Esophagus
Protocol applies to all
carcinomas of the esophagus.
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 (eg, previous diagnoses; previous radiotherapy or chemotherapy)
b. Relevant findings (eg, endoscopic/imaging studies)
c. Clinical diagnosis
d. Procedure (eg, brushing, washing, other)
e. 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 (eg, cytologic preparation from tissue)
e. Results of intraprocedural consultation
2. Material submitted for microscopic evaluation
3. Special studies (specify) (eg, cytochemistry, immunocytochemistry, DNA analysis [specify type], morphometry, cytogenetic)
1. Adequacy of specimen (if unsatisfactory for evaluation, specify reason)
2. Tumor, if present
a. Histologic type, if possible (Note A)
b. Histologic grade, if possible (Note B)
c. Other features (eg, 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 or excisional 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 findings (eg, endoscopic/imaging studies)
b. Clinical diagnosis
c. Procedure (eg, endoscopic biopsy/polypectomy)
d. Operative findings
e. 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. Tumor (if discernible)
a. Location
b. Descriptive features
c. Dimensions
d. Configuration
e. Relation to margins (excisional biopsy)
3. Tissue submitted for microscopic evaluation
a. Incisional biopsy: all
b. Excisional biopsy: lesion; margin(s) of excision (if identified)
c. Frozen section tissue fragment(s)(unless saved for special studies)
4. Special studies (specify) (eg, histochemistry, immunohistochemistry, DNA analysis [specify type], morphometry, cytogenetic analysis)
1. Tumor
a. Histologic type (Note A)
b. Histologic grade (Note B)
c. Extent of invasion (as appropriate)
d. Blood/lymphatic vessel invasion
2. Additional pathologic findings, if present
a. Esophagitis
b. Barrett's esophagus
c. Squamous dysplasia
d. Glandular dysplasia
e. Microorganisms
f. Other(s)
3. Status/results 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. Esophageal resection 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 (eg, previous diagnoses; previous radiotherapy or chemotherapy)
b. Relevant findings (eg, endoscopic and/or imaging studies)
c. Clinical diagnosis
d. Procedure
e. Operative findings
f. Anatomic site(s) of specimen(s)
1. Specimen
a. Organ(s)/tissue(s) included
b. Unfixed/fixed (specify fixative)
c. Open/unopened
d. Dimensions (measure each piece separately)
e. Orientation (if indicated by surgeon)
f. Results of intraoperative consultation
2. Tumor
a. Location (Note C)
b. Configuration (Note D)
c. Dimensions (three)
d. Descriptive features (eg, color/consistency)
e. Ulceration/perforation
f. Distance from margins (Note F)
(1) proximal
(2) distal
(3) radial (soft tissue margin closest to deepest tumor penetration)
g. Estimated depth of invasion
h. Extension to other organ(s)/structure(s) (specify)
3. Lesions in noncancerous esophagus
a. Barrett's esophagus
b. Ulcer
c. Other(s)
4. Regional lymph nodes (Note E)
a. Number
b. Location (if possible)
5. Other organs/tissues submitted (eg, non-regional lymph nodes)
6. Tissues submitted for microscopic evaluation
a. Carcinoma, including
(1) point of deepest penetration
(2) interface with adjacent proximal and distal esophagus
b. Margins (Note F)
(1) proximal
(2) distal
(3) radial (soft tissue margin closest to deepest tumor penetration)
c. All lymph nodes (Note E)
d. Other lesions (eg, ulcers/polyps/Barrett's esophagus)
e. Esophagus uninvolved by tumor
f. Frozen section tissue fragment(s) (unless saved for special studies)
g. Other organ(s)/tissue(s)
7. Special studies (specify) (eg, histochemistry, immunohistochemistry, DNA analysis [specify type], morphometry, cytogenetic analysis)
1. Tumor
a. Histologic type (Note A)
b. Histologic grade (Note B)
c. Depth of invasion (pT) (Note G)
d. Invasion into stomach
e. Blood/lymphatic vessel invasion
2. Margins (Note F):
a. Proximal
b. Distal
c. Radial (soft tissue margin closest to deepest tumor penetration)
d. Additional pathologic findings, if present
(1) Squamous dysplasia
(2) Barrett's esophagus
(3) Glandular dysplasia
(4) Therapy-related atypia
(5) Other(s)
3. Regional lymph nodes (Note G)
a. Number (location if possible)
b. Number with metastatic tumor
4. Distant metastasis (specify sites) (Note G)
5. Other organs/tissues submitted
6. Results/status of special studies (specify)
7. 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. Histologic Type back Top Main Page
For consistency in reporting, the histologic classification proposed 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.
• Squamous cell carcinoma
• Verrucous (squamous) carcinoma
• Spindle cell (squamous) carcinoma
• Adenocarcinoma
• Adenosquamous carcinoma
• Mucoepidermoid carcinoma*
• Adenoid cystic carcinoma*
• Small cell carcinoma
• Undifferentiated carcinoma
• Others
* These types are not generally graded.
The term carcinoma, NOS (not otherwise specified) is not part of the WHO classification.
B. Histologic Grade back Top Main Page
The histologic grades for esophageal squamous cell carcinomas are:
Grade X Grade cannot be assessed
Grade 1 Well differentiated
Grade 2 Moderately differentiated
Grade 3 Poorly differentiated
[Grade 4 Undifferentiated*]
*Undifferentiated tumors cannot be categorized as squamous (or other) type and are classified as "undifferentiated carcinomas" in the WHO classification of tumor types (see above) which are, by definition, Grade 4.
If there are variations in the differentiation within the tumor, the highest (least favorable) grade is recorded. In general, mucoepidermoid carcinoma and adenoid cystic carcinoma of the esophagus are not amenable to grading. By convention, small cell carcinoma is assigned Grade 4.
For adenocarcinomas, a suggested grading system based on the proportion of the tumor that is composed of glands is as follows:
Grade X Grade cannot be assessed
Grade 1 Well differentiated (>95% of 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)
Undifferentiated tumors cannot be categorized as adenocarcinoma (or other) type and are classified as "undifferentiated carcinomas" in the WHO classification of tumor types (see above) which are, by definition, Grade 4.
C. Location back Top Main Page
The location of the tumor with respect to the gastroesophageal junction (defined as where the tubular esophagus meets the stomach) should be noted. For tumors involving the gastroesophageal junction (GEJ), specific observations should be recorded in an attempt to establish the exact site of origin of the tumor. GEJ is defined as the junction of the tubular esophagus and the stomach irrespective of the type of epithelial lining of the esophagus. The pathologist should record the:
· proportion of tumor mass located in the esophagus and stomach
· greatest dimensions of esophageal and gastric portions of the tumor
· anatomic location of the center of the tumor (cervical, upper thoracic, midthoracic, lower thoracic)
D. Configuration back Top Main Page
Configuration includes exophytic (fungating), endophytic (ulcerative), and diffusely infiltrative, but overlap among these types is common. Reporting of complex configurations may require more than one descriptor.
E. Regional Lymph Nodes back Top Main Page
Regional lymph nodes comprise the cervical nodes (including the supraclavicular nodes) for the cervical esophagus and the mediastinal nodes for the intrathoracic esophagus.(2)
Margins include the proximal, distal, and radial margins. The radial margin represents the adventitial soft tissue margin closest to the deepest penetration of tumor. Sections to evaluate the proximal and distal resections margins can be obtained in two orientations: 1) en face sections parallel to the margin, or 2) longitudinal sections perpendicular to the margin. Depending on the closeness of the tumor to the margin, select the orientation(s) that will most clearly demonstrate the status of the margin. The distance from the tumor edge to the closest resection margin(s) should be measured. Proximal and distal resection margins should be evaluated for dysplasia and/or Barrett's metaplasia. It may be helpful to mark the margin(s) closest to the tumor with ink. Margins marked by ink should be designated in the macroscopic description.
G. TNM and Stage Groupings back Top Main Page
The TNM Staging System for esophageal carcinoma of the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) is recommended and shown below.(2-4) Category T1 has been expanded according to recommendations published in the TNM Supplement.(4)
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 (eg, 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” (eg, 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” (eg, 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 (including high-grade dysplasia)
T1 Tumor invades lamina propria or submucosa
T1a Tumor invades lamina propria*
T1b Tumor invades submucosa*
T2 Tumor invades muscularis propria
T3 Tumor invades adventitia
T4 Tumor invades adjacent structures
*Separation into T1a and T1b is justified by differences in frequency of lymph node metastasis and subsequent prognosis.(4-7) T1a and T1b correlate with lymph node metastasis and prognosis as follows.(7)
Lymph node metastasis 5-year survival rate
T1a 0% 100%
T1B 47% 86% without nodal metastasis
43% with nodal metastasis
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
N1a 1-3 nodes involved*
N1b 4-7 nodes involved*
N1c >7 nodes involved*
†A mediastinal lymphadenectomy specimen will ordinarily include 6 or more regional lymph nodes.
††Separation into N1a, N1b, and N1c is justified by differences in prognosis as follows.(4,8,9)
2-year survival rate 5-year survival rate Median survival (months)
N1a 22% 11% 12
N1b 18% 0% 9
N1c 0% 0% 6
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
*For tumors of the lower thoracic esophagus:
M1a Metastasis in celiac lymph nodes
M1b Other distant metastasis
*For tumors of the upper thoracic esophagus:
M1a Metastasis in cervical nodes
M1b Other distant metastasis
*For tumors of the mid-thoracic esophagus:
M1a Not applicable
M1b Non-regional lymph nodes or other distant metastasis
Tumors of the midthoracic esophagus are staged only M1b, since tumors with metastasis in non-regional lymph nodes as well as in other sites have an equally poor prognosis.
Stage 0 Tis N0 M0
Stage I T1 N0 M0
Stage IIA T2 N0 M0
T3 N0 M0
Stage IIB T1 N1 M0
T2 N1 M0
Stage III T3 N1 M0
T4 Any N M0
Stage IV Any T Any N M1
Stage IVA Any T Any N M1a
Stage IVB Any T Any N M1b
1. Watanabe H, Jass JR, Sobin LH. Histologic Typing of Oesophageal and Gastric Tumours. World Health Organization. 2nd ed. Berlin-New York: Springer-Verlag; 1990.
2. Sobin LH, Wittekind C, eds. TNM Classification of Malignant Tumours: International Union Against Cancer. 5th ed. New York, NY: Wiley; 1997.
3. Fleming ID, Cooper JS, Henson DE, et al. eds. AJCC Manual for Staging of Cancer. 5th ed. Philadelphia, Pa: Lippincott Raven; 1997.
4. Hermanek P, Henson DE, Hutter RVP, Sobin LH. TNM Supplement. Berlin-New York: Springer-Verlag; 1993.
5. Endo M, Takeshita K, Yoshino K. Oesophagoscopy for the diagnosis of superficial oesophageal cancer. Surg Endosc. 1988;2:205-208.
6. Hirayama K, Mori S. Prognostic factors in early esophageal cancer. Gan To Kagaku Ryoho. 1990;17:37-45.
7. Yoshinaka H, Shimazu H, Fukumoto T, Baba M. Superficial esophageal carcinoma: A clinicopathologic review of 59 cases. Am J Gastroenterol. 1991;86:1413-1418.
8. Kato H, Tachimori Y, Watanabe H, Iizuka T. Evaluation of the new (1987) TNM classification for thoracic esophageal tumors. Int J Cancer. 1993;53:220-223.
9. Roder JD, Busch R, Stein HJ, Fink U, Siewert JR. Prognostic factors in patients with squamous cell cancer of the oesophagus undergoing transthoracic end-bloc resection. In: Nabeya K, Nanaoka T, eds. Diseases of the Esophagus. Tokyo: Springer-Verlag; in press.
BIBLIOGRAPHY
Ide H, Nakamura T, Hayashi K, et al. Esophageal squamous cell carcinoma: Pathology and prognosis. World J Surg. 1994;18:321-330.
Klimstra D. Pathologic prognostic factors in esophageal carcinoma. Sem Oncol. 1994;21:425-430.
Kuwano H, Watanabe M, Sadanaga N, et al. Univariate and multivariate analyses of the prognostic significance of discontinuous intramural metastasis in patients with esophageal cancer. J Surg Oncol. 1994;57:17-21.
Lal N, Bhasin DK, Malik AK, Gupta NM, Singh K, Mehta SK. Optimal number of biopsy specimens in the diagnosis of carcinoma of the oesophagus. Gut. 1992;33:724-726.
Lieberman MD, Shriver CD, Bleckner S, Burt M. Carcinoma of the esophagus. Prognostic significance of histologic type. J Thor Cardiovasc Surg. 1995;9:130-138.
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Robey-Cafferty SS, el-Naggar AK, Sahin AA, Bruner JM, Ro JY, Cleary KR. Prognostic factors in esophageal squamous carcinoma: A study of histologic features, blood group expression, and DNA ploidy. Am J Clin Pathol. 1991;95:844-849.
Roder JD, Stein HJ, Siewart JR. Esophageal carcinoma. In: Hermanek P, Gospodarowicz MK, Henson DE, Hutter RVP, Sobin LH, eds. Prognostic Factors in Cancer. Berlin-New York: Springer-Verlag; 1995:37-46.
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Authors:
Randall G. Lee, MD; Carolyn C. Compton, MD, PhD
Originally published in the Archives of Pathology & Laboratory
Medicine,
September 1997.
Contributors: back Top Main Page
CAP Cancer Committee; Leslie H. Sobin, MD; Donald Antonioli, MD; Harvey Goldman, MD; Rodger C. Haggitt, MD; Robert V. P. Hutter, MD; J. Milburn Jessup, MD; Klaus Lewin, MD; Pablo Ross, MD; Heidrun Rotterdam, MD; Leslie Sobin, MD; Stuart Spechler, MD; Christopher Willett, MD; Donald E. Henson, MD