Document k6J2OOjyj9wrYkeKxeXLdLqw0

KMESA Medical Literature Protocol for the Examination of Specimens From Patients With Malignant Pleural Mesothelioma A Basis for Checklists Gerald Nash, MD; Christopher N. Otis, MD; for the Members of the Cancer Committee, College of American Pathologists This protocol is intended to assist pathologists in pro viding clinically useful and relevant information as a result of the examination of surgical specimens. Use of this protocol is intended to be entirely voluntary. If equally valid protocols or similar documents are applicable, the pathologist is, of course, free to follow those authorities. Indeed, the ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of the individual circumstances presented by a spe cific patient or specimen. ' It should be understood that adherence to this protocol will not guarantee a successful result. Nevertheless, pathol ogists are urged to familiarize themselves with this docu ment. Should a physician choose to deviate from die protocol owing to the circumstances of a particular patient or speci men, Ae physician is advised to make a contemporaneous written notation of the reason for the procedure followed. The College recognizes that this document may be used by hospitals, attorneys, managed care organizations, insur ance carriers, and other payers. However, the document was developed solely as a tool to assist pathologists in the diag nostic process by providing information that reflects the state of relevant medical knowledge at the time the protocol was first published. It was not developed for credentialing, liti gation, or reimbursement purposes; The College cautions that any uses of the protocol for these purposes involve con siderations that are beyond the scope of this document. PROTOCOL FOR THE EXAMINATION OF SPECIMENS FROM PATIENTS WITH MALICNANT PLEURAL MESOTHELIOMA I. Cytologic Material A. Clinical information 1. Patient identification a. Name b. Identification number c. Age (birth date) d. Gender 2. Responsible physidan(s) Accepted for publication August 26, 1998. ` From the Department of Pathology, Baystate Medical Center, Spring field, Mass. This protocol was developed by the Cancer Committee of the Col lege of American Pathologists and was submitted for editorial review and publication. It represents the views of the Cancer Committee and is not the official policy of the College of American Pathologists. Reprints: Joe Schramm, College of American Pathologists, 325 Wau- kegan.Rd, NorthfielcUL 60093-2750. ' .. Arch Pathol Lab Med--Vo! 123, January 1999 3. Date of procedure 4. Other clinical information a. Relevant, history (1) Present/past occupation (2) Asbestos exposure (3) Radiation exposure (4) Previous diagnosis of cancer or active infection (5) Previous treatment b. Relevant findings , (1) Pleural effusion(s) (duration) (2) Pleural plaque(s) or thickening (3) Imaging studies c. Clinical diagnosis d. Procedure (eg, thoracentesis, percutaneous fine-needle aspiration, thoracoscopy) e. Operative findings f. Anatomic site of specimen (eg, pleural space, including laterality, pericardial space) g. Type of specimen (eg, pleural fluid, pleu ral-based mass) B. Macroscopic examination 1. Specimen a. Unfixed/fixed (specify fixative) b. Number of slides received, if appropriate c. Quantity and appearance of fluid sped- men, if appropriate (including viscosity) d. Other (eg, cytologic preparation from tis sue) " e Results of intraprocedural consultation 2. Material prepared for microscopic evaluation (eg, smear, cytocentrifuge, thin preparation of fluid, cell block) 3. Spetial studies (specify) (eg, immunohisto- cnemistry, electron microscopy) (note A) C. Microscopic evaluation 1. Adequacy of spedmen (if unsatisfactory for evaluation, specify reasons) 2. Tumor, if present a. Histologic type, if possible (note B) b. Other features (eg, nuclear grade, necrosis) 3. Additional pathologic findings, if present (eg, ferruginous bodies) 4. Results/status of spedal studies (spedfy) (eg, immunohistodhemistry, electron microscopy) (note A) - 5. Comments Malignant Pleural Mesothelioma--Nash et al 39 a. Correlation with intraprocedural consul , tation, as appropriate , b. Correlation with other specimens, as ap propriate c. Correlation with clinical information, as appropriate II. Incisional Biopsy A. Clinical information 1. Patient identification . a. Name b. Identification number c. Age {birth date) d. Gender 2. Responsible physidan{s) 3. Date of procedure 4. Other clinical information a. Relevant history (1) Present/past occupation (2) Asbestos exposure (3) Radiation exposure (4) Previous diagnosis of cancer or active infection (5) Previous treatment b. Relevant findings (1) Pleural effusion(s) (duration) (2) Pleural plaque(s) or thickening (3) Imaging studies c. Clinical diagnosis . d. Procedure (eg, percutaneous needle biop sy, thoracoscopic biopsy of pleura and/or lung, open thoracotomy biopsy of pleura and/or lung, lymph node biopsy) e. Operative findings . f. Anatomic site(s) of specimen (eg, parietal / visceral pleura, lung indicating lobe and laterality, mediastinal node, diaphragm, pericardium) g. Type(s) of specimen (eg, pleura, lung, lymph node, tumor nodule) B. Macroscopic examination 1. Specimen a. Unfixed / fixed (specify fixative) b. Size (3 dimensions) . c. Descriptive features (color, hemorrhage, necrosis) d. Results of intraoperative consultation 2. Tissue submitted for microscopic evaluation a. Submit entire specimen, if possible b. Frozen section tissue fragments) (unless saved for special studies) 3. Special studies (specify) (eg, immunohisto- cnemistry, electron microscopy) (note A) C. Microscopic evaluation 1. Tumor a. Histologic type (note B) b. Histologic grade (note C) c. Extent of invasion (note D) 2. Additional pathologic findings, if present a. Ferruginous bodies b. Pleural plaque . c. Pulmonary interstitial fibrosis d. Other(s) . 3, Other tissue(s) present - 4. Results/status of special studies (specify) 5. Comments 40 Arch Pathol Lab Med--Vol 123, January 1999 a. Correlation with intraoperative consulta-; tion, as appropriate \ b. Correlation with other specimens, as ap-j propriate j c. Correlation with clinical information, as appropriate III. Resection A. Clinical information 1. Patient identification a. Name b. Identification number . c. Age (birth date) d. Gender 2. Responsible physidan(s) 3. Date of procedure 4. Other clinical information a. Relevant history (1) Present/past occupation (2) Asbestos exposure (3) Radiation exposure (4) Previous diagnosis of cancer or active,* infection (5) Previous treatment b. Relevant findings (1) Pleural effusion(s) (duration) (2) Pleural plaque(s) or thickening ' (3) Imaging studies c. Clinical diagnosis d. Procedure e. Operative findings f. Anatomic site(s) of specimen B. Macroscopic examination 1. Specimens a. Organ(s)/tissue(s) included b. Unfixed/fixed (specify fixative) c. Size (3 dimensions) d. Weight e. External aspect (extent of resection) | f. Visceral pleura, as appropriate g. Attached tissue, as appropriate (eg, pleu ra / pericardium / diaphragm) h. Orientation, if designated by surgeon i. Results of intraoperative consultation j 2* Tumor a. Location b. Size (3 dimensions and minimum / maxi mum thickness of involved pleura) c. Descriptive features (eg, color, diffuse/lo calized/circumscribed, consistency) d. Extent of invasion, as appropriate (note D) j 3. Margins (resections performed for surgical! cure) I a. Bronchus | b. Pulmonary vessels c. Parietal pleura (1) Chest wall f j I (2) MediastinaL (includingpericardium,| great vessels, esophagus, trachea, ver- 5 tebral bodies) 1 d. Diaphragm ? e. Extrapleural chest wall (including excised . ... . thoracoscopic- site andoldscars) ; f. Note areas designated by surgeon 4. Other pleura/lung Malignant Pleural Mesothelioma--Nash el a! > consulta-: i ns, as apnation, as r or active > ing ion) {eg, pleurgeon tation lum/maxiira) diffuse/Joncy) riate {note it surgical ricardium, achea, verng excised > :on a. Normal b. Abnormal (specify)' 5. Regional lymph nodes (note E) a. Total number* * All nodes included in a pulmonary specimen are designated N1 (note E) un less otherwise specified by surgeon. b. Number involved by tumor (1) Extracapsular extension (2) Distinguish metastasis from nodal in volvement by direct extension, as ap propriate 6. Separately submitted lymph nodes (report each node station separately) (note E) a. Location (station) specified by surgeon b. . Total number c. Number involved by tumor (1) Extracapsular extension (2) Distinguish metastasis from nodal in volvement by direct extension, as ap propriate 7. Tissues submitted for microscopic evaluation a. Tumor relation to pleura b. Tumor relation to adjacent lung c. Tumor relation to extrapleural tissues (1) Chest wall (2) Diaphragm (3) Pericardium , (4) Mediastinal tissues d. Margins, as appropriate (1) Bronchus (2) Pulmonary vessels (3) Parietal pleura i. Chest wall . ii. Mediastinal (pericardium, great vessels, esophagus, trachea, verte bral bodies) (4) Diaphragm (5) Extrapleural chest wall (6) Areas marked by surgeon e. Nonneoplastic pleura/lung (1) Normal (2) Abnormal f. Attached tissue g. All lymph nodes h. Frozen section tissue fragments) (unless saved for special studies) i. Other(s) (specify) 8. Special studies (specify) (eg, immunohisto- chemistry, electron microscopy) (note A) C. Microscopic evaluation 1. Tumor a. Histologic type (note B) . b. Histologic grade (note C) c. Site (laterality, visceral/parietal pleura, pericardium) d. Size (from gross description, diffuse/lo calized) . e. Extent of invasion (note D) * 2. Regional lymph nodes (note E) a. Site(s) (1) Included in pulmonary specimen (2) Separately submitted (report each ......................node -station- separately,- as specified) b. Number s--Nash et at Arch Pathol Lab Med--Vo! 123, January 1999 (1) Total number (2) Number with metastasis (note extra capsular invasion,,if present) 3. Margins a. Bronchus b. Pulmonary vessels c. Parietal pleura (1) Chest wall (2) Mediastinal i. Pericardium ii. Great vessels iii. Esophagus iv. Trachea v. Vertebral bodies d. Diaphragm e Extrapleural chest wall (including excised thoracoscopic site and old scars) f. Areas marked by surgeon 4. Additional pathologic findings, if present a. Nonneoplastic lung b. Ferruginous bodies c. Pleural plaque d. Interstitial fibrosis e. Other(s) 5. Distant metastasis, specify site(s) (note D) 6. Other tissue(s)/organ(s) 7. Results/status of special studies (specify) 8. Comments a. Correlation with intraoperative consulta tion, as appropriate b. Correlation with other specimens, as ap propriate c. Correlation with clinical information, as ' appropriate EXPLANATORY NOTES A: Special Studies.--Immunohistochemistry and elec tron microscopy have become important adjuncts to rou tine microscopic evaluation in the diagnosis and classifi cation of malignant mesothelioma.1-7 B: Histologic Type.--For consistency in reporting, the histologic classification published by the World Health Or ganization is recommended. However, other classifications may be used. The more detailed histologic classification of malignant mesothelioma by Hammar recognizes histologic variations that might be confused with other neoplasms and points out light microscopic similarities to benign pleu ral cells, including the surface mesothelial cell and the mul tipotential subserosal spindle cell.9 The localized fibrous tumor of the pleura (previously referred to as localized fibrous mesothelioma) is not in cluded in this protocol because it is generally regarded as a benign tumor arising from the subserosal .fibrous tissue rather than from the mesotheliiim.10 World Health Organization Classification8 Epithelial Fibrous (spindle cell) Biphasic Hammar Classification9 Epithelial T-ubulopapillary Epithelioid . Malignant Pleural Mesothelioma--Nash et al 41 mm Glandular Large cell / giant cell Small cell Adenoid-cystic Signet ring Sarcomatoid (fibrous, sarcomatous, mesenchymal) Mixed epithelial-sarcomatoid (biphasic) Transitional Desmoplastic - C: Histologic Grading.--There is no specific recom mended histologic grading system for malignant meso thelioma of the pleura. D: Staging.--The protocol recommends the American Joint Committee on Cancer (AJCC) and International Union Against Cancer (UICC) TNM Staging System, as follows.11-11 However, the protocol does not preclude the use of other staging systems such as the staging system of the International Mesothelioma Interest Group, which is also shown.13 TNM and Stage Groupings Primary Tumor (T)* TX Primary tumor cannot be assessed TO No evidence of primary tumor T1 Tumor limited to ipsilateral parietal and/or vis ceral pleura T2 Tumor invades any of the following: ipsilateral lung, endothoradc fasda, diaphragm, or pericardium T3 Tumor invades any of the following: ipsilateral chest wall muscle, ribs, or mediastinal organs or tissues * T4 Tumor directly extends to any of the following: contralateral pleura, contralateral lung, peritone um, intra-abdominal organs, cervical tissues * By AJCC/UICC convention, the designation "T" of the TNM dassification refers exdusively to the first resection of a primary tumor. The prefix symbol "p" refers to the path ologic dassification of the TNM (pTNM), as opposed to the clinical dassificatioa Pathologic dassification is based on gross and microscopic examination. Therefore pT entails a resection of the primary tumor or biopsy adequate to eval uate the highest pT category; pN entails removal of nodes adequate to validate lymph node metastasis; and pM implies microscopic examination of distant lesions. Clinfcal dassifi cation (cTNM) is usually carried out by he referring physidan before treatment during initial evaluation of the patient or when pathologic dassification is not possible The absence or presence of residual tumor following preoperative nonsurgical therapy (eg, chemotherapy or ra diation treatment) may be described by the symbol "R" and is classified as follows: RX Presence of residual tumor cannot be assessed RO No residual tumor R1 Microscopic residual tumor R2 Macroscopic residual tumor If residual tumor is present, its extent may be documented by the TNM classification preceded by the symbol "y" (eg, ypTl). Local recurrence following a previous resection should be classified with the prefix "r" (eg, rpTl). Regional Lymph Nodes (N) NX Regional lymph nodes cannot be assessed 42 Arch PaShoI Lab Med--Vol 123, January 1999 NO No regional lymph node metastasis N1 Metastasis in ipsilateral peribronchial and/or ip- silateral 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, contralatera! hilar, ipsilateral or contralateral scalene, or su praclavicular lymph node(s) Distant Metastasis (M) MX Presence of distant metastasis cannot be assessed MO No evidence of distant metastasis Ml Distant metastasis AJCC/UICC TNM Stage Groupings Stage I Stage II Stage HI Stage IV T1 T2 T1 T2 T1 T2 T3 Any T T4 Any T NO NO N1 N1 N2 N2 NO, 1, 2 N3 Any N Any N MO MO MO MO MO MO MO MO MO Ml International Mesothelioma Interest Group Staging System Primary Tumor (T) T1 Tla Tumor limited to the ipsilateral parietal pleura, including mediastinal and diaphragmatic pleu ra; no involvement of the visceral pleura Tib Tumor involving the ipsilateral parietal pleura, including mediastinal and diaphragmatic pleu ra; scattered foci of tumor also involving the vis ceral pleura T2 Tumor involving each of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least 1 of the follow ing features: Involvement of diaphragmatic muscle Confluent visceral pleural tumor (including the fissures) or extension of tumor from vis ceral pleura into the underlying pulmonary parenchyma T3* Tumor involving all of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least 1 of the follow ing features: Involvement of the endothoradc fasda Extension into the mediastinal fat Solitary, completely resectable focus of tumor extending into the soft tissues of the chest wall Nontransmural involvement of the pericardi um * T3 describes locally advanced but potentially resect able tumor. Malignant Pleural Mesothelioma--Nash et at T4t Tumor involving all of the ipsilateral pleural surfaces (parietal, mediastinal diaphragmatic, and visceral pleura) with at least 1 of the follow ing features: Diffuse extension or multifocal masses of tu mor in the chest wall with or without as sociated rib destruction Direct transdiaphragmatic extension of tumor to the peritoneum Direct extension of tumor to the contralateral pleura Direct extension of tumor to 1 or more me diastinal organs Direct extension of tumorinto the spine Tumor extending through to the internal sur face of the pericardium with or without a pericardial effusion; or tumor involving the myocardium t T4 describes locally advanced technically unresectable tumor. Regional Lymph Nodes (N) NX Regional lymph nodes cannot be assessed NO No regional lymph node metastasis N1 Metastasis in the ipsilateral bronchopulmonary or hilar lymph nodes N2 Metastasis in the subcarinal or the ipsilateral me diastinal lymph nodes, including the ipsilateral in ternal mammary nodes N3 Metastasis in the contralateral mediastinal, contra lateral internal mammary, ipsilateral or contralat eral supraclavicular lymph nodes Distant Metastasis (M) MX Distant metastasis cannot be assessed MO No distant metastasis Ml Distant metastasis present International Mesothelioma Interest Group Stage Groupings Stage I la lb Stage II Stage ID Stage IV Tla Tib T2 T3 T1 T2 T1 T2 T4 Any T Any T NO NO NO NO Nl Nl N2 N2 Any N N3 Any N MO MO MO MO MO MO MO MO MO MO Ml E: Regional Lymph Node Classification.--A classifi cation of regional lymph nodes adapted from Naruke14 and recommended by the AJCC follows.51 This anatomic classification of nodal groups is not to be confused with N categories of regional lymph node metastasis of the TNM Staging System detailed in note D. N2 nodes Superior mediastinal.nodes Highest mediastinal Arch Pathol Lab Med--Vol 123, January 1999 Upper peritracheal Pretracheal and retrotracheal Lower peritracheal (including azygos nodes) Aortic nodes Subaortic (aortic window) Periaortic (ascending aorta or phrenic) Inferior mediastinal nodes Subcarinal Periesophageal (below carina) Pulmonary ligament Nl nodes Hilar Interlobar Lobar Segmental Classification of lymph nodes, as recommended by the American Thoracic Society,15 is as follows. Definitions of Lymph Node Stations 2R Right upper peritracheal (suprainnominate) nodes: nodes to the right of the midline of the trachea be tween the intersection of the caudal margin of the innominate artery with the trachea and the apex of the lung (includes highest R mediastinal node) 2L Left upper peritracheal (supra-aortic nodes): nodes to the left of the midline of the trachea between the top of the aortic arch and the apex of the lung (in cludes highest L mediastinal node) 4R Right lower peritracheal nodes: nodes to the right of the midline of the trachea between the cephalic bor der 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 (indudes some pretracheal nod) 5 Aortopulmonary nodes: subaortic and para-aortic 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 as cending aorta or the innominate artery (indudes some pretracheal and preaortic nodes) 7 Subcarinal nodes: nodes arising caudal to the carina of the trachea but not assodated with the lower lobe bronchi or arteries within the lung 8 Paraesophageal nodes: nodes dorsal to the posterior wall of the trachea and to the right or left of the midline of the esophagus (includes retrotracheal but not subcarinal nodes) 9 Right or left pulmonary ligament nodes: nodes with in 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 ce phalic border of the azygos vein to the origin of the right upper lobe bronchus I0L 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 Malignant Pleural Mesothelioma--Nash et a I 43 11 Intrapulmonary nodes: nodes removed in the right or left lung specimen plus those distal to the mainstem bronchi or secondary carina (includes interlo bar, lobar, and segjnental nodes); postthoracotomy staging may designate 11 interlobar, 12 lobar, 13 seg mental, 14 subsegmental Contributors: the College of American Pathologists Cancer Committee; Karen Antman, MD; Samuel P. Hammar, MD; Eu gene Mark, MD; Harvey I. Pass, MD; and Peter B. Schiff, MD, PhD. References 1. Frisman D, McCarthy W, Schleiff P, Buckner S, Nocito), O'Leary T. Imirsunocytochemislry in the differential diagnosis of effusions: use of logistic regression to select a panel of antibodies to distinguish adenocarcinomas from mesothelial proliferations. Mod Pathol, 1993;6:179-184. 2. Gaffey M, Mills S, Swanson P, Zarbo R, Shah A, Wick M. immunoreadivity for Ber-EP4 in adenocarcinomas, adenomatoid tumors and malignant mesothe liomas. Am I Surg Pathol. 1992;16:593-599. 3. Otis CN, Carter D, Cole S, Battifora H. Immunohistocbemical evaluation of pleural mesothelioma and pulmonary adenocarcinoma; a bi-institutional study of 47 cases. Am I Surg Pathol. 1987;11:445-456. 4. Sheibani K, Azumi N, Battifora H. Further evidence demonstrating the value of leu Ml antigen in the differential diagnosis of malignant mesothelioma and adenocarcinoma: an Smmunohistologic evaluation of 395 cases jabstradj. Lab Invest. 1988;58:B4A. 5. Sheibani K, Shin S, Kerzirian J, Weiss L. Ber-EP4 antibody as a discriminant in the differential diagnosis of malignant mesothelioma versus adenocarcinoma. Am) Surg Pathol. 1991;15:779-784. ' 6. Suzuki Y, CHurg f, Kannerstetn M. Infrastructure of human malignant diffuse mesothelioma. Am j Pathol. 1976;85:241-262. . 7. Warhol Mf, Corson JM, An ultrastrudural comparison of mesotheliomas with adenocarcinomas of the lung and breast. Hum Pathol. 1985;16:50-55. 8. World Health Organization. Histologic Typing of Lung Tumours. 2nd ed. Geneva, Switzerland: World Health Organization; 1981. 9. Hammar S. Pleural diseases. In: Dail D, Hammer S, eds. Pulmonary ft- thology. 2nd ed. New York, NY; Springer-Verlag: 1994:1494. 10. England DM, Hochhofzer L, McCarthy MJ, Localized benign and malig nant fibrous tumors of the pleura: a clinicopathoiogic review of 223 cases. Am l Svrgfbthol. 1989;13:640-658. 11. Fleming ID, Cooper JS, Henson DE, et al, eds. A/CC Manual for Staging of Cancer. 5th ed. Philadelphia, Pa; Lippincot! Raven; 1997. 12. Hermanek P, Sobin L. TNM Classification of Malignant Tumours. 4th ed. Berlin, Germany: Springer-Verlag; 1992. 13. Rusch VW. A proposed new international TNM staging system for malig nant pleural mesothelioma from the International Mesothelioma Interest Group. Chest. 1995;108:1122-1128. 14. Naruke T, Suemasu K, Ishikawa S. Lymph node mapping and curability at various levels of metastases in resected lung cancer. ) Thome Cardiovasc Surg. 1978;76:832-839. 15. American Thoracic Society: Clinical staging of primary lung cancer. Am Rev Respir Dis, 1983;127:659-664. Bibliography Aisner J. Current approach to malignant mesothelioma of the pleura. Chest. 1995; 107.332S-344S. Antman K. Natural history and epidemiology of malignant mesothelioma. Chest. 1993;103lsuppl):373-376. DiBonlto L, Falconteri G, Colautti I, Bonifacio God D, Dudine S, Giarelli L. Cytopathology of malignant mesothelioma; a study of its patterns and histological bases. Diagn Cytopathol. 1993;9:25-31. Grove A, Paulson SM, Gregersen M. The value of immunohistochemistry of pleu ral biopsy specimens in the differential diagnosis between malignant mesothe lioma and metastatic carcinoma. Pathol Res Pract 1994;190:1044-1055. Johansson L, Under) CJ. Aspects of histopathologic subtype as a prognostic factor in 85 pleural mesotheliomas. Chest. 1996;109:109-114. Leong AS, Vernon-Roberts E. The itnmunochemistry of malignant mesothelioma. Pathol Annu. 1994;29(pl 2):157-179. Pass H. Contemporary approaches in the investigation and treatment of malignant pleural mesothelioma. Chest Surg Clin N Am. 1994;4:497-5IS. Pass H, Pogrebniak H. Malignant pleural mesothelioma. In: Wells S, ed. Current Problems in Surgery. Vol 30. 1993:923-1012. Qua j, Rao U, Takita H, Malignant pleural mesothelioma: a clinicopathoiogic study.../ Surg Oncol. 1993;54:47-50. 5ugarbaker D, Strauss G, Lynch T, et al. Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelioma.) Clin Oncol. 1993;11:1172-1178. Tammilehto L, Maasilta P, Kostianinen S, et al. Diagnosis and prognostic factors in malignant pleural mesothelioma: a retrospective analysis of 65 patients. Res piration. 1992;59:129-135. 44 Arch Pathol Lab Med--Vol 123, January 1999 Malignant Pleural Mesothelioma--Nash et a!