Ne Oplasia Revi Ew Plu S
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NE OPLASIA REVI EW Plu s 9-18-2009 T. Davis
1. A new test for prostate cancer (PC) is developed. 90% of men wi th PC test positive. 80% of men wi th out PC test negative. 2. In a population of 1000 men, 30% (300 men) have the disease (the prevalence is 30%). Calculate sensitivity, specificity and PPV.
Sen sit ivit y a nd speci ficit y
90% sensitivity 90% of 1000 or 900 would be the tru e posit ive s 10% of 1000 or 100 would be the fals e neg at iv es
80% specificity 80% of 1000 or 800 would be the tru e nega tives 20% of 1000 or 200 would be the fa lse pos it ives
PPV (predictive value of a +) with a prevalence of 30%
410 men have a positive test: 270 TP (90%x300) and 140 FP (20%x700)
PPV= TP/FP+TP PPV= 270 / 270 + 140 270/410 or about 66%
Ca ncer P recu rsor L es ion s
________ Atyp. Hyp. Breast _______ Endom. Hyperplasia _________ Gastric metaplasia (Helicobacter) ___________
Sq. Cell CA __________ Adeno CA colon ___________ Esoph. Adeno CA _____________
Adeno CA liver
Ca ncer P recu rsor L es ion s
Actinic keratosis Atyp. Hyp. Breast Ulcerative Colitis Endom. Hyperplasia Esoph. Metaplasia (Barrett’s) Gastric metaplasia (Helicobacter)
Sq. Cell CA Ductal CA Adeno CA colon Adeno CA endom. Esoph. Adeno CA Gastric Adeno CA Adeno CA liver
Ca ncer P recu rsor L es ion s
Actinic keratosis __________ Ulcerative Colitis __________ Esoph. Metaplasia (Barrett’s) ___________ Cirrhosis
___________ Ductal CA ___________ Adeno CA endom. _____________ Gastric Adeno CA __________
Ca ncer P recu rsor L es ion s
Actinic keratosis Atyp. Hyp. Breast Ulcerative Colitis Endom. Hyperplasia Esoph. Metaplasia (Barrett’s) Gastric metaplasia (Helicobacter)
Sq. Cell CA Ductal CA Adeno CA colon Adeno CA endom. Esoph. Adeno CA Gastric Adeno CA Adeno CA liver
Precu rs or s ( 2)
____________
Adeno CA
Sq. Dysplasia/cervix, lung/larynx
___________
______________
Adeno CA colon
Precu rs or s ( 2)
Scar in lung
Adeno CA
Sq. Dysplasia/cervix, lung/larynx
Ss. Cell CA
Adenomatous polyp
Adeno CA colon
Precu rs or s ( 2)
Scar in lung
____________
____________
Ss. Cell CA
Adenomatous polyp
_____________
Precu rs or s ( 2)
Scar in lung
Adeno CA
Sq. Dysplasia/cervix, lung/larynx
Ss. Cell CA
Adenomatous polyp
Adeno CA colon
Malig nan t Tu mo rs a nd En docrin op athies
_________ ___________ ___________ ____________ Insulin/hypoglycemi ADH/hypoNa+ Erythropeitin/>Hct
Small Cell, Med. CA ChorioCA/testis SC CA/lung Med CA/thyroid Islet cell Small Cell Renal Cell, Hepatocellular CA
Malig nan t Tu mo rs a nd En docrin op athies
ACTH/Cushings HCG/gynecomastia PTH/hyperCa++ Calcitonin/hypoCa+ Insulin/hypoglycemi ADH/hypoNa+ Erythropeitin/>Hct
Small Cell, Med. CA ChorioCA/testis SquaC CA/lung Med CA/thyroid ___________ __________ _____________
Malig nan t Tu mo rs a nd En docrin op athies
ACTH/Cushings HCG/gynecomastia PTH/hyperCa++ Calcitonin/hypoCa+ Insulin/hypoglycemi ADH/hypoNa+ Erythropeitin/>Hct
_________ ___________ ____________ ___________ Islet cell Small Cell Renal Cell, Hepatocellular CA
Malig nan t Tu mo rs a nd En docrin op athies
ACTH/Cushings HCG/gynecomastia PTH/hyperCa++ Calcitonin/hypoCa+ _________ _________ ____________
Small Cell, Med. CA ChorioCA/testis SquaC CA/lung Med CA/thyroid Islet cell Small Cell Renal Cell, Hepatocellular CA
The f oll owi ng im ag e is mos t c/w wh ic h ma lign anc y
A. B. C. D. E.
Medullary Carcinoma of Thyroid Small cell carcinoma of Lung Sq. Cell Carcinoma of Lung Metastatic melanoma Renal Cell Adenocarcinoma
An s. C, SCC o f L ung
These tumors frequently make a parathormone-like substance
Ana pla si a = __ _____ ____ ______ __ Anaplasia is considered a hallmark of ______________. Anaplastic features include:
- ? ? ? ? - Undi ffere nt iat ed, po orl y di ffere nti at ed, hig h gr ade
Ana pl asi a = L ack
of diffe rentia ti on
Anaplasia is considered a hallmark of malignant transformation. Anaplastic features include:
- Cellular/nuclear pleomorphism - Increased nuclear-cytoplasmic ratio - Nuclear hyperchromasia (increased DNA content) - Large nucleoli - Und iffer ent iat ed , po orly dif fer ent iat ed , hig h g rade
GR AD ING TU MORS
__________ tumors only Look at: ? And ? Grades I-III/IV (higher grades are more __________) Important for some tumors: breast, prostate, endometrium, astocytomas Dysplasias of the cervix are “graded” Based on microscopic features
GR AD ING TU MORS
Malignant tumors only Differentiation and mitotic rate Grades I-III/IV (higher grades are more anaplastic) Important for some tumors: ?, ?, ?, ? Dysplasias of the cervix are “graded” Based on microscopic features
GR AD ING TU MORS
Malignant tumors only Differentiation and mitotic rate Grades I-III/IV (higher grades are more anaplastic) Important for some tumors: breast, prostate, endometrium, astocytomas Dysplasias of the cervix are “graded” Based on microscopic features
SP
SP
SP
SP
Squamous cell carcinoma with “squamous pearls” (SP)
SP
SP
Squamous Pearls (SP)
*
*
*
* Intercellular bridges (*)
Anaplastic rhabdomyosarcoma
STAGI NG TU MORS
How far has the tumor spread Malignant tumors only ?, ?, ? Staging often involves: the Pathologist, radiology or other imaging, lab tests (tumor markers) CIS is referred to as __ ___ __ ___
STAGI NG TUMORS
How far has the tumor spread Malignant tumors only Tumor size (T ), lymph node (N ) involvement, distant metastases (M ) Staging often involves: the Pathologist, radiology or other imaging, lab tests (tumor markers) CIS is referred to as Sta ge Zero
METASTA SIS
LIVER: (portal circulation) ______________ LUNG: breast, stomach, sarcomas BONE: 3rd most frequent site for ??; lung, breast, prostate, kidney, thyroid; PROSTATE to bone gives osteoblastic lesions on Xray and high serum alkaline phosphatase ADRENAL: most common ____________
METASTA SIS
LIVER: (portal circulation) GI tract and pancreas; lung, breast, melanomas LUNG: ?, ?, ? BONE: 3rd most frequent site for metastases; ?, ?, ?, ?, ?; PROSTATE to bone gives _____________ on Xray and high serum ______________ ADRENAL: most common endocrine site
METASTA SIS
LIVER: (portal circulation) GI tract and pancreas; lung, breast, melanomas LUNG: breast, stomach, sarcomas BONE: 3rd most frequent site for metastases; lung, breast, prostate, kidney, thyroid; PROSTATE to bone gives osteoblastic lesions on Xray and high serum alkaline phosphatase ADRENAL: most common endocrine site
Neop las ia Ca se
A 38-y.o. male has a family history of colectomies performed between ages 30 and 40. The slide shows the total colectomy specimen from this patient.
Familial polyposis
Tubular adenomas (adenomatous polyps)
AC
AC
Adenomatous Change (AC)
Carcinoma in situ
invasive
CO LON CANC ER
Grading is helpful/not very helpful STAGING: predicts _________ TNM Robbins Table 17-11
CO LON CANC ER
Grading is not very helpful STAGING: predicts clinical outcome TNM Robbins Table 17-11
Tu mor Siz e ( T)
Tis- ??? T1- ____________ T2- ___________ T3- ___________ T4- ______________
Tu mor Size ( T)
Tis- insitu; not through the muscularis mucosa T1- invades submucosa T2- into but not through the muscularis propria T3- through muscularis propria T4- invades adjacent organs
??? Staging System
TNM Staging System
Lymph Nodes ( N)
N0N1N2-
?? ?? ??
Lymph Nodes ( N)
N0N1N2-
no nodes involved 1-3 regional LNs 4+ regional LNs
Dis tant Met astas es (M)
M0- ?? M1- ??
*note Tx, Nx, Mx- can/cannot be assessed
Dis tant Met astas es (M)
M0- no distant metastasis M1- distant mets present
*note Tx, Nx, Mx- cannot be assessed
Whi ch of the f ollowi ng best desc ri bes th is d is easeco lon ca ncer?
A. Crohn’s Disease B. Ulcerative colitis C. Inactivation of a supressor gene D. X-linked recessive inheritance pattern E. Autosomal recessive inheritance pattern
An swer : C, in activ ation of AP C
This disorder is autosomal dominant with the APC supressor gene on chromosome 5.
CO LON CANC ER
OTHER 50% of colorectal carcinomas show “??” mutations; 50% of adenomas > 1cm show ________ mutations _________ can be used to follow patients after surgery- tumor monitoring Deeply infiltrating tumors cause ______ ____ __ and ???? appearance
CO LON CANC ER
OTHER 50% of colorectal carcinomas show “ras” mutations; 50% of adenomas > 1cm also show ras mutations CEA (carcinoembryonic Ag) can be used to follow patients after surgery- tumor monitoring Deeply infiltrating tumors cause des mop la si a and “apple core/ napkin-ring” appearance
????
?????
Normal
Adenocarcinoma
Tumor: napkin ring lesion
Normal, pretty!
Na me th e m ost c om mo n huma n tum or su presso r gen es a nd p ro to onc ogene (R ESPE CTIV ELY)
A. B. C. D. E.
P53 and RB P53 and RAS RB and RAS APC and P53 APC and RB
An swer : B, P 53 a nd R AS
P53 is the tumor supressor gene mutated in over 50% of human tumors. The mutation prevents DNA repair and inhibits apoptosis. The point mutation in the proto-oncogene RAS allows cell proliferation (GTP signal transduction) and is seen 30+% of human tumors
Wha t tu mo r m ar kers ar e usef ul in ma na gement o f co lon ca ncer?
A. CEA is used to monitor tumor recurrence B. CEA is used as a screening test for colon cancer C. CEA is used as a confirmation test if the test for occult blood is positive D. High PSA in serum is diagnostic E. High AFP in serum is diagnostic
An swer : A, u sed to mon it or t umor recu rre nce
CEA is not specific for colon cancer and not a sensitive test. CEA levels are determined pre- and post-surgery. The CEA level should fall to near zero. If the level falls and then increases, the patient may receive chemotherapy for the recurrence.
Tu mor Ma rk er s
Management Detection (staging) Diagnosis (screening)- PSA and CA 125
Marker s
? - colon, pancreas, stomach, lung, breast, (19% smokers, 3% gen. pop.) ?- hepatocellular, germ cell (>500ng/ml) ??- 80% non-mucinous ovarian CA ??- pancreatic CA (80%)
Marker s
CEA - colon, pancreas, stomach, lung, breast, (19% smokers, 3% gen. pop.) AFP- hepatocellular, germ cell (>500ng/ml) CA 125 - 80% non-mucinous ovarian CA CA 19-9- pancreatic CA (80%)
Marker s ( 2)
PSA- (?? ng/ml normal) (> ?? ng/ml highly suspicious); also ??? elevation in prostate CA assoc. with bone metastasis (osteoblastic) HCG- ?, ?
Marker s ( 2)
PSA- (0-4 ng/ml normal) (>10 ng/ml highly suspicious); also AlkPhos elevation in prostate CA assoc. with bone metastasis (osteoblastic) HCG- gestational trophoblastic tumors, testicular tumors
L
L
Benign breast ducts and lobules
Fibroadenoma
Fibroadenoma of breast
C
C CN
C
C CN
Intraductal carcinoma with cribbiforming (C) and comedonecrosis (CN)
Invasive CA
Stellate tumor
Mammogram shows a mass and Ca**
BR EA ST CAR CI NO MA GR AD ING
Bloom and Richardson ?? (1-3) ?? (1-3) ?? (1-3) Total score 3-5: Grade I Total score 6,7: Grade II Total score 8,9: Grade III
BR EA ST CAR CI NO MA GR AD ING
Bloom and Richardson Tubules present (1-3) Nuclear atypia (1-3) Mitoses (1-3) Total score 3-5: Grade I Total score 6,7: Grade II Total score 8,9: Grade III
Breast carcinoma- Grade I
BR EA ST CAR CI NO MA STAGI NG
Stage 0 (in situ or CIS): 5-year 92% Stage I. (<2 cm & LN-): 5-year 87% Stage II. (2-5 cm & 1-3 LN+): 5-year 75% *Stage III. (5 cm & >4 LN+): 5-year 46% Stage IV. Distant mets: 5-year 13%
Invasive (infiltrating) ductal carcinoma with lymphatic invasion
BR EA ST CAR CI NO MA
OTHER Estrogen receptor (+): tumor is stimulated by ?? and can be treated with the ?? This is palliation. HER-2 Neu amplification: by immunostaining or FISH. If HER-2 Neu is amplified (20%), the patient can be treated with ?? This is very expensive and tends to be used in high grade/high stage lesions that are ??
BR EA ST CAR CI NO MA
OTHER Estrogen receptor (+): tumor is stimulated by estrogen and can be treated with the “anti-estrogen” tamoxifen. This is palliation. HER-2 Neu amplification: by immunostaining or FISH. If HER-2 Neu is amplified (20%), the patient can be treated with Herceptin. This is very expensive and tends to be used in high grade/high stage lesions that are HER-2 Neu positive.
ER (+)
HER-2 Neu (+)
Sq uamou s Ca rcin om a of Cervix
? ? ? ? (<5mm below BM) ? (>5mm below BM Stage I: 5-year is 90% Stage II: 5-year is 70% Stage IV: 5-year is 10%
Sq uamou s Ca rcin om a of Cervix
Squamous metaplasia Dysplasia CIS Microinvasive cancer (<5mm below BM) Invasive cancer (>5mm below BM Stage I: 5-year is 90% Stage II: 5-year is 70% Stage IV: 5-year is 10%
HPV an d Cer vica l Ca ncer
HPV DNA types ? And ?: condyloma HPV ?, ?, ? others: carcinoma Viral protein _____ acts via retinoblastoma gene protein Viral protein E6 acts via ___________ Proliferation is stimulated and apoptosis is inhibited
HPV an d Cer vica l Ca ncer
HPV DNA types 6 and 11: condyloma HPV 16, 18, 13 others: carcinoma Viral protein E7 acts via retinoblastoma gene protein Viral protein E6 acts via to P53 (TP53). Proliferation is stimulated and apoptosis is inhibited
??
Endocervical glands
Squamous metaplasia
Normal epithelium shows maturation at the surface
Carcinoma Insitu
?
??
??
??
koilocyte
Normal
Moderate
Low Grade
Severe/CIS
?
?
K
K
Koilocytes (K)
??
Microinvasive Squamous Cell CA
Invasive squamous cell CA
Wha t i s the m ost s ensi ti ve te st f or hi gh gr ad e dy sp las ia of the c ervix ?
A. B. C. D. E. 16
Pap smear HPV DNA test for high risk types HPV test for DNA type 16 HPV test for DNA type 18 HPV serum antibodies to DNA type
HP V DNA is m ost s ensi ti ve te st f or Hi gh G ra de dy sp las ia
Pap smear 55% HPV DNA 95%
LUNG CANCE R
?, ?, and ?: can be cured by surgery if caught early (<1/3); radiation may offer _______; chemotherapy works _________ SMALL CELL carcinoma: “always” metastatic at diagnosis, therefore, surgery is not possible; chemotherapy an option but works poorly
LUNG CANCE R
Large cell carcinoma, adenocarcinoma and squamous cell carcinoma: can be cured by surgery if caught early (<1/3); radiation may offer palliation; chemotherapy works poorly SMALL CELL carcinoma: “always” _________ at diagnosis, therefore, surgery is/is not possible; chemotherapy an option but works poorly/well
LUNG CANCE R
Large cell carcinoma, adenocarcinoma and squamous cell carcinoma: can be cured by surgery if caught early (<1/3); radiation may offer palliation; chemotherapy works poorly SMALL CELL carcinoma: “always” metastatic at diagnosis, therefore, surgery is not possible; chemotherapy an option but works poorly
??
Normal
Squamous CA CIS
Bronchogenic CA
??
??
??
??
keratin
Nuclear molding
Squamous Cell Carcinoma
Small Cell Carcinoma
??
??
??
??
Squamous CA
Small cell undifferentiated carcinoma
Adeno CA
Large cell CA
Small Cell Carcinoma
??
Normal esophagus
??
Barrett’s syndrome
Para neop lastic Sy ndromes
_________ Eaton-Lambert _________ Seborrheic keratosis ___________
Adeno CA (gastric) __________ Bronchogenic CA __________
Pancreatic CA
Para neop lastic Sy ndromes
Acanthosis nigricans Eaton-Lambert Osteoarthropathy Seborrheic keratosis Migratory thrombophlebitis (Trousseau’s)
Adeno CA (gastric) Small Cell CA Bronchogenic CA Gastric CA
Pancreatic CA
Para neop lastic Sy ndromes
Acanthosis nigricans ______________ Osteoarthropathy ___________ Migratory thrombophlebitis (Trousseau’s)
_____________
Small Cell CA ___________ Gastric CA ______________
Para neop lastic Sy ndromes
Acanthosis nigricans Eaton-Lambert Osteoarthropathy Seborrheic keratosis Migratory thrombophlebitis (Trousseau’s)
Adeno CA (gastric) Small Cell CA Bronchogenic CA Gastric CA
Pancreatic CA
PARA NEO PLASTI C SY NDR OMES
Small Cell CA
_________
__________
Carcinoid tumor (lung or liver usually)
PTH-like (Hypercalcemia) _____________
PARA NEO PLASTI C SY NDRO MES
Small Cell CA
Squamous cell CA hypercalcemia
Carcinoid tumor (lung or liver usually)
ACTH (Cushings); ADH (iADH) PTH-like (Hypercalcemia) Serotonin, bradykinin (Carcinoid syndrome)
PARA NEO PLASTI C SY NDRO MES
_____________
Squamous cell CA hypercalcemia
____________
ACTH (Cushings); ADH (iADH) __________
Serotonin, bradykinin (Carcinoid syndrome)
PARA NEO PLASTI C SY NDRO MES
Small Cell CA
Squamous cell CA hypercalcemia
Carcinoid tumor (lung or liver usually)
ACTH (Cushings); ADH (iADH) PTH-like (Hypercalcemia) Serotonin, bradykinin (Carcinoid syndrome)
Vir uses a nd Ca ncer (RNA )
_____________
Hepatocellular
HTLV-1
____________
Vir uses a nd Ca ncer (RNA )
HCV HTLV-1
Hepatocellular
T-cell leukemia/ lymphoma
Vir uses a nd Ca ncer (RNA )
HCV ___________
_____________
T-cell leukemia/ lymphoma
Vir uses a nd Ca ncer (RNA )
HCV HTLV-1
Hepatocellular
T-cell leukemia/ lymphoma
Vir uses a nd Ca ncer (DNA)
_________
HBV (
Burkitt L., NP CA, MC Hodgkin ________ SC CA cervix, anus Same as HPV 16 ___________
Vir uses a nd Ca ncer (DNA)
EBV t(8;14)
HBV (
Burkitt L., NP CA, MC Hodgkin Hepatocellular CA SC CA cervix, anus Same as HPV 16 Kaposi’s sarcoma in AIDS
Vir uses a nd Ca ncer (DNA)
EBV t(8;14) ___________ ____________ HPV 18 (E7/RB) ___________
___________ Hepatocellular CA SC CA cervix, anus __________ Kaposi’s sarcoma in AIDS
Vir uses a nd Ca ncer (DNA)
EBV t(8;14)
HBV (
Burkitt L., NP CA, MC Hodgkin Hepatocellular CA SC CA cervix, anus Same as HPV 16 Kaposi’s sarcoma in AIDS
1. A new test for prostate cancer (PC) is developed. 90% of men wi th PC test positive. 80% of men wi th out PC test negative. 2. In a population of 1000 men, 30% (300 men) have the disease (the prevalence is 30%). Calculate sensitivity, specificity and PPV.
Sen sit ivit y a nd speci ficit y
90% sensitivity 90% of 1000 or 900 would be the tru e posit ive s 10% of 1000 or 100 would be the fals e neg at iv es
80% specificity 80% of 1000 or 800 would be the tru e nega tives 20% of 1000 or 200 would be the fa lse pos it ives
PPV (predictive value of a +) with a prevalence of 30%
410 men have a positive test: 270 TP (90%x300) and 140 FP (20%x700)
PPV= TP/FP+TP PPV= 270 / 270 + 140 270/410 or about 66%
Ca ncer P recu rsor L es ion s
________ Atyp. Hyp. Breast _______ Endom. Hyperplasia _________ Gastric metaplasia (Helicobacter) ___________
Sq. Cell CA __________ Adeno CA colon ___________ Esoph. Adeno CA _____________
Adeno CA liver
Ca ncer P recu rsor L es ion s
Actinic keratosis Atyp. Hyp. Breast Ulcerative Colitis Endom. Hyperplasia Esoph. Metaplasia (Barrett’s) Gastric metaplasia (Helicobacter)
Sq. Cell CA Ductal CA Adeno CA colon Adeno CA endom. Esoph. Adeno CA Gastric Adeno CA Adeno CA liver
Ca ncer P recu rsor L es ion s
Actinic keratosis __________ Ulcerative Colitis __________ Esoph. Metaplasia (Barrett’s) ___________ Cirrhosis
___________ Ductal CA ___________ Adeno CA endom. _____________ Gastric Adeno CA __________
Ca ncer P recu rsor L es ion s
Actinic keratosis Atyp. Hyp. Breast Ulcerative Colitis Endom. Hyperplasia Esoph. Metaplasia (Barrett’s) Gastric metaplasia (Helicobacter)
Sq. Cell CA Ductal CA Adeno CA colon Adeno CA endom. Esoph. Adeno CA Gastric Adeno CA Adeno CA liver
Precu rs or s ( 2)
____________
Adeno CA
Sq. Dysplasia/cervix, lung/larynx
___________
______________
Adeno CA colon
Precu rs or s ( 2)
Scar in lung
Adeno CA
Sq. Dysplasia/cervix, lung/larynx
Ss. Cell CA
Adenomatous polyp
Adeno CA colon
Precu rs or s ( 2)
Scar in lung
____________
____________
Ss. Cell CA
Adenomatous polyp
_____________
Precu rs or s ( 2)
Scar in lung
Adeno CA
Sq. Dysplasia/cervix, lung/larynx
Ss. Cell CA
Adenomatous polyp
Adeno CA colon
Malig nan t Tu mo rs a nd En docrin op athies
_________ ___________ ___________ ____________ Insulin/hypoglycemi ADH/hypoNa+ Erythropeitin/>Hct
Small Cell, Med. CA ChorioCA/testis SC CA/lung Med CA/thyroid Islet cell Small Cell Renal Cell, Hepatocellular CA
Malig nan t Tu mo rs a nd En docrin op athies
ACTH/Cushings HCG/gynecomastia PTH/hyperCa++ Calcitonin/hypoCa+ Insulin/hypoglycemi ADH/hypoNa+ Erythropeitin/>Hct
Small Cell, Med. CA ChorioCA/testis SquaC CA/lung Med CA/thyroid ___________ __________ _____________
Malig nan t Tu mo rs a nd En docrin op athies
ACTH/Cushings HCG/gynecomastia PTH/hyperCa++ Calcitonin/hypoCa+ Insulin/hypoglycemi ADH/hypoNa+ Erythropeitin/>Hct
_________ ___________ ____________ ___________ Islet cell Small Cell Renal Cell, Hepatocellular CA
Malig nan t Tu mo rs a nd En docrin op athies
ACTH/Cushings HCG/gynecomastia PTH/hyperCa++ Calcitonin/hypoCa+ _________ _________ ____________
Small Cell, Med. CA ChorioCA/testis SquaC CA/lung Med CA/thyroid Islet cell Small Cell Renal Cell, Hepatocellular CA
The f oll owi ng im ag e is mos t c/w wh ic h ma lign anc y
A. B. C. D. E.
Medullary Carcinoma of Thyroid Small cell carcinoma of Lung Sq. Cell Carcinoma of Lung Metastatic melanoma Renal Cell Adenocarcinoma
An s. C, SCC o f L ung
These tumors frequently make a parathormone-like substance
Ana pla si a = __ _____ ____ ______ __ Anaplasia is considered a hallmark of ______________. Anaplastic features include:
- ? ? ? ? - Undi ffere nt iat ed, po orl y di ffere nti at ed, hig h gr ade
Ana pl asi a = L ack
of diffe rentia ti on
Anaplasia is considered a hallmark of malignant transformation. Anaplastic features include:
- Cellular/nuclear pleomorphism - Increased nuclear-cytoplasmic ratio - Nuclear hyperchromasia (increased DNA content) - Large nucleoli - Und iffer ent iat ed , po orly dif fer ent iat ed , hig h g rade
GR AD ING TU MORS
__________ tumors only Look at: ? And ? Grades I-III/IV (higher grades are more __________) Important for some tumors: breast, prostate, endometrium, astocytomas Dysplasias of the cervix are “graded” Based on microscopic features
GR AD ING TU MORS
Malignant tumors only Differentiation and mitotic rate Grades I-III/IV (higher grades are more anaplastic) Important for some tumors: ?, ?, ?, ? Dysplasias of the cervix are “graded” Based on microscopic features
GR AD ING TU MORS
Malignant tumors only Differentiation and mitotic rate Grades I-III/IV (higher grades are more anaplastic) Important for some tumors: breast, prostate, endometrium, astocytomas Dysplasias of the cervix are “graded” Based on microscopic features
SP
SP
SP
SP
Squamous cell carcinoma with “squamous pearls” (SP)
SP
SP
Squamous Pearls (SP)
*
*
*
* Intercellular bridges (*)
Anaplastic rhabdomyosarcoma
STAGI NG TU MORS
How far has the tumor spread Malignant tumors only ?, ?, ? Staging often involves: the Pathologist, radiology or other imaging, lab tests (tumor markers) CIS is referred to as __ ___ __ ___
STAGI NG TUMORS
How far has the tumor spread Malignant tumors only Tumor size (T ), lymph node (N ) involvement, distant metastases (M ) Staging often involves: the Pathologist, radiology or other imaging, lab tests (tumor markers) CIS is referred to as Sta ge Zero
METASTA SIS
LIVER: (portal circulation) ______________ LUNG: breast, stomach, sarcomas BONE: 3rd most frequent site for ??; lung, breast, prostate, kidney, thyroid; PROSTATE to bone gives osteoblastic lesions on Xray and high serum alkaline phosphatase ADRENAL: most common ____________
METASTA SIS
LIVER: (portal circulation) GI tract and pancreas; lung, breast, melanomas LUNG: ?, ?, ? BONE: 3rd most frequent site for metastases; ?, ?, ?, ?, ?; PROSTATE to bone gives _____________ on Xray and high serum ______________ ADRENAL: most common endocrine site
METASTA SIS
LIVER: (portal circulation) GI tract and pancreas; lung, breast, melanomas LUNG: breast, stomach, sarcomas BONE: 3rd most frequent site for metastases; lung, breast, prostate, kidney, thyroid; PROSTATE to bone gives osteoblastic lesions on Xray and high serum alkaline phosphatase ADRENAL: most common endocrine site
Neop las ia Ca se
A 38-y.o. male has a family history of colectomies performed between ages 30 and 40. The slide shows the total colectomy specimen from this patient.
Familial polyposis
Tubular adenomas (adenomatous polyps)
AC
AC
Adenomatous Change (AC)
Carcinoma in situ
invasive
CO LON CANC ER
Grading is helpful/not very helpful STAGING: predicts _________ TNM Robbins Table 17-11
CO LON CANC ER
Grading is not very helpful STAGING: predicts clinical outcome TNM Robbins Table 17-11
Tu mor Siz e ( T)
Tis- ??? T1- ____________ T2- ___________ T3- ___________ T4- ______________
Tu mor Size ( T)
Tis- insitu; not through the muscularis mucosa T1- invades submucosa T2- into but not through the muscularis propria T3- through muscularis propria T4- invades adjacent organs
??? Staging System
TNM Staging System
Lymph Nodes ( N)
N0N1N2-
?? ?? ??
Lymph Nodes ( N)
N0N1N2-
no nodes involved 1-3 regional LNs 4+ regional LNs
Dis tant Met astas es (M)
M0- ?? M1- ??
*note Tx, Nx, Mx- can/cannot be assessed
Dis tant Met astas es (M)
M0- no distant metastasis M1- distant mets present
*note Tx, Nx, Mx- cannot be assessed
Whi ch of the f ollowi ng best desc ri bes th is d is easeco lon ca ncer?
A. Crohn’s Disease B. Ulcerative colitis C. Inactivation of a supressor gene D. X-linked recessive inheritance pattern E. Autosomal recessive inheritance pattern
An swer : C, in activ ation of AP C
This disorder is autosomal dominant with the APC supressor gene on chromosome 5.
CO LON CANC ER
OTHER 50% of colorectal carcinomas show “??” mutations; 50% of adenomas > 1cm show ________ mutations _________ can be used to follow patients after surgery- tumor monitoring Deeply infiltrating tumors cause ______ ____ __ and ???? appearance
CO LON CANC ER
OTHER 50% of colorectal carcinomas show “ras” mutations; 50% of adenomas > 1cm also show ras mutations CEA (carcinoembryonic Ag) can be used to follow patients after surgery- tumor monitoring Deeply infiltrating tumors cause des mop la si a and “apple core/ napkin-ring” appearance
????
?????
Normal
Adenocarcinoma
Tumor: napkin ring lesion
Normal, pretty!
Na me th e m ost c om mo n huma n tum or su presso r gen es a nd p ro to onc ogene (R ESPE CTIV ELY)
A. B. C. D. E.
P53 and RB P53 and RAS RB and RAS APC and P53 APC and RB
An swer : B, P 53 a nd R AS
P53 is the tumor supressor gene mutated in over 50% of human tumors. The mutation prevents DNA repair and inhibits apoptosis. The point mutation in the proto-oncogene RAS allows cell proliferation (GTP signal transduction) and is seen 30+% of human tumors
Wha t tu mo r m ar kers ar e usef ul in ma na gement o f co lon ca ncer?
A. CEA is used to monitor tumor recurrence B. CEA is used as a screening test for colon cancer C. CEA is used as a confirmation test if the test for occult blood is positive D. High PSA in serum is diagnostic E. High AFP in serum is diagnostic
An swer : A, u sed to mon it or t umor recu rre nce
CEA is not specific for colon cancer and not a sensitive test. CEA levels are determined pre- and post-surgery. The CEA level should fall to near zero. If the level falls and then increases, the patient may receive chemotherapy for the recurrence.
Tu mor Ma rk er s
Management Detection (staging) Diagnosis (screening)- PSA and CA 125
Marker s
? - colon, pancreas, stomach, lung, breast, (19% smokers, 3% gen. pop.) ?- hepatocellular, germ cell (>500ng/ml) ??- 80% non-mucinous ovarian CA ??- pancreatic CA (80%)
Marker s
CEA - colon, pancreas, stomach, lung, breast, (19% smokers, 3% gen. pop.) AFP- hepatocellular, germ cell (>500ng/ml) CA 125 - 80% non-mucinous ovarian CA CA 19-9- pancreatic CA (80%)
Marker s ( 2)
PSA- (?? ng/ml normal) (> ?? ng/ml highly suspicious); also ??? elevation in prostate CA assoc. with bone metastasis (osteoblastic) HCG- ?, ?
Marker s ( 2)
PSA- (0-4 ng/ml normal) (>10 ng/ml highly suspicious); also AlkPhos elevation in prostate CA assoc. with bone metastasis (osteoblastic) HCG- gestational trophoblastic tumors, testicular tumors
L
L
Benign breast ducts and lobules
Fibroadenoma
Fibroadenoma of breast
C
C CN
C
C CN
Intraductal carcinoma with cribbiforming (C) and comedonecrosis (CN)
Invasive CA
Stellate tumor
Mammogram shows a mass and Ca**
BR EA ST CAR CI NO MA GR AD ING
Bloom and Richardson ?? (1-3) ?? (1-3) ?? (1-3) Total score 3-5: Grade I Total score 6,7: Grade II Total score 8,9: Grade III
BR EA ST CAR CI NO MA GR AD ING
Bloom and Richardson Tubules present (1-3) Nuclear atypia (1-3) Mitoses (1-3) Total score 3-5: Grade I Total score 6,7: Grade II Total score 8,9: Grade III
Breast carcinoma- Grade I
BR EA ST CAR CI NO MA STAGI NG
Stage 0 (in situ or CIS): 5-year 92% Stage I. (<2 cm & LN-): 5-year 87% Stage II. (2-5 cm & 1-3 LN+): 5-year 75% *Stage III. (5 cm & >4 LN+): 5-year 46% Stage IV. Distant mets: 5-year 13%
Invasive (infiltrating) ductal carcinoma with lymphatic invasion
BR EA ST CAR CI NO MA
OTHER Estrogen receptor (+): tumor is stimulated by ?? and can be treated with the ?? This is palliation. HER-2 Neu amplification: by immunostaining or FISH. If HER-2 Neu is amplified (20%), the patient can be treated with ?? This is very expensive and tends to be used in high grade/high stage lesions that are ??
BR EA ST CAR CI NO MA
OTHER Estrogen receptor (+): tumor is stimulated by estrogen and can be treated with the “anti-estrogen” tamoxifen. This is palliation. HER-2 Neu amplification: by immunostaining or FISH. If HER-2 Neu is amplified (20%), the patient can be treated with Herceptin. This is very expensive and tends to be used in high grade/high stage lesions that are HER-2 Neu positive.
ER (+)
HER-2 Neu (+)
Sq uamou s Ca rcin om a of Cervix
? ? ? ? (<5mm below BM) ? (>5mm below BM Stage I: 5-year is 90% Stage II: 5-year is 70% Stage IV: 5-year is 10%
Sq uamou s Ca rcin om a of Cervix
Squamous metaplasia Dysplasia CIS Microinvasive cancer (<5mm below BM) Invasive cancer (>5mm below BM Stage I: 5-year is 90% Stage II: 5-year is 70% Stage IV: 5-year is 10%
HPV an d Cer vica l Ca ncer
HPV DNA types ? And ?: condyloma HPV ?, ?, ? others: carcinoma Viral protein _____ acts via retinoblastoma gene protein Viral protein E6 acts via ___________ Proliferation is stimulated and apoptosis is inhibited
HPV an d Cer vica l Ca ncer
HPV DNA types 6 and 11: condyloma HPV 16, 18, 13 others: carcinoma Viral protein E7 acts via retinoblastoma gene protein Viral protein E6 acts via to P53 (TP53). Proliferation is stimulated and apoptosis is inhibited
??
Endocervical glands
Squamous metaplasia
Normal epithelium shows maturation at the surface
Carcinoma Insitu
?
??
??
??
koilocyte
Normal
Moderate
Low Grade
Severe/CIS
?
?
K
K
Koilocytes (K)
??
Microinvasive Squamous Cell CA
Invasive squamous cell CA
Wha t i s the m ost s ensi ti ve te st f or hi gh gr ad e dy sp las ia of the c ervix ?
A. B. C. D. E. 16
Pap smear HPV DNA test for high risk types HPV test for DNA type 16 HPV test for DNA type 18 HPV serum antibodies to DNA type
HP V DNA is m ost s ensi ti ve te st f or Hi gh G ra de dy sp las ia
Pap smear 55% HPV DNA 95%
LUNG CANCE R
?, ?, and ?: can be cured by surgery if caught early (<1/3); radiation may offer _______; chemotherapy works _________ SMALL CELL carcinoma: “always” metastatic at diagnosis, therefore, surgery is not possible; chemotherapy an option but works poorly
LUNG CANCE R
Large cell carcinoma, adenocarcinoma and squamous cell carcinoma: can be cured by surgery if caught early (<1/3); radiation may offer palliation; chemotherapy works poorly SMALL CELL carcinoma: “always” _________ at diagnosis, therefore, surgery is/is not possible; chemotherapy an option but works poorly/well
LUNG CANCE R
Large cell carcinoma, adenocarcinoma and squamous cell carcinoma: can be cured by surgery if caught early (<1/3); radiation may offer palliation; chemotherapy works poorly SMALL CELL carcinoma: “always” metastatic at diagnosis, therefore, surgery is not possible; chemotherapy an option but works poorly
??
Normal
Squamous CA CIS
Bronchogenic CA
??
??
??
??
keratin
Nuclear molding
Squamous Cell Carcinoma
Small Cell Carcinoma
??
??
??
??
Squamous CA
Small cell undifferentiated carcinoma
Adeno CA
Large cell CA
Small Cell Carcinoma
??
Normal esophagus
??
Barrett’s syndrome
Para neop lastic Sy ndromes
_________ Eaton-Lambert _________ Seborrheic keratosis ___________
Adeno CA (gastric) __________ Bronchogenic CA __________
Pancreatic CA
Para neop lastic Sy ndromes
Acanthosis nigricans Eaton-Lambert Osteoarthropathy Seborrheic keratosis Migratory thrombophlebitis (Trousseau’s)
Adeno CA (gastric) Small Cell CA Bronchogenic CA Gastric CA
Pancreatic CA
Para neop lastic Sy ndromes
Acanthosis nigricans ______________ Osteoarthropathy ___________ Migratory thrombophlebitis (Trousseau’s)
_____________
Small Cell CA ___________ Gastric CA ______________
Para neop lastic Sy ndromes
Acanthosis nigricans Eaton-Lambert Osteoarthropathy Seborrheic keratosis Migratory thrombophlebitis (Trousseau’s)
Adeno CA (gastric) Small Cell CA Bronchogenic CA Gastric CA
Pancreatic CA
PARA NEO PLASTI C SY NDR OMES
Small Cell CA
_________
__________
Carcinoid tumor (lung or liver usually)
PTH-like (Hypercalcemia) _____________
PARA NEO PLASTI C SY NDRO MES
Small Cell CA
Squamous cell CA hypercalcemia
Carcinoid tumor (lung or liver usually)
ACTH (Cushings); ADH (iADH) PTH-like (Hypercalcemia) Serotonin, bradykinin (Carcinoid syndrome)
PARA NEO PLASTI C SY NDRO MES
_____________
Squamous cell CA hypercalcemia
____________
ACTH (Cushings); ADH (iADH) __________
Serotonin, bradykinin (Carcinoid syndrome)
PARA NEO PLASTI C SY NDRO MES
Small Cell CA
Squamous cell CA hypercalcemia
Carcinoid tumor (lung or liver usually)
ACTH (Cushings); ADH (iADH) PTH-like (Hypercalcemia) Serotonin, bradykinin (Carcinoid syndrome)
Vir uses a nd Ca ncer (RNA )
_____________
Hepatocellular
HTLV-1
____________
Vir uses a nd Ca ncer (RNA )
HCV HTLV-1
Hepatocellular
T-cell leukemia/ lymphoma
Vir uses a nd Ca ncer (RNA )
HCV ___________
_____________
T-cell leukemia/ lymphoma
Vir uses a nd Ca ncer (RNA )
HCV HTLV-1
Hepatocellular
T-cell leukemia/ lymphoma
Vir uses a nd Ca ncer (DNA)
_________
HBV (
Burkitt L., NP CA, MC Hodgkin ________ SC CA cervix, anus Same as HPV 16 ___________
Vir uses a nd Ca ncer (DNA)
EBV t(8;14)
HBV (
Burkitt L., NP CA, MC Hodgkin Hepatocellular CA SC CA cervix, anus Same as HPV 16 Kaposi’s sarcoma in AIDS
Vir uses a nd Ca ncer (DNA)
EBV t(8;14) ___________ ____________ HPV 18 (E7/RB) ___________
___________ Hepatocellular CA SC CA cervix, anus __________ Kaposi’s sarcoma in AIDS
Vir uses a nd Ca ncer (DNA)
EBV t(8;14)
HBV (
Burkitt L., NP CA, MC Hodgkin Hepatocellular CA SC CA cervix, anus Same as HPV 16 Kaposi’s sarcoma in AIDS
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