Standards and datasets for reporting cancers
Dataset for the histopathological reporting of carcinomas of the
pancreas, ampulla of Vater and common bile duct
May 2010
Unique document
number
G091
Document name
Dataset for the histopathological reporting of carcinomas of the
pancreas, ampulla of Vater and common bile duct
Version number
1
Produced by
Dr F Campbell, Royal Liverpool University Hospital
Dr AK Foulis, Glasgow Royal Infirmary
Dr CS Verbeke, St James’ University Hospital, Leeds
Date active
May 2010
Date for review
May 2013
Comments
In accordance with the College’s pre-publications policy, this
document was on The Royal College of Pathologists’ website for
consultation from 13 January to 10 February 2010. 26 items of
feedback were received and the authors considered them and
amended the document if deemed appropriate. Please email
publications@rcpath.org if you wish to see the responses and
comments.
Dr Peter Cowling
Director of Communications
The Royal College of Pathologists
2 Carlton House Terrace, London, SW1Y 5AF
Tel: 020 7451 6700
Fax: 020 7451 6701
Web: www.rcpath.org
Registered charity in England and Wales, no. 261035
© 2010, The Royal College of Pathologists
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Contents
Foreword ......................................................................................................... 3
1.
Introduction .............................................................................................. 4
2.
Clinical information required on specimen request form ........................... 5
3.
Specimen handling and dissection ........................................................... 5
4.
Core data items ....................................................................................... 7
5.
Non-core data items................................................................................. 7
6.
Notes on macroscopic assessment .......................................................... 8
7.
Notes on microscopic assessment ........................................................... 10
8.
Pathological staging ................................................................................. 13
9.
Diagnostic coding .................................................................................... 13
10.
Reporting of frozen sections .................................................................... 13
11.
Criteria for audit and standards ................................................................ 14
12.
References .............................................................................................. 14
Appendix A ICD-10 and SNOMED ‘T’ coding for tumour site ............................ 20
Appendix B WHO classification of malignant exocrine pancreatic tumours
and SNOMED ‘M’ Codes .................................................................................. 21
Appendix C WHO classification of carcinomas of the ampulla of Vater
and extrahepatic bile ducts and SNOMED ‘M’ codes ........................................ 22
Appendix D UICC TNM classification ................................................................ 23
Appendix E Proforma for pancreatic carcinoma ................................................ 24
Appendix F Proforma for ampulla of Vater carcinoma ....................................... 25
Appendix G Proforma for common bile duct carcinoma..................................... 26
Appendix H Periampullary cancer dataset monitoring sheet ............................. 27
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Foreword
The Cancer Datasets published by the Royal College of Pathologists are guidelines that should
assist pathologists in providing a high standard of care for patients. Guidelines are systematically
developed statements to assist the decisions of practitioners and patients about appropriate health
care for specific clinical circumstances and are based on the best available evidence at the time
the dataset was prepared. It may be necessary or even desirable to depart from the guidelines in
the interests of specific patients and special circumstances. Just as adherence to the guidelines
may not constitute defence against a claim of negligence, so deviation from them should not
necessarily be deemed negligent.
The dataset has been reviewed by the Cancer Services Working Group and placed on the College
website for consultation with the membership between 13 January and 10 February 2010. All
comments received from the Working Group and memberships have been addressed by the
authors to the satisfaction of the chair of the Working Group and the Director of the Professional
Standards Unit.
No major organizational changes or costs have been identified that would hinder the
implementation of the Dataset.
Each year, the College will ask the authors of the Dataset, in conjunction with the relevant subspecialty advisor to the College, to consider whether or not the Dataset needs to be revised.
This Dataset was developed without external funding to the writing group. The College requires
the authors of datasets to provide a list of potential conflicts of interest; these are monitored by the
Director of the Professional Standards Unit and are available on request.
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1.
Introduction
1.1
General background to the dataset
Pathology reporting of pancreatic, ampulla of Vater and common bile duct cancers is
important for the following reasons:
a)
to make or confirm the diagnosis
b)
to inform prognosis
c)
to select potential patients for future trials of adjuvant therapy
d)
to correlate with radiology and surgery
e)
to collect accurate data for cancer registration and epidemiology
f)
to allow the accurate and equitable comparison of surgical practice in different units
and the comparison of patients in clinical trials.
The number of resections for periampullary cancer has increased over the last 10 years.
This has led to the identification of new pathological entities and investigation of numerous
potential prognostic factors, the majority of which can only be assessed after surgery.
Those histological tumour characteristics that have been reported (in most studies) to have
significant prognostic value in resected pancreatic adenocarcinoma include tumour size,
tumour differentiation, lymph node involvement and resection margin status.1−7 Tumour
stage and lymph node status are the most important prognostic factors identified to date for
ampullary adenocarcinoma and common bile duct adenocarcinoma.8,9
1.2
Developments since the first edition was published
Since the first edition of this dataset in 2002, there have been many requests for guidance
particularly on dissection of the pancreatoduodenectomy specimen, identification of
resection margins and definition of a positive resection margin. Many of these requests
were sought following the British Society of Gastroenterology survey of ‘Pathologists'
approach to pancreatectomies for ampullary, pancreatic and bile duct cancer’ published in
2009 (www.bsg.org.uk/sections/pancreas-news/pancreatic-section-survey.html). These
requests have been addressed but it is emphasized that the dataset is for guidance and is
not prescriptive.
The reporting proformas and guidance are based on the WHO classifications of tumours of
the exocrine pancreas, ampulla of Vater and extrahepatic bile duct10 and the UICC TNM
staging system, 7th edition (2009).11
The UICC TNM staging system has the advantage of being widely accepted and familiar,
and is adhered to throughout this document. The separation of extrahepatic bile duct
cancers into perihilar and distal cancers in the 7th edition of the TNM staging system (2009)
is welcomed. The new T classification and the definition of regional lymph nodes in distal
bile duct cancers are much more appropriate for the common bile duct cancers removed by
a standard Kausch-Whipple’s resection or a pylorus-preserving pancreatoduodenectomy.
The T3 and T4 classifications for distal extrahepatic bile duct cancers, like those for
pancreatic cancers, also reflect what is operable (T3) and what is deemed unresectable in
most centres (T4). There have been no changes to the T classifications for cancers of the
pancreas or ampulla of Vater since the 6th edition of the TNM staging system (2002).
However, pMx and pMo have now been removed from the histopathological (pTNM)
classification system in the 7th edition of the TNM staging system (2009). pM1 may be used
when a distant metastasis is proven histologically. If a potential (cM1) metastasis is
biopsied but is negative histologically, it is classed as cM0 but not pM0.
These guidelines mainly apply to the reporting of pancreatic exocrine carcinomas, 90% of
which are ductal adenocarcinomas, but similar principles may be applied to the reporting of
carcinomas arising in the ampulla of Vater or common bile duct. The reporting of endocrine
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tumours is addressed in the separate Dataset for Endocrine Tumours of the
Gastrointestinal Tract Including the Pancreas.12
1.3
Assessment of literature
This document has been devised to include the data required for adequate reporting of
pancreatic, ampulla of Vater or common bile duct specimens containing cancer. Where
possible, core data that represent a minimum standard for patient management have been
distinguished from non-core data that may form part of a complete report. The proformas
may be used as the main reporting format or may be combined with free text as required.
Evidence for the revised dataset was obtained from a review of relevant literature up to
June 2009 using the PubMed and Medline databases. A consensus view was taken on
selection of the information to be included, on grounds of robustness of evidence reinforced
by the authors’ own experience.
1.4
Consultation with stakeholders
Approval of the dataset has been sought from the Pancreas Society of Great Britain and
Ireland, the Pancreatic Section of the British Society of Gastroenterology, the Pathology
Section of the British Society of Gastroenterology, and panels of specialized and general
histopathologists acting on behalf of the College.
2.
Clinical information required on the specimen request form
Whilst the nature of the resection is usually obvious to the pathologist from the specimen
that is submitted to the laboratory, it is good practice to confirm this with the specimen
request form. A diagram of the surgical procedure or a good clinical description is important
for complex specimens. Patients often proceed to pancreatic surgery on the basis of
imaging and/or cytology without a biopsy having been taken. Therefore, it is desirable for
the pathologist to be told the presumed site and type of the tumour.
3.
Specimen handling and dissection
Resection specimens should, preferably, be opened and partially sectioned immediately
after resection, to aid fixation. The margins of the pancreas (see Section 6.5) should be
painted with an agreed colour code, either when the specimen is fresh or when fixed,
according to the preference of the examining pathologist, but before blocks are taken. The
presence of a stent or a named vessel (e.g. portal vein, superior mesenteric vein) should
be noted. Identification of a resected vessel, particularly if small in size, may be facilitated
by painting it with an extra colour. The specimen may then be pinned to a cork board but
should be placed in a large volume of formalin and allowed to fix for 24−48 hours.
Currently, several different techniques are used for dissecting pancreatoduodenectomy
specimens.13 A detailed dissection protocol is beyond the scope of these guidelines.
However, a brief discussion of the axial dissection method is included, because this
technique has several advantages. After orientation of the specimen (Figure 1a), axial
dissection (Figure 1b) serially slices the pancreatic head in an axial plane, i.e.
perpendicular to the long axis of the duodenum. It is easy to perform, does not include
longitudinal opening of the common bile duct or pancreatic duct, and allows key anatomical
structures (e.g. ampulla, common bile duct, main pancreatic duct) to be seen in the same
slices, which facilitates gross examination. This dissection technique usually results in 8−10
slices, allowing thorough examination of the tumour and its relationship to the key
anatomical structures and margins.
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a
b
Figure 1 (a) Head of the pancreas and (b) axial dissection, i.e. slicing perpendicular to the
long axis of the duodenum. SMV = superior mesenteric vein, SMA = superior mesenteric
artery. (With acknowledgement to Paul Brown, St James’s University Hospital, Leeds.)
For distal pancreatectomy specimens, the anterior and posterior surfaces may be painted,
and the entire specimen can then be serially sliced in the sagittal plane. For total
pancreatectomy specimens, a combined approach of axial slicing of the pancreatic head
followed by serial slicing of the body and tail in the sagittal plane is recommended.
Overview photographs of the lined-up specimen slices and close-up images of individual
slices may be helpful for reporting (e.g. to identify the tumour origin), for multidisciplinary
case discussion and for review of the gross findings if required (e.g. for audit or clinical
trials).
3.1
Tissue sampling
The transection margins of the pancreatic neck, common bile duct and duodenum/distal
stomach are usually sampled (by en-face sections) prior to specimen dissection. Tissue
blocks are taken to include the tumour where it approaches or involves anatomical
structures relevant to (UICC TNM) T-staging, e.g. duodenum, ampulla, common bile duct or
peripancreatic tissue. Similarly, samples should be taken from the tumour and the adjacent
resection margin(s). It is often difficult to identify accurately the invasive tumour front
macroscopically and, therefore, extensive sampling of the tumour and the adjacent margins
is recommended.14 The importance of extensive sampling from the margins is supported by
molecular studies.15,16 If available, sampling of one or more whole mount blocks may be
helpful for assessing the relationship of the tumour to anatomical structures and to margins,
as well as allowing accurate measurement of tumour dimensions.
When a segmental resection of the portal/superior mesenteric vein is removed en-bloc with
the pancreatoduodenectomy, then the proximal and distal ends of this vessel should be
examined as additional transection margins. If a lateral sleeve resection of the vein is
included in the specimen, then the entire edge of the vessel should be examined.
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All lymph nodes (Figure 2 and see Section 7.6) should be sampled, and samples of the
ampulla of Vater, common bile duct and background pancreas should be taken.
Figure 2 Lymph nodes. Inferior includes lymph nodes around superior mesenteric vessels.
PPD = posterior pancreatoduodenal.
4.
Core data items
4.1
Macroscopic
• Type of specimen
• Site of tumour
• Maximum tumour dimension
• Resection margins (measurement confirmed microscopically)
• Named vessel present
• Background pathology (e.g. intraductal papillary mucinous neoplasm, mucinous cystic
neoplasm, adenoma of the ampulla)
4.2
Microscopic
• Histological type of tumour
• Tumour grade
• Maximum extent of local invasion
• Perineural invasion
• Named vessel involvement
• Lymph node status (number present, number involved)
• Resection margin status
• Distant metastases
4.3
Other
• UICC TNM stage
• Completeness of excision (R stage)
• SNOMED codes
5.
Non-core data items
5.1
Macroscopic
•
Specimen measurements for each organ included
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•
•
Stent in place
Other organs
6.
Notes on macroscopic assessment
Measurements made on the gross specimen are recorded in millimetres. They are
confirmed or amended, where appropriate, by microscopy.
6.1
Type of specimen
The type of specimen should be recorded, e.g. a standard Kausch-Whipple’s
pancreatoduodenectomy (PD), a pylorus-preserving PD, a total PD, a subtotal or left
pancreatectomy. The standard Kausch-Whipple’s PD includes the head of pancreas,
duodenum, common bile duct, gall bladder and two thirds of the stomach; the pyloruspreserving PD does not include the stomach; the total PD also includes the body and tail of
pancreas with or without the spleen and/or stomach; the subtotal pancreatectomy includes
the body of the pancreas with or without the stomach; and the left (or distal)
pancreatectomy only consists of the body and tail of pancreas, with or without the spleen.
The type of operation will depend upon the site and size of the tumour. Recent trials,
single-centre studies and a Cochrane Database Systematic Review did not show any
difference in patient survival between standard PD versus pylorus-preserving PD,17−20 PD
with or without vascular resection,21 and PD with or without extended
lymphadenectomy.22−24
6.2
Specimen measurements
Record the lengths of the duodenum, stomach (lesser curve and greater curve), gall
bladder, cystic duct and extrapancreatic bile duct, and the maximum dimensions of the
pancreas. The diameters of the common bile duct and main pancreatic duct can indicate
the location of an obstruction and are useful for correlation with radiology.
6.3
Site of tumour (Appendix A)
State, when possible, whether the tumour arises in the ampulla of Vater, in the
intrapancreatic or extrapancreatic bile duct, or in the head, body or tail of the pancreas. The
precise origin of a tumour in the head of the pancreas may be difficult to determine,
particularly when the tumour is large and involves more than one potential site of origin.
The tumour origin may then be determined by the location of the centre of the tumour.
Microscopic confirmation should be sought and, in some cases, the presence of
microscopic precursor lesions may be helpful (adenoma or flat dysplasia in the ampulla,
dysplasia in the bile duct). However, note that pancreatic intraepithelial neoplasia (PanIN)
is a frequent finding and can be found in the background pancreas of specimens with
ampullary or bile duct cancer.25,26 Although immunohistochemistry may distinguish
intestinal type carcinomas from biliary type carcinomas arising in the ampulla, there are
currently no immunohistochemical markers that distinguish between biliary type carcinomas
of the ampulla and pancreatic ductal adenocarcinoma or cholangiocarcinoma.
The head is that part of the pancreas to the right of the left border of the superior
mesenteric vein; the uncinate process is considered part of the head; the body lies
between the left border of the superior mesenteric vein and the left border of the aorta; and
the tail lies between the left border of the aorta and the hilum of the spleen. Carcinomas of
the body or tail are usually more advanced than those of the head at the time of diagnosis,
because of lack of obstructive symptoms, and because they usually spread into
extrapancreatic tissue and metastasize before detection. They are, therefore, seldom
resected. Note that pancreatic carcinomas may be multicentric (fill in a separate proforma
for each carcinoma).
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Macroscopic examination is essential for determining whether pancreatic adenocarcinoma
has arisen in an intraductal papillary mucinous neoplasm (IPMN) or in a mucinous cystic
neoplasm (MCN).27 For IPMNs, the resection specimen should also be assessed to
determine whether the IPMN is of main duct type, branch duct type or mixed/combined duct
type, because of the better prognosis with branch duct IPMNs.
6.4
Tumour size
Optimally, three dimensions should be measured but, for staging purposes, at least the
maximum diameter of the tumour should be measured. The tumour size is based on
macroscopic assessment but confirmed or amended on the basis of microscopy. Tumour
size in pancreatic carcinoma is a prognostic factor in most studies, on either univariate or
multivariate analysis.3−5
Pancreatic adenocarcinomas < 2 cm in size are associated with better survival.28,29 Note,
however, that lymph node metastasis and portal vein or resection margin involvement can
be seen in small pancreatic (< 2 cm) tumours.30
6.5
Distance from tumour to nearest margin
Completeness of excision should be assessed macroscopically and be confirmed by
microscopic examination. The transection margins are those of the pancreatic neck,
common bile duct and stomach/duodenum. The dissected margins are the superior
mesenteric vessel (sometimes referred to as the medial or uncinate) margin and the
posterior margin (Figure 1a and Figure 3). The superior mesenteric vessel margin includes
the superior mesenteric vein margin (defined as the smooth groove-like surface facing the
superior mesenteric vein) and the superior mesenteric artery margin (defined as the rough
area to the left of the superior mesenteric vein margin and facing the superior mesenteric
artery) (Figure 1a). The posterior margin is defined as the fibrous but smooth surface of the
pancreatic head overlying the aorto-caval groove.
Figure 3 Resection margins for the head of the pancreas.
The anterior surface of the pancreas is not a surgical margin but invasion of this surface
has been shown to be associated with local recurrence and decreased survival time.31−34
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7.
Notes on microscopic assessment
7.1
Tumour type
The histological classification is based on the WHO typing of tumours of the exocrine
pancreas, ampulla of Vater and extrahepatic bile duct10 (Appendices B and C). Ductal
adenocarcinoma, including its variants, accounts for 90% of the pancreatic tumours.
Recognition of the variants of pancreatic ductal adenocarcinoma (PDAC) is important
because they can differ in clinical behaviour, e.g. colloid carcinoma has a significantly
better prognosis than conventional PDAC.35 Undifferentiated carcinoma with osteoclast-like
giant cells is now considered a variant of PDAC. Other recently described variants of PDAC
include clear cell carcinoma,36 foamy gland carcinoma37 and intestinal type
adenocarcinoma.38
It is important to recognize and state whether adenocarcinoma has arisen from a mucinous
cystic neoplasm (when the invasive tumour is typically a tubular/ductal type carcinoma) or
from an IPMN (when the invasive carcinoma may be tubular/ductal type or colloid type).27
This is because the 5-year survival rates for resected mucinous cystic neoplasms (MCNs)
and IPMNs with associated invasive carcinoma can be much better than for conventional
non-MCN/non-IPMN associated ductal adenocarcinoma.39−43
Adenocarcinomas originating in the ampulla of Vater may have intestinal and/or
pancreatobiliary differentiation. Ampullary carcinomas of intestinal type behave like
duodenal adenocarcinomas, while those of pancreatobiliary type behave like pancreatic
adenocarcinoma and are associated with a poorer prognosis.44−46
7.2
Tumour grade
Histological grading of pancreatic ductal adenocarcinoma into well, moderately and poorly
differentiated, according to the criteria of Klöppel et al47 (Table 1), has been found to be of
prognostic significance, on univariate and/or multivariate analysis, in most studies.1,4,48,49
The tumour is graded according to the least differentiated area, regardless of prevalence.
A more recently proposed grading system for pancreatic ductal adenocarcinoma, which
uses a scheme similar to the Gleason scoring system, has been shown to have prognostic
value but awaits further evaluation.50
TABLE 1 Histological grading of pancreatic ductal adenocarcinoma47
Differentiation
Well
Moderate
Poor
Duct
structures
Well
formed
Nuclei
Some well
formed
Very
irregular or
absent
Loss of polarization,
anisonucleosis
Marked
anisonucleosis,
clumped chromatin
Basal
47
*High power field of Klöppel et al
7.3
Mitotic figures per 10
high power fields*
<5
measured 1356 µm
Mucin
production
Marked
5−10
Variable
> 10
Minimal
2
Local invasion
UICC TNM staging for pancreatic carcinoma requires assessment of the maximum size of
the tumour and whether or not tumour extends beyond the pancreas (Appendix D). The
UICC pT stage correlates well with prognosis.51 Peripancreatic tissue invasion has been
reported in up to 90% of cases52 and correlates with poor prognosis. Note that involvement
of the intrapancreatic common bile duct by pancreatic carcinoma should be staged as pT3.
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The UICC TNM staging of carcinomas of the distal extrahepatic bile duct and ampulla of
Vater is different from that of pancreatic carcinoma (Appendix D).11
7.4
Neural invasion
Perineural invasion is a histological characteristic of pancreatic carcinoma. There is a
significant correlation between intrapancreatic neural invasion and extrapancreatic plexus
invasion,53 which is a major cause of local recurrence. Although the frequency of perineural
invasion differs between studies, it still remains a significant prognostic factor for
periampullary carcinoma.54−58
7.5
Vascular invasion
Large named-vessel involvement is a factor determining survival. Radiological evidence of
tumour extension into the coeliac axis (i.e. T4 tumour, Appendix D) is a contraindication for
surgery. Resection of pancreatic carcinoma infiltrating the superior mesenteric artery or
hepatic artery is technically possible and performed in some European and American
centres.21 However, it is currently a contraindication for surgery in the UK. Named-venous
involvement (i.e. portal vein or superior mesenteric vein) is not a contraindication to
surgery, provided venous reconstruction is possible. Involvement is diagnosed when there
is a segment of vein wall attached to the resection specimen that is clearly infiltrated by
tumour on histological examination. In a significant proportion of cases, however, there is
no histological evidence of tumour invasion of the resected vessel wall, and the tethering of
the vessel is caused by fibro-inflammatory changes. Controversy still exists as to whether
the presence or absence of microscopic tumour infiltration of the vessel wall influences
survival.21,58,59
7.6
Lymph node spread
Multivariate analysis has shown lymph node involvement to be a negative prognostic
indicator in pancreatic carcinoma.4,60−62 However, the lymph node ratio (the ratio of the
number of lymph nodes with metastatic cancer to the total number of lymph nodes
examined) is now considered a more powerful prognostic marker than the overall nodal
status in resected pancreatic cancer.63−65 In ampullary carcinoma, lymph node involvement
and the lymph node ratio are also independent prognosticators on multivariate analysis.66,67
Although lymph node involvement in ampullary carcinoma is associated with a poorer
prognosis, survival figures are still better than for node-positive pancreatic
adenocarcinoma. In extrahepatic bile duct carcinoma, increasing numbers of lymph node
metastases are also associated with poorer survival.68,69
The regional lymph nodes (Figure 2) for the pancreas and ampulla of Vater can be grouped
into anterior pancreatoduodenal, posterior pancreatoduodenal, inferior (including the lymph
nodes around the superior mesenteric vessels), common bile duct, infrapyloric (for tumours
of head of pancreas or ampulla), superior and (not shown in Figure 2) proximal
mesentery.11 Coeliac lymph nodes (sent separately) are regional lymph nodes for tumours
of the head of the pancreas only. Lymph nodes in the hilum of the spleen and tail of the
pancreas are regional lymph nodes for tumours of the body and tail only. The regional
lymph nodes for the distal extrahepatic bile duct are along the common bile duct, common
hepatic artery, back towards the coeliac trunk, posterior and anterior pancreaticoduodenal
nodes, and nodes along the superior mesenteric vein and the right lateral wall of the
superior mesenteric artery.11
In the Japan Pancreas Society (JPS) classification of lymph node stations,70 numbers are
given to these groups of lymph nodes (Table 2). Lymph nodes 8 (around the common
hepatic artery) and 16 (para-aortic) may be sent with pancreatoduodenectomy specimens.
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All of the lymph nodes that are identified in the specimen should be examined
histologically. A Whipple's resection should yield a minimum of 15 lymph nodes from the
main specimen.3,65 The number of retrieved/evaluated lymph nodes has been shown to
influence survival.67,71,72 Direct extension of the primary tumour into lymph nodes is
classified as lymph node metastasis.11
TABLE 2 Japan Pancreas Society (JPS) classification of lymph node stations.70
JPS node stations
6
8
9
10
11
12
13
14
16
17
18
Equivalent UICC node stations
Infrapyloric
Common hepatic artery
Coeliac
Splenic hilum
Superior/along splenic artery
Hepatoduodenal ligament (portal/bile duct)
Posterior pancreatoduodenal
Superior mesenteric vessel
Para-aortic
Anterior pancreatoduodenal
Inferior
In one study, immunohistochemistry to detect micrometastases in haematoxylin and eosin
(H&E) stained tumour-free lymph nodes has shown that nodal micro-involvement is an
independent adverse prognostic factor on multivariate analysis.73 However, the use of
immunohistochemistry is not currently recommended for routine practice.
7.7
Margins
The rates of microscopic margin involvement (R1) vary markedly between studies.
Although resection margin status is believed to be a key prognostic factor, the rates of
margin involvement and local tumour recurrence are often incongruous.1,3,5,6,65,74 The
disparities in R1 rate and its prognostic value may be due to differences in opinion on what
constitutes a resection margin, controversy over the definition of microscopic margin
involvement, and lack of standardization of the histopathology examination of
pancreatoduodenectomy specimens.13 When a fully standardized, detailed pathology
examination protocol is used, microscopic margin involvement is a common finding in
pancreatic carcinoma (> 75%) and correlates with survival.7,14,75,76
The rate of margin involvement in common bile duct carcinoma is similar to that for
pancreatic carcinoma, but is less common in ampullary carcinoma.76−80 The posterior and
superior mesenteric vessel margins are the most frequently involved margins in pancreatic
carcinoma.7,14,75,76
Currently, there is controversy over the adequate minimum clearance for pancreatic,
common bile duct and ampullary carcinoma. While some pathologists define margin
involvement when carcinoma is present at the margin (i.e. 0 mm clearance), others use the
1 mm rule adopted from margin assessment in rectal carcinoma. It has been shown in two
recent studies that there is no significant difference in survival for those patients with
carcinoma less than 1 mm from a margin compared to those with direct tumour involvement
of a resection margin.75,81 Carcinoma less than 1 mm from a resection margin is considered
to be incompletely excised, while further studies on this are awaited. Since the anterior
surface of the pancreatic head is an anatomical surface rather than a surgical margin, it
would seem appropriate to apply the 0 mm clearance rule for the assessment of the
anterior surface.
When there is no direct margin involvement by tumour, it is unclear whether those rare
cases in which tumour cells are found within lymph nodes, lymphovascular channels or
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perineural clefts at, or less than 1 mm, from a resection margin should be classed as R1
resections.13 In the UICC TNM classification, when tumour cells are found in the lumen of a
lymphovascular channel at the resection margin, without contact with the endothelium, the
classification is R0.82 When tumour is attached to the vessel wall or invades the vessel wall
at the resection margin, a classification of R1 is appropriate.82 In the current absence of
evidence about lymph node or perineural involvement at a resection margin, it is suggested
that such margin involvement should be considered as incomplete excision if it is the only
reason to report a case as a R1 resection, but this should be clearly stated in the report.
7.8
Distant metastases
The presence of histologically confirmed distant metastases (pM1) and their site should be
recorded.
Metastases to the liver, peritoneum, omentum or extra-abdominal
contraindications for resection in pancreatic ductal adenocarcinoma.31
7.9
sites
are
Background pathology
As stated in Section 6.3, the presence of microscopic precursor lesions (e.g. adenoma, flat
dysplasia) may be helpful in determining the primary origin of a tumour.
PanINs25 are the most common precursors to pancreatic ductal adenocarcinoma but are a
frequent finding in all resected pancreata, i.e. including resections for non-neoplastic
disease.25,26 The presence of an underlying IPMN or MCN should always be stated.83,84
7.10
Other markers
A number of molecular markers, such as k-ras, SMAD4, S100A6 and cyclin E, have been
shown to be of prognostic value following resection, but inclusion of these into routine
practice is currently not justified.15,16,85−88
8.
Pathological staging
Multivariate analysis shows that tumour stage is the most significant factor in predicting
long-term survival in pancreatic carcinoma.51 The UICC TNM classification obtained from
the histopathological data can be converted to a stage grouping,11 but full clinical data will
need to be taken into account before the final stage can be determined.
9.
Diagnostic coding
Tumours should be coded according to the SNOMED system (see Appendices A-C).
10.
Reporting of frozen sections
Histological confirmation of the primary diagnosis, assessment of the presence or absence
of carcinoma or IPMN at the pancreatic transection margin, the presence of carcinoma at
the bile duct margin, or histological confirmation of a potentially metastatic nodule in the
liver, peritoneum or a lymph node are the commonest indications for intraoperative frozen
section diagnosis.89
Distinction between a liver metastasis and a bile duct hamartoma/adenoma may prove
problematic. The presence of necrosis, irregularity of ducts and mitoses in ducts, all favour
a diagnosis of malignancy. The distinction between pancreatitis and adenocarcinoma in the
pancreas may also be difficult on frozen section, because of cautery or freezing artefacts,
or the distortion and reactive nuclear atypia in small residual ductules in chronic
pancreatitis. Often a low power microscopic view is most useful in order to appreciate the
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lack of a lobular distribution of the ducts and the irregularity of duct outline in carcinoma of
the pancreas.
Occasionally, the distinction between invasive ductal adenocarcinoma and PanIN-3 in a
background of atrophy at the transection margin can be problematic, but this is of limited
practical importance since the latter diagnosis is likely to result in the removal of additional
tissue if feasible.90 Similarly, the presence of high grade dysplasia or invasive carcinoma
within an IPMN at the transection margin will usually lead to further resection.
11.
Criteria for audit and standards
It is recommended that multidisciplinary teams and/or pathology departments audit their
pathology reports at regular intervals (perhaps yearly) to ensure the completeness of data
within pathology reports. As regards the standard of pathology, there is currently little
evidence on the frequencies with which important adverse prognostic features are found
between individual pathologists and multidisciplinary teams. However, it has been shown
that the mean harvest of lymph nodes from a Whipple’s resection should be at least 15
nodes3,65 and that the number of retrieved/evaluated lymph nodes does influence
survival.67,71,72 Therefore, to evaluate the standard of pathology dissection, it is
recommended that in a series of Whipple’s resections for carcinoma, the mean number of
lymph nodes examined should be 15. As more evidence accumulates, it may be possible to
adjust this level and to introduce other outcome measures for pathology.
12.
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APPENDIX A
ICD-10 and SNOMED ‘T’ coding for tumour site
Tumour site
ICD-10
SNOMED code
Head of pancreas
Body of pancreas
Tail of pancreas
Whole pancreas
Extrahepatic bile ducts
Ampulla of Vater
C25.0
C25.1
C25.2
C25.8
C24.0
C24.1
T-65100
T-65200
T-65300
T-65000
T-64000
T-64700
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APPENDIX B
WHO classification of malignant exocrine pancreatic tumours10 and SNOMED ‘M’ codes
Ductal adenocarcinomaa
Mucinous non-cystic carcinoma (colloid adenocarcinoma)
Signet-ring cell carcinoma
Adenosquamous carcinoma
Undifferentiated (anaplastic or sarcomatoid) carcinoma
Undifferentiated carcinoma with osteoclast-like giant cells
Mixed ductal−endocrine carcinoma
SNOMED code
M85003
M84803
M84903
M85603
M80203
M80353
M81543
Serous cystadenocarcinoma
M84413
Mucinous cystadenocarcinoma (non-invasive)b
Mucinous cystadenocarcinoma (invasive)c
M84702
M84703
Intraductal papillary mucinous carcinoma (non-invasive)d
Intraductal papillary mucinous carcinoma (invasive)e
M84532
M84533
Acinar cell carcinoma
Acinar cell cystadenocarcinoma
Mixed acinar−endocrine carcinoma
M85503
M85513
M81543
Pancreatoblastoma
M89713
Solid-pseudopapillary carcinoma
M84523
10
NOTE: Since the publication of the WHO classification in 2000 (a) new variants of ductal adenocarcinoma
have been identified (e.g. hepatoid carcinoma, medullary carcinoma) and new terminology has been
introduced for the mucinous neoplasms; (b) mucinous cystic neoplasm (carcinoma in situ), (c) mucinous
cystic neoplasm with invasive carcinoma, (d) intraductal papillary mucinous neoplasm (carcinoma in situ)
and (e) intraductal papillary mucinous neoplasm with invasive carcinoma. An oncocytic variant of intraductal
papillary neoplasm has also been described, as has an intraductal tubular neoplasm.
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APPENDIX C
WHO classification of carcinomas of the ampulla of Vater and extrahepatic bile ducts10 and
SNOMED ‘M’ codes
SNOMED code
M81403
M82603
M81443
M81453
M84803
M83103
M84903
M85603
M80703
M80413
M80203
M82443
Adenocarcinoma (NOS)
Papillary adenocarcinoma
Adenocarcinoma, intestinal type
Adenocarcinoma, gastric foveolar type
Mucinous adenocarcinoma
Clear cell adenocarcinoma
Signet-ring cell carcinoma
Adenosquamous carcinoma
Squamous cell carcinoma
Small cell carcinoma
Undifferentiated carcinoma
Mixed carcinoid−adenocarcinoma
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APPENDIX D
UICC TNM histopathological classification11
General
Pancreas
TX
T0
Tis
Primary tumour cannot be assessed histologically
No histological evidence of primary tumour
Carcinoma in situ
NX
N0
N1
Regional lymph nodes cannot be assessed histologically
No regional lymph node metastasis histologically
Regional lymph node metastasis histologically*
M1
Distant metastasis confirmed histologically
T1
Tumour limited to the pancreas, 20 mm or less in greatest
dimension
Tumour limited to the pancreas, more than 20 mm in greatest
dimension
Tumour extends beyond pancreas, but without involvement
of coeliac axis or superior mesenteric artery
Tumour involves coeliac axis or superior mesenteric artery
T2
T3
T4
Ampulla of Vater
T1
T2
T3
T4
Tumour limited to ampulla of Vater or sphincter of Oddi
Tumour invades duodenal wall
Tumour invades pancreas
Tumour invades peripancreatic soft tissues, or other adjacent
organs or structures
Distal extrahepatic
bile duct
T1
Tumour confined to the bile duct
T2
T3
Tumour invades beyond the wall of the bile duct
Tumour invades the gall bladder, liver, pancreas, duodenum,
or other adjacent organs
Tumour involves the coeliac axis or the superior mesenteric
artery
T4
*For regional lymph nodes, see Section 7.6
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APPENDIX E
PROFORMA FOR PANCREATIC CARCINOMA
Surname: ........................
Forenames: ............................
Date of birth: ....….........
Hospital: .................…….
Hospital no: ...............………… NHS no: ......……..….....
Date of receipt: …….......
Date of reporting:……..….......
Sex: ....………................
Pathologist: ………….....
Surgeon: ………………………
Report no:..………….…..
Specimen type ………………………………………………………………………………………
Gross description
Length of duodenum (mm)
……
Length of lesser curve (mm)……….
Length of greater curve (mm)….…...
Length of gall bladder (mm)
…….
Length of bile duct (mm)……...
Size of pancreas (mm)……… x ……… x ………
Site of tumour ……………………..………
Maximum tumour diameter (mm) …….….
Other organs …………………..…………..
Named vessel identified
Yes
No
Which vessel? ………………………………
Stent in place
Yes
No
Type of tumour: Ductal adenocarcinoma
Other
Differentiation Well
Moderate
(specify) .…………………...……..
Poor
Maximum depth of invasion (T)
Tumour involvement of margins
Yes (R1) No (R0)
Tis: Carcinoma in situ
Transection margin
T1: Tumour limited to the pancreas, 20 mm
(gastric, duodenal, pancreatic, bile duct)
or less in greatest dimension
Dissection margin (SMV, SMA, posterior)
T2: Tumour limited to the pancreas, more than Anterior pancreatic surface
20 mm in greatest dimension
Which margins involved (specify)?.......................................
T3: Tumour extends beyond pancreas but
without involvement of coeliac axis or
SMA
T4: Tumour involves coeliac axis or
SMA
Perineural invasion
Yes
No
Named vessel involved
Lymph node involvement (N)
Total number of nodes
………
Number of nodes involved
………
NX: Cannot be assessed
N0: Regional lymph nodes not involved
N1: Regional lymph nodes involved
Distant metastasis (M)
Not applicable
M1: Distant metastasis
Background pathology
MCN
IPMN
Yes
No
Site….........
Other…………………………..
Comments
Pathological staging pT pN
pM (if applicable)
Completely excised at all margins? Yes (R0)
No (R1 /R2)
Signature:…………………….….…… Date:…………………SNOMED codes: T………M………..
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APPENDIX F
PROFORMA FOR AMPULLA OF VATER CARCINOMA
Surname: ........................
Forenames: ............................
Date of birth: ....….........
Hospital: .................…….
Hospital no: ...............………… NHS no: .......……..….....
Date of receipt: …….......
Date of reporting:……..….......
Sex: ....………................
Pathologist: …………......
Surgeon: ………………………
Report no:..………….…...
Specimen type ………………………………………………………………………………………
Gross description
Length of duodenum (mm)
……
Length of lesser curve (mm)……….
Maximum tumour diameter (mm) …….….
Length of greater curve (mm)….…...
Other organs …………………..…………..
Length of gall bladder (mm)
…….
Length of bile duct (mm)……...
Stent in place
Yes
No
Size of pancreas (mm)……… x ……… x ………
Type of tumour
Adenocarcinoma
Differentiation
Well
Other
Moderate
(specify) .……………...……..
Poor
Maximum depth of invasion (T)
Tumour involvement of margins
Yes (R1) No (R0)
Tis: Carcinoma in situ
Transection margin
T1: Tumour limited to ampulla of Vater
(gastric, duodenal, pancreatic, bile duct)
or sphincter of Oddi
Dissection margin (SMV, SMA, posterior)
T2: Tumour invades duodenal wall
Anterior pancreatic surface
T3: Tumour invades pancreas
Which margins involved (specify)?................................................
T4: Tumour invades peripancreatic soft tissues,
or other adjacent organs or structures
Perineural invasion
Yes
No
Lymph node involvement (N)
Total number of nodes ………
Number of nodes involved ………
NX: Cannot be assessed
N0: Regional lymph nodes not involved
N1: Regional lymph nodes involved
Distant metastasis (M)
Not applicable
M1: Distant metastasis
Background pathology
Other………………………..
Adenoma
Site…
Comments
Pathological staging pT pN
pM (if applicable)
Completely excised at all margins? Yes (R0)
No (R1 /R2)
Signature:…………………….….…… Date:…………………
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APPENDIX G
PROFORMA FOR COMMON BILE DUCT CARCINOMA
Surname: ........................
Forenames: ............................
Date of birth: ....….........
Hospital: .................……
Hospital no: ...............………… NHS no: ......……..….....
Date of receipt: ……........
Date of reporting:……..….......
Sex: ....……….................
Pathologist: …………......
Surgeon: ………………………
Report no: .………….…...
Specimen type ………………………………………………………………………………………
Gross description
Length of duodenum (mm)
……
Length of lesser curve (mm)……….
Length of greater curve (mm)….…...
Length of gall bladder (mm)
…….
Length of bile duct (mm)……...
Size of pancreas (mm)……… x ……… x ………
Maximum tumour diameter (mm) …….….
Other organs …………………..…………..
Named vessel identified
Yes
No
Which vessel? ………………………………
Stent in place
Yes
No
Type of tumour
Adenocarcinoma
Other
Differentiation
Well
Moderate
(specify) .……………...……..
Poor
Maximum depth of invasion (T)
Tumour involvement of margins
Tis: Carcinoma in situ
T1: Tumour confined to bile duct
T2: Tumour invades beyond wall
of bile duct
T3: Tumour invades the gall bladder,
liver, pancreas, duodenum, or other
adjacent organs
T4: Tumour involves the coeliac axis or
the superior mesenteric artery
Transection margin
(gastric, duodenal, pancreatic, bile duct)
Dissection margin (SMV, SMA, posterior)
Anterior pancreatic surface
Perineural invasion
Yes
No
Lymph node involvement (N)
Total number of nodes ………
Number of nodes involved
………
NX: Cannot be assessed
N0: Regional lymph nodes not involved
N1: Regional lymph nodes involved
Background pathology
Named vessel involved
Yes (R1) No (R0)
Yes
Distant metastasis (M)
Not applicable
M1: Distant metastasis
No
Site….......
………………………………………………………..
Comments
Pathological staging pT pN
pM (if applicable)
Completely excised at all margins? Yes (R0)
No (R1 /R2)
Signature:…………………….….…… Date:…………………
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APPENDIX H
PERIAMPULLARY CANCER DATASET MONITORING SHEET
The Cancer Datasets of the Royal College of Pathologists comply with the AGREE standards for good
quality clinical guidelines (www.agreecollaboration.org). The sections of this dataset that indicate compliance
with each of the AGREE standards are indicated in the table.
Section of
AGREE standard
dataset
SCOPE AND PURPOSE
1. The overall objective(s) of the guideline is (are) specifically described.
1
2. The clinical question(s) covered by the guidelines is (are) specifically described.
1
3. The patients to whom the guideline is meant to apply are specifically described.
1
STAKEHOLDER INVOLVEMENT
4. The guideline development group includes individuals from all the relevant
professional groups.
1.4
5. The patients’ views and preferences have been sought.
N/A
6. The target users of the guideline are clearly defined.
1
7. The guideline has been piloted among target users.
Based on
previous edition
RIGOR OF DEVELOPMENT
8. Systematic methods were used to search for evidence.
1.3
9. The criteria for selecting the evidence are clearly described.
1.3
10. The methods used for formulating the recommendations are clearly described.
1.3
11. The health benefits, side effects and risks have been considered in formulating
the recommendations.
1
12. There is an explicit link between the recommendations and the supporting
evidence.
6
13. The guideline has been externally reviewed by experts prior to its publication.
1
Foreword
14. A procedure for updating the guideline is provided.
CLARITY OF PRESENTATION
15. The recommendations are specific and unambiguous.
6
16. The different options for management of the condition are clearly presented.
6
17. Key recommendations are easily identifiable.
4−6
18. The guideline is supported with tools for application.
Appendices A−G
APPLICABILITY
19. The potential organizational barriers in applying the recommendations have been
discussed.
Foreword
20. The potential cost implications of applying the recommendations have been
considered.
Foreword
21. The guideline presents key review criteria for monitoring and audit purposes.
1, 11
EDITORIAL INDEPENDENCE
22. The guideline is editorially independent from the funding body.
1
23. Conflicts of interest of guideline development members have been recorded.
1
Standard 5 is currently regarded as not directly applicable to this dataset.
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