Lung cancer is a malignant tumor originating from bronchial mucosa or glands. In China, the incidence of lung cancer is the first among male tumors and exceeds 20% of cancer deaths, and the incidence and mortality rate are still increasing rapidly. For clinicians, lung cancer is not unfamiliar, but today, it is the paraneoplastic syndrome that we want to talk about.
We all know the typical symptoms of lung cancer include cough, hemoptysis and chest pain. When we encounter such patients, we would think of taking a chest X-ray, but there are some lung cancer patients whose early clinical manifestations are not typical, and if we overlook certain details, we may misdiagnose or miss the diagnosis.
So, what is paraneoplastic syndrome?
Paraneoplastic syndrome refers to the non-metastatic extrathoracic manifestation of lung cancer, which is a clinical manifestation caused by some special hormones, antigens, enzymes or metabolites produced by cancer cells. Paraneoplastic syndrome can manifest in all organs outside the thorax, and the symptoms can be relieved when the lung cancer is removed or effectively treated, and then reappear when the lung cancer recurs.
First, hypertrophic pulmonary osteoarthropathy
The main clinical manifestations are pestle-like fingers (toes), extensive periosteal new bone formation and joint pain and effusion. Pulmonary hypertrophic osteoarthropathy often precedes pulmonary symptoms by several months or years, and is often combined with lung cancer. There are many theories of its etiology, and toxic substances are thought to be the possible cause of the disease.
Clinically, there is swelling and pressure in the soft tissues of the diseased bone area, more prominent in the distal tibiofibula and radius-ulnar, and in severe cases, the femur, humerus, metacarpals and metatarsals. This has also involved large joints such as the knee, ankle and wrist. The diagnosis depends mainly on imaging evidence, which shows symmetrical periosteal hyperplasia of the tubular bones bilaterally. The hyperplastic periosteum may be laminar, onion skin-like or lace-like, and a translucent line between the periosteal new bone and the bone cortex is mostly visible; the joint lesions are mostly manifested by swelling of joint soft tissues, joint effusion and periarticular osteoporosis. Hypertrophic osteoarthropathy is characterized by symmetrical “double track sign” and/or symmetrical peri-articular radiolucency.
Large cell carcinoma, squamous carcinoma, adenocarcinoma and hypertrophic pulmonary osteoarthropathy are closely related.
Second, male breast enlargement
The pathogenesis is the increased secretion of ectopic gonadotropins, which is related to the imbalance and disorder of sex hormones in the body of lung cancer patients due to the increase of estrogen level and decrease of androgen level in peripheral blood, thus causing male breast enlargement symptoms. There are not many lung cancers with combined ectopic gonadotropins, and most of them are large cell lung cancers.
Third, Cushing’s syndrome
Cushing’s syndrome is a general term for the condition caused by excessive secretion of glucocorticoids (mainly cortisol) by the adrenal glands due to various etiologies. Typical manifestations may include centripetal obesity, full-moon face, hypertension, low potassium, etc.
Patients with lung cancer often have elevated adrenocorticotropic hormone (ACTH) detectable in cancer tissue or even blood, which constantly stimulates normal adrenal tissue to secrete excessive adrenocorticotropic hormone. Small cell lung cancer or bronchial carcinoid tumor is the most common cell type causing Cushing’s syndrome.
Fourth, antidiuretic hormone dysregulation syndrome
The syndrome of dysregulated secretion of antidiuretic hormone (SIADH) is a group of syndromes in which endogenous antidiuretic hormone secretion is abnormally increased or its activity is hyperactive, resulting in clinical manifestations such as water retention, increased urinary sodium excretion and dilutional hyponatremia.
With increasing symptoms of water intoxication, neurological complications such as psychiatric symptoms, blurred consciousness or even coma may even occur. Patients with serum sodium below 135 mmol/L or even below 120 mmol/L in severe cases, plasma osmolality below 280 mOsm/kg and urinary sodium above 20 mmol/L. The correlation between small cell lung cancer and SIADH can reach 75%.
Fifth, polymyositis (PM) and dermatomyositis (DM)
The first symptom is usually weakness of the proximal extremities, often starting from the pelvic girdle muscle and gradually involving the shoulder girdle muscle, with muscle pain or pressure in only 5% of patients. Dysphagia may occur with involvement of the pharyngeal muscles; involvement of the cervical muscles is common and may present with difficulty in raising the head and may also accumulate in the respiratory muscles. Dermatitis may precede or accompany myositis. Typical changes include erythema and edema around the periorbital area, corners of the mouth, cheekbones, neck, anterior chest, lateral extremities, extensor phalanges, and nails. The later stage presents with desquamation, hyperpigmentation and hard nodules.
Clinically, about 8% of PM/DM patients present with malignant tumors, which may precede the malignant tumors by 1 to 2 years, or may occur simultaneously or later. The common tumors are lung cancer, ovarian cancer, breast cancer, and gastrointestinal tract cancer. The higher the age, the higher the chance of concomitant tumors. In the case of lung cancer, small cell carcinoma and squamous carcinoma are associated with PM/DM.
Sixth, hypercalcemia
It is mainly found in squamous carcinoma, and the mechanism of occurrence is related to ectopic parathyroid hormone and its associated proteins, but can also be directly caused by bone metastasis. It was found that in the absence of bone metastases, hypercalcemia occurs in 40% of cases. Ectopic parathyroid hormone can be produced by many tumors, with a particularly high incidence in lung cancer. Patients with hypercalcemia often present with drowsiness, anorexia, nausea, vomiting and weight loss, and mental changes. Blood calcium can be as high as 3.5 mmol/L or more, and blood calcium levels can often return to normal after removal of the tumor.
Seventh, carcinoid syndrome
The typical manifestations of carcinoid syndrome are abnormal skin, cardiovascular, gastrointestinal and respiratory functions. The main manifestations are flushing or edema of the face and trunk of upper limbs, increased gastrointestinal motility, diarrhea, tachycardia, wheezing, itching and abnormal sensation. The symptoms are mostly paroxysmal and the mechanism is the release of different vasoactive substances by the tumor, including 5-hydroxytryptamine, bradykinin, vasopressor, catecholamines, and histamine. It is commonly seen in small cell lung cancer.
Eighth, neuromuscular syndrome
Neuromuscular syndromes include cerebellar cortical degeneration, spinal cerebellar degeneration, peripheral neuropathy, and myasthenia gravis syndrome (Lambert-Eaton syndrome).
Cerebellar cortical degeneration manifests as acute or subacute organic dysfunction, difficulty in movement of both upper and lower extremities, motor tremor, dysphonia, vertigo, but nystagmus is uncommon, and the above symptoms have been reported to subside on their own after removal of lung cancer.
In case of peripheral neuropathy, such as motor and sensory, there may be acute or subacute attacks. The main manifestations of sensory or sensorimotor nerve involvement are abnormal limb sensation, pain, and loss of deep tendon reflexes.
Myasthenia gravis syndrome (Lambert-Eaton syndrome) is different from myasthenia gravis associated with thymic lesions, and the application of drugs such as neostigmine has no remission effect, but corticosteroids may be effective.
When the tumor disappears or remits after treatment, its muscle weakness symptoms also remit. The specific pathogenesis is not clear, but studies have found that these symptoms are related to the site of the tumor and the presence or absence of metastatic wukan, which can occur several years before the appearance of the tumor or simultaneously with the tumor, mostly in small cell undifferentiated carcinoma.
Ninth, skin disease
Some studies found that lung cancer can also cause some skin diseases, such as acanthosis nigricans, exfoliative dermatitis. Acanthosis nigricans is mostly seen in adults, and its incidence is higher in men than women.
Exfoliative dermatitis is an inflammatory disease characterized by flushing and flaking of the skin all over the body. In addition, unexplained pruritus, hyperkeratosis of palmoplantar skin, recurrent eczema, herpes zoster and ichthyosis should also be alerted to malignant tumor.
Tenth, others
It has also been found that there is a correlation between lung cancer and scleroderma, embolic phlebitis, non-bacterial embolic endocarditis, thrombocytopenic purpura, and capillary disease exudative anemia, and the specific pathogenesis needs further study.