Division of Surgical, Molecular and Ultrastructural Pathology University of Pisa Pisa University...

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


prognosis:

worst than in cases with known primary

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matter of size


0 mm

few mm


0 mm: SPONTANEOUS REGRESSION

few mm


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



PRE – IMAGING

ERA

The lesson of Anatomy of Dott. Nicolaes Tulp Rembrandt, 1632

Prof. Rupert A WILLIS

1898 - 1980

in case of


LUNG

IMAGING & MOLECULAR PROFILING

lung

pancreas

liver / bile ducts

kidney / adrenals

bowel

genital system

stomach

bladder / ureter

breast

smallvery

aggressive


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


early acquisition of

the invasive

genotype / phenotype


early acquisition of

the invasive

genotype / phenotype

small primary

early metastasis

bad prognosis

PRIMARY METor =

PRIMARYMET

molecular characterization for molecular therapy

Division of Surgical, Molecular and Ultrastructural Pathology University of Pisa Pisa University...

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