GI Malignant

Question 1

Signs of PPI drug use?

Answer 1

Parietal cell hyperplasia

Parietal cell hypertrophy

Parietal cell vaculolation

Semi-serrated apperance

Question 2

Familial adenomatous polyposis (genes)?

What is Menerier’s disease?

Answer 2

APC (90%), b-catenin (10%) in familair/ sporatic is reversed

Multiple hyperplastic polyps, Watermelon stomach, dilated corkscrew glands, can extend into muscularis mucosa, possible increased intraepithelial lymphocytes

Question 3

Findings in Peutz-Jegher’s Hamartomatous polyp?

Answer 3

Epithelium: Unremarkable

Pit and Glands: Grouped or packed with intervening septation of smooth muscle

Lamina propria: Unremarkable

Smooth Muscle: Short wispy or chunky bundles not connecte dto muscularis mucosae; vs Hyperplastic that connect

Question 4

Findings in Juvenile Polyp (Hamartomatous)?

Answer 4

Epithelium: Eroded or Normal

Pits and glands: Disorganized with varying shapes/sizes. Edematous club shapped or irredular villiform structures

Lamina propria: Edematours, Granulation tissue common

Smooth muscle: Unremarkable

Question 5

Hyperplastic (Hamartomatous polyp) findings?

Answer 5

Epithelium: Damaged wtih reactive or regenreative chagnes, chemical gastropathy changes

Pit and Gland: Surface pits connected to deeper portions of glands (linear trajectory), small, regular and orderly glands with possible surface erosion

Lamina Propria: Unremarkable or inflammed

Smooth muscle: Long sweeping bundles that connected to muscularis mucosae

Question 7

Gene in Peutz-Jegher syndrome?

What cancers in skin, GI, breast, and GYN?

Answer 7

LKB1/STK11

Skin: Melanotic pigmentation of digits, genitalia, lips, oral mucosa, etc.

GI: Hamartoma, increased colorectal risk, intussusception and bleeding, Adeno of GI (including pancreas)

Breast: CA

GYN: Sex-cord tumor with annular tubules (almost all), ovarian mucinous tumor, adenoma malignum of cervic well differentiated gastic type mucosa)

Question 8

Juvenile polyposis syndrome, Autodominant genes?

True or false large proportion have no family history?

Diagnostic criteria?

True or false: Increased risk of colorectal gastric carcinoma?

Answer 8

Dysregulation of TGF-B, SMAD4 (20% familial cases), BMPR1A (25%)

True: incomplete penetrance=large population w/o family history

3-10 juvenile polyps or JP in entire GI tract, Any number with history of juvenile polyposis

True; 55% increase in colorectal and gastric

Question 9

Cowden syndrome?

What is Cronkhite-Canada Syndomre?

Answer 9

Hamartomatous overgrowths:
Skin: Trichilemmoma, Acral Keratosis, Oral papillomas

GI: Hamartoma polyps (similar to juvenile), increased CA risk

Breast: Fibroadenoma, FCC, CA

Endometrium: increased risk of CA

Thyroid: Goiter, Adenoma, CA

Gene: AD/Germline PTEN 70-80% of patients, SDH less common

Question 10

Cronkhite-Canada syndrome?

Is it possibly an autoimmune disorder?

Answer 10

Not inheritied-unknown etiology (autoimmune?)

Entire GI tract (except esophagus) with polyps (CA 25% of cases), ectodermal changes (alopecia, nail atrophy, hyperpigmentation),

Polyps are of juvenile morphology

Question 11

In what familial disease do gastric adenomas occurs?

Are they more common in the US or Asia?

Answer 11

FAP, or spontaneously

Asia 9-27% in Japan/China, 0.6-4% in Western Countries

Question 12

Stomach dysplasia IHCs?

Intestinal ademona/dysplasia: CD10, MUC2?

Foveolar MUC5AC, MUC6?

Pyloric MUC5AC, MUC6?

Answer 12

Intestinal ademoa: CD10+, MUC2+, looks like colonic TA

Foveolar: MUC5AC+, MUC6+/-, MUC2- Tall cells with clear cytoplasma and low columnar cuboidal nuclei

Pyloric: MUC5AC+/-, MUC6+, pale eosinophilic ground glass cytomplasm with round/oval nuclei

Question 13

Glomus tumor tumor morphology/stains?

Arises from?

Common locations?

Confused with?

Answer 13

SMA+, Caponin+, Coollagen 4+, S-100-, C-kit-, chromogramin-: Cellular nodules, hemorrhage common, Staghorn vessels, Sharp cell membranes

Neuromyoarterial glomus body

Common in fingers

Confused with GIST (DOG1+, C-kit+)

Question 14

GIST, 3 histologic types/stains?

What is seen in the paranuclear space?

Can it have myxoid changes and osseous metaplasia?

What is the Kit status of dedifferentieded GIST?

Answer 14

Circumscribed in wall of stomach, Spindle, Epithelioid, Mixed

C-kit, DOG1 Positive

**Paranuclear vaculolization (vs leiomyoma)

Yes, can mimic schwanoma

C-kit Negative c/ atypia**

Question 15

GIST (KIT and PDGFRA are on what chromosome?

GIST on Exon 11 what is better “inframe deletion or missense”?

Small intesting GIST good or bad prognosis/exon?

Do some GISTS have BRAF mutations?

Answer 15

Long arm 4; PDGFRA (7%); activated tyrosine kinase

Missense! ; deletion bad prognosis

BAD! Exon 9

Yes, Classic V600E

Question 16

In stomach were are inflammatory myofibroblastic tumors seem?

Uniform or not?

IHC stains?

Schwanoma stains?

Answer 16

Mesenary?

Uniform spindle cells

Actin +, calponin +, focal desmin +, caldesmon +, CD34-

S100+, CD117-, CD34-

Question 17

Inflammatory fibroid polyp (gene involved)?

Staining pattern?

Answer 17

Can look like anaplastic cells with some spindled; PDGFRA

CD34+, PDGFR-a +, Calponin +, Cyclin D1 +, Fascin +, CD117-, Caldesmon -, S100 -, Desmin -, keratin -

Question 18

T/F Diffuse type adeno carcinoma comes from athrophic metaplasia?

What is the mutation in diffuse type?

Intestinal type comes from?

Answer 18

F: Comes from chronic inflammation

Her-2neu mutation with poor prognosis

Multiple steps form atrophy to metaplasia to cancer, H. pylori and diet

Better prognosis

Question 19

Gastric xanthoma mimics? IHC?

Hepatoid/a-fetoprotein Carcinomas, IHC vs metastatic HCC?

Medullary Carcimoma of stomach, microscopic finding and viral association?

Answer 19

Foamy cytoplasm can mimic gastric adeno; CD68+, CK-

CK19+,CK20+, Hep-par1-

EBV, see lymphoepithelioma-like areas

Question 20

Serous cystadenoma, assocated with?

CEA level?

Gross finding?

H and E?

Answer 20

Well circumscribed thin wall cyst, VHL; NORMAL CEA

Microcysstic without communication to normal ducts

Central stellate fibrous scar (other board finding is FNH in liver)

Cuboidal lined cysts with flat epithelium (CK7+, GLUT1+)

Question 22

Mucinous cystadenoma?

CEA levels?

Cancer risk?

H and E/IHC?

High grade transformation has what gene issue?

Answer 22

~40 yrs old; does not communicate with duct

Multiloculated cystic mass; CEA levels >250 ng/mL

15% have cancer

Ovarian stroma, ER/PR+

KRAS2+

Question 23

IPMN?

Amylase levels?

4 types?

Genes?

Answer 23

Grossly visable, papillary, non-invasive; must involve main or branch duct; head of pancreas

High (also high in pseudocyst)

Gastric (MUCSAC+), intestinal (MUC2/CDX2+), pancreatobiliar (MUC1+), oncocytic (MUC6); high and low dysplasia

KRAS, TP53, CDKN2A

Question 24

PanIN definition?

Answer 24

Microscopic (vs IPMN); flat or papillary non invasive neoplasm; <5 mm

Can be low or high grade (non discript- to TA like; low grade); high grade smaller and ugly

Question 25

Intraductal tubulopapillay neoplasm (ITPN)? H and E? IHC? Molecular?

Answer 25

Solid and nodule tumor obstructing **dilated main pancreatic ducts without mucin** Tubulopapillary (cribiform) growth, **High grade atypia** **CK7+, CK19+**, typsin -, MUC2-, MUC5AC- Genes: Loss of CDKN2A; PI3K pathway Mutation of chromatin remodeling genes (MLL1/2/3, BAP1)

Question 26

What is colloid carcinoma (variant of pancreatic ductal adenocarcinoma)? Association?

Answer 26

Large extracellular stromal mucin with pools of floating tumor (80%)s **A/W IPMN**

Question 27

Hepatoid carcinoma (Pancreatic ductal variant)? IHC?

Answer 27

Large polygonal cells with eosinophlic cyto **AFP/HepPar1+, canaliclular CD10 and pCEA**

Question 28

Medullary carcinoma (Pancreatic ductal variant)? H and E? Associated/exclude? IHC?

Answer 28

Poorly differentiated with pushing boarders, syncytial growth, and lots of lymphocytes **Lynch associated; also sporatic** **Keratin +, MMR loss in many; EXCLUDED ACINIC CELL**

Question 29

Pancreatic ductal variant with large cells? H and E? IHC?

Answer 29

Undifferentiated carcinoma with Osteoclast like giant cells, **Rare older patients**, poor prognosis **Highly pleomorphic cells and large non-neoplastic giant cells** CK7+, Vimentin +, CD68+ giant cells

Question 30

Pancreatic ductal adenocarcinoma genes? AJCC staging based on?

Answer 30

KRAS 60-90% TP53 CDKN2A (p16) SMAD4/DPC4 ~60% SIZE: pT3\>4cm!; extending outside pancreas is not T3 but T4

Question 31

Common causes of chronic pancreatitis? Gross? H and E?

Answer 31

Alcohol (70%); smoking 10x risk Changes are irreversible Gross: Focal or diffuse with indurated and fibrosis and obstruction of ducts with Calcs H and E: Lobular configuration is maintained even if acinar are lost!

Question 32

Autoimmune pancreatitis? Diagnosis? Tx with steroids

Answer 32

Mass forming lesion; Prominent periductal lymphoplasmacytic infiltrate, periductal sclerosis, storiform fibrosis, and obliterative phlebitis Full organ involvement IgG4\>135 mg/DL \>10 IgG4 plasma cells/HPF IgG4:IgG.--\>at least 40% on slides

Question 33

Hereditary pancreatitis family pattern? Genes? Risk?

Answer 33

``` AD PRSS1 (cationic trypsin gene) SPINK1 (serine peptidase inhibitor, Kazal type 1 ``` 50x risk of pancreatic adenocarcinoma; 40% lifetime

Question 34

Acinar cell carcinoma? H and E? Secretes? Gross?

Answer 34

Elderly pancreatic carcinoma; **early mets; poor survival (liver and LN's)** Dense tumor with (acinar, glandular, trabecular); granular cytoplasm, prominent nucleoli, **PAS-D+, Trypsin +, Chymotrypsin +, Focal Snapto and Chromo, CK8+, CK18+,** Some Amlylase/CK7/CK20/aFP+ Secretes: Lipase: Subq fat necrosis, poly arthralgia Solid, well circumscribed and fleshy

Question 35

Who gets solid pseudopapillary neoplasm? Genes? Histology

Answer 35

Young women; large mass but rare mets; solid and cystic areas **Missense exon 3 CTNNB1; prevents B-Catenin degredation** Solid, monomorphic sheet polygonal cells with fine chromatin and possible roseets, **PASD+ globules and blood lakes, CD10+ (perinucler), Nuclear B-catenin**

Question 37

More common secreting pancreatic NE tumor? Gastrinoma associated with?

Answer 37

Insulinoma \> Glucogonoma ZE syndrome and MEN1

Question 38

Pancreatoblastoma? H and E? Lab? Genes?

Answer 38

Maligant from multiple lines of differentiation; **rare but seen in kids; liver mets w/ poor prognosis** Uniform small cells with ducts and acinie and endocrine differentiation; **Squamous corpuscles ARE DIAGNOSTIC** (**B-cat+, cyclin D1+)** AFP increased **APC/B-catinin**: LOH Chr 11p15.5, Abnormal SMAD4/DPC4 and **Isolated Bechwith-Wiedmann FAP**

Question 40

Ducts dilated with eosinophlic material, think? Gene? Random ?: Pancreatic pseudocyst cytology? Solid pseudopapillary neoplasm cyto? Acinar cytology?

Answer 40

Cystic fibrosis **CFTR Chr7q3.1 delta F508** Has macrophages/histeocytes in grungy background; high amylase (**Also IPMN)** and lipase SPN: Globules and papillae Acinic: ugly nuclei with nucleoli