Pulmonary Tumors and Lymphoproliferative Disorders

Clinical Features.

Adenocarcinoma ( Box 21.3 ) is the most frequent histologic type and accounts for approximately 50% of all lung cancers. It is the most common histologic type in women and in nonsmokers. Typically located in the periphery of the lung, these lesions may not produce symptoms and are found incidentally on routine chest radiography. One of the more unusual symptoms of adenocarcinoma is bronchorrhea, which is the production of more than 100 mL/day of watery sputum.

Pathologic Features.

Adenocarcinomas typically show slow growth and tend to metastasize early. They can occur in areas of preexisting pulmonary fibrosis. They are most frequently peripheral and subpleural in location and may arise endobronchially.

The classification of lung adenocarcinoma by the 2011 International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) includes a multidisciplinary diagnostic approach using data from pathology, imaging, and molecular biology. The IASLC/ATS/ERS system introduces the use of clearer terminology with respect to the degree of growth along the alveolar surface (lepidic growth) and invasive components to define pre-invasive and invasive lesions. Preinvasive lesions include atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS), both defined as lesions with lepidic growth. AAH is a localized, small (≤5 mm) proliferation of mildly to moderately atypical type II pneumocytes or Clara cells lining alveolar walls. AIS is a localized small (≤3 cm) adenocarcinoma with lepidic growth without evidence of stromal, vascular, or pleural invasion. AAH and AIS are pathologic entities considered to be part of a spectrum and cannot be reliably differentiated on cytology. The term bronchioloalveolar carcinoma (BAC) is no longer used.

Invasive lesions include minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma. MIA is defined as a predominantly lepidic lesion lacking necrosis and invasion of lymphatics, blood vessels, or pleura and measuring less than 3 cm with an invasive component measuring no more than 5 mm in any one location. Invasive adenocarcinomas are further classified into histologic subtypes according to the predominant histology present: lepidic, acinar, papillary, micropapillary, or solid-predominant patterns. For example, lepidic-predominant adenocarcinoma (LPA) is defined as a lepidic lesion that may have necrosis, invade lymphatics or blood vessels, and the focus of invasion is greater than 5 mm. The nonmucinous adenocarcinomas are more common than mucinous forms. The term invasive mucinous adenocarcinoma has replaced mucinous bronchoalveolar carcinoma .

Various gene mutations have been identified in lung adenocarcinoma. There is a strong association between KRAS mutations in white smokers. Mutations in the epidermal growth factor receptor (EGFR) are more often seen in adenocarcinomas of nonsmokers and Asian women. Rearrangements of the gene encoding anaplastic lymphoma kinase (ALK) are uncommon, mostly seen in young never- or light smokers with adenocarcinoma. Testing of adenocarcinoma for various mutations has become increasingly important because of availability of targeted drug therapies and prognostic significance.

Imaging Features.

Adenocarcinoma may manifest distinct radiologic patterns. The most common is a solitary peripheral nodule or mass often with lobulated, spiculated, and ill-defined borders. On CT, they may present with pure ground-glass, solid, or mixed (both ground-glass and solid) attenuation. AAH and AIS present as pure ground-glass nodules ( Figs. 21.4 and 21.5 ). MIA is usually of ground-glass or mixed attenuation. Correlation of CT features with histopathologic diagnosis using the IASLC/ ERS/ATS system is still evolving, and studies describing CT manifestations of mixed attenuation nodules relating to the more common nonmucinous forms of adenocarcinoma are summarized in Table 21.1 . In contradistinction, the less common mucinous form of AIS, MIA, and LPA and other forms of invasive adenocarcinomas can manifest as solid nodules. The soft tissue component of mixed attenuation lesions can represent the invasive component or fibrosis and alveolar collapse ( Fig. 21.6 ). The degree of invasion is reported to correlate directly with the size of the soft tissue component on CT. The solitary nodule is associated with an excellent prognosis when it is resected in early-stage disease. Bubbly internal lucencies termed pseudocavitation is caused by alveoli or bronchi spared by tumor infiltration ( Fig. 21.7 ). An air bronchogram may be identified on standard radiography and CT.

The second appearance is an area of consolidation, which occurs in approximately 20% of cases ( Fig. 21.8 ). This appearance can mimic pneumonia, which is more common than lung cancer. Differential considerations for chronic consolidation also include lymphoma, organizing pneumonia, and chronic infection. The consolidation may be associated with nodules in the same lobe or in other lobes of either lung, reflecting tumor dissemination via the tracheobronchial tree.

The third appearance is that of multiple nodules and masses scattered throughout the lungs ( Fig. 21.9 ).

There is also increased awareness in recent years that adenocarcinoma and SCC can initially present as cystic lesions with progressive increase in wall nodularity, thickness, or size ( Fig. 21.10 ).

Adenocarcinoma can have variable degree of fludeoxyglucose (FDG) avidity. Pre- or minimally invasive, ground-glass attenuation, and small-sized lesions are known to have minimal or absent FDG uptake on PET. The degree of FDG avidity pretreatment has been found to have prognostic value for recurrence and survival in those with stage I NSCLC treated with stereotactic body radiotherapy (SBRT). Please see additional detail regarding PET in Chapter 4 .

Clinical Features.

Squamous cell carcinoma represents approximately 30% of all lung cancers ( Box 21.4 ). There is a strong association with cigarette smoking. SCC is the histologic type most commonly associated with hypercalcemia caused by PTHrP production by the tumor.

Pathologic Features.

Squamous cell carcinoma often arises in areas of squamous metaplasia, and there appears to be an orderly progression of alterations in bronchial mucosa in cigarette smokers from squamous metaplasia to invasive carcinoma. Typically, these tumors occur in main, segmental, or subsegmental bronchi, and they grow endobronchially. Bronchial wall invasion occurs with growth proximally along the bronchial mucosa. Spread to regional lymph nodes is common and may occur by direct extension. Central necrosis is a common feature. Histologic features typical for SCCs include the formation of keratin pearls and intercellular bridges.

Imaging Features.

The radiologic presentation depends on the location of the tumor. The most common presentation is a central mass in the hilar or perihilar region obstructing the bronchus ( Fig. 21.11 ). Involvement of the central bronchus may range from focal thickening to complete occlusion. When the lesion is small, the tumor may not be evident on chest radiography, but the bronchial wall abnormalities are more readily detected on CT. Atelectasis or postobstructive pneumonia is usually identified distal to the obstructed bronchus. Any patient presenting with lobar collapse and signs of infection should be followed radiographically to complete resolution with reexpansion of the involved lobe. Persistent atelectasis strongly suggests a central lung carcinoma.

Approximately one third of SCC occurs in the lung periphery. The most characteristic appearance is a thick-walled cavitary nodule or mass that usually does not contain an air–fluid level. The diameter ranges from 2 to 10 cm ( Fig. 21.12 ). The cavitary malignancy may be indistinguishable from a lung abscess based on imaging. A solitary nodule or mass without cavitation can occur in the periphery of the lung parenchyma.

Squamous cell carcinoma is usually FDG avid, although the central necrotic region can be photopenic. PET, MRI, or dual-energy CT is often helpful in distinguishing central tumor from adjacent postobstructive atelectasis.

Clinical Features.

Superior sulcus tumor ( Box 21.5 ) is not a distinct pathologic entity. It refers to NSCLC arising in the lung apex and is also known as Pancoast tumor. In recent series, adenocarcinomas have accounted for the majority of superior sulcus tumors, although in earlier series, SCC were predominant. Superior sulcus tumors often cause Pancoast syndrome, which is pain in the shoulder girdle and ulnar nerve distribution of the arm and hand. Horner syndrome, characterized by ipsilateral anhidrosis of the face, miosis, and ptosis with narrowing of the palpebral fissure caused by paralysis of the Muller muscle, is seen when the stellate ganglion is involved. These tumors typically invade the chest wall and extend into the neck. Local extension may result in involvement of the brachial plexus, spread to the vertebral bodies and spinal canal, involvement of the sympathetic ganglion, and anterior extension with invasion of the subclavian artery. In patients with potentially resectable tumor, multimodality treatment in which surgery (en bloc resection of the tumor and chest wall) is combined with pre- or postoperative radiation therapy, with or without chemotherapy now forms the standard of care for patients with superior sulcus tumors .

Imaging Features.

Brachial plexus involvement is suspected when tumor infiltration of the interscalene triangle and around the subclavian artery is observed on CT. MRI is the preferred modality for evaluating superior sulcus tumors because it allows visualization of structures at the apex of the thorax in multiple planes ( Fig. 21.13 ).

Clinical Features.

Small cell lung carcinoma, the most aggressive form of lung cancer, is characterized by rapid growth and early metastases, which are seen in two thirds of patients at the time of presentation ( Box 21.6 ). It is associated with the poorest prognosis and has the strongest association with cigarette smoking. It accounts for approximately 15% to 20% of all lung cancers.

Bulky lymphadenopathy associated with SCLC can cause compression of the superior vena cava (SVC) and lead to SVC syndrome (facial swelling, dyspnea, and headache) ( Fig. 21.14 ). SCLC is also associated with Cushing syndrome (central obesity, hypertension, glucose intolerance, plethora, and hirsutism) and SIADH, resulting in hyponatremia and serum hyposmolarity.

When found in the early stage as an isolated pulmonary nodule, SCLC can be resected and is associated with a better prognosis. However, most patients present in the late stage and are often managed with chemotherapy with or without radiation. The long-term survival is extremely poor because of a high rate of recurrence. Even when treated, the median survival time is 9 to 18 months.

Pathologic Features.

Small cell lung carcinoma is a high-grade neuroendocrine tumor with more than 10 mitoses per 2 mm ² that manifests histologically as sheets of small oval to slightly spindle-shaped cells with scant cytoplasm and hyperchromatic nuclei with small to absent nucleoli. SCLC is characterized by extensive tumor necrosis and hemorrhage.

Imaging Features.

The primary tumor is typically small and often central in location with extensive and bulky hilar and mediastinal adenopathy ( Fig. 21.15 ). Rarely, SCLC manifests as a small, peripheral, solitary nodule. SCLC tends to exhibit avid FDG uptake.

Clinical Features.

Large cell neuroendocrine carcinomas (LCNEC) account for 3% of lung cancers in surgical series and have a strong association with cigarette smoking. They are characterized by rapid growth, early metastases, and a poor prognosis.

Pathologic Features.

Similar to SCLC, LCNEC is a high-grade neuroendocrine tumor with more than 10 mitoses per 2 mm ² . It is characterized by large cells with low nuclear to cytoplasmic ratio. Typically, these tumors are peripheral in location. On gross inspection, they are large, with mean diameter of 3 to 4 cm with areas of necrosis.

Imaging Features.

The lesions are usually peripheral and quite large ( Fig. 21.16 ).

Clinical Features.

Carcinoid tumors are low-grade malignant neoplasms that represent between 1% and 2% of all primary pulmonary malignancies ( Box 21.7 ). Males and females are equally affected over a wide age range. The median age is 50 years. There is no association with cigarette smoking. Patients may present with cough and hemoptysis. Carcinoid tumors may be associated with ectopic hormone production, specifically ACTH. However, these tumors do not produce the clinical carcinoid syndrome unless liver metastases are present. Typical carcinoid (TC) tumors rarely metastasize, but atypical carcinoid (AC) tumors metastasize in 40% to 50% of patients. AC tumors are usually peripheral in location and account for 10% of carcinoid tumors. They may be associated with involvement of hilar and mediastinal lymph nodes and distant metastases, such as the liver or bone.