B5 HistoPath Buzzwords & Genes

Genes for Juvenile Polyposis Syndrome

SMAD4 & BMPR1A

Inheritance pattern forJuvenile Polyposis Syndrome

AD

Genes for Peutz-Jeghers Syndrome

STK11 & AMPK

Inheritance for Peutz-Jeghers Syndrome

AD

Gene for Sessile Serrated Adenoma

BRAF

Genes for Familial Adenomatous

Polyposis

APC

Inheritance for Familial Adenomatous

Polyposis

AD

Genes for Gardner Syndrome

APC

Inheritance for Gardner Syndrome

AD

Genes for Turcot Syndrome

APC

Inheritance for Turcot Syndrome

AD

Genes for Lynch Syndrome

MLH1 & MSH2

Inheritance for Lynch Syndrome

AD

Gene for MUTYH-Associated

Polyposis

MUTYH

Inheritance for MUTYH-Associated

Polyposis

AR

Genes for Gastric MALT Lymphoma

t(11;18) -- BIRC3 & MALT1

t(14;18) -- MALT1 & IgH

Genes for Gastrointestinal Stromal

Tumor

c-KIT (GoF)

Genes for IPEX Syndrome

FOXP3

Inheritance for IPEX Syndrome

X-Linked

Genes for APECED

AIRE

Genes for Lactase Deficiency

LTC

Inheritance for Lactase Deficiency

AR

Genes for Abetalipoproteinemia

MTTP

Inheritance for Abetalipoproteinemia

AR

Genes for Microvillus Inclusion Disease

MYO5B

Inheritance for Microvillus Inclusion Disease

AR

Genes for Sporadic Colon Cancer

APC

MSH2, MLH1

BRAF

• HPV infection acquired via anal intercourse !!!!

• Can be keratinizing or non-keratinizing

Anal Canal Carcinoma

• More common proximally (duodenum)

• Include ampulla of Vater and periampullary region

Adenocarcinoma of the SI

Cancer associated with a high consumption of RED MEAT and glandular formation composed of columnar cells

Colorectal Adenocarcinoma

Precursor for Colorectal Adenocarcinoma

Aberrant crypt foci!

Gene for early Colorectal Adenocarcinoma

APC mutation

genes for late Colorectal Adenocarcinoma

APC + KRAS mutations

genes for LATE LATE Colorectal Adenocarcinoma

SMAD 4 & 2

gene associated with decreased beta-catenin in Colorectal Adenocarcinoma

CTNNB1

what are the annlar constricting lesions of Colorectal Adenocarcinoma?

napkin ring or apple core

characteristics of the cytokeratins of Colorectal Adenocarcinoma

+CK20, -CK7

R-sided issues with Colorectal Adenocarcinoma appears as…

unexplained iron deficiency anemia

L-sided issues with Colorectal Adenocarcinoma appears as…

change in bowel habits

Important markers of Colorectal Adenocarcinoma

increased CEA (carcinoembryonic antigen) and CA19-9

Mutyh-Associated Polyposis gene and inheritance

AR – MUTYH gene (base excision repair gene)

inheritance and gene for Lynch Syndrome

AD – one of the MMR genes – GCàTA transversion

what is associated with Lynch Syndrome

Associated with endometrial carcinoma

inheritance and genes of Familial Adenomatous

Polyposis

AD – APC gene – neg regulator of Wnt pathway

what is Gardener syndrome associated with Familial Adenomatous Polyposis

supernumerary teeth, osteomas of skull, thyroid

/ duodenal / pancreatic carcinoma, epidermoid cysts, lipomas, desmoid

what is Turcot syndrome associated with Familial Adenomatous Polyposis

primary brain malignances (medulloblastoma) +

colorectal carcinoma by age 40

• Crypt bases are dilated à look like boot or anchor

• Serration is along entire crypt (not just top like in hyperplastic

Sessile Serrated Adenomas

Can be tubular (looks like lava lamp) or villous (looks like zebra stripes) or tubulovillous (combo)

Adenomatous Polyps

Hallmark of Adenomatous Polyps

dysplasia ( decreased goblets, nuclear hyperchromasia, long nuclei)

• Hx of smoking

• Small dome shaped nodules with saw tooth upper level crypts

• Normal cellular components – no dysplasia or hyperchromatic nuclei

Hyperplastic Polyps

Pigmented mucocutaneous macules on lips, hands, feet in teens

• Smooth muscle proliferation form bundles around lamina —> tree-like

Peutz-Jeghers Syndrome

• Pulm AV malformations and digital clubbing

• Numerous cystic spaces and dilated crypts

Juvinile Polypopsis Syndrome

• Inflammatory polyps

• Abnormal contraction of puborectalis muscle

Solitary Rectal Ulcer Syndrome (SRUS)

(Carcinoid Tumors) =

Neuroendocrine Tumors

what has an association with Liver metastases → carcinoid syndrome → likely in small intestine

Neuroendocrine Tumors

serum changes associated with Neuroendocrine Tumors

INCREASED urinary levels of 5-HIAA, chromogranin, synaptophysin

Signature cell pattern of Neuroendocrine Tumors

Nested pattern – spheres separated by fibrous bands, salt and pepper chromatin

what Develops from pluripotential mesenchymal stem cell programmed to diff

into interstitial cell of Cajal located in muscularis propria

Gastrointestinal Stromal Tumor (GIST)

genes of GIST

GOF in c-KIT gene !!! or maybe PDGFRA

cell pattern of GIST

Spindle cells with elongated nuclei in eosinophilic cytoplasm

Immunoproliferative Small Intestine Disease (IPSID)

MALT Lymphoma of SI

Main cause of MALT Lymphoma of SI

Campylobacter jejuni !!!

major cell change in MALT Lymphoma of SI

INCREASED a heavy chain protein

• Lymphoepithelial lesions in lower duodenum and upper jejunum

• Younger mid-eastern male present with chronic diarrhea - malabsorption

MALT Lymphoma of SI

• Arise from mature B lymphocytes

• H. pylori + with + anti-CagA Ab !!!

Gastric MALT Lymphoma

genes of Gastric MALT Lymphoma

MALT1 and BCL10 gene fusion - translocation on chr 11 and 18 !!

Gastric MALT Lymphoma

• Thickened cerebroid gastric folds with enlarged gastric lymph nodes

• Lymphoepithelial lesions – destroy glands

• Dilated veins in muscularis propria

• Modified squamous epithelium

• Below dentate line

• PAINFUL

External Hemorrhoids

® Dilated veins in submucosa

® Columnar epithelium

® Above dentate line

® Present with painless hematochezia, perianal pruritis, mild incontinence

Internal Hemorrhoids

® Red lesions with ectatic blood vessels radiating from central vessel

® Similar to telangiectasias

® Tortuous dilated blood vessels in mucosa consist of endothelium with no smooth muscle

Angiodysplasia

® Mainly in left colon – usually sigmoid à LLQ pain

® Risks = red meat, obesity, physical inactivity, aging

® Slow digestion → stool builds up → incresed pressure → herniates thru defects of mucosa thru weak tunica muscularis → diverticula

Diverticular Disease of the Colon

genes for Microvillus Inclusion Disease

MYO5B gene - AR

• In infants – weight loss and dehydration

• Biopsy → villous atrophy, absence of inflam cells in lamina, absence brush border, PAS+ intracytoplasmic vesicles, microvillous inclusions

Microvillus Inclusion Disease

genes for Abetalipoproteinemia

MTTP gene – AR

• Infants < 1 mo failure to thrive → steatorrhea, decerased cholesterol and TGs, fat sol vit deficiencies

• Acanthocytes in peripheral blood smears

Abetalipoproteinemia

• LTC gene – codes lactase is inherited in AR pattern instead

• GI sx after ingestion of dairy products

Lactase Deficiency

® Affects infants in first 6 mo of life

® + IgG anti-enterocyte Ab with complement fixing ability

® Villous atrophy in SI + dense lymphoplasmacytic infiltration in lamina

Autoimmune Enteropathy (AIE)

AIE + AI endocrinopathy + atopic dermatitis

IPEX syndrome

gene for IPEX syndrome

FOXP3

gene for APECED

AIRE

AI polyendrinopathy + candidiasis + ectodermal dysplasia

APECED

• Stunted growth in kids in developing countries

• Villous atrophy / blunted villi + crypt hyperplasia (elongation) – just like celiac BUT ABSENCE OF DIARRHEA!

Environmental Enteric Dysfunction

genes of Celiac Disease

HLA-DQ2 and HLA-DQ8 (I want 2 take u on a d8 to Dairy Queen)

immune related things with Celiac Disease

+ IgA-tTG (transglutaminase) and IgA-EMA antibodies

• Stools = greasy, foul smelling, frothy

• Extraintestinal sx → dermatitis herpetiformis (pruritic lesion on elbows/knees), osteoporosis, anemia, bleeding diathesis

• Villous atrophy / blunted villi + crypt hyperplasia (elongation)

Celiac Disease

gene for Desmoplastic Small Round Cell Tumor

t(11;22)(p13;q12) fusion of EWS (Ewing gene) + WT1 (Wilms)

• In kids!!!!

• Originate from a submesothelial progenitor cell

• Resembles Ewing Sarcoma

Desmoplastic Small Round Cell Tumor

Women only – arise from extraovarian mesothelium

Primary Peritoneal Serous Carcinoma

Asbestos

Peritoneal Malignant Mesothelioma

Can be caused by drugs, etanercept, or radiation therapy

Retroperitoneal Fibrosis

• Polymicrobial

• Most common cause is perforation of an abdominal organ

Secondary Peritonitis

• Abdominal swelling due to ascites formation followed by vague abdominal pain with fever, night sweats, weight loss, anorexia

• Biopsy of greater omentum show caseating granulomas

Tuberculous Peritonitis

• Monomicrobial cause → usually G- like E. coli

• Absence of obvious source of contamination

Spontaneous Bacterial Peritonitis

• Hella accumulation of mucus within peritoneal cavity secondary to mucinous neoplasm or tumors of ovary (4x more common in women)

• Abundant gelatinous mucin with cystic peritoneal implants

Pseudomyxoma Peritonei (PMP)

• Activating mutations of GNAS and KRAS genes

• Lots of mucus accumulates in lumen

Appendiceal Mucinous Neoplasms

Suspect in pt with 103+ temp + increased leukocytes with L shift + imaging reveals fluid collection in RLQ

Perforated Appendix

• Perforated appendix walled off by greater omentum

• Palpable mass in RLQ

Periappendicular Abscess

Lymphoid hyperplasia

Acute Appendicitis

• Vague periumbilical pain progressing to RLQ pain with rebound tenderness and reflex N/V

• E. coli

• Grossly surface is covered by fibrinous exudate

Acute Appendicitis

large signs of Acute Appendicitis

Rovsing sign, obturator sign, psoas sign