Hypertrophic osteoarthropathy associated with lung cancer: Possible links among hypoxia‐inducible factor‐1α, vascular endothelial growth factor, and hypervascularization

• Published in: Thoracic cancer 2023-05, Vol.14 (14), p.1320-1324
• Main Authors: Tagawa, Ryuta, Soda, Hiroshi, Dotsu, Yosuke, Senju, Hiroaki, Irifune, Satoshi, Yoshida, Masataka, Nakashima, Shota, Umemura, Asuka, Iwasaki, Keisuke, Taniguchi, Hirokazu, Takemoto, Shinnosuke, Fukuda, Yuichi, Mukae, Hiroshi
• Format: Article
• Language: English
• Subjects: Aged; Angiogenesis; Antigens; Biopsy; Carcinoma, Non-Small-Cell Lung; Case Report; Case Reports; Chemotherapy; Cloning; Cytokeratin; Cytokines; Edema; Humans; hypertrophic osteoarthropathy; hypervascularization; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; hypoxia‐inducible factor‐1α; Legs; Lung cancer; Lung Neoplasms - complications; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Magnetic resonance imaging; Male; Pain; Patients; Peptides; Plasma; Radiation therapy; Scintigraphy; Smooth muscle; Tomography; Transcription factors; Tumor Microenvironment; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factors
• ISSN: 1759-7706; 1759-7714
• DOI: 10.1111/1759-7714.14869

Hypertrophic osteoarthropathy (HOA) is a paraneoplastic syndrome, the exact pathogenesis of which remains to be elucidated. The case of a 69‐year‐old man who developed intractably painful HOA secondary to lung cancer is presented. Contrast‐enhanced computed tomography of the chest showed an 80‐mm solid nodule with a large low‐density area. The patient was diagnosed as having stage IIIA undifferentiated non–small cell lung cancer. The combination of carboplatin and paclitaxel with bevacizumab reduced tumor size and plasma vascular endothelial growth factor (VEGF) levels, relieving his leg pain. On immunohistochemical examination, lung cancer cells were positive for VEGF. A hypoxic tumor microenvironment may have caused some lung cancer cells to express hypoxia‐inducible factor‐1α, which contributed, at least in part, to the production of VEGF. The deep dermis vessels showed proliferation in the shin, with their thickened walls positive for VEGF. These findings may encourage investigators to explore novel management strategies for painful HOA. Lung cancer cells express vascular endothelial growth factor (VEGF), possibly releasing it into the circulation. The hypoxic tumor microenvironment may have caused some lung cancer cells to express hypoxia‐inducible factor‐1α (HIF‐1α), which contributes, at least in part, to VEGF production. Circulating VEGF potentially promotes the proliferation of subcutaneous vessels. These processes may be involved in the onset of hypertrophic osteoarthropathy.