Chapter 085. Neoplasms of the Lung (Part 2)

Major treatment decisions are made on the basis of whether a tumor is classified as a small cell lung carcinoma (SCLC) or as one of the non-small cell lung cancer (NSCLC) varieties (squamous, adenocarcinoma, large cell carcinoma, bronchioloalveolar carcinoma, and mixed versions of these). The histologic distinctions between SCLC and NSCLC include the following: SCLC has scant cytoplasm, small hyperchromatic nuclei with fine chromatin pattern and indistinct nucleoli with diffuse sheets of cells, while NSCLC has abundant cytoplasm, pleomorphic nuclei with coarse chromatin pattern, prominent nucleoli, and glandular or squamous architecture. ...
Nội dung trích xuất từ tài liệu:
Chapter 085. Neoplasms of the Lung (Part 2) Chapter 085. Neoplasms of the Lung (Part 2) Major treatment decisions are made on the basis of whether a tumor isclassified as a small cell lung carcinoma (SCLC) or as one of the non-small celllung cancer (NSCLC) varieties (squamous, adenocarcinoma, large cell carcinoma,bronchioloalveolar carcinoma, and mixed versions of these). The histologicdistinctions between SCLC and NSCLC include the following: SCLC has scantcytoplasm, small hyperchromatic nuclei with fine chromatin pattern and indistinctnucleoli with diffuse sheets of cells, while NSCLC has abundant cytoplasm,pleomorphic nuclei with coarse chromatin pattern, prominent nucleoli, andglandular or squamous architecture. Among the molecular distinctions, SCLCdisplays neuroendocrine properties absent in NSCLCs, production of specificpeptide hormones [such as adrenocorticotropic hormone (ACTH),arginine vasopressin (AVP), atrial natriuretic factor (ANF), gastrin-releasingpeptide (GRP)] and differences in oncogene and tumor-suppressor gene changes(SCLCs have RB mutations in 90% and p16 abnormalities in 10% but never haveKRAS or EGFR mutations, while NSCLCs have RB mutations in only 20%, p16changes in 50%, KRAS mutations in 30%, and EGFR mutations in ~10%). Bothtypes have frequent p53 mutations (>70% in SCLC and >50% in NSCLC), 3pallele loss (>90% in both), telomerase expression (>90% in both), and tumor-acquired promoter methylation in multiple genes (>80% in both, often involvingthe same genes, including RASSF1A). SCLCs are initially very responsive tocombination chemotherapy (>70% responses, with 30% complete responses) andto radiotherapy (>90% responses); however, most SCLCs ultimately relapse. Bycontrast, NSCLCs have objective tumor shrinkage following radiotherapy in 30–50% of cases and response to combination chemotherapy in 20–35% of cases. Atpresentation, SCLCs usually have already spread such that surgery is unlikely tobe curative and, given their responsiveness to chemotherapy, are managedprimarily by chemotherapy with or without radiotherapy. Chemotherapy clearlyprovides symptom relief and survival advantage. By contrast, NSCLCs that areclinically localized at the time of presentation may be cured with either surgery orradiotherapy. The beneficial role of chemotherapy in NSCLC is in palliation ofsymptoms and improving survival modestly. Although it is important to differentiate whether a tumor is SCLC orNSCLC for both prognostic and therapeutic reasons, it is less important to identifythe histologic subtypes of NSCLC. Stage for stage, the histology of NSCLC is notan important prognostic factor, and in the past the different subtypes of NSCLCwere rarely treated differently. However, lung adenocarcinomas (often withbronchioloalveolar features) may be responsive to therapy aimed at the epidermalgrowth factor receptor (EGFR) (see below). In addition, patients with squamouscell carcinoma may not be appropriate candidates for antiangiogenic therapy dueto an increased risk of bleeding (see below). Eighty-five percent of patients with lung cancer of all histologic types arecurrent or former cigarette smokers. Of the annual 213,380 new cases of lungcancer, ~50% develop in former smokers. With increased success in smokingcessation efforts, the number of former smokers will grow, and these individualswill be important candidates for early detection and chemoprevention efforts. All histologic types of lung cancer are due to smoking. However, lungcancer can also occur in individuals who have never smoked. By far the mostcommon form of lung cancer arising in lifetime nonsmokers, in women, and inyoung patients (multinodular lesion; as a fluffy infiltrate; and on screening CT scans as a groundglass opacity. The male to female ratio is 1:1, and while BAC can be associatedwith smoking, it is often found in nonsmokers. Histologically pure BAC isrelatively rare. More common is adenocarcinoma with BAC features. BAC maypresent in a mucinous form, which tends to be multicentric, and a nonmucinousform, which tends to be solitary. Many of the EGFR mutations found innonsmoking lung cancers occur in adenocarcinomas with BAC histologic features. Etiology Most lung cancers are caused by carcinogens and tumor promoters inhaledvia cigarette smoking. The prevalence of smoking in the United States is 28% formales and 25% for females, age 18 years or older; 38% of high school seniorssmoke. The relative risk of developing lung cancer is increased about thirteenfoldby active smoking and about 1.5-fold by long-term passive exposure to cigarettesmoke. Chronic obstructive pulmonary disease, which is also smoking-related,further increases the risk of devel ...