Division of Surgical, Molecular and Ultrastructural
Pathology
Division of Surgical, Molecular and Ultrastructural
Pathology
University of Pisa
Pisa University Hospital
[email protected]@med.unipi.it
Research Doctorate in Molecular and Experimental Oncology
1343 1338
UNKNOWN PRIMARY TUMORS
a vanishing chapter of pathology
METASTASIS PRIMARY
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CUP – Carcinoma of Unknown Primary
UPC – Unknown Primary Cancer
ACUP – Adeno Carcinoma of Unknown Primary
UPT – Unknown Primary Tumor
OPT – Occult Primary Tumor
a biopsy-proven metastatic malignancy
this diagnosis requires:
after a thorough clinical evaluation that includes physical examination and laboratory and imaging diagnostic tests
no identifiable primary tumor
5 % of all metastatic cancer
CUP - UPC - UPT - OPT
source identification:
- molecular profiling: 60 – 85 %
- morphology, IHC: 20 – 30 % of cases
CUP - UPC - UPT - OPT
prognosis:
worst than in cases with known primary
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CUP - UPC - UPT - OPT
matter of size
CUP - UPC - UPT - OPT
0 mm
few mm
CUP - UPC - UPT - OPT
0 mm: SPONTANEOUS REGRESSION
few mm
CUP - UPC - UPT - OPT
SPONTANEOUS REGRESSION of a TUMOR
1 : 60,000 – 100,000 cases
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SPONTANEOUS REGRESSION of a CANCER
1 : 60,000 – 100,000 cases
ischemia
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immune response
“unofficial” chemical compounds
Hicks AM et al:Transferable anticancer innate immunity in spontaneous regression/complete resistance mice. PNAS 103: 7753–7758, 2006
size imaging
CUP - UPC - UPT - OPT
CUP - UPC - UPT - OPT
PRE – IMAGING
ERA
The lesson of Anatomy of Dott. Nicolaes Tulp Rembrandt, 1632
Prof. Rupert A WILLIS
1898 - 1980
in case of
CUP - UPC - UPT - OPT
LUNG
IMAGING & MOLECULAR PROFILING
lung
pancreas
liver / bile ducts
kidney / adrenals
bowel
genital system
stomach
bladder / ureter
breast
smallvery
aggressive
CUP - UPC - UPT - OPT
ductal; NOS: not otherwise specified; NST: no special type
lobular
tubular / cribriform
medullary
mucinous
papillarymetaplasticapocrine
80%
10%
6%2%
2%
1%
< 1%< 1%
breast carcinoma
DUCTAL LOBULAR
sexual maturityaging
pre-puberal
DCIS LCIS
INFILTRATING DUCTAL CARCINOMA
DCIS: FREQUENT
LCIS: RARE
INFILTRATING LOBULAR CARCINOMA
LOBULAR
early loss of intercellular junctions
DUCTAL
late loss of intercellular junctions
terminal duct – lobule unit
ductal carcinoma
lobular carcinoma
UNFOLDING of the LOBULE
DESTRUCTION of the LOBULE
natural history of a carcinoma
1 initiation: 2 promotion:
3 progression:
normal
hyperplastic
atypical
cancer
invasive
metastatic
invasive ca metastasis clones
vascular invasion
CUP - UPC - UPT - OPT
early acquisition of
the invasive
genotype / phenotype
CUP - UPC - UPT - OPT
early acquisition of
the invasive
genotype / phenotype
small primary
early metastasis
bad prognosis
PRIMARY METor =
PRIMARYMET
molecular characterization for molecular therapy