GI Flashcards
Diagnosis?
Inheritance pattern?
Gene?
Most common mutation?
Pathophysiology?
Symptoms?
Hereditary Hemochromatosis
- homozygous autosomal recessive
- HFE gene
- C282Y
- HFE protein in small intestinal cells, regulation of iron uptake. Mutation –> unregulated uptake of iron regardless of need
- liver, pancreas, heart, pituitary, and skin –> hepatomegaly, diabetes, cardiomyopathy, amenorrhea, and hyperpigmentation
- __ testing has now become the serologic test of choice for evaluation of celiac disease, largely replacing the __ for initial testing.
- Genetic testing for __ is utilized in selected cases as part of the clinical evaluation of celiac disease.
- __ is present in approximately 95% of patients with celiac disease and most of the remaining 5% are positive for __.
- __testing is not diagnostic of celiac disease (present in approximately __ of the Caucasian population), but absence of these haplotypes virtually excludes celiac disease.
Celiac disease
- IgA antitissue transglutaminase (tTG) testing has now become the serologic test of choice for evaluation of celiac disease, largely replacing the more labor-intensive (although similarly accurate) antiendomysium antibody for initial testing.
- Genetic testing for HLA DQ2 and DQ8 is utilized in selected cases as part of the clinical evaluation of celiac disease. HLA DQ2 is present in approximately 95% of patients with celiac disease and most of the remaining 5% are positive for HLA DQ8. Although positive DQ2/DQ8 testing is not diagnostic of celiac disease (present in approximately one-third of the Caucasian population), absence of these haplotypes virtually excludes celiac disease.
In typical cases of celiac disease, intraepithelial lymphocytes are CD__+/CD__+.
Abnormal lymphocyte populations (with __ phenotype) may be seen in cases of refractory celiac disease and these patients are at increased risk for development of __.
- Histopathologic features of celiac disease include )__, and variable architectural abnormalities, including __.
- Most or all features of celiac disease, including intraepithelial lymphocytosis and variable amount of villous atrophy, may be present in cases of __.
Celiac disease
- In typical cases of celiac disease, intraepithelial lymphocytes are CD3+/CD8+. Abnormal lymphocyte populations (with CD3+/CD8- phenotype) may be seen in cases of refractory celiac disease and these patients are at increased risk for development of enteropathy-associated T cell lymphoma.
- Histopathologic features of celiac disease include intraepithelial lymphocytosis (characteristically showing a “tip-heavy” distribution), and variable architectural abnormalities, including villous atrophy (ranging from none to total) with variable crypt hyperplasia and expansion of the lamina propria by chronic inflammatory cells, especially plasma cells. None of the previous findings, however, are specific for celiac disease and clinical correlation is required to establish this diagnosis.
- Most or all features of celiac disease, including intraepithelial lymphocytosis and variable amount of villous atrophy, may be present in cases of tropical sprue. Correlation with clinical (i.e., traveling to tropical regions) and laboratory findings (negative celiac disease workup) are generally required to establish this diagnosis.
- The prevalence of celiac disease is higher in __ and __ than in the general population.
- Patients with celiac disease (also known as gluten-sensitive enteropathy) are at risk for developing __.
Celiac disease
- The prevalence of celiac disease is higher in patients with Down’s syndrome and diabetes mellitus than in the general population.
- Patients with celiac disease (also known as gluten-sensitive enteropathy) are at risk for developing enteropathy-associated T-cell lymphoma.
4 forms?
Virus?
Stain?
Kaposi sarcoma involving stomach
Four forms of Kaposi sarcoma (KS) are described:
(1) classic form, an indolent, primarily cutaneous disease typically affecting older men of Mediterranean ancestry
(2) endemic form, primarily affecting HIV-negative children in Africa
(3) iatrogenic form, affecting organ transplantation patients on immunosuppressive therapy
(4) HIV-associated cases.
- Human herpesvirus-8 (HHV-8) is thought to play a major role in all forms of KS.
- Histology
- proliferation of relatively bland spindle to epithelioid cells forming slitlike spaces containing red blood cells
- +/- eosinophilic, PAS-positive hyaline inclusions within tumor cells
- monoclonal antibody to HHV-8 latent nuclear antigen (LANA) is a highly sensitive and specific marker of HHV-8 infection in paraffin-embedded tissue sections of KS
- other spindle cell lesions, such as spindle cell hemangioma, dermatofibrosarcoma protuberans, and pyogenic granuloma, are LANA negative
Helicobacter pylori and Gastric Carcinoma
Helicobacter pylori and Gastric Carcinoma
- sixfold increased risk of gastric carcinoma in individuals infected with H. pylori.
- Infection and gastric cancer risk are high in Japan and Colombia.
- Africa, where the infection rate is also high, the gastric cancer rate is very low.
- This so-called African enigma remains unexplained.
- CagA and VacA genes are being studied as possible oncogenes. CagA-positive H. pylori strains are associated with alterations in the gastric epithelial cell cycle and apoptosis, more severe mononuclear and neutrophilic infiltrates, and more severe glandular atrophy and intestinal metaplasia. VacA-positive strains are frequently isolated from distal gastric cancers.
- Host factors include certain interleukin-1β subtypes, tumor necrosis factor-α expression, and genetic polymorphisms of mucin (MUC-1) and human leukocyte antigens (HLA).
- Known environmental risk factors are excessive dietary salt and inadequate intake of fruits and vegetables.
Spirochetosis.
- Intestinal spirochetosis is a noninvasive infection by spirochetes, most commonly Brachyspira pilosicoli and Brachyspira aalborgi, which proliferate along the colonic epithelial surface.
- Although thought to represent an incidental finding in some cases, spirochetosis has been associated with diarrhea, anal discharge, and abdominal pain in immunosuppressed individuals, especially in the setting of HIV/AIDS (definite cause-effect relationship still uncertain because of the concomitant infections and other confounding factors in these cases).
- Prevalence of 2% to 16% in Western countries, being significantly higher in developing countries. Most commonly seen in homosexual men with HIV/AIDS.
- Gross/endoscopic appearance of the mucosa is usually normal.
- This infection must be suspected and a “fringed,” basophilic line is seen along the apical border of colonicytes (including colonocytes within crypts). Organisms along the epithelial surface are highlighted by silver stains (Warthin-Starry and Steinter stains). Alcial blue pH 2.5 and PAS stains can also be used, while Gram stains usually fails to highlight these organisms.
Listeria villitis
- placenta and fetus are infected with Listeria via the hematogenous route
- important cause of second trimester abortion
- acquired by the mother from consumption of contaminated meat or unpasteurized dairy
- premature delivery or stillbirth
- most common in pregnant women, immunocompromised hosts, the elderly, and newborns
What causes pipestem fibrosis in the liver?
Schistosomiasis and Pipestem Fibrosis
- Symmers fibrosis refers to the dense, rounded, and fibrotic portal tracts that are seen on the cut surface of the liver in late schistosomiasis.
- Early changes in schistosomiasis include schistosomal granulomas within portal vein branches, sometimes with an extensive surrounding eosinophil infiltrate and corona of degranulated bright red eosinophil granules (Hoeppli-Splendore effect).
- Later changes in schistosomiasis include portal tract fibrosis, loss of portal vein lumina, and acquisition of schistosomal finely granular black pigment in Kupffer cells and portal macrophages.
- Acid-fast stain is useful to apply to suspected schistosomal granulomas or other suspicious areas because the outer cuticle and lateral spike of Schistosoma mansoni and other species are positive on acid-fast bacilli.
DDx?
Fibrin Ring Granulomas and Q Fever
- Fibrin ring granulomas (also called “donut granulomas”) are lobular granulomas that are distinguished from other types of granulomas by their central, seemingly empty space (a lipid vacuole) surrounded by strands of fibrin with outer lymphocytes and macrophages.
- Fibrin ring granulomas are chiefly formed as a result of infections, the most frequent association being with Q fever (C. burnetii infection).
- The histologic differential diagnosis of fibrin ring granulomas includes cytomegalovirus, Leishmania spp., hepatitis A virus infection, and allopurinol toxicity. These granulomas have been considered a nonspecific reaction, chiefly to infections.
- Fibrin ring granulomas are typically located within the lobular parenchyma and are not within portal tracts. Their central empty hole and surrounding strands of fibrin are histologically distinct from sarcoid granulomas, which are usually fibrosing and often clustered adjacent to portal tracts, and drug-related granulomas, which lack the central vacuole and sometimes contain eosinophils.
Dx in infant?
Increased risks?
Tx?
Infant of a diabetic mother
- 3-10% of all pregnancies are affected by abnormal glucose regulation
- increased risk of growth abnormalities, respiratory distress, hypoglycemia, and congenital anomalies
- If maternal blood glucose is tightly controlled, the risk of adverse events is markedly decreased (but is still increased over baseline).
- Nesidioblastosis generally refers to congenital hyperinsulinism with an abnormal microscopic appearance of the pancreas.
- If severe, near-total pancreatectomy may be needed (rare).
Who gets it?
Endoscopy?
Histology?
DDx?
Gastric antral valscular ectasia (GAVE)
- older women, history of autoimmune conditions
- presents with anemia due to chronic blood loss
- Endoscopically,(“watermelon stomach”) longitudinal raised red mucosal stripes along the antrum and pylorus
- Microscopically, thrombi within dilated mucosal vessels
- Associated less specific histologic features include regenerative epithelial changes and fibromuscular hyperplasia of the lamina propria.
- spare the gastric body (in contrast with portal hypertensive gastropathy, which also involves the gastric body).
- Abnormal antral motility and mucosal prolapse are thought to be involved in the pathogenesis of this disease.
Dx?
Histology?
Subtypes?
Stains?
Children and young adults with multiple__ and diabetes?
Most likely to progress an special staining?
Hepatocellular Adenoma (Liver Cell Adenoma)
- benign tumor of hepatocytes
- Histology
- thickened cords of hepatocytes
- interspersed blood vessels (thin venous and arterial profiles are seen)
- NO bile ducts
- subclassified into four groups based on genomic classification:
- type 1, HNF-1α mutations, with large droplet steatosis and without atypia
- type 2, β-catenin mutations, with atypia and features that may transition to hepatocellular carcinoma
- type 3, interleukin-6 ST mutations, including inflammatory or telangiectatic adenoma
- type 4, no known mutation, with no specific features
- to distinguish it from carcinoma
- reticulin (which should show preserved reticulin framework throughout, in contrast to the “paucireticulin” pattern seen in hepatocellular carcinoma
- possibly CD34 (should show limited expression near pseudo–portal tracts).
- immunostains can be added
- trio of glypican-3, glutamine synthetase, and heat shock protein 70 (which all should be negative)
- Children and young adults with multiple adenomas (adenomatosis is defined as ≥10 adenomas) and diabetes are very likely to haveHNF-1α mutation and maturity-onset diabetes of the young type 3.
- Adenomas with suspicious features for the development of or transition to hepatocellular carcinoma (nuclear atypia, pseudoglandular growth, increased mitotic activity, focal loss of reticulin) and harboring β-catenin mutations should demonstrate glutamine synthetase expression and nuclear overexpression of β-catenin on immunohistochemical staining.
Adult Dx?
DDx?
Icreased prevalence in what population?
Histology?
Postinfantile Giant Cell Hepatitis
- rare in adults (in contrast to multinucleated giant hepatocytes in a neonatal liver biopsy specimen, a frequent change).
- affects only centrilobular hepatocytes
- Histologic DDx:
- autoimmune hepatitis
- HCV infection with or without HIV coinfection
- drug hepatotoxicity
- primary sclerosing cholangitis (less common)
- prevalence is slightly more than 2% in chronic hepatitis C