Extrahepatic Bile Ducts
Protocol applies to
all carcinomas of the extrahepatic bile ducts.
Sarcomas and carcinoid tumors are excluded.
Procedures
• Cytology
• Local or Segmental Bile Duct Resection
I. Cytologic
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1. Patient identification
a. Name
b. Identification number
c. Age (birth date)
d. Gender
2. Responsible physician(s)
3. Date of procedure
4. Other clinical information
a. Relevant history
(1) inflammatory bowel disease
(2) sclerosing cholangitis
(3) choledochal cyst
b. Relevant findings (e.g., jaundice, serum
bilirubin, ERCP)
c. Clinical diagnosis (e.g., bile duct
obstruction)
d. Procedure (e.g., brushing, washing, other)
e. Operative findings
f. Anatomic site(s) of specimen(s) (e.g.,
left/right hepatic ducts, common bile duct)
1. Specimen
a. Unfixed/fixed (specify fixative)
b. Number of slides received, if appropriate
c. Quantity and appearance of fluid specimen, if
appropriate
d. Other (e.g., cytologic preparation from
tissue)
e. Results of intraprocedural consultation
2. Material submitted for microscopic evaluation
3. Special studies (specify) (e.g.,
cytochemistry, immunocytochemistry)
1. Adequacy of specimen (if unsatisfactory for
evaluation, specify reason)
2. Tumor, if present (Note A)
a. Histologic type, if possible (Note
B)
b. Histologic grade, if possible (Note
C)
c. Other features (e.g., necrosis)
3. Additional pathologic findings, if present
4. Results/status of special studies (specify)
5. Comments
a. Correlation with intraprocedural consultation,
as appropriate
b. Correlation with other specimens, as
appropriate
c. Correlation with clinical information, as
appropriate
II. Local or segmental bile duct resection back
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1. Patient identification
a. Name
b. Identification number
c. Age (birth date)
d. Gender
2. Responsible physician(s)
3. Date of procedure
4. Other clinical information
a. Relevant history
(1) inflammatory bowel disease
(2) sclerosing cholangitis
(3) choledochal cyst
b. Relevant findings (e.g., jaundice, serum
bilirubin, ERCP)
c. Clinical diagnosis (e.g., bile duct
obstruction)
d. Procedure
e. Operative findings
f. Anatomic site(s) of specimen(s)(e.g.,
left/right hepatic ducts, common duct)
1. Specimen
a. Organ(s)/tissue(s) included
b. Unfixed/fixed (specify fixative)
c. Orientation (if indicated by surgeon)
d. Previously opened
e. Dimensions of bile duct (include thickness of
wall)
f. External surface of bile duct
(color/adhesions/mass)
g. Obstruction (partial/complete)
h. Stones present (number/type)
i. Description of other tissues (as
appropriate)
j. Results of intraoperative consultation
2. Tumor (Note A)
a. Location
(1) origin in bile duct segment
(2) origin in choledochal cyst (Note D)
b. Configuration (Note E)
c. Dimensions (three)
d. Descriptive features (e.g.,
color/consistency/necrosis)
e. Extent of invasion (Note F)
3. Additional pathologic findings
4. Margins (as appropriate) (Note G)
5. Regional lymph nodes
a.
Location,
if possible (Note F)
b.
Number
6. Other organ(s) or structure(s)
a. Involved by tumor by direct extension
b. Metastatic involvement by tumor
c. Additional pathologic findings
7. Tissues submitted for microscopic evaluation
a. Carcinoma, including:
(1) point of deepest penetration
(2) interface with adjacent tissue
b. Uninvolved mucosa
c. Margins of extrahepatic ducts (Note
G)
d. Other margins (as appropriate) (Note
G)
e. Periductal soft tissue
f. All lymph nodes
g. Other lesions
h. Frozen section tissue fragment(s) (unless
saved for special studies)
i. Other tissue(s)/organ(s) (e.g.,
liver/pancreas/gallbladder/duodenum) (specify)
7. Special studies (specify) (e.g.,
histochemistry, immunohistochemistry, morphometry, DNA analysis)
1. Tumor
a. Histologic type (Note B)
b. Histologic grade (Note C)
c. Extent of invasion (Note F)
d. Blood/lymphatic vessel invasion
e. Perineural invasion (Note H)
2. Margins (Note G)
a. Bile duct margins
b. Other margins (as appropriate)
3. Regional lymph nodes
a. Number
b. Number involved by tumor (specify location if
possible) (Note F)
4. Additional pathologic findings, if present
a. Dysplasia
b. Carcinoma in situ
c. Sclerosing cholangitis
d. Other(s)
5. Metastasis to other organ(s) or structure(s)
(specify site)
6. Other tissue(s)/organ(s)
7. Results/status of special studies (specify)
8. Comments
a. Correlation with intraoperative consultation,
as appropriate
b. Correlation with other specimens, as
appropriate
c. Correlation with clinical information, as
appropriate
EXPLANATORY NOTES
A. Application back
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This protocol
applies only to carcinomas arising in the extrahepatic bile ducts (including
choledochal cysts) and in the cystic duct. It does not include carcinoid tumors
or tumors arising in the ampulla of Vater. More than 98% of the malignant
tumors of the extrahepatic bile ducts are carcinomas. They are often
associated with a history of ulcerative colitis.
B.
Histologic Type back Top Main Page
For consistency
in reporting, the histologic classification published by the World Health
Organization (WHO) is recommended.(1)
However, this protocol does not preclude the use of other systems of
classification or histologic types. The WHO classification is shown below but
has been modified to exclude endocrine tumors.
It is
recommended that the term “cholangiocarcinoma” be reserved for carcinomas
arising in the intrahepatic bile ducts.
• Carcinoma in
situ*
• Adenocarcinoma
• Papillary
adenocarcinoma*
•
Adenocarcinoma, intestinal type
• Mucinous
adenocarcinoma
• Clear cell
adenocarcinoma*
• Signet ring
cell carcinoma**
• Adenosquamous
carcinoma
• Squamous cell
carcinoma
• Small cell
carcinoma (oat cell carcinoma)***
•
Undifferentiated carcinoma***
* These
histologic types are not usually graded (see below)
** By
convention, signet ring cell carcinomas are assigned grade 3 (see below).
*** Small cell
carcinomas and undifferentiated (histologic type) carcinomas are assigned grade
4 (see below).
C. Histologic Grade back
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For
adenocarcinomas, a quantitative grading system based on the proportion of gland
formation within the tumor is suggested and shown below.
Grade X Grade cannot be assessed
Grade 1 Well differentiated (>95% or
tumor composed of glands)
Grade 2 Moderately differentiated (50-95%
of tumor composed of glands)
Grade 3 Poorly differentiated (5-49% of
tumor composed of glands)
Grade 4 Undifferentiated (<5% of tumor
composed of glands)
Definitions
corresponding to the above histologic grades are as follows:
Grade 1: Composed entirely of glands or has
less than 5% solid or cord-like growth patterns.
Grade 2: Has from 6% to 49% solid or cord-like
growth patterns.
Grade 3: Has 50% to 95% solid or cord-like
growth patterns.
Grade 4: Has less than 5% glands and consists
primarily of pleomorphic spindle and giant cells or small cells with
considerable nuclear atypia, small amounts of mucin and no significant
endocrine differentiation.
For squamous
cell carcinomas, a rare tumor type in the extrahepatic bile ducts, a suggested
grading system is shown below. If there are variations in the differentiation
within the tumor, the highest (least favorable) grade is recorded.
Grade X Grade cannot be assessed
Grade 1 Well differentiated
Grade 2 Moderately differentiated
Grade 3 Poorly differentiated
Grade 4 Undifferentiated
Published data
indicate a relation between histologic grade and post-operative outcome.(1)
D. Choledochal Cyst back
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Carcinomas may
arise in choledochal cysts (congenital cystic dilatation or duplications) of
the bile duct. Histologically, they are classified the same as those arising in
the gallbladder or bile ducts. Stones may be found in these cysts. If carcinoma
in situ is found, then multiple sections should be examined to exclude invasive
cancer in other areas of the cyst.
E. Configuration back
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Configuration
includes papillary, nodular, diffusely infiltrating, or combined features.
Papillary carcinomas have a better prognosis and should be specifically
reported.(2)
F. TNM and Stage Groupings back Top Main Page
The TNM Staging
System for malignant tumors of the extrahepatic bile ducts of the American
Joint Committee on Cancer/International Union Against Cancer is recommended by
the protocol and shown below.(3,4)
The staging system also applies to tumors arising in choledochal cysts.
By AJCC/UICC
convention, the designation "T" refers to a primary tumor that has
not been previously treated. The symbol "p" refers to the pathologic
classification of the TNM, as opposed to the clinical classification and is
based on gross and microscopic examination. pT entails a resection of the
primary tumor or biopsy adequate to evaluate the highest pT category; pN
entails removal of nodes adequate to validate lymph node metastasis; and pM
implies microscopic examination of distant lesions. Clinical classification
(cTNM) is usually carried out by the referring physician before treatment
during initial evaluation of the patient or when pathologic classification is
not possible.
Tumor remaining
in a patient after definitive therapy (e.g., surgical resection for cure) is
categorized by a system known as R classification, shown below.
RX Presence of residual tumor cannot be
assessed
R0 No residual tumor
R1 Microscopic residual tumor
R2 Macroscopic residual tumor.
For the surgeon,
the R classification may be useful to indicate the known or assumed status of
the completeness of a surgical excision. For the pathologist, the R
classification is relevant to the status of the margins of a surgical resection
specimen. That is, tumor involving the resection margin on pathologic
examination may be assumed to correspond to residual tumor in the patient and
may be classified as macroscopic or microscopic according to the findings at
the specimen margin(s).
In contrast,
tumor remaining in a resection specimen from a patient who has undergone
previous (neoadjuvant) treatment of any type (radiation therapy alone,
chemotherapy therapy alone, or any combined modality treatment) is codified by
the TNM using a prescript "y" (e.g.,, ypT1). Thus, yTNM indicates the
post-treatment status of the tumor. For many neoadjuvant therapies, the
classification of residual disease may be a strong predictor of postoperative
outcome. In addition, the ypTNM classification provides a standardized
framework for the collection of data needed to accurately evaluate new
neoadjuvant therapies.
In contrast to
"residual" tumor, classification of a tumor as "recurrent"
requires a documented disease-free interval after definitive therapy. Recurrent
tumor may also be classified according to the TNM categories, but the prefix
"r" (e.g.,, rpT1) is used to indicate the recurrent status of the
tumor.
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor invades subepithelial connective
tissue or fibromuscular layer
T1a Tumor invades subepithelial connective
tissue
T1b
Tumor invades fibromuscular layer
T2 Tumor invades perifibromuscular
connective tissue
T3 Tumor invades adjacent structures:
liver, pancreas, duodenum, gallbladder, colon, stomach
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in cystic duct, pericholedochal
and/or hilar lymph nodes (i.e.,, in the hepatoduodenal ligament)
N2 Metastasis in peripancreatic (head only),
periduodenal, periportal, celiac, and/or superior mesenteric and/or posterior
pancreaticoduodenal lymph nodes
* To separate
pN1 from pN2 nodal extension, the lymph nodes must be specifically identified.
Peripancreatic nodes located along the body and tail of the pancreas are
considered sites of distant metastasis.
Distant Metastasis (M)
MX Presence of distant metastasis cannot be
assessed
M0 No distant metastasis
M1 Distant metastasis
Stage 0 Tis N0 M0
Stage I T1 N0 M0
Stage II T2 N0 M0
Stage III T1 N1 M0
T1 N2 M0
T2 N1 M0
T2 N2 M0
Stage IVA T3 Any
N M0
Stage IVB Any T Any
N M1
It is important
to evaluate carefully all surgical margins, including an assessment of vascular
and perineural invasion. Local
recurrence is often related to residual tumor located in the proximal or distal
surgical margins of the bile duct or from tumor located along the dissected
soft tissue margin in the portal area. (5)
Local recurrence (usually at the surgical margins) is most common with
carcinomas arising in the hepatic duct(s).
In addition,
malignant tumors of the extrahepatic bile ducts are often multifocal. (6) Therefore, microscopic foci of carcinoma or
dysplasia may be found at the margin(s) even though the main tumor mass has
been resected. In some cases it may be
difficult to evaluate margins on frozen section preparations because of
inflammation and reactive atypia of the surface epithelium or within the
intramural mucous glands. If surgical
margins are free of carcinoma, the distance between the closest margin and the
tumor edge should be measured.
Since 5% of
patients with bile duct carcinoma have synchronous carcinomas of the
gallbladder, examination of the entire surgical specimen including the gallbladder
is advised.
This is seen in
almost every case that is adequately sampled.
It should be specifically evaluated since it is associated with adverse
outcome.(7) It is also useful for
distinguishing carcinoma from primary sclerosing cholangitis.
1. Albores-Saavedra J, Henson DE, Sobin
LH. Histological Typing of Tumours of the
Gallbladder and Extrahepatic Bile Ducts, WHO International Histological
Classification of Tumours. Berlin: Springer-Verlag; 1991.
2. Henson DE, Albores-Saavedra J, Corle D.
Carcinoma of the extrahepatic bile ducts. Cancer.
1992;70:1498-1501.
3. Sobin LH, Wittekind C, eds. TNM Classification of Malignant Tumours:
International Union Against Cancer. 5th ed. New York, NY: Wiley; 1997.
4. Fleming ID, Cooper JS, Henson DE, et
al., eds. AJCC Manual for Staging of
Cancer. 5th ed. Philadelphia, Pa: Lippincott Raven; 1997.
5. Ogura Y, Takahashi K, Tabata M, Mizumoto
R. Clinicopathological study on carcinoma of the extrahepatic bile-duct with
special focus on cancer invasion on the surgical margins. World J Surg. 1994;18:778-784.
6. Suzuki M, Takahashi T, Ouchi K, Matsuno
S. The development and extension of hepatohilar bile duct carcinoma. Cancer. 1989;64:658-666.
7. Bhuiya MR., Nimura Y, Kamiya J, et al.
Clinicopathologic studies on perineural invasion of bile duct carcinoma. Ann Surg. 1992;215:344-349.
BIBLIOGRAPHY
Albores-Saavedra
J, Henson DE. Tumors of the Gallbladder and Extrahepatic Bile Ducts, Atlas of
Tumor Pathology, 2nd Series, Fascicle 22. Washington, DC. Armed Forces
Institute of Pathology, 1986.
Braasch JW,
Warren KW, Kune GA. Malignant neoplasms of the bile ducts. Surg Clin N Am. 1967;47:627-638.
Davis RI, Sloan
JM, Hood JM, Maxwell P. Carcinoma of the extrahepatic biliary tract: A
clinicopathological and immunohistochemical study. Histopathology. 1988:12:623-631.
Gertsch P,
Thomas P, Baer H, Lerut J, Zimmermann A, Blumgart LH. Multiple tumors of the
biliary tract. Am J Surg.
1990;159:386-388.
Kayahara M,
Nagakawa T, Ueno K, Ohta T, Takeda T, Miyazaki I. Lymphatic flow in carcinoma
of the distal bile duct based on a clinicopathologic study. Cancer. 1993;72:2112-2117.
Kozuka S,
Tsubone M, Hachisuka K. Evolution of carcinoma in the extrahepatic bile ducts. Cancer. 1984;54:65-72.
Longnecker DS,
Guay Terhune P. The case for parallel classification of biliary tract and
pancreatic neoplasms. Mod Pathol.
1996;9:828-837.
Ludwig J.
Surgical pathology of the syndrome of primary sclerosing cholangitis. Am J Surg Pathol. 1989;13 (Suppl
1):43-49.
Maxwell P,
Davis RI, Sloan JM. Carcinoembryonic antigen (CEA) in benign and malignant
epithelium of the gall bladder, extrahepatic bile ducts, and ampulla of Vater. J Pathol. 1993;170:73-76.
Ouchi K, Suzuki
M, Hashimoto L, Sato T. Histologic findings and prognostic factors in carcinoma
of the upper bile duct. Am J Surg.
1989;157:552-556.
Todoroki T,
Okamura T, Fukao, K, Nishimura A, et al. Gross appearance of carcinoma of the
main duct carcinoma. Surg Gynec Obstet.
1980;150:33-40.
Tompkins RK,
Thomas D, Wile A, Longmire, WP Jr. Prognostic factors in bile duct carcinoma. Ann Surg. 1981;194:447-455.
Wanebo JH,
Grimes OF. Cancer of the bile ducts: the occult malignancy. Am J Surg. 1975;130:262-268.
Authors
Donald E.
Henson, MD, Jorge Albores-Saavedra, MD, Carolyn C. Compton, MD, PhD
Contributors: back Top Main Page
CAP Cancer
Committee