Familial tumoral calcinosis is a rare disease with genetic predilection characterized by continuous accumulation of calcium crystals inside soft tissues near big joints of the body

1. Familial tumoral calcinosis

2. Contents
• Definition
• Privilege
• Types
• Pathophysiology
• Pathology
• Clinical presentation
• Case presentation

3. Tumoral calcinosis
• Teutschlaender [1] mentioned 2 French dermatologists, Giard and Duret, as the first to
clinically describe FTC in 1898 and he himself described the same condition under the
name of lipocalcinogranulomatosis in 1935. The current term, tumoral calcinosis, was
proposed by Inclan et al. in 1943 and subsequently was widely adopted.
• Are a heterogeneous group of a hereditary disorders.
• Characterized by cutaneous and sub-cutaneous large, globular calcified masses, usually
adjacent to large joints “ectopic calcification” such as hips, shoulders, and elbows and may
be associated with hyperphosphatemia.
Definition
Calcinosis :
Abnormal formation of calcium deposits in any soft tissue.
Types:
Dystrophic calcification Metastatic calcification Tumoral calcinosis

4. Privilege
• FTC is an extremely rare condition, occurring without sex predilection,
which has been mainly reported in patients from Africa and the Middle East
and, to a lesser extent, in white individuals.

5. Types of FTC
Hyperphosphatemic FTC
(HFTC)
Two major types of FTC have been recognized
Normophosphatemic FTC
(NFTC)

6. HFTC Pathophysiology:
1- Increased levels of circulating phosphate (>5–7 mg/dl) due to
decreased of phosphate excretion through the renal proximal tubules and
increased intestinal absorption.
2- Calcium serum and PTH levels usually are within the normal range.
3- 1,25-dihydroxyvitamin-D levels may be normal or inappropriately
increased.

7. Gene defect Defect in fibroblast growth factor 23
The body can’t know if there is enough level of phosphate
The body continue to absorb the phosphate from GIT and decrease its excretion from kidney
Continues raise of phosphate level Phosphate binds to calcium  Hydroxyapetite
“Inorganic crystals “ Ca₅(PO₄)₃” that binds to collagen”
Tendons
Blood vessels
Uterus
Subcutaneous connective tissues
Calcinosis

8. Pathology [5]
• Lesions are commonly cystic and contain a white to pale yellow chalky
material identified as calcium hydroxyapatite crystals with amorphous
calcium carbonate and calcium phosphate.
• At histopathologic examination, epithelioid
elements and multinucleated giant cells
surround calcium granules are noted.

9. Clinical presentation

10. Normophosphatemic FTC
(NFTC)
• During the first year of life initially
manifests with:
• Non-specific erythematous rash
usually followed by rapid development
of calcified nodules with ulceration of
the overlying skin and chalky exudate.
• Mucosal inflammation in the oral
cavity (e.g., gingivitis) can be
particularly debilitating [2].
Hypermophosphatemic FTC
(HFTC)
• Relatively late onset during the first to the
third decade of life [3] :
• Slowly growing calcified masses with
predilection for the peri-articular tissues
overlying large joints, the hip being more
frequently involved.
• The calcified masses are asymptomatic,
but progressively grow in a pseudo-
neoplastic fashion, thus causing ulcers,
pain, and secondary infections, which may
occasionally become fatal.

11. HFTC patients
→Pulmonary hypertension.
→Restrictive lung diseases.
→Dental manifestations, including pulp
calcifications and obliteration of the pulp
cavity[4].

12. Case Presentation

13. Plasma Carbon Dioxide 28 23-32 mmol/L
Plasma Anion GAP 20 3-17 mmol/L
Calcium 9.3 8.5-10.5 mg/dL
Phosphorus 5.6 2.6-4.5mg/dL
TSH 1.74
Vitamin D 43 "Desired: > 32 ng/ml".
67 years old African American female with long history of FTC complain of left thigh mass

18. 1-Garringer HJ, Fisher C, Larsson TE, et al. The role of mutant UDP-N-acetyl-alpha-Dgalactosamine- polypeptide N-
acetylgalactosaminyltransferase 3 in regulating serum intact fibroblast growth factor 23 and matrix extracellular phosphoglycoprotein
in heritable tumoral calcinosis. J Clin Endocrinol Metab. 2006;91:4037–42.
2- Head and neck manifestations of tumoral calcinosis.
Gal G, Metzker A, Garlick J, Gold Y, Calderon S
Oral Surg Oral Med Oral Pathol. 1994 Feb; 77(2):158-66
3- Hyperphosphatemic tumoral calcinosis: association with elevation of serum 1,25-dihydroxycholecalciferol concentrations.
Prince MJ, Schaeffer PC, Goldsmith RS, Chausmer AB
Ann Intern Med. 1982 May; 96(5):586-91.
4- Dental lesions in tumoral calcinosis.
Burkes EJ Jr, Lyles KW, Dolan EA, Giammara B, Hanker J
J Oral Pathol Med. 1991 May; 20(5):222-7.
5- Tumoral Calcinosis: Pearls, Polemics, and Alternative Possibilities. Olsen K.M. and Felix S.C RSNA Radiographics DOI:
http://dx.doi.org/10.1148/rg.263055099
References

19. Thank you