Chapter 085. Neoplasms of the Lung (Part 2) ppt

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 ca

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 Among the molecular distinctions, SCLC displays neuroendocrine properties absent in NSCLCs, production of specific peptide hormones [such as adrenocorticotropic hormone (ACTH), arginine vasopressin (AVP), atrial natriuretic factor (ANF), gastrin-releasing peptide (GRP)] and differences in oncogene and tumor-suppressor gene changes

(SCLCs have RB mutations in 90% and p16 abnormalities in 10% but never have

KRAS or EGFR mutations, while NSCLCs have RB mutations in only 20%, p16

changes in 50%, KRAS mutations in 30%, and EGFR mutations in ~10%) Both types have frequent p53 mutations (>70% in SCLC and >50% in NSCLC), 3p

allele loss (>90% in both), telomerase expression (>90% in both), and tumor-acquired promoter methylation in multiple genes (>80% in both, often involving

the same genes, including RASSF1A) SCLCs are initially very responsive to

combination chemotherapy (>70% responses, with 30% complete responses) and

to radiotherapy (>90% responses); however, most SCLCs ultimately relapse By contrast, NSCLCs have objective tumor shrinkage following radiotherapy in 30– 50% of cases and response to combination chemotherapy in 20–35% of cases At presentation, SCLCs usually have already spread such that surgery is unlikely to

be curative and, given their responsiveness to chemotherapy, are managed primarily by chemotherapy with or without radiotherapy Chemotherapy clearly provides symptom relief and survival advantage By contrast, NSCLCs that are clinically localized at the time of presentation may be cured with either surgery or radiotherapy The beneficial role of chemotherapy in NSCLC is in palliation of symptoms and improving survival modestly

Although it is important to differentiate whether a tumor is SCLC or NSCLC for both prognostic and therapeutic reasons, it is less important to identify the histologic subtypes of NSCLC Stage for stage, the histology of NSCLC is not

an important prognostic factor, and in the past the different subtypes of NSCLC

were rarely treated differently However, lung adenocarcinomas (often with bronchioloalveolar features) may be responsive to therapy aimed at the epidermal growth factor receptor (EGFR) (see below) In addition, patients with squamous cell carcinoma may not be appropriate candidates for antiangiogenic therapy due

to an increased risk of bleeding (see below)

Eighty-five percent of patients with lung cancer of all histologic types are current or former cigarette smokers Of the annual 213,380 new cases of lung cancer, ~50% develop in former smokers With increased success in smoking cessation efforts, the number of former smokers will grow, and these individuals will be important candidates for early detection and chemoprevention efforts

All histologic types of lung cancer are due to smoking However, lung cancer can also occur in individuals who have never smoked By far the most common form of lung cancer arising in lifetime nonsmokers, in women, and in young patients (<45 years) is adenocarcinoma However, in nonsmokers with adenocarcinoma involving the lung, the possibility of other primary sites should be considered Squamous and small cell cancers usually present as central masses with endobronchial growth, while adenocarcinomas and large cell cancers tend to present as peripheral nodules or masses, frequently with pleural involvement Squamous and large cell cancers cavitate in 10–20% of cases Bronchioloalveolar carcinoma (BAC) is a subtype of adenocarcinoma that grows along the alveoli without invasion and can present radiographically as a single mass; as a diffuse,

multinodular lesion; as a fluffy infiltrate; and on screening CT scans as a "ground glass" opacity The male to female ratio is 1:1, and while BAC can be associated with smoking, it is often found in nonsmokers Histologically pure BAC is relatively rare More common is adenocarcinoma with BAC features BAC may present in a mucinous form, which tends to be multicentric, and a nonmucinous form, which tends to be solitary Many of the EGFR mutations found in nonsmoking lung cancers occur in adenocarcinomas with BAC histologic features

Etiology

Most lung cancers are caused by carcinogens and tumor promoters inhaled via cigarette smoking The prevalence of smoking in the United States is 28% for males and 25% for females, age 18 years or older; 38% of high school seniors smoke The relative risk of developing lung cancer is increased about thirteenfold

by active smoking and about 1.5-fold by long-term passive exposure to cigarette smoke Chronic obstructive pulmonary disease, which is also smoking-related, further increases the risk of developing lung cancer The lung cancer death rate is related to the total amount (often expressed in "cigarette pack-years") of cigarettes smoked, such that the risk is increased 60- to 70-fold for a man smoking two packs

a day for 20 years as compared with a nonsmoker Conversely, the chance of developing lung cancer decreases with cessation of smoking but may never return

to the nonsmoker level The increase in lung cancer rate in women is also associated with a rise in cigarette smoking Women have a higher relative risk per

given exposure than men (~1.5-fold higher) This sex difference may be due to a greater susceptibility to tobacco carcinogens in women, although the data are controversial