a 39 y.o woman with a hx of chronic renal failure on dialysis, peripheral vascular disease presents with a 3 wk hx of an enlarging mass over the upper sternum.

what could it be?

Our patient had a large calcified mass over  the upper sternum.  ..  The differential in this case includes a tumor such as : osteosarcoma or fibrosarcoma or ectopic calcification from her renal disease. It can be challenging to determine if a lesion is benign or malignant and a biopsy is necessary.

osteosarcoma can present with calcifications in soft tissue

MALIGNANCY

The fastest doubling time of any tumor is the glioblastoma which doubles in about 27 days.  By our patient’s history, the lesion was the size of a mosquito bite on July 4 and when she presented 7/22/22, about three weeks later it was 5 cm.  So growth may have been too fast for a tumor. Yet, there were bony erosions suggestive of malignancy.

ECTOPIC CALCIFICATIONS IN RENAL DISEASE

Hyperparathyroidism, hyperphosphatemia and an elevated plasma  calcium x phosphate product (>70) have been implicated in both calciphylaxis and metastatic calcification. Our patient’s phosphorus was 8 and Ca was  9.4 giving her a Ca x phosphorus product of 75. 

Calciphlaxis- . Is a condition where calcification occurs in arterioles causing skin ulcers.  While animal studies have shown that  high PTH induces skin necrosis by deposition of calcium in arterioles,  no human studies have been conducted to date in dialysis  patients with high PTH. Moreover, in the German Calciphylaxis registry only 6 percent of patients with calciphylaxis had PTH  levels that were  elevated. Risk factors for calciphylaxis also include warfarin use and autoimmune disease. Ongoing research suggests high phosphate may be more important than calcium in calciphylaxis.  High phosphate is associated with not only calcification of arteries but breakdown of elastin in vessels and

Metastatic pulmonary calcification-  is also associated with a calcium phosphorus product greater than 70.   Calcium salts are deposited in the epithelial basement membranes of the lung.  At autopsy 60-75% of pattients with renal failure have lung calcifications. The calcifications can resolve after kidney transplant. Since it can occur with hypercalcemia of other causes like administration of vit D, sarcoidosis  or massive osteolysis from metastases it is thought the Ca level is the driver of the calcifications.

metastatic pulmonary calcification from renal disease

Tumoral calcinosis- this was first described in 1943.  It has more recently been associated  with genetic mutations in Ga1NAc transferase 3 and causes hyperphosphatemia. There are calcifications in juxta-articular lesions which on biopsy show multiple cysts filled with calcium.  There are no skin lesions and the calcium and phosphorus are normal except in a small subset with high phosphous.   The lesions are most common at the hips and shoulders.

Why is dialysis such a risk for calcification? 

1.       Acidosis in the intervals between dialysis leaches calcium from bone so that in the alkalotic period after dialysis it can be deposited in tissue.

2.       Hyperparathyroidism is an independent risk factor for  ectopic calcification.

3.       The elevated calcium phosphorus product leads to calcification.

tumoral calcinosis

Our patient had a biopsy showing tumoral calcinosis. She was treated with dialysis, sevelamer and cinaclcet to lower her phosphorus.  Since tumoral calcinosis  is only rarely associated with bony erosions, she is also being followed by oncology.

Nigwekar S, Thadhani R. Calciphylaxis (calcific uremic arteriolopathy)   Up to Date June 2022. https://www.uptodate.com/contents/calciphylaxis-calcific-uremic-arteriolopathy?search=Calcium%20phosphate%20product&source=search_result&selectedTitle=1~45&usage_type=default&display_rank=1

Lau W, Festing M, Giachelli C. Phosphate and vascular calcification: emerging role of the sodium-dependent phosphate cotransporter PlT-1.  Thromb Haemost 2010 Sep;104(3):464-470.

Cadavid J, DiVietro M, Torres E, et al. Warfarin-induced pulmonary metastatic calcification and calciphylaxis in a patient with end-stage renal disease. Case Reports Chest . 2011Jun; 139(6):1503-1506. 

Fathi I, Sakr M. Review of tumoral calcinosis: a rare clinic-pathological entity. World J Clin Cases 2014 Sep 16;2(9):409-414. 

Kwee R, Kwee T. Calcified or ossified benign soft tissue lesions that may simulate malignancy. Skeletal Radiol 2019;48(12):1875-1890.

Girard C, Wasserman P, Lenchik l. Secondary tumoral calcinosis with intraosseous penetration. Radiology Case Reports 2009;4:213.