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Squamous cell carcinoma producing parathyroid hormone
35%
85/242
Squamous cell carcinoma producing a peptide with hormonal activity
49%
119/242
Carcinoid tumor causing carcinoid syndrome
0%
1/242
Metastatic abdominal cancer
Small cell carcinoma producing a peptide with hormonal activity
10%
25/242
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This man is presenting with hypercalcemia in the setting of smoking-associated lung cancer. This is most likely due to squamous cell carcinoma (SCC) producing parathyroid hormone related peptide. SCC of the lung occurs more commonly in men and has a strong link to smoking. It usually presents with a central (hilar) cavitating lesion. SCC can ectopically secrete PTH-related protein (PTHrP), which has effects similar to parathyroid hormone and can cause hypercalcemia and hypophosphatemia. SCC has a unique histology which includes keratin pearls and intercellular bridges. The treatment for SCC of the lung involves surgical resection if possible and may involve radiation and/or chemotherapy. Carroll and Schade discuss hypercalcemia due to malignancy. PTHrP is the main cause associated with hypercalcemia in malignancy with solid tumors. PTHrP has a terminus that is similar to PTH at the receptor-binding domain and thus is able to bind to and activate PTH receptors. Serum PTH levels will generally be low in these patients, as negative feedback suppresses endogenous PTH secretion. Donovan et al. retrospectively reviewed the causes of PTHrP-caused hypercalcemia from a registry at their institution. The authors found that 83% of cases were due to a solid organ malignancy, with SCC and adenocarcinomas being the two leading causes. The authors also found cases associated with myxoid sarcoma, plasma cell leukemia, Merkel cell carcinoma, and epithelioid hemangioendothelioma. Illustration A depicts a gross pathological specimen of a squamous cell carcinoma of the lung. Note the central location of the tumor. Incorrect Answers: Answer 1: Hypercalcemia in SCC is due to PTHrP, not PTH. Indeed, PTH levels are likely suppressed due to negative feedback (caused by the hypercalcemia) suppressing endogenous PTH secretion. Answer 3: Carcinoid syndrome presents with flushing and diarrhea, not constipation. Answer 4: The patient has a primary lung malignancy and no indication of metastatic abdominal cancer. Answer 5: Small cell carcinoma is associated with ACTH production.
2.2
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