GI and Hepatobiliary Pathology Flashcards Preview

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Flashcards in GI and Hepatobiliary Pathology Deck (190):
1

What are the microscopic features of a bronchogenic cyst?

pseudostratified columnar epithelium with cillia

2

What are the microscopic features of a duplication cyst?

Must have muscle layer! Usually squamous mucosa BQ! Closed relationship with main esophagus

3

What are common causes of achalasia? BQ! What organism can cause achalasia?

not common primary, usually secondary - defined by saccular dilitation - Scleroderma, Amyloidosis, Chagas - "SAC"

Organism? Trypanosoma cruzi from South America Glass side has been on board--lymphoid aggregates infiltrating myenteric plexus on glass slide

4

1. What is the most common cause of ulceration in the GI tract?

2. BQ! What anatomic location is the most common site for pill esophagitis?

3. BQ! Most common medication associations with pill esophagitis/gastritis?

1. Reflux (GERD) is number one cause of ulceration in GI

2. This is more common mid esophagus where aorta crosses over! Expect to see ulcer with pill esophagitis--foreign material hopefully polarized or birefringent

3. Iron very common etiology - esp stomach Alendronate - bone resorption

5

BQ! Etiology of esophageal SCC?

Tobacco, alcohol, vitamin A deficiency and zinc (aging population)

6

BQ! Esophageal squamous cell carcinoma can be associated with what rare autosomal dominant syndrome?

Palmaris et plantaris disseminata

Approx 1/3 will have esophageal carcinoma

7

What molecular alterations are found in esophageal adenocarcinoma?

Aneuploidy, loss of heterozygosity, mutation of p53, c-erbB-2 oncogene expression is present

8

What are the best predictors of survival for esophageal adenocarcinoma?

Depth of mural invasion, lymph node or distant metastasis

9

What does H pylori produce which enhances its binding to a certain blood group type?

urease and adhesion production--enhanced binding of blood Group O

10

What is Type A gastritis?

5% of gastritis, diffuse corporal gastritis, immune mediated (antiparietal and anti intrinsic factor Abs), high serum gastrin, F>M, low vitamin B12, H. pylori

11

What is Type B gastritis?

Multifocal atrophic gastritis, not immune mediated, normal or low serum gastrin, F=M, normal Vitamin B12, H. pylori 90-100%

12

BQ! What are some of the differences between fundic gland polyps secondary to PPI use and fundic gland polyps in someone with FAP syndrome?

PPI predisposes to fundic gland polyps, usually single or multiple, less than 1% dysplastic, have beta-catenin mutations

FAP syndrome usually multiple, large, 40% dysplastic BUT DO NOT PROGRESS to ADENOCARCINOMA usually, young patients, APC gene mutation

13

What is the mutation seen in Peutz-Jeghers? They have increased risk for what cancers?

Autosomal dominant, STK11/LKB1 mutation at 19p13 Increased risk for:

"PASS Boards"--Pancreatic adenoca, Adenoma malignum of cervix, Sertoli cell tumor, SCTAT, Breast carcinoma

14

How to distinguish inflammatory fibroid polyps from GIST?

Not cellular enough to be GIST, too many eosinophils, onionskins around vessels, CD34 positive CD117 negative except for MAST cells, usually 2-5 cm can be LARGE 11 cm, PDGFR mutation positive

15

What are the 3 types of gastric carcinoid and what are their associations?

Type I - type A gastritis

Type II - MEN, zollinger ellison

Type III - sporatic more aggressive, less amenable to resection, usually SINGLE, higher mitotic rate

*Type I and II are less aggressive because if you remove the gastrin stimulus, the carcinoid will go away. Sporadic ones should be treated as possibly malignant.

16

What are the staining characteristics of GIST?

90% positive CD117 look for MAST cells

70% CD34

20% SMA

10% S100 - not always schwannoma - LOOK For lymphoid cuffing to call it schwannoma

17

Criteria for grading GIST?

● Low mitotic rate: 5 or fewer per 50 HPF
● High mitotic rate: over 5 per 50 HPF

Grading

TX: Primary tumor cannot be assessed
T0: No evidence for primary tumor
T1: Tumor 2 cm or less
T2: Tumor more than 2 cm but not more than 5 cm
T3: Tumor more than 5 cm but not more than 10 cm
T4: Tumor more than 10 cm in greatest dimension

Stage IA: T1-2 N0 M0 low mitotic rate
Stage IB: T3 N0 M0 low mitotic rate
Stage II: T1-2 N0 M0 high mitotic rate or T4 N0 M0 low mitotic rate
Stage IIIA: T3 N0 M0 high mitotic rate
Stage IIIB: T4 N0 M0 high mitotic rate
Stage IV: N1 or M1


 

18

BQ! What is the most common protozoal infection in the US?

Giardia is most common protozoal infection in USA

5% of usa have it

In the world? Amoeba most common by worldwide standard 10%

19

What is the differential diagnosis when you see macrophages in the small bowel?

Mycobacterium avium intracellular vs Whipples

20

What organism causes Whipple's disease? BQ! Where are the organisms located?

Tropheryma whipplei bacteria IN MACROPHAGES and in the lamina propria! (not only in macrophages) Stain with PAS-D!

Even patient's after therapy will be positive so be careful! Need to use PCR to test after treatment. MAI can also be positive for PAS-D but the organisms look very different

21

What infectious agent is shown here ?

Cryptosporidium

BLUE BLEBS on surface of mucosa

Found in crypts, gallbladder and intestine

It is a coccidio infection usually animal infection, more in immunocompromised

22

What parasitic GI infection is endemic to Kentucky and Eastern Tennessee?

Strongyloides stercolaris

Can live as larval form for years, is an eosinophillic rich disease; however there are higher eosinophils in southern region anyway

hyperinfection filariform larvae - upper right

23

BQ! What is the Splendore-Hoeppli phenomenon?

Radiating or anular eosinophilic deposits of host-derived materials (Charcot Laden crystals) and possibly of parasite antigens, which form around fungi, helminths, or bacterial colonies in tissue

24

What is diaphragm disease and what causes it?

Use of slow release NSAIDS may lead to this peculiar form of strictures called diaphragm disease in the small bowel (terminal ileum)

Characterized by strips of fibrosis perpendicular to lumen

25

BQ! What is gluten sensitive enteropathy?

Systemic autoimmune disorder induced by exposure to gliadin or prolamin graction of gluten proteins in wheat, barley, rye, etc.

26

BQ! Is gluten sensitive enteropathy always a diagnosis of kids?

NO! Adults can develop it from adenovirus 12 exposure E1B protein which has alpha gliadin crossreaction--sensitizes the T cells so patient can develop gluten sensitive enteropathy

27

What is refractory sprue?

Celiac patients that stop responding to diet restrictions. Normal IELs should be both CD3 and CD8 positive. If the IELS are CD3+ and CD8-, sign they are developing refractory sprue which puts them at risk for EATL - enteropathy associated T-cell lymphoma

28

BQ! What do you see in tissue specimens from patients with Waldenstrom macroglobulinemia?

Deposit IgM in mucosa, can be PASD positive--deposits pink accellular material and Congo red neg

29

What is goblet cell carcinoid?

Specific to appendix, prognosis between carcinoid and adenocarcinoma - more aggressive prognosis Suggested term--adenocarcinoid, older than 30 with acute appendicitis

30

What is a small bowel tumor with psammoma bodies and is associated with NF1?

Pseudopsammomatous somatostatinoma

Also called psammomatous carcinoid--EXCLUSIVELY in the periampullary region

Commonly misdiagnosed as adenoCA, near ampulla of vater, glandular appearance, large

LOOK FOR PSAMMOMA BODIES

May not be somatostatin positive, physiologic effect vs stain, cut deeper - synaptophysin, neurofibromatosis I syndrome association

31

What 3 molecular alterations do periampullary adenocarcinomas exhibit and which of those is predictive of a short survival?

p53, c-neu (predictive of short survival) and TGF-alpha

32

What are the microscopic characteristics of amebic colitis?

FLASK SHAPED ULCER turns out to undermine normal mucosa not FISSURE (as in Crohn's disease--how you distinguish).

You will also erythrophagocytosis! Organisms are Giemsa stain positive

33

BQ! What are the differences between MSI adenoCA and typical adenoCA?

Mucinous appearance >50% of lesion, Crohn-like response lymphoid aggregates, tumor infiltrating lymphocytes (only 2 is significant)

34

What is the mode of inheritance and mutated gene in Peutz-Jegher syndrome?

AD, STK11 (LKB1) at 19p13 Intestinal lesions--Hamartomatous polyps, small bowel most common Extraintestinal lesions--Up to 40% risk of CRC and >50 % risk of Breast CA. Also pancreatic and gastric CA

35

What is the mode of inheritance and mutated gene in familial juvenile polyposis?

AD, SMAD4 (18q21.1) or BMPR1A (10q22.3) Intestinal lesion--Lobulated hamartomatous polyps Extraintestional lesions-- >50% risk of GI CA including small bowel and stomach

36

What is the mode of inheritance and mutated gene in Cronkhite-Candada syndrome?

TRICK QUESTION! None, No known inhertiance

Intestinal lesions-- Broad based hamartomatous polyps with edema

Extraintestinal lesions--Severe disease, electrolyte imbalance and protein loss; greater than 50% mortality

37

What is the mode of inheritance and mutated gene in Cowden's disease (facial trichilemmomas, acral keratosis, gastrointestinal hamartomatous polyposis)?

AD, PTEN at 10q23

Intestinal lesions-- Hamartomatous polyps throughout the GIT

Extraintestinal lesions--Up to 50% risk of breast CA, up to 10% risk for thyroid CA and unknown risk of CRC

38

What is the mode of inheritance and mutated gene in Familial adenomatous polyposis?

AD, APC (5q21-22)

Intestinal lesions--CRC, fundic gland polyps, duodenal adenomas, and CA

Extraintestinal lesions--100% risk of CRC, Up to 5% risk of duodenal CA

39

What is the mode of inheritance and mutated gene in Gardner's syndrome?

AD, APC (5q21-22)

Intestinal lesions--CRC, fundic gland polyps, duodenal adenomas, and CA

Extraintestinal lesions--100% risk of CRC, Up to 5 % risk of duodenal CA and osteomas, epidermoid cysts, fibromas, and desmoid tumors

40

What is the mode of inheritance and mutated gene in Turcot syndrome?

AD (66%), AR (33%), Gene is APC (5q21-22) but also involves mismatch repair dysfunction

Intestinal lesions--CRC, fundic gland polyps, duodenal adenomas, and CA

Extraintestinal lesions--PNET of CNS, Glioblastoma

To clarify:

Turcot Types: GBM + HPNCC and medulloblastoma + FAP

41

What is the mode of inheritance and mutated gene in Type I Lynch Syndrome?

AD Genes: MLH1 (39%), MSH2 (38%), MSH6 (6%), PMS2 (7%) (3p21.3, 2p22-p21, 2p16, 7p22) Intestinal lesions--CRC at age 50 years of age Extraintestinal lesions--None

42

What is the mode of inheritance and mutated gene in Type 2 Lynch Syndrome?

AD Genes: MLH1 (39%), MSH2 (38%), MSH6 (6%), PMS2 (7%) (3p21.3, 2p22-p21, 2p16, 7p22) Intestinal lesions--CRC at age 50 years of age Extraintestinal lesions--Endometrial CA, also gastric, small bowel, HCC, cholangioCA, and CA of pancreas, ovary, renal pelvis, brain, and skin

43

What is the triad in Plummer-Vinson syndrome?

Glossitis, esophageal webs, and iron-deficiency anemia

44

What is the most common site for extrapulmonary small cell carcinoma?

Esophagus

45

How are FAP associated fundic gland polyps different from somatic fundic gland polyps?

If FAP-related, they have been associated with somatic mutations of the APC gene with high-risk of dysplasia (up to 42%).

If sporadic, they are associated with mutations in the b-catenin gene with a low risk of dysplasia. There is a controversial association with the use of proton pump inhibitors.

46

What is Menetrier disease and what is the genetic mutation?

Extreme foveolar hyperplasia that spares the antrum. Patients present with abdominal pain, nausea and vomiting, and anemia (due to gastric bleeding). Hypochlorhydria results from loss of parietal cells, whereas hypoproteinemia and edema result from gastric protein loss. In adults, the disease is progressive; however, in children, it tends to resolve spontaneously and may be CMV-related. Although the etiology is uncertain, Ménétrier disease probably results from local TGF-a overproduction and increased signaling through the EGFR pathway. Preliminary evidence suggests that pharmacologic blockage of EGFR signaling is beneficial and may obviate the need for gastrectomy for intractable disease.

47

Which entity in the stomach has a "watermelon" appearance endoscopically?

GAVE (Gastric Antral Vascular Ectasia)

Red patches or longitudinal, nearly parallel linear streaks radiating proximally from the pylorus are identified endoscopically, imparting a watermelon-like appearance. The cause of GAVE is unknown, but it is associated with cirrhosis and portal hypertension, bone marrow transplantation, renal insufficiency, and scleroderma.

48

Hypertrophic gastritis: what are the 4 things in the DDx?

Menetrier's disease, lymphoid lesions, Zollinger Ellison syndrome, and signet ring cell carcinoma

49

The phenomenon of duplication of the musclaris mucosa is associated with what?

Barrett's esophagus

This is important in assessing the depth of invasion because infiltration of dysplastic glands into or between the two layers of duplicated muscularis mucosae should not be interpreted as submucosal invasion

50

What is Carney's triad?

multiple GISTs, extra-adrenal paraganlioma, and pulmonary chondroma

51

If you see a gross picture of a tumor that is causing kinking of the mucosa which has lead to a stricture causing a small bowel obstruction, what tumor should be on the top of the differential?

Carcinoid due to the desmoplasia

Random fact: carcinoids >2cm have 90% chance of metastasizing and those <1cm have 5% chance of metastasizing

52

What benign neuronal tumor is seen exclusively in the duodenum (periampullary)?

Gangliocytic paraganglioma

*associated with NF1

53

Other than C. Diff, in what other condition can pseudomembranous colitis be seen?

ischemic colitis, Enterohemorrhagic E. coli and rarely collagenous colitis

54

What is shown in this GI biopsy?

Balantidium coli

55

What is shown in this GI biopsy?

Trichuris trichiura 

56

What is shown in this GI biopsy?

Amebiasis

57

Colonic cystica profunda: when this is solitary what is the assocation and when it is multiple what is the association?

When solitary it is associated with solitary rectal ulcer syndrome

When multiple it is associated with IBD

58

According to 2010 Crohn's and Colitis Foundation guidelines, when should surveillance begin following initial diagnosis of pancolitis or left-sided colitis?

8-10 years following initial diagnosis of pancolitis or left-sided colitis

A repeat colonoscopy should be performed within 1-2 years. After two negative exams, colonoscopy is performed every 1-3 years provided the duration of disease does not exceed 20 years. Current guidelines also recommend that for an adequate surveillance, a minimum of 33 biopsies should be obtained using jumbo forceps.

59

What organism is shown on this GI biopsy?

Giardia lamblia

Pear shaped trophozoites with two ovoid nuclei and a central karyosome.

60

What features are specific for ischemic colitis?

Hyalinization of lamina propria, lamina propria hemorrhage and withered/atrophic crypts are typically associated with an ischemic etiology

61

What flagellate organism is implicated in causing megaesophagus and megacolon?

Trypanosoma cruzi

Due to inflammatory destruction of the myenteric plexus

62

What primary immunodeficiency disorder results from mutation in TNFRSF13B gene and is associated with celiac disease as its most common noninfectious GI complication?

Selective IgA deficiency

*both CVID and selective IgA deficiency show mutations in this gene

63

All of the choices listed are categorized as secondary causes of intestinal lymphangiectasia except:

1) constrictive pericarditis

2) lymphangioma

3) mesenteric tuberculosis

4) Milroy disease

5) neuroblastoma

Milroy disease

This is primary aka hereditary lymphedema and results from congenital obstruction of lymphatic flow or presence of abnormal lymphatics. It can involve multiple organs. Patients usually present with protein losing enteropathy, malabsorption and secondary immunodeficiency. In general, secondary lymphangiectasia occurs due to cardiovascular disorders or from conditions leading to lymphatic obstruction (the other choices listed)

64

Which finding in a GI biopsy is specific for H. pylori gastritis?

Lymphoid aggregates with germinal centers is considered to be the most specific finding

65

Which segment of GI tract is most commonly involved by eosinophilic gastroenteritis?

Stomach

Eosinophilic gastroenteritis is characterized by eosinophilic infiltration within one or more segments of the GI tract along with peripheral blood eosinophilia. Most patients also have a clinical history of allergies or asthma. Stomach is the msot common site of involvement. Based on the layer of bowel wall involved, three subtypes have been described: mucosal, mural and subserosal. 

The DDx of eosinophilia in the GI tract includes parasitic infections, vasculitis, collagen vascular disease, drugs, and Crohn's disease

66

What protein is deleted in 55% of pancreatic carcinomas and loss of its staining supports a diagnosis of a pancreatic primary?

DPC4

67

Why doesn't AE1/AE3 stain hepatocellular carcinomas and what is used in addition to help confirm this diagnosis?

AE1/AE3 does not contain CK18 and hepatocytes express CK18.

Cam5.2 is a good complement because it does cover CK18 (this is a low molecular weight keratin stain that covers CK8 and CK18

 

68

This is a lesion from the small bowel  composed of nodules with pinpoint white areas. Patient's with this lesion present with protein losing enteropathy (steatorrhea) and malabsorption (should give you that history in stem). What is it?

Cavernous hemangioma/lymphangioma

Patients with intestinal lymphangectasia present with malabsorption and protein losing enteropathy

69

In fibrous obliteration of the appendix, what do the spindle cells stain for?

S100

Therefore this process has also been referred to as neural hyperplasia or neuroma

70

What is the most common parasitic infection of the appendix?

Enterobius vermicularis

71

The hyperplastic gastropathy in Menetrier's disease is from excessive secretion of what?

Transforming growth factor alpha (TGF-alpha)

72

Which lymphoma most commonly presents as lymphomatosis polyposis of the GI tract?

Mantle Cell Lymphoma

Ileocecal valve region tends to contain the largest number of polyps

73

In Cowden's syndrome, besides hamartomatous polyps, what other GI lesions are common?

Colonic lipomas, fibrolipomas, fibromas, ganglioneuromas, and adenomas

74

In sessile serrated polyps, what genetic mutation do most of them harbor?

Most show BRAF mutations and show a high rate of DNA methylation

MSI is usually not associated with these lesions unless they develop epithelial dysplasia or carcinoma

75

What autosomal recessive syndrome is from a germline mutation in a gene associated with DNA base pair excision repair and results in numerous colon polyps and colon cancer?

MUTYH associated polyposis (MAP)

MUTYH is part of the DNA base excision repair system that protects genomic information from oxidative damage. MAP is a hereditary colon cancer syndrome inherited in an autosomal recessive pattern. It is caused by biallelic mutations in the MUTYH gene. Usually, the MUTYH gene product excises adenine bases from DNA at sites where adenine is inappropriately paired (such as with guanine or cytosine). When the MUTYH gene product is impaired by bi-allelic germline mutation, it leads to the mutation of cancer-related genes, such as APC, from inappropriate G:C to T:A transversions. The clinical features of MAP include 10-100 adenomatous polyps in the colon, and early onset of colorectal cancer. MAP is currently the only known recessive hereditary colon cancer syndrome. Approximately two-thirds of colon cancers in MAP are right-sided.

76

What genotype accounts for >85% of the cases of hereditary hemochromatosis?

One genotype (C282Y/C282Y) accounts for >85% of all cases of hereditary hemochromatosis (HH)

77

What recently described stain has been shown to be positive in 88% of pancreatic neuroendocrine tumors?

Recently, polyclonal antibody to Pax8 has been described to be positive in neuroendocrine tumors of the pancreas (up to 88%). Although the specificity and biological significance of this staining has been questioned due to antibody promiscuity of the Pax family, it is worthwhile for pathologists to know that polyclonal Pax8 can be positive in pancreatic neuroendocrine tumors (i.e. in a situation where an immunohistochemical workup is being performed for a metastasis from an unknown primary that includes potential pancreatic, renal, or gynecological origins). 

78

What stain is positive in appendiceal carcinoids but negative in ileal carcinoids?

Interestingly, S100 staining in appendiceal carcinoids highlights peripheral sustentacular cells (Ileal carcinoids do NOT) making them more similar to paragangliomas than to ileal neuroendocrine tumors.

79

What mutation is associated with Hereditary Diffuse Gastric Cancer (HDGC) and what types of cancers do these patients get?

Germline mutations in the CDH1 gene are the major cause of HDGC. Given that the protein E-Cadherin is encoded by the CDH1 gene it is not surprising that patients with HDGC are at risk for lobular breast cancer and diffuse, signet ring cell carcinoma. Prophylactic gastrectomy is the only option to prevent gastric cancer in individuals with a CDH1 mutation. The finding of early gastric lesions with patchy intramucosal signet ring cells illustrated in this patient’s resection can be easily missed on random sampling. 

80

What is the most common extra colonic neoplasm in the setting of FAP?

Periampullary adenocarcinoma

 

81

What subtype of colon cancer is more common in patient's with longstanding ulcerative colitis?

Signet ring cell carcinoma

82

A GIST with the morphology shown is most commonly found in what part of the GI tract and what are the structures shown that tell you where in the GI tract this is likely from?

Small bowel

The picture is showing spindle cells admixed with dense collagen fibers (skenoid fibers). Tumors arising in the small bowel are often associated with this peculiar stromal change referred to as skenoid fibers

83

Morphologically, how are GI schwannomas different from peripehral schwannomas?

GI schwannomas typically show a discontinuous cuff of lymphoid aggregates, lack the characteristic Antoni A and Antoni B areas and often do not harbor the thick-walled hyalinized blood vessels.

84

What antibodies are elevated in autoimmune hepatitis?

Elevated serum anti-smooth muscle antibodies and anti-liver kidney microsomal antibodies

In addition, serum HYPERgammaglobulinemia is present

85

CEA generally lacks specificity and is usually not used to differentiate carcinomas but there is one exception. What is this exception and what is the staining pattern?

Hepatocellular Carcinoma

In HCC, POLYCLONAL (not monoclonal) CEA stains in a canalicular pattern. It cross reacts wiht biliary epithelium in normal and neoplastic liver

86

What GI tumor shows cross reactivity with PSAP?

Rectal carcinoids

*also salivary tumors have been shown to be reactive with PSA

87

What is the histologic pattern of injury for HepC?

• Portal inflammation
• Lymphoid aggregates in portal tracts
• Lesions of bile ducts (Poulsen's lesion--shown here)
• Interface hepatitis
• Lobular inflammation
• Fibrosis

88

What is the histologic features and lab features of autoimmune hepatitis?

Marked interface inflammation with bridging necrosis
and plasma cells

Hypergammaglobulinemia (IgG)
ANA, ASMA, LKM1, soluble liver antigen or LP (liver
pancreas) antibodies
Only chronic hepatitis that responds to corticosteroids

89

What common drug can damage your bile ducts and lead to cholestasis?

Augmentin (amoxicillin and clavulanic acid)

90

What disease:

• Affects females, 40 – 60 years old, assoc w/ HLA DR
• Autoimmune diseases
     – Sjogren syndreom, scleroderma
• AMA positive
     – Minority of cases are AMA negative
• Elevated IgM
• Cholestasis
• Florid duct lesion
     – Bile duct injury
• Granulomas and have increased risk for HCC

PBC

Anti mitochondrial antibodies are targeted against the E2 component of pyruvate dehydrogenase complex present within mitochondria

91

What disease: 

• Fibroinflammatory disease affecting intra and extrahepatic biliary tree,
leading to strictures and cirrhosis
• Affects males more commonly, 25 – 60 year old
• Assoc with UC
• Fibrous obliteration of bile ducts
     – Periductal fibrosis
     – Ductopenia
• ↑ cholangiocarcinoma
• ERCP or MRCP
     – Beaded appearance with segmental strictures and dilations of bile ducts

PSC

92

What drug causes:

Foamy granular hepatocytes from phospholipids which show lysosome inclusions by EM?

Amiodarone

93

What stains highlight Mallory-Denk bodies of steatohepatitis?

p62+, ubiquitin+

Ropey, pink material
• Intermediate filaments metabolized
by cytokeratin from liver cell injury
 

94

BQ!! What is the structure shown in the liver and what infectious agent is it associated with? 

Ring fibrin granuloma (histiocytes surrounding fat lobule)

associated with Q fever (Coxiella burnetti)

95

What are the two most common mutation in hereditary hemochromatosis?

– C282Y and H63D
– C282Y cysteine to tyrosine substitution at
amino acid position 282
– C282Y has highest iron overload

96

What are the classifications of hereditary hemochromatosis? (Types 1-4 and what are the genes that are mutated)

Type Gene mutated
• 1 HFE
• 2A hemojuvelin-
• 2B hepcidin
• 3 transferrin receptor2
• 4 ferroportin

Hemojuvelin and hepcidin mutations are often seen in children
Iron granules are more coarse and refractile than bile or lipofuscin

97

What is the mutation in Wilson's disease?

Mutated ATP7B gene, a copper transport protein in Golgi with accumulation of copper in liver and other organs
• Labs
– ↓Cerruloplasm—not sensitive or specific
– ↑Hepatic copper concentration— best test
• Liver failure and neurologic signs
• Liver morphology
– Steatosis, hepatitis, glycogenated nuclei, Mallory hyaline, copper by Rhodanine or
Orcein stains (UNRELIABLE)

98

If you see a vascular lesion in the liver where the central vein is abnormally close to the portal area, what is the diagnosis?

Hepatoportal sclerosis

DDx includes portal vein thrombosis but they will show an occluding thrombus

99

What are the two types of cholangiocarcinoma and what are their different mutations?

Mass forming CC: better prognosis, from small bile ductules, K-ras mutation neg, p53 pos
Periductal CC: worse prognosis, from branches of hepatic bile ducts, K-ras mutation pos, p53 neg

100

In ampulla of Vater cancer staging, what is considered T1?

Tumor limited to ampulla of Vater or sphincter of Oddi

Tis         Carcinoma in situ

T1         Tumor limited to ampulla of Vater or sphincter of Oddi

T2         Tumor invades duodenal wall

T3         Tumor invades pancreas

T4         Tumor invades peripancreatic soft tissues or other adjacent organs or structures other than pancreas

101

In ampulla of Vater cancer staging, what is considered T2?

Tumor invades duodenal wall

Tis         Carcinoma in situ

T1         Tumor limited to ampulla of Vater or sphincter of Oddi

T2         Tumor invades duodenal wall

T3         Tumor invades pancreas

T4         Tumor invades peripancreatic soft tissues or other adjacent organs or structures other than pancreas

102

In ampulla of Vater cancer staging, what is considered T3?

Tumor invades pancreas

Tis         Carcinoma in situ

T1         Tumor limited to ampulla of Vater or sphincter of Oddi

T2         Tumor invades duodenal wall

T3         Tumor invades pancreas

T4         Tumor invades peripancreatic soft tissues or other adjacent organs or structures other than pancreas

103

In ampulla of Vater cancer staging, what is considered T4?

Tumor invades peripancreatic soft tissues or other adjacent organs or structures other than pancreas

Tis         Carcinoma in situ

T1         Tumor limited to ampulla of Vater or sphincter of Oddi

T2         Tumor invades duodenal wall

T3         Tumor invades pancreas

T4         Tumor invades peripancreatic soft tissues or other adjacent organs or structures other than pancreas

104

What is the T and N staging for anal carcinoma?

Tis           Carcinoma in situ

T1           Tumor 2 cm or less in greatest dimension

T2           Tumor more than 2 cm but not more than 5 cm in greatest dimension

T3           Tumor more than 5 cm in greatest dimension

T4           Tumor of any size invades adjacent organ(s), eg, vagina, urethra, bladder#

#Direct invasion of the rectal wall, perianal skin, subcutaneous tissue, or the sphincter muscle is not classified as T4.

N1          Metastasis in perirectal lymph node(s)

N2          Metastasis in unilateral internal iliac and/or inguinal lymph node(s)

N3          Metastasis in perirectal and inguinal lymph nodes and/or bilateral internal iliac and/or inguinal lymph nodes

105

What stains help differentiate between poorly diff anal squamous cell CA and anal gland carcinoma?

Squamous cell carcinomas of the anal canal express cytokeratin (CK) 7, CK5/6, p53,12 and p63 but are negative for CK20.  In contrast, anal gland carcinomas are mucin positive and express CK 20 and CK7, but are negative for CK5/6 and p63

106

With Paget's disease of the anus, what stains help differentiate if there is underlying rectal adenoCA vs primary cutaneous intraepithelial malignancy?

Demonstration of CK20 expression has been shown to identify Paget disease that is likely to be associated with underlying rectal adenocarcinoma (presenting either synchronously or metachronously). In contrast, Paget cells that do not express CK20 but instead are positive for gross cystic disease fluid protein (GCDFP), a marker for apocrine differentiation, are likely to represent primary cutaneous intraepithelial malignancy

107

What is the T and N staging for appendix?

Tis           Carcinoma in situ: intraepithelial or invasion of lamina propria

T1           Tumor invades submucosa

T2           Tumor invades muscularis propria

T3           Tumor invades through muscularis propria into subserosa or into mesoappendix

T4           Tumor penetrates visceral peritoneum, including mucinous peritoneal tumor within the right lower quadrant and/or directly invades other organs or structures

T4a         Tumor penetrates visceral peritoneum, including mucinous peritoneal tumor within the right lower quadrant

T4b         Tumor directly invades other organs or structures

N1          Metastasis in 1 to 3 regional lymph nodes

N2          Metastases in 4 or more regional lymph nodes#

# The regional lymph nodes for the appendix include the anterior cecal, posterior cecal, ileocolic, and right colic lymph nodes.

 

108

What is the T and N staging for colon?

pTis:      Carcinoma in situ, intraepithelial (no invasion of lamina propria)

pTis:      Carcinoma in situ, invasion of lamina propria/muscularis mucosae (intramucosal)

pT1:      Tumor invades submucosa

pT2:      Tumor invades muscularis propria

pT3:      Tumor invades through the muscularis propria into pericolorectal tissues

pT4a:    Tumor penetrates the visceral peritoneum

pT4b:    Tumor directly invades or is adherent to other organs or structures

pN1a:   Metastasis in 1 regional lymph node

pN1b:   Metastasis in 2 to 3 regional lymph nodes

pN1c:   Tumor deposit(s) in the subserosa, or non-peritonealized pericolic or perirectal tissues without regional lymph node metastasis

pN2a:   Metastasis in 4 to 6 regional lymph nodes

pN2b:   Metastasis in 7 or more regional lymph nodes

109

What cancer related gene is most frequently ACTIVATED in pancreatic cancer?

KRAS

It is activated by point mutations in 80-90% of pancreatic cancer.

CDKN2A (p16), SMAD4 and P53 are typically INACTIVATED in pancreatic cancer

110

What percent of sporadic colon cancers are due to MSI-H abnormalities?

15%

This is usually due to hypermethylation of MLH1

 

111

Why is PCR and IHC performed together when looking at MSI?

PCR is just going to tell you if MSI stabile or unstable. Patients with MSI-H indicates mismatch repair deficiency in their cancer may have a germline mutation in one of several DNA mismatch repair (MMR) genes (eg, MLH1, MSH2, MSH6, or PMS2) or an altered EPCAM (TACSTD1) gene.

IHC will tell you WHICH gene is messed up. MLH1 pairs with PMS2 and MSH1 pairs with MSH6. For example, a patient whose tumor shows loss of MSH2 and MSH6 expression, but retention of MLH1 and PMS2 expression, is likely to have an MSH2 germline mutation.

112

Does intact expression of all 4 MMR proteins exclude Lynch syndrome?

No

approximately 5% of families may have a missense mutation (especially in MLH1) that can lead to a nonfunctional protein with retained antigenicity. Defects in lesser-known MMR enzymes may also lead to a similar result, but this situation is rare.

113

When working an MSI case, how do you interpret loss of staining in 1) MLH1, 2) MSH2, 3) PMS2, 4) MSH6?

1) Loss of expression of MLH1 may be due to Lynch syndrome or methylation of the MLH1 promoter region (as occurs in sporadic MSI colorectal carcinoma). Genetic testing is ultimately required for this distinction, although a specific BRAF gene mutation (V600E) is present in many sporadic cases, but not familial cancers.

2) Loss of MSH2 expression strongly suggests Lynch syndrome.

3) PMS2 loss is often associated with loss of MLH1 and is only independently meaningful if MLH1 is intact.

4) MSH6 is similarly related to MSH2.  One should also keep in mind that nucleolar staining or complete loss of MSH6 staining has been described in colorectal cancer cases with prior radiation or chemotherapy,

114

When you have a MSI-H case with loss of MLH1 staining, what mutation can tell you if it is sporadic from hypermethylation or familial from Lynch syndrome?

The V600E mutation of the BRAF gene may be present in up to 70% of tumors with hypermethylation of the MLH1 promoter.  In colorectal cancer, this mutation has been associated with a limited clinical response to epidermal growth factor receptor (EGFR) targeted therapies (cetuximab or panitumumab).

115

What is the T and N staging for distal extrahepatic bile duct cancer?

pT1: Tumor confined to the bile duct histologically

pT2: Tumor invades beyond the wall of the bile duct

pT3: Tumor invades the gallbladder, pancreas, duodenum, or other adjacent organs without involvement of the celiac axis or the superior mesenteric artery

pT4: Tumor involves the celiac axis or the superior mesenteric artery

pN0: No regional lymph node metastasis

pN1: Regional lymph node metastasis

116

Tumors in the biliary tree are classified into three groups: intrahepatic, perihilar and distal.

What does perihilar and distal mean?

Perihilar tumors are defined as those involving the hepatic duct bifurcation or extrahepatic biliary tree proximal to the origin of the cystic duct,

Distal tumors are those lesions arising between the junction of the cystic duct-bile duct and the ampulla of Vater

117

What is the T and N staging for primary carcinomas of the intrahepatic bile ducts and combined hepatocellular-cholangiocarcinoma?

Tis:  Carcinoma in situ (intraductal tumor)

T1: Solitary tumor without vascular invasion

T2a: Solitary tumor with vascular invasion

T2b: Multiple tumors, with or without vascular invasion

T3: Tumor perforates the visceral peritoneum or involves local extrahepatic structures by direct invasion

T4: Tumor with periductal invasion

N0: No regional lymph node metastasis

N1: Regional lymph node metastasis

118

What is the T and N staging for esophagus?

pTis: High-grade dysplasia

pT1: Tumor invades lamina propria, muscularis mucosae, or submucosa

-pT1a: Tumor invades lamina propria or muscularis mucosae

-pT1b: Tumor invades submucosa

pT2:  Tumor invades muscularis propria

pT3: Tumor invades adventitia

pT4: Tumor invades adjacent structures (specify):

pT4a: Resectable tumor invading pleura, pericardium, or diaphragm

pT4b: Unresectable tumor invading other adjacent structures, such as aorta, vertebral body, trachea, etc

pN0: No regional lymph node metastasis

pN1: Regional lymph node metastasis involving 1 to 2 nodes

pN2: 3 to 6 nodes involved

pN3:  7 or more nodes involved

119

What is the T and N staging for hepatocellular carcinoma?

T1 Solitary tumor without vascular invasion

T2 Solitary tumor with vascular invasion; or multiple tumors, none more than 5 cm in greatest dimension

T3 Multiple tumors more than 5 cm in greatest dimension or tumor iinvolving a major branch of the portal or hepatic veins(s)

                   --T3a Multiple tumors more than 5 cm

                   --T3b Tumor(s) any size involving a major branch of the portal or hepatic vein(s)

T4 Tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum

N0 No regional lymph node metastasis

N1 Regional lymph node metastasis

120

What is T and N staging for gallbladder?

pT1:  Tumor invades lamina propria or muscular layer

pT1a: Tumor invades lamina propria

pT1b: Tumor invades muscle layer

pT2: Tumor invades perimuscular connective tissue; no extension beyond serosa or into liver

pT3: Tumor perforates serosa (visceral peritoneum) and/or directly invades the liver and/or one other adjacent organ or structure, such as the stomach, duodenum, colon, pancreas, omentum, or extrahepatic bile ducts

pT4: Tumor invades main portal vein or hepatic artery or invades 2 or more extrahepatic organs or structures

pN1: Metastases to nodes along the cystic duct, common bile duct, hepatic artery, and/or portal vein

pN2: Metastases to periaortic, pericaval, superior mesentery artery, and/or celiac artery lymph nodes

121

What is the T and N staging for GISTs?

pT1: Tumor 2 cm or less

pT2: Tumor more than 2 cm but not more than 5 cm

pT3: Tumor more than 5 cm but not more than 10 cm

pT4: Tumor more than 10 cm in greatest dimension

pN1: Regional lymph node metastasis

122

What is the T and N staging for pancreatic exocrine tumors (ie adenocarcinoma)?

Tis Carcinoma in situ

T1 Tumor limited to the pancreas, 2 cm or less in greatest dimension

T2 Tumor limited to the pancreas, more than 2 cm in greatest dimension

T3 Tumor extends beyond the pancreas but without involvement of the celiac axis or the superior mesenteric artery

T4 Tumor involves the celiac axis or the superior mesenteric artery (unresectable primary tumor)

*If more than 1 tumor is present in the pancreas, the tumor with the highest T category should be classified according to the pT definitions and either the multiplicity (“m”) or the actual number of simultaneous multiple tumors (eg, “3”) should be indicated in parentheses after the T category of the primary tumor (eg, pT3[m] or pT3[2]).

N0 No regional lymph node mets

N1 Regional lymph node mets

123

What is the T and N staging for small bowel?

T1a Tumor invades lamina propria

T1b Tumor invades submucosa

T2 Tumor invades muscularis propria

T3 Tumor invades through the muscularis propria into the subserosa or the nonperitonealized perimuscular tissue (mesentery or retroperitoneum) with extension 2 cm or less

T4 Tumor perforates the visceral peritoneum or directly invades other organs or structures (includes other loops of small intestine, mesentery, or retroperitoneum more than 2 cm, and abdominal wall by way of serosa; for duodenum only, invasion of pancreas or bile duct)

N1 Metastasis in 1 to 3 regional lymph nodes

N2 Metastasis in 4 or more regional lymph nodes

124

What is the T and N staging for stomach cancer?

Tis Carcinoma in situ (including high-grade dysplasia): intraepithelial tumor without invasion of the lamina propria

T1 Tumor invades lamina propria, muscularis mucosae, or submucosa

T1a Tumor invades lamina propria

T1b Tumor invades submucosa

T2 Tumor invades muscularis propria

T3 Tumor penetrates subserosal connective tissue without invasion of visceral peritoneum or adjacent structures (distal extension to duodenum does not affect T stage)

T4 Tumor invades serosa (visceral peritoneum) or adjacent structures

T4a Tumor invades serosa (visceral peritoneum)

T4b Tumor invades adjacent structures

N1 Metastasis in 1 to 2 perigastric lymph nodes

N2 Metastasis in 3 to 6 perigastric lymph nodes

N3 Metastasis in more than 6 lymph nodes

*Lymph nodes containing isolated tumor cells, defined as single tumor cells or small clusters of cells not more than 0.2 mm in diameter, are classified as pN0. Discontinuous tumor deposits without evidence of residual lymph node and located in the subserosal tissue adjacent to a gastric carcinoma are considered regional lymph node metastases. Nodules implanted on the peritoneal surface are considered distant metastases (M1). 

 

125

What stain is positive in a DALM from an IBD patient that can help distinguish from reactive atypia?

p53

DALMs will be p53 positive and beta-catenin negative whereas sporadic tubular adenomas will be positive for beta-catenin and negative for p53 (early in disease--as it progresses to higher grade lesions will pick up p53)

126

How does staining of fibrolamellar hepatocellular carcinoma differ from usual HCC?

Fibrolamellar is CK7 positive and AFP negative

127

What lung stain also stains hepatocellular carcinoma but is cytoplasmic in HCC?

TTF1

128

In a patient with a bone marrow transplant, what esophageal endoscopic findings is DIAGNOSTIC of chronic GVHD?

Upper esophageal webs

 

129

What specific mutation is found in WIlson's disease?

ATP7B for copper-transporting ATPase located in the trans-Golgi network of the liver

130

This liver tumor is typically found in infants. What is it? Which histologic type has the BEST prognosis? What IHC stain is characteristic with the small cell variant?

Hepatoblastoma

Fetal epithelial type has best prognosis

Small cell variant has INI1 LOSS

Associated with Beckwith-Weideman, FAP

• 90% seen < 5 Y/O
• Associated with FAP and APC gene
• Precocious puberty due to elevated HCG
• Elevated AFP

131

This is a gross image of a stomach. Name this entity.

Hyperplastic gastropathy--Menetrier's disease

132

This is a PAS stain of a small bowel biopsy. Is this MAI or Whipple's and how can you tell?

Whipples disease! In this, you have organisms that stain in the macrophages AND the lamina propria.

This is a PAS stain of a case of MAI  and not only do the organisms stain differently but the organisms are predominately in macrophages

133

Name this infectious agent.

Microsporidiosis

Notice the peculiar round organisms just beneath the brush border

134

Name this infectious agent.

Cryptosporidiosis

135

Name this disease.

Ulcerative colitis

136

Name this disease.

Crohn's disease

137

Name this disease.

Collagenous colitis

138

Name this entity.

Pseudomembranous colitis

(volcano eruptions)

139

Name this entity.

Mucosal prolapse

140

Name this lesion.

Traditional serrated adenoma

141

What percentage of carcinomas occuring in the distal 1/3 of the esophagus are adenocarcinoma?

80%

142

The three mutations are commonly seen in esophageal adenoCA?

c-myc

H-ras (seen in both high grade dysplasia and carcinoma)

TP53 (60%)

143

What subtype of esophageal squamous cell carcinoma is most likely to present as a submucosal lesion?

Papillary

144

How much mucin is needed to diagnose mucinous carcinoma of the esophagus or stomach?

>50%

145

How often are GISTs of the stomach malignant?

30%

146

What is MYH associated polyposis?

Autosomal recessive disorder phenotypically similar to attenuated FAP. Think of this disease if you have a patient with attenuated FAP like disease but no evidence of AD transmission

147

What autosomal dominant condition is also caused by PTEN mutation on 10q23 (like Cowden's) but manifests as hamartomatous polyps (like Peutz-Jeghers), lipomas, hemangiomas and MACROcephaly?

Ruval-Caba-Myhre-Smith (aka Bannayan-Riley-Ruvalcaba)

*don't ask me how you are supposed to remember TWO crazy names like that.....

148

What syndrome is autosomal dominant mutation of p16 on 9p21 and results in 100+ dysplastic nevi, has increased risk of melanoma and 12-20 fold increase in pancreatic adenoCA?

Familial Atypical Multiple Mole Melanoma Syndrome (FAMMM)

149

BQ slide!

Name this lesion.

Mucosal prolapse/cloacogenic polyp of solitary rectal ulcer syndrome 

150

BQ! Make sure you can differentiate Mallory's hyaline and alpha-1-antitrypsin on H&E. Which one is this?

Mallory's hyaline.

This is A1AT (autosomal RECESSIVE inheritance)

151

BQ SLIDE!

Name this liver lesion.

Primary biliary cirrhosis

152

BQ SLIDE!

Name this liver entity.

Autoimmune hepatitis

Typical morphological changes:

Portal plasma cell rich inflammation

Interface hepatitis, formerly referred to as piecemeal necrosis: portal inflammatory cells eroding through the limiting plate between the portal tract and liver parenchyma

Emperipolesis: apparent engulfment of lymphocytes by hepatocytes

Hepatocyte rosette formation

Variable fibrosis (about 10% of AIH does not show any fibrosis at initial presentation)

Lobular necroinflammatory activity: usually accompanied by portal and periportal inflammation

153

BQ GROSS PHOTO!

Name this pancreatic lesion.

Serous cystadenoma (serous microcystic tumor)

154

What recent stain has been shown to be specific for the serrated neoplasia pathway of colon cancer?

Annexin A10 expression is associated with poor clinical behavior and can be used a supportive surrogate marker of the serrated neoplasia pathway in invasive CRCs (negative in TA)

155

In addition to Cowden's syndrome, PTEN mutations are implicated in many other cancers. Regarding the immunostain, what are its main uses by pathologists?

LOSS OF NUCLEAR PTEN

(positive staining in almost all body tissues, similar to INI1 in that way)

-seen in adenomatous thyroid nodules part of Cowden's syndrome

-distinguishes intraductal prostatic carcinoma from HGPIN

-seen in EM hyperplasia and cancer (early marker)

156

This is from a liver biopsy from a patient with hepatitis. What type of hepatitis (based on this lesion) and what is this lesion called?

Hepatitis C

Picture is showing a Poulsen's lesion which is defined by bile duct lymphocytosis and reactive epithelial change. Can be seen in Hep C or B but more common in Hep C

157

What is being shown in this liver biopsy?

Hep B ground class hepatocytes

The appearance is classically associated with abundant hepatitis B antigen in the endoplasmic reticulum, but may also be drug-induced (IHC stain for anti-HBs). In the context of hepatitis B, GGHs are only seen in chronic infections, i.e. they are not seen in acute hepatitis B.

"Sanded nuclei" shown here are seen in HepB replicative hepatocytes (IHC for anti-HBc).

158

What is the criteria to diagnose AIH/PBC overlap syndrome? 

At least two for each AIH and PBC
• AIH
     – ALT>5X ULN
     – IgG>2X ULN, or positive SMA
     – Chronic hepatitis pattern of injury on liver Bx
• PBC
     – ALP>2X ULN
     – Positive AMA
     – Florid duct lesion on liver Bx

159

What is the definition of autoimmune cholangiopathy?

• aka AMA-negative PBC
• Histologically, clinically, and biochemically 
indistinguishable from AMA positive PBC
• Elevated ANA and anti-SMA

160

What entity is this?

PSC

• Chronic non-specific inflammatory damage/fibrosis in the wall of the biliary tree causing cholestasis
     – Ductular reaction
     – Cholate stasis
• Concentric periductal ("onion-skin") fibrosis
• Fibroobliteration of the bile ducts
• Biliary type cirrhosis

161

What disease is shown in this gross image?

Hereditary hemochromatosis

• Autosomal recessive disorder
• HFE gene located at chromosome 6
• Most common mutation is a cysteine to tyrosine substitution at aa 282.
• Primary defect lies in the excessive intestinal absorption of iron
• Subsequent excessive accumulation of body iron in liver and pancreas

162

What liver tumor has this gross appearance:

– Single mass (56%)
– Scalloped, firm to hard margin
– White fibrous septa, central scar
– Calcium
– Lobulated, tan, gray or brown

Fibrolamellar variant of HCC

• 1% of all HCC
• Mostly occurs in non-cirrhotic HCC
• Predominantly adolescent or young adults (25-34Y/O)
• 1:1 (M:F)
• More favorable prognosis

163

What liver tumor has this micro appearance:

• Fibrous stroma forms lamella that vary in thickness
• Sheet-like pattern of tumor cells but microtrabeculae may be present
• Pseudogland
• Calcification

Fibrolamellar variant of HCC

• Tumor cells larger than normal hepatocytes, polyhedral, or rounded
• Deeply eosinophilic, coarsely granular cytoplasm
• Cytoplasmic inclusions
     – Ovoid “pale bodies” (ground glass but HBV-PAS-/fibrinogen+)
     – Mallory hyalines (rare)

• Large, hyperchromatic, and vesicular nuclei
• Prominent nucleoli
• Mitoses and multinucleation infrequent

164

What liver tumor has this appearance?

Fibrolamellar variant of HCC

• Tumor cells larger than normal hepatocytes, polyhedral, or rounded
• Deeply eosinophilic, coarsely granular cytoplasm
• Cytoplasmic inclusions
     – Ovoid “pale bodies” (ground glass but HBV-PAS-/fibrinogen+)
     – Mallory hyalines (rare)

• Large, hyperchromatic, and vesicular nuclei
• Prominent nucleoli
• Mitoses and multinucleation infrequent

165

What liver lesion is this?

Bile Duct Hamartoma
(von Meyenburg Complex)

166

What liver lesion is this?

Peribiliary Gland Hamartoma
(Bile Duct Adenoma)

167

This is a gross lesion of what tumor found in the liver?

Cholangiocarcinoma in non-cirrhotic liver

Here is one in a cirrhotic liver

168

What are the MUC staining patterns for the subtypes of IPMN?

169

What is this pancreatic neoplasm?

Solid pseudopapillary tumor

Positive:
– α1-antitrypsin
– NSE
– Vimentin
– Progesterone receptor
– CD10
– CD56
– β-catenin
– Synaptophysin

170

What infectious agent is seen in this biopsy?

Cyclospora cayetanensis

171

What infectious agent is this?

Isospora belli

PAS positive banana shaped parasites surrounded by parasitophorous vacuole

172

What is the most common location in the GI tract for a granular cell tumor?

ESOPHAGUS

It can occur anywhere but esophagus is most common site

173

This EM is from a 3 week old boy with history of refractory diarrhea. The biopsy showed severe villous atrophy WITHOUT IELs or inflammation. A PAS stain showed absence of brush border. What is the disease and what features are being shown on EM?

Microvillous inclusion disease

Autosomal recessive disease with pathognomonic EM findings: absent or small stubby microvilli, vesicular structures located towards the apex of the enterocytes with microvilli, and granules containing dense amorphous material

Treatment is small bowel transplant

174

What location is most often affected by necrotizing enterocolitis?

Ileocecal valve region

This is a watershed region

NEC is most common cause of intestinal perforation in the NICU

175

A patient with cirrhosis undergoes endoscopic evaluation for GI bleeding. The stomach shows this finding (mosaic mucosal pattern) and the biopsy reveals numerous ectatic capillaries and venules within the lamina propria, without evidence of vascular thrombi. What is the most likley cause of the GI bleeding?

Portal hypertensive gastropathy

Occurs in 90% of patients with cirrhosis

176

What is the most common cause of lower GI bleeding?

Diverticular disease

177

What entity has characteristic circumferential ulcers which helps differentiate it from Crohn's?

Intestinal tuberculosis

178

This finding in the esophagus of one to several nodular lesions with prominent intracytoplasmic glycogen is associated with what TWO syndromes?

Cowden's and Tuberous Sclerosis

179

Type I NF is associated with all of the following GI neoplasms EXCEPT:

a) ampullary adenoCA

b) gangliocytic paraganglioma

c) GIST

d) inflammatory fibroid polyp

e) somatastatinoma

d) inflammatory fibroid polyp

NF1 is associated with all of the other choices in addition to neurofibromas

NF1 is from germline mutation of the NF1 tumor suppressor gene on Ch17

NF2 usually does NOT affect the GI tract

180

What is the serrated pathway of developing CRC?

This pathway involves BRAF and KRAS (see schematic)

MVHP: Microvesicular hyperplastic polyp 

GCHP: Globet cell hyperplastic polyp 

MPHP: Mucin-poor hyperplastic polyp

TSA: Traditional serrated adenoma

MP: Mixed polyp

CIMP: CpG island methylator phenotype

181

Which of the following histologic types of CRC is more common in patients with longstanding UC?

a) adenosquamous CA

b) medullary carcinoma

c) mucinous carcinoma

d) signet ring cell CA

e) small cell CA

d) signet ring cell CA

More common in pts with UC and like mucinous CA, present at advanced stage.

Medullary CA are associated with MSI

Adenosquamous are VERY rare and are associated with paraneoplastic hypercalcemia and often present at higher stage

182

Which rare subtype of CRC is associated with paraneoplastic hypercalcemia and often present at higher stage?

Adenosquamous 

183

Which of the following drugs/toxins/meds causes bland cholestasis WITHOUT accompanying inflammation or liver injury?

a) alcohol

b) amiodarone

c) cocaine

d) methotrexate

e) OCPs

OCPs

Alcohol and amiodarone cause a steatohepatitis pattern of injury. In addition, amiodarone also causes phospholipidosis.

Cocaine leads to microvascular injury and parenchymal necrosis.

Methotrexate causes steatosis and manifests as chronic hepatitis pattern of injury.

184

What is sinusoidal obstruction syndrome?

A veno-occlusive disease secondary to chemotherapy and radiation therapy. 

The sinusoidal injury eventually results in non thromotic occlusion of the terminal hepatic vein.

185

What liver lesion is defined by the presence of 1 to 2mm nodules separated by hepatocyte atrophy without accompanying fibrosis and what conditions are implicated in its pathogenesis?

Nodular regenerative hyperplasia

RA, colon cancer chemo, and polyarteritis nodosa

Microscopically, the condensation or collapse of reticulin fibers around the nodular parenchyma is considered to be diagnostic of this entity.

186

Macrovesicular steatosis is caused by all of the following conditions EXCEPT:

a) acute fatty liver of pregnancy

b) alcohol

c) obesity

d) Type II DM

e) Wilson disease

a) acute fatty liver of pregnancy

This has MICROvesicular steatosis.

This is believe to be the result of mitochondrial injury and is chracterized by the presence of multiple small fat vacuoles within the cytoplasm of the hepatocyte. The nucleus remains within the center of the cell.

Reye's syndrome and drug toxicity (tetracycline and valproic acid) are some other conditions causing microvesicular steatosis

187

A 16 month old baby with severe jaundice and high unconjugated bilirubin levels from a hereditary disorder of bilirubin metabolism that lacks the conjugating enzyme is a result of what mutation?

Deficiency of a conjugation enzyme UDP-glucuronsyl transferase 1A1 (UGT1A1)

Crigler-Najjar syndrome

In Type I the enzyme is COMPLETELY absent and without transplant is fatal,

Type II is less severe and has reduced levels of enzyme. Phenobarbital therapy promotes bilirubin glucuronidation by inducing hypertrophy of endoplasmic reticulum and is thus useful in treating the type II form.

 

188

What disorder of bilrubin metabolism causes a conjugated hyperbilirubinemia and the liver shows black-brown pigment (shown here) due to the accumulation of a chemical polymer in lysosomes that resembles epinephrine? What is the defective protein?

Dubin Johnson syndrome

Results from defect in the canalicular transport protein called multidrug resistance protein-2 (MRP-2)

189

What mutation if present significantly increases the risk of progression to HCC with this entity?

The picture is showing a hepatic adenoma

Hepatocytes without significant atypia, mitotic activity or necrosis. The cells are arranged in cords 1-2 cells thick. Does not contain normal portal tracts but instead numerous unpaired arteries. More common in women with OCP use but also in anabolic steroid use, tyrosinemia and glycogen storage disorders

Classified into three subtypes:

Beta catenin mutated adenomas: HIGHER RISK OF HCC

Inflammatory adenomas

HNF1-alpha-mutated adenomas

 

190

DEFINITE BQ!

What organism is shown here by EM that causes diarrhea in an immunocompromised pt?

Tropheryma whippelii 

unusual trilaminar cell wall ultrastructure

They show EM on boards!