Paraneoplastic Syndromes (Case 37: A Problem Set of Three Common Cases)

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Chapter 45
Paraneoplastic Syndromes (Case 37: A Problem Set of Three Common Cases)

Nishanth Sukumaran MD and Mary Denshaw-Burke MD

Case 1: A 70-year-old man presents to the ED with confusion and dehydration. Family members report a weight loss of 30 pounds over the last 6 months and increased forgetfulness over the last several weeks. He has a 50-pack-year smoking history. He has dry mucous membranes on examination. Laboratory values reveal a blood urea nitrogen (BUN) of 50 mg/dL, serum creatinine of 2.5 mg/dL, and serum calcium of 17 mg/dL. Chest radiograph shows a 5 cm × 4 cm mass in the right upper lobe.

Differential Diagnosis

Hypercalcemia and Abnormal Chest Radiograph

Tumor secretion of parathyroid hormone–related peptide (PTHrP)

Bone metastasis

Tumor secretion of calcitriol

Ectopic secretion of parathyroid hormone (PTH)

Case 2: A 65-year-old woman presents to the ED with progressive confusion. Laboratory values reveal serum sodium of 120 mEq/L, serum osmolality of 245 mOsm/kg water, urine osmolality of 600 mOsm/kg water, and urine sodium of 65 mmol/L. A CT scan of the chest shows a mass in the right middle lobe.

Differential Diagnosis

Hyponatremia in Malignancy

Poor dietary intake

Increasedt gastrointestinal losses from tumor or treatment

Syndrome of inappropriate secretion of antidiuretic hormone (SIADH)

Renal failure or congestive heart failure secondary to chemotherapy

Adrenocortical insufficiency from tumor metastasis to adrenal glands

Case 3: A 68-year-old man presents to his family doctor with a 2-month history of dry cough. He also reports a 1-year history of difficulty in getting up from a chair and climbing stairs. He describes muscle aches and cramping, especially after long walks. Chest radiograph shows a left upper lobe mass.

Differential Diagnosis

Weakness in Malignancy


Brain metastasis

Lambert-Eaton myasthenic syndrome (LEMS)

Spinal metastasis with cord compression


Speaking Intelligently

Paraneoplastic syndromes are diseases or symptoms that are the consequence of the presence of cancer in the body, but they are not directly due to the local presence of cancer cells. These phenomena are mediated by humoral factors (hormones and cytokines) secreted by the tumor cells or an immune response directed against the tumor. Paraneoplastic syndromes may parallel the underlying malignancy, and successful treatment of the malignancy may lead to disappearance of the syndrome. However, many paraneoplastic syndromes, especially of immunologic or neurologic etiology, may not respond predictably to treatment of the underlying malignancy. Selected paraneoplastic syndromes are discussed in more detail in the Clinical Entities section.


Clinical Thinking

• Paraneoplastic syndromes may be the presenting symptom in someone who has not yet been diagnosed with cancer or may develop during the course of treatment for cancer.

• The incidental finding of a possible paraneoplastic syndrome should lead to a prompt workup to rule out an underlying malignancy.

• The identification and treatment of the underlying malignancy not only improves symptoms from the paraneoplastic syndrome but also may improve survival if the malignancy is diagnosed at an earlier stage.

• In some patients with a known malignancy, the discovery of a paraneoplastic syndrome may indicate a worse outcome.


• Patients with paraneoplastic syndromes may be either acutely symptomatic needing emergent care or asymptomatic.

• Some patients present with mental status changes such as confusion and coma. The history can be obtained from the patient’s spouse or other family members in the event that the patient is too obtunded to provide any history.

• History of clinically significant weight loss, anorexia, and smoking should draw attention to malignancy as an underlying cause.

• Once a malignancy is suspected, it is imperative to elicit a focused history related to identifying the underlying malignancy.

• A history of drenching night sweats and pruritus could indicate a lymphoproliferative disorder.

• Symptoms such as hemoptysis, persistent cough, hoarseness, and shortness of breath could be indicative of a lung malignancy.

• History should always include questions regarding age-appropriate screening.

• A comprehensive social history including smoking, alcohol use, and occupational exposure to various chemicals should be obtained.

• Family history of malignancies, especially at a younger age, may indicate a genetic link.

Physical Examination

• Patients with hypercalcemia of malignancy have a very high serum calcium level and generally present with signs of volume depletion, such as hypotension, tachycardia, confusion, and dry mucous membranes.

• Patients with SIADH are euvolemic and may present with confusion.

• Patients with LEMS present with proximal muscle weakness.

• The presence of confluent macular erythema (heliotrope rash) and discrete erythematous papules overlying the metacarpophalangeal and interphalangeal joints (Gottron papules) suggests a diagnosis of dermatomyositis, which may be associated with an underlying malignancy.

• Brown to black velvety hyperpigmentation of skin, usually found in body folds, is termed acanthosis nigricans. When seen in individuals over 40 years of age, it is suggestive of an internal malignancy, especially of the gastrointestinal tract.

• Explosive onset of multiple seborrheic keratoses (sign of Leser-Trélat) is a sign of possible internal malignancy of the gastrointestinal tract, breast, or lung.

• Physical exam findings suggesting malignancy also include clubbing, lymphadenopathy, palpable breast mass, and hepatosplenomegaly.

Tests for Consideration

Comprehensive metabolic profile: Used to diagnose hyponatremia, hypercalcemia, and renal failure either secondary to hypercalcemia or from volume depletion.
It may also provide a clue to diagnosis of underlying pancreatic and hepatobiliary malignancies.


CBC with differential count: Eosinophilia is commonly associated with Hodgkin lymphoma and mycosis fungoides.
Basophilia is associated with chronic myelogenous leukemia and other myeloproliferative disorders.



→ Chest radiograph, CT scanning, and MRI can help identify the tumor. They are most often used along with bone scans

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