INTRODUCTION

Pulmonary manifestations of extrathoracic neoplasms (PMENs) are clinically significant entities. Many carcinomatous conditions in different parts of the body manifest pulmonary metastasis. In fact, lung is more often affected by metastatic growth compared to primary neoplasm, and is estimated to be 30% of all primary tumors. Carcinomas and sarcomas from anywhere in the body can spread to the lungs. Even gestational and teratomatous choriocarcinoma and melanomas can give rise to pulmonary secondaries. Primary growth of thyroid, breast, gastrointestinal tract, kidneys, prostate, uterus, ovaries, and bones are the common extrathoracic sites from where pulmonary metastasis can occur.

ROUTES OF SPREAD

Hematogenous spread as lung metastasis may occur from malignancy in any part of the body. Such deposits are generally multiple and bilateral. Hemoptysis may occur, but as such there is no symptom, and the diagnosis is made on radiological examination. Nevertheless, severe and rapidly progressive dyspnea may occur due to extensive infiltration of lung tissue by metastasis from extrathoracic neoplasms of breast, stomach, and pancreas and is called pulmonary lymphatic carcinomatosis. Clinically, there is no completely characteristic feature of pulmonary metastatic deposits. However, the roentgenographic appearance of the lesion often provides useful clues to the etiology of the primary neoplasm much before the appearance of local symptoms of the growth. Pulmonary metastatic presentation from different extrathoracic neoplasms may be taken up as follows.

    Thyroid

Carcinoma thyroid produces an impressive degree of lung metastatic infiltration, resembling a diffuse inflammatory process. These secondaries may remain unchanged for a long period and may exhibit low-grade growth. Exudative bilateral pleural effusion/pericardial effusion has been reported with anaplastic thyroid cancer.

    Breast

Lung involvement is either direct or through the chest wall, or more frequently via lymphatic or bloodstream. Lung metastases are often numerous and mostly small. Pleural extension is frequent. Carcinoma of breast has the characteristics to remain dormant and then suddenly flares into activity with pulmonary metastasis. Rarely, extensive pulmonary fibrosis may occur with slow-growing carcinoma of breast.

    Gastrointestinal Tract

Carcinoma of stomach produces a lymphangitic type of pulmonary spread, while carcinoma of colon is a more frequent source of pulmonary metastasis and causes extensive miliary metastases much before the symptoms of carcinoma colon appear locally. This happens more so with carcinoma colon of the right side. The metastatic lesions are nodular masses and are few in number, rarely solitary lesions may be seen.

    Kidney

Cannonball tumors are produced due to lung metastases in malignant renal and adrenal tumors. Primary tumor may not manifest but for the pulmonary deposits. Microscopic hematuria, if present, strongly suggests renal carcinoma much before the X-ray chest appearances, thus requiring further urologic investigations.

    Testicals

Multiple malignant lung metastases are often cannonball type, particularly in seminomas.

    Prostate

Fine miliary or nodular type of pulmonary metastatic deposits are seen in prostatic carcinoma. However, course markings or bronchopneumonia-like lesions may also be produced sometimes. These too appear much before the appearance of significant symptoms of urinary obstruction.

    Female Genital Tract

Carcinomas of female genitalia much less metastasize to lungs, except chorionepithelioma, which have higher pulmonary affliction for secondaries. Incidence of choriocarcinoma after delivery, metastasizing, is 1 in 160,000 live births, and metastases after evacuation of the vesicular mole are seen in 4% of cases. Patient presents with chest pain, cough, hemoptysis, and dyspnea, and chest X-ray may show an alveolar snowstorm pattern, rounded opacities, pleural effusion, and an embolic infarct in lungs. Pelvic manifestation may be absent, and sometimes no primary lesions are seen in the reproductive system, despite widespread pulmonary metastases. Severe respiratory distress due to extensive intrathoracic bleeding has been documented.

    Sarcomas

Sarcomas arising in mesodermal elements of bone, skin, and soft tissue frequently have lung metastasis. The characteristic feature of these metastatic deposits is that they may differ both clinically and microscopically from the primary tumors, e.g., metastatic melanosarcoma may not contain any pigment, and metastatic osteogenic sarcoma may not have any bone tissue. Interestingly, lung metastasis might grow more rapidly than primary growth.

CLINICAL PRESENTATION

The history of the patient is important, especially the past history of surgery of breast, thyroid, or colon. A lung lesion appearing 12 months after resection of primary tumor is likely to be a metastasis. Pattern of growth is another feature, e.g., rapid changes indicate malignancy or growth. Symptoms may be of some help, although secondary deposits in the lung, many a time, do not exhibit any symptoms. A severe cough may be quite disturbing. If obstruction occurs by lung deposits, or by infection, then symptoms of fever and other signs of pneumonia or abscess may develop. Pain may occur due to pleuritis, because of invasion of the thoracic wall or spinal or intercostal nerves. Hemoptysis is less common but may occur due to bronchial invasion. Rarely, it may be the first evidence of a malignant metastatic deposit in the lung. Dyspnea may be severe and distressing in extensive lymphogenous metastasis; however, it may be due to the replacement of normal lung tissue in cases of solid tumor deposits. Lung manifestations of extrapulmonary neoplasms are shown in Box 1.

LABORATORY FINDINGS

These are not much contributory. However, indirect evidence may be found. There may be unexplained anemia; erythrocyte sedimentation rate (ESR) may not be a deciding factor; pleural fluid cytology is sometimes contributory, and so is the sputum cytologic analysis; skin and serological tests have no value; bronchoscopy is not of much help since metastatic lesions are not in direct communication with bronchi, most of the time, computed tomography (CT)-guided aspiration biopsy may be of some value in selected solitary metastasis. To sum up, conventional studies are not likely to establish the diagnosis of pulmonary metastasis.

RADIOLOGICAL EXAMINATION

X-ray findings in lung metastasis reflect the pleomorphic pattern of numerous different kinds of malignancies that may be encountered. Metastatic lesions are of varied size, generally spherical, and have a sharp margin. In case there is an indistinct margin, gradation between lung tissue and metastatic nodule is quite clear. The density of the lesions, however, may vary. Calcification may occur in metastatic sarcomas/chondrosarcomas, while other deposits have a translucent, ground-glass appearance. Kerley A and B lines with linear or nodular densities are seen if involvement is primarily lymphatic, e.g., carcinomas of the colon, rectum, breast, kidney, testes, cervix, and sarcomas of bone and skin. Multiple miliary nodules of hematogenous origin are from carcinomas of thyroid, breast, and prostate sarcomas. Cannonball metastatic deposits are from primary carcinomas of the kidney and testes.

CERTAIN IMPORTANT POINTS

There are no characteristic features marking the clinical presentation of lung metastasis of extrapulmonary neoplasm. Roentgenographic appearance often provides a useful clue to the etiology of primary neoplasm. Thorough general physical examination including pelvic examination in females is important. Dissemination via lymphatics is found positive, the more the disease has spread beyond the immediate chain, the more it becomes incurable. Distant metastasis indicates the progression of malignancy, and many a time, pulmonary metastases present before the symptoms of primary growth appear, and sometimes may overshadow the original growth.

DIFFERENTIAL DIAGNOSIS

• If a pulmonary deposit from extrathoracic neoplasm appears as a solitary pulmonary nodule, as in carcinoma of the thyroid, breast, kidney, or bone, common differential diagnoses include bronchogenic carcinoma, tuberculomas benign lung tumors, hydatid cyst, pneumonitis, abscess, or infarction of lung.

• If a patient has symptoms such as cough, malaise, and weight loss but is afebrile then apart from lung metastasis, infections such as tuberculosis (TB), histoplasmosis, and blastomycosis form an important part of the diagnosis.

• Leukemic lung deposits are diagnosed by blood examination, while other lymphomatoses are diagnosable on clinical grounds by the time the lung is involved.

• If dyspnea is a prominent feature, metastatic diffuse pulmonary carcinomatosis and lymphomatosis have to be differentiated from the following:

○ Diffuse interstitial lung disease, e.g., fibrosing alveolitis and allergic alveolitis

○ Connective tissue disorders such as rheumatoid lung, honeycomb lung, and hemosiderosis

Lung manifestations of extrathoracic neoplasm are clinically significant. Often, these are radiologically appreciated much before the symptoms of primary growth appear. General physical examination is of much help to pinpoint the primary growth, often assisted by previous history of surgery such as mastectomy or in case of malignancy of thyroid or occult blood in colonic carcinoma or raised levels of serum acid phosphatase in an elderly with prostatic carcinoma. Multifocal TB mimics as a metastatic tumor. Positron emission tomography (PET) scan is useful. Palliative care in oncology is applied holistically by skilled, trained, and caring staff and physicians having family communication skills, and avoiding unnecessary interventions, especially in the elderly is often rewarding.

CONCLUSION

Systemic neoplastic disorders often metastasize in the liver, lungs, and bones. Apart from the endobronchial local spread, hematogenous and lymphatic spread is responsible for tumor secondaries in one-fourth to half number of cases. Generally, lung deposits are multiple but can rarely present as solitary pulmonary nodules in < 3% cases. Thyroid, parathyroid, breast, stomach and colon, kidney and adrenals, prostate and testicles, and sarcomas of bone or skin are common, apart from leukemia and lymphomatosis. Lung metastasis of right colon malignancy may even manifest before the presentation of primary colon cancer in a patient. A combination of surgery and radiotherapy as well as chemotherapy is selected to treat lung metastasis. Palliative care stands of higher value, especially in geriatric patients.

SUGGESTED READINGS

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