TABLE 1:

PRINCIPLES OF PATHOLOGIC ASSESSMENT OF PRIMARY TUMORS^†

LUNG TUMOR BED
How to Recognize the Tumor bed, which is the area where the original pre-treatment tumor was considered to be located.
1.	To identify the tumor bed, look for the presence of pleural retraction and palpate the intact specimen.
2.	In cases where identification and/or orientation of the tumor are difficult, review of the pretherapy and preoperative CT can be helpful.
3.	Look for any identifying marks/stiches placed by the surgeon.
4.	After the tumor bed has been identified, lung specimens should be sectioned in the plane that demonstrates the maximum dimension and best reveals the tumor bed and its relationship to the surrounding structures relevant for staging and the surgical resection margin(s).
5.	Photograph the cut surface demonstrating the tumor bed and the adjacent structures. Save the images in the pathology electronic records.
6.	The gross size of the tumor bed should be assessed using a ruler to measure three-dimensional size.
7.	Document the distance between tumor bed and surgical resection margins in the gross description.
8.	Estimate percentage of gross necrosis that will be correlated with the estimated necrosis on the microscopic slides.
SAMPLING
How to sample the suitable area for assessment of response to neoadjuvant therapy
1.	Following the tumor bed measurement, the surgical specimens may be processed fresh or with routine fixation in 10% neutral buffered formalin least six hours and no longer than 48 hours.
2.	Cases with marked necrosis and cavitation are difficult to cut fresh. Overnight fixation may be helpful in such cases
3.	If the tumor is small (<3 cm) it should be entirely sampled.
4.	If the tumor is larger than 3 cm, an approximately 0.5 cm thick cross section of tumor in its maximum dimeson should be made and photographed.
5.	On this gross photograph, a map should be superimposed of the complete histologic sectioning corresponding to the submitted blocks (See Figure 5. These photographs should be saved with the pathology report, electronically if possible. Additional histologic sections can be submitted if desired.
6.	Histologic sections at the periphery of the tumor should include the border of the tumor with at least 1 centimeter of the surrounding nonneoplastic lung parenchyma in order to define the edge of the tumor.
HISTOLOGIC ASSESSMENT OF PRIMARY TUMORS
How to define the Border of the Tumor Bed from Surrounding Non-neoplastic Lung
1.	Identify reactive changes in surrounding non-neoplastic lung (for example: organizing pneumonia, interstitial fibrosis, hemorrhage, marked type II pneumocyte hyperplasia /reactive atypia and inflammatory infiltrates).
2.	Inflammatory cells that are part of the reactive changes surrounding the tumor bed must be distinguished from tumor stromal inflammation where the inflammatory cells should be confined to the tumor bed.
3.	The true tumor bed should consist only of viable tumor along with concurrent necrosis and stroma which includes both fibrosis and inflammation. The size of tumor bed should be adjusted for histologic changes related to neoadjuvant treatment in the surrounding lung.
4.	Correlate with the gross photograph with mapping of histologic sections in order to determine whether the gross measurement of the tumor bed size is an accurate assessment or if it includes non-neoplastic reactive changes.
How to Record the Histologic Features in Tumor Bed
1.	The percentages of viable tumor, stromal tissue, and necrosis should be estimated on the basis of the review of the microscopic sections on each slide and then the total percentage of viable tumor is estimated. The percentage should total 100% of the tumor bed.
2.	Each component should be assessed in 10% increments unless the amount is below 5% when an estimate of single percentages should be recorded.
3.	There are two stromal tissue components: fibrosis and inflammation. Although more detailed assessment of stroma can be made (Fibrosis: dense hyalinized connective tissue, fibroelastotic scarring and loose or myxoid connective tissue. Inflammation: chronic inflammation, acute inflammation, histiocytes, xanthogranulomatous, cholesterol clefts and granulomatous reaction), until there is sufficient validation that any of these are clinically relevant, recording of these features is not needed for routine clinical purposes.
DETERMINATION OF THE PATHOLOGIC RESPONSE TO NEOADJUVANT THERAPY
1)	The final pathological response should be determined on the basis of the histological features correlated with the gross findings. Particularly the mapped gross photograph and corresponding histological sections can be helpful, especially in markedly necrotic and cavitated tumors.
2)	Until digital and/or computational approaches are routinely available, a semiquantitative approach can be done.

^†For processing of lymph nodes, see recommendation 9.