A 54-year-old man comes to the office due to several episodes of coughing up bloody sputum. The patient has also noticed weight loss, anorexia, constipation, increased thirst, and fatigue. He smoked 2 packs of cigarettes daily for 32 years but quit last month. Vital signs are within normal limits. The patient appears slim and pale. Physical examination is otherwise normal. Laboratory results are as follows: Chest x-ray shows a left-sided hilar mass. Whole-body bone scan is normal. Histopathology of the hilar mass is most likely to reveal which of the following?

Question

A 54-year-old man comes to the office due to several episodes of coughing up bloody sputum.  The patient has also noticed weight loss, anorexia, constipation, increased thirst, and fatigue.  He smoked 2 packs of cigarettes daily for 32 years but quit last month.  Vital signs are within normal limits.  The patient appears slim and pale.  Physical examination is otherwise normal.  Laboratory results are as follows:  Chest x-ray shows a left-sided hilar mass.  Whole-body bone scan is normal.  Histopathology of the hilar mass is most likely to reveal which of the following?

Quizplus · Accepted Answer

This patient's presentation is most consistent with lung cancer, with his extensive smoking history, hemoptysis, hypercalcemia, and hilar mass raising strong suspicion for squamous cell carcinoma (SCC) of the lung. Most cases of SCC arise in the central portion of the lung, therefore manifesting as a hilar mass (due to squamous metaplasia → dysplasia → carcinoma-in-situ within the central tracheobronchial tree). Patients generally present with cough, dyspnea, and/or hemoptysis due to erosion of the airway mucosa. Smoking is the single greatest risk factor. SCC is associated with hypercalcemia of malignancy (mnemonic: sCa++mous) due to the release of parathyroid hormone-related protein (PTHrP), which binds to the PTH receptor in bones and in the distal tubule of the kidney and increases calcium reabsorption. Common manifestations of hypercalcemia include anorexia/constipation, renal dysfunction (eg, nephrogenic diabetes insipidus [polydipsia]), and musculoskeletal pain. Hypercalcemia of malignancy is generally due to either osteolytic bone metastases or the release of PTHrP. Differentiation can be made with whole-body bone scan and PTHrP testing. This patient's normal whole-body bone scan (no metastatic bone lesions) indicates that the source of his hypercalcemia is PTHrP. (Choice A) Most cases of adenocarcinoma of the lung are associated with peripheral lung lesions. Although hypercalcemia of malignancy can occur, it is usually due to osteolytic bone metastases (not PTHrP release). The presence of a central lesion and normal bone scan make adenocarcinoma less likely. (Choice B) Sarcoidosis can cause hypercalcemia, but most patients have bilateral hilar lymphadenopathy, not a unilateral hilar mass. In addition, this patient's age and smoking history make lung cancer more likely. (Choice C) Small cell carcinoma of the lung is not typically associated with PTHrP-induced hypercalcemia; it can sometimes cause other paraneoplastic syndromes such as ACTH production and syndrome of inappropriate antidiuretic hormone secretion. (Choice E) Tuberculosis can cause hemoptysis, cough, fatigue, and hilar lymphadenopathy but is unlikely to cause hypercalcemia or a hilar mass. Educational objective: Squamous cell carcinoma of the lung usually arises in the central tracheobronchial tree (eg, hilar mass) and is often associated with cough, hemoptysis, dyspnea, and hypercalcemia (due to parathyroid hormone-related protein release). In contrast, small cell carcinoma of the lung causes other paraneoplastic syndromes (eg, ACTH production, syndrome of inappropriate antidiuretic hormone secretion), and adenocarcinoma of the lung typically causes peripheral lung lesions.

A 54-Year-Old Man Comes to the Office Due to Several