registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in...
TRANSCRIPT
![Page 1: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/1.jpg)
Registration of neoplasia of the
digestive system: towards a better
understanding (presented 25 and 27 nov 2014)
Pieter Demetter
Department of Pathology
Erasme University Hospital
Université Libre de Bruxelles (ULB)
Slightly adapted by BCR and approved by P. Demetter
![Page 2: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/2.jpg)
THE COMPONENTS OF THE DIGESTIVE SYSTEM
Digestive tract: oesophagus, stomach, small
intestine, colon and rectum, anal canal
Pancreas
Liver and bile ducts
2
![Page 3: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/3.jpg)
Wall of the digestive tract: general structure
mucosa
submucosa
muscularis propria
subserosa
serosa
MUCOSA : 1. Epithelium 2. Basal
membrane 3. Lamina
propria 4. Muscularis
mucosae
Tumours originating in the epithelium carcinomas : the most frequent tumour of the digestive tract
![Page 4: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/4.jpg)
normal > premalignant > malignant
Dysplasia : alteration of cells but not yet capacity to invade other structures ; basal membrane remains intact
Invasive tumour (malignant tumour) : cells are capable to invade deeper structures and to spread to other organs by means of lymph/blood vessels ; basal membrane is ruptured
High grade dysplasia /2 ; in situ tumour ; not yet invasive tumour
![Page 5: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/5.jpg)
DEVELOPMENT OF METASTASES
![Page 6: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/6.jpg)
6
THE NORMAL OESOPHAGUS
Normal squamous epithelium, no glands present
![Page 7: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/7.jpg)
![Page 8: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/8.jpg)
OESOPHAGUS: 2 MAIN CANCER TYPES
Squamous cell cancer
(epidermoid cancer,
spinocellular carcinoma,
mainly 8070/3)
Most frequent in upper third and
middle third of oesophagus (but
possible in the lower part!)
Risk factors : tobacco, alcohol,
hot liquids, …
Adenocarcinoma
(mainly 8140/3)
More frequent in the lower part of
the oesophagus (but possible in the
higher parts !)
Risk factors : reflux of gastric acid,
tobacco, alcohol, obesity,…
![Page 9: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/9.jpg)
DEVELOPMENT OF SQUAMOUS CELL CANCER
(mainly 8070/3)
DYSPLASIA : dysplastic cells remain in the epithelial layer : no rupture of the basal membrane
Most frequently in upper 1/3 (and middle 1/3) of the oesophagus. Risk factors: smoking, alcohol
> Search for other cancer locations (lung, ORL)
CANCER : basal membrane is ruptured invasive tumour
![Page 10: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/10.jpg)
DEVELOPMENT OF ADENOCARCINOMA
IN THE OESOPHAGUS (mainly 8140/3)
METAPLASIA Barrett oesophagus :
non-dysplastic glandular structures appear in the
lamina propria
DYSPLASIA ADENOCARCINOMA
No evolution from Barrett oesophagus to squamous cell cancer !
Metaplasie = alteration in type of epithelium (not to be registered for BCR) Dysplasie = premalignant alteration in epithelium (to be registered if severe/ high grade dysplasia)
![Page 11: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/11.jpg)
BARRETT OESOPHAGUS: ENDOSCOPIC IMAGE
and progression to adenocarcinoma
Barrett : always in the lower part of the oesophagus ( adenocarcinoma appearing in higher part of the oesophagus does not originate from Barrett areas).
![Page 12: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/12.jpg)
![Page 13: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/13.jpg)
STOMACH: 2 MAIN CANCER TYPES
Adenocarcinoma of
intestinal type (8144/3)
Adenocarcinoma of
diffuse type (including
signet-ring cell cancer) (8145/3 & 8490/3)
Well organised glandular structures Chaotic arrangement of cells, no glandular structures, bad prognosis
![Page 14: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/14.jpg)
! ADENOCARCINOMA OF INTESTINAL TYPE !
Adenocarcinoma in the
intestine (8140/3) does
not equal
adenocarcinoma of the
intestinal type
(8144/3)!
Adenocarcinoma of the
intestinal type can also
be found in nasal
cavity, paranasal
sinuses and
nasopharynx!
![Page 15: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/15.jpg)
STOMACH : LINITIS PLASTICA
Linitis plastica
(8142/3) is used by
clinicians and refers to
radiologic/endoscopic
image. If used by
pathologists, the tumour
can be classified as
adenoca of diffuse type
(8145/3).
Thickened wall stiffness
![Page 16: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/16.jpg)
GASTRIC TUMOURS
M
Malignant gastric ulcus : tumour arising in the epithelium (carcinoma)
GIST (large) (8936/3) : tumour arising in the mesenchymal part (sarcoma)
![Page 17: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/17.jpg)
GASTRO-INTESTINAL STROMAL TUMOUR (GIST)
GIST (8936/3) may occur
anywhere along the GI
tract or elsewhere in the
abdomen or
retroperitoneum
GIST TUMOURS and GASTRIC CARCINOMAs have a different TNM-
classification !
ALL GIST-TUMOURS HAVE A MALIGNANT POTENTIAL! always /3 (although weak in small gists with few mitoses)
![Page 18: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/18.jpg)
GASTRO-INTESTINAL STROMAL TUMOUR (GIST)
CD117
CD117 : typical immunohistochemical marker for GIST (present in > 95 % of GIST-tumours)
![Page 19: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/19.jpg)
TUMOURS OF THE CARDIA / GASTRO-
OESOPHAGEAL JUNCTION
A tumour the epicentre of which
is within 5 cm of the gastro-
oesophageal junction and also
extends in the oesophagus is
classified and staged using the
oesophageal scheme. Tumours
with an epicentre in the stomach
greater than 5 cm from the
gastro-oeophageal junction or
those within 5 cm of the gastro-
oesophageal junction without
extension in the oesophagus are
classified and staged using the
gastric carcinoma scheme.
![Page 20: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/20.jpg)
Gastro-oesophageal junction
Squamous epithelium of oesophagus
Glandular epithelium of the stomach Junction
![Page 21: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/21.jpg)
![Page 22: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/22.jpg)
SMALL INTESTINE
Duodenum, jejunum,ileum
Complex anatomy
duodenum/pancreas/bile
ducts
In the small intestine,
neuroendocrine tumours
are more frequent than
adenocarcinomas
![Page 23: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/23.jpg)
![Page 24: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/24.jpg)
GROSS ANATOMY OF THE COLON
![Page 25: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/25.jpg)
![Page 26: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/26.jpg)
NORMAL COLON MUCOSA
Mucosa with - Epithelium - Basal membrane - Lamina propria - Muscularis Mucosae
submucosa
Muscularis mucosae
Submucosa
ONLY IN COLO-RECTUM (exceptional situation) All intramucosal tumours, regardless intact or ruptured basal membrane /2
![Page 27: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/27.jpg)
WELL DIFFERENTIATED ADENOCARCINOMA
Well differentiated : nice glandular structures with a good resemblance to normal glands
![Page 28: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/28.jpg)
POORLY DIFFERENTIATED ADENOCARCINOMA
Poorly differentiated : less resemblance to normal glandular structures bad prognosis
![Page 29: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/29.jpg)
THE PROBLEM OF GRADING
No consensus : what has to be reported by the pathologist ? - The grade that is present in the largest part of the tumour?
- The worst grade that is present, even in only a (very) small part of the tumour?
Datamanagers have to report the worst grade, mentioned by the pathologist
![Page 30: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/30.jpg)
THE PROBLEM OF DEFINING A LYMPH NODE
According to the TNM 7th edition, the pathologist may choose himself how to consider a tumoural nodule in a lymph drainage area : - as a lymph node that has been completely
replaced by tumour cells ( N-classification) - as discontinuous spread of the primary
tumour ( T-classification) - as venous invasion ( V-classification) (no
existing classification for arterial invasion)
This lack of consensus may cause multiple problems when staging the tumour !
When a tumour nodule still contains some lymphoid tissue, one can consider the nodule as a positive lymph node. But what with a nodule in a lymph drainage area without residual lymphoid cells ?
![Page 31: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/31.jpg)
Adenocarcinoma of caecum
Benign lipoma of ileo-caecal valve
![Page 32: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/32.jpg)
Mucinous adenoCA >< adenoCA with mucinous differentiation
In mucinous/colloid adenocarcinoma (8480/3), at least 50% of the mass is composed of mucus ; If less than 50 % of mucus, use 8481/3 for mucin producing adenocarcinoma
![Page 33: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/33.jpg)
RECTAL CANCER : TME – resection (PROCARE)
TME – resection : the rectum (with the rectal carcinoma) with the intact mesorectum (in which lymph nodes can be found) is resected
![Page 34: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/34.jpg)
DEFINITION OF RECTUM
Last 15 cm of glandular mucosa Lower than rectum: anal canal or anus! Rectal adenocarcinoma is typically treated by radiochemotherapy before surgery > can lead to complete disappearance of tumour cells! ( ypT0) Do not take into account mucus without viable cells for ypTNM- staging! (viable cells stain positively for pancytokeratin)
![Page 35: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/35.jpg)
The problem of malignant polyps
Villous rectal polyp
![Page 36: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/36.jpg)
STAGING OF MALIGNANT SESSILE POLYPS
sm1 – sm2 – sm3 currently not in TNM-classification. Classification according to Kikuchi.
The Kikuchi classification gives an idea about the depth of submucosal invasion.
After complete local resection of sm1-lesion no additional surgery with lymph node resection necessary (one can
assume that lymph nodes will be negative) After complete local resection of sm3-lesion additional surgery with lymph node resection is recommended because
10% of these tumours are accompanied by positive lymph nodes
![Page 37: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/37.jpg)
STAGING OF MALIGNANT PEDUNCULATED POLYPS
Classification according to Haggitt. ! Sampling error !
If biopsy of polyp says ‘in situ’ but metastasis (at distance or in lymph nodes) present : tumour has to be considered to be invasive (and at least with submucosal infiltration
/3)
![Page 38: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/38.jpg)
Microsatellite instability (MSI)
15% of colorectal cancers (3 % of these are associated with the Lynch syndrome) Associated with better prognosis Associated with resistance to 5-fluorouracil (5-FU = classical chemo for
colon cancer which means that other chemo has to be administered).
MSI indicates a condition in which one is very sensible for DNA-mutations/errors, arising during replication. Normally, these errors will be corrected which is called DNA MisMatchRepair. In MSI, the repair mechanism is impaired so the errors will not be corrected but will accumulate. The micro-satellite DNA fragments will influence other genes in their neighbourhood who are responsible for cell proliferation or cell death.
![Page 39: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/39.jpg)
Lynch syndrome
What is Lynch syndrome? Lynch syndrome, often called hereditary nonpolyposis colorectal cancer (HNPCC), is an inherited disorder that increases the risk of many types of cancer, particularly cancers of the colon (large intestine) and rectum, which are collectively referred to as colorectal cancer. People with Lynch syndrome also have an increased risk of cancers of the stomach, small intestine, liver, gallbladder ducts, upper urinary tract, brain, and skin. Additionally, women with this disorder have a high risk of cancer of the ovaries and lining of the uterus (the endometrium). People with Lynch syndrome may occasionally have noncancerous (benign) growths (polyps) in the colon, called colon polyps. In individuals with this disorder, colon polyps occur earlier but not in greater numbers than they do in the general population.
![Page 40: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/40.jpg)
AUAUAUAU
UAUAUAUA
AUACGCGCGUAU
UAUAUAUA
AUAUAUAU
UAUAUAUA
MMR
Enzymes
Réplication Repair
HNPCC
Instabilité
micro-satellitaire
Les régions MS sont des séquences répétitives d’ADN qui sont situés autour
de gènes importants dans le contrôle de la prolifération ou l’apoptose
AUACGCGCGUAU
UAUAUAUA
TGFbRII
Bax
IGF-2R
TATA
![Page 41: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/41.jpg)
MLH1 MSH2 MSH6 PMS2
DNA MISMATCH REPAIR PROTEINS and MSI
Some proteins (MLH1, MSH2, MSH6, PMS2, …) are involved in the repair mechanism of DNA-errors (DNA Mismatch repair proteins) : When they are present no MSI (first row) When they are absent MSI + (second row)
![Page 42: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/42.jpg)
Progression-free survival by treatment within KRAS groups
Amado RG, J Clin Oncol 2008
Mutations of the KRAS oncogenes are considered to be negative predictors of response to anti-epidermal growth factor receptor antibodies. This means that therapy with anti-EGFR is useless when KRAS mutation is present. This information is – together with information about MSI – important to choose the correct treatment for the patient with colorectal cancer !
![Page 43: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/43.jpg)
ASSAY METHODS
Ross JS, Arch Pathol Lab Med 2012
![Page 44: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/44.jpg)
![Page 45: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/45.jpg)
Pseudomyxoma peritonei
Pseudomyxoma peritonei is a clinical diagnosis (not a pathological one) and can be seen after a benign or malignant tumour of the appendix or ovary. If originating from a mucinous adenocarcinoma (8480/3) of the appendix metastasis outside the abdomen possible. If originating from a low grade appendiceal mucinous neoplasm (LAMN) (8480/1) never gelatinous metastasis outside the abdomen (but even then serious disease)
Jelly belly : gelatinous ascites, abdomen full of mucine
![Page 46: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/46.jpg)
Anal canal and anus
![Page 47: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/47.jpg)
Anal canal and anus
![Page 48: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/48.jpg)
A-RJ = ano-rectal junction (anus – rectum) M-CJ = muco-cutaneous junction (anal mucosa – anal skin)
![Page 49: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/49.jpg)
Anus en anaal anaal: histologische verdeling, België 2008
Overgangsepitheel
(Basaloid-
Cloacogeen
carcinoom)
4%
Carcinoid
1%
Maligne
melanoom
6%
GIST
1%
Adenocarcinoom
14%
Spinocellulair
carcinoom
74%
No endocrine tumours in anal canal since WHO 2010 ( to locate in rectum)
This figure dates from 2008, so endocrine tumours could be registered in the anal canal
![Page 50: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/50.jpg)
Squamous cell carcinoma (8070/3) : subtypes
Large cell keratinising subtype (8071/3)
Large cell nonkeratinising subtype (8072/3)
Basaloid subtype (cloacogenic carcinoma)
(8123/3 – 8124/3)
Not always clear difference between those different types very subjective interpretation of the pathologist. Prognosis similar for the 3 types. Frequently more than one subtype present in one tumour. Future evolution towards 1 type (squamous carcinoma ; 8070/3) possible.
![Page 51: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/51.jpg)
Main risk factor: human papillomavirus (HPV)
75 – 80 % of squamous anal tumours HPV+ Incidence of HPV+ tumours
![Page 52: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/52.jpg)
p16
Condyloma with typical koilocytes related to HPV infection and may give rise to carcinoma
Detection of HPV by PCR is expensive and not easily accessible ; p16 immunohisto-chemistry can be used as an alternative test (p16+ HPV+)
![Page 53: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/53.jpg)
Squamous cell carcinoma: precursor lesions
Chronic HPV infection
Intraepithelial neoplasia (to be registered only if high grade dysplasia HSIL = High-grade
Squamous Intra-epithelial Lesion)(8077/2 – topo C21.1)
Anal Squamous Intraepithelial Neoplasia (ASIN) (to be registered only if high grade dysplasia) (8077/2 – topo C21.1)
Perianal Squamous Intraepithelial Neoplasia
(PSIN) (Bowen’s disease) (always to be registered because in situ lesion : 8081/2 – topo C44.5)
![Page 54: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/54.jpg)
Anal adenocarcinoma (15 % of anal tumours)
mainly 8140/3
Adenocarcinoma arising in anal mucosa
Extramucosal (perianal) adenocarcinoma
Adenocarcinoma within anorectal fistulae (e.g. in
Crohn’s disease)
Adenocarcinoma of anal glands
Prognosis poorer than for squamous cell
carcinoma (less respons to radiotherapy when
compared to squamous lesions)
![Page 55: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/55.jpg)
Adenocarcinoma in anal canal (glandular structures)
![Page 56: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/56.jpg)
Basal cell carcinoma of the anal margin (skin tumour)
mainly 8090/3 ; topo C44.5
>100 cases reported
No evidence for role of HPV infection
![Page 57: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/57.jpg)
Simo AC, Gastroenterol Clin Biol 2008
Basal cell carcinoma of anal skin
![Page 58: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/58.jpg)
Paget’s disease of perianal skin (8542/2 ; topo C44.5)
![Page 59: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/59.jpg)
Paget’s disease
At sites with high density of glands (anus, breast)
Often associated with invasive adenocarcinoma
(e.g. adenoca of the rectal mucosa)
To be registered as in situ lesion (8542/2) unless
pathologist confirms invasion
ICD-O-3 / CIM-O-3 in which 8542/3 can be found
![Page 60: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/60.jpg)
Balachandra B, Histopathology 2007
To know which tumour is involved, immunohistochemistry can help the pathologist :
![Page 61: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/61.jpg)
ANATOMY OF THE PANCREAS
Possible problems with pancreatic tumours due to its particular localisation : - Gastric tumour with
invasion of the adjacent pancreas or just the opposite ?
- Tumour of the pancreas, the bile ducts or the duodenum ?
![Page 62: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/62.jpg)
THE NORMAL PANCREAS
Enzymes, produced by the exocrine part of the pancreas and important for the digestion of the food, are released in the pancreatic ducts
The acini are composed of exocrine cells, producing enzymes to digest the food (enzymes are released in the pancreatic ducts)
The islets of Langerhans are composed of endocrine cells, producing hormones (eg insulin) directly released into the bloodstream
![Page 63: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/63.jpg)
THE ORIGIN OF PANCREATIC TUMOURS
PANCREATIC PARENCHYMA
ACINI DUCTS ISLETS OF
LANGERHANS
ACINAR CELL
TUMOURS
-ADENOCARCINOMA
-IPMT
(NEURO)ENDOCRINE
TUMOURS
Rare tumours Most frequent tumours Less frequent tumours
![Page 64: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/64.jpg)
PANCREATIC ADENOCARCINOMA
Processus uncinatus (part of the head)
head
body tail
Adenocarcinoma mostly in the pancreatic head
(neuro)endocrine tumours more frequent in the pancreatic tail
![Page 65: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/65.jpg)
PANCREATIC ADENOCARCINOMA
Glandular cells and a lot of fibrous stroma (less blood vessels) little respons to chemotherapy bad prognosis
![Page 66: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/66.jpg)
SURGICAL TREATMENT OF PANCREATIC
TUMOURS
The Whipple procedure (pancreatoduodenectomy) is an operation to remove a portion of the pancreas, as well as a portion of the stomach, small intestine (duodenum), the gallbladder and part of the bile duct. The remaining organs are reattached to allow digestion of food.
![Page 67: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/67.jpg)
INTRADUCTAL PAPILLARY MUCINOUS TUMOUR
IPMT with severe dysplasia has to be registered (once the basal membrane is ruptured no longer IPMT but invasive ductal adenoca arising from IPMT)
Tumour growing in the main duct of the pancreas (Wirsung)
![Page 68: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/68.jpg)
NEURO-ENDOCRINE TUMOURS
Histology : tissue available for analysis : more accurate than cytology
Cytology : only cells available for analysis : less accurate (adenoca or endocrine ca?)
Macroscopic appearance
![Page 69: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/69.jpg)
IMMUNOHISTOCHEMISTRY
FOR NEURO-ENDOCRINE TUMOURS
CD56 chromogranin
synaptophysin Ki-67
Frequently 2/3 or 3/3 colorations + if real endocrine tumour. If only 1/3 + (CD56 OR chromogranin OR synaptophysin), be careful because this can also be seen with classical adenocarcinoma ! The higher the value of Ki-67, the more aggressive the behaviour of the tumour !
![Page 70: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/70.jpg)
Rindi classification for grading of neuro-endocrine tumours
![Page 71: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/71.jpg)
Neuro-endocrine tumours
Neuro-endocrine tumour >< tumour with some
neuro-endocrine differentiation (e.g. when CD56 OR
chromogranin OR synaptophysin is positive)
Mixed adeno-neuro-endocrine tumour (MANEC):
at least 30% of each component : very rare and
bad prognosis !
![Page 72: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/72.jpg)
![Page 73: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/73.jpg)
Hepatocellular carcinoma is also possible in non-cirrhotic livers !
![Page 74: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/74.jpg)
Hepatocellular carcinoma (HCC) (8170/3):
macroscopy
![Page 75: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/75.jpg)
Hepatocellular carcinoma (HCC)(8170/3) :
microscopy
Different subtypes of HCC without prognostic relevance…
![Page 76: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/76.jpg)
Fibrolamellar carcinoma (8171/3)
Particular subtype of
hepatocellular
carcinoma
Children and young
adults
On non-cirrhotic liver
No known risk factors
Better prognosis
![Page 77: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/77.jpg)
Cholangiocarcinoma
A lot of fibrous tissue (desmoplastic reaction) less blood vessels little reaction to chemotherapy bad prognosis
![Page 78: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/78.jpg)
Mixed hepatocellular/cholangiocarcinoma (8180/3)
Rare tumour with
features of both
Bad prognosis (prognosis of
this mixed tumour is determined by the
cholangiocarcinoma-part)
![Page 79: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/79.jpg)
Liver: site of metastasis of other tumours
![Page 80: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/80.jpg)
Liver metastasis
![Page 81: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/81.jpg)
Hepatocellular carcinoma >< cholangiocarcinoma > < metastasis
Immunohistochemistry of cholangiocarcinoma : - Cytokeratins 7 and 19 : usually positive - Cytokeratin 20 : positive or negative Immunohistochemistry of metastasis of colonic cancer : - Cytokeratins 7 and 19 : usually negative - Cytokeratin 20 : usually positive
![Page 82: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/82.jpg)
The different locations of cholangiocarcinoma
Klatskin tumour = perihilar tumour
![Page 83: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/83.jpg)
BILE DUCT CANCER
TNM classification: gallbladder ><intrahepatic bile ducts >< extrahepatic bile ducts Extrahepatic bile ducts – perihilar (Klatskin) >< extrahepatic bile ducts – distal >< extrahepatic bile duct named ductus cysticus (see TNM galbladder)
![Page 84: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/84.jpg)
![Page 85: Registration of neoplasia of the digestive system: towards a … · 2018-08-08 · be found in nasal cavity, paranasal sinuses and ... Linitis plastica (8142/3) is used by clinicians](https://reader034.vdocuments.site/reader034/viewer/2022050514/5f9e685de3225a6da609cba8/html5/thumbnails/85.jpg)
STAGING OF TUMOURS
Degree of extension in organ, in draining lymph
nodes and at distance
TNM classification: Tumour, Nodes, Metastasis