GI Flashcards
Acute liver failure can have 3 categories of histologic manifestations: necrosis with marked inflammatory activity, necrosis with little or no inflammation, or extensive microvesicular steatosis with little necrosis or inflammation. What etiologies fall under each category?
-Necrosis with marked inflammatory activity: idiosyncratic drug reactions, autoimmune hepatitis, viral hepatitis, Wilson disease. -Necrosis with little or no inflammation: acetaminophen toxicity, herpes simplex hepatitis, vascular diseases, Wilson disease. -Extensive microvesicular steatosis with little necrosis or inflammation: Reye syndrome, acute fatty liver of pregnancy, drugs (such as valproate and antiretrovirals).
Bile duct hamartomas, bile duct adenomas, and bile ductular proliferation.
Bile duct hamartoma or von Meyenburg complex is a type of ductal malformation that often occurs sporadically or as part of the spectrum of polycystic liver disease. It is commonly multifocal and located in or near the periphery of portal tracts. This lesion is usually small (0.5 cm), gray or white, and irregularly shaped. It consists of dilated, small to medium-sized ductular structures that usually contain inspissated bile. The ductules are separated by dense collagen and lined by cuboidal to flattened epithelium that shows no or minimal cytologic atypia. Bile duct adenoma is less common than bile duct hamartoma. It is typically noted in a subcapsular location but can be seen deep in the hepatic parenchyma. Bile duct adenomas may occur singly or as multiple lesions. This lesion is typically small (2 cm), white or gray, and firm. Microscopically, it consists of relatively uniform ductules lined by bland cuboidal epithelium and separated by fibrotic stroma, sometimes containing dense chronic inflammation. Mucinous differentiation and neuroendocrine cells can be found in bile duct adenomas. Since they are neoplasms, bile duct adenomas can display mild nuclear enlargement and atypia, but they lack marked variation in nuclear size and shape. Bile ductular proliferation is a reactive process that occurs in noncirrhotic or cirrhotic liver (especially when cirrhosis is associated with large areas of fibrosis). It can be seen as a reaction to obstruction of bile flow, a reaction to infarction, or as a sequela of tumor ablation. The reactive ductules usually show a uniform lobular architecture with bland, atrophic, flattened biliary epithelium. Acute inflammation is commonly present. Metastatic pancreatic adenocarcinoma can be difficult to differentiate from the benign biliary lesions mentioned above, especially on frozen section.
Carney Triad.
Characterized by the presence of at least 2 of the following 3: Gastric epithelioid leiomyosarcoma (now called GIST), extraadrenal paraganglioma, pulmonary hamartoma/chondroma. Primarily affects young women. Not familial.
Dieulafoy disease.
AKA Dieulafoy lesion, Dieulafoy ulcer, caliber persistent artery, gastric aneurysm, gastric arteriosclerosis, submucosal arterial malformation, cirsoid aneurysm, and solitary exulceration simplex. Defined as an abnormally large artery that retains a large caliber as it approaches the mucosa. The mean diameter of pathogenic arteries at the level of the muscularis mucosae is ~1mm, versus normal arteries having a diameter of ~0.1mm. There is also an accompanying vein. MC location is the lesser curvature of the stomach, b/c the submucosal arteries of the lesser curvature are direct branches of the left gastric artery, whereas in the rest of the stomach, the submucosal vessels are of much smaller caliber b/c of their serial branching. The disease usually occurs in males, and there is a wide age range at time of occurrence.
Differential diagnosis for spindle cell neoplasms of the GI tract?
GISTs, leiomyosarcoma, schwannoma, solitary fibrous tumor, desmoid-type fibromatosis, metastatic melanoma.
Dysplasia of the biliary tract, considered as preinvasive biliary neoplasia, has been noted in __% to __% of patients with invasive carcinoma, __% of patients with sclerosing cholangitis, and incidentally in __% to __% of cholecystectomy specimens.
Dysplasia of the biliary tract, considered as preinvasive biliary neoplasia, has been noted in 40% to 60% of patients with invasive carcinoma, 30% of patients with sclerosing cholangitis, and incidentally in 1% to 3.5% of cholecystectomy specimens.
Examples of pseudoneoplastic lesions in the alimentary tract and their related neoplastic mimes.
Pseudocarcinomatous epithelial hyperplasia (adenocarcinoma). Enteritis/colitis cystica profunda (adenocarcinoma). Adenomyoma of duodenum (well-differentiated adenocarcinoma). Tumefactive chronic pancreatitis (well-differentiated ductal adenocarcinoma). Mycobacterial pseudotumors (sarcomas). Bacillary angiomatosis (hemangiomas). Florid lymphoid hyperplasia (lymphomas). Hepatic bile duct hamartoma (metastatic adenocarcinoma). Hepatic focal nodular hyperplasia (fibrolamellar hepatocellular carcinoma). Inflammatory cloacogenic polyp (tubulovillous adenoma). Xanthogranulomatous cholecystitis (sarcomatoid carcinoma).
Gallbladder carcinoma epidemiology.
Gallbladder carcinoma shows female predominance (F:M = 3–4:1). The mean age of patients is 65 years. It is more common in some Latin American countries such as Chili, Mexico, and Bolivia. In the United States, Native and Hispanic Americans have a higher rate of gallbladder cancer than other ethnic groups. Gallbladder carcinomas are associated with gallstones (80%), porcelain gallbladder (20%), and abnormal choledochopancreatic duct junction.
In what pattern does hepatocellular carcinoma stain with pCEA?
Canalicular pattern. This pattern results from cross-reactivity with biliary glycoprotein I and is demonstrated in 90% of HCCs and is not seen with monoclonal CEA. Similar to pCEA, villin and CD10 also show a canalicular pattern of staining.
List mesenchymal lesions of the GI tract with typical histologic and anatomic locations.
Inflammatory fibroid polyp; submucosal; antrum, small bowel, colon, esophagus. GIST; mural (muscularis propria); stomach, small bowel, colon, esophagus. Inflammatory myofibroblastic tumor; mesenteric, rarely mural; colon, small bowel, stomach, esophagus. Schwannoma; mesenteric, rarely mural (muscularis propria); stomach, colo-rectum, esophagus, small bowel. Fibroblastic polyp; mucosal; left colon. Mesenteric fibromatosis; mesenteric, retroperitoneal; small bowel, colon, stomach secondary involvement. Perineurioma; mucosal, submucosal; left colon, jejunum. Synovial sarcoma; mucosal, submucosal; esophagus, stomach. F and I dendritic cell sarcoma; mesenteric or, rarely, mural; stomach, duodenum, small bowel, colon. Leiomyosarcoma; mural; rare - found from esophagus to rectum.
List pathologic processes characterized by infiltrates of eosinophilic cells in the alimentary tract.
Malakoplakia. Crystal-storing histiocytosis (plasma cell dyscrasias, lymphoproliferative disorders, clofazimine-induced histiocytosis, eosinophilic colitis). Russell bodies gastritis. Granular cell tumor. Decidual reaction. Histiocytic infiltrate or infections.
List pathologic processes characterized by infiltrates of foamy cells in the alimentary tract.
Xanthoma. Muciphages. Whipple disease. Infections (Histoplasmosis, Rhodococcus equi, Mycobacterium avium-intracellulare complex). Melanosis coli. Hereditary metabolic storage disorders.
List pseudoneoplasms of the GI tract according to location (entire alimentary tract, esophagus, stomach, and intestines).
Entire alimentary tract: inflammatory fibroid polyp, xanthoma, lipoma-like lesions, ectopias and heterotopias, pseudotumors due to infections, benign signet ring cell infiltrates. Esophagus: fibrovascular polyp, melanosis of the esophagus, pseudodiverticulosis. Stomach: gastritis cystica profunda, inverted hyperplastic polyp, Russell bodies gastritis. Intestines: mucosal prolapse-related lesions, malakoplakia, tumefactive endometriosis, prolapsing mucosal folds of diverticular disease, hypertrophic and papilla, elastofibromatous lesions.
List type and sites (in decreasing order of frequency) of heterotopias of the GI tract.
Gastric; upper esophagus, duodenum, Meckel diverticulum, rectum. Pancreatic; antrum, ampulla, Meckel diverticulum, remaining segments of intestine. Sebaceous glands; throughout esophagus. Salivary glands; rectum, perianal. Prostate gland; anal canal. Thyroid and parathyroid glands; upper esophagus.
M:F of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma?
M=F for intrahepatic cholangiocarcinoma, and M>F for extrahepatic cholangiocarcinoma.
Metastatic Crohn disease.
MCD is an entity characterized by cutaneous, noncaseating granulomas at sites anatomically separate from the GI tract. It is the least common dermatologic manifestation of Crohn disease. In adults, the age of onset of MCD ranges from approximately 29 to 39 years, and the majority of patients have a previous diagnosis of Crohn disease. Twenty percent of patients with MCD may present without classical manifestations of Crohn disease. In these patients, Crohn disease manifests in 2 months to 4 years after the initial presentation of MCD. Cutaneous lesions of MCD may present as papules, plaques, nodules, and ulcerations, which may involve the arms, legs, genitalia, and face. Lesions have also been noted to have predilection for the moist environment of skin folds, including submammary and abdominal creases as well as the perineal and inguinal regions. MCD may present as a solitary lesion or occur in multiple sites and may be painless or tender upon palpation. In the pediatric population, MCD typically presents from the ages of 10 to 14, with about 50% of these patients having concurrent Crohn disease. Of these patients, approximately one-half have active gastrointestinal symptoms. In children who present with MCD lesions without evidence of Crohn disease, subsequent onset of gastrointestinal manifestations occurs from 9 months to 14 years after the initial presentation of MCD. The genitalia appear to be the most common area of involvement in children with MCD; the most common cutaneous manifestation presents as labial, penile, and/or scrotal swelling with or without accompanying erythema. Genital ulcerations have also been reported. MCD presents microscopically as sterile, noncaseating granulomatous inflammation located primarily in the superficial papillary and deep reticular dermis with occasional extension into the subcuticular fat. The granulomas consist of Langerhans giant cells, epithelioid histiocytes, lymphocytes, and occasional plasma cells. The underlying etiology of MCD is currently unknown. It has been suggested that antigens or immune complexes stemming from the GI tract in primary Crohn disease travel through the circulatory system and deposit in the skin, creating perivascular granulomatous features seen on microscopic examination of MCD lesions. Autoimmune cross-reactivity has also been suggested, where antibodies specific to antigens in the GI tract that may be responsible for inflammatory Crohn disease react with skin antigens of similar structure. The differential diagnosis of MCD consists of any granulomatous entities that may involve the skin, including but not limited to cutaneous sarcoidosis, erythema nodosum, pyoderma gangrenosum, hidradenitis suppurativa, mycobacterial disease, and foreign body reaction.
Morphologic features to distinguish reactive atypia from dysplasia in gallbladder.
Acute inflammation and/or ulceration; + in RA, - in D. Intraepithelial neutrophils; + in RA, - in D. Abrupt transition between normal and atypical epithelium; - in RA, + in D. Fine nuclear chromatin; - in RA, + in D. Prominent nucleoli; + in RA, -/+ in D. Surface maturation; + in RA, -/+ in D. Loss of polarity; - in RA, + in D. History of instrumentation; + in RA, - in D.
Relationship of EGFR and KRAS to colorectal carcinomas?
The EGFR signaling pathway is overexpressed in ~80% of CRCs. When EGF, as well as several other ligands, occupies the EGFR, it activates a signaling pathway cascade through the downstream effectors of the mitogen-activated protein kinases (MAPK) pathway. These effectors (KRAS, BRAF, ERK, and MAPK) influence cellular proliferation, adhesion, angiogenesis, migration, and survival. Blocking EGFR with cetuximab (Erbitux) or panitumumab (Vectibix) blocks all downstream effects of this receptor and is the basis of these therapeutic agents. ~30-40% of CRCs harbor mutations in KRAS that yield a constitutively active protein, where blockage of the EGFR does not affect the downstream signaling cascade of the MAPK pathway. KRAS mutations typically occur in codons 12 or 13 (exon 2) or in codon 61 (exon 3) of the KRAS gene. Only patients whose CRCs carry a wild-type sequence of KRAS have a favorable response to cetuximab or panitumumab; patients with mutations in codons 12 or 13 do not benefit. Hence, the NCCN guidelines with the recommendation that mutation analysis of the KRAS gene on the primary tumor or a site of metastasis should be part of the pretreatment workup for all patients with stage-IV CRC.
Sarcomatoid carcinoma of the esophagus.
AKA carcinosarcoma, pseudosarcoma, pseudosarcomatous squamous cell carcinoma, spindle cell carcinoma, and polypoid carcinoma, reflecting the uncertainty of its pathogenesis. Sarcomatoid carcinoma represents ~2% of esophageal carcinomas. Most authors believe the sarcomatous component results from metaplasia of carcinoma cells, others believe that 2 distinct malignancies coexist, and others believe the sarcomatoid component is of epithelial origin. More common in men, age is usually 60-70 years. ~60% arise in the midesophagus, ~33% in the distal, and <10% in the proximal. Grossly, these tumors are polypoid masses, commonly attached to the wall by a pedicle, but occasionally the tumors have a broad base. The surrounding mucosa is normal. Cut surface is white-gray, soft, and fleshy. Microscopically, these tumors are biphasic, containing a mixture of carcinoma and malignant sarcomatoid elements, with the latter generally forming the bulk of tumor. The epithelial component is usually squamous in nature and ranges from in situ or minimally invasive to infiltrating nests admixed with spindle cells. The sarcomatous component is typically composed of undifferentiated, spindled cells arranged in a fascicular or storiform pattern. These cells are embedded in an undifferentiated matrix that is edematous and contains scattered collagen fibers. Stromal differentiation has been reported with bizarre giant cells and with osseous and cartilagenous differentiation. The epithelial component is cytokeratin positive. The mesenchymal component is strongly vimentin positive; it may occasionally have cytokeratin immunoreactivity, but when present is almost always focal and less intense. The sarcomatoid cells are occasionally reactive with actin and desmin. The prognosis is much better than that of common squamous cell carcinoma b/c the sarcomatoid carcinoma tumors tend to grow into the lumen rather than the wall. Despite their size (up to 15 cm), they typically invade no deeper than the lamina propria or the submucosa. Usually treated surgically with esophagogastrectomy. Metastases may be carcinomatous, sarcomatoid, or mixed.
Small intestinal bacterial overgrowth.
SIBO is a common cause of chronic diarrhea and malabsorption. It results from colonization of the proximal small bowel by gram-negative aerobic and anaerobic bacteria that are normally restricted to the colon or, less frequently, from overgrowth of oropharyngeal flora. A predisposition to SIBO exists in diverse conditions where there is altered anatomy from prior surgery (eg, blind loop syndrome) or stricture or where there is impaired gut motility and prolonged orocecal transit time. The gold standard for diagnosis is a small intestinal aspirate culture showing growth of at least 10^5 colony-forming units of bacteria per milliliter (CFU/mL) of duodenal or jejunal fluid. Cultures of small-bowel mucosal biopsies can be substituted when there are inadequate luminal secretions. Histologically, mild or moderate villous blunting is the only change seen, and this is seen in only ~50% of symptomatic pts with the culture diagnosis of SIBO. The high rate of histologically “normal” biopsies does not negate the pathogenic role of bacterial overgrowth in symptomatic pts. It has been hypothesized that excess colonic flora within the small intestine can impede fat digestion by deconjugating bile acids and hindering the formation of micelles, that these bacteria can induce vitamin B12 deficiency, and that they can result in osmotic or secretory diarrhea through the production of organic acids. All of these proposed mechanisms can coexist with microscopically health small bowel mucosa.
What % of colorectal adenocarcinomas express nuclear CDX2 and apical/luminal/cytoplasmic villin?
Nearly 100%.
What 2 CK immunostains can be used to distinguish cholangiocarcinoma and hepatocellular carcinoma?
CK7 and CK19. Cholangiocarcinoma is CK7+ CK19+, while hepatocellular carcinoma is CK7- CK19-.
What are some non-gastrointestinal manifestations of Crohn disease?
Along with the characteristic GI findings of this disease, patients with Crohn disease may also present
with extraintestinal manifestations including ocular findings, musculoskeletal pathology, and mucocutaneous manifestations. Mucocutaneous findings are the most frequent extraintestinal manifestation of Crohn disease; 22% to 44% of patients present with mucocutaneous changes, which may be categorized as granulomatous skin disease, oral manifestations, cutaneous changes secondary to nutritional deficiencies, and cutaneous disorders that have been associated with Crohn disease (eg, pyoderma gangrenosum, erythema nodosum, erythema multiforme, and epidermolysis bullosa acquisita). Included within the granulomatous cutaneous category are perianal, peristomal, and perifistular inflammatory lesions, which are contiguous with the gastrointestinal tract and are the most common cutaneous manifestations of Crohn disease.
What are the current endoscopic and histologic criteria of the mucosal esophagogastric junction?
For endoscopy:
1. The distal end of esophageal longitudinal mucosal veins.
2. The proximal end of gastric longitudinal mucosal folds.
3. The squamocolumnar junction in most Japanese and Chinese subjects.
For histology:
1. The distal end of squamous mucosa.
2. The distal end of deep esophageal glands and ducts.
3. The distal end of multilayered epithelium.
In patients with active esophagitis, ulcers, or hiatal hernias, endoscopy #1 and #2 landmarks may not be determined with certainty, and patients should be treated with PPIs before endoscopy.
In a healthy person, the SCJ overlaps with mucosal EGJ; however, in patients with ulcers, hiatal hernias, and columnar-lined epithelium, the SCJ is not stable and cannot be used as the landmark for the true mucosal EGJ. In most Japanese and Chinese individuals, the SCJ overlaps with the EGJ, so the SCJ may be used as a surrogate landmark of the mucosal EGJ in these populations. However, that seems not to be the case in other populations.