Lungs Involvement In Lymphoma

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the lungs (curved arrow). (B) High-resolution image at 1.25-mm slice thickness better displays the ground-glass (curved arrow) and associated thickened interlobular septa.

prior radiographs to show that a nodule is new, other considerations should include granuloma, amyloid, or hamartoma. Metastatic mucinous adenocarcinoma originating from the pancreas, small bowel, or ovary; thyroid carcinoma; and on rare occasions soft tissue sarcomas and choriocarcinoma may also contain calcifications.114-119

Multiple cavitary metastases are more likely to result from squamous cell carcinoma but may also be seen with transitional cell carcinoma, adenocarcinoma, sarcoma, and lymphoma.120-125 Cavitation of metastases may be seen before therapy but may also reflect response after chemotherapy (Figure 29.12).122,126 The initial finding of multiple cavitary

Hot Nodule Radioactive Scan
figure 29.11. A 19-year-old man with history of osteosarcoma of the femur. CT scan of the thorax in soft tissue windows shows a pulmonary nodule (arrow) with central calcification that was a metastasis on resection.

nodules does not necessarily suggest tumor.127-129 Inflammatory disease, such as Wegener granulomatosis, rheumatoid arthritis, eosinophilic granulomatosis, and amyloid, may be characterized by numerous cavitary nodules. Pulmonary infections, such as fungal infection, mycobacterial disease, septic emboli, and tracheobronchial papillomatosis, should also be considered.

Tumor emboli are the result of hematogenous metastases that occlude and enlarge within the pulmonary arteries. On CT images they appear as branching lobulated enlargement of the small- to medium-sized vessels (Figure 29.13).130 This unusual pattern of metastasis is seen with tumors that spread hematogeneously, such as sarcoma, renal cell carcinoma, hepatoma, and melanoma. Distal infarction may result, with distal ground-glass pattern or consolidation.130,131 Microscopic emboli, which may manifest as idiopathic cor pulmonale, are rare complications associated with tumors from the breast, liver, and gastrointestinal tract. Frequently, the lungs are clear on chest radiographs and CT images.108 On rare occasions, CT may show evidence of interstitial disease consistent with associated lymphangitic involvement.132 Angiography results may be normal or may show delayed vessel filling.133 Ventilation-perfusion scanning may demonstrate multiple subseg-mental perfusion defects.133,134

Endobronchial Metastases

Endobronchial obstruction of an airway by metastasis is rare; the reported incidence is 2%.135 The most common tumor to metastasize to the airways is renal cell carcinoma.125,136,137 Other tumors that spread to the airways include melanoma, lymphoma, and tumors of the breast, larynx, thyroid, and colon.125,135-138 Patients with tumor involving the airways frequently have metastases to other areas of the thorax, including the lymph nodes and pulmonary parenchyma.136 The proximal airways, rather than the small airways, are generally involved. Complete occlusion results in mucous filling of the distal occluded airways. On CT images, these occluded airways appear as arborizing opaque structures that are separate from the vasculature. Called the finger-in-glove sign on

-i
Arborating Vasculature

figure 29.12. A 55-year-old man with pharyngeal carcinoma of the lungs. (A) CT scan in lung windows demonstrates multiple pul monary metastases (arrows). (B) Following chemotherapy, CT scan shows interval decrease in size of the nodules with cavitation (arrow).

figure 29.12. A 55-year-old man with pharyngeal carcinoma of the lungs. (A) CT scan in lung windows demonstrates multiple pul monary metastases (arrows). (B) Following chemotherapy, CT scan shows interval decrease in size of the nodules with cavitation (arrow).

chest radiographs, the branching plugged airways resemble white-gloved fingers. If airway plugging extends into the subpleural distribution, a tree-in-bud pattern can be seen.

Lymphangitic Carcinomatosis

Lymphangitic tumor involvement of the lungs predominantly affects the pulmonary lymphatics and the investing perilym-phatic connective tissue. The patterns most frequently described on HRCT are thickened interlobular septae and bronchovascular interstitium, reticular lines, and polygonal structures.139,140 Thickened interstitial compartments can be smooth or nodular.140,141 A smooth pattern may be the result of direct tumor infiltration in the interstitium and lymphat-

Pneumocystis Pneumonie Bilder
figure 29.13. A 24-year-old man with metastatic soft tissue sarcoma, axial chest CT (lung windows). Some of the nodules appear as focal symmetric enlargement of the small pulmonary arteries (arrows) consistent with tumor emboli.

ics or of interstitial edema from a more proximal tumor of the lymphatics (i.e., with hilar or mediastinal lymph-adenopathy).142,143 Nodular lymphangitic disease is more indicative of direct tumor deposition in the interstitium (Figure 29.14). Malignancies commonly associated with a lymphangitic carcinomatosis pattern in the lungs include adenocarcinoma from lung, breast, and gastrointestinal tract, melanoma, lymphoma, and leukemia.108,142-145 Disease may initially reach the lungs by either embolic spread or direct extension from hilar lymphatic disease.132,146 On chest radiographs the pattern frequently resembles edema, with thickening of the perihilar bronchovasculature and subpleural Kerley B lines (see Figure 29.14). Frequently, however, the distribution is asymmetric and therefore suggestive of neoplasm. Alternatively, if a patient appears febrile, a lobar or segmental pattern may mimic pneumonia.

CT and HRCT are more sensitive and specific in identifying lymphangitic involvement. However, Hirakata et al. showed that detection of pulmonary involvement with HRCT is limited in comparison to that of histopathology.108 Interstitial involvement can extend from the perihilar axial interstitium to the subpleural interlobular septa and also may involve the subpleural interstitium leading to thickened fis-sures.143,147 Johkoh et al. correlated HRCT findings to those of histopathology and found that the distribution in most patients with lymphangitic carcinomatosis was in the peri-hilar axial interstitium.147 Other interstitial diseases may resemble lymphangitic carcinomatosis, including sarcoidosis and lymphoma. The distribution of disease and pattern of associated nodules may help to distinguish between disorders. Honda et al. found that lymphangitic carcinomatosis tended to involve the subpleural interstitial spaces, whereas sarcoidosis tended to be more symmetric and to occur in the upper lungs.148

Metastases of Mixed Parenchymal Patterns

Lymphoma involvement of the lungs may be mixed, manifesting as a combination of consolidative, nodular, or interstitial involvement (Figure 29.15).144 The latter form

figure 29.14. A 68-year-old woman who presented with weight loss and a dry cough. (A) Chest radiograph shows asymmetric opacities in the right lung and hilum. The right hilum is enlarged, and there are diffuse reticular opacities. (B) CT scan of the thorax at 2.5-mm slice thickness in lung windows shows enlargement of the right hilum (arrow), thickening of the bronchovasculature (curved arrow), and diffuse thickened interlobular septa (arrowheads). There is also a dependent right pleural effusion. (C) Prone images at 1.25-mm slice thickness better display the thickened interlobular septa (arrowheads). The pleural effusion is free flowing and collects in the dependent anterior pleural space.

figure 29.14. A 68-year-old woman who presented with weight loss and a dry cough. (A) Chest radiograph shows asymmetric opacities in the right lung and hilum. The right hilum is enlarged, and there are diffuse reticular opacities. (B) CT scan of the thorax at 2.5-mm slice thickness in lung windows shows enlargement of the right hilum (arrow), thickening of the bronchovasculature (curved arrow), and diffuse thickened interlobular septa (arrowheads). There is also a dependent right pleural effusion. (C) Prone images at 1.25-mm slice thickness better display the thickened interlobular septa (arrowheads). The pleural effusion is free flowing and collects in the dependent anterior pleural space.

Lymphoma Lungs Scan

figure 29.15. A 19-year-old woman with recurrent Hodgkin's lymphoma in the thorax. (A) CT scan in lung windows demonstrated a consolidative mass (large arrow) in the left upper lobe and left pleural effusion. In the right thorax, there is perihilar lymph-

adenopathy (curved arrow) and cavitary nodules (arrow). (B) High-resolution CT, 1.25-mm slice thickness, prone images show thickened interlobular septa (arrowheads) consistent with lymphan-gitic spread.

figure 29.15. A 19-year-old woman with recurrent Hodgkin's lymphoma in the thorax. (A) CT scan in lung windows demonstrated a consolidative mass (large arrow) in the left upper lobe and left pleural effusion. In the right thorax, there is perihilar lymph-

adenopathy (curved arrow) and cavitary nodules (arrow). (B) High-resolution CT, 1.25-mm slice thickness, prone images show thickened interlobular septa (arrowheads) consistent with lymphan-gitic spread.

Showing Man Consistency
figure 29.16. A 36-year-old man with Kaposi's sarcoma of the lungs. CT scan in lung windows shows multiple airspace nodules and masses with surrounding ground-glass appearance. The nodules in the right lower lobe are distributed along the bronchovasculature (arrows).

commonly is seen as an extension of tumor along the axial bronchovascular interstitium from hilar lymphatic disease or from an adjacent pulmonary mass. An air bronchogram is commonly seen in consolidative and nodular forms. Nodules also may cavitate. The presence of lymphadenopathy may help in the differential diagnosis, especially in patients with Hodgkin disease. However, lymphadenopathy is not necessarily present in involvement of the lungs by primary non-Hodgkin lymphoma.144,149

The consolidative form of adenocarcinoma and its subtype, bronchoalveolar cell carcinoma, are often initially misdiagnosed as lobar pneumonia. Presenting symptoms include fever, cough, and systemic symptoms consistent with infection that may accompany tumor.23 Coexisting pulmonary findings, such as associated subcentimeter nodules (possibly with a ground-glass appearance, and cavitary) or scattered areas of ground-glass pattern should signal possible malignancy. On rare occasions, cystlike changes in the consolidation may develop.150 These changes may be mistaken for bronchiectasis or cavitation from necrosis. A ground-glass appearance with septal thickening mimicking a crazy-paving pattern is unusual for metastatic adenocarcinoma but is well described.23,151

Involvement of the lungs by Kaposi's sarcoma commonly includes mediastinal and hilar lymphadenopathy. Tumor tends to extend along the bronchovasculature into the parenchyma (Figure 29.16). Multiple flame-shaped lesions or nodules with poorly defined borders or ground-glass pattern develop in the same distribution and commonly contain an air bronchogram.109,152 Other manifestations, however, include a single pulmonary nodule, pleural effusion, or tracheal and bronchial lesions.152

FDG-PET Detection of Pulmonary Metastases

The detection of thoracic metastases from all tumor sources with FDG-PET has not been completely evaluated in the current literature. However, available results show that PET

can be useful in the detection of thoracic metastases for melanoma and tumors of the colon and breast. The major weakness of PET imaging is the nodule size threshold for detection. Limitations exist with metastases smaller than 1 cm. Therefore, PET imaging should be accompanied by an imaging modality with excellent anatomic resolution, such as CT.

Lymph Node Metastases in the Thorax

The detection of unsuspected distant lymph node disease has a significant impact on tumor staging and patient prognosis. On chest radiographs, multiple pulmonary nodules are the most common manifestation of intrathoracic metastases; lymph node disease is second.124,153-155 Tumors that most frequently have metastases identifiable on chest radiographs include renal and other genitourinary tumors, melanoma, breast tumors, and head and neck tumors (Figure 29.17). Distribution of lymphadenopathy most commonly identified on radiographs is in the mediastinal, especially the right para-tracheal, region.153

Numerous studies of lung cancer imaging have demonstrated that CT is superior to chest radiography in detecting lymph node metastases. Williams et al.156 demonstrated that CT is superior to chest radiography in the detection of metastatic testicular seminoma. With chest radiography, metastases were found in 25 of 200 patients. These results included mediastinal lymph nodes in 17 patients, pulmonary metastases in 7, pleural effusions in 5, and pleural masses in 2. With CT, however, metastases were found in 30 patients, including 21 with mediastinal nodes, 12 with lung metastases, 6 with pleural effusions, and 2 with pleural masses. CT showed disease in 5 patients whose chest radiography results were normal and revealed additional metastases in 4 patients with abnormal findings on chest radiographs.

The characterization of lymph node disease by means of CT is limited by the size threshold for detecting abnormal nodes. Lymph nodes are generally interpreted as abnormal if their short-axis diameter exceeds 1 cm. For this reason, lymph node enlargement due to inflammatory or infectious disease

Internal Mammary Nodes

figure 29.17. A 52-year-old man with esophageal carcinoma. Dual fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT scan of the thorax shows increased uptake in paraesophageal lymph node (white arrow). Subcarinal lymph node (black arrow) of the same caliber shows no evidence of FDG uptake, suggesting the absence of metastases.

figure 29.17. A 52-year-old man with esophageal carcinoma. Dual fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT scan of the thorax shows increased uptake in paraesophageal lymph node (white arrow). Subcarinal lymph node (black arrow) of the same caliber shows no evidence of FDG uptake, suggesting the absence of metastases.

Fdg Pet Rheumatoid Arthritis Lymph Node
figure 29.18. A 56-year-old woman with previous left mastectomy for breast cancer. Dual FDG-PET/CT scan images show increased uptake of FDG in small subpectoral lymph nodes (arrow), indicating metastatic nodal disease. These lymph nodes are normal in size by CT criteria.

is frequently misinterpreted as neoplastic. Early metastases to small nodes are often overlooked. FDG-PET improves specificity by better identifying lymph node disease on the basis of tumor glycolysis rather than visual size criteria (Figure 29.18). Eubank et al. found PET more accurate than CT (88% and 73%, respectively) for detecting metastatic breast cancer to the mediastinum and internal mammary lymph nodes.32 Other studies have demonstrated the usefulness of PET in detecting metastases from the abdomen and lung.157 However, PET also has limitations with regard to lymph node size. The size threshold for tumor detection in metastatic foci is limited with PET because of camera resolution constraints. Lymph nodes with metastases that measure 5mm or less can be missed.32 For instance, although FDG-PET is useful for detecting distant metastases in patients with breast cancer, it should not be the study of choice for axillary lymph node staging. Numerous studies have shown the sensitivity of PET for the detection of sentinel node disease to be as low as 20%.158,159

Pleural Metastatic Disease

In adult patients, 22% of newly diagnosed pleural effusions identified on chest radiographs are caused by malignancy.160 The likelihood that a newly diagnosed unilateral pleural effusion is malignant increases with a patient's age and the size of the effusion.160,161 Even the presence of bilateral pleural effusions should warrant further evaluation, especially if the patient's heart is of normal size. According to Blackman et al., 50% of patients with such findings have a malignancy.162 Metastatic adenocarcinoma is responsible for 80% of malignant pleural effusions; however, in 7% to 10%, the primary site remains unknown.163-165 Overall, bronchogenic cancer accounts for 36% to 43% of malignant pleural effusions, followed by breast cancer at 9% to 25% and lymphoma at 7% to 10%.164,165

The upright chest radiograph is of limited value in detecting small volumes of fluid in the pleural space. According to Blackmore et al., the smallest amount of fluid detected is 50 mL when a meniscus sign at the costophrenic angle is identified on a lateral chest film.166 The approximate volume of fluid identified on a posteroranterior radiograph is 200 mL when a meniscus sign is present. At a volume of 500 mL, fluid typically obscures the diaphragm. Lateral decubitus films can reveal as little as 5 mL fluid; however, this technique can be limited by soft tissues, bedding, and clothing that may overlie the dependent thorax.167

As determined with chest radiographs, the incidence of pleural effusion in patients with primary Hodgkin disease is 7% to 13%.168-170 It is approximately 10% in patients with primary non-Hodgkin lymphoma.169,171 With the use of cross-sectional imaging modalities, such as CT, the sensitivity for detecting additional metastases in the thorax increases. Filly et al. reported that 80% of patients with primary Hodgkin disease and pleural effusion had lymphadenopathy that was demonstrated on chest radiographs.169 However, Castellino et al. reported a higher incidence (100%) on the basis of CT results.170

Ultrasonography is sensitive in the detection and quantification of pleural effusions.172,173 Yang et al. found ultrasound useful in characterizing the nature of pleural effusions.174 Transudates were usually anechoic. Although exudative effusions could also appear anechoic, fluid that was complex, homogenously echogenic, or that contained complex septations was specific for an exudate. Associated findings, including a thickened pleura or underlying pulmonary lesions, also indicated an exudate. Only the presence of pleural nodules was useful in detecting malignancy in the pleural space (Figure 29.19). Similar results were reported by Gorg et al., who also reported that only the presence of pleural masses was specific for malignancy.175 According to Bradley et al., imaging of the pleura with ultrasonography was useful in evaluating malignant effusions to distinguish benign from

Pleural Malignancy
figure 29.19. A 55-year-old man with metastatic adenocarcinoma and a pleural effusion. Ultrasound image shows lobulated soft tissue tumor (curved arrow) in the pleural space consistent with malignancy.
Hot Nodule Radioactive Scan
figure 29.20. A 75-year-old woman with lung cancer. CT scan of the thorax (soft tissue windows) demonstrates an enhancing pleural nodule (arrow) consistent with tumor deposit.

malignant pleural masses and to provide real-time guidance for needle placement during percutaneous biopsy.176 Vascular abnormalities and other benign masses were readily identified as anechoic and pulsatile. Malignant tumors showed varied echogenicity indicating soft tissue, interruption of the pleural line (90%), and decreased motion with respiration.

Although the spatial resolution of CT is excellent, small tumor deposits on the pleura can be missed.177 According to Akaogi et al., small nodules in the interlobar fissures in a patient with lung cancer without an effusion may be the only indication of pleural involvement.178 Malignant effusions frequently do not demonstrate any pleural changes on contrast-enhanced CT studies. Approximately 50% of malignant effusions resemble simple transudative effusions without pleural changes.177,179 Therefore, the absence of associated pleural thickening or nodularity does not preclude a malignant effusion. Several studies have evaluated the use of CT in establishing criteria for detecting malignant pleural disease.177,179-182 Arenas-Jimenez et al. found that pleural nodules and nodular pleural thickening were the most sensitive and specific findings for malignant pleural effusion (Figure 29.20).177 The finding of medias-tinal and circumferential pleural thickening was also more frequent in malignant disease but could be seen with an empyema. Associated findings such as a pulmonary mass or nodules, enlarged mediastinal lymph nodes, a chest wall mass, or liver nodules helped to confirm radiologic evidence. In patients with lymphoma, ancillary findings of extrapleural tumor or enlarged lymph nodes in the extrapleural space demonstrated with CT may also help to explain the source of pleural disease. Aquino et al. found that 41% of patients with lymphoma and pleural effusion had abnormal pleural or extrapleural disease or both. Ninety-five percent of patients with extrapleural tumors had adja cent paraspinal and posterior mediastinal lymph node disease.183

MR imaging is useful in the detection of pleural malignancy; however, because of the duration of scan time, limitations in whole-body imaging due to the need for varying sequences for specific organs, limited fields of view, and high costs, this modality is the second choice, after CT. Falaschi et al. found that MR imaging was equal to CT in the detection of morphologic changes suggesting malignant pleural disease.184 They also found that MR imaging provided additional information as a result of changes in signal intensity with malignancy. In six patients, CT results were equivocal, whereas benign disease was distinguishable from malignant disease on the basis of MR imaging information. The most useful findings on MR images were high signal intensity on proton-density-weighted and T2-weighted studies and the use of lesion-to-muscle ratio in each sequence. Similar results were found by Hierholzer et al.185 Both CT and MR imaging were sensitive (93% and 96%, respectively) in detecting morphologic changes of malignant pleural disease (i.e., mediasti-nal pleural thickening, nodularity, irregular pleural contour, and infiltration of the chest wall or diaphragm). MR images displayed increased signal indicating malignancy in T2-weighted and contrast-enhanced T1-weighted series, with sensitivities of 91% and 93%, respectively. No significant features were found on noncontrast-enhanced T1-weighted images.

As a general imaging tool for routine pretreatment evaluation of thoracic malignancy, CT is more practical and cost-effective. However MR imaging is more sensitive in detecting tumor involvement of the chest wall and diaphragm. As mentioned earlier in the chapter, MR imaging is superior to CT in the assessment of chest wall and mediastinal involvement by superior sulcus tumors. Carlsen et al. also found MR imaging useful in the pretreatment assessment of patients with mediastinal lymphoma and suspected involvement of the chest wall and pleura.186 MR imaging detected chest wall or pleural malignancy or both in 22 of 57 patients; by comparison, with CT, disease was detected in only 2 patients.

FDG-PET is more sensitive than CT for the detection of malignant pleural disease. Bury et al. described an increase in FDG uptake in the pleura in all 16 patients with malignant pleural disease in their study group.187 As in most FDG-PET studies, infection could mimic malignancy. In the study by Bury and colleagues, two patients with pleural empyema also showed abnormal uptake, which mimicked tumor. Gupta et al. reported a sensitivity and specificity of 88.8% and 94.1%, respectively, for FDG-PET in correctly distinguishing benign from malignant pleural disease in patients with lung cancer.188 Extra care should be taken when interpreting any FDG-PET image of a patient with malignant pleural disease who was previously treated by means of talc pleurodesis. Talc, which causes a chronic granulomatous response in the pleural space, appears intensely hot on FDG-PET images and mimics tumor.189 Careful correlation of PET findings with those of CT is necessary to distinguish abnormal foci of increased attenuation on PET from true neoplasm (Figure 29.21). This abnormal uptake will not resolve over time; therefore, areas of new increased FDG uptake suggest recurrent disease.

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    What do calcified hilar lymph nodes look like on ct scan?
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