Ampulla of Vater
Protocol applies to all
intra-ampullary, peri-ampullary,
and mixed intra- and peri-ampullary carcinomas.
Procedures:
Cytology
I. Cytologic material back Top Main Page
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 (e.g., pancreatitis, familial adenomatous polyposis syndrome)
b. Relevant findings (e.g., endoscopic, ERCP, and/or imaging studies)
c. Clinical diagnosis
d. Procedure (e.g., brushing, washing, other)
e. Operative findings
f. Anatomic site(s) of specimen(s)
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. Incisional biopsy back Top Main Page
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 (e.g., pancreatitis, familial adenomatous polyposis syndrome)
b. Relevant findings (e.g., endoscopic, ERCP, and/or imaging studies)
c. Clinical diagnosis
d. Procedure (e.g., endoscopic biopsy, ERCP biopsy)
e. Operative findings
f. Anatomic site(s) of specimen(s)
1. Specimen
a. Unfixed/fixed (specify fixative)
b. Number of pieces
c. Largest dimension of each piece
d. Results of intraoperative consultation
2. Submit entire specimen and frozen section tissue fragment(s) (unless saved for special studies)
3. Special studies (specify) (e.g., histochemistry, immunohistochemistry)
1. Tumor (Note A)
a. Histologic type (Note B)
b. Histologic grade (Note C)
c. Invasion
2. Additional pathologic findings, if present
a. Duodenitis
b. Adenoma
c. Other
3. Results/status of special studies (specify)
4. Comments
a. Correlation with intraoperative consultation, as appropriate
b. Correlation with other specimens, as appropriate
c. Correlation with clinical information, as appropriate
III. Ampullectomy back Top Main Page
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 (e.g., pancreatitis, familial adenomatous polyposis syndrome)
b. Relevant findings (e.g., endoscopic, ERCP, and/or imaging studies)
c. Clinical diagnosis
d. Procedure (e.g., gastroduodenal pancreatectomy, partial or complete)
e. Operative findings
f. Anatomic site(s) of specimen(s)
1. Specimen
a. Organ(s)/tissue(s) included (specify)
b. Unfixed/fixed (specify fixative)
c. Number of pieces
d. Dimensions (three)
e. Orientation (if indicated by surgeon)
f. Results of intraoperative consultation
2. Tumor
a. Location
b. Configuration
c. Dimensions (best estimate) (Note D)
d. Descriptive features (e.g., color/consistency/necrosis/hemorrhage)
e. Distance from margin of resection
3. Tissues submitted for microscopic evaluation
a. Carcinoma, submit entire specimen, include margin
b. Frozen section tissue fragment(s) (unless saved for special studies)
4. Special studies (specify) (e.g., histochemistry, immunohistochemistry, electron microscopy)
1. Tumor (Note A)
a. Histologic type (Note B)
b. Histologic grade (Note C)
c. Extent of invasion (Note D)
d. Blood/lymphatic vessel invasion (Note E)
e. Perineural invasion (Note F)
2. Margins (as appropriate)
3. Additional pathologic findings, if present
4. Results/status of special studies (specify)
5. Comments
a. Correlation with intraoperative consultation, as appropriate
b. Correlation with other specimens, as appropriate
c. Correlation with clinical information, as appropriate
IV. Whipple
procedure: Pancreaticoduodenectomy,
partial or complete,
with or without partial gastrectomy back Top Main Page
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 (e.g., pancreatitis, familial adenomatous polyposis syndrome)
b. Relevant findings (e.g., endoscopic, ERCP, and/or imaging studies)
c. Clinical diagnosis
d. Procedure (e.g., gastroduodenal pancreatectomy, partial or complete)
e. Operative findings
f. Anatomic site(s) of specimen(s)
1. Specimen
a. Organ(s)/tissue(s) included (specify)
b. Unfixed/fixed (specify fixative)
c. Number of pieces
d. Dimensions (measure attached tissues individually)
e. Orientation (if indicated by surgeon)
f. Results of intraoperative consultation
2. Tumor
a. Location
b. Configuration
c. Dimensions (best estimate) (Note D)
d. Descriptive features (e.g., color/ consistency/necrosis/hemorrhage)
e. Estimated extent of invasion (Note D)
3. Margins (Note G)
4. Regional lymph nodes (Note D)
5. Additional pathologic findings, if present
a. Common bile duct obstruction
b. Pancreatic duct obstruction
c. Pancreatitis
d. Other
6. Tissues submitted for microscopic evaluation
a. Carcinoma, including
(1) points of deepest penetration of surrounding structures
(2) points of deepest penetration of closest margins
(3) interface of tumor with adjacent tissues
b. Accessory papilla, if present
c. Margins
(1) distal pancreas
(2) common bile duct
(3) posterior pancreatic surface (deep radial margin)
(4) proximal (gastric or duodenal)
(5) distal (duodenal)
d. All lymph nodes (Note D)
(1) regional
(2) non-regional
e. Other lesions (e.g., pseudocysts)
f. Pancreas uninvolved by tumor
g. Other tissue(s)/organ(s)
h. Frozen section tissue fragment(s) (unless saved for special studies)
7. Special studies (specify) (e.g., histochemistry, immunohistochemistry, electron microscopy)
1. Tumor (Note A)
a. Histologic type (Note B)
b. Histologic grade (Note C)
c. Extent of invasion (Note D)
d. Blood/lymphatic vessel invasion (Note E)
e. Perineural invasion (Note F)
2. Margins (Note G)
a. Distal pancreas
b. Common bile duct
c. Posterior pancreatic surface (deep radial margin)
d. Proximal (gastric)
e. Distal (duodenal)
3. Regional lymph nodes (Note D)
a. Number
b. Number with metastases
4. Distant metastasis (specify site)
5. Additional pathologic findings, if present
a. Chronic pancreatitis
b. Dysplasia
c. Metaplasia
d. Helicobacter pylori gastritis (Note H)
e. Other
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 Top Main Page
The Ampulla of Vater is a complex structure that represents the confluence of the distal common bile duct and main pancreatic duct which traverses the duodenal wall and opens into the duodenal lumen through a small mucosal elevation, the duodenal papilla. Tumors of the Ampulla of Vater include tumors arising in the ampulla (intra-ampullary type), tumors arising on the ampulla (peri-ampullary type), and tumors arising at the junction of the mucosa of the ampulla with that of the papilla or involving both the intra-ampullary and peri-ampullary region of the duodenum (mixed type). Thus, tumors of the Ampulla of Vater may show biliary and/or intestinal features. Tumors may be exophytic or ulcerated. The origin of the tumor may be difficult, and occasionally impossible, to determine. This protocol applies to all primary carcinomas of the Ampulla of Vater including those showing endocrine focal differentiation, but it does not apply to carcinoid tumors or to lymphomas.(1,2)
B. Histologic Type back Top Main Page
This protocol applies to the following histologic classification but does not preclude the use of other histologic types or systems of classification. A modified classification of carcinomas of the extrahepatic bile ducts published by the World Health Organization (WHO) that is applicable to the Ampulla of Vater is as follows:(3)
Carcinoma in situ
Papillary adenocarcinoma*
Adenocarcinoma, intestinal type
Mucinous adenocarcinoma
Clear cell carcinoma
Signet ring cell carcinoma**
Adenosquamous carcinoma
Squamous cell carcinoma
Small cell carcinoma
Carcinoid tumor***
Mixed carcinoid-adenocarcinoma
Carcinoma, NOS
Other (specify)
*Ampullary tumors of the papillary histologic type have been shown to have a favorable prognosis compared to tumors of non-papillary histologic types.(4,5)
**Signet ring cell carcinomas are, by convention, classified as poorly differentiated (grade 3/4) adenocarcinomas, and poor differentiation has been shown to be an adverse prognostic factor for ampullary carcinomas (see below).(5,6)
***As stated above, this protocol does not apply to carcinoid tumors of the Ampulla of Vater.
C. Histologic Grade back Top Main Page
For non-papillary adenocarcinomas, the following grading system is suggested:
GX Grade cannot be assessed
G1 Well differentiated (>95% of tumor composed of glands)
G2 Moderately differentiated (50-95% of tumor composed of glands)
G3 Poorly differentiated* (5-49% of tumor composed of glands)
G4 Undifferentiated (<5% of tumor composed of glands)
*Poor differentiation has been shown to be an adverse prognostic factor.(5,6)
D. TNM and Stage Groupings back Top Main Page
TNM Staging System for tumors of the Ampulla of Vater of the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) is recommended and shown below.(1) The post-resection prognosis of a patient with ampullary carcinoma is primarily determined by the anatomic extent of disease as defined by the TNM classification and stage groupings.(6-10)
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 therapy with curative intent (e.g., surgical resection for cure) is categorized by a system known as R classification, shown below.
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.
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor limited to the ampulla of Vater or sphincter of Oddi***
T2 Tumor invades the duodenal wall
T3 Tumor invades 2 cm or less into the pancreas
T4 Tumor invades more than 2 cm into the pancreas and/or into other adjacent organs
*Although tumor size is not included in the TNM staging system for tumors of the ampulla of Vater, it has been shown to have independent prognostic significance as follows:(11)
Tumor
Size 5-Year Survival Rate (%
± SE)
> 2.5cm 20%
The difference is statistically significant (p=0.039).
** Invasion of the muscle of the sphincter of Oddi has been shown to be an adverse prognostic factor.(5)
NX Regional lymph nodes cannot be assessed
N1 Regional lymph node metastasis
The regional nodes may be subdivided as follows:
Superior lymph nodes superior to head and body of pancreas.
Inferior lymph nodes inferior to head and body of pancreas.
Anterior anterior pancreaticoduodenal, pyloric, and proximal mesenteric lymph nodes.
Posterior posterior pancreaticoduodenal, common bile duct or pericholedochal, and proximal mesenteric nodes.
The following lymph nodes are also considered regional: hepatic artery nodes, infrapyloric nodes, subpyloric nodes, celiac nodes, superior mesenteric nodes, retroperitoneal nodes, and lateral aortic nodes. Tumor involvement of other nodal groups is considered distant metastasis.
Lymph node metastases have been shown to have independent significance as an adverse prognostic factor.(4,6,7,11)
Distant Metastasis (M)
MX Presence of distant metastasis cannot be assessed
M0 No distant metastasis
Stage Groupings
Stage 0 Tis N0 M0
Stage II T2 N0 M0
T3 N0 M0
Stage III T1 N1 M0
T2 N1 M0
T3 N1 M0
Stage IV T4 Any N M0
Any T Any N M1
E. Blood/Lymphatic Invasion back Top Main Page
Lymph and small blood vessel invasion has been shown to be an adverse prognostic factor.(5,9)
F. Perineural Invasion back Top Main Page
Perineural infiltration by tumor has been shown to be an adverse prognostic factor.(5)
Local recurrence from invasive carcinoma in the region of the pancreatic head most often arises in corresponding to the deep radial posterior margin of the pancreatic head. Since this is a critical margin, the protocol recommends inking the posterior retroperitoneal surface of the pancreas and submitting sections through the tumor at its closest approach to this margin. Local recurrence from intraductal tumor, however, is most likely to occur at a ductal resection margin (i.e., the main pancreatic duct and/or the common bile duct margin). Thus, complete en face sections through the distal pancreatic margin (representing the distal margin of the main pancreatic duct) and the margin of the common bile duct should also be taken. Involvement of resection margins has been shown to be an adverse prognostic factor.(6,12)
H. Other Evaluation back Top Main Page
Sections of gastric antrum may be evaluated for gastritis (e.g., Helicobacter pylori gastritis, chemical gastritis).
REFERENCES
1. Fleming ID, Cooper JS, Henson DE, et al. eds. AJCC Manual for Staging of Cancer. 5th ed. Lippincott Raven; Philadelphia, Pa: 1997.
2. Cubilla AL, Fitzgerald PJ. Tumors of the Exocrine Pancreas. Atlas of Tumor Pathology. 2nd Series. Fascicle 19. Washington, DC; Armed Forces Institute of Pathology; 1984.
3. Albores-Saavedra J, Henson DE, Sobin LH. The WHO classification of tumors of the gallbladder and extrahepatic bile ducts. Cancer. 1992; 70:410-414.
4. Makipour H, Cooperman A, Danzi JT, Farmer RG. Carcinoma of the ampulla of Vater: Review of 38 cases with emphasis on treatment and prognostic factors. Ann Surg. 1976; 183:341-344.
5. Griffanti-Bartoli F, Arnone GB, Ceppa P, Ravera G, Carrabetta S, Civalleri D. Malignant tumors in the head of the pancreas and the periampullary region, diagnostic and prognostic aspects. Anticancer Res. 1994; 14:657-666.
6. Willett CG, Warshaw AL, Convery K, Compton CC. Patterns of failure after pancreaticoduo-denectomy for ampullary carcinoma. Surg Gynecol Obstet. 1993; 176:33-38.
7. Bakkevold KE, Kambestad B. Staging of carcinoma of the pancreas and ampulla of Vater. Tumor (T), lymph node (N), and distant metastasis as prognostic factors. Int J Pancreatol. 1995; 17:249-259.
8. Bakkevold KE, Kambestad B. Long-term survival following radical and palliative treatment of patients with carcinoma of the pancreas and papilla of Vater: The prognostic factors influencing the long-term results. A prospective multicentre study. Eur J Surg Oncol. 1993; 19:147-161.
9. Mori K, Ikei S, Yamane T, et al. Pathological factors influencing survival of carcinoma of the ampulla of Vater. Eur J Surg Oncol. 1990; 16:183-188.
10. Yamaguchi K, Enjoji M. Carcinoma of the ampulla of Vater: A clinicopathologic study and pathologic staging of 109 cases of carcinoma and 5 cases of adenoma. Cancer. 1987; 59:506-515.
11. Delcore R, Connor CS, Thomas JH, Friesen SR, Hermreck AS. Significance of tumor spread in adenocarcinoma of the ampulla of Vater. Am J Surg. 1989; 158:593-597.
12. Allema JH, Reinders ME, van Gulik TM, et al. Prognostic factors for survival after pancreaticoduodenectomy for patients with carcinoma of the pancreatic head region. Cancer. 1995; 75:2069-2076.
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Author:
Carolyn C. Compton, MD, PhD
Originally published in the Archives of Pathology & Laboratory Medicine, July 1997.
Contributors: back Top Main Page
CAP Cancer Committee