Staging of Lung Cancer



Staging of Lung Cancer


Andre L. Moreira, M.D.

Fabio R. Tavora, M.D., Ph.D.

Marie-Christine Aubry, M.D.



Introduction

Staging of lung cancer currently follows the eighth edition of the American Joint Committee on Cancer (AJCC) cancer stage manual. The seventh edition as published in 20021,2,3 is at the time of this writing being replaced by the eighth edition as proposed by the International Association for the Study of Lung Cancer (IASLC) in association with AJCC and the International Union Against Cancer (UICC).

The IASLC stage committee evaluated over 80,000 cases of lung cancer obtained from multiple centers in twenty countries and four continents. This large study provided a robust validation of the system and proposed changes from the previous editions. The current staging system is also based on the TNM system, where T stands for the size and local extent of the tumor, N stands for the extent of nodal metastasis, and M for the presence or absence of metastasis. The TNM staging system is the most important prognostic marker for patients with lung cancer. It is also an important guide for patient management.

In a very simplified way, patients with stage one are treated with surgery alone. Patients with stages two and three receive adjuvant therapy after excision of the carcinoma; patients with lung cancer within stage three can also be candidates for neoadjuvant therapy followed by resection of residual tumor. Patients with stage four are treated predominately with chemotherapy and are not usually surgical candidates.

The staging system can be clinical or pathologic. The pathologic stage is based on the examination of excised tumor or the presence of local or distant metastasis by biopsy material including cytology specimens. Pathologic stage should be preceded by the letter p, therefore pTNM. The clinical staging is composed of radiographic, nuclear medicine, and surgical information that is not always available to the pathologist during the time of examination of the excised specimen. The final stage should be done by the treating physician and incorporates the information obtained by the pathologic and clinical TNM.

Compared to the seventh edition of the cancer staging manual, the changes in the eighth edition are predominately seen on the size of tumor (T). pT1a (mi) has been added for minimally invasive carcinomas. pT1a is currently ≤1 cm (previously ≤2 cm). pT1b is now ≤ 2 cm (previously ≤3 cm). pT1c has been added for tumors between 2 cm and 3 cm. pT2a designates tumors 3 to 4 cm, pT2b 4 cm to 5 cm, pT3 5 cm to 7 cm, and pT4 tumors ≥ 7 cm. Other features override size. If there is involvement of the main bronchus without involving the carina, visceral pleural invasion, or obstructive pneumonitis that extends to the hilum, tumors ≤ 3 cm are designated pT2a tumors. pT3 tumors include tumors < 5 cm that invade the chest wall, phrenic nerve, parietal pericardium, or associated separate tumor nodule(s) seen grossly or by imaging in the same lobe (satellite nodules). pT4 tumors include those < 7 cm involving the diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina, or tumor nodules in a different ipsilateral lobe.


Modifications in the T Category

The key changes in the current staging system occurred in T category. In the seventh AJCC edition, T1 was subclassified as T1a and T1b according to tumor size.1 In the eighth edition, there are three stages, T1a-c, <1, 1 to 2, and 2 to 3 cm (see above). Similar changes occurred in T2 tumors. In the seventh AJCC edition, T2a are tumors larger than 3 cm but smaller than 5 cm, and T2b are larger than five centimeters but <7 cm in greatest dimension; the corresponding sizes have been changed to 3 to 4 and 4 to 5 cm. As previously, a T1 tumor can be upgraded to T2 if pleural invasion is identified, if located within 2 cm of the carina, or if associated with atelectasis or obstructive pneumonitis.

The designation of T3 is used for tumors that measure more than 5 cm in the eighth edition, as compared to 5 cm previously, or tumors of any size with direct involvement of the chest wall or any other structure such as mediastinal pleura or pericardium.

T4 tumors are tumors now > 7 cm (previously of any size) or that invade the mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, and carina. Patients with tumor nodules showing the same morphologic characteristics in a different ipsilateral lobe from that of the main primary tumor are still designated as T4. The analysis of survival data shows that patients with ipsilateral lung nodules with the same morphology behave as stage IIIB and not as stage IV if these satellite nodules were to be considered metastatic sites.4


Problems with the Determination of T Category


Assessment of Tumor Size

One of the most important problems with the T category is the accurate determination of the size of the tumor.5,6,7,8 The tumor size can be overestimated when it is accompanied by a prominent reactive process assumed to represent the true dimensions of the neoplastic process. Examples of these reactive processes are obstructive pneumonia, organizing pneumonia, and even scars. These overestimations can be done during the pathologic examination of the excised specimen, but tumor size can also be overestimated radiographically. In most cases, these discrepancies become irrelevant when there is a good correlation between gross and radiographic measurements. In case of a large discrepancy, the microscopic measurement of the tumor is adequate, especially when obstructive pneumonia or an extensive area of organizing pneumonia is diagnosed under the microscope. A microscopic measurement of the tumor should be indicated in the report with an explanation about the discrepancy between macroscopic and microscopic size determination.

Differences between measurements in fresh or formalin-fixed tissue have also been reported.6,9,10 However, eventhough the discrepancy may be small, it could lead to reporting a T2a tumor as a T1b. In reality, the survival curves for T2a and T1b are not significantly different when tumor size is the only prognostic indicator.9

On the other hand, the tumor size can be underestimated, which is more commonly seen when an adenocarcinoma with a predominant lepidic component is present. In these cases, the gross measurements are often determined by the invasive component of the tumor that forms a solid mass due to desmoplastic reaction or tumor growth. This is particularly important in the setting of the new classification where adenocarcinoma in situ and minimally invasive adenocarcinomas are diagnosed based on the size of the invasive component.

Lepidic or papillary patterns of growth may resemble normal lung tissue and are often difficult to see grossly during specimen evaluation of fresh tissue. Awareness of the radiographic image of the tumor and radiographic size estimation is an important aspect of gross examination to ensure that appropriate numbers of sections are taken and all components of an adenocarcinoma are sampled. Lepidic growth pattern is often described radiographically as ground-glass opacities, whereas invasive components are often described as solid.11 There is currently discussion in the thoracic pathology literature on tumor
size determination for adenocarcinoma with a prominent or exclusive lepidic component.11,12,13,14,15 The lepidic component is largely believed to represent in situ carcinoma, and as with other organs, it has been suggested that it should not be included in total tumor size estimate.1 However, as this chapter is being written, there is no consensus on this issue; the total size of the tumor including the in situ component currently remains included in the pathologic tumor size (pT).


Assessing Distance from Carina

The relationship of the tumor with anatomic structures such as the distance from the carina is an important determinant of the T category because it is independent of tumor size; however, this spatial relationship cannot be determined by the examination of a lobectomy or pneumonectomy specimen. Thus, refinement of the T classification should be done in conjunction and in consultation with the surgeon.


Assessing Invasion into Adjacent Organs

Another problem that may emerge for an accurate determination of T category by pathologists is invasion into adjacent organs. Often, adjacent organ involvement by tumor is dealt by surgeons at the time of excision; in most cases, the pathologist receives a separate additional specimen-labeled pericardial biopsy or soft tissue nodule in the ascending aorta, for example. These separate materials, if positive, can modify the T determination and should be incorporated into the final pathologic stage for the specimen. In another scenario, a fragment of pericardium or pleura may be attached to the main specimen. The role of the pathologist is to determine if the tumor invades into these structures or is simply adhered, which is important for an accurate determination of the pT category.

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Aug 19, 2016 | Posted by in CARDIOLOGY | Comments Off on Staging of Lung Cancer

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