Slide to syndrome - board study

Question 1

5 syndromes caused by inherited defects in DNA repair

Answer 1

Ataxia Telangiectasia, Bloom syndrome, MYH-associated polyposis, Xeroderma pigmentosa, Fanconi Anemia (all have autosomal recessive mode of inheritance)

Question 2

Inheritance pattern of Lynch syndrome

Answer 2

also HNPCC, autosomal dominant - DNA mismatch repair gene inactivation

Question 3

MEN1

Answer 3

AD inheritence, gene inactivated is MEN1, chromosome is 11q13 - Pituitary adenoma (or hyperplasia); parathyroid hyperplasia; Pancreateic endocrine neoplasm/islet cell tumor; duodenal gastrin producing carcinoid (causing zollinger ellison syndrome)

Question 4

Combination of pituitary tumor, hyperparathyroidism, pancreatic endocrine tumor and duodenal carcinoid producing a hormonal syndrome…

Answer 4

MEN1, especially with gastrinoma and zollinger ellison syndrome

Question 5

Birt-Hogg-Dubé syndrome (germline folliculin mutation)

Answer 5

Skin adnexal tumors, kidney tumors (bilateral), lung cysts with pneumothorax presentation
(fibrofolliculoma), (renal cell carcinoma)

Question 6

Hereditary leiomyomatosis and RCC syndrome

Answer 6

(germline fumarate hydratase mutation)
autosomal dominant
characterized by the presence of cutaneous and uterine leiomyomas and RCCs. These renal tumors are now regarded as a specific subtype of RCC (i.e. HLRCC associated [or fumarate hydratase deficient] RCC)

Question 7

fumarate hydratase deficient RCC is the same thing as…

Answer 7

HLRCC associated RCC (referring to Hereditary leiomyomatosis and RCC syndrome)

Question 8

Ataxia Telangiectasia –> inheritance and diseases

Answer 8

Autosomal recessive, inherited defect in DNA repair , ATM is gene product (ataxia-telangiectasia mutated), chromosome 11q22-23, 100-fold risk of malignancies (ALL in children, solid tumors in adults) –> progressive ataxia, ocular and cutaneous telangectasia, thymic hypoplasia, IgA immunodeficiency –> b/c of DNA repair problem, ionizing radiation sensitive
*on list of hereditary breast cancer ddx

Question 9

Bloom syndrome –> inheritance and diseases

Answer 9

autosomal recessive, gene product BLM helicase, chromosome 15 –> predisposition to wide range of cancers, especially leukemias (in context of developmental defects)

Question 10

Fanconi anemia –> inheritance and diseases

Answer 10

Autosomal recessive, Several candidate genes identified (no specific chromosome) –> predisposition to leukemias and solid tumors (HCC in 10% of patients), hypoplasia of bone marrow, kidney, spleen, bone (particularly thumbs and radius)

Question 11

Carney complex / carney syndrome –> inheritance and diseases

Answer 11

autosomal dominant, protein kinase A gene product, chromosome 17q22-24 and 2p16 –> myxoid lesions, pigmented and calcifying lesions, endocrine hyperactivity
myxoid –> cardiac myxoma, skin angiomyxoma, myxoid fibroadenoma of breast
pigmented and calcifying –> spotty skin pigmentation, epitheloid blue nevus, pigmented nodular adrenocortical hyperplasia, psammomatous melanotic schwannoma, large cell calcifying sertoli cell tumor
endocrine hyperactivity –> pituitary adenoma
*chondroid hamartoma (association)

Question 12

tumors/lesions that make you think carney syndrome (not triad)

Answer 12

myxoid –> cardiac myxoma, skin angiomyxoma, myxoid fibroadenoma of breast
pigmented and calcifying –> spotty skin pigmentation, epitheloid blue nevus, pigmented nodular adrenocortical hyperplasia, psammomatous melanotic schwannoma, large cell calcifying sertoli cell tumor
endocrine hyperactivity –> pituitary adenoma
*chondroid hamartoma (association)
*AD inheritance, PRKAR1A gene, PKA gene product

Question 13

you see myxoma with other pigmented or calcifying things and you think…

Answer 13

Carney complex / carney syndrome –> AD inheritance, PKA gene product, 17q22-24 and 2p16 locations

Question 14

you see large cell calcifying sertoli cell tumor and you think…

Answer 14

look for myxoma or something else ‘pigmented’ and endocrine manifestations or a chondroid hamartoma –> CARNEY –> 17q22-24 and 2p16 (PKA), AD inheritance
*could also be Peutz-Jegher’s syndrome (intra-tubular deposits in large sertoli cells)

Question 15

Retinoblastoma syndrome –> inheritance and diseases

Answer 15

40% are inherited in AD fashion, RB gene product on chromosome 13q14 –> bilateral retinoblastomas, pineoblastoma, osteosarcoma (and other sarcomas)

Question 16

You see osteosarcoma + other sarcoma with any hint of blindness and you think…

Answer 16

inherited RB gene mutation, retinoblastoma syndrome, 13q14, look for pineoblastoma

Question 17

you make a dx of pineoblastoma and you think….

Answer 17

inherited RB gene mutation, retinoblastoma syndrome, 13q14, look for osteosarcoma /other sarcoma and bilateral retinoblastomas

Question 18

Carney triad vs. Carney complex/syndrome

Answer 18

Triad: paraganglioma, pulmonary chondroma (chondroid hamartoma), GIST (gastric epitheloikd) —> classically young female
syndrome/complex: PKA gene product, 17q22-24 and 2p16, myxoid, pigmented/calcifying, endocrine (pituitary adenoma)

Question 19

what is the other name for hereditary hemorrhagic telangiectasia

Answer 19

Rendu-osler-weber syndrome, AD, ACVRL1 + ENG gene products (both in TGFbeta pathway) —> aneurysmal telangiectasias in multiple organs (bleeding)

Question 20

Rendu-osler-weber syndrome…

Answer 20

(AKA: hereditary hemorrhagic telangiectasia)
AD inheritance, ACVRL1 + ENG gene products (both in TGFbeta pathway) —> aneurysmal telangiectasias in multiple organs (bleeding)

Question 21

Li-Fraumeni syndrome —> inheritance and diseases

Answer 21

Autosomal dominant (AD), p53 gene product, chromosome 17p13 —> multiple primary tumors at a young age
sarcoma, carcinoma (breast, colon, pancreas, adrenal cortex), leukemia, melanoma, glioma
*on list of ‘hereditary breast cancer’ ddx

Question 22

A young person has multiple primary tumors of different organs and you think…

Answer 22

Li-fraumeni? Inherited AD, problem with p53, sarcoma, carcinoma (breast, colon, pancreas, adrenal cortex), leukemia, melanoma, glioma

Question 23

Hereditary breast and ovarian cancer….

Answer 23

BRCA1 and 2 (AD inheritance pattern)
BRCA1 - 40-50% of hereditary breast carcinoma –> 17q21 –> >70% of these patients get breast cancer (especially medullary breast ca) —> 30-60% of these patients get ovarian cancer (serous carcinoma and STICs therefore look at entire tube and section the fimbriae)
BRCA2 - 20-30% of hereditary breast carcinoma –> >60% of patients with this mutation get breast cancer, increased risk for ovarian (though less than BRCA1) —> also prostate cancer and pancreas cancer associations

Question 24

male breast cancer hereditary association

Answer 24

BRCA2 >BRCA1
*after this, some other inherited solid tumor predisposition

Question 25

Breast cancer and prostate cancer have what in common?

Answer 25

BRCA2 mutation

Question 26

Chromosomal location of BRCA1

Answer 26

17q21 ---> breast and ovarian cancer

Question 27

Chromosomal location of BRCA2

Answer 27

13q ---> breast and ovarian (less than BRCA1) and prostate and pancreas, *male breast cancer*

Question 28

Cowden's disease / syndrome ---> inheritance and manifestation

Answer 28

Autosomal Dominant (AD), PTEN gene product, chromosome 10q *multiple neoplasms and HAMARTOMAS (all cell origins) *breast cancer, skin changes and trichilemmomas, GI polyps, soft tissue benign tumors (hemagiomas, lymphangiomas, lipomas, neurofibromas, leiomyomas) *thyroid, RCC, merkel cell, lymphoma, melanoma, meningioma

Question 29

Chromosomal location and gene product mutated in Cowden's disease/syndrome

Answer 29

PTEN, 10q (AD inheritance) HAMARTOMAS 'plus' *thyroid (follicular>ptc), RCC, merkel cell, lymphoma, melanoma, meningioma

Question 30

Cowden's disease/syndrome and breasts...

Answer 30

Increased likeliehood of breast cancer (>50% lifetime risk, like 5 fold elevated risk from baseline) *PTEN, 10q, AD *thyroid, RCC, merkel cell, lymphoma, melanoma, meningioma HAMARTOMAS

Question 31

A patient has a ton of HAMARTOMAS, and now another cancer...

Answer 31

Cowden's disease/syndrome *multiple neoplasms and HAMARTOMAS (all cell origins) *breast cancer, skin changes and trichilemmomas, GI polyps, soft tissue benign tumors (hemagiomas, lymphangiomas, lipomas, neurofibromas, leomyomas) *medullary (thyroid), RCC, merkel cell, lymphoma, melanoma, meningioma *HAMMMMARTOMMMMAS (mmmmmooooooo) - cowdens

Question 32

DDX of anything 'hereditary breast cancer'

Answer 32

Start with BRCA1 and BRCA2 *then cowden's syndrome/disease *then Ataxia-telangiectasia (AT), Li-fraumeni

Question 33

Familial atypical multiple mole melanoma syndrome (FAMMM) or B-K Mole syndrome) ---> inheritance and diseases

Answer 33

Autosomal dominant (AD), p16 is gene product, chromosome 9p21 ---> TONS (more than 100) nevi *will present with atypical/dysplastic nevi and/or melanoma *ALSO pancreatic adenocarcinoma (10-20 fold increased relative risk)

Question 34

Gorlins syndrome and FAMMM / B-K Mole syndrome have something in common...

Answer 34

chromosome 9 *FAMMM has 9p21 location with p16 gene product mutation (CDKN2A gene) *Gorlins syndrome has 9q22.3-q31 location with PTCH gene product mutation

Question 35

Gorlin's syndrome ---> inheritance and diseases

Answer 35

PTCH gene product, location 9q22.3-q31, inherited AD *two or mor basal cell carcinomas before 20 years old *odontogenic keratocyst of jaw *ovarian fibroma (particularly bilateral, multinodular, calcified) *medulloblastoma (ALSO skeletal abnormalities particularly macrocephaly)

Question 36

What does STK11 have to do with breast cancer?

Answer 36

STK11 (serine/threonine kinase 11) is mutated in the autosomal dominant condition Peutz-Jeghers syndrome. Patients with this syndrome have a 30% to 50% risk of developing breast cancer. *also have: specific GI polyps and some risk of GI cancer but not from those polyps

Question 37

What does PTEN have to do with breast cancer?

Answer 37

Germline mutations in PTEN (phosphatase and tensin homolog) can lead to a rare autosomal dominant inherited cancer syndrome, Cowden syndrome, which is characterized by a high risk of breast cancer.

Question 38

What does CDH1 have to do with breast cancer?

Answer 38

Mutations in the CDH1 gene cause familial diffuse gastric cancer, an autosomal dominant cancer syndrome. Patients with a familial diffuse gastric cancer have a risk of about 50% of getting breast cancer.

Question 39

Male breast cancer....what genes should you think about?

Answer 39

*BRCA2 primarily *Other mutations associated with male breast cancer include androgen receptor, CHEK2 mutations (associated with Li-Fraumeni syndrome), PTEN (Cowden syndrome), HNPCC (Lynch syndrome), and CYP17 polymorphism.

Question 40

Tumors associated with von Hippel Lindau Syndrome (VHL gene)

Answer 40

*Clear cell renal cell carcinoma* Along with Hemangioblastomas, pheochromocytoma, pancreatic serous cystadenomas, and endolymphatic sac tumor

Question 41

Germline DICER mutations...

Answer 41

(DICER1-PPB familial tumor predisposition syndrome) Think, in a pediatric patient, pleuropulmonary blastoma PPBs are characterized by DICER1 mutations, and about two-thirds of children with PPB have heterozygous germline DICER1 mutations Children with germline mutations are at risk for other tumors: cystic nephroma of the kidney, nasal chondromesenchymal hamartoma, Sertoli-Leydig tumor of the ovary, embryonal rhabdomyosarcoma of the cervix (and other sites), pituitary blastoma pineoblastoma.

Question 42

You see these together.... cystic nephroma of the kidney, nasal chondromesenchymal hamartoma, Sertoli-Leydig tumor of the ovary, embryonal rhabdomyosarcoma of the cervix (and other sites), pituitary blastoma pineoblastoma.

Answer 42

(DICER1-PPB familial tumor predisposition syndrome) Think, in a pediatric patient, pleuropulmonary blastoma

Question 43

(DICER1-PPB familial tumor predisposition syndrome)

Answer 43

Think, in a pediatric patient, pleuropulmonary blastoma also: cystic nephroma of the kidney, nasal chondromesenchymal hamartoma, Sertoli-Leydig tumor of the ovary, embryonal rhabdomyosarcoma of the cervix (and other sites), pituitary blastoma pineoblastoma.

Question 44

Peutz-Jegher polyp in the stomach...

Answer 44

Peutz-Jegher's syndrom *sex cord tumor with annular tubules *breast cancer *skin mucocutaneous melanin pigmentation *lots of GI polyps (which should NOT be dysplastic) *autosomal dominant *young patient *STK11/LKB1 genes *arborizing vessels *gastric type adenocarcinoma in the cervix *sertoli cell tumor

Question 45

Gastric type adenocarcinoma in the cervix

Answer 45

Peutz Jeger's syndrome *deeply penetrating glands that look like foveolar cells with tons of mucin *p16 negative , ER/PR negative (not HPV associated *poor prognosis

Question 46

Do PJS patients have increased risk of GI cancer?

Answer 46

PGJ = Peutz Jeger's syndrome *yes, they do have increased risk *tends to NOT come from PJ polyps *gastric, small intestinal, colonic *also breast and pancreas

Question 47

hamartomatous polyposis syndrome characterized by macrocephaly, lipomatosis, hemangiomas, and hamartomatous polyps in the gastrointestinal tract.

Answer 47

Bannayan-Ruvalcaba-Riley syndrome is a hamartomatous polyposis syndrome characterized by macrocephaly, lipomatosis, hemangiomas, and hamartomatous polyps in the gastrointestinal tract.

Question 48

Bannayan-Ruvalcaba-Riley syndrome

Answer 48

hamartomatous polyposis syndrome characterized by macrocephaly, lipomatosis, hemangiomas, and hamartomatous polyps in the gastrointestinal tract.

Question 49

Most common hamartomatous polyp syndrome

Answer 49

The most common of the hamartomatous syndromes is familial juvenile polyposis, which has an estimated incidence of 1 per 100,000 births

Question 50

JPS in the world of syndromes

Answer 50

juvenile polyposis syndrome *The most common of the hamartomatous syndromes is familial juvenile polyposis, which has an estimated incidence of 1 per 100,000 births. This disorder shows an autosomal dominant pattern of inheritance, and patients show germline mutations in the SMAD4 gene or in the BMPR1A gene. *cystically dilated glands *AD inheritance

Question 51

There is a polyp in the small intestine...

Answer 51

Adenomas of the small intestine are relatively rare lesions that grossly and microscopically resemble colonic adenomas. The majority occur in the duodenum. Most small intestinal adenomas are asymptomatic, although larger ones may present with obstruction or bleeding. Adenomas involving the ampulla of Vater may present with biliary colic and obstruction. Sporadic adenomas in the small intestine are usually solitary and the finding of multiple lesions should raise the possibility of familial adenomatous polyposis (FAP).

Question 52

you see a bone marrow with FOCAL replacement by aggregates of pink, almost spindled cells with 'striated' cytoplasm

Answer 52

Gauchers syndrome/disease Lack of Glucocerebrosidase (Acid β-glucosidase) ➢ Causes accumulation of glucosylceremide (glucocerebroside) in phagocytes * Present as hepatosplenomegaly, thrombocytopenia, anemia or leukopenia * 3 major phenotypes: ➢ Type I: presence of bone disease, hepatosplenomegaly, anemia and thrombocytopenia, lung; 60% of cases diagnosed before second decade of life ➢ Type II (infantile): acute neuropathic disease ➢ Type III (juvenile): chronic neuropathic disease * Treatment: type I and type III can be treated with enzyme replacement * Molecular: mutation in GBA resulting in a c.1226A>G ➢ GBA encodes glucocerebrosidase on chromosome 1q21

Question 53

Inheritance Gauchers disease

Answer 53

AR Lack of Glucocerebrosidase (Acid β-glucosidase) ➢ Causes accumulation of glucosylceremide (glucocerebroside) in phagocytes

Question 54

Syndrome with SPOT diagnosis of a neutrophil with super big azurophilic granules in it

Answer 54

*Chediak-Higashi Syndrome Presents with partial oculocutaneous albinism, neutropenia and recurrent infections, mild bleeding from mucosal surfaces *think platelet aggregation problem with second wave of aggregation *molecular = LYST or CHS1

Question 55

What does Chediak-Higashi Syndrome normally present with?

Answer 55

Presents with partial oculocutaneous albinism, neutropenia and recurrent infections, mild bleeding from mucosal surfaces

Question 56

What is a syndrome associated with 2nd wave platelet aggregation problems?

Answer 56

*Chediak-Higashi Syndrome Presents with partial oculocutaneous albinism, neutropenia and recurrent infections, mild bleeding from mucosal surfaces *think platelet aggregation problem with second wave of aggregation *molecular = LYST or CHS1 *neutrophils with azurophilic large granules

Question 57

Macrophages are weird in Gauchers...why?

Answer 57

Glucocerebrosides, formed by the catabolism of glycolipids from the cell membranes of aging erythrocytes and leukocytes, accumulate in large amounts in the phagocytes of some organs (bone marrow, liver, spleen, lymph nodes). *AR --> functional deficiency of acid β-glucocerebrosidase

Question 58

you see a renal angiomyolipoma and you think....

Answer 58

could this be Tuberous Sclerosis associated? (make sure it's not a sarcoma or sarcomatoid RCC first)

Question 59

Carney syndrome patient with a sertoli cell tumor. how do you prove it with IHC?

Answer 59

IHC: Positive for inhibin-α, calretinin, Melan-A (MART-1), SF1, WT1, chromogranin, synaptophysin, AE1/AE3, nuclear β-catenin

Question 60

bilateral chromophobe RCC (familial chromophobe RCC)

Answer 60

birt-hogg-dube

Question 61

germline mutation of c-met gene AND kidneys...

Answer 61

hereditary papillary renal cell carcinoma *papillary RCC (type 1, the true PRCC)

Question 62

This patient is absolutely classic for which syndrome? Pancytopenic 6 year old girl from South Africa, severe thrombocytopenia and normocytic normochromic anemia with low reticulocyte count. Cafe au lait spots, short stature, bruises and petechiae, scoliosis

Answer 62

Fanconia Anemia *AR, 25% chance their sibling will get it *DNA breakage studies will be positive

Question 63

what kind of syndrome would be implicated by a POSITIVE 'DNA breakage study'

Answer 63

inherited disorders of DNA repair (the 5 AR inherited DNA repair disorders)

Question 64

you see wilms tumor...

Answer 64

WAGR syndrome *wilms *aniridia (no iris in the eye) *genitourinary malformation *mental Retardation

Question 65

which neuropath entity belongs with nevoid basal cell carcinoma syndrome?

Answer 65

Gorlin syndrome = nevoid basal cell carcinoma syndrome *medulloblastoma

Question 66

follicular adenoma of thyroid...

Answer 66

PTEN-hamartoma tumor syndrome (PHTS): Cowden disease and Bannayan-Riley-Ruvalcaba syndrome (BRRS) syndrome Pendred syndrome Carney complex

Question 67

malignant form of a PEComa in tuberus sclerosis patients

Answer 67

epithelioid angiomyolipoma

Question 68

you see epithelioid angiomyolipoma...

Answer 68

you think tuberous sclerosus (50% of cases have TS history) even sporadic cases have a TSC2 mutation

Question 69

McCune-Albright syndrome is associated with...

Answer 69

polyostotic fibrous dysplasia, cutaneous pigmentation (café au lait spots), and endocrinopathy that includes precocious puberty. The bone lesions lead to severe skeletal deformities, such as the "shepherd crook" deformity of the hips. *also GI polyps

Question 70

You see polyostotic fibrous dysplasia...

Answer 70

McCune-Albright *polyostotic fibrous dysplasia, cutaneous pigmentation (café au lait spots), and endocrinopathy that includes precocious puberty. The bone lesions lead to severe skeletal deformities, such as the "shepherd crook" deformity of the hips.

Question 71

Maffucci syndrome is characterized by ...

Answer 71

the association of multiple chondromas and spindle cell hemangiomas located in the overlying skin and soft tissues.

Question 72

Gardner syndrome...

Answer 72

FAP + extra GI *intestinal polyposis, multiple osteomas, (mesenteric desmoid fibromatosis), and epidermal cysts. *congenital hyperplasia of the retinal epithelium, &/or adrenal adenomas. ****cribriform morular variant of PTC

Question 73

combination of intestinal polyposis, multiple osteomas, fibromatosis, and epidermal cysts.

Answer 73

Gardner syndrome

Question 74

t(11;22)(q24;q12)

Answer 74

ewing sarcoma; FLI1-EWS

Question 75

Ewing sarcoma

Answer 75

t(11;22)(q24;q12)

Question 76

What do Gardners and FAP have in common?

Answer 76

Gardner syndrome refers to FAP patients with extracolonic manifestations, including multiple osteomas, epidermal cysts, and fibromas.

Question 77

What pathway of carcinoma development do polyps in FAP go through?

Answer 77

Carcinomas arising in FAP develop through the chromosomal instability pathway and do not show microsatellite instability. The latter is found in the colorectal carcinomas that occur in the setting of Lynch/hereditary nonpolyposis colorectal cancer (HNPCC).

Question 78

Turcot syndrome

Answer 78

Turcot syndrome refers to the coexistence of a hereditary colonic cancer syndrome and CNS tumors.

Question 79

FAP messes with what gene pathway?

Answer 79

FAP is caused by a germline mutation in the adenomatous polyposis coli (APC) gene, which is a negative regulator of the Wnt signaling pathway. adenomatous polyposis coli (APC), which is located on chromosome 5q21.

Question 80

LOH at 18q21 is common in what?

Answer 80

Loss of heterozygosity at 18q21 is seen in approximately 50% of colorectal carcinomas. Loss of heterozygosity at 18q21 is thought to be a late event in the adenoma-to-carcinoma progression and results in the loss of the tumor suppressor gene, SMAD4. Colorectal carcinomas showing loss of heterozygosity at 18q21 have been shown to have a worse prognosis

Question 81

tumors in lynch syndrome family

Answer 81

Tumors in this family cancer syndrome include colonic, endometrial, urothelial, small intestinal, stomach, and hepatobiliary carcinomas, and demonstrate microsatellite instability (MSI).

Question 82

You see CNS hemangioblastoma...

Answer 82

VHL syndrome *inhibin IHC

Question 83

CNS medulloblastoma...

Answer 83

Turcot syndrome (CNS manifestations of FAP *also NBCCS or Gorlin's

Question 84

CNS plexiform and diffuse neuofibroma

Answer 84

NF1

Question 85

Psammomatous melanotic schwannoma

Answer 85

Carney complex

Question 86

CNS subependymal giant cell astrocytoma

Answer 86

tuberus sclerosis *big cells, not multinucleated osteoclast like giant cells

Question 87

Lymphangioleimoyomatosis of the lung

Answer 87

tuberus sclerosis *PEComa family

Question 88

Mediastinal carcinoid tumor

Answer 88

MEN1

Question 89

Rhabdomyoma

Answer 89

Tuberous sclerosis

Question 90

Medullary carcinoma of breast

Answer 90

BRCA1

Question 91

gangliocytic paraganglioma of duodenum

Answer 91

NF1

Question 92

diffuse ganglioneuromatosis

Answer 92

MEN2b NF1

Question 93

GI tract neurofibromas

Answer 93

NF1

Question 94

Gastrinoma in GI tract

Answer 94

MEN1

Question 95

Somatostatinoma of GI tract

Answer 95

*do NOT click MEN1 *it's actually NF1, quite tricky. MEN1 is best associated with gastrinoma and zollinger-ellison

Question 96

A kid with adrenocortical carcinoma

Answer 96

BWS MEN1 Li-Fraumeni

Question 97

Congenital adrenal cytomegaly

Answer 97

BWS *ugly cells, NOT mitotically active

Question 98

Pheochromocytoma

Answer 98

MEN2A MEN2B VHL NF1

Question 99

Hybrid chromophobe RCC and onococytoma

Answer 99

birt-hogg-dube

Question 100

inverted Urothelial cell carcinoma of renal pelvis

Answer 100

lynch syndrome

Question 101

papillary cystadnoma of epididymis

Answer 101

VHL

Question 102

Renal medullary carcinoma

Answer 102

Sickle cell trait

Question 103

RCC with lots of calcium oxalate

Answer 103

ESRD associated

Question 104

papillary RCC with macronucleoli and clear halo

Answer 104

HLRCC or FH deficient

Question 105

Wilms tumor

Answer 105

WAGR Denys-Drash BWS

Question 106

Disorder characterized by ambiguous genitalia or pseudohermaphroditism, early-onset nephrotic syndrome, and ↑ risk for Wilms tumor (WT)

Answer 106

Denys-Drash

Question 107

Meningioma

Answer 107

NF2 monosomy of chromosome 22 is the most common cytogenetic abnormality in meningiomas *can happen through LOH NF2 mutation is 22q12

Question 108

tumors of tuberous sclerosus

Answer 108

Tuberous sclerosis complex is an autosomal dominant disorder with the lesions in the central nervous system (CNS), including cortical tubers, subependymal nodules, and subependymal giant cell astrocytomas. Other lesions: *cutaneous lesions (hypomelanic macules, facial angiofibromas, periungual or subungual fibromas, and shagreen patches or fibrous hamartomas), *cardiac rhabdomyomas *pulmonary lymphangioleiomyomatosis, *renal angiomyolipomas

Question 109

RET germline mutation, autosomal dominant inheritance

Answer 109

MEN2 (both A and B)

Question 110

MEN2B tumors

Answer 110

Pheochromocytoma Medullary thyroid carcinoma Mucosal neuromas Marfanoid features *ganglioneuromas

Question 111

MEN2A

Answer 111

Parathyroid hyperplasia Pheochromocytoma Medullary thyroid carcinoma *hirschsprung

Question 112

Genes of tuberous sclerosis

Answer 112

Two different genes are associated with tuberous sclerosis: *TSC1 gene: hamartin located in chromosome 9q34, *TSC2 gene: tuberin located in chromosome 16p13.3

Question 113

RET M918T mutation is present in up to 98% of patients with

Answer 113

MEN2B *medullary thyroid carcinoma

Question 114

Eosinophilic solid and cystic renal cell carcinoma

Answer 114

*tuberous sclerosis Pathogenesis: Mutations in TSC1 or TSC2 in majority, upregulation of m TOR pathway

Question 115

Lymphangioleiomyomatosis in the lung

Answer 115

*tuberous sclerosis *PEComa, so look for HMB-45 or mart-1 or something *destructive and metastatsizing, cystic thing in b/l lungs

Question 116

Desmoid type fibromatosis (mesentery)....

Answer 116

*FAP/Gardner This disease usually occurs due to sporadic mutations in CTNNB1 (beta-catenin) gene or in the setting of familial adenomatous polyposis/Gardner syndrome due to germline APC gene mutation, particularly in mesenteric examples. Desmoid-type fibromatosis may be the first manifestation of this syndrome. Sporadic APC mutations are very rare but may occur.

Question 117

Carney-Stratakis syndrome....

Answer 117

Carney-Stratakis syndrome is associated with a germline mutation in the succinate dehydrogenase complex (SDH) genes and presents with paragangliomas and gastrointestinal stromal tumors (GIST) of the stomach.

Question 118

Brooke-Spiegler syndrome

Answer 118

Brooke-Spiegler syndrome is an autosomal dominant familiar tumor syndrome that is associated with CYLD1 mutations and characterized by multiple cylindromas, trichoepitheliomas, and eccrine spiradenomas

Question 119

multiple cylindromas, trichoepitheliomas, and eccrine spiradenomas

Answer 119

Brooke-Spiegler syndrome is an autosomal dominant familiar tumor syndrome that is associated with CYLD1 mutations and characterized by multiple cylindromas, trichoepitheliomas, and eccrine spiradenomas

Question 120

AD inherited CYLD1 mutations

Answer 120

Brooke-Spiegler syndrome is an autosomal dominant familiar tumor syndrome that is associated with CYLD1 mutations and characterized by multiple cylindromas, trichoepitheliomas, and eccrine spiradenomas

Question 121

MEN 2A/2B

Answer 121

*Multiple endocrine neoplasia types 2A and 2B (MEN 2A AND MEN 2B) are autosomal dominant syndromes that result from mutation of RET. Definitive diagnosis of MEN 2 relies almost exclusively upon RET mutational analysis. *Features of MEN 2A include medullary thyroid carcinoma, pheochromocytoma, and primary hyperparathyroidism. Manifestations of MEN 2B also include neuroma of the tongue, but do not include primary hyperparathyroidism. *Medullary thyroid carcinoma occurring within the context of MEN 2 is frequently associated with C cell hyperplasia. This finding does not generally characterize sporadic cases of medullary carcinoma.

Question 122

Optic pathway pilocytic astrocytoma

Answer 122

NF1

Question 123

Bilateral acoustic schwannomas

Answer 123

NF2

Question 124

Location of NF1 mutation

Answer 124

Neurofibromatosis type 1 (NF1) is an autosomal dominant disease associated with the NF1 gene on chromosome 17q11, which codes for neurofibromin. *Neoplasms associated with NF1 include: neurofibromas, malignant nerve sheath tumors, optic nerve gliomas, rhabdomyosarcomas, pheochromocytomas, and carcinoid tumors. *Other findings in NF1 patients include: café-au-lait spots, Lisch nodules, and axillary freckling.

Question 125

NF2 has to do with chromosome 22. So what common molecular abnormality do meningiomas have?

Answer 125

monosomy 22 *meningioma is associated with NF2