Adenoma cancerizzato con
infiltrazione sottomucosa: chirurgia o
follow up?
Dottor Claudio Avellini
Triveneta di Chirurgia
marzo 2009
Polipectomia endoscopica
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The choice between surveillance and major surgery when an
endoscopically removed polyp is found to be an ACIC will depend on
its metastatic potential, ranging from 8 to 16%, and roughly equivalent
to the range that occurs in colorectal carcinoma stage pT1 (10–17%).
At present, histopathologic parameters alone determine whether a
high (35%) or low (7%) risk of nodal metastases exists
Risio, Tech. Coloproctol. 2004
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The state of the resection margins, the grade of the
invasive carcinoma, the presence or absence of
vascular invasion.
(Coverlizza, Cancer ‘89)
Esame macroscopico e prelievo per
esame istologico
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Valutazione dimensioni (> diam testa, peduncolo a parte),
tipo (peduncolato, sessile, rilevato, piano, escavato etc),
distanza dai margini laterali, evidenza e dimensione di
lesione invasiva.
Supporto per evitare deformazioni e indicare la base (specie
se peduncolo < 0.3 cm). Marcatura margine( china e bouin)
profondo (en bloc), ricostruzione frammenti e marcatura
(piecemeal).
Fissazione.
Riduzione per sezioni parallele di 2-3 mm di spessore
(sagittale mediana e paramediane)
Seriazione shaving sui margini/prelievi ppd ai margini
(Burroughs. JCP 2000)
Valutazione istologica di adenoma
cancerizzato
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Asportazione completa
Grading (G1-2: low; G3: high; G4 anaplastico)
Emboli (ven., linf.): assente, focale, discreta, massiva
Budding tumorale: cellule isolate (<5) in stroma margine di
infiltrazione (low: 0-9 foci; high 10 foci o + a 25X)
Microstadiazione : rapporto % tessuto adenomatoso
/carcinomatoso (> rapporto < rischio). Livello infiltraz.
peduncolo (livelli di Haggitt--> 0:im; 1: testa lesione(sm1) 2:
collo lesione e 3: tutto peduncolo(sm2); 4: sm base polipo
(sm3--> superf. int. muscolare propria).
Risio. Pathologica 2006
Invasione sottomucosa
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Diagnosi di invasione: sez. sagittale mediana e
paramediane di polipo peduncolato o su forceps biopsy di
lesione sessile o più grande (artefatti che occultano il carcinoma o
lesione invasiva retratta, non visibile su prelievo superficiale da ad. villoso)
Profondità e ampiezza invasione per rilevanza clinica e
rischio di metastasi linfonodali: gruppo 1 (m, sm1): EMR possibile;
gruppo 2 (sm2): preferita chirurgia. Cut off sm1/2 = 1000 micron(misura
ecoendo o istologica,.
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Invasione submucosa profonda: non attendibile valutazione
dei margini profondi ed elevato rischio di metastasi. Biopsie su
fondo asportazione /margine profondo piecemeal.
Bergmann. Surg Endosc 2003
Margini (2006)
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La completa escissione prevede assenza di neoplasia su
sezioni seriate dei margini, sia verticali che laterali in
EMR(entro 0.5 mm , Bergmann.Surg Endosc 2003; 2-3 mm. Greff.
Endoscopy 2001). Individuare il peduncolo.
Valutare la profondità di invasione in micron, su sezione
istologica, dal bordo profondo della muscolaris mucosae
e la distanza tra punto di massima infiltrazione e margine
di resezione.
Ca su o vicino al margine= outcome negativo anche
senza parametri istologici sfavorevoli. Invasione del
peduncolo a margini liberi: non outcome
necessariamente negativo
Parametri istologici
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Grade III cancers comprise 5–10% of cases
and are associated with a higher incidence of adverse outcomes
than grades I and II.
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Tumours with prevalence of signet ring cells (greater than 50%) should be
considered signet ring cell carcinoma and regarded as high-grade cancers
(grade III). An anaplastic component in ACIC (even in the form of small, single
or scattered foci) should be identified, as its occurrence strongly correlates with
the risk of lymph node metastases.
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Histological detection of lymphatic invasion requires the presence of
cancer cells within endothelial-lined channels or spaces
distinguishing such features from retraction artefacts.
Venous invasion  tumour emboli within endothelial-lined channels surrounded
by a smooth muscle wall.
Risio, Tech. Coloproctol. 2004
Margini
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The ACIC resection margin obtained by endoscopic
polypectomy is histologically indicated by a strip of coagulative
necrosis (i.e., diathermy change) covering the
entire width of the stalk and with an average thickness of
about 1 mm.
The presence of cancer cells at or near the
resection margin is a reliable histological marker of
adverse outcome.
A negative margin is reported when
there is an absence of cancer within the diathermy and one
high-power field from diathermy, or more than 1 mm from
the actual margin of resection
Risio, Tech. Coloproctol. 2004
Tumor budding
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Tumor budding (Figure 4) is defined
as the presence of tiny detached clusters and cords of tumors cells
embedded in desmoplastic stroma at the leading edge of the invasive
front of the tumor and is assessed on high magnification.
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The tumor cells in tumor budding often assume a spindled
configuration, and that phenotypic change is often designated as an
epithelial-mesenchymal transition.
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Underlying the light morphologic changes are loss of junctional
complexes, incomplete desmosomes, and extension of podia into the
adjacent stroma.
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The number of tumor cells per bud is arbitrarily defined as 5 or fewer in
most publications.
(Washington, CAP, Arch Pathol Lab Med 2008)
Tumor budding
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Because of incomplete validation and
lack of standardized criteria for evaluation, reporting of
tumor border configuration and tumor budding is
optional.(Washington, CAP, Arch Pathol Lab Med 08)
Profili di rischio
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A positive resection margin is clearly predictive of local disease,
the presence of poorly differentiated carcinoma is associated
with a higher mortality, and that of vascular invasion with
a higher risk of lymph node metastasis.
These observations clearly suggest that, following endoscopic
polypectomy, all the histological risk factors need to be carefully
evaluated by the pathologist and that the classification of
patients in low- and high-risk groups is clinically meaningful
Risio, Tech. Coloproctol. 2004
Rischio metastasi
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Lymph node metastases were found in 19 patients (12.3
percent). Univariate analysis showed that lymphatic invasion,
focal dedifferentiation at the submucosal invasive front, status
of the remaining muscularis mucosa, and depth of submucosal
invasion all had a significant influence on lymph node
metastasis.
Multivariate analysis showed lymphatic invasion (P = 0.014)
and high-grade focal dedifferentiation at the submucosal
invasive front (P = 0.049) to be independent factors predicting
lymph node metastasis. No lymph node metastasis was found
in tumors with a depth of submucosal invasion of <1.3 mm.
(Tominaga, Dis colon rectum 2005)
Molecular changes
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In the early stages, acquisition of the metastatic phenotype could be
solely dependent on alterations of the molecular mechanisms
in cell-cell and cell-matrix interactions integrated with cell motility multiple
genomic alterations ( DCC and Met genes are involved whereas the expression
of matrix metalloproteinase 7 (MMP-7) is crucial)
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Recent cytogenetic evidence supports the possibility of a stochastic model for
colorectal carcinoma, in which the transition from early to advanced stages is
probabilistically regulated by loss of chromosome 17 versus 17p subtelomeric
deletions. ACIC with loss of chromosome 17 in cancer sectors actually
represents the emergence from high-grade dysplasia adenomatous tissue of a
cell clone with genotypically determined low evolution rates
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Conversely, ACIC with 1p13.3 deletions in early cancer are likely to represent a
fast transition toward the progressive invasion through the intestinal wall
Risio, Tech. Coloproctol. 2004
Field cancerization
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Field cancerization may have an etiologic role in
a substantial number of recurrences. For example, a surgical
resection margin that includes a genetically altered
field can explain the occurrence of scar recurrence.
Since multiple independent patches of cancer fields may be present in
the same organ exposed to the same insult, clean molecular
margins may not necessarily prevent recurrences in the
residual organ.
In this study, 53% of patients with positive molecular margins had
unfavorable overall survival outcome
(Dakubo , Cancer cell International 2007)