Review Question - QID 104400

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Lung Cancer Classification Non-Small Cell Lung Cancer (NSCLC) Type Location Associated Findings Histology Adenocarcinoma Peripheral Most common cause of lung cancer in non-smokers cause of lung cancer (excluding metastasis) Adenocarcinoma in situ tumor QID: 104400 (M2.ON.12.75)

QID 104400 (Type "104400" in App Search)

A 62-year-old Caucasian male presents to his primary care physician following a week long history of abdominal pain, nausea and vomiting. The patient also reports reduced appetite, fatigue, polyuria, and pain in his lower back. The patient has a 40-pack year history of smoking. Laboratory values are notable for the following: Serum calcium: 12.2 mg/dL, Serum phosphorus: 2.4 mg/dL, and Alkaline phosphatase: 80 U/L. Chest radiograph shows a left middle lobe mass that was not present on prior chest radiograph 2 years ago. Serum parathyroid hormone-related peptide is elevated. Serum electrophoresis is shown in Figure A. Which of the following is the most likely diagnosis?

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Multiple myeloma

0/25

Small cell lung cancer

24%

6/25

Adenocarcinoma of the lung

1/25

Squamous cell lung cancer

68%

17/25

Sarcoidosis

0/25

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The patient presents with elevated serum calcium and parathyroid hormone-related peptide (PTH-rP) in the setting of new onset left middle lobe mass consistent with squamous cell lung cancer.

Hypercalcemia of squamous cell lung cancer is due to the production of PTH-rP by malignant cells. PTH-rP is structurally homologous to parathyroid hormone and can stimulate PTH receptors, causing symptoms similar to primary hyperparathyroidisim. Such symptoms include ‘stones (renal or biliary), bones (bone pain), groans (abdominal pain, nausea, and vomiting), and psychiatric moans (anxiety, lethargy, confusion)’.

Collins et al. review the diagnosis and management of squamous cell lung cancer. Squamous cell lung cancers are typically centrally located, and may present with hemoptysis, postobstructive pneumonia, hypercalcemia, or lobar collapse. The disease is closely linked to smoking.

Alcantara et al. discuss PTH-rP. Hypercalcemia due to PTH-rP is the most common paraneoplastic syndrome and is most often associated with squamous cell carcinoma of the lung and renal cortical cell carcinoma.

Figure A shows a normal serum electrophoresis. Though multiple myeloma can present with back pain and hypercalcemia, the disease produces an M-spike in the gamma globulin region, as seen in Illustration A [Answer 1]. Illustration B is a chest radiograph with squamous cell carcinoma in the left middle lobe of the subject’s lungs.

Incorrect Answers:
Answer 1: Multiple myeloma can present with hypercalcemia (largely from bone breakdown) but has an M-spike in the gamma globulin region on electrophoresis. This is due to production of a paraprotein that can be detected in the blood or urine.
Answer 2 and 3: Hypercalcemia due to PTH-rP is much more commonly due to squamous cell lung cancer than other lung cancers. Small cell lung cancer is associated with several other paraneoplastic syndromes, such as ectopic ACTH secretion and SIADH.
Answer 5: Sarcoidosis is associated with hypercalcemia due to excess production of 1-alpha-hydroxylase and thus increased levels of active vitamin D. It is not associated with PTH-rP

ILLUSTRATIONS: