Recommendations for the Reporting of Pleural Mesothelioma Association of Directors of Anatomic and Surgical Pathology * DOI: 10.1309/6A30YQHBMTHEJTEM It has been evident for decades that pathology reports are very variable even within a single institution. Standardization of reporting is the optimal way to ensure that information necessary for patient management, prognostic and predictive factor assessment, grading, staging, analysis of outcomes, and tumor registries is included in pathology reports. In recent years, 2 societies (first the Association of Directors of Anatomic and Surgical Pathology [ADASP] and then the College of American Pathologists [CAP]) have undertaken the publishing of guidelines for the reporting of common cancers. The CAP assigned multidisciplinary groups of pathologists, surgeons, and radiation and medical oncologists to develop the protocols. Other pathologists and clinicians then reviewed them. After the reviews, the protocols were reviewed by multiple CAP committees and finally approved by its Board of Governors. The ADASP, in contrast, chose a pathologist expert in each field to assemble a group from within the pathology community (with clinician input if desired) to write specific cancer protocols. These were then approved by the ADASP council and subsequently by the membership. Even though both societies began the process at approximately the same time, the streamlined approach adopted by the ADASP enabled it to publish years earlier in pathology journals frequented by anatomic pathologists. Although the formats are somewhat different, the contents are essentially the same. The American College of Surgeons Commission on Cancer (COC) accredits cancer centers in the United States. Recently, the COC decided to require elements deemed as essential by the CAP to be described in all pathology reports in accredited cancer centers as of January 2004. It is important to note that it does not require that the specific CAP protocols or synoptic reports be used. ADASP has updated all of its protocols to comply with the COC requirements in the form of 37 uniform checklists. The checklists use the staging criteria cited in the American Joint Committee on Cancer 2002 staging manual (sixth edition) but include a variety of other references listed in each of the checklists. Moreover, the checklists are formatted for ease of use. They may be used as templates for uniform reporting and are designed to be compatible with voice-activated transcription. The different elements in these revised ADASP diagnostic checklists have been divided into required and optional. The term required in this context only signifies compliance with the COC guidelines. ADASP realizes that specimens and practices vary and that it will not be possible to report these elements in every case. However, ADASP hopes that pathologists will find these checklists useful in daily clinical practice, while facilitating compliance with the new COC requirements. The checklists are in standard PDF file format and may be easily downloaded from the ADASP Web site. They are not to be reproduced, altered, or used for commercial purposes without consent from ADASP. Features Required to Be Included in the Final Report The following features are required by ADASP to be included in the final report because they are generally accepted as being of prognostic importance, required for therapy, and/or traditionally expected. These guidelines are primarily intended for extrapleural pneumonectomy specimens, but may also be used to report features in less extensive resection and biopsy specimens as appropriate. 1-4 Am J Clin Pathol 2007;127:15-19 15 15 DOI: 10.1309/6A30YQHBMTHEJTEM 15
ADASP / REPORTING PLEURAL MESOTHELIOMA I. Gross description A. How the specimen was received unfixed or in formalin, intact or disrupted, oriented or not B. How the specimen was identified and procedure labeled (with, eg, patient s name, medical record number, surgical pathology accession number), designated as pleura (and other organs, as applicable), laterality, and procedure (core needle biopsy, thoracoscopic biopsy, thoracotomy and incisional biopsy, pleurectomy, or extrapleural pneumonectomy) C. Size and tissue(s) included overall size of the specimen should be measured in 3 dimensions and the tissues included in the specimen (eg, pleura, chest wall adipose tissue and/or skeletal muscle, rib[s], diaphragm, lymph nodes, mediastinal structures) documented D. Tumor description 1. Distribution diffuse, nodular, localized/solitary 2. Extent of pleura involved (circumferential, subtotal) and presence or absence of involvement of fissures and interlobular septa 3. Document dominant tumor mass(es) and size 4. Appearance color(s), texture (eg, firm, soft, gritty), infiltrative 5. Distance to closest resection margins (lateral soft tissue [chest wall] margin, bronchus, pulmonary vessels, mediastinal structures [if included], diaphragm) 6. Document appearance of excised thoracoscopic sites, if applicable (usually submitted separately) NOTE: Closest resection margins should be inked and sampled using perpendicular sections for areas where there is gross suspicion of involvement. 7. Involvement of adjacent tissues (eg, diaphragm, pericardium, lung, ribs, chest wall adipose tissue or skeletal muscle) 8. Lymph nodes number received (if any), site of origin, size, and description of cut surface 9. Specify location or orientation of each tissue block taken for routine processing 10. Description of the nonneoplastic pleura, lung, and other tissues 11. Whether a diagnostic frozen section was performed and the intraoperative diagnosis II. Diagnostic information A. Site, laterality, and procedure B. Histologic type 5 1. Epithelioid 2. Sarcomatoid 3. Biphasic 4. Desmoplastic 5. Other (specify) C. Extent of invasion document involvement of parietal and visceral pleura, diaphragm, lung, endothoracic fascia, mediastinal adipose tissue and/or organs, chest wall soft tissue (solitary or diffuse involvement), rib(s) D. Resection margin status positive (state which margin) or negative E. Lymph node status (if present) specific site(s) and number involved out of total for each site F. Pathologic stage based on pathologic features as reported above Features Optional for the Final Report Features in the following list may impact on the likelihood of recurrence or overall prognosis. They represent specific institutional preferences, or they are considered inconclusive vis-à-vis prognostic significance. Lymphovascular invasion Blood vessel invasion Findings in the nonneoplastic pleura and lung (eg, changes consistent with prior talc pleurodesis, plaques, fibrosis, asbestos bodies, asbestosis) NOTE: Owing to the etiologic association between asbestos exposure and malignant mesothelioma, quantitative fiber burden analysis may be requested in cases that include lung tissue as part of the specimen. Formalin-fixed, nonneoplastic lung tissue (at least 5 g), preferably from the lower lobe, may be stored for this purpose. Results of any ancillary studies (eg, histochemical stains, immunohistochemical analysis, electron microscopy) NOTE: Given the cytomorphologic overlap between malignant epithelioid mesothelioma and metastatic adenocarcinoma or malignant sarcomatoid mesothelioma and primary or metastatic sarcomas, ancillary techniques (eg, immunohistochemical analysis and/or electron microscopy) are routinely used to facilitate diagnosis. Because no single immunohistochemical marker is entirely sensitive or specific for malignant mesothelioma, a panel of stains should be used. The ADASP does not prescribe a particular panel of markers but recommends that at least 2 mesothelialassociated markers (eg, calretinin, cytokeratins 5/6, D2-40, WT1) be used in conjunction with 2 or more markers that are usually negative in malignant mesothelioma (eg, carcinoembryonic antigen, thyroid transcription factor-1, Ber- EP4, MOC-31). 6-10 The results of ancillary techniques should be carefully correlated with the radiographic and gross distribution of tumor. * Committee members are Kelly J. Butnor, MD 1 (chairperson); Thomas A. Sporn, MD, 2 and Nelson G. Ordonez, MD, 3 from the Departments of Pathology, 1 University of Vermont, Burlington; 2 Duke University, Durham, NC; and 3 M.D. Anderson Cancer Center, Houston, TX. 16 Am J Clin Pathol 2007;127:15-19 16 DOI: 10.1309/6A30YQHBMTHEJTEM
References 1. Rusch VW. A proposed new international TNM staging system for malignant pleural mesothelioma: from the International Mesothelioma Interest Group. Chest. 1995;108:1122-1128. 2. Rusch VW, Venkatraman ES. Important prognostic factors in patients with malignant pleural mesothelioma, managed surgically. Ann Thorac Surg. 1999;68:1799-1804. 3. Sugarbaker DJ, Garcia JP, Richards WG, et al. Extrapleural pneumonectomy in the multimodality therapy of malignant pleural mesothelioma: results in 120 consecutive patients. Ann Surg. 1996;224:288-294. 4. Sugarbaker DJ, Flores RM, Jaklitsch MT, et al. Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients. J Thorac Cardiovasc Surg. 1999;117:54-63. 5. Churg A, Roggli VL, Galateau-Salle F, et al. Mesothelioma. In: Travis WD, Brambilla E, Muller-Hermelink HK, et al, eds. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus, and Heart. Lyon, France: IARC Press; 2004:128-136. World Health Organization Classification of Tumours. 6. Chu AY, Litzky LA, Pasha TL, et al. Utility of D2-40, a novel mesothelial marker, in the diagnosis of malignant mesothelioma. Mod Pathol. 2005;18:105-110. 7. Cury PM, Butcher DN, Fisher C, et al. Value of the mesothelium-associated antibodies thrombomodulin, cytokeratin 5/6, calretinin, and CD44H in distinguishing epithelioid pleural mesothelioma from adenocarcinoma metastatic to the pleura. Mod Pathol. 2000;13:107-112. 8. Di Loreto C, Puglisi F, Di Lauro V, et al. TTF-1 protein expression in pleural malignant mesotheliomas and adenocarcinomas of the lung. Cancer Lett. 1998;124:73-78. 9. Ordonez NG. Value of cytokeratin 5/6 immunostaining in distinguishing epithelial mesothelioma of the pleura from lung adenocarcinoma. Am J Surg Pathol. 1998;22:1215-1221. 10. Ordonez NG. Value of the Ber-EP4 antibody in differentiating epithelial pleural mesothelioma from adenocarcinoma: the M.D. Anderson experience and a critical review of the literature. Am J Clin Pathol. 1998;109:85-89. Association of Directors of Anatomic and Surgical Pathology (Ver 1.2 2-06) Final Anatomic Diagnosis Checklist Pleural Mesothelioma Accession No.: Part No.: Date: Patient Name: Organ Site Operation Parietal pleura Right Core needle biopsy * Left Thoracoscopic biopsy * Visceral pleura Diaphragmatic Thoracotomy and incisional biopsy * Pleurectomy * Extrapleural pneumonectomy Other: * This checklist is primarily for extrapleural pneumonectomy specimens. For less extensive resection/biopsy specimens, not all of the checklist elements will apply. Primary Tumor Diagnosis (Required) Epithelioid (epithelial) mesothelioma Sarcomatoid mesothelioma Biphasic mesothelioma Desmoplastic mesothelioma Other: Am J Clin Pathol 2007;127:15-19 17 17 DOI: 10.1309/6A30YQHBMTHEJTEM 17
ADASP / REPORTING PLEURAL MESOTHELIOMA I. Extent of tumor (Required) A. Tumor involves parietal pleura with/without involvement of the ipsilateral visceral pleura B. Tumor involves ipsilateral parietal/visceral/parietal and visceral pleura with 1. Confluence of tumor involving the visceral pleura (including the fissure) 2. Invasion into but not through the diaphragm 3. Invasion of lung parenchyma 4. Invasion of the endothoracic fascia 5. Invasion into mediastinal adipose tissue 6. Solitary focus of tumor invading the soft tissue of the chest wall 7. Invasion into but not through the pericardium 8. Diffuse or multiple foci of tumor invading the soft tissue of the chest wall 9. Invasion of rib 10. Invasion through the diaphragm into the peritoneum 11. Invasion into great vessels/esophagus/trachea/other (mediastinal organ) 12. Direct extension into contralateral pleura 13. Invasion of the vertebra 14. Involvement of the inner surface of the pericardium 15. Invasion of the myocardium 16. Invasion of the brachial plexus II. Margins of excision (Required) 1. Surgical margins are free of malignant mesothelioma 2. Malignant mesothelioma is present at margin(s) of excision NOTE: All of the following lymph node groups will not be identified in most cases. However, appropriate designations are provided below. Lymph nodes (peribronchial, specify laterality): Lymph nodes (hilar, specify laterality): NOTE: Regional lymph nodes include internal mammary, intrathoracic, scalene, and supraclavicular lymph nodes. The regional lymph node mapping and staging are the same as for pulmonary carcinoma. 18 Am J Clin Pathol 2007;127:15-19 18 DOI: 10.1309/6A30YQHBMTHEJTEM
Additional Tumor Features (Optional) A. Lymphatic vessel invasion: Identified Not identified B. Blood vessel invasion: Identified Not identified Nonneoplastic lung/pleura (Optional) A. Asbestos bodies identified B. Pleural plaques identified C. Interstitial fibrosis present D. Changes consistent with prior talc pleurodesis identified Comment: Ancillary Studies (Optional) Special stains are performed, the results are as follows: A. B. C. D. Interpretation Immunohistochemical studies are performed, the results are as follows: A. B. C. D. E. F. G. H. Interpretation ptn stage 1 (Required) A. Primary tumor 1. ptx Primary tumor cannot be assessed 2. pt0 No evidence of primary tumor 3. pt1a Tumor involves ipsilateral parietal (mediastinal, diaphragmatic) pleura, without involvement of the visceral pleura 4. pt1b Tumor involves ipsilateral parietal (mediastinal, diaphragmatic) pleura, with focal involvement of the visceral pleura 5. pt2 Tumor involves any of the ipsilateral pleural surfaces with at least one of the following: Confluent visceral pleural tumor (including fissure) Invasion of diaphragmatic muscle Solitary focus of tumor invading the soft tissues of the chest wall Invasion of lung parenchyma 6. pt3 Tumor involves any of the ipsilateral pleural surfaces with at least one of the following: Invasion of the endothoracic fascia Invasion intro mediastinal fat Solitary focus of tumor invading the soft tissues of the chest wall Nontransmural involvement of the pericardium 7. pt4 Tumor involves any of the ipsilateral pleural surfaces with at least one of the following: Diffuse or multifocal invasion of the soft tissues of the chest wall Any involvement of rib Invasion through the diaphragm into the peritoneum Invasion of any mediastinal organs Direct extension to the contralateral pleura Invasion into the spine Extension to the internal surface of the pericardium Pericardial effusion with positive cytology Invasion of the myocardium Invasion of the brachial plexus B. Regional lymph nodes 1. pnx Regional lymph nodes cannot be assessed 2. pn0 No regional lymph node metastasis 3. pn1 Metastasis in ipsilateral bronchopulmonary and/or hilar lymph node(s) 4. pn2 Metastasis in the subcarinal lymph node(s) and/or ipsilateral internal mammary or mediastinal lymph node(s) 5. pn3 Metastasis in contralateral mediastinal, internal mammary, or hilar lymph node(s) and/or the ipsilateral or contralateral supraclavicular or scalene lymph node(s) C. Distant metastasis 1. pmx Cannot be assessed 2. pm0 No distant metastasis 3. pm1 Distant metastasis Reference 1. Greene FL, Page BL, Fleming ID, et al (American Joint Committee on Cancer), eds. AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer; 2002:179-184. Am J Clin Pathol 2007;127:15-19 19 19 DOI: 10.1309/6A30YQHBMTHEJTEM 19