Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California
William D. Travis, MD
Department of Pulmonary and Mediastinal Pathology, Armed Forces Institute of Pathology, Washington, DC
For the Members of the Cancer Committee, College of American Pathologists
Previous contributors: Gerald Nash, MD; Robert V.P. Hutter, MD;
Donald E. Henson, MD
Surgical Pathology Cancer Case Summary (Checklist)
Protocol revision date: January 2004
Applies to invasive carcinomas only
Based on AJCC/UICC TNM, 6th edition
(Note: Use of checklist for biopsy specimens is optional)
___ Adenocarcinoma, other variant (specify): ____________________________
___ Large cell undifferentiated carcinoma
___ Large cell neuroendocrine carcinoma
___ Large cell carcinoma, other variant (specify): ____________________________
___ Basaloid carcinoma
___ Adenosquamous carcinoma
___ Typical carcinoid tumor
___ Atypical carcinoid tumor
___ Adenoid cystic carcinoma
___ Mucoepidermoid carcinoma
___ Other tumor of salivary gland type (specify): ____________________________
___ Carcinoma with pleomorphic, sarcomatoid, or sarcomatous elements
(specify variant): ____________________________
___ Other (specify): ____________________________
___ Carcinoma, type cannot be determined
___ Not applicable
___ GX: Cannot be assessed
___ G1: Well differentiated
___ G2: Moderately differentiated
___ G3: Poorly differentiated
___ G4: Undifferentiated
___ Other (specify): ____________________________
Pathologic Staging (pTNM)
Primary Tumor (pT)
___ pTX: Cannot be assessed, or tumor proven by presence of malignant cells in sputum or bronchial washings but not visualized by imaging or bronchoscopy
___ pT0: No evidence of primary tumor
___ pTis: Carcinoma in situ
___ pT1: Tumor 3 cm or less in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (ie, not in the main bronchus)
___ pT2: Tumor with any of the following features of size or extent: greater than 3 cm in greatest dimension; involves main bronchus, 2 cm or more distal to the carina; invades the visceral pleura; associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung
___ pT3: Tumor of any size that directly invades any of the following: chest wall (including superior sulcus tumors), diaphragm, mediastinal pleura, parietal pericardium; or
Tumor of any size in the main bronchus less than 2 cm distal to the carina but without involvement of the carina; or
Tumor of any size associated atelectasis or obstructive pneumonitis of the entire lung
___ pT4: Tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, esophagus, vertebral body, carina; or
Tumor of any size with separate tumor nodule(s) in same lobe; or
Tumor of any size with a malignant pleural effusion
Regional Lymph Nodes (pN)
___ pNX: Cannot be assessed
___ pN0: No regional lymph node metastasis
___ pN1: Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, including intrapulmonary nodes involved by direct extension of the primary tumor
___ pN2: Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s)
___ pN3: Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s)
Specify: Number examined: ___
Number involved: ___
Distant Metastasis (pM)
___ pMX: Cannot be assessed
___ pM1: Distant metastasis; includes separate tumor nodule(s) in a different lobe (ipsilateral or contralateral)
*Specify site(s), if known: ____________________________
Margins (check all that apply)
___ Cannot be assessed
___ Margins uninvolved by invasive carcinoma
Distance of invasive carcinoma from closest margin: ___ mm
Specify margin: ____________________________
___ Squamous cell carcinoma in situ present at bronchial margin
___ Margin(s) involved by invasive carcinoma
___ Bronchial margin
___ Vascular margin
___ Parenchymal margin
___ Parietal pleural margin
___ Chest wall margin
___ Other attached tissue margin (specify): ____________________________
Direct Extension of Tumor (check all that apply)
___ None identified
___ Chest wall (including superior sulcus tumors)
___ Mediastinal pleura
___ Visceral pleura
___ Parietal pericardium
___ Tumor in the main bronchus less than 2 cm distal to the carina
___ Tumor-associated atelectasis or obstructive pneumonitis of the entire lung
___ Great vessels
___ Other (specify): ____________________________
Venous (Large Vessel) Invasion (V)
Arterial (Large Vessel) Invasion
*Lymphatic (Small Vessel) Invasion (L)
*Additional Pathologic Findings (check all that apply)
e. Vascular invasion (arteriolar or venous) (Note D)
f. Lymphatic invasion (Note D)
g. Perineural invasion
(1) pulmonary artery
(2) pulmonary vein
d. Pleural/extrapleural (Note C)
(1) the visceral pleura is free of involvement
(2) the tumor invades into the visceral pleura but not through it
(3) the tumor invades through the visceral pleura
(4) the tumor is in subpleural lymphatics
(5) multifocal pleural involvement
(6) the tumor extends into superficial or deep chest wall
e. Other (eg, attached ribs)
3. Regional lymph nodes included in main specimen (N1) (Notes E and F)
a. Total number examined
b. Number involved by tumor
c. Size of the largest metastasis
d. Extracapsular extension present or absent (Note D)
4. Separately submitted N1 or N2 lymph nodes (report each node station separately, as specified) (Note G)
a. Total number examined
Number involved by tumor
Size of the largest metastasis
d. Extracapsular extension present or absent (Note D)
5. Additional pathologic findings, if present
6. Results of special studies (specify)
a. Correlation with intraoperative consultation, as appropriate
b. Correlation with other specimens, as appropriate
c. Correlation with clinical information, as appropriate
A. Histologic Type
For consistency in reporting, the histologic classification published by the World Health Organization (WHO) for carcinomas of the lung is recommended.1 This protocol does not preclude the use of other systems of classification of histologic types.2
World Health Organization (WHO) Classification of Lung Neoplasms
Soft tissue tumors
Secondary tumors (metastatic)
Each category of lung neoplasms includes a variety of benign and malignant tumors. A detailed list of all these neoplasms is beyond the scope of this protocol. Most lung neoplasms are malignant epithelial tumors.
Combined small cell carcinoma (small cell carcinoma and non-small cell component)
Mixed mucinous and nonmucinous type
Solid adenocarcinoma with mucin
Adenocarcinoma with mixed subtypes
Well-differentiated fetal adenocarcinoma
Mucinous (“colloid”) adenocarcinoma
Clear cell adenocarcinoma
Large cell carcinoma
Large cell neuroendocrine carcinoma
Combined large cell neuroendocrine carcinoma
Clear cell carcinoma
Large cell carcinoma with rhabdoid phenotype
Carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements
Carcinomas with spindle and/or giant cells
Spindle cell carcinoma
Giant cell carcinoma
Carcinomas of salivary-gland type
Adenoid cystic carcinoma
B. Histopathologic Grade (G)
To standardize histologic grading, the following grading system is recommended.3 Grade X (GX): Cannot be assessed
Grade 1 (G1): Well differentiated
Grade 2 (G2): Moderately differentiated
Grade 3 (G3): Poorly differentiated
Grade 4 (G4): Undifferentiated
Undifferentiated (grade 4) is reserved for carcinomas that show minimal or no specific differentiation in routine histologic preparations. According to the definition of grading, a squamous cell carcinoma or an adenocarcinoma arising in the lung can be classified only as grade 1, grade 2, or grade 3, since by definition these tumors show squamous or glandular differentiation, respectively. If there are variations in the differentiation of a tumor, the least favorable variation is recorded as the grade, using grades 1 through 3. By definition, small cell and large cell carcinomas of the lung are assigned grade 4, as they are high-grade tumors with poor prognosis.
C. Visceral Pleural Invasion
The presence of visceral pleural invasion in tumors smaller than 3 cm will change the stage from T1 to T2 and increase stage IA to IB or stage IIA to IIB.4 There are situations in which pleural invasion is difficult to assess, and evaluation of elastic stains may provide useful information.4.5 Visceral pleural invasion may not, by itself, be an independent prognostic factor.6
D. Venous/Lymphatic Vessel Invasion, Extracapsular Extension
Although the presence or absence of venous/lymphatic vessel invasion by the tumor7,8 and extracapsular extension of a positive mediastinal lymph node9-12 may represent unfavorable prognostic findings, they do not change the pT and pN classifications, respectively, or the TNM stage grouping (see Note E).13 Nonetheless, this information is considered important by some clinicians and may influence their selection of therapy.
E. TNM and Stage Grouping
The TNM Staging System for carcinoma of the lung of the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) is recommended and is shown below.3,14
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.
Pathologic staging is usually performed after surgical resection of the primary tumor. Pathologic staging depends on pathologic documentation of the anatomic extent of disease, whether or not the primary tumor has been completely removed. If a biopsied tumor is not resected for any reason (eg, when technically unfeasible) and if the highest T and N categories or the M1 category of the tumor can be confirmed microscopically, the criteria for pathologic classification and staging have been satisfied without total removal of the primary cancer.
Primary Tumor (T)
TX Primary tumor cannot be assessed, or tumor proven by presence of malignant cells in sputum or bronchial washings but not visualized by imaging or bronchoscopy
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor 3 cm or less in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus# (ie, not in the main bronchus)
T2 Tumor with any of the following features of size or extent:
- involves main bronchus, 2 cm or more distal to the carina
- invades the visceral pleura
- associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung
T3 Tumor of any size that directly invades any of the following:
- chest wall (including superior sulcus tumors)
- mediastinal pleura
- parietal pericardium
Tumor of any size in the main bronchus less than 2 cm distal to the carina but without involvement of the carina
Tumor of any size associated atelectasis or obstructive pneumonitis of the entire lung
T4 Tumor of any size that invades any of the following:
- great vessels
- vertebral body
Tumor of any size with separate tumor nodule(s) in same lobe
Tumor of any size with a malignant pleural effusion##
# The uncommon superficial spreading tumor of any size with its invasive component limited to the bronchial wall, which may extend proximal to the main bronchus is also classified as T1.
## Most pleural effusions with lung cancer are due to tumor. However, in a few patients, multiple cytopathologic examinations of pleural fluid are negative for tumor, the fluid is nonbloody and is not an exudate. Where these elements and clinical judgment dictate that the effusion is not related to the tumor, the effusion should be excluded as a staging element, and the tumor should be classified as T1, T2, or T3.
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, including intrapulmonary nodes involved by direct extension of the primary tumor
N2 Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s)
N3 Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene or supraclavicular lymph node(s)
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis; includes separate tumor nodule(s) in a different lobe (ipsilateral or contralateral)
TNM Stage Groupings
Occult T0 N0 M0
Stage 0 Tis N0 M0
Stage IA T1 N0 M0
Stage IB T2 N0 M0
Stage IIA T1 N1 M0
Stage IIB T2 N1 M0
T3 N0 M0
Stage IIIA T1 N2 M0
T2 N2 M0
T3 N1 M0
T3 N2 M0
Stage IIIB Any T N3 M0
T4 Any N M0
Stage IV Any T Any N M1
For identification of special cases of TNM or pTNM classifications, the “m” suffix and “y,” “r,” and “a” prefixes are used. Although they do not affect the stage grouping, they indicate cases needing separate analysis.
The “m” suffix indicates the presence of multiple primary tumors in a single site and is recorded in parentheses: pT(m)NM.
The “y” prefix indicates those cases in which classification is performed during or following initial multimodality therapy (ie, neoadjuvant chemotherapy, radiation therapy, or both chemotherapy and radiation therapy). The cTNM or pTNM category is identified by a “y” prefix. The ycTNM or ypTNM categorizes the extent of tumor actually present at the time of that examination. The “y” categorization is not an estimate of tumor prior to multimodality therapy (ie, before initiation of neoadjuvant therapy).
The “r” prefix indicates a recurrent tumor when staged after a documented disease-free interval, and is identified by the “r” prefix: rTNM.
The “a” prefix designates the stage determined at autopsy: aTNM.
Residual Tumor (R)
Tumor remaining in a patient after therapy with curative intent (eg, surgical resection for cure) is categorized by a system known as R classification, as 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).
By AJCC/UICC convention, vessel invasion (lymphatic or venous) does not affect the T category indicating local extent of tumor unless specifically included in the definition of a T category. In all other cases, lymphatic and venous invasion by tumor are coded separately as follows.
Synchronous primary carcinomas of the lung of different histologic types are generally considered separate primaries, and they are staged independently.15-18 Recommendations for staging of multiple pulmonary tumor masses of similar histology are provided in Note E (such as in tumor of any size with separate tumor nodule[s] in same lobe and would be considered as T4).
G. Regional Lymph Node Classification by Anatomic Site
The anatomic classification of regional lymph nodes adopted by the AJCC and UICC18 is shown below.
All N2 nodes lie within the mediastinal pleural envelope.
Superior Mediastinal Nodes
1. Highest mediastinal nodes: Nodes lying above a horizontal line at the upper rim of the bracheocephalic (left innominate) vein where it ascends to the left, crossing in front of the trachea at its midline.
2. Upper paratracheal nodes: Nodes lying above a horizontal line drawn tangential to the upper margin of the aortic arch and below the inferior boundary of No. 1 nodes.
3. Prevascular and retrotracheal nodes: Prevascular and retrotracheal nodes may be designated 3A and 3P; midline nodes are considered to be ipsilateral.
4. Lower paratracheal nodes: The lower paratracheal nodes on the right lie to the right of the midline of the trachea between a horizontal line drawn tangential to the upper margin of the aortic arch and a line extending across the right main bronchus at the upper margin of the upper lobe bronchus, contained within the mediastinal pleural envelope. The lower paratracheal nodes on the left lie to the left of the midline of the trachea between a horizontal line drawn tangential to the upper margin of the aortic arch and a line extending across the left main bronchus at the level of the upper margin of the left upper lobe bronchus, medial to the ligamentum arteriosum and contained within the mediastinal pleural envelope. Researchers may wish to designate the lower paratracheal nodes as No. 4s (superior) and No. 4i (inferior) subsets for study purposes; the No. 4s nodes may be defined by a horizontal line extending across the trachea and drawn tangential to the cephalic border of the azygos vein; the No. 4i nodes may be defined by the lower boundary of No. 4s and the lower boundary of No. 4, as described above.
5. Subaortic nodes (aorto-pulmonary window): Subaortic nodes are lateral to the ligamentum arteriosum or the aorta or left pulmonary artery and proximal to the first branch of the left pulmonary artery and lie within the mediastinal pleural envelope.
6. Para-aortic nodes (ascending aorta or phrenic): Nodes lying anterior and lateral to the ascending aorta and the aortic arch or the innominate artery, beneath a line tangential to the upper margin of the aortic arch.
Inferior Mediastinal Nodes
7. Subcarinal nodes: Nodes lying caudal to the carina of the trachea, but not associated with the lower lobe bronchi or arteries within the lung.
8. Paraesophageal nodes (below carina): Nodes lying adjacent to the wall of the esophagus and to the right or left of the midline, excluding subcarinal nodes.
9. Pulmonary ligament nodes: Nodes lying within the pulmonary ligament, including those in the posterior wall and lower part of the inferior pulmonary vein.
All N1 nodes lie distal to the mediastinal pleural reflection and within the visceral pleura.
10. Hilar nodes: The proximal lobar nodes, distal to the mediastinal pleural reflection and the nodes adjacent to the bronchus intermedius on the right; radiographically, the hilar shadow may be created by enlargement of both hilar and interlobar nodes.
11. Interlobar nodes: Nodes lying between the lobar bronchi.
12. Lobar nodes: Nodes adjacent to the distal lobar bronchi.
13. Segmental nodes: Nodes adjacent to the segmental bronchi.
14. Subsegmental nodes: Nodes around the subsegmental bronchi.
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