practice protocol for the examination of specimens from patients with lung cancer

21 67

College of American Pathologists

Task Force Members: Gerald Nash, M.D. (Chair- man); Penfield Faber, M.D.; David Bragg, M.D.; Johnathan Nesbit, M.D.: Robert Ginsberg, M.D.; Frederick Askin, M.D.; Clifton Mountain, M.D.; Robert Fontanna, M.D.; Thomas Colby, M.D.; John C. Ruckdeschel, M.D.; David Johnson, M.D.; Darryl Carter, M.D.; Willis Taylor, M.D.; Roger W. Byhardt, M.D.; Robert Pugatch, M.D.; Robert V. P. Hutter, M.D.; and Donald E. Hen- son, M.D.

Cancer Committee Members: Donald E. Henson, M.D.; Diane Coppock, M.D.; George M. Farrow, M.D.; Fred Gorstein, M.D.; Kyung-Whan Min, M.D.; Gerald Nash. M.D.; Mary L. Nielsen, M.D.; Stephen G. Ruby, M.D.; Robert E. Scully, M.D.; L. Leonard Weiss, M.D.; and Mark R. Wick, M.D.

Reprinted from Archives of Pathology & Labo- ratory Medicine, Vol. 119:695-700, 1995, with permission of the College of American Patholo- gists.

Practice Protocol for the Examination of Specimens from Patients with Lung Cancer

Gerald Nash, M.o.’ Robert V. P. Hutter, M.D? Donald Earl Henson, M . D . ~ for the Members of the Cancer Committee, College of American Pathologists, and the Task Force on the Examination of Specimens From Patients With Lung Cancer

’ Department of Pathology, Baystate Medical Center, Springfield, Massachusetts.

Department of Pathology, St. Barnabas Hospital, Livingston, New Jersey.

Early Detection Branch, Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, Maryland.

he Cancer Committee of the College of American Pathologists, T as part of its program to ensure quality for anatomic pathology, continues to develop protocols for the examination of surgical specimens resected from patients with cancer. This report describes the protocol for data to be included in routine consultation reports for patients with carcinoma of the lung. Previously, the Committee has published protocols for carcinomas of the prostate gland,’ colon,‘ breast, urinary bladder, and for Hodgkin’s disease.3 Protocols for other anatomic sites are under development. This protocol is not a man- date, but a guide for pathologists who would like assistance. It is not intended for pathologists who have already satisfied their quality assurance commitments with their own protocols.

PURPOSE The purpose of this protocol is to serve as a basis for the development of checklists, as an outline for full narrative reporting, as a basis for research protocols, or as a guide for synoptic or other types of reporting formats. The protocol specifies the inclusion of information that documents the adequate examination of the specimen as well as the anatomic extent of tissue removed, extent of the carcinoma, the histologic type, histologic grade, lymph node status, and other information needed by the referring physician to select treatment, evaluate therapy, estimate prognosis, and analyze outcome. The protocol was designed for patient care in all types of practice settings, including community hospitals, large urban centers, and universities. Although not specifically designed for research, the protocol can serve as the basis for developing more detailed pathology protocols for clinical studies on lung cancer. Pathologists may report additional

2168 CANCER May 15,1996 / Volume 77 / Number 10

information not specified by the protocol or modify this protocol to suit individual institutional needs.

PROTOCOL DEVELOPMENT A provisional protocol was developed by a multidisci- plinary Task Force established by the Cancer Commit- tee. Pathologists, surgeons, medical oncologists, and radiation oncologists constituted the Task Force, which initially met in 1992. The Task Force was charged to document the basic diagnostic information appropriate for the management of patients with carcinoma of the lung. Documentation was obtained from the medical literature, personal experience, and consultation with colleagues. The provisional protocol was further reviewed by pathologists, surgeons, and other specialists involved in the care of patients with lung cancer who offered constructive comments. The protocol emphasizes that the referring physician must provide all relevant clinical information for pathologists to consult effectively.

SURVEY After the provisional recommendations were approved by the Cancer Committee and the Task Force, a pro- cess survey was conducted to determine whether pathologists agreed with the proposed protocol and whether they would tend to follow it in practice. One thousand pathologists were randomly selected from a Laboratory Master List and surveyed by mail. The survey included pathologists engaged in different types of laboratory practice: governmental, community hospital, independent, and medical center. For the Cancer Committee, these surveys provided the opportunity for broad consultation with pathologists on the type and extent of data that should be transmitted in consultation reports on patients with carcinoma of the lung. The survey results were compiled and analyzed, and taken into consideration in developing the final protocol. This protocol was approved by the Board of Governors of the College in February 1994 and will become effective upon publication in the ARCHIVES.

SYNOPTIC REPORTING Recently, attention has focused on the needs to en- hance the clarity of surgical pathology reports and to ensure that all of the pertinent details that influence patient care are always included in them. This has led to interest in the synoptic form of reporting as a replacement for the traditional narrative descriptive f ~ r m a t , ~ ' ~ and in standardized reporting of surgical pathology diagnoses6 as ways to achieve these goals. Checklists or worksheets that serve as prompts for data input would facilitate development of synoptic formats and a uniform system of reporting consonant

with quality are.^^^ All appropriate information that is needed clinically would be provided. The Cancer Committee is developing various types of checklists based on this protocol that will be available through the College of American Pathologists.

DIAGNOSTIC AND THERAPEUTIC PROCEDURES This protocol applies to all malignant epithelial tumors that arise in the lung. It is stratified on diagnostic and therapeutic procedures usually used for carcinoma of the lung, including acquisition of cytologic material, biopsy, and resection. The following procedures are covered by the protocol.

I. Acquisition of Cytologic Material A. B. C. D. E.

F.

G.

Sputum Bronchial brushing Bronchial washing/lavage Pleural fluid Fine-needle aspiration 1. Percutaneous (specify site; eg, lymph node,

lung) 2. Transbronchial 3. Other Cytologic preparation of tissue specimen (eg, touch preparation) Other (eg, pericardial fluid)

11. Biopsy A. Lung B. Bronchus C. Pleura D. Lymph node E. Other (specify)

111. Resection (specify anatomic sitelsl) A.

B. C.

D.

E.

Major airway resection 1. Trachea 2. Carina 3. Main bronchus Wedge (subsegmentectomy) Segmentectomy 1. Standard segmentectomy 2. En bloc with chest wall or other parietal tis-

Lobectomy/ bilobectomy 1. Sleeve lobectomy 2. En bloc with chest wall or other parietal tis-

Pneumonectomy

sue (eg, diaphragm, pericardium)

sue (eg, diaphragm, pericardium)

1. 2.

3.

Standard pneumonectomy Pneumonectomy with tracheal and carinal resection Complex pneumonectomy (eg, pleuropneu- monectomy/extrapleural pneumonectomy including en bloc [more common] resection)

Carcinoma of the Lung/Nash et al. 2169

PROTOCOL FOR THE EXAMINATION OF SPECIMENS FROM PATIENTS WITH LUNG CANCER

I. Cytologic Material A. Relevant clinical information should be pro-

vided to the pathologist for optimal pathology consultation. The following minimal data set should be supplemented as appropriate. 1. Patient identification

a. Name b. Age (birth date) c. Gender d. Unique patient number e. Physician (submitting physician’s name

f. Patient location (if hospital patient) g. Date specimen obtained h. Date specimen received by laboratory

2. Clinical diagnosis 3. Clinical findings (eg, imaging, operative) 4. Relevant history (eg, smoking, previous di-

agnosis, treatment) 5. Procedure (eg, bronchoscopy with bron-

chial washing, percutaneous fine-needle aspiration)

6. Anatomic site of specimen (eg, upper lobe of left lung, right pleural space)

7. Type of specimen as specified on the requisition (eg, sputum, bronchial washing, pleural fluid)

B. Gross examination

andlor clinic)

1. Description of specimen a. Fresh, in fixative (specify type) b. Number of slides received, if appropriate c. Quantity and appearance of fluid speci-

d. Other (eg, cytologic preparation from tis-

2. Material prepared for microscopic evalua-

3. Special studies, specify

1. Adequacy of specimen for diagnostic evaluation (if unsatisfactory or limited, specify reason)

a. Presence or absence of neoplastic cells b. Histologic type of neoplasm, when possi-

c. Other pathologic findings, specify

men, if appropriate

sue)

tion (eg, smear of fluid, cell block)

C. Microscopic evaluation and diagnosis

2. Cytopathology diagnosis

ble (see note A)

3. Results of special studies, specify 4. Correlation with other relevant specimens

5. Correlation with clinical information, as rel- (cytologic or histologic)

evant

11. Biopsy A. Relevant clinical information should be pro-

vided to the pathologist for optimal pathology consultation. The following minimum data set should be supplemented as appropriate. 1. Patient identification

a. Name b. Age (birth date) c. Gender d. Unique patient number e. Physician (submitting physician’s name



5. Procedure (eg, fiberoptic bronchoscopy,

6. Anatomic site of specimen (eg, upper lobe

7. Type of specimen (eg, transbronchial bi-

and/or clinic)

agnosis, treatment)

mediastinoscopy)

of left lung)

opsy, mediastinal node[sl) B. Gross examination

1. Fresh or in fixative (specify type) 2. Size (three dimensions) 3. Gross features 4. Tissue submitted for microscopic evalua-

5 . Special studies, specify

1. No neoplasm 2. Neoplasm

tion

C. Microscopic evaluation and diagnosis

a. Histologic type (see note A) b. Histologic grade (see note B) c. Local extension, as appropriate

(1) in situ vs invasive (bronchial biopsy) (2) extra capsular invasion (mediastinal

(3) other (specify) lymph node, see note C)

3. Other lesion(s), specify 4. Correlation with frozen section, as relevant 5 . Correlation with previous specimens (cyto-

6. Results of special studies, specify logic and/or histologic) as relevant

111. Resection A. Relevant clinical information should be pro-

vided to the pathologist for optimal pathology consultation. The following minimal data set should be supplemented as appropriate. 1. Patient identification

a. Name

2170 CANCER May 15,1996 / Volume 77 / Number 10

b. Age (birth date) c. Gender d. Unique patient number e. Physician (submitting physician’s name



5 . Procedure (specify anatomic site[sl)

andlor clinic)

agnosis, treatment)

a. Major airway resection (1) trachea (2) carina (3) main bronchus

b. Wedge (subsegmentectomy) c. Segmentectomy

(1) standard segmentectomy (2) en bloc with chest wall or other pari-

etal tissue (eg, diaphragm, pericardium)

d. Lobectomyl bilobectomy (1) sleeve lobectomy (2) en bloc with chest wall or other pari-

etal tissue (eg, diaphragm, pericardium)

e. Pneumonectomy (1) standard pneumonectomy (2) pneumonectomy with tracheal and

carinal resection (3) complex pneumonectomy (eg, pleu-

ropneumonectomy/extrapleural pneumonectomy including en bloc [more common] resection)

6. Specimen as specified on the requisition

7. Documentation of area(s) marked by sur- (eg, right lung)

geon B. Gross examination

1. Fresh or in fixative (specify type) 2. External aspect (documentation of extent of

resection) a. Size (three dimensions) b. Weight c. Visceral pleura d. Attached tissue (eg, chest wall) e. Margins

(1) bronchial (2) vascular (3) parenchymal (4) attached tissue

f. Note marked areas of documentation applied by surgeon

3. Neoplasm a. Location

(1) bronchial (a) main (b) lobar (c) segmental

(2) peripheral lung (3) pleural

b. Size (three dimensions] c. Description

(1) color (2) shape (3) circumscription (4) cavitation (5) other (specify)

d. Anatomic extent (1) bronchial involvement (2) vascular invasion (3) visceral pleural invasion or shortest

distance from visceral pleura, as appropriate

(4) interlobar fissure extension, as appropriate

(5) attached tissues (depth of invasion), as appropriate

e. Relation to margins (as appropriate, specify shortest distance from) (1) bronchial (2) vascular (3) resected parenchymal surface(s1 (4) attached tissue

(a) chest wall (b) pericardium (c) diaphragm (d) other

f. Additional tumors (1) describe each possible primary tu-

(2) multiple nodules not regarded as pri- mor as above (see note D)

maries (see note D) (a) size (range) (b) number (c) location

4. Nonneoplastic lung a. Normal b. Abnormal (specify)

a. All nodes included in specimen will be designated pN1 unless otherwise specified by the surgeon (see notes E and F)

5. Lymph nodes (part of specimen)

b. Total number c. Number positive

Carcinoma of the LunglNash et al. 2171

6.

7.

8.

(1 1 extra capsular extension d. Ikscription Separately Submitted nodes (report each node station separately, as specified) (see note E) a. Location (station) specified by surgeon b. Total number c. Number positive

(1) extra capsular extension (see note C) d. Description Sections of tissue for microscopic evaluation (as appropriate) a. Tumor b. Tumor and adjacent lung c. Tumor and wall of bronchus (if arising

d. Bronchial mucosa proximal to tumor e. Tumor relationship to pleura f. Margins

in bronchus)

(1) bronchial (2 ) vascular (3 ) parenchymal (4) attached tissue (5) areas marked by surgeon

g. Norineoplastic lung (1) normal (2) abnormal

h. Attached tissue i. All lymph nodes should be submitted for

Tissue submitted for special studies, specify microscopic evaluation

C. Microscopic evaluation and diagnosis 1 . Neoplasm

a. Histologic type (see note A) b. Histologic grade (see note B) c. Site (bronchus, peripheral lung, pleura) d. Size (from gross description) e. Anatomic extent

priate (1) bronchial involvement, as appro-

(2) vascular/lymphatic vessel invasion (3) visceral pleural invasion (present or

(4) attached tissues

(1) bronchial (2) vascular (3 ) parenchymal (4) attached tissue

absent)

f. Margins

g. Area(s) marked by surgeon

a. Site 2. Lymph nodes

( I ) included in specimen (pN1) (see notes E, F)

(2) separately submitted (report each node station separately, as specified) (see note E)

b. Number (1) total number examined (2) number positive (note extracapsular

invasion) (see note C) c. Other lesion(s) (specify)

a. Normal b. Abnormal (specify)

3. Nonneoplastic lung

4. pT classification (see note F) 5. pN classification (see note F) 6. Correlation with frozen section, as relevant 7. Correlation with previous specimens (cyto-

logic and histologic), as relevant 8. Results of special studies (specify)

EXPLANATORY NOTES A: For consistency in reporting, the histologic classification published by the World Health Organization (WHO) for carcinomas of the lung is recommended.' However, the Cancer Committee recognizes that other classification systems are in use. This protocol does not preclude the use of other systems of classification or other histologic types."

Histologic Classification of Malignant Epithelial lung Tumors (WHO) Squamous cell carcinoma (epidermoid carcinoma)

Variant: Spindle cell (squamous) carcinoma Small-cell carcinoma

Oat cell carcinoma Intermediate cell type Combined oat cell carcinoma

Acinar adenocarcinoma Papillary adenocarcinoma Bronchiolo-alveolar carcinoma Solid carcinoma with mucus formation

Variants: giant cell carcinoma, clear cell carci-

Adenocarcinoma

Large-cell carcinoma

noma Adenosquamous carcinoma Carcinoid tumor Bronchial gland carcinomas

Adenoid cystic carcinoma Mucoepidermoid carcinoma Others

Others

B: Histopathologic Grade.-To standardize histologic grading, the Cancer Committee recommends that four grades should be used.'

2172 CANCER May 15,1996 I Volume 77 / Number 10

Grade X = grade cannot be assessed Grade 1 = well differentiated Grade 2 = moderately differentiated Grade 3 = poorly differentiated Grade 4 = undifferentiated

“Undifferentiated” (grade 4) should be reserved for carcinomas that show 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 classi- fied only as grades 1,2, or 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 re- corded as the grade, using grades 1 through 3. By definition, small (oat) -cell and large-cell carcinomas of the lung are assigned grade 4, since these tumors show no differentiation in routine preparations.

C: Although the presence or absence of extracapsular invasion of a positive mediastinal lymph node does not change the pN classification or stage group- ing by TNM (see Note F), this information is considered important by many clinicians, and it may influence their selection of therapy.”-12

D: Synchronous primary carcinomas of the lung of different histologic types are generally considered separate primaries, and they are staged indepen- dently.I3-l5 Recommendations for diagnosis and staging of multiple pulmonary tumor masses are given in references 14 and 15.

E. Regional Lymph Node Classifications.

Classification Adapted From NarukeL6 Recom- mended by the American Joint Committee on Can- cer.’--

N2 Nodes Superior Mediastinal Nodes

1. Highest mediastinal 2. Upper paratracheal 3. Pre- and retrotracheal 4. Lower paratracheal (including azygos nodes)

5. Subaortic (aortic window) 6. Paraaortic (ascending aorta or phrenic)

7. Subcarinal 8. Paraesophageal (below carina) 9. Pulmonary ligament

10. Hilar 11. Interlobar 12. Lobar

Aortic Nodes

Inferior Mediastinal Nodes

N l Nodes

13. Segmental

Classification Recommended by the American Tho- racic Socievl7.-

Definitions of Lymph Node Stations 2R. Right upper peritracheal (suprainnominate)

nodes: nodes to the right of the midline of the trachea between the intersection of the caudal margin of the innominate artery with the trachea and the apex of the lung. (In- cludes highest R mediastinal node.)

2L. Left upper peritracheal (supraaortic nodes): nodes to the left of the midline of the trachea between the top of the aortic arch and the apex of the lung. (Includes highest L mediastinal node.)

4R. Right lower peritracheal nodes: nodes to the right of the midline of the trachea between the cephalic border of the azygos vein and the intersection of the caudal margin of the brachiocephalic artery with the right side of the trachea. (Includes some pretracheal and paracaval nodes.)

4L. Left lower peritracheal nodes: nodes to the left of the midline of the trachea between the top of the aortic arch and the level of the carina, medial to the ligamentum arteriosum. (Includes some pretracheal nodes.)

5. Aortopulmonary nodes: subaortic and paraaortic nodes, lateral to the ligamentum arteriosum or the aorta or left pulmonary artery, proximal to the first branch of the left pulmonary artery.

6. Anterior mediastinal nodes: nodes anterior to the ascending aorta or the innominate artery. (Includes some pretracheal and preaor- tic nodes.)

7. Subcarinal nodes: nodes arising caudal to the carina of the trachea but not associated with the lower lobe bronchi or arteries within the lung.

9. Right or left pulmonary ligament nodes: nodes within the right or left pulmonary ligament.

10R. Right tracheobronchial nodes: nodes to the right of the midline of the trachea from the level of the cephalic border of the azygos vein to the origin of the right upper lobe bronchus.

1OL. Left peribronchial nodes: nodes to the left of the midline of the trachea between the carina and the left upper lobe bronchus, medial to the ligamentum arteriosum.

Carcinoma of the LunglNash et al. 2173

11. Intrapulmonary nodes: nodes removed in the right or left lung specimen plus those distal to the mainstem bronchi or secondary carina. (Includes interlobar, lobar, and segmental nodes.) Post-thoracotomy staging may designate 11 interlobar, 12 lobar, 13 segmental, and 14 subsegmental.

F: AJCC/UICC (American Joint Committee on Can- CerlInternational Union Against Cancer) Staging Sys- tem.’”’

Primary Tumor (TI 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

TO 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: more than 3 cm in greatest dimension; involving main bronchus, 2 cm or more distal to the carina; invading the visceral pleura; or 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 sul- cus tumors), diaphragm, mediastinal pleura, or parietal pericardium; or tumor in the main bronchus less than 2 cm distal to the carina but without involvement of the carina; or associated atelectasis or obstructive pneumonitis of the entire lung

T4 Tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, esophagus, vertebral body, carina; or tumor with a malignant pleural effusion

Regional Lymph Nodes (N) NX Regional lymph nodes cannot be assessed NO No regional lymph node metastasis N1 Metastasis in ipsilateral peribronchial and/or

ipsilateral hilar lymph nodes, including direct extension

N2 Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s)

N3 Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral sca- lene, or supraclavicular lymph node(s)

Distant Metastases (M)

sessed MX Presence of distant metastasis cannot be as-

MO No distant metastasis M1 Distant metastasis

Lung Cancer Stage Groupings by TNM Subsets Occult Tx Stage 0 Tis Stage I T1

T2 Stage I1 T1

T2 Stage IIIA T1

T2 T3

T4 Stage IIIB MY T

Stage N Any T

NO NO NO NO N1 N1 N2 N2 NO, N1, N2 N3 AnY N Any N

MO MO MO MO MO MO MO MO MO MO MO M1

The symbol “pT” refers to the pathologic classification of the TNM, as opposed to the clinical classification. Pathologic classification is based on gross and microscopic examination. pT entails a resection of the primary tumor or biopsy adequate to evaluate the highest pT cate- gory; pN entails removal of nodes adequate to validate lymph node metastasis; and pM implies microscopic veri- fication 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.

Recommendations for staging tumors to which no specific staging rules apply are given in reference 15.

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