Chapter 118: Extrapulmonary Syndromes Associated with Lung Tumors

Introduction

A wide variety of extrapulmonary syndromes have been reported with lung cancer. This chapter will focus primarily on paraneoplastic syndromes, a heterogeneous group of disorders associated with cancer but not due to direct invasion, obstruction, or metastasis.^1,2 As many paraneoplastic syndromes share similar underlying mechanisms, they may be classified as endocrine, hematologic, and neurologic syndromes. More broadly speaking, they are either hormonally or immunologically based.

Paraneoplastic syndromes affect up to 8% of patients with cancer,³ and of all malignancies, lung cancer is most commonly associated with these syndromes. The subtype of lung cancer most commonly associated with paraneoplastic syndromes is small-cell lung cancer (SCLC), but some such as hypertrophic pulmonary osteoarthropathy (HPO) and hypercalcemia are more common in non–small-cell lung cancer (NSCLC).⁴

Endocrine and hematologic syndromes associated with lung tumors are listed in Table 118-1. The endocrine syndromes are characterized by the ectopic production by tumor cells of biologically active peptide hormones that bind to receptors in adjacent or distant organs, giving rise to a clinical syndrome. Hematologic syndromes develop in patients with lung cancer through the production by tumor cells of cytokines that activate progenitor cells in the bone marrow. Neurologic syndromes, such as encephalomyelitis and subacute sensory neuropathy, are caused by the induction of antibodies directed against proteins expressed by the lung cancer cells and directed against antigens present on cells in the nervous system. In clinical practice, an understanding of the extrapulmonary syndromes is important for several reasons: (1) recognition of a syndrome may serve as a harbinger of an occult malignancy or may signify disease recurrence; (2) the course of the endocrine and hematologic syndromes usually parallels the course of the lung cancer, although the neurologic syndromes frequently do not; and (3) appropriate treatment of the extrapulmonary syndrome often reduces the patient's morbidity and may allow definitive treatment of the cancer. In general, definitive treatment of the underlying tumor is the most effective form of therapy for the paraneoplastic syndromes, so their presence should not preclude treatment of lung cancer with curative intent as most syndromes are reversible once the patient receives treatment.

Hypercalcemia of Malignancy

Hypercalcemia is commonly seen in cancer patients^5,6 and lung cancer is the most common solid tumor associated with it, occurring in up to 20% of patients.^...