Eugene Oncology Flashcards
increased lifetime estrogen exposure, BRCA, 1st degree relative, increased density, obesity, alcohol
Breast Cancer : Epi/Risk Factors
Most common cancer in women in US (rising), 2nd leading cause of death (falling), 1 in 8
Breast Cancer : Signs/Symptoms/Findings
sporadic>familial>hereditary(BRCA1)>BRCA2
Breast Cancer Etiology
chro 17q OR 13q mutation of dsDNA repair
BRCA 1 and 2
1:400 (1:40 Ash. Jews), 40%-60% breast, 20-40%ovarian, earlier onset, male risk of breast, prostate and pancreative cancer
BRCA cancer prevalence
> 1% of cells are ER+ or PR+ (treat with tamoxifen)
Breast Cancer : Good Prognosis (most have 85-100% 5 year survival
LN mets, more aggressive/less differentiated, HER2 gene
Breast Cancer, poor prognosis
EGFR, chro 17, amplification of cell proliferation and resistance to apoptosis, tx: trastuzumab + chemo
HER2 mutations
don’t treat with doxy. Increased risk of cardiotoxicity
HER2 mutation Breast Cancer (Trastuzumab)
lumpectomy & radiation or total mastectomy
Local therapy for Breast Cancer
antiestrogen therapy: oophorectomy, leuprolide (blocks hypo-pit axis), tamoxiphen. Post-menopuase: anastrole, letrozole, tamoxifen
Er+ breast tumors
cyclophosphamide/cytotoxan, doxorubicin/adriamycin, paclitaxel/taxol
general chemo for breast cancer
paclitaxel/taxol
indicated for breast cancer in young women with poorly differentiated triple negative tumors (ER-,PR-,HER-)
cancerous cells but no invasion
stage 0 breast cancer
tumor <2cm, no LN
stage 1 breast cancer
tumor 2-5 cm or <4 LN
stage 2 breast cancer
tumor >5 cm or >4 LN
stage 3 breast cancer
metastatic
stage 4 breast cancer
25% of breast Ca
Ductal Carcinoma In Situ (DCIS): Epi/Risk Factors
microcalcification on mamm, fills ductal lumen, nuclear atypia, stage 0
Ductal Carcinoma In Situ (DCIS): Signs/Symptoms/Findings
stage 0 neoplastic transformation of E-cadherin+ large ductal epithelial cells (noninvasive)
Ductal Carcinoma In Situ (DCIS): Pathophysiology/Diagnosis
8-10x risk of invasive carcinoma, most don’t progress, worse if younger onset, larger size, high histo grade, small margin width
Ductal Carcinoma In Situ (DCIS): Prognosis
Ipsilateral risk of invasive cancer
Ductal Carcinoma In Situ (DCIS): Treatment/Notes
Often misdiagnosed as inflammatory (e.g. eczema)
Paget’s Disease: Epi/Risk Factors AND Signs/Symptoms/Findings AND Picture
Carcinoma of ducts, nipple
Paget’s Disease: Pathophysiology/Diagnosis
High risk
Paget’s Disease: Prognosis
Ulcerated, scaling nipple lesions
Paget’s Disease: Treatment/Notes
Most common breast Ca
Invasive Ductal Carcinoma: Epi/Risk Factors
Grossly irregular; better prognosis if one of the better differentiated types
Invasive Ductal Carcinoma: Signs/Symptoms/Findings
infiltrative epithelial neoplasm resembing cells lining the ducts/lobules (E-cadherin +)
Invasive Ductal Carcinoma: Pathophysiology/Diagnosis
Prognosis: Medullary, colloid, tubular, mucinous good; inflammatory (erythematous, dermal lymphatics involved) bad
Invasive Ductal Carcinoma: Prognosis AND Treatment/Notes
invasive ductal carcinoma with abundant lyphocytes, mucin, or dilated tubules
medullary, colloid mucinous, or tubular carcinoma; good prognosis
invasive ductal carcinoma with dermal lymphocytic invasion, peau d’orange skin
inflammatory carcinoma; bad prognosis
E-cadherin(-) epithelial cells lining acini and terminal ducts
Lobular Carcinoma In Situ (LCIS): Signs/Symptoms/Findings
bilateral, multifocal small cells in lobules or ducts. Defined by cell type, not location
Lobular Carcinoma In Situ (LCIS): Pathophysiology/Diagnosis
6-9x risk of invasive cancer bilaterally, regardless of original side
Lobular Carcinoma In Situ (LCIS): Prognosis
general risk factor for cancer, but not a precursor, not treated surgically
Lobular Carcinoma In Situ (LCIS): Treatment/Notes
Bulls eye v. Indian file pattern of small cells with scant cytoplasm, decreased E-cadherin expression
Invasive Lobular Carcinoma: Signs/Symptoms/Findings
5-10% of breast cancers, 20% bilateral
Invasive Lobular Carcinoma: Epi
rare, advanced age, BRCA2
male breast cancer
Infiltrating carcinoma resembling cells lining lobules
Invasive Lobular Carcinoma: Pathophysiology/Diagnosis
Tends to be bilateral
Invasive Lobular Carcinoma: Treatment/Notes
40-50% of lumps
Fibrocystic Changes: Epi/Risk Factors
Fibrosis, cysts, apocrine metaplasia, expansion of periductal stroma
Fibrocystic Changes: Signs/Symptoms/Findings AND Picture
Normal part of aging process; increased risk for invasive breast cancer with atypical ductal/lobular hyperplasia, papilloma, adenosis
Fibrocystic Changes: Pathophysiology/Diagnosis AND Prognosis AND Treatment/Notes
Cookie-cutter, spherical appearance of ducts; some but not all features of in situ carcinoma
Atypical Ductal Hyperplasia: Signs/Symptoms/Findings
8-10% risk of progressing t ocarcinoma (ALH>ADH)
Atypical Ductal Hyperplasia: Prognosis
Bimodal: 20s, 40s
Fibroadenoma: Epi/Risk Factors
Lots of stroma, small mobile firm ball-like mass w/sharp edges, increased breast size and tenderness, esp. menses, pregnancy
Fibroadenoma: Signs/Symptoms/Findings
Benign fibroepithelial tumor, most common benign tumor, rarely leads to cancer
Fibroadenoma
Benign papillary neoplasm within duct, bloody discharge
Intraductal Papilloma: Signs/Symptoms/Findings
Can be peripheral or central (nipple), up to 2x risk if peripheral
Intraductal Papilloma: Pathophysiology/Diagnosis
50 yo, cured via excision
Cystosarcoma Phyllodes: Epi/Risk Factors
fibroepithelial neoplasm, Lots of stroma, invaginates into ducts
Cystosarcoma Phyllodes: Signs/Symptoms/Findings AND Picture
p53 inactivating, k-ras activating, EGFR mutation (activates k-ras), chimeric gene of EML4 & ALK
genetic abnormalities in lung cancer
chimeric gene of EML4 and ALK
genetic abnormality in nonsmoking lung cancer
k-ras activating mutation, constituitive activation of a GTPase and all downstream enzymes
genetic abnormality in 25% of adenocarcinoma, often in smokers
asbestos, ionizing radiation, benzypyrene (steel smelting), chloro-methyl ether
lung cancer carcinogens
percent of heavy smokers who get lung cancer
10-20%
risk increases greatly with exposure to multiple carcinogens (synergy)
lung cancer
highest cancer mortality, 2nd highest incidence (decreasing)
lunger cancer
Smoking causes 80-90%
Lung Cancer: Epi/Risk Factors
Cough, dyspnea, SVC syndrome, hoarseness (bad prognosis), clubbing, infxn/pneumonia, etc.
Lung Cancer: Signs/Symptoms/Findings
Dx: transbronchial biopsy, bronchoscopy, CT screening (decreases mortality 20%)
Lung Cancer: Picture
mets to brain, bones, liver, ADRENALS
lung cancer
Precursor lesions: atypical adenomatous hyperplasia, squamous, DIPNECH
Lung Cancer: Pathophysiology/Diagnosis
Screening by low-dose helical CT = 20% mortality reduction; EGFR TKIs helpful (see drug chart)
Lung Cancer: Treatment/Notes
Central, hilar, high grade poorly differentiated tumor
Small Cell Lung Carcinoma (aka Oat Cell): Signs/Symptoms/Findings
Older Age, smoking related
Small Cell Lung Carcinoma Epi
large central tumor w/necrosis, extrapulmonary disease, high N:C, nuclear molding, salt and pepper chromatin, high grade (mitoses and apoptosis), poorly differentiated (few granules)
Small Cell Lung Carcinoma (aka Oat Cell): Pathophysiology/Diagnosis
Only 5% found early
Small Cell Lung Carcinoma (aka Oat Cell): Prognosis
Poor prognosis, associated with SIADH, Cushing’s
Small Cell Lung Carcinoma (aka Oat Cell): Treatment/Notes
cell type: neuroendocrine: neurosecretory cells in airway epithelium which control smooth muscle tone
Carcinoid, Small Cell Lung Carcinoma
central, low grade, salt & pepper chromatin, nests and chords, well-differentiated w/neurosecretory granules
Carcinoid Lung Cancer: Signs/Symptoms/Findings
NE cell hyperplasia, tumorlet invades through airway wall, formation of microscopic nodule
Carcinoid Lung Cancer
Younger, nonsmoker
Carcinoid Lung Cancer Epi
Invasive, peripheral tumor can produce umbilicated lesion, may form glands (goblet cells, clara cells, type 2 pneumocytes)
Adenocarcinoma: Signs/Symptoms/Findings
most common cancer of nonsmokers
Adenocarcinoma: Epi
atypical adenomatous hyperplasia, in situ: ground glass histo, still has some functional alveoli, then forms invasive adenocarcinoma
Adenocarinoma
Disorganized, nested keratinization (pearls), central tumor with squamous differentiation, adhesions and bridges
Squamous Cell Carcinoma: Signs/Symptoms/Findings
squamous dysplasia in metaplastic bronchial cells, nuclear stratification and atypia
Squamous Cell Carcinoma: Signs/Symptoms/Findings
Early stage NSCLC: Surgery (lobectomy vs. wedge), XRT/RF ablation if nonsurgical, adjuvants: Cisplatin + Vinorelbine, Gemcitabine or Pemetrexed
treatment for all non-small cell carcinomas: adeno, squamous, large and giant cell
radiotherapy at site, LN, and brain prophylactic Etoposide and Cisplatin
treatment for all small-cell
Cisplatin and second agent, plus Erlotinib (TK inhibitor, for EGFR mutation) or Crizotinib (TKi for ALK)
treatment for metastatic lung cancer (e.g. of skeleton/brain)
High grade, non-differentiated tumor, poor prognosis, giant cell variant
Large Cell Carcinoma: Signs/Symptoms/Findings
3rd most common cancer, 10% of cancer deaths
Colorectal Cancer: Epi/Risk Factors
over 50, first degree relative, polyps(15-20%), IBD (15-40%), western diet
Colorectal Cancer: Epi/Risk Factors
AK53 leads to loss of APC/beta-catenin leads to k-ras mutation leads to p53 mutation
Colorectal Cancer
Tends to metastasize to lymphatics, liver via portal circulation
Colorectal Cancer: Signs/Symptoms/Findings
65-85% sporadic, 10-25% familial, 6% hereditary syndromes; stage I even if invades muscularis
Colorectal Cancer: Pathophysiology/Diagnosis
1 Cause of Ca death in non-smokers
Colorectal Cancer: Prognosis
Risk factors: developed nations , age, smoking, meat, decreased fiber and exercise, family history, polyps, IBD < HNPCC (~80%) < FAP (~95%)
Colorectal Cancer: Treatment/Notes
AD APC loss, 30% de novo. 1% of CRCs, 100% lifetime risk of CRC
Familial Adenomatous Polyposis (FAP): Epi/Risk Factors
100s-1000s of polyps
Familial Adenomatous Polyposis (FAP): Signs/Symptoms/Findings
blocks beta-catenin, stopping growth and proliferation via Wnt pathway
normal APC gene
APC gene sequencing, k-ras, congential hypertrophy of retinal pigment epithelium
Familial Adenomatous Polyposis (FAP): Pathophysiology/Diagnosis
desmoid tumors (benign), brain, thyroid and duodenal cancers
Familial Adenomatous Polyposis (FAP): Prognosis
Screening: Sigmoidoscopy at 10-12 yo, q2yr after for FAP (start yearly colonoscopy in 20s for Lynch) Tx: Surgery for localized, XRT for rectal; Stg. III/IV: 5-FU, Irinotecan, Oxaliplatin, Bevacizumab, Cetuximab/Panitumumab
Familial Adenomatous Polyposis & Lynch Syndrome
AD, early age (40s)
Lynch Syndrome (HNPCC): Epi/Risk Factors
Multiple primary cancers (endometrium, ovary, GU tract, etc.); more likely to be right-sided, MSIs
Lynch Syndrome (HNPCC): Signs/Symptoms/Findings
lifetime risk of CRC 70%, accelerated polyp to tumor timeline
Lynch Syndrome
Right v. left in CCR
Right bleeds, left obstructs (look for anemia, not blood)
IHC staining for MLH1 and 2 shows decrease, BRAF mutation
Lynch Syndrome (HNPCC): Diagnosis
DNA mismatch repair defects leads to MSIs leads to normal tumor initiation, increased progression
Lynch Syndrome (HNPCC): Pathophysiology
Bethesda guidelines for risk
Lynch Syndrome (HNPCC): Prognosis
precancerous, low surface maturation, enlarged nuclei, low mucin, purple/ble, MIB-1/Ki67 positive (proliferation)
Adenomatous Polyp: Signs/Symptoms/Findings
Malignancy risk, endoscopic resection if pedunculated, sessile if small
Adenomatous Polyp: Prognosis
no risk, grossly flatter, sawtooth appearance of surface epithelium due to increased epithelium
Hyperplastic Polyp
Benign except for sessile serrated adenomas (SSAs)
Hyperplastic Polyp
Most lethal US cancer, average prognosis 1 y
Pancreatic Cancer
M>F, >50 yo, mean age 72, smoking, DM, family history
Pancreatic Ductal Adenocarcinoma (90% of Pancreatic Cancers): Epi/Risk Factors
k-ras mutation leads to p16/CDKN2a, leads to TP53 and SMAD4
pancreatic ductal adenocarcinoma: sporadic over time
BRCA2 and the pancreas
pancreatic ductal adenocarcinoma: familial mutation
hMLH1 and hMSH2
pancreatic ductal adenocarcinoma: sporadic or familial (5% of cancers)
most arise from exocrine cells, surrounded by dense stroma/fibrosis
pancreatic ductal adenocarcinoma
Sx: Painless jaundice, weight loss, linear lower back pain relieved in fetal position, malabsorption, depression. Histo: Loss of polarity and lobular architecture, atypia, neural invasion
Pancreatic Ductal Adenocarcinoma (90% of Pancreatic Cancers): Signs/Symptoms/Findings
diffuse upper abdominal pain
tail/body pancreatic cancer
obstructive jaundice (rare)
head pancreatic cancer, obstructs common bile duct
new onset diabetes (rare)
pancreatic cancer, secondary to destruction of pancrease
gastric outlet obstruction, gastric bleeding, pain and impaired motility, liver, bone, lung, CNS
pancreatic cancer metastasis
Poor (most present late stage), <4% 5-yr OS; biliary obstruction = better (since in head)
Pancreatic Ductal Adenocarcinoma (90% of Pancreatic Cancers): Prognosis
Tx: Whipple pancreatoduodenectomy if resectable (<20%); adjuvant chemo or radiation always, gemcitabine for palliative chemo
Pancreatic Ductal Adenocarcinoma (90% of Pancreatic Cancers): Treatment/Notes
Trousseau’s syndrome (hypercoagulability) if Lewis blood group antigens are >1000; redness and tenderness on palpation of hands and feet
complications of pancreatic ductal adenocarcinoma
Parenchymal necrosis, PMN infiltrate, bacterial or parasitic (amebiasis) if abscess, echinococcus if cyst
Liver Abscess or Cyst
Young women’s Livers
Hemangioma, Liver Cell adenoma, focal nodular hyperplasia
Large, painful, rarely rupture, veins > arteries, most common benign liver tumor
Hemangioma
No bile ducts, benign hepatocyte tumor, central scarring, arterial malformations
Liver Cell Adenoma
Too much perfusion, results in nodules resembling cirrhosis
Focal Nodular Hyperplasia
Most common tumor in liver
Metastatic Liver Cancer: Epi/Risk Factors
Desmoplasia, hemorrhage, central necrosis
Metastatic Liver Cancer: Signs/Symptoms/Findings
Commonly from colorectal, pancreas, lung breast
Metastatic Liver Cancer: Pathophysiology/Diagnosis
Elderly, M>F, cirrhosis; most common primary tumor
Hepatocellular Carcinoma (HCC): Epi/Risk Factors
Microtrabecular pattern, look normal but falling apart because of decreased adhesion molecules
Hepatocellular Carcinoma (HCC): Signs/Symptoms/Findings
75% have cirrhosis + serum AFP(+), HBV biggest cause worldwide, steatohepatitis is another common cause
Hepatocellular Carcinoma (HCC): Pathophysiology/Diagnosis
Invades veins (portal, hepatic, IVC to lungs)
Hepatocellular Carcinoma (HCC): Prognosis
Screen cirrhosis pts; Tx: transplant based on Milan criteria, resect if liver fxn good, RF ablation / chemoembolization, Sorafenib
Hepatocellular Carcinoma (HCC): Treatment/Notes
Young, 20s, no risk factors
Fibrolamellar Carcinoma of Liver: Epi/Risk Factors
Parallel lamellae of fibrosis + big hepatocytes
Fibrolamellar Carcinoma of Liver: Signs/Symptoms/Findings
Better prognosis than HCC
Fibrolamellar Carcinoma of Liver: Prognosis
Liver: Local resection
Fibrolamellar Carcinoma of Liver: Treatment/Notes
Malignant glands + desmoplasia
Cholangiocarcinoma: Signs/Symptoms/Findings AND Picture
Bile duct carcinoma; caused by liver flukes from fish, PSC, gallstone disease
Cholangiocarcinoma: Pathophysiology/Diagnosis AND Prognosis AND Treatment/Notes
Men in 40s
Biliary Cancers: Epi/Risk Factors
Caused by PSC, gallbladder dz, parasites, genetic; resect ± liver transplant
Biliary Cancers: Pathophysiology/Diagnosis AND Prognosis AND Treatment/Notes
M>F, smoking, achalasia, black
Squamous Cell Carcinoma (SCC): Epi/Risk Factors
Dysphagia, wt loss, dysplastic epithelium (GI/esophageal)
Squamous Cell Carcinoma (SCC): Signs/Symptoms/Findings
Dx: Upper endoscopy + biopsy
Squamous Cell Carcinoma (SCC): Pathophysiology/Diagnosis
Poor (37% localized, 3% met)
Squamous Cell Carcinoma (SCC): Prognosis
Early: EMR; Advanced: chemoradiation ± esophagectomy; Mets: palliative
Squamous Cell Carcinoma (SCC): Treatment/Notes
M>F, smoking, white, GERD
Esophageal Adenocarcinoma (EAC): Epi/Risk Factors
Dysphagia, wt loss, tends to be lower 1/3
Esophageal Adenocarcinoma (EAC): Signs/Symptoms/Findings
Dx: Upper endoscopy + biopsy
Esophageal Adenocarcinoma (EAC): Pathophysiology/Diagnosis
Poor (37% localized, 3% met)
Esophageal Adenocarcinoma (EAC): Prognosis
Early: EMR; Advanced: chemoradiation ± esophagectomy; Mets: palliative
Esophageal Adenocarcinoma (EAC): Treatment/Notes
Intestinal metaplasia 2/2 GERD can lead to EAC, EMR indicated in high grade dysplasia
Barrett’s Esophagus
M=F, Wt loss, Virchow’s node, Sis. Mary Joseph’s nodule, Krukenberg’s tumor, acanthosis nigricans
Diffuse Gastric Cancer: Signs/Symptoms/Findings
Signet ring cells, linitis plastica
Diffuse Gastric Cancer: Picture
AD inherited CDH1/E-cadherin mutations
Diffuse Gastric Cancer: Pathophysiology/Diagnosis
Poor, usually late stage
Diffuse Gastric Cancer: Prognosis
Prophylactic gastrectomy
Diffuse Gastric Cancer: Treatment/Notes
H. Pylori, M>F, developing
Intestinal Pattern Gastric Cancer: Epi/Risk Factors
Wt loss, Virchow’s node, Sis. Mary Joseph’s nodule, Krukenberg’s tumor, acanthosis nigricans
Intestinal Pattern Gastric Cancer: Signs/Symptoms/Findings
Resembles adenocarcinoma, gland-forming
Intestinal Pattern Gastric Cancer: Picture
Most common histology for early gastric cancer
Intestinal Pattern Gastric Cancer: Pathophysiology/Diagnosis
More likely to be caught early
Intestinal Pattern Gastric Cancer: Prognosis
Surgery + adjuvant chemo, trastuzumab if Her2(+), palliative if unresectable
Intestinal Pattern Gastric Cancer: Treatment/Notes
Gyn Cancer Mortality
ovarian>uterine>cervial>vulvar>vaginal
Gyn Cancer Incidence
uterine/endo>ovarain>cervical>vulvar>vaginal
poor middle aged female, young first intercourse, multiple partners, smoking, immunosuppression
Cervical Cancer: Epi/Risk Factors
bleeding: intermenstrrual, postcoital, heavy. Cachexia, wt. loss, anemia of chronic inflammation
Cervical Cancer: Signs/Symptoms/Findings
HPV16, 19 persistent infxn (10%) leads to viral encoded E6 (degrades p53) and E7 (increase DNA synth enzymes) leads to dysplasia, leads to cancer. HPV is causative agent (99.9%) along with other cofactors (OCPs, STDs, etc.)
Cervical Cancer: Pathophysiology/Diagnosis
Good but very stage-dependent
Cervical Cancer: Prognosis
Early: Radical surgery w/ adjuvant chemoradiation (cisplantin); Advanced: RT + brachy, chemo; Recurrent: no cure
Cervical Cancer: Treatment/Notes
80% of cervical cancer, ectocervix, eosinophils cytoplasm w/multiple nucleoli, premaginancy can be IDed on Pap
squamous cell type cervical cancer
10-15% of cervical cancer, arises in cervical canal
adenocarninoma type cervical cancer
Gardasil (HPV 16, 18, 6, 11) for M/F 9-26. most efficacy pre-sexual activity onset
Cervical cancer prevention
60 yo, post-menopausal
uterine cancer epi
obesity, estrogen replacement, tamoxifen, late menopause
uterine cancer risks
use of OCPs is protective
uterine cancer, ovarian cancer
HNPCC/Lynch (MLH1, MSH2/6, PMS2); PTEN or p53 LOF
etiologies of uterine cancer
poor prognosis in uterine cancer
sarcomas, arise in muscular wall of uterus
endo cancer in uterus
stage 1
endo cancer in uterus and cervix
stage 2
endo cancer in local pelvis tissue
stage 3
endo cancer with mets
stage 4
90-95% adenocarcinomas, rest sarcomas (carcino-sarcoma, leiomyosarcoma)
Uterine Cancer: Pathophysiology/Diagnosis
F, 50-70 yo, W>B, industrialized nations
Ovarian Cancer Epi
Abd/pelvic mass, early satiety, pain , ascites, N/V, pleural effusion, distention
Ovarian Cancer: Signs/Symptoms/Findings
increased # menstrual cycles, no OCP use, BRCA, HNPCC
ovarian cancer risks
use of OPC cuts Ovarian cancer risk
by half
10% from Hereditary Cancer Syndrome or HNPCC, 90% sporadic
Ovarian Cancer: Pathophysiology/Diagnosis
Poor, 70% advanced
Ovarian Cancer: Prognosis
Early: Surgery (TAH/BSO, lymphadenectomy / omentectomy) ± adjuvant chemo (carboplatin/paclitaxel); Advanced: Surgical cytoreduction + adjuvant chemo (IV or intraperitoneal) ± neoadjuvant; High relapse rate (80% advanced)
Ovarian Cancer: Treatment/Notes
Serous (fronds of papillary tissue), mucinous (glandular, mucinous, colonic-like tissue)
Epithelial Ovarian Tumors: Pathophysiology/Diagnosis
F 16-20, acute abdominal pain, fertility-conserving surgery, good prognosis, unique markers
Germ Cell tumor epi
dysgerminoma, yolk sac tumor, im/mature teratomas, embryonal carcinoma, choriocarcinoma, gonadoblastoma
Germ cell tumors
unique marker: LDH
germ cell tumor: dysgerminoma
unique marker: AFP, Schiller-Duval bodies (cleared out spaces around vessels)
germ cell tumor: yolk sac tumor
unique marker: hCG
germ cell tumor: choriocarcinoma
Sex cord stromal tumors arise from ovarian mesenchyme, leads to early sexual development, secrete estrogen, inhibin
Granulosa Cell Ovarian Tumors, Sertoli-Leydig Tumors
Call-Exner bodies, coffee-bean nuclei, secrete estrogen, inhibin
Granulosa Cell Ovarian Tumors
95% adult type, Tx: Surg
Granulosa Cell Ovarian Tumors: Pathophysiology/Diagnosis
Good prognosis gyn cancers
Granulosa Cell Ovarian Tumors, Germ cell tumors
Secrete androgen, poorly differentiated
Sertoli-Leydig Cell Tumors: Signs/Symptoms/Findings
Dysgerminoma (50%), yolk-sac tumors (20%)
Germ Cell Tumors: Pathophysiology/Diagnosis
smokers, obese, HTN
Renal Cell Carcinoma: Epi/Risk Factors
Nearly 50% found incidentally on CT, 1/3 met@dx; paraneoplastic syndromes
Renal Cell Carcinoma: Signs/Symptoms/Findings
Triad of hematuria, flank pain, abdominal mass only seen in 10%
Renal Cell Carcinoma: Picture
fever w/o infxn, hypercalcemia (due to PTHrP or prostaglandins), Erythrocytosis (Epo), cachexia, weight loss, anemia
Renal Cell carcinoma: pareneoplastic syndrome
HIF almost always involved: 75% clear cell (VHL gene mut), papillary (HPRC (MET pathway) or HLRCC), chromophobe or oncocytoma (Birt-Hogg Dube)
Renal Cell Carcinoma: Pathophysiology/Diagnosis AND Prognosis
Tx: nephrectomy (even if mets), sorafenib and sunitinib only decent treatments, mTOR inhibitors also approved
Renal Cell Carcinoma: Treatment/Notes
Hemangioblastomas in CNS, retina; pheochromocytoma
extrarenal renal cell carinoma presentation
loss of chro 3p (VHL)’ nests of clear cells, separated by delicate vascularture, most common
Clear Cell RCC, worst prognosis
chro 7 & 17 trisomy, cuboid to columnar epithelial cells lining fibrovascular cores, papillary architecture, 10-20%
Papillary RCC, more favorable prognosis than clear cell
loss of chro 1,6,10; sheets of eosinophils w/prominent PM and raisinoid nuclie, 5-10%
Chromophobe RCC, ver ygood prognosis
oncocytoma, collecting duct carcinoma, urothelial carcinoma
very rare RCC variants
limited to kidney, excellent 5y survival
stage 1 & 2 RCC
extrarenal invasion of veins, (renal vein to IVC), LN, or peri-renal tissue
stage 3 RCC
metastatic spread with relatively poor five year survival
stage 4 RCC
most common peds kidney cancer, 2-5 yo
Wilms Tumor (nephroblastoma)
LOF in Wt1 (11p13), from hereditary syndrome (denys-drash) or sporadic mutation
Wilms Tumor (nephroblastoma)
huge flank mass, grossly hemorrhagic with blastemal, stromal and epithelial (triphasic) elements
Wilms Tumor (nephroblastoma)
7-8% of renal cancers, arise from renal pelvis
epithelial carcinoma
Most common Ca and Ca death cause in 20-34yo
Testicular Cancer: Epi/Risk Factors
Most are germ cell tumors (95%)
testicular cancers (other: gonadal stromal and mesenchyme of supporting stroma)
15-35 y/o male, low mortality, white>black, asian
testicular cancer epi
most are malignant (95%)
Testicular tumors
cryptorchidism, HIV, estrogen/DES exposure in utero
Testicular Cancer: Risks
Choriocarcinoma - increased HCG; yolk sac + embryonal - increased AFP
Testicular Cancer: Picture
painless mass, dull ache or heavy sensation in lower abdomen, perianal area or scrotum, or acute pain
Testicular Cancer Presentation
40% seminoma, 30% NSGCT (choriocarcinoma, yolk sac, teratoma, embryonal)
Testicular Cancer: Pathophysiology/Diagnosis
Cure rate 95% but risk of 2° malig w/ Tx
Testicular Cancer: Prognosis
Seminoma Tx: surg + prophylactic XRT, chemo if fail; NSGCT: cisplatin, etoposide, bleomycin
Testicular Cancer: Treatment/Notes
increased APF and/or betaHCG +/- LDH
non-seminomatous testicular cancer
increased betaHCG +/- LDH
seminomatous testicular cancer
stromal tumor, benign, excess androgen leads to precocious puberty, gynecomastia
leydig cell tumor
bright yellow lipidy tumor with pink granular cytoplasm, Reinke crystals
leydig cell tumor
benign tumor from tunica mesothelium
adenomatoid tumor
most common testicular tumor in males over 50
malignant lymphoma
M>F, smoking, urine cytology
Bladder Cancer: Epi/Risk Factors/Dx
90-95% Transitional cell; localized (80%) and invasive cancers very different
Bladder Cancer: Pathophysiology/Diagnosis
Low invasion risk but field effects
Bladder Cancer: Prognosis
Early Tx: intravesical BCG; Invasive: radical cystectomy ± neoadjuvant chemo Mets: cisplatin combos
Bladder Cancer: Treatment/Notes
increased Age biggest factor, family Hx, black>white
Prostate Cancer: Epi/Risk Factors
Prevention hasn’t really panned out. PSA screening no longer recommended
Prostate Cancer: Signs/Symptoms/Findings
Loss of GSTP1 starts down road towards PTEN/p53/Rb/Myc loss
Prostate Cancer: Pathophysiology/Diagnosis
Localized Tx: brachytherapy, radical surg, fancy radiotherapy; Locally advanced: radiotherapy + neoadjuvant hormonal therapy; Mets: androgen ablation if high grade, hormonal tx if resistant
Prostate Cancer: Prognosis AND Treatment/Notes
M>F, 60-70yo, poor prognosis
Conventional Squamous Cell Carcinoma (SCC): Epi/Risk Factors
Histo: keratin pearls
Conventional Squamous Cell Carcinoma (SCC)
hoarseness: throat, nasal fullness and bleeding: nose; mass or ulcer: tongue
Conventional Squamous Cell Carcinoma (SCC)
Tobacco + EtOH are risk factors, loss of p16
Conventional Squamous Cell Carcinoma (SCC): Pathophysiology/Diagnosis
I&II: unimodal radiation. III (LN involvement): ? IV (mets or below clavicle): palliative
Conventional Squamous Cell Carcinoma (SCC): Treatment/Notes
M>F, oral sex, oropharynx, younger pt
HPV-Related SCC: Epi/Risk Factors
p16 overexpression, Generally non-keratinizing, better prognosis
HPV-Related SCC: Pathophysiology/Diagnosis
Geographic necrosis, perineural, bone, vascular invasion, infiltrative growth
Salivary Gland Cancer: Signs/Symptoms/Findings
Mucoepidermoid most common, adenoid cystic common in minor glands
Salivary Gland Cancer: Pathophysiology/Diagnosis
Peds, Embryonal good, alveolar (PAX-FKHR) bad
Rhabdomyosarcoma: Pathophysiology/Diagnosis AND Prognosis
Peds, Painless mass, sclerosis, Codman’s triangle, lace-like osteoid deposition on histology
Osteosarcoma: Epi/Risk Factors AND Signs/Symptoms/Findings
Peds: Small, round blue cell tumor, with anemia, permeating appearance on XR, increased ESR
Ewing’s Sarcoma
EWS-FLI1 gene product, responsive to chemo
Ewing’s Sarcoma
Lipid vesicles, adults
Liposarcoma: Signs/Symptoms/Findings AND Pathophysiology/Diagnosis
adultss, fibrous tissue, Spindled cells, uniform features
Fibrosarcoma: Signs/Symptoms/Findings AND Picture
adults: Malaligned smooth muscle fibers
Leiomyosarcoma: Signs/Symptoms/Findings AND Picture
aka Malignant fibrous histiocytoma, Not good prognosis
High Grade Undifferentiated Pleomorphic Sarcoma: Pathophysiology/Diagnosis
c-KIT mutation leads to sarcoma, treat w/Imatinib
GI Stromal Tumor (GIST)