5Indagini istologiche e preservazione della fertilita (S. Carinelli).

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5Indagini istologiche e preservazione della fertilita (S. Carinelli).
Caravaggio 16 – 18 maggio, 2013
Maternità e Tumori
Indagini istologiche
e
Preservazione della fertilità
Silvestro Carinelli
Istituto Europeo di Oncologia
Modern and Practical Problems
Endometrium
Syndromic cancer
BRCA
Lynch
Histologic Alterations in Endometrial Hyperplasia and
Well-differentiated Carcinoma Treated With Progestins
Darren T. Wheeler, Robert E. Bristow, and Robert J. Kurman
Am J Surg Pathol 2007;31:988–998
Classification
Progestin-treated Lesions of the Endometrium
Progestin-treated CH
No cytologic atypia with crowded, back-to-back
glands and/or a confluent glandular pattern
(cribriform and/or papillary pattern)
Progestin-treated CAH
Cytologic atypia with crowded, back-to-back glands
that lack a confluent glandular pattern
Progestin-treated SAH
Cytologic atypia with widely spaced glands
Progestin-treated G1 AdCa
Cytologic atypia with confluent glandular pattern
(cribriform and/or papillary pattern)
Jolie: "Ho tolto i seni per salvarmi dal cancro"
Comunità scientifica divisa
L'attrice parla della sua doppia mastectomia:
il rischio di cancro al seno è sceso dall'87% a meno del 5%.
Prima di lei l'aveva fatto Sharon Osbourne.
Il parere dei medici:
secondo Veronesi, non è una via obbligata
HEREDITARY SUSCEPTIBILITY
TO OVARIAN CANCER
__________________________________________________________________
BRCA2 (30%)
BRCA1 (65%)
HNPCC (5%)
Hereditary (10%)
Sporadic (90%)
Piek JM, van Diest PJ, Zweemer RP, et al.
Dysplastic changes in prophylactically removed Fallopian tubes of
women predisposed to developing ovarian cancer.
J Pathol. 2001;195:451–456
Piek JM, van Diest PJ, Zweemer RP, et al.
Tubal ligation and risk of ovarian cancer.
Lancet. 2001;358:844
Piek JM, Verheijen RH, Kenemans P, et al.
BRCA1/2-related ovarian cancers are of tubal origin: a hypothesis.
Gynecol Oncol. 2003;90:491
… we postulate that most (hereditary) serous carcinomas do originate from
Fallopian tube epithelium and not from the ovarian surface epithelium.
Prophylactic oophorectomy in BRCA1 and BRCA2 carriers
__________________________________________________________________
Rebbeck et al.
Kauff et al.
Powel et al.
Finch et al.
Pts
age
259
98
67
159
42.0
47.8
47
47.7
Occult Ca
6 (2.3%)
3 ( 3%)
7 (10.4%)
7 (4.4%)
age
46.9
50.6
50
Rebbeck et al. N Engl J Med 2002;346:1616-1622.
Kauff et al. N Engl J Med 2002;346:1609-1615.
Powel et al. J Clin Oncol 2005;23:127-132.
Finch et al. Gynecol Oncol 2006;100:58-64.
Coexisting serous carcinomas
on the tubal fimbria (A–D) and ovarian surface (E).
Kindelberger DW, et al. Am J Surg Pathol 2007;31:161-169
A proposed model for the pathogenesis of pelvic serous carcinoma.
Kindelberger DW, et al. Am J Surg Pathol 2007;31:161-169
CARCINOMA OF ENDOMETRIUM
“type one”
PTEN (30-60%)
MI (20-30%)
PIK3CA
K-ras (10-20%)
beta-catenin (28-35%)
Lynch syndrome
Hereditary non-polyposis colorectal cancer (HNPCC)
o Colon-rectum
o Endometrium
o Ovary
o Renal pelvis and ureter
o Stomach, pancreas and small bowel
o Brain
Lynch syndrome
pathogenic germline mutations in one of the DNA mismatch-repair genes
o MLH1
o MSH2
o MSH6
o PMS2
Lynch syndrome
Women w Lynch
o Incidence EC = CRC
o First sentinel EC = 50%
o Mutation in EC
total = 1.8 – 2.1 %
<50yr = 9%
Lynch syndrome
o Population incidence abt 1/370
o In Italy abt 162,000/60,000,000 people
o <1.2% of individuals with LS are aware
of their diagnosis at present
Colorectal carcinoma. Loss of PMS2 (A); note the presence of staining for MLH1 (B), MSH2 (C), and MSH6 (D).
Shia J et al. Am J Surg Pathol 2009;33:1639-1645.
Colorectal carcinoma. Isolated loss of MSH6 (A); presence of staining for MSH2 (B), MLH1 (C), and PMS2 (D)
Shia J et al. Am J Surg Pathol 2009;33:1639-1645.
MLH1
MSH2
MSH6
PMS2
Garg K. Am J Surg Pathol 2009;33:925-933
OUI
ALGORITHM
1° step
<50yr
>50yr + personal or family hystory
endometrial morphology or LUS
synchronous ovarian CCC
2° step
IHC-MMR MLH1/PMS2 loss >see DNA HyM
MSH2/MSH6
3° step Gene mutation analysis

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