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Article: New TNM Classification for Lung Cancer. Part II: A review Back to article | View all comments

Author: Dr. A. De la Guerra | February 07, 2010

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March 01, 2010 04:03 PM
Dr. A. De la Guerra's avatar

Dear Dr. M. Jagesh Kamath,

I am glad you enjoyed the article; thank you for your kind words.

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March 01, 2010 09:01 AM
Dr. Safaa Mahmoud's avatar

Dr. A. De la Guerra, thank you so much for this prompt and comprehensive answer. I learned a lot from your article and your reply. The information you wrote about the diagnostic approach to PE is very useful and your comment to justify excluding the M descriptor from the pathology staging templates is very much appreciated.
Best Regards.

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February 28, 2010 06:46 AM
Dr. A. De la Guerra's avatar

ERRATUM: Re: New TNM Classification for Lung Cancer. Part II: A review. by Dr. A. De la Guerra. Doctors Lounge Website. Available at: http://www.doctorslounge.com/index.php/articles/page/342. Accessed February 27 2010. In the section: Pleural dissemination and pericardial effusion, in the second paragraph, lines 2 and 3, the sentence: “Notice that diagnosis of a MPE can also be made by pleural biopsy, but in such cases disease is listed as M1 - stage IV”, should not be present. Both citologic and pathologic diagnosis of a MPE were considered T4 in the 6th edition of the TNM. The author regrets the error.

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February 28, 2010 06:43 AM
Dr. A. De la Guerra's avatar

Dear Dr. Safaa Mahmoud,

Thank you for your comments.

Your observation about the different forms of pleural involvement and their classification is almost exact, except for separate pleural nodules; they were T4, now M1a, the same as MPE.

On your first question, about the diagnosis and clinical staging of pleural effusions (PE) in patients with NSCLC, these are the rules for classification, word for word, according to the 6th edition of the TNM staging system (1-3):

“Most pleural effusions associated with lung cancer are due to tumor. However, there are a few patients in whom multiple cytopathologic examinations of pleural fluid are negative for tumor. In these cases, the fluid is non-bloody and is not an exudate. When 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 patient should be staged T1, T2, and T3.”

The opposite is also valid, that is to say, when the clinical picture is highly suggestive of MPE, despite a negative fluid cytology. We have to consider that pleural fluid cytology is diagnostic in only 60% of MPE (4, 5). There is evidence that clinical evaluation, including antecedent of cancer and CT characteristics, has a sensitivity of more than 90% in the diagnosis of MPE (6).

Clinical judgment is appropriate to establish the diagnosis of a MPE, when common diagnostic procedures had failed, in patients with microscopic confirmation of lung cancer, that due to the stage of the disease are not considered for treatment with curative intent (surgery with or without adjuvant therapy), and pathologic proof of MPE has no clinical relevance; consider that clinical stage guides initial management; pathologic stage defines prognosis.

If the diagnosis of cancer has not been established yet, or the patient has early stage disease, pathologic confirmation is mandatory. Most accepted approach for the diagnosis of exudative PE is:

• Cytological examination of pleural fluid; if negative repeat.
About 50% of MPE are negative at first thoracentesis (7).

• If second examination of pleural fluid is negative, do a contrast enhanced thoracic CT scanning to evaluate any pleural abnormality and make a decision to carry out a biopsy.
CT sensitivity for malignant pleural dissemination is about 85% (4, 8, 9).

• If thickening or nodularity is found, perform an imaging-guided pleural biopsy.
CT-guided pleural biopsy has almost 100% of sensitivity against 50% of blind biopsy (10, 11).

• If pleural biopsy is negative: do a thoracoscopy.

Your concern about the inconsistency in the statement that “diagnosis of a MPE can also be made by pleural biopsy, but in such cases disease is listed as M1 - stage IV” is absolutely justified. I appreciate very much your observation (and applaud your perspicaciousness). I didn’t notice the mistake; the correct statement must be that both, positive fluid cytology and pleural biopsy are valid to classify the tumor as T4 (according to the 6th edition). I am publishing an erratum right now.

On your commentary regarding the new pathology staging templates, I agree with you. Ideally every member of the multi-disciplinary team dedicated to the management of lung cancer should have the most complete and accurate information of the patient. In practice, communication between clinicians and pathologists is far from optimal.

The reason to exclude the M descriptor from the pathology staging templates is, as you mention, that pathologists usually do not have data about metastasis. The problem is that the pathologic assignment of the presence of metastases (pM1) requires a positive biopsy, consequently pMX does not exist. Pathologic classification of the absence of distant metastases (pM0) can only be made at autopsy. The risk of maintaining the M factor on the pathology staging templates is that if the pathologist does not know the clinical M he may consign a MX and exclude the case from staging.

Thank you again for your interest in the article.


References.

1. Mountain CF. Revisions in the international system for staging lung cancer. Chest 1997; 111 (6): 1710-1717.

2. Sobin LH, Wittekind C eds. Lung and pleural tumours. In: Sobin LH, Wittekind C eds. UICC International Union Against Cancer, TNM classification of malignant tumours, 6th ed. New York: Wiley-Liss, 2002; pp. 97-107.

3. Lung. In: American Joint Committee on Cancer. AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 167-181.

4. Maskell NA, Butland RJ; Pleural Diseases Group, Standards of Care Committee, British Thoracic Society. BTS guidelines for the investigation of a unilateral pleural effusion in adults. Thorax 2003; 58 Suppl 2: ii8-17.

5. Villena Garrido V, Ferrer Sancho J, Hernández Blasco L, de Pablo Gafas A, Pérez Rodríguez E, Rodríguez Panadero F, Romero Candeira S, Salvatierra Velázquez A, Valdés Cuadrado L; Area de Tecnicas y Trasplantes. SEPAR. Diagnosis and treatment of pleural effusion. Arch Bronconeumol 2006; 42 (7): 349-372.

6. Alemán C, Sanchez L, Alegre J, Ruiz E, Vázquez A, Soriano T, Sarrapio J, Teixidor J, Andreu J, Felip E, Armadans L, Fernández De Sevilla T. Differentiating between malignant and idiopathic pleural effusions: the value of diagnostic procedures. QJM 2007; 100 (6): 351-359.

7. Moffett PU, Moffett BK, Laber DA. Diagnosing and managing suspected malignant pleural effusions. J Support Oncol 2009; 7 (4): 143-146.

8. Traill ZC, Davies RJ, Gleeson FV. Thoracic computed tomography in patients with suspected malignant pleural effusions. Clin Radiol 2001; 56 (3): 193-196.

9. Arenas-Jiménez J, Alonso-Charterina S, Sánchez-Payá J, Fernández-Latorre F, Gil-Sánchez S, Lloret-Llorens M. Evaluation of CT findings for diagnosis of pleural effusions. Eur Radiol 2000;10 (4): 681-690.

10. Maskell NA, Gleeson FV, Davies RJ. Standard pleural biopsy versus CT-guided cutting-needle biopsy for diagnosis of malignant disease in pleural effusions: a randomised controlled trial. Lancet 2003; 361 (9366): 1326-1330.

11. Adams RF, Gleeson FV. Percutaneous image-guided cutting-needle biopsy of the pleura in the presence of a suspected malignant effusion. Radiology 2001; 219 (2): 510-514.

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February 26, 2010 02:58 PM
Dr. Safaa Mahmoud's avatar

Dr. A. De la Guerra, thank you so much for this comprehensive article.  Based on the new staging classifications, pleural involvement in lung cancer would follow one of these forms: direct tumor extension to visceral pleura described as T2, to parietal pleura described as T3; separate pleural nodules described as T4 and malignant pleural effusion (MPE) described as M1a.  Would you please comment on this statement if correctly received: MPE is considered as T4 if diagnosed only by clinical findings, but I find it strange that MPE is considered T4 if diagnosed by cytology but M1a if diagnosed by biopsy. And this how it is stated in the article (In TNM staging, either pleural fluid cytology or clinical judgment are valid to establish the diagnosis of a MPE and consider it as a T4 factor (26). Notice that diagnosis of a MPE can also be made by pleural biopsy, but in such cases disease is listed as M1 - stage IV).

Second as mentioned in your article, (since pathologists normally do not have information about metastasis, the M factor will not appear in pathology staging templates on the 7th edition (83)). We all understand that this information is always missing in the request sent to pathologist but do not you agree that pathologists should insist of getting the request with complete information including metastasis status when available rather than omitting this part at all. Would you kindly comment on this too?
Thank you again for this very comprehensive review, great effort indeed.

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February 24, 2010 02:23 AM
M. Jagesh Kamath, M.D.'s avatar

Very comprehensive study on the new TNM System.Well done, and neatly presented by Dr.Guerra.Congratulations!

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