The pivotal role of pathology in the management of lung cancer

Abstract

The last decade has seen significant advances in our understanding of lung cancer biology and management. Identification of key driver events in lung carcinogenesis has contributed to the development of targeted lung cancer therapies, heralding the era of personalised medicine for lung cancer. As a result, histological subtyping and molecular testing has become of paramount importance, placing increasing demands on often small diagnostic specimens. This has triggered the review and development of the first structured classification of lung cancer in small biopsy/cytology specimens and a new classification of lung adenocarcinoma from the IASLC/ATS/ERS. These have enhanced the clinical relevance of pathological diagnosis, and emphasise the role of the modern surgical pathologist as an integral member of the multidisciplinary team, playing a crucial role in clinical trials and determining appropriate and timely management for patients with lung cancer.

Keywords: Lung Neoplasms; non-small-cell lung carcinoma (NSCLC); pathology; small cell lung carcinoma (SCLC).

Figure 1

Squamous preneoplasia progresses through mild (A); moderate and severe (B) stages to carcinoma in situ (C).

Figure 2

Atypical adenomatous hyperplasia (A) and adenocarcinoma in situ (B) are similar histologically and are differentiated on the basis of the overall size of the lesion with a cut-off of 5 mm.

Figure 3

Squamous cell carcinoma typically is a central, often cavitating, malignancy (A); Well-differentiated tumours show keratin pearl formation (B); Individual cell keratinisation and intercellular bridges are evident at high power (C) but are less obvious in poorly differentiated examples (D).

Figure 4

Adenocarcinoma is typically a peripheral lesion (A) showing histological heterogeneity. Architectural patterns include lepidic (B); acinar (C); papillary (D); micropapillary (D,E) and solid (F); the predominant pattern is recorded and lesser patterns are listed as percentages, e.g., in (G), papillary 70%, solid 20%, acinar 10%.

Figure 5

Large cell carcinoma is often large and partially necrotic (A) and comprises patternless sheets of large polygonal cells showing no obvious evidence of histological differentiation (B).

Figure 6

Small cell lung carcinoma in a core biopsy (A,B) showing positive immunoperoxidase staining for synaptophysin (C) and CD56 (D).

Figure 7

Immunohistochemistry on an undifferentiated non-small cell carcinoma in a bronchial biopsy (A,B) favours a diagnosis of adenocarcinoma. Staining for p63 (C) is negative (note the positive internal control comprising benign basal bronchial epithelial cells) while there is strong TTF-1 positivity (D).