Hef's Lectures Flashcards
what is the most common form of germ cell tumor?
seminoma
classical seminoma
- 15-35 y/o and PAINLESS
- “fried egg” due to collagen -> large cells w/ clear cytoplasm and central nuclei
spermatocytic seminoma
- 60 y/o
- NO fried egg appearance (no glycogen)
embryonal carcinoma
- 20-30 y/o and PAINFUL
- high hCG or AFP or both
- HEMORRHAGE and NECROSIS -> Acute abdomen
yolk sac tumor
- <4 y/o
- high AFP
- Schiller-Duval bodies
- AFP and alpha 1 antitrypsin markers
choriocarcinoma
- 20s and PAINFUL
- mimic placental tissue
- high hCG -> GYNECOMASTIA
- blood metastasis to lungs
- syncytiotrophoblasts and cytotrophoblasts
Teratoma
- more than 1 of the 3 germline layers
- high hCG or AFP or both
Leydig cell tumors
- 20-60 y/o
- precocious puberty or gynecomastia
- GOLDEN BROWN cholesterol nodules
- crystalloids of Reinke
testicular lymphoma
- men >60 y/o
- metastis in testes
- diffuse large B cell type
where do carcinomas arise from in prostate?
peripheral zone
where does BPH arise from in prostate?
transitional zone
what is the main androgen leading to BPH?
DHT
-formed by type 2 5a-reductase stromal cells
BPH
- benign, men >50 y/o
- NOT premalignant
- DHT activates FGF and TGF-B
- BRCA, HOXB13, PTEN, TP53 mutations
prostatic intraepithelial neoplasia (PIN)
- cancer has NOT invaded BM
- can progress to prostatic adenocarcinoma
adenocarcinoma of the prostate
- a-methylacyl-coenzyme A-racemase (AMACR) markers
- grading based on architecture alone, not nuclear atypia
are prostatic crystalloids a sign of good or bad prognosis?
-GOOD prognosis -> highly differentiated and less invasive
where does prostate cancer like to spread to?
-bone (osteoblastic), lungs, kidneys, Brain
prostatic biomarkers
- PAP
- PSA (>10 -> cancer)
- PCA3
what type of epithelium is the outside of the cervix compared to inside?
outside -> stratified squamous
inside -> columnar
acute vs. chronic cervicitis
acute -> neutrophil infiltrate
chronic -> lymphocytes, plasma cells, Mac infiltrate
squamous intraepithelial lesion (aka cervical intraepithelial neoplasia)…CIN
-NOT invading BM
- CIN 1 -> <1/3
- CIN 2 -> <2/3
- CIN 3 -> full thickness (CIS)
cervical dysplasia
- iodine stains of glycogen are BROWN
- acetic acid stains WHITE (no glycogen)
test with Pap smear from the transformation zone
most common type of invasive cervical carcinoma?
- SCC
- Adenocarcinoma is 2nd
when is dysfunctional uterine bleeding most worrisome?
- post-menopausal women
- can indicate cancer
endometriosis
- ectopic endometrial tissue OUTSIDE the uterus
- usually due to retrograde menstruation
- usually in ovaries -> CHOCOLATE CYSTS
- gun powder nodules
adenomyosis
-endometrial tissue in myometrium
endometrial hyperplasia
- precursor to endometrial carcinoma
- unopposed estrogen
- associated w/ Cowden syndrome & PTEN mutations
endometrial carcinoma
- post-menopausal bleeding >40 y/o
- unopposed estrogen
- type I (endometrioid) -> PTEN mutations…less aggressive (high differentiation) and arises from endometrial hyperplasia
- type II (serous) -> p53 mutations…more aggressive (poor differentiation) and arises from endometrial atrophy
Leiomyoma aka fibriod
- BENIGN
- tumor of smooth muscle
- “Whorled pattern”
- Red degeneration -> ACUTE ABDOMEN
- pre-menopause
Leiomyosarcoma
- MALIGNANT
- tumor of smooth muscle
- MED12 mutations
- do NOT arise from leiomyomas
- post-menopause
PCOS
- excess androgens -> hirsutism
- associated w/ DM and obesity
- hyperinsulinemia -> displace IGF
cystadenoma
- 30-40 y/o
- benign
- SINGLE layer, FLAT lining
brenner tumor
- bladder-like epithelium
- benign
borderline tumor
- low malignant potential
- MULTIPLE layers
cystadenocarcinoma
- JAGGED lining
- Psammoma bodies
- CA-125 marker
Dysgerminoma***
-ovarian counterpart of testicular seminoma
- 20-30 y/o
- “fried egg” appearance
- all are MALIGNANT
- high hCG and LDH
granulosa theca cell tumor
- Call-Exner bodies
- coffee-bean nuclei
- excess androgens and estrogen
- FOXL2 gene mutations
fibroma
- benign tumor of fibroblasts
- Meigs syndrome (ascites, effusion)
- Gorlin syndrome
Sertoli-Leydig tumor
- mimics testicles
- reinke crysals
- produce androgens -> virulization and hirsutism
Krukenberg tumor
- metastatic mucinous tumor (GI/breast) -> spread to ovary
- mucin -> SIGNET RING
- bilateral
fibroadenoma
- benign
- MOBILE marble like mass (slippery)
intraductal papilloma
- benign
- fibrovascular stalks -> BLOODY discharge from nipple
- 2 layers (epith. + myoepith.)
Phyllodes tumor
- benign or malignant (based on STROMA)
- “leaf-like” due to overgrowth of fibrous part
mutations in what are at high risk for breast cancer?
- BRCA 1 and BRCA 2
- p53
ductal carcinoma in situ (DCIS)
- NO invasion of BM
- microcalcifications
- NO mass
- solid -> plugging
- comedo** -> CHEESY necrotic debris in center w/ calcification
- papillary -> lack fibrovascular stalk
- cribriform -> fenestrations
Paget disease
if DCIS travels to the epidermis in the nipple
-always associated w/ carcinoma of breast
invasive ductal carcinoma
HAS MASS
- NST
- extensive FIBROSIS -> DESMOPLASIA
- Peau d’ Orange (dimpling)
- form ducts
- NO myoepithelial layer (single) - Medullary
- SOFT & fleshy (encephaloid carcinoma)
- most Anaplastic, BEST prognosis - Mucinous
- islands of cells “floating” in mucin - tubular
- no myoepith. layer
- VERY good prognosis
Lobular carcinoma in situ
- NO invasion of BM
- loosely cohesive cells (lack cadherin)
- mucin -> SIGNET RING
- ER+ and PR +, no HER2
invasive lobular carcinoma
- INDIAN FILE -> single file spread of cells
- bad prognosis
do ER/PR negative tumors have a good or bad prognosis?
BAD
-want ER+ and PR+ tumors to treat w/ anti estrogen therapy (ex. tamoxifen)
HER2
- receptor seen on some types of breast cancer
- respond to anti-HER2 Abs (trastuzumab/herceptin) if present
where does breast cancer 1st metastasize to?
AXILLARY lymph nodes
-disseminate to lung, liver, bone, brain
thyroid follicular adenoma
- benign & encapsulated
- COLD nodule
- Hurthle cell type -> seen in parathyroid lesions also
- Atypical type -> indicate malignancy
thyroid carcinoma
- multiple types
- COLD nodules
- normal TSH values
- FNA if nodules 1-4 cm (>4 -> surgery)
- arise from follicular cells (except Medullary)
most common type of thyroid carcinoma
PAPILLARY thyroid carcinoma
Papillary thyroid carcinoma
- TRANSLOCATION/inversion of RET
- gain of function mut. in BRAF
- RADIATION is risk factor
- fibrovascular core
- ORPHAN ANNIE EYE nuclei
- Pseudo-inclusion bodies
- PSAMOMMA bodies
Follicular thyroid carcinoma
- q13;p25 translocation -> fusion of PAX8 w/ PPARG
- IODINE DEFICIENCY is risk factor -> stimulate TSH
- produces more T3, T4 -> suppress TSH
- INFILTRATE through capsule
- COLLOID follicles
- HOT iodine scan
Anaplastic thyroid carcinoma
- undifferentiated
- B-catenin activation mutation
- WORSE PROGNOSIS -> aggressive
- ELDERLY (65 y/o)
Medullary thyroid carcinoma
- arise from PARAFOLLICULAR C cells -> Calcitonin
- high Calcitonin w/ NORMAL Ca2+ levels
- point mutations in RET (sporadic) or germline mut. in RET (MEN-2A/B)
- markers: CEA and CALCITONIN
- AMYLOID deposits -> SOFT
Are most thyroid nodules malignant or benign?
BENIGN**
Adrenocortical Adenocarcinoma
-11C-metomidate-PET is diagnostic -> binds to 11B-hydroxylase
Pheochromocytoma
- BENIGN -> tumor of adrenal MEDULLA
- ADULT (20-40)***
- dark brown in K+ dichromate***
- Zellballen Pattern***
- neuron-specific enolase (NSE) marker
- HTN 90% of time
- catecholamines in urine (Vanillylmandelic acid and Metanephrines)**
Neuroblastoma
- MALIGNANT
- 4th most common childhood malignancy -> CHILD <5 y/o**
- small blue tumor cells
- Schwann cells**
- Homer-Wright Pseudorosettes**
- markers: NSE, neurofilaments, chromagranin
- Raccoon eyes, Heterochromia iridis
Pituitary cancers
- BENIGN
- FUNCTIONAL -> PRL, ACTH, GH
- nm23 tumor suppressor mutation**
- c-MYC activating mutation
MEN type 1 (Wermer syndrome)
- 3 ps -> parathyroid, pancreatic, pituitary adenomas**
- inactivating mutation in MEN-1 (chrom. 11)
Zollinger-Ellison syndrome
-gastrinomas (pancreatic tumor) w/ MEN1 mutations -> peptic/gastric ulcers
Carcinoid tumors
- MEN1 mutations
- metastasize -> death
- no cure
- release Serotonin** -> 5-hydroxytryptamine metabolite in urine**
- pallagra, flushing, diarrhea
MEN type 2A (Sipple syndrome)
- gain of function mut. in RET
1. Medullary thyroid carcinoma
2. Pheochromocytoma
3. Parathyroid hyperplasia
MEN-2B
- M918T variant of RET mut.
- NO hyperparathyroidism
1. medullary thyroid carcinoma
2. pheochromocytoma
3. mucosal neuromas
4. Marfanoid Habitus
Von Hippel-Linau (VHL) disease
- benign
- mut. in VHL
- HEMANGIOBLASTOMAS*** and pheochromocytoma
Pancreatic Neuroendocrine Tumors (PanNETs)
- MEN1 and PTEN mutations
- MONOTONOUS cells
- AMYLOID deposits
pancreatic beta cells
- produce insulin by pro hormone convertase 1/3 (PC1/3)
- ATP-regulated K+ channels
- INSULINOMA
what drug blocks K+ efflux leading to an increase in insulin
SULFONYLUREA
pancreatic alpha cells
- secrete glucagon
- GLUCAGONOMA -> Necrolytic Migratory Erythema*** (AA and zinc deficiency)
pancreatic delta cells
- secrete Somatostatin
- SOMATOSTATINOMA -> low gastric acid, gallstones, steatorrhea
Gastrinoma (Zollinger-Ellison syndrome)
-increase acidity, ulcers, high serum gastrin
VIPoma (Verner-Morrison syndrome)
- diarrhea -> hypokalemia, dehydration
- treat and image w/ OCTREOTIDE
mutations that can cause DM
- MODY
- glucokinase mut.
- hepatic nuclear factor mut.
- insulin promotor factor 1 mut. - GATA6
- DNA 3243
HbA1c
- glycated Hb from DM
- high levels -> retinopathy and CV problems
type I DM
- HLA-DR3 and HLA-DR4 class II antigens (higher w/ DQ8)***
- HLA-DQ5 and DQ6 -> protection from type 1
- hyperglycemia
- increase risk for Candida
- DIABETIC KETOACIDOSIS
type 2 DM
- insulin resistance due to obesity -> adipokines (resistin and RBP4)**
- beta cell dysfunction -> AMYLOID deposits*
- beta cell burnout
- excess FAs
Hyperosmolar Hyperglycemic state
- seen in type 2 DM
- hyperglycemia, dehydrated, uremia, coagulability, rhabdomyolysis -> high mortality
AGE from DM
- ECM accumulation -> cross-link ECM type I collagen -> REDUCE ELASTICITY
- trap LDL proteins -> cholesterol deposits (Kimmelstiel-Wilson Nodules)
activation of kinases and cytokines w/ DM
High glucose -> increase DAG -> increase PKCbeta -> increase TGFbeta and VEGF -> increase vascular permeability and angiogenesis
-Avastin (VEGF antagonist) -> treat diabetic retinopathy
