Syndromes

Question 1

Desmoid tumor

Answer 1

cytologically bland fibrous neoplasm with local infiltration, slowly enlarging, classically on anterior abdominal wall

from fibroaponeurotic tissue, can be multifocal and locally aggressive with high recurrence rate

associated with previous abdominal surgery or trauma

Assoc w/ inherited syndromes (FAP, Gardner)

Bx: spindle cells, fibrous stroma, +beta-catenin, +actin, +vimentin, -cytokeratin, -S-100

Tx: resection w/ wide margins. radiation for unresectable tumors

Question 2

Sturge-Weber syndrome

Answer 2

Facial port-wine stain
glaucoma
leptomeningeal angioma

Seizures/Epilepsy
Tram track calcifications
U/L port wine stain/Weakness
Retardation
Glaucoma
Eye (Bupthalmos)

Question 3

MEN 1

Answer 3

MEN1 gene mutation

1) 4-gland parathyroid hyperplasia (Calc level)
2) Pancreatic islet cell tumors (MC non-functioning and gastrinomas) (Gastrin level)
3) Pituitary adenoma (MC prolactinomas) (Prolactin level)

Question 4

Carcinoid syndrome

Answer 4

sxs that occur d/t well-differentiated neuroendocrine tumor (NET)

MC location of tumor: rectum
2nd MC location: small bowel (ileum is MC)

Heart: pulm & tricuspid valve thickening/stenosis, endocardial fibrosis
Liver: hepatomegaly
GI: n/v/d, cramps
Skin: flushing, cyanosis
Resp: cough, wheezing, SOB
retroperitoneal & pelvic fibrosis

Question 5

FAP

Answer 5

mutation of APC gene on 5q21. AD (10% don’t have APC mutation). 100-1000s adenomatous polyps.
CRC risk - q1-2 yr colo starting at age 10-15
Polyps develop at ~16 yo, cancer by ~40

Assoc w/:

• Gastric polyps (MC fundic gland polyps)
• Duodenal adenomas (10% cancer; EGD starting at age 20-25 or when colon polyps appear)
• Desmoid tumor (mesenchymal tumors; CT A/P if fam hx of Desmoid tumors, palpable abd mass, sxs of abd organ obstruction)
• Papillary thyroid cancer (thyroid US q2-5 yrs starting in late teenage years)
• Hepatoblastoma, brain tumors (medulloblastoma MC), sebaceous cysts, lipomas, osteomas, supernumerary teeth

Question 6

Cowden syndrome

Answer 6

AD - germ-line mutation of PTEN (tumor suppressor gene)

Hamartomatous colon polyps

Assoc w/ CAs: breast, thyroid, endometrium, renal cell cancer

Other manifestations: benign hamartomatous growths of skin & mucosa, oral papillomas, trichelommomas, mucocutaneous neuromas, acral keratoses, macrocephaly

MC malignancy - breast cancer; lifetime risk of 25-50%

Clinical breast exam every 6 months w/ imaging alternating b/w MRI & mammography

Question 7

Li Fraumeni syndrome

Answer 7

mutation in TP53 (tumor suppressor gene)

Increased risk of: breast, sarcomas, brain, leukemia, medulloblastoma, adrenocortical cancers

Question 8

Peutz-Jeghers syndrome

Answer 8

mutation is STK11

mucocutaneous lesions/freckles, hamartomatous polyps GI tract (small bowel > colon > stomach)
Increased risk of cancers of GI tract (gastric), breast, pancreas, uterus, cervical, ovaries, testis, lung

Question 9

Lynch syndrome (hereditary nonpolyposis colon cancer)

Answer 9

MLH1, MSH2, MSH6, PMS2 -> mismatch repair genes

Adenomatous colon polyps (few, right-sided)

Assoc w/ CA of: endometrium, ovaries, urinary tract (renal pelvis, ureter, bladder), gastric, small bowel, pancreatic, hepatobiliary, skin

Question 10

Diffuse gastric cancer

Answer 10

Mutation in cadherin 1 gene (CDH1)

Assoc w/ breast ca

Question 11

von-Hippel-Lindau syndrome

Answer 11

AD
Germline mutation in VHL gene
CNS, retinal hemangioblastomas, clear cell renal cell carcinoma, pheochromocytoma, pancreatic cystadenomas, NETs, endolymphatic sac tumors (ELST), papillary cystadenomas of epididymis and broad ligament

Dx: 1 tumor + fam hx of VHLs, 2 CNS hemangioblastomas, or 1 CNS hemangioblastomas and 1 visceral tumor

Tx:

• CNS tumors: resect if sxs
• Retinal hemangioblastomas: laser photocoag or cryo
• RCC: MCC of death (50% deaths); resection

Surveillance:

• Annual metanephrines, starting at 5 yo
• Abd US, MRI brain, at 16 yo

Question 12

MEN IIA

Answer 12

RET gene mutation

1) 4-gland parathyroid hyperplasia (Calc level)
2) MTC (Calcitonin)
3) Pheo (Plasma metanephrines)

Question 13

MEN IIB

Answer 13

RET gene mutation

1) MTC (calcitonin)
2) Pheo (Plasma metanephrines)
3) Mucosal neuromas

Question 14

MutY homolog-associated polyposis (MAP)

Answer 14

Mutation in MUTYH gene. AR

10+ synchronous adenomatous polyps. Mostly R-sided.
High risk of developing CRC (40-60% by age 60)
Increased risk of CA of: duo, ovaries, bladder, breast

Question 15

Juvenile polyposis syndrome

Answer 15

mutation of SMAD4

Hamartomatous polyps of colon

Assoc with: gastric & pancreatic cancers, hereditary telangiectasis of brain/lungs/liver

Question 16

Turcot syndrome

Answer 16

Mutation of MLH1, PMS2, APC

Adenomatous colon polyps

Assoc w/: medulloblastoma, glioblastoma