Slide to syndrome - board study Flashcards
5 syndromes caused by inherited defects in DNA repair
Ataxia Telangiectasia, Bloom syndrome, MYH-associated polyposis, Xeroderma pigmentosa, Fanconi Anemia (all have autosomal recessive mode of inheritance)
Inheritance pattern of Lynch syndrome
also HNPCC, autosomal dominant - DNA mismatch repair gene inactivation
MEN1
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)
Combination of pituitary tumor, hyperparathyroidism, pancreatic endocrine tumor and duodenal carcinoid producing a hormonal syndrome…
MEN1, especially with gastrinoma and zollinger ellison syndrome
Birt-Hogg-Dubé syndrome (germline folliculin mutation)
Skin adnexal tumors, kidney tumors (bilateral), lung cysts with pneumothorax presentation
(fibrofolliculoma), (renal cell carcinoma)
Hereditary leiomyomatosis and RCC syndrome
(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)
fumarate hydratase deficient RCC is the same thing as…
HLRCC associated RCC (referring to Hereditary leiomyomatosis and RCC syndrome)
Ataxia Telangiectasia –> inheritance and diseases
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
Bloom syndrome –> inheritance and diseases
autosomal recessive, gene product BLM helicase, chromosome 15 –> predisposition to wide range of cancers, especially leukemias (in context of developmental defects)
Fanconi anemia –> inheritance and diseases
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)
Carney complex / carney syndrome –> inheritance and diseases
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)
tumors/lesions that make you think carney syndrome (not triad)
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
you see myxoma with other pigmented or calcifying things and you think…
Carney complex / carney syndrome –> AD inheritance, PKA gene product, 17q22-24 and 2p16 locations
you see large cell calcifying sertoli cell tumor and you think…
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)
Retinoblastoma syndrome –> inheritance and diseases
40% are inherited in AD fashion, RB gene product on chromosome 13q14 –> bilateral retinoblastomas, pineoblastoma, osteosarcoma (and other sarcomas)
You see osteosarcoma + other sarcoma with any hint of blindness and you think…
inherited RB gene mutation, retinoblastoma syndrome, 13q14, look for pineoblastoma
you make a dx of pineoblastoma and you think….
inherited RB gene mutation, retinoblastoma syndrome, 13q14, look for osteosarcoma /other sarcoma and bilateral retinoblastomas
Carney triad vs. Carney complex/syndrome
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)
what is the other name for hereditary hemorrhagic telangiectasia
Rendu-osler-weber syndrome, AD, ACVRL1 + ENG gene products (both in TGFbeta pathway) —> aneurysmal telangiectasias in multiple organs (bleeding)
Rendu-osler-weber syndrome…
(AKA: hereditary hemorrhagic telangiectasia)
AD inheritance, ACVRL1 + ENG gene products (both in TGFbeta pathway) —> aneurysmal telangiectasias in multiple organs (bleeding)
Li-Fraumeni syndrome —> inheritance and diseases
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
A young person has multiple primary tumors of different organs and you think…
Li-fraumeni? Inherited AD, problem with p53, sarcoma, carcinoma (breast, colon, pancreas, adrenal cortex), leukemia, melanoma, glioma
Hereditary breast and ovarian cancer….
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
male breast cancer hereditary association
BRCA2 >BRCA1
*after this, some other inherited solid tumor predisposition
Breast cancer and prostate cancer have what in common?
BRCA2 mutation
Chromosomal location of BRCA1
17q21 —> breast and ovarian cancer
Chromosomal location of BRCA2
13q —> breast and ovarian (less than BRCA1) and prostate and pancreas, male breast cancer
Cowden’s disease / syndrome —> inheritance and manifestation
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
Chromosomal location and gene product mutated in Cowden’s disease/syndrome
PTEN, 10q (AD inheritance)
HAMARTOMAS ‘plus’
*thyroid (follicular>ptc), RCC, merkel cell, lymphoma, melanoma, meningioma
Cowden’s disease/syndrome and breasts…
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
A patient has a ton of HAMARTOMAS, and now another cancer…
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
DDX of anything ‘hereditary breast cancer’
Start with BRCA1 and BRCA2
*then cowden’s syndrome/disease
*then Ataxia-telangiectasia (AT), Li-fraumeni
Familial atypical multiple mole melanoma syndrome (FAMMM) or B-K Mole syndrome) —> inheritance and diseases
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)
Gorlins syndrome and FAMMM / B-K Mole syndrome have something in common…
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
Gorlin’s syndrome —> inheritance and diseases
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)
What does STK11 have to do with breast cancer?
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
What does PTEN have to do with breast cancer?
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.
What does CDH1 have to do with breast cancer?
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.
Male breast cancer….what genes should you think about?
*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.
Tumors associated with von Hippel Lindau Syndrome (VHL gene)
Clear cell renal cell carcinoma
Along with Hemangioblastomas, pheochromocytoma, pancreatic serous cystadenomas, and endolymphatic sac tumor
Germline DICER mutations…
(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.
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.
(DICER1-PPB familial tumor predisposition syndrome)
Think, in a pediatric patient, pleuropulmonary blastoma
(DICER1-PPB familial tumor predisposition syndrome)
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.
Peutz-Jegher polyp in the stomach…
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
Gastric type adenocarcinoma in the cervix
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
Do PJS patients have increased risk of GI cancer?
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
hamartomatous polyposis syndrome characterized by macrocephaly, lipomatosis, hemangiomas, and hamartomatous polyps in the gastrointestinal tract.
Bannayan-Ruvalcaba-Riley syndrome is a hamartomatous polyposis syndrome characterized by macrocephaly, lipomatosis, hemangiomas, and hamartomatous polyps in the gastrointestinal tract.
Bannayan-Ruvalcaba-Riley syndrome
hamartomatous polyposis syndrome characterized by macrocephaly, lipomatosis, hemangiomas, and hamartomatous polyps in the gastrointestinal tract.
Most common hamartomatous polyp syndrome
The most common of the hamartomatous syndromes is familial juvenile polyposis, which has an estimated incidence of 1 per 100,000 births
JPS in the world of syndromes
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
There is a polyp in the small intestine…
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).
you see a bone marrow with FOCAL replacement by aggregates of pink, almost spindled cells with ‘striated’ cytoplasm
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
Inheritance Gauchers disease
AR
Lack of Glucocerebrosidase (Acid β-glucosidase)
➢ Causes accumulation of glucosylceremide (glucocerebroside) in phagocytes
Syndrome with SPOT diagnosis of a neutrophil with super big azurophilic granules in it
*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
What does Chediak-Higashi Syndrome normally present with?
Presents with partial oculocutaneous albinism, neutropenia and recurrent infections, mild bleeding from mucosal surfaces
What is a syndrome associated with 2nd wave platelet aggregation problems?
*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
Macrophages are weird in Gauchers…why?
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
you see a renal angiomyolipoma and you think….
could this be Tuberous Sclerosis associated?
(make sure it’s not a sarcoma or sarcomatoid RCC first)
Carney syndrome patient with a sertoli cell tumor. how do you prove it with IHC?
IHC: Positive for inhibin-α, calretinin, Melan-A (MART-1), SF1, WT1, chromogranin, synaptophysin, AE1/AE3, nuclear β-catenin
bilateral chromophobe RCC (familial chromophobe RCC)
birt-hogg-dube
germline mutation of c-met gene AND kidneys…
hereditary papillary renal cell carcinoma
*papillary RCC (type 1, the true PRCC)
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
Fanconia Anemia
*AR, 25% chance their sibling will get it
*DNA breakage studies will be positive
what kind of syndrome would be implicated by a POSITIVE ‘DNA breakage study’
inherited disorders of DNA repair (the 5 AR inherited DNA repair disorders)
you see wilms tumor…
WAGR syndrome
*wilms
*aniridia (no iris in the eye)
*genitourinary malformation
*mental Retardation
which neuropath entity belongs with nevoid basal cell carcinoma syndrome?
Gorlin syndrome = nevoid basal cell carcinoma syndrome
*medulloblastoma
follicular adenoma of thyroid…
PTEN-hamartoma tumor syndrome (PHTS): Cowden disease and Bannayan-Riley-Ruvalcaba syndrome (BRRS) syndrome
Pendred syndrome
Carney complex
malignant form of a PEComa in tuberus sclerosis patients
epithelioid angiomyolipoma
you see epithelioid angiomyolipoma…
you think tuberous sclerosus (50% of cases have TS history)
even sporadic cases have a TSC2 mutation
McCune-Albright syndrome is associated with…
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
You see polyostotic fibrous dysplasia…
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.
Maffucci syndrome is characterized by …
the association of multiple chondromas and spindle cell hemangiomas located in the overlying skin and soft tissues.
Gardner syndrome…
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
combination of intestinal polyposis, multiple osteomas, fibromatosis, and epidermal cysts.
Gardner syndrome
t(11;22)(q24;q12)
ewing sarcoma; FLI1-EWS
Ewing sarcoma
t(11;22)(q24;q12)
What do Gardners and FAP have in common?
Gardner syndrome refers to FAP patients with extracolonic manifestations, including multiple osteomas, epidermal cysts, and fibromas.
What pathway of carcinoma development do polyps in FAP go through?
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).
Turcot syndrome
Turcot syndrome refers to the coexistence of a hereditary colonic cancer syndrome and CNS tumors.
FAP messes with what gene pathway?
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.
LOH at 18q21 is common in what?
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
tumors in lynch syndrome family
Tumors in this family cancer syndrome include colonic, endometrial, urothelial, small intestinal, stomach, and hepatobiliary carcinomas, and demonstrate microsatellite instability (MSI).
You see CNS hemangioblastoma…
VHL syndrome
*inhibin IHC
CNS medulloblastoma…
Turcot syndrome (CNS manifestations of FAP
*also NBCCS or Gorlin’s
CNS plexiform and diffuse neuofibroma
NF1
Psammomatous melanotic schwannoma
Carney complex
CNS subependymal giant cell astrocytoma
tuberus sclerosis
*big cells, not multinucleated osteoclast like giant cells
Lymphangioleimoyomatosis of the lung
tuberus sclerosis
*PEComa family
Mediastinal carcinoid tumor
MEN1
Rhabdomyoma
Tuberous sclerosis
Medullary carcinoma of breast
BRCA1
gangliocytic paraganglioma of duodenum
NF1
diffuse ganglioneuromatosis
MEN2b
NF1
GI tract neurofibromas
NF1
Gastrinoma in GI tract
MEN1
Somatostatinoma of GI tract
*do NOT click MEN1
*it’s actually NF1, quite tricky. MEN1 is best associated with gastrinoma and zollinger-ellison
A kid with adrenocortical carcinoma
BWS
MEN1
Li-Fraumeni
Congenital adrenal cytomegaly
BWS
*ugly cells, NOT mitotically active
Pheochromocytoma
MEN2A
MEN2B
VHL
NF1
Hybrid chromophobe RCC and onococytoma
birt-hogg-dube
inverted Urothelial cell carcinoma of renal pelvis
lynch syndrome
papillary cystadnoma of epididymis
VHL
Renal medullary carcinoma
Sickle cell trait
RCC with lots of calcium oxalate
ESRD associated
papillary RCC with macronucleoli and clear halo
HLRCC or FH deficient
Wilms tumor
WAGR
Denys-Drash
BWS
Disorder characterized by ambiguous genitalia or pseudohermaphroditism, early-onset nephrotic syndrome, and ↑ risk for Wilms tumor (WT)
Denys-Drash
Meningioma
NF2
monosomy of chromosome 22 is the most common cytogenetic abnormality in meningiomas
*can happen through LOH
NF2 mutation is 22q12
tumors of tuberous sclerosus
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
RET germline mutation, autosomal dominant inheritance
MEN2 (both A and B)
MEN2B tumors
Pheochromocytoma
Medullary thyroid carcinoma
Mucosal neuromas
Marfanoid features
*ganglioneuromas
MEN2A
Parathyroid hyperplasia
Pheochromocytoma
Medullary thyroid carcinoma
*hirschsprung
Genes of tuberous sclerosis
Two different genes are associated with tuberous sclerosis:
*TSC1 gene: hamartin located in chromosome 9q34,
*TSC2 gene: tuberin located in chromosome 16p13.3
RET M918T mutation is present in up to 98% of patients with
MEN2B
*medullary thyroid carcinoma
Eosinophilic solid and cystic renal cell carcinoma
*tuberous sclerosis
Pathogenesis: Mutations in TSC1 or TSC2 in majority, upregulation of m TOR pathway
Lymphangioleiomyomatosis in the lung
*tuberous sclerosis
*PEComa, so look for HMB-45 or mart-1 or something
*destructive and metastatsizing, cystic thing in b/l lungs
Desmoid type fibromatosis (mesentery)….
*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.
Carney-Stratakis syndrome….
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.
Brooke-Spiegler syndrome
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
multiple cylindromas, trichoepitheliomas, and eccrine spiradenomas
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
AD inherited CYLD1 mutations
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
MEN 2A/2B
*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.
Optic pathway pilocytic astrocytoma
NF1
Bilateral acoustic schwannomas
NF2
Location of NF1 mutation
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.
NF2 has to do with chromosome 22. So what common molecular abnormality do meningiomas have?
monosomy 22
*meningioma is associated with NF2
