitus* - in tumors that arise in body or tail -*pancreatitis* -*migratory thrombophleibitis (Trousseau syndrome)* with swelling, erythema, and tenderness in extremities tumor marker: *CA-19-9* treatment: whipple very poor prognosis 1 year survival less than 10%
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Insulinoma
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most common islet cell tumor (tumor of endocrine pancreas) tumor of pancreatic beta cells -> overproduction of insulin --> hypoglycemia characterized by whipple triad: low blood glucose, symptoms of low blood sugar (lethargy, syncope, diplopia), and resolution of symptoms after normalization of glucose levels
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Adenocarcinoma of Gallbladder
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adenocarcinoma arising from glandular epithelium that lines gallbladder wall cause: gallstones are major risk factor, especially when accompanied by porcelain gallbladder (chronic cholecystitis) symptoms: typically appears as cholecystitis in elderly woman (normally occurs in 40-50 year olds so this would be weird) so RUQ pain that may radiate to right scapula, nausea/vomiting, fever, weight loss
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Cholangiocarcinoma
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rare, malignant tumor of bile ducts cause: associated with primary sclerosing cholangitis cytology: often CA-19-9 + and P-anca +
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Cavernous Hemangioma of Liver
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most common benign liver tumor made of dilated blood vessels cause: unknown typically seen in 30-50 year olds histo: cherry spot on liver biopsy contraindicated because of risk of hemorrhage
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Hepatic Adenoma
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benign tumor of hepatocytes cause: associated with *oral contraceptives or anabolic steroid use; often present during pregnancy (high estrogen)* symptoms: may be none but *risk of rupture* (abdominal pain and shock) 10% progress to cancer treatment: stop taking oral contraceptives or steroids
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Hepatocellular Carcinoma
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malignant tumor of hepatocytes risk factors: chronic hepatitis, cirrhosis, or aflatoxins derived from Aspergillus fungus which induce P53 mutations symptoms: often masked by cirrhosis so detected late -Budd-Chiari Syndrome -weight loss tumor marker: alpha-fetoprotein poor prognosis; strange for a carcinoma (usually prefer lymph spread), HCC likes hematoginous (blood spread) in that it *often invades the hepatic vein*
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Budd-Chiari Syndrome
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thrombosis or compression of hepatic veins with centrilobular congestion and necrosis -> congestive liver disease (liver infarction secondary to hepatic vein obstruction) associated with HCC and hypercoagulable states, polycythemia vera, and post partum symptoms: painful hepatomegaly and ascites (fluid in abdominal cavity)
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Angiosarcoma of Liver
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malignant tumor of endothelial origin cause: associated with exposure to *arsenic or vinyl chloride (PVC pipes)* serum tumor markers: factor 8+ and CD31+ very poor prognosis
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Metastasis to Liver
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*more common than primary liver tumors* causes: colon, pancreas, lung, and breast carcinomas results in multiple nodules in the liver symptoms: -hepatomegaly with a nodular free edge of liver (may be felt on physical exam)
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Colonic Polyps: what are they? What is neoplastic mean again? What is sessile vs. pedunculated? When is a polyp considered malignant?
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Raised protrusions of colonic mucosa; classified by histology, may be neoplastic (clonal -> may be benign or malignant) or non-neoplastic (polyclonal -> no cancer risk). Polyps can be *flat, sessile, or pedunculated* (on a stalk); sessile = most likely malignant. A polyp is considered malignant once it invades through mucosa + into submucosa.
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Hyperplastic Colonic Polyp
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due to hyperplasia of glands; most common type of polyp; generally smaller + most common arise in rectosigmoid (left) colon non neoplastic :)
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Hamartomatous Colonic Polyp
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growths of normal colonic tissue with distorted architecture Generally non-neoplastic Associated with Peutz-Jeghers syndrome + Juvenile Polyposis (juvenile polyp syndromes).
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Adenomatous Colonic Polyp
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Due to neoplastic proliferation of glands; 2nd most common type of polyp Can be *tubular, villous, or tubulovillous histologically.* Villous = increased risk of progression to carcinoma Tubulovillous = intermediate malignant potential. Associated with chromosomal instability pathway + Familial Adenomatous Polyposis (FAP) Usually asymptomatic, may present with occult bleeding (blood in feces not visibly apparent).
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Serrated Colonic Polyp
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premalignant polyps with "saw-tooth" pattern of crypts on biopsy Associated with microsatellite instability and sporadic CRC
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What are the two molecular pathways to progress to colonic adenocarcinoma?
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Adenoma-Carcinoma Pathway - most common; associated with polyposis syndromes and most sporadic colorectal carcinomas on Left side of colon Microsatellite Instability Pathway (lynch syndrome + sporadic via serrated pathway); on R side of colon
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Adenoma-Carcinoma Pathway
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Normal colon ----*loss of APC (tumor suppressor) gene (5q21)* ----> decreased intercellular adhesion + increased cell proliferation ----*KRAS (oncogene) mutation* ----> unregulated intracellular signaling ---> Adenoma ----*loss of tumor suppressor genes (P53, DCC) + increased COX expression* ----> Adenocarcinoma (more on L. side) Associated with Polyposis Syndromes + most sporadic CRC Interestingly, *aspirin can help prevent progression from adenocarcinoma to carcinoma !*
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Microsatelite Instability Pathway
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Mutations or methylations of *mismatch repair genes* ----> *microsatelilite (repeating sequences of noncoding DNA that should remain stable during division) instability* ---> mutations ---> adenocarcinoma (more on R. side) Associated with Lynch Syndrome (HNPCC) + sporadic CRC via serrated pathway
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Familial Adenomatous Polypsosis (FAP)
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Autosomal Dominant disorder characterized by 100s to 1000s of adenomatous colonic polyps. Cause: AD APC mutation (Chromosome 5q21) Symptoms: almost all pts over age 40 develop carcinoma; highly associated with *gastric adenomas/adenocarcinomas, fundic gland polyps + thyroid cancers* *Cancer usually on LEFT side of colon.* Tx: colon + rectum removed prophylactically
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Gardner Syndrome
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Gardner Syndrome = FAP (l sided colon cancer)+ osseous and soft tissue tumors
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Turcot Syndrome
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Turcot Syndrome = FAP (L sided colon cancer) + malignant CNS tumor
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Attenuated FAP
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Similar to FAP except mutations of ACP occur at peripheral regions, so there is some functional APC protein. Symptoms: fewer adenomas (10-20) but colon cancer lifetime risk still 80%.
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MYH Polyposis Syndrome
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Autosomal Recessive disorder with normal APC sequencing. Symptoms: lifetime risk of colon cancer 100%
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Lynch Syndrome (Hereditary Non-Polyposis Colorectal Cancer)
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Cause: Autosomal Dominant germline mutations in MMR proteins ---> microsatellite instability Symptoms: associated with *uterine cancer, as well as stomach, and ovarian cancer*;* patient has NO polyps!* *Cancer usually RIGHT side of colon.*
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Juvenile Polyposis
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juvenile polyp AD mutation at chromosome 18 ---> TGF-beta mutations---> 10 or more juvenile polyps 20% increase in colon cancer
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Peutz-Jeghers Syndrome
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juvenile polyps AD mutation at chromosome 19 ---> dysfunction fo gene encoding serine threonine kinase (STK11) Symptoms: hamartomatous polyps throughout GI tract + mucocutaneous hyperpigmentation on lips, oral mucosa, an genital skin High lifetime risk of breast, colon + pancreatic cancers
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Colonic Adenocarcinoma
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carcinoma arising from colonic or rectal mucosa; 3rd most common site of cancer and 3rd most common cause of cancer related death; *can arise anywhere along length of colon* risk factors: *family history, alcohol, smoking, obesity, ulcerative colitis or chrons disease, any childhood polyps* occurs in 60-70yos cause: adenocarcinoma pathway, microsatellite instability pathway or spontaneous symptoms: depend on R or L side; all have increased risk of *S. bovis endocarditis* screening begins at 50 via colonoscopy and fetal occult blood test + FIT (detects hemoglobin via antigen) tumor marker: *CEA* if it has metastasized to liver (where it most often likes to spread)
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Left Sided Colon Cancer
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cause: adenoma-carcinoma sequence; associated with FAP *Grows in napkin-ring lesion* Symptoms: *decreased stool-caliber* (stool is solid by then and squished), left lower quadrant pain, *blood-streaked stool (can see blood = *hematochezia*)
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Right Sided Colon Cancer
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cause: microsatellite pathway; associated with Lynch syndrome *Grows in raised lesion from one side* Symptoms: *iron-deficiency anemia*(occult bleeding so cannot see blood) and vague pain.
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Iron Deficiency Anemia in an Elderly Pt is ____ until proven otherwise
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colorectal carcinoma
