Tumoral Calcinosis Research Articles

Navigation-assisted resection of tumoral calcinosis of the lumbosacral spine: illustrative case

BACKGROUNDTumoral calcinosis is an uncommon disease resulting from dystrophic calcium phosphate crystal deposition, with only 7% of cases involving the spine, and it may diagnostically mimic neoplasms.OBSERVATIONSIn this case, a 54-year-old woman with history of systemic scleroderma presented with 10 months of progressive left lumbosacral pain. Imaging revealed an expansile, 4 × 7-cm, well-circumscribed mass in the lumbosacral spine with L5–S1 neuroforaminal compression. Because intractable pain and computed tomography (CT)-guided needle biopsy did not entirely rule out malignancy, operative management was pursued. The patient underwent L4–S2 laminectomies, left L5–S1 facetectomy, L5 and S1 pediculectomies, and en bloc resection, performed under stereotactic CT-guided intraoperative navigation. Subsequently, instrumented fusion was performed with L4 and L5 pedicle screws and S2 alar-iliac screws. Pathological examination was consistent with tumoral calcinosis, with multiple nodules of amorphous basophilic granular calcified material lined by histiocytes. There was no evidence of recurrence or neurological deficits at 5-month follow-up.LESSONSBecause spinal tumoral calcinosis may mimic neoplasms on imaging or gross intraoperative appearance, awareness of this clinical entity is essential for any spine surgeon. A review of all case reports of lumbosacral tumoral calcinosis (n = 14 from 1952 to 2016) was additionally performed. The case featured in this report presents the first known case of navigation-assisted resection of lumbosacral tumoral calcinosis.

A rare occurrence of tumoural calcinosis of long head biceps tendon post-COVID-19 infection

Tumoural calcinosis is a rare entity commonly caused by hyperphosphatemia due to bone mineral disease, hyperparathyroidism of chronic renal failure. However, our case demonstrated a normo-phosphatemic tumoural calcinosis post-COVID-19. This is a 36-year-old with a multiple history of soft-tissue calcification presented with acute onset severe right shoulder pain associated with anterior shoulder swelling at day 20 post-COVID-19. The clinical examination reveals anterior shoulder swelling at bicipital groove with severe restriction of range of motion due to pain. Ultrasound revealed an initial solid mass arising from the sheath of long head of biceps tendon which turns into cystic mass at week 4 of the disease. Computed tomography scan demonstrate sedimentation sign. His blood parameters revealed normo-calcemic, normo-phosphatemic bone profile, normal renal function and no sign suggestive of rheumatological disease. He was started on short course on non-steroidal anti-inflammatory drugs (NSAIDs) for 3 week and does not require surgical intervention. His symptoms completely resolved after 4 weeks with persistent shoulder swelling. He was started with prophylaxis low phosphate diet to prevent future recurrence. Our case demonstrates that conservative management using the short course of NSAIDs can be beneficial in treating primary normophosphatemic tumoural calcinosis.

Long follow-up of Multiple Recurrent Calcific Masses–A rare case report of Hyperphosphatemic Familial Tumoral Calcinosis

Hyperphosphatemic familial tumoral calcinosis (HFTC) is an autosomal recessive benign condition of dysregulated phosphate metabolism (biallelic mutation in GLANT3, KLOTHO or FGF23) due to deficiency or resistance of intact fibroblast growth factor 23 resulting in deposition of large amount of ectopic calcium salts in periarticular soft tissues. We present a 21-year male with multiple recurrent masses around both hips, feet, left knee, and left elbow. His serum inorganic phosphate levels and ratio of renal tubular reabsorption rate of phosphate to corrected glomerular filtration rate were markedly elevated. Medical treatment to lower serum phosphate levels by placing him on tablet sevelamer hydrochloride and acetazolamide and surgical excision of the periarticular masses lead to disease remission. At 4 years follow up he has no recurrence and his functional scores (SF 36 and Harris Hip Score) have tremendously improved. Tumoral calcinosis, though rare must be kept in mind as a differential in abnormal calcific masses and with good radiological and laboratory support can be diagnosed early.

Skeletal and extraskeletal disorders of biomineralization.

The physiological process of biomineralization is complex and deviation from it leads to a variety of diseases. Progress in the past 10 years has enhanced understanding of the genetic, molecular and cellular pathophysiology underlying these disorders; sometimes, this knowledge has both facilitated restoration of health and clarified the very nature of biomineralization as it occurs in humans. In this Review, we consider the principal regulators of mineralization and crystallization, and how dysregulation of these processes can lead to human disease. The knowledge acquired to date and gaps still to be filled are highlighted. The disorders of mineralization discussed comprise a broad spectrum of conditions that encompass bone disorders associated with alterations of mineral quantity and quality, as well as disorders of extraskeletal mineralization (hyperphosphataemic familial tumoural calcinosis). Included are disorders of alkaline phosphatase (hypophosphatasia) and phosphate homeostasis (X-linked hypophosphataemic rickets, fluorosis, rickets and osteomalacia). Furthermore, crystallopathies are covered as well as arterial and renal calcification. This Review discusses the current knowledge of biomineralization derived from basic and clinical research and points to future studies that will lead to new therapeutic approaches for biomineralization disorders.

Abstract #1183932: Management Challenge in Hyperphosphatemic Tumoral Calcinosis

Tumoral calcinosis (TC) is a rare metabolic disorder causing abnormal calcium salt deposition in different peri-articular soft tissue regions. The most common site is lateral hips. TC can be primary normo-phosphatemic or primary hyperphosphatemic. It can be secondary also, seen commonly in chronic renal failure. We describe a case report of 14 years old girl who presented with primary hyperphosphatemic tumoral calcinosis with recurrent swellings even after surgery and medical therapy. A 14-year-old girl presented to us with recurrent soft tissue mass and persistent hyperphosphtemia associated with pain and decreased movements. She was operated twice for this soft tissue. Her medical record stated that patient had undergone 6 surgeries till date for these periarticular swellings at multiple sites (right elbow, left hip, right hip and left knee) but it recurs after 3-4 months of surgery and progressively enlarges in size. Physical examination revealed firm tender 9 X 4 cm oval shaped swelling in the left greater trochanteric area with restriction in abduction, internal rotation and rotator movements at hip joint and 4 X 4 cm circular hard, non-sessile mass over medial aspect of left knee joint with slight difficulty in complete flexion of knee. Biochemical work up showed hyperphosphatemia with normal serum calcium and low iPTH levels, low serum 25 hydroxyvitamin-D and slightly high 1,25 vitamin D with calculated TmP/GfR of 5.7 mg/dl. C-terminal FGF23 level was grossly elevated to 1200 RU/ml. Histological evaluation of previously surgically excised soft tissue mass revealed fibrocollagenous stroma with clusters of crystalline and amorphous calcium enclosed by band of histiocytes and lymphocytes compatible with findings seen in tumoral calcinosis. Presently the patient is maintaining the near normal phosphate level with oral phosphate restricted diet and multiple phosphate binder and acetazolamide. Hyperphosphatemic Tumoral calcinosis is a disorder of dysregulated phosphate metabolism characterized by hyperphosphatemia and deposition of calcium salts in soft tissue regions of the body usually in the periarticular sites. FGF23 is a 251-amino acid peptide secreted by osteoblasts, osteocytes and erythroid precursor cells of the bone marrow that plays a critical role in phosphate regulation. In the proximal tubule of the kidney, FGF23 binds to the FGF receptor 1 (FGFR1) and its co-receptor KLOTHO, downregulating expression of the sodium-phosphate cotransporters NPT2a and NPT2c, which leads to phosphaturia. Additionally, FGF23 inhibits 1-alpha-hydroxylase and stimulates 25-vitamin D-24 hydroxylase, resulting in decreased 1,25-(OH)2-vitamin D (1,25D), the active form of vitamin D. Recently an entitity named autoimmune hyperphosphataemic tumoral calcinosis has been reported in which pathogenetic autoantibodies mediate FGF23 resistance.Treatment is to lower serum phosphorus by blocking dietary phosphate absorption and increasing renal phosphate excretion. Surgery is usually reserved for patients with significant pain or restricted movements of joint.

Spinal calcifying pseudoneoplasm of the neuraxis (CAPNON) and CAPNON-like lesions: CAPNON overlapping with calcified synovial cysts

Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumour-like fibro-osseous lesion in the neuraxis including the spine. It is diagnosed by the presence of the following histological features: granular amorphous to chondromyxoid fibrillary cores with calcification/ossification, peripheral palisading of spindle to epithelioid cells, variable fibrous stroma, and foreign body reaction with multinucleated giant cells, as well as positive NF-L immunostaining. Spinal CAPNON is sometimes named as tumoural calcinosis that is tumour-like dystrophic calcification usually in the periarticular tissue and also described in calcified synovial cyst (CSC). We examined clinical, radiological and pathological features of five spinal CAPNONs and 21 spinal CSCs including three recurrent lesions. The results demonstrated some radiological and pathological overlaps between these two entities, as well as distinct features of each entity to be diagnosed. All CAPNONs showed the diagnostic histological features with NF-L positivity mainly in lesion cores and variable CD8+ T-cells. In contrast, CSCs exhibited the synovial lining and variable degenerative/reactive changes with some CAPNON-like features, but mostly no to occasionally limited NF-L positivity and less CD8+ T-cells with statistically significant differences between groups of CAPNONs and CSCs. Four CSCs contained CAPNON-like foci with the CAPNON diagnostic features including prominent NF-L positivity, and some transitional features from CSC to CAPNON. As the pathogenesis of CAPNON is likely reactive/degenerative in association with an inflammatory/immunological process involving NF-L protein deposition, our findings suggest the link between spinal CAPNON and CSC, with possible transition from CSC to CAPNON or CAPNON developing in reaction to CSC.

Abstract 149: Hyperphosphatemic familial tumoral calcinosis due to homozygous mutation at Leu366Arg: First case report

Background: Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare disabling autosomal recessive metabolic disorder characterized by hyperphosphatemia and manifestations ranging from progressive deposition of calcium phosphate crystals in the skin, soft tissues and bone, and hyperostosis. The most common cause of HFTC is related to loss-of-function mutations in GALNT3 (Polypeptide N-Acetylgalactosaminyl transferase 3) gene causing defective glycosylation of FGF23.Material and Methods: A 16 year boy presented with lump in the left gluteal area and hyperphosphatemia. Serum ionized calcium, alkaline phosphate, intact PTH, 25-OH vitamin D, serum creatinine and C terminal FGF 23, magnetic resonance imaging of hip, dental CBCT , bone mineral density at lumbar spine and hip by dual x-ray absorptiometry (DEXA) BMD, and 99Tc MDP bone scan, followed by next generation sequencing (NGS) and Sanger's sequencing.Results: A 16 year otherwise healthy boy presented with hard painless lump in the left gluteal area and hyperphosphatemia for last one year. His parents had third degree consanguinity with ancestral roots in Middle East. Father has small calcinosis in the right hand and mother was asymptomatic. Child had no associated bone pain, proximal muscle weakness, fracture or constitutional symptoms. S. phosphorus was 6.98mg/dl (normal: 3.5–5.5) with inappropriately increased TRP (95%) and TMP-GFR (7.2). Serum ionized calcium, alkaline phosphate, intact PTH, 25-OH vitamin D and serum creatinine were normal. MRI showed 5.7x3.7x3 cm lobulated heterogenous hypointensity near left greater trochanter. This mass was excised and showed tissue calcification. 99Tc-MDP bone scan and bone density parameters were normal. CBCT scan maxilla and mandible showed generalized hypercementosis with irregular root morphology. Serum C-terminal FGF 23 was 2401 RU/ml (normal: <150). NGS revealed normal FGF23 and Alpha Klotho genes. Exon 5 of GALNT3 gene showed homozygous mutation at Leu 366 Arg. GALNT3 Leu 366 Arg mutation causing HFTC has been described as compound heterozygous.Conclusion: This is the first case report of homozygous mutation at Leu366Arg causing HFTC.

Uremic tumoral calcinosis with atypical manifestation. Case report

Uremic tumoral calcinosis with atypical manifestation. Case report

Parathyroidectomy May Cause Remission of Uraemic Tumoral Calcinosis in Haemodialysis Patients

AbstractFew cases of uraemic tumoral calcinosis (UTC) have been reported. This study aimed to investigate the clinical efficacy of parathyroidectomy for UTC. Historical clinical data of patients with end-stage renal disease and UTC who underwent parathyroidectomy were analysed. Absorption of metastatic calcification was compared before and after operation. Changes in intact parathyroid hormone, serum calcium, phosphorus, and alkaline phosphatase levels were analysed before parathyroidectomy and at 1 week and 3, 6, and 12 months after parathyroidectomy. Eight patients met the enrolment criteria (men, 6; mean age, 38.6 SD 10.9 years). Uraemic tumoral calcinosis, which developed 2–8 years after dialysis began, was caused by secondary hyperparathyroidism. Massive calcium deposition was found in the shoulder (n = 6), hip (n = 3), and elbow (n = 2). Four patients had &gt; 2 joints affected, and a single joint was involved for four patients. Seven patients had rapid remission (&lt; 6 months) of the masses after parathyroidectomy. In one patient, the mass remained unabsorbed until 6 months postoperatively. Hypocalcaemia occurred in all patients where parathyroidectomy was successful, and calcium supplementation was required 1 year postoperatively. Serum intact parathyroid hormone levels on day 7 and at 3 and 6 months postoperatively decreased significantly from baseline and remained low 1 year postoperatively (22.015 SD33.134 pg/mL). Postoperative phosphorus levels were significantly lower than preoperative levels (p &lt; 0.05), but no significant difference was found in alkaline phosphatase levels (p &gt; 0.05). Parathyroidectomy has promising efficacy for UTC treatment and regulation of serum intact parathyroid hormone and phosphorus. Hypocalcaemia is a common complication after parathyroidectomy. Current Controlled Trials ChiCTR2000041311, date of registration: Dec. 23, 2020.

Recurrent Bilateral Lower Motor Neuron Type of Facial Palsy with Hearing Impairment: Hyperphosphatemic Familial Tumoral Calcinosis.

Hyperphosphatemic familial tumoral calcinosis (HFTC) presents with varied neurological manifestations that have been reported in the literature like facial palsy, vision and hearing impairment, stroke, and headache. In this article, we reported a 12-year-old girl child patient with recurrent facial weakness with bilateral hearing impairment and multiple ulcerative lesions on lower limbs and elbows. On examination, she had lower motor neuron (LMN) facial palsy with conductive hearing loss. The investigations showed hyperphosphatemia (9.3 mg/dL) with normal serum calcium (10.4 mg/dL), alkaline phosphatase (147.9 U/L), parathyroid hormone (23.12 pg/mL), and renal function tests. Elevated serum calcium and phosphorus product (96.72 mg 2 /mL 2 ) and elevated renal tubular reabsorption of phosphate (TMPxGFR) value (9.16) were noted. Skeletal survey showed hyperostosis in the long bone diaphysis, vertebrae, ribs, pelvic bone, skull, and facial bones with narrowing of cranial ostium, characteristically without any peri-articular soft tissue calcifications. An angiogram showed multiple intravascular calcifications. She was managed with a low-phosphate diet, sevelamer, niacinamide, acetazolamide, sucroferric oxyhydroxide to lower serum phosphate level, and topical sodium thiosulfate ectopic cutaneous calcification. Exome sequencing showed novel homozygous inframe deletion of ACG in FGF23 gene exon 3 at c.374_376 delins position (p. Asp125del) in the proband and a mutation in the heterozygous state in the mother and elder sibling, thus confirming a molecular diagnosis of HFTC. Our case had a unique neurological presentation of recurrent bilateral lower motor nerve facial palsy, hearing loss, multiple ectopic cutaneous calcifications without peri-articular deposits, multiple intravascular, intracranial, and vertebral endplate calcification, which has not been reported earlier. The proband showed a novel pathogenic variant suggesting an expanding phenotype of HFTC.

Phosphate-Sensing.

The blood level of phosphate is tightly regulated in a narrow range. Hyperphosphatemia and hypophosphatemia both lead to the development of diseases, such as hyperphosphatemic tumoral calcinosis and rickets/osteomalacia, respectively. Although several humoral factors have been known to affect blood phosphate levels, fibroblast growth factor 23 (FGF23) is the principal hormone involved in the regulation of blood phosphate. This hormone is produced by bone, particularly by osteocytes and osteoblasts, and has the effect of lowering the blood level of phosphate in the renal proximal tubules. Therefore, some phosphate-sensing mechanism should exist, at least in the bone. However, the mechanisms through which bone senses changes in the blood level of phosphate, and through which the bone regulates FGF23 production remain to be fully elucidated. Our recent findings demonstrate that high extracellular phosphate phosphorylates FGF receptor 1c (FGFR1c). Its downstream extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signaling pathway regulates the expression of several transcription factors and the GALNT3 gene, which encodes GalNAc-T3, which plays a role in the regulation of posttranslational modification of FGF23 protein, which in turn enhances FGF23 production. The FGFR1c-GALNT3 gene axis is considered to be the most important mechanism for regulating the production of FGF23 in bone in the response to a high phosphate diet. Thus-in the regulation of FGF23 production and blood phosphate levels-FGFR1c may be considered to function as a phosphate-sensing molecule. A feedback mechanism, in which FGFR1c and FGF23 are involved, is present in blood phosphate regulation. In addition, other reports indicate that PiT1 and PiT2 (type III sodium-phosphate cotransporters), and calcium-sensing receptor are also involved in the phosphate-sensing mechanism. In the present chapter, we summarize new insights on phosphate-sensing mechanisms.

Idiopathic tumoral calcinosis in children: Case report

Tumoral calcinosis is a rare, benign entity characterized by the deposition of calcium in periarticular soft tissues. We report the original case of an idiopathic tumoral calcinosis of the elbow in a 6-year-old girl successfully treated by drainage with no signs of recurrence after a 3-year follow-up. We discuss the particularities of this joint location and our therapeutic management.

Inflammatory Tumoral Calcinosis in a Dialysis Patient.

Inflammatory Tumoral Calcinosis in a Dialysis Patient.

Tumoral Calcinosis in Distal Femur: First Documented Case in a Tertiary Medical Center in Philippines

Tumoral calcinosis is a rare clinical and histopathologic syndrome characterized by calcium phosphate deposition in peri-articular soft tissue regions, most commonly in the large joints of the hips, shoulders, and elbows. We present the case of a 49-year old female with 8 months history of gradual increasing, painless swelling along her left distal thigh. Plain radiography demonstrated a dense lobulated cluster of calcific nodules within soft tissues consistent with a diagnosis of tumoral calcinosis, as confirmed by histopathological examination. Using this case as illustration, the first case of such nature in our institution, we reviewed pertinent literature related to the management of tumoral calcinosis. Although the pathogenesis in tumoral calcinosis is controversial, the ideal management is surgical excision with complete removal of abnormal tissue to prevent recurrence and to focus on the reduction of serum phosphate levels.

Hyperphosphatemic Familial Tumoral Calcinosis Hidden in Plain Sight for 73 Years: A Case Report

While dental pulp calcifications and root anomalies may be inconsequential incidental findings in dental radiographs, they can, especially in combination, represent a clue, hidden in plain sight, for the diagnosis of hyperphosphatemic familial tumoral calcinosis (HFTC). HFTC is an autosomal recessive disease of mineral metabolism characterized by sometimes massive, painful calcification around large joints, systemic inflammation, dental pulp calcification, and thistle-shaped roots. This paper describes a woman with HFTC who endured not only the symptoms of HFTC for decades, but also the frustration of not knowing the cause. The diagnosis was finally made at the age of 73 years, when the connection between a large right shoulder calcification and hyperphosphatemia was made. The dental findings were likely present on her initial radiographs taken in childhood. Increased awareness of the association between characteristic dental findings and HFTC may allow for earlier diagnosis and interventions to improve the care of patients with this rare condition.

Two Cases of Tumoral Calcinosis

Two Cases of Tumoral Calcinosis

Esophageal Obstruction Secondary to Massive Tumoral Calcinosis.

Calcinosis is a well-known manifestation of systemic sclerosis (SSc) and is hypothesized to arise from sites of chronic inflammation and tissue hypoxia1. Calcinosis associated with connective tissue disease has been treated with calcium channel blockers, colchicine, bisphosphonates, warfarin, intravenous Ig, and sodium thiosulfate, albeit with no consistent benefits shown in studies2. Palliative cases have also been treated with CO2 laser3 and shock wave lithotripsy4 …

Tumoral calcinosis

Tumoral calcinosis

A Cross-Sectional Cohort Study of the Effects of FGF23 Deficiency and Hyperphosphatemia on Dental Structures in Hyperphosphatemic Familial Tumoral Calcinosis.

ABSTRACTHyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disorder caused by mutations in FGF23, GALNT3, KLOTHO, or FGF23 autoantibodies. Prominent features include high blood phosphate and calcific masses, usually adjacent to large joints. Dental defects have been reported, but not systematically described. Seventeen patients with HFTC followed at the National Institutes of Health underwent detailed clinical, biochemical, molecular, and dental analyses. Studies of teeth included intraoral photos and radiographs, high‐resolution μCT, histology, and scanning electron microscopy (SEM). A scoring system was developed to assess the severity of tooth phenotype. Pulp calcification was found in 13 of 14 evaluable patients. Short roots and midroot bulges with apical thinning were present in 12 of 13 patients. Premolars were most severely affected. μCT analyses of five HFTC teeth revealed that pulp density increased sevenfold, whereas the pulp volume decreased sevenfold in permanent HFTC teeth compared with age‐ and tooth‐matched control teeth. Histology revealed loss of the polarized odontoblast cell layer and an obliterated pulp cavity that was filled with calcified material. The SEM showed altered pulp and cementum structures, without differences in enamel or dentin structures, when compared with control teeth. This study defines the spectrum and confirms the high penetrance of dental features in HFTC. The phenotypes appear to be independent of genetic/molecular etiology, suggesting hyperphosphatemia or FGF23 deficiency may be the pathomechanistic driver, with prominent effects on root and pulp structures, consistent with a role of phosphate and/or FGF23 in tooth development. Given the early appearance and high penetrance, cognizance of HFTC‐related features may allow for earlier diagnosis and treatment. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Giant Joints in Association with Chronic Renal Failure

Tumoral Calcinosis (TC) is an uncommon benign entitiy characterized by solitary or multiple tumorlike densely calcified periarticular masses located typically in the extensor surfaces of the large joints. TC can be primary or secondary. The primary TC is a rare hereditary familial disorder of phosphate regulation. On the other hand, secondary TC is associated with an underlying disease, most frequently, chronic renal faliure (CRF). Herein, we present a case of 40 year old male patient with CRF and 10 years history of hemodialysis, presenting with swellings around the right hip and left shoulder joints. The diagnosis of secondary TC has been made with typical computed tomography (CT) and magnetic resonance imaging (MRI) findings. Secondary TC is an uncommon condition particularly occuring in association with CRF. Typical radiologic findings and clinical history are leading in the diagnosis and prevent unnecessary further evaluations.