Tumoral Calcinosis Research Articles

Extensive Tumoral Calcinosis and Acral Osteolysis

Extensive Tumoral Calcinosis and Acral Osteolysis

Infected Tumoral Calcinosis Associated With Rheumatoid Arthritis.

Tumoral calcinosis (TC) is a syndrome of unknown etiology characterized by calcium salt deposition in soft tissues.1 A case of infected TC with rheumatoid arthritis (RA) is described.

Hyperphosphatemic Familial Tumoral Calcinosis (HFTC) in a One-Year-Old Child: A Case Report and Literature Review

Introduction: Hyperphosphatemic Familial Tumoral Calcinosis (HFTC) is a rare autosomal recessive metabolic disorder characterized by abnormal phosphate regulation and soft tissue calcifications. Early diagnosis is crucial for optimal management to prevent complications. Case Presentation: A one-year-old child presented with intermittent fevers and a gluteal mass. Ultrasound revealed a calcified abscess, and biopsy confirmed a pseudocyst. Further workup identified elevated blood calcium, phosphorus, and neutropenia. The patient was ultimately diagnosed with HFTC. Discussion: Early diagnosis of HFTC is challenging due to the rarity of the disease and the potential for non-specific initial symptoms. This case highlights the importance of considering HFTC in the differential diagnosis for a young child with unexplained soft tissue masses or skeletal abnormalities, even outside the usual age range. Conclusions: This case report emphasizes the need for a high index of suspicion for HFTC in pediatric patients with suggestive clinical features, regardless of age. Early diagnosis and prompt intervention are essential to improve long-term outcomes and prevent complications.

7984 A Challenging Case Of Hyperphosphatemic Familial Tumoral Calcinosis

Abstract Disclosure: T.G. de Souza: None. T.J. Weber: None. Introduction: Hyperphosphatemic Familial Tumoral Calcinosis (hFTC) is a rare, autosomal recessive metabolic disorder characterized by elevated serum phosphate levels and the accumulation of calcium phosphate deposits in soft tissues. There are fewer that 150 genetically confirmed cases in the literature. There are no consensus guidelines; therapeutic approaches are guided by case reports or series. This case serves to heighten awareness of therapeutic strategies including global health considerations for the disabled adult with a rare bone disorder. Case: A 32-year-old African-American woman presented to establish care for hFTC, for which she takes ibuprofen for disabling bilateral hip pain. hFTC was diagnosed in early childhood and managed at a large children’s hospital. Therapeutic modalities relied on operative resection of skin lesions on eruption. She describes cosanguinous parentage, consignment to foster care as a child and homelessness as an adult. She has not had adult endocrine care for her hFTC. Her medical comorbidities include major depressive disorder, PTSD and suicide attempt. She reports one uncle with hFTC noting that his phenotype was not significantly disabling and apparent recession of his lesions with age. Her parents did not have symptoms of hFTC. Radiographically, she had amorphous calcium deposits over both hips (her primary sites of severe pain), upper back (site of painless spontaneous eruptions), and left elbow without pain or skin penetration, as well as hyperostosis of the ilium bilaterally. She noticed waxing and waning of her eruptions with her menstrual cycle, such that lesions worsen in the luteal phase. Megestrol acetate also induced new eruptions. Examination shows brown staining to all teeth with several missing teeth. She had a marked lower extremity limb length discrepancy with severe restriction of hip abduction. Blood chemistries were grossly normal, including renal function, calcium, uric acid and PTH. Serum phosphorous was elevated at 5.2 (2.3 - 4.5 mg/dL). CT showed bilateral nephrocalcinosis. We instituted treatment with a low phosphorous diet, sevelamer to reduce intestinal phosphate absorption and acetazolamide to increase urinary phosphate excretion. For her pain and functional disability, we recommended continued NSAIDs, physical therapy and social work consultation to facilitate continued access to care. Conclusions: This case uniquely describes hFTC symptom fluctuation with the menstrual cycle, worsening with increased progesterone, suggesting a possible role of gonadal hormones on FGF-23 biology. It also highlights the socioeconomic burdens that can accompany rare bone disease, which become more pronounced as the patient achieves adulthood. Successful transition of care from pediatric to adult endocrinologist, in addition to engaging multi-disciplinary support, is essential in optimizing life-long care in hFTC. Presentation: 6/1/2024

Ocular manifestations in a case of tumoral calcinosis

Tumoral calcinosis is a rare genetic disease characterized by calcium-containing crystal deposition as masses in the major joints of the body. We are presenting tumoral calcinosis with ocular manifestations. Clinical examination and imaging were performed. The patient presented with a bilateral hip mass. The radiology of the buttocks showed a calcified heterogeneous mass [Fig. 1]. Calcific depositions from the gluteal region and lid margin were excised and sent for cytology. The histopathological examination (HPE) report showed giant cells and calcifications [Fig. 2]. Blood reports revealed increased serum phosphate and parathyroid hormone (PTH) with normal calcium levels.

Unexpected Early Hypercalcemia after Parathyroidectomy in a Patient with Tumoral Calcinosis and Severe Calciphylaxis

Unexpected Early Hypercalcemia after Parathyroidectomy in a Patient with Tumoral Calcinosis and Severe Calciphylaxis

In vivo mapping of the mouse Galnt3-specific O-glycoproteome

The UDP-N-acetylgalactosamine polypeptide:N-acetylgalactosaminyltransferase (GalNAc-T) family of enzymes initiates O-linked glycosylation by catalyzing the addition of the first GalNAc sugar to serine or threonine on proteins destined to be membrane-bound or secreted. Defects in individual isoforms of the GalNAc-T family can lead to certain congenital disorders of glycosylation (CDG). The GALNT3-CDG, is caused by mutations in GALNT3, resulting in hyperphosphatemic familial tumoral calcinosis (HFTC) due to impaired glycosylation of the phosphate-regulating hormone FGF23 within osteocytes of the bone. Patients with hyperphosphatemia present altered bone density, abnormal tooth structure and calcified masses throughout the body. It is therefore important to identify all potential substrates of GalNAc-T3 throughout the body to understand the complex disease phenotypes. Here, we compared the Galnt3-/- mouse model, which partially phenocopies GALNT3-CDG, with wild-type mice and employed a multi-component approach utilizing chemoenzymatic conditions, a product-dependent method constructed using EThcD triggered scans in a mass spectrometry workflow, quantitative O-glycoproteomics, and global proteomics to identify 663 Galnt3-specific O-glycosites from 269 glycoproteins across multiple tissues. Consistent with the mouse and human phenotypes, functional networks of glycoproteins that contain GalNAc-T3-specific O-glycosites involved in skeletal morphology, mineral level maintenance and hemostasis were identified. This library of in vivo GalNAc-T3-specific substrate proteins and O-glycosites will serve as a valuable resource to understand the functional implications of O-glycosylation and to unravel the underlying causes of complex human GALNT3-CDG phenotypes.

Structural and molecular imaging-based characterization of soft tissue and vascular calcification in hyperphosphatemic familial tumoral calcinosis.

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare disorder caused by deficient FGF23 signaling and resultant ectopic calcification. Here, we systematically characterized and quantified macro- and micro-calcification in a HFTC cohort using CT and 18F-sodium fluoride PET/CT (18F-NaF PET/CT). Fourier-transform infrared (FTIR) spectroscopy was performed on 4 phenotypically different calcifications from a patient with HFTC, showing the dominant component to be hydroxyapatite. Eleven patients with HFTC were studied with CT and/or 18F-NaF PET/CT. Qualitative review was done to describe the spectrum of imaging findings on both modalities. CT-based measures of volume (eg, total calcific burden and lesion volume) and density (Hounsfield units) were quantified and compared to PET-based measures of mineralization activity (eg, mean standardized uptake values-SUVs). Microcalcification scores were calculated for the vasculature of 6 patients using 18F-NaF PET/CT and visualized on a standardized vascular atlas. Ectopic calcifications were present in 82% of patients, predominantly near joints and the distal extremities. Considerable heterogeneity was observed in total calcific burden per patient (823.0 ± 670.1cm3, n = 9) and lesion volume (282.5 ± 414.8cm3, n = 27). The largest lesions were found at the hips and shoulders. 18F-NaF PET offered the ability to differentiate active vs quiescent calcifications. Calcifications were also noted in multiple anatomic locations, including brain parenchyma (50%). Vascular calcification was seen in the abdominal aorta, carotid, and coronaries in 50%, 73%, and 50%, respectively. 18F-NaF-avid, but CT-negative calcification was seen in a 17-year-old patient, implicating early onset vascular calcification. This first systematic assessment of calcifications in a cohort of patients with HFTC has identified the early onset, prevalence, and extent of calcification. It supports 18F-NaF PET/CT as a clinical tool for distinguishing between active and inactive calcification, informing disease progression, and quantification of ectopic and vascular disease burden.

Tumoral Calcinosis at a Finger Metacarpophalangeal Joint.

A 51-year-old patient presented with a painful swelling palmar to the metacarpophalangeal joint of the ring finger. A round tumor was detected using X-rays and MRI. After excision, tumoral calcinosis could be verified histologically.

Tumoral calcinosis cutis universalis in a patient with systemic sclerosis

Abstract: We report a 75-year-old female with long standing systemic sclerosis presenting with tumoral calcinosis of the hands, wrists, elbows and pelvis.

Clinical Characteristics, Therapeutic Options, and Outcomes in Hyperphosphatemic Tumoral Calcinosis: A Systematic Review.

This systematic review was performed to understand better the myriad presentations, various therapeutic options, response to therapy, and its clinical outcomes in hyperphosphatemic tumoral calcinosis (HTC). Full texts were selected according to strict inclusion criteria. All case reports of HTC wherein baseline phosphate was measured, treatment offered was mentioned, and information on follow-up and response to therapy that were available were included. A total of 43 of 188 eligible studies (N = 63 patients) met the inclusion criteria. A list of desired data was extracted and graded for methodological quality. A total of 63 individuals (Males = 33) were included from the 43 eligible case studies. The median age of the patients was 18 (IQR 8-32) years. The most frequently involved sites were the hip/gluteal region (34/63; 53.9%) followed by the elbow/forearm (26/63; 41.2%), and the shoulder (18/63; 28.5%). Three patients had conjunctival calcific deposits. The mean (SD) phosphate was 6.9 (1.1) mg/dL. Among the subjects, 36/63 (57.1%) underwent surgical excision with some form of medical therapy. Two patients underwent only surgical excision (2.1%). One patient was maintained on follow-up (1.6%) and 24/63 (38.1%) patients were treated with medical measures. The median (IQR) follow-up duration was 3 (1-9) years. Regression or reduction in lesion size was reported in 19/63 (30.2%) subjects; 20/63 (31.7%) showed progression, 24/63 (38.1%) had features of stable disease, and mortality was reported in 3 patients (4.7%). We report for the first time a detailed description of the clinical and therapeutic response of HTC. A combination of medical measures aimed at lowering serum phosphate appears to be the cornerstone of treatment, although clinical responses may vary.

GALNT3 Mutation in Hyperphosphatemic Familial Tumoral Calcinosis – Novel Etiology of Secondary Amyloidosis

Tumoral calcinosis is a rare syndrome characterized by calcium salt deposition in different periarticular soft tissue regions. We report this case of tumoral calcinosis with history of persistent soft tissue calcifications for over three decades. He presented with nephrotic syndrome and kidney biopsy revealed secondary amyloidosis. Genetic evaluation revealed GALNT3 mutation and diagnosis of hyperphosphatemic familial tumoral calcinosis was made. With this case report, we want to reiterate the need to consider tumoral calcinosis in secondary amyloidosis differentials and the pivotal role of genetic workup in chronic soft tissue calcifications.

Spatial Atlas for Mapping Vascular Microcalcification Using 18F-NaF PET/CT: Application in Hyperphosphatemic Familial Tumoral Calcinosis.

Vascular calcification causes significant morbidity and occurs frequently in diseases of calcium/phosphate imbalance. Radiolabeled sodium fluoride positron emission tomography/computed tomography has emerged as a sensitive and specific method for detecting and quantifying active microcalcifications. We developed a novel technique to quantify and map total vasculature microcalcification to a common space, allowing simultaneous assessment of global disease burden and precise tracking of site-specific microcalcifications across time and individuals. To develop this technique, 4 patients with hyperphosphatemic familial tumoral calcinosis, a monogenic disorder of FGF23 (fibroblast growth factor-23) deficiency with a high prevalence of vascular calcification, underwent radiolabeled sodium fluoride positron emission tomography/computed tomography imaging. One patient received serial imaging 1 year after treatment with an IL-1 (interleukin-1) antagonist. A radiolabeled sodium fluoride-based microcalcification score, as well as calcification volume, was computed at all perpendicular slices, which were then mapped onto a standardized vascular atlas. Segment-wise mCSmean and mCSmax were computed to compare microcalcification score levels at predefined vascular segments within subjects. Patients with hyperphosphatemic familial tumoral calcinosis had notable peaks in microcalcification score near the aortic bifurcation and distal femoral arteries, compared with a control subject who had uniform distribution of vascular radiolabeled sodium fluoride uptake. This technique also identified microcalcification in a 17-year-old patient, who had no computed tomography-defined calcification. This technique could not only detect a decrease in microcalcification score throughout the patient treated with an IL-1 antagonist but it also identified anatomic areas that had increased responsiveness while there was no change in computed tomography-defined macrocalcification after treatment. This technique affords the ability to visualize spatial patterns of the active microcalcification process in the peripheral vasculature. Further, this technique affords the ability to track microcalcifications at precise locations not only across time but also across subjects. This technique is readily adaptable to other diseases of vascular calcification and may represent a significant advance in the field of vascular biology.

Tumoral Calcinosis (TC) of iliac Crest in a 70 year-Old Female: A Case Report

A seventy-year-old lady had a hard tumor mass in left sacroiliac region. She was operated. Biopsy was taken from the left iliac crest and histopathological examination was done. Tumor measured 3×2×2 cms approximately. It was chalky-white ball-like. Its surface was lobulated. Microscopically, it showed small and large areas of necrosis and calcification. Areas of mild-to-moderate lymphocytic infiltration were seen. Fibrosis and hyalinization were seen. Bony trabeculae and osteoid formation were also seen. The patient was finally diagnosed as a case of primary tumoral calcinosis of sacroiliac region. Keywords: Soft tissue calcification necrosis osteoid formation chronic inflammation

Idiopathic Localised Perforating Calcinosis Cutis Over the Bilateral Distal Phalanx of the Middle Finger - A Rare Case Report

Calcinosis cutis or cutaneous calcification occurs when calcium is deposited into the skin and subcutaneous tissue. It is classified into five primary types: Dystrophic, metastatic, idiopathic, iatrogenic and calciphylaxis. Idiopathic calcinosis cutis is a rare phenomenon that occurs in the absence of a known tissue injury or systemic metabolic defect. The various types of idiopathic calcinosis are idiopathic calcinosis of scrotum/penis/vulva, milia-like idiopathic calcinosis cutis, subepidermal calcified nodule, tumoural calcinosis, localised calcinosis cutis and calcinosis universalis. It is essential to delineate it from other calcification disorders for further plan of management. We report one such case of idiopathic localised perforating calcinosis cutis, symmetrically over a bilateral distal phalanx of the middle finger in a 72-year-old female.

Tumoral Calcinosis: Clinical and Radiological Findings

Tumoral Calcinosis: Clinical and Radiological Findings

Sedimentation Sign in Tumoral Calcinosis in Systemic Sclerosis.

Sedimentation Sign in Tumoral Calcinosis in Systemic Sclerosis.

Pseudo Tumoral Calcinosis and Renal Ostedystrophy in Pathien under Hemodialysis: About a Case

Pseudo tumoral calcinosis is a rare affection, characterized by the deposition of calcium phosphate crystals in peri- articular soft tissues, forming giant mass, calcified and appearing as a compressive tumor. This affection can be hereditary of secondary to chronic renal failure undergoing hemodialysis. In this case, this affection is included in renal osteodystrophy. Radiology is the key for the diagnosis. We herein report the case of 68 years old, with chronic hemodialysis history, presenting with a latero-cervical mass, evolving since one year. CT showed diverse locations of pseudo tumoral calcinosis, associated to renal osteodystrophy and surgical resection was indicated for symptomatic locations.

Elderly-onset calcinosis of hyperphosphataemic familial tumoural calcinosis/hyperostosis-hyperphosphataemia syndrome: the role of comorbid scleroderma.

A 73-year-old woman with type 2 diabetes mellitus was referred to our department for glycaemic control. Physical examination revealed two subcutaneous hard masses around the left shoulder and the right hip joint. The patient could not fully extend her fingers because of skin sclerosis in both hands. Laboratory studies showed hyperphosphataemia and a high ratio of renal tubular maximum reabsorption of phosphate to glomerular filtration rate. There were no abnormalities in serum calcium, creatinine, alkaline phosphatase, and intact parathyroid hormone levels, whereas serum fibroblast growth factor 23 was low. Hyperphosphataemic familial tumoural calcinosis/hyperostosis-hyperphosphataemia syndrome (HFTC/HHS) was diagnosed using whole genome sequencing that revealed a novel frameshift beyond the 584th threonine located in the lectin domain of UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 associated with a duplication of the 1748th thymine in the coding region of the corresponding gene. Furthermore, anti-nuclear, anti-centromere, and anti-cardiolipin antibodies were positive, implying that comorbid limited type scleroderma might play a role in tumoural calcinosis (TC) development. A low phosphate diet was prescribed with phosphate-lowering medications, including aluminium hydroxide, acetazolamide, and sevelamer hydrochloride. The patient displayed a decrease in serum phosphate levels from 6.5 to 5.5 mg/dL 10 months after the initiation of treatment, but her TC had not improved during treatment for more than 1 year. This case was interesting because the patient with HFTC/HHS exhibited TC despite being over her 60s, and subsequent scleroderma might contribute to the specific clinical course. When HFTC/HHS presents with elderly-onset TC, the involvement of comorbidities in exacerbating TC should be considered. HFTC/HHS occurs on an autosomal recessive basis, but its clinical course and manifestations differ significantly throughout the cases. HFTC/HHS may be undiagnosed until later in life because of its rarity, unfamiliarity, and phenotype diversity; therefore, HFTC/HHS should be included in the differential diagnosis of elderly patients with unexplained hyperphosphataemia or ectopic calcinosis. Comorbidities, including rheumatologic disorders, may contribute to developing HFTC/HHS-associated calcinosis.

Prepatellar tumoral calcinosis mimicking soft tissue sarcoma: A case report and review of literature

Tumoral calcinosis is a rare, painless tumour-like mass often seen as soft tissue calcifications around joints in adolescents and young adults. The occurrence of this rare entity in the middle aged or elderly population is also rare. The pathology may mimick sarcomatous lesions or granulomatous diseases. A high index of suspicion, imaging and laboratory studies, including histopathological examinations, are needed to make a diagnosis. A 59-year old Nigerian woman that complained of a progressive and painless anterior knee mass, which turned out to be a tumoral calcinosis, is presented.