Üçüncü Primer Tümör Nedeniyle Gelişen, Tümör İlişkili Osteomalaziye Bağlı Bir Hipofosfatemi Olgusu.

Yıl 2022, , 890 - 898, 28.11.2022

Gülşah Elbüken , Hünkar Ağgül Ogün Bilen , Sayid Shafi Zuhur

https://doi.org/10.20515/otd.1032870

Öz

Tümörle ilişkili osteomalazi (TİO), genellikle mezenkimal kaynaklı bir tümörün sıklıkla Fibroblast Büyüme Faktörü‐23 (FGF-23) üreterek osteomalaziye neden olduğu paraneoplastik bir durumdur. FGF-23, fosfatürik etki ile hipofosfatemiye neden olur. Olgu: Altmışbeş yaşında erkek hasta, kas güçsüzlüğü, zor yürüme ve şiddetli kemik ağrıları şikayetleri ile başvurdu. Tıbbi öyküsünde: 4 cm çapta orta riskli gastrointestinal sistem stromal tümör (GİST) sebebiyle distal gastrektomi, Billroth 2 antekolik gastroenterostomi ve sonrasında Evre 1 multisentrik mikropapiller karsinom (CA) sebebiyle total tiroidektomi operasyonları mevcuttu. Kemik sintigrafisindeki yaygın lezyonları GİST’in kemik metastazı olarak kabul edilmişti. Laboratuvar tetkiklerinde: Kalsiyum (Ca):8.3 mg/dL, fosfor (P): 1.5 mg/dL, parathormon (PTH): 75 pg/mL, 25-OH vit D3: 31 ng/mL, 1-25-(OH)2 vit D3: 36 pg/mL, kreatinin: 0.75 mg/dL alkalen fosfataz (ALP: 109 IU/L, idrar fosforu: 2.54 gr/gün idi. Hastanın hipofosfatemisinin olası sebebi GIST kemik metastazlarına bağlı olarak gelişmiş TİO’ye bağlı olduğu düşünüldü. Metastazların cerrahi olarak çıkartılması mümkün olmadığından, hastaya oral fosfat ve kalsitriol tedavisi başlandı. Ancak tedavi başlandıktan sonra Ca düzeyleri düzelmesine rağmen, P düzeyleri yaklaşık 2 mg/dl düzeylerinde seyretti. Tedavi başlandıktan bir yıl sonra sağ ayak birinci parmağında ülser gelişmesi üzerine, bu lezyon eksize edildi ve patoloji sonucu “ekstraskeletal miksoid kondrosarkom” olarak raporlandı. Tümörün eksizyonu sonrasında Ca ve P değerleri tamamen normale geldi. GIST ve tiroid CA ile TİO gözlenmesi genellikle beklenilen bir durum değildir. Nitekim hipofosfatemi sebebi olarak, hastamızda üçüncü primer tümöre bağlı olarak gelişmiş bir TİO tespit edildi. Üçüncü primer tümöre bağlı olarak gelişen TİO bildiğimiz kadarıyla literatürde ilk ve tek olgudur. Eğer hastada halihazırda primer bir tümör var ve bu tümör TİO’ye sık neden olan tümörlerden değilse, başka bir primer tümör odağının olup olmadığı dikkatle araştırılmalıdır.

Anahtar Kelimeler

Üçüncü primer tümör, tümör ilişkili osteomalazi, hipofosfatemi, hipofosfatemik osteomalazi

Destekleyen Kurum

Yok

Proje Numarası

Olgu sunumudur.

Hypophosphatemia Associated with Tumor-Induced Osteomalacia Caused by A Third Primary Tumor: A Case Report

Öz

Tumor-induced osteomalacia (TIO) is a paraneoplastic condition in which a tumor, usually of mesenchymal origin, causes osteomalacia often by producing Fibroblast Growth Factor-23 (FGF-23). FGF-23 induces hypophosphatemia through its phosphaturic action. Case Presentation: A 65-year-old male patient presented with complaints of muscle weakness, difficulty walking and severe bone pain. His medical history included distal gastrectomy for a moderate-risk gastrointestinal stromal tumor (GIST) of 4 cm in diameter, Billroth II antecholic gastroenterostomy and subsequently total thyroidectomy for Stage 1 multicentric micropapillary carcinoma (CA). Widespread lesions detected on bone scintigraphy were considered as bone metastases of GIST. Laboratory investigations revealed the following results: calcium (Ca): 8.3 mg/dL; phosphate (P): 1.5 mg/dL; Parathormone (PTH): 75 pg/mL; 25-OH vit D3: 31 ng/mL; 1-25-(OH)2 vit D3: 36 pg/mL; creatinine: 0.75 mg/dL; alkaline phosphatase (ALP): 109 IU/L, urine phosphate: 2.54 g/day. His hypophosphatemia was considered to be most probably due to TIO induced by bone metastases of GIST. Since it was not possible to remove the metastases, the patient was started on oral phosphate and calcitriol therapy. However, despite an improvement in Ca levels after the initiation of the treatment, P levels persisted around 2 mg/dL. After one year of treatment, an ulcer developed on his right first toe, which was excised and identified as “extraskeletal myxoid chondrosarcoma” on pathological examination. Following excision of the tumor, the patient’s Ca and P values returned to normal range. The development of TIO in the presence of a GIST and thyroid CA is an unusual occurrence. As a matter of fact, the cause of hypophosphatemia was TIO which induced by a third primary tumor in this patient. To the best of our knowledge, TIO due to a third primary tumor is the first and only case in the literature. Another primary tumor focus should be suspected and carefully investigated if the patient already has a primary tumor and that tumor is not among those frequently inducing TIO.

Anahtar Kelimeler

Third primary tumor, tumor-induced osteomalacia, hypophosphatemia, hypophosphatemic osteomalacia

Proje Numarası

Olgu sunumudur.

Kaynakça

• Minisola S, Peacock M, Fukumoto S, et al. Tumour-induced osteomalacia. Nat Rev Dis Primers. 2017 Jul 13;3:17044.
• Drezner MK: Tumor-induced osteomalacia. In: Favus MJ (ed), Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 4th edition. Philadelphia: Lippincott Williams & Wilkins, 1999; 331.
• William J, Laskin W, Nayar R, et al. Diagnosis of phosphaturic mesenchymal tumor (mixed connective tissue type) by cytopathology. Diagn. Cytopathol. 2012; 40:E109-E113.
• De Beur SMJ, Finnegan RB, Vassiliadis J, et al. Tumors associated with oncogenic osteomalacia express genes important in bone and mineral metabolism. J Bone Miner Res. 2002;17(6):1102–1110.
• Feng J, Jiang Y, Wang O, et al. The diagnostic dilemma of tumor induced osteomalacia: a retrospective analysis of 144 cases. Endocr J. 2017 Jul 28;64(7):675-683.
• Yin Z, Du J, Yu F, et al. Tumor-induced osteomalacia. Osteoporos Sarcopenia. 2018 Dec;4(4):119-127.
• Wagner CA, Rubio-Aliaga I, Biber J, et al. Genetic diseases of renal phosphate handling. Nephrol. Dial. Transplant. 2014; 29 (Suppl. 4), iv45–iv54.
• Wolf M, White KE. Coupling fibroblast growth factor 23 production and cleavage: iron deficiency, rickets, and kidney disease. Curr Opin Nephrol Hypertens. 2014; 23:411.
• Florenzano P, Hartley IR , Jimenez M, et al. Tumor-Induced Osteomalacia. Calcif Tissue Int. 2021;108, 128–142.
• Razzaque MS, Lanske B. The emerging role of the fibroblast growth factor-23-klotho axis in renal regulation of phosphate homeostasis. J Endocrinol. 2007;194(1):1.
• Scheinman SJ: Dent's disease, Chapter 12. In: Lifton RP, Somlo S, Giebisch GH, Seldin DW (eds), Genetic Diseases of the Kidney. New York: Academic Press, 2009.
• Mumford E, Marks J, Wagner T, et al. Oncogenic osteomalacia: diagnosis, localisation, and cure. Lancet Oncol. 2018;19(7):e365.
• Qaseem A, Forciea MA, McLean RM,et al. Clinical Guidelines Committee of the American College of Physicians: Barry MJ, Cooke M, Fitterman N, et al. Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians. Ann Intern Med. 2017 Jun 6;166(11):818-839
• Spizzo G, Seeber A, Mitterer M. Routine use of pamidronate in NSCLC patients with bone metastasis: results from a retrospective analysis. Anticancer Res. 2009 Dec;29(12):5245-9.
• Di Scioscio V, Greco L, Pallotti MC, et al. Three cases of bone metastases in patients with gastrointestinal stromal tumors. Rare Tumors. 2011 Apr 4;3(2):e17.
• Cohen MH, Dagher R, Griebel DJ, et al. U.S. Food and Drug Administration drug approval summaries: imatinib mesylate, mesna tablets, and zoledronic acid. Oncologist. 2002;7(5):393-400.
• De Beur SMJ, Miller PD, Weber TJ, et al. Burosumab for the Treatment of Tumor-Induced Osteomalacia. J Bone Miner Res 2021; 36:627.