Tumoral calcinosis (TC) is a rare clinical and histopathologic disorder affecting a very small fraction of the population and is scarcely documented in the foot and ankle. TC is characterized by calcium salt deposits in the soft tissue surrounding large joints. While classically described as peri‑articular, particularly in primary forms, secondary tumoral calcinosis associated with systemic metabolic disturbances such as end-stage renal disease (ESRD) may occur in non-articular soft tissues, including areas of prior trauma, surgery, or chronic mechanical stress. These deposits generally present as painless, firm, tumor-like masses, but are variable in size, shape, and symptomology. Some patients can experience pain and functional limitations depending on the size and location of the tumors. The most common sites are larger joints such as the shoulder, elbow, and hip; while other anatomic locations are less commonly affected, such as the spine, temporo-mandibular, metacarpals, metatarsals, and popliteal area.

Though the exact etiology of this disease is not fully understood, there are several theories. The most widely accepted theory contains a classification system developed by Smack et al. (1996), which categorizes the disease into primary normo-phosphatemic TC (type 1), primary hyper-phosphatemic TC (type 2), and secondary TC (type 3). Type 1 and type 2 differ on the basis of serum calcium and phosphate levels: Type 1 patients will have normal calcium and phosphate levels, while type 2 patients will have normal calcium and elevated phosphate. Type 1 generally presents itself when patients are <20 years old, with close to 50 % of patients residing in tropical or subtropical regions. Traditionally, type 1 was considered not to have a familial pattern; however, recent theories suggest that it may be linked to mutations in the SAMD9 gene, which codes for a regulatory protein in cell proliferation. Type 2 typically presents in the earlier years of life as well, with most patients being of African descent. There is an established genetic predisposition for type 2 patients caused by recessive genetic mutations in the GalNAc transferase 3 gene, which encodes GALNT3 and KLOTHO proteins. The absence or malfunction of these proteins inactivates FGF23, which is a phosphaturic hormone, in turn decreasing urinary phosphate excretion. Patients with type 3 TC, or secondary TC, must have an underlying systemic disease that affects calcium and phosphate metabolism and balance. Possible diseases include ESRD, hyperparathyroidism, vitamin D toxicity, milk-alkali syndrome, osteolysis, and more.

The pathogenesis of TC varies depending on subtype. In primary forms, particularly type 1, repetitive microtrauma or preceding macro-traumatic injury has been implicated in lesion development. In contrast, secondary TC associated with ESRD is primarily driven by disturbances in calcium-phosphate homeostasis and secondary hyperparathyroidism, which promote ectopic calcium-phosphate deposition in soft tissues. However, in type 1 TC, there is commonly a macro-traumatic injury preceding the development of the lesions. This trauma leads to hemorrhages in the peri‑articular tissue, initiating a trauma response involving foamy histiocytes. From this, a reparative cascade is initiated, consisting of neobursae formation, or new fluid-filled sacs. Within the neobursae, there is calcification and collagenolysis occurring at the same time. Active TC lesions, occurring in the active Stage of TC, consist of loculi filled with viscous, liquified calcium material. Once calcified debris fills the loculi, there is bone formation with cessation of bursae formation. Fibrosis then surrounds the lesions, and this stage of the disease is called the quiescent Stage. While these lesions mainly calcify peri‑articular soft tissue, they can also calcify blood vessels, leading to myocardial infarction, stroke, corneal manifestations, and dental deformities

A 37-year-old woman with a complex medical history—including coronary artery bypass grafting, ST-elevation myocardial infarction, status post drug-eluting stent placement to the right coronary artery and first diagonal branch, chronic limb ischemia, peripheral vascular disease (PVD), status post left lower extremity angioplasty with microvascular disease noted to the forefoot with single vessel runoff to the ankle via the peroneal artery with no further possible vascular intervention, ischemic cardiomyopathy with heart failure with mid-range ejection fraction, hypertension, type 2 diabetes mellitus, diabetic gastroparesis, gastroesophageal reflux disease (GERD), obesity, prior splenic infarct, and ESRD on hemodialysis (HD) who presented to the emergency department in November of 2024, with three weeks of progressively worsening pain localized to a chronic wound on her left foot. Her Podiatric history was significant for multiple prior surgical interventions, including a left transmetatarsal amputation (TMA) performed in 2016. Of note, the patient’s ESRD was secondary to diabetic nephropathy. She initially began peritoneal dialysis in September 2018 and transitioned to HD in June 2020.

On initial physical examination, the left foot demonstrated a plantar bulbous soft tissue protrusion with mild fluctuance and significant overlying callus formation ( Fig. 1 ). The area was tender to direct palpation. Bedside sterile debridement was performed using a #15 blade and dermal curette, revealing a 1 × 1 cm full-thickness ulceration at the base of the lesion. The wound was explored with blunt instrumentation and was negative for probe-to-bone. No purulence was expressed, and only minimal sanguinous drainage was noted. There was no crepitus or proximal streaking, though edema and erythema were present throughout the foot. There was vascular compromise to the left lower extremity with diminished pedal pulses noted.

Initial presentation of wound to the left foot with plantar bulbous soft tissue protrusion.

Laboratory studies revealed a white blood cell count of 9.7 × 10⁹/L (4.0–11 × 10 ⁹/L), elevated C-reactive protein (CRP) at 127.0 mg/L (<10 mg/L), erythrocyte sedimentation rate (ESR) of 100 mm/hr (0–20 mm/hr), calcium of 10.6 mg/dL (8.8–10.2 mg/dL), markedly elevated parathyroid hormone (PTH) at 641.6 pg/mL (10–65 pg/mL), and phosphorus of 8.1 mg/dL (2.5–4.5 mg/dL). These results were suggestive of systemic inflammation and significant mineral metabolism dysregulation in the setting of ESRD. Given the patient’s long-standing ESRD, markedly elevated phosphorus and parathyroid hormone levels, and absence of familial history suggestive of primary TC, her presentation was most consistent with secondary (type 3) tumoral calcinosis.

Following debridement, the patient was admitted for further evaluation and treatment. Plain radiographs of the left foot did not reveal evidence of osteomyelitis but were notable for dystrophic calcifications along the distal forefoot along with vascular calcifications ( Fig. 2 ). Magnetic resonance imaging (MRI) was subsequently obtained, demonstrating multifocal, lobulated calcified soft tissue lesions at the distal amputation stump, keeping with tumoral calcinosis given the patient’s history of chronic renal disease. The MRI also showed evidence of osteomyelitis involving the second and third metatarsal remnants, without associated fluid collections or abscess .

Plain radiographs notable for dystrophic calcifications along the distal forefoot, along with vascular calcifications.

Multidisciplinary discussions were had between Podiatry, Infectious disease, Internal Medicine, and Vascular surgery. Given the patient’s known PVD status post prior angioplasty with documented single-vessel runoff to the ankle via the peroneal artery and no further revascularization options, Vascular surgery determined that no additional intervention was feasible prior to operative management. In light of the concerning findings on plain radiographs and advanced imaging suggestive of possible osteomyelitis, operative debridement was recommended. Limb salvage was favored over more proximal amputation given preserved bone stock and absence of gross osteomyelitis intraoperatively. Plans were made for staged management, potentially including skin substitute grafting and wound vacuum-assisted closure (VAC) application pending intraoperative findings. These options and potential need for further intervention were discussed with the patient as part of shared decision-making. She underwent partial resection of the first through fifth metatarsals with extensive incision and drainage of the left foot extending proximally to the tarsometatarsal joints. The incision was then made along the original TMA incision dorsally. This was extended plantarly as well to obtain adequate exposure of the metatarsals. Intraoperatively, multiple pockets of the thick, viscous white-yellow material were encountered within the plantar and midfoot soft tissues. No frank purulence was noted. These pockets were completely evacuated, and representative tissue samples were sent for microbiologic and histopathologic analysis, including one specimen labeled “left foot soft tissue mass,” consisting of the gelatinous material encountered intraoperatively. The bone stock of metatarsals 1–5 was noted to be hard and firm with a normal appearance, findings not consistent with osteomyelitis.

The surgical site was closed with a combination of sutures and staples ( Fig. 3 ). There was no drain inserted at this level given that all of the gelatinous material encountered was evacuated at this level. Postoperatively, the patient was initiated on intravenous vancomycin in accordance with infectious disease recommendations. Pathologic analysis of the soft tissue specimen demonstrated “benign superficial squamous cells with inflammatory debris” as a primary finding. The pathology report did not specifically describe calcium phosphate crystal deposition; however, no alternative pathologic process was identified. In the context of the characteristic radiographic findings, markedly abnormal calcium–phosphate metabolism, and intraoperative appearance of chalky calcific material, the overall findings were consistent with tumoral calcinosis. The pathologic analysis for the clean margins of metatarsals 2 and 3 was negative for osteomyelitis .

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