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*211900 CALCINOSIS, TUMORAL, WITH HYPERPHOSPHATEMIA
Alternative titles; symbols
TUMORAL CALCINOSIS, HYPERPHOSPHATEMIC
TABLE OF CONTENTS
TEXT
REFERENCES
SEE ALSO
CREATION DATE
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CLINICAL SYNOPSIS
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TEXT
Baldursson et al. (1969) observed 4 affected sibs out of 12 in a black family.
Hyperphosphatemia was documented as early as
21 months of age in one of them in whom tumoral calcinosis appeared at 4 years
of age. A majority of the cases of this condition
reported in the Anglo-American literature have been in blacks. Other familial
cases have been reported by Barton and Reeves
(1961), Harkess and Peters (1967), and Wilber and Slatopolsky (1968). Dodge et
al. (1965) described 3 sibs with heterotopic
calcification, hyperphosphatemia, unresponsiveness to parathyroid hormone, and
elevated renal tubular maximum for phosphate
reabsorption. Stigmata of Albright hereditary osteodystrophy (103580, 203330,
300800) were not present. Some reported
patients have had angioid streaks of the retina (McPhaul and Engel, 1961).
This is consistent with the view that angioid streaks in
pseudoxanthoma elasticum (PXE), sickle cell anemia, and Paget disease are due
to a brittle state of Bruch membrane produced
by deposition of calcium, iron and perhaps other cations. Ghormley (1942)
reported multiple affected sibs. McPhaul and Engel
(1961) reported affected brothers; in another family the proband's paternal
grandfather was thought to have been affected and he
was related to a family reported as PXE. From Beirut, Najjar et al. (1968)
described 2 sibs with periarticular calcified masses,
increased blood phosphorus, normal blood calcium, calcified vessels, and skin
changes of PXE. The parents may have been
related. An aunt was said to have heterotopic calcification. I suspect that
this disorder is distinct from ordinary PXE, although with
many similar features. In a review of the radiologic findings of PXE, James et
al. (1969) pictured a large calcified mass in the
region of the elbow. The patient probably had the entity discussed here, which
was called lipocalcinogranulomatose by
Teutschlaender (1935).
Inclan et al. (1943) first gave the name 'tumoral calcinosis' to this
condition, which was probably first described by Duret (1899).
Collard (1966) described 2 affected sisters in a sibship of 5. Calcification
of the media was limited to arteries of the leg. The
parents were normal and unrelated. Large calcified tophus-like nodules were
situated around the joints of the fingers and toes.
Although rheumatic symptoms had begun at age 20 in both, the sisters were in
their 50s at the time of report. McClatchie and
Bremner (1969) reported 26 cases from Kenya, where the condition has an
unusually high frequency. Until the publication of the
papers by Palmer (1966) and Thomson (1966), only 25 cases had been reported;
they reported an additional 50 cases, mostly
from Rhodesia, and mentioned seeing others in Nigeria and elsewhere.
McClatchie and Bremner (1969) documented its
occurrence in Uganda. Eight different Kenyan tribes were represented among 17
cases. Balachandran et al. (1980) reported a
family in which 7 of 15 sibs were affected. Goldfarb (1979) proposed that
there is an intrinsic defect in phosphate-handling by the
proximal renal tubule, leading to increased reabsorption. Involvement at the
shoulders and buttocks is the rule. It is puzzling that
visceral involvement does not occur. Prince et al. (1982) reported a sibship
in which 7 of 13 sibs were affected. Serum
phosphorus and 1,25-dihydroxycholecalciferol concentrations were increased and
parathormone and 25-hydroxycholecalciferol
concentrations decreased. Balance studies indicated increased gastrointestinal
absorption and decreased renal excretion of
calcium and phosphorus. The authors interpreted the data to indicate a
hereditary abnormality of vitamin D metabolism, and
suggested a defect in the normal feedback mechanism regulating the
25-hydroxy-1-alpha-hydroxylase enzyme. Mozaffarian et al.
(1972) proposed treatment with a low-phosphorus diet combined with large oral
doses of aluminum hydroxide. Clarke et al.
(1984) studied 3 black children, including 2 sibs, who presented with
recurrent pain and swelling of the legs. In addition to
tumoral calcinosis and hyperphosphatemia, the children showed hyperostosis of
diaphyses of long bones of the leg. The authors
suggested that the syndrome of hyperostosis and hyperphosphatemia reported by
Mikati et al. (1981) is fundamentally the same
disorder despite the lack of tumoral calcinosis. Steinherz et al. (1985)
observed 5 affected persons in 2 branches of a Druze Arab
kindred. The patients presented with calcified deposits in or about the hips
and knees beginning in childhood. The authors
concluded that serum calcitriol levels do not decline in response to
hyperphosphatemia and that hyperphosphatemia with elevated
renotubular reabsorption of phosphate is a constant feature of this disorder.
Low phosphorus diet and oral aluminum hydroxide
gel did not lower serum phosphate levels or improve the calcified deposits.
Slavin et al. (1993) reviewed the histopathologic and ultrastructural changes
of tumoral calcinosis occurring in 7 affected sibs in a
sibship of 15. This was the black family cared for in Galveston, Texas, over a
period of 25 years and described in the medical
literature a total of 9 times (.i.e., Abbud et al., 1979; Balachandran et al.,
1980; Baldursson et al., 1969; Chausmer et al., 1982;
Clarke et al., 1984; Prince et al., 1982; Pursley et al., 1979; Viegas et al.,
1985; Witcher et al., 1989). A useful summary of the
clinical findings in the 7 patients was provided. In order of frequency for
the site of first lesions, hips, elbows, shoulders, and
scapulae led the list. All 7 patients has elevated serum phosphorus levels,
and elevated levels of 1,25-vitamin D were detected in
3. One patient, who also had calcinosis cutis involving the antecubital,
popliteal, and axillary areas and legs, died at age 19 of
pulmonary hypertension. The other sibs varied in age from 20 to 40 years at
the time of this report. Onset had varied from 22
months to 5 years of age. Three of the sibs were males. Slavin et al. (1993)
concluded that tumoral calcinosis is triggered by
bleeding, followed by aggregation of foamy histiocytes. These, in turn, are
transformed, with participation of collagenolysis, into
cystic cavities lined by osteoclast-like giant cells and histiocytes,
resulting in lesions resembling adventitious bursae. Movement
and friction resulting from the periarticular location of the lesions were
thought to be key to this transformation.
SEE ALSO
Hacihanefioglu (1978) ; Mitnick et al. (1980) ; Teutschlaender (1949) ;
Zerwekh et al. (1980)
REFERENCES
1. Abbud, Y.; Balachandran, S.; Prince, M. J.; Chausmer, A. B. :
Scintiscans of two siblings with tumoral calcinosis. Clin. Nucl. Med. 4:
117-119, 1979.
PubMed ID : 428164
2. Balachandran, S.; Abbud, Y.; Prince, M. J.; Chausmer, A. B. :
Tumoral calcinosis: scintigraphic studies of an affected family. Brit. J.
Radiol. 53: 960-964, 1980.
3. Baldursson, H.; Evans, E. B.; Dodge, W. F.; Jackson, W. T. :
Tumoral calcinosis with hyperphosphatemia: a report of a family with
incidence in four siblings. J. Bone Joint
Surg. 51B: 913-925, 1969.
PubMed ID : 5793850
4. Barton, D. L.; Reeves, R. J. :
Tumoral calcinosis: report of 3 cases and review of the literature. Am.
J. Roentgen. 86: 351-358, 1961.
5. Chausmer, A.; Meyer, W.; Prince, M. :
Phosphate depletion therapy in two ectopic calcification syndromes. J.
Am. Coll. Nutr. 1: 275-283, 1982.
PubMed ID : 7185859
6. Clarke, E.; Swischuk, L. E.; Hayden, C. K., Jr. :
Tumoral calcinosis, diaphysitis, and hyperphosphatemia. Radiology 151:
643-646, 1984.
PubMed ID : 6718723
7. Collard, M. :
Une forme familiale de lipocalcinogranulomatose avec calcinose
arterielle. J. Radiol. Electr. 47: 31-40, 1966.
8. Dodge, W. F.; Travis, L. B.; Assemi, M. :
Familial heterotopic calcification and hyperphosphatemia unresponsive to
parathyroid extract. (Abstract) J.
Pediat. 67: 944-945, 1965.
9. Duret, M. H. :
Tumeurs multiples et singulieres des bourses sereuses. Bull. Mem. Soc.
Ant. Paris 74: 725-731, 1899.
10. Ghormley, R. K. :
Multiple calcified bursae and calcified cysts in soft tissues. Trans.
West. Surg. Assoc. 51: 292-309, 1942.
11. Goldfarb, S. : Personal Communication. Philadelphia, Pa., 4/6/1979.
12. Hacihanefioglu, U. :
Tumoral calcinosis: a clinical and pathological study of eleven
unreported cases in Turkey. J. Bone Joint Surg.
60A: 1131-1135, 1978.
PubMed ID : 721867
13. Harkess, J. W.; Peters, H. J. :
Tumoral calcinosis: a report of six cases. J. Bone Joint Surg. 49A:
721-731, 1967.
PubMed ID : 6026005
14. Inclan, A.; Leon, P.; Camejo, M. G. :
Tumoral calcinosis. J.A.M.A. 121: 490-495, 1943.
15. James, A. E., Jr.; Eaton, S. B.; Blazek, J. V.; Donner, M. W.; Reeves, R.
J. :
Roentgen findings in pseudoxanthoma elasticum (PXE). Am. J. Roentgen.
106: 642-647, 1969.
16. McClatchie, S.; Bremner, A. D. :
Tumoural calcinosis--an unrecognized disease. Brit. Med. J. 1: 153-155,
1969.
17. McPhaul, J. J., Jr.; Engel, F. L. :
Heterotopic calcification, hyperphosphatemia and angioid streaks of the
retina. Am. J. Med. 31: 488-492, 1961.
18. Mikati, M. A.; Melhem, R. E.; Najjar, S. S. :
The syndrome of hyperostosis and hyperphosphatemia. J. Pediat. 99:
900-904, 1981.
PubMed ID : 6273518
19. Mitnick, P. D.; Goldfarb, S.; Slatopolsky, E.; Lemann, J., Jr.; Gray, R.
W.; Agus, A. S. :
Calcium and phosphate metabolism in tumoral calcinosis. Ann. Intern. Med.
92: 482-487, 1980.
PubMed ID : 6244768
20. Mozaffarian, G.; Lafferty, F. W.; Pearson, O. H. :
Treatment of tumoral calcinosis with phosphorus deprivation. Ann. Intern.
Med. 77: 741-745, 1972.
PubMed ID : 4538804
21. Najjar, S. S.; Farah, F. S.; Kurban, A. K.; Melhem, R. E.; Khachadurian,
A. K. :
Tumoral calcinosis and pseudoxanthoma elasticum. J. Pediat. 72: 243-247,
1968.
PubMed ID : 5635805
22. Palmer, P. E. S. :
Tumoural calcinosis. Brit. J. Radiol. 39: 518-525, 1966.
23. Prince, M. J.; Schaefer, P. C.; Goldsmith, R. S.; Chausmer, A. B. :
Hyperphosphatemic tumoral calcinosis: association with elevation of serum
1,25-dihydroxycholecalciferol
concentrations. Ann. Intern. Med. 97: 586-591, 1982.
24. Pursley, T. V.; Prince, M. J.; Chausmer, A. B.; Raimer, S. S. :
Cutaneous manifestations of tumoral calcinosis. Arch. Derm. 115:
1100-1102, 1979.
PubMed ID : 485189
25. Slavin, R. E.; Wen, J.; Kumar, D.; Evans, E. B. :
Familial tumoral calcinosis: a clinical, histopathologic, and
ultrastructural study with an analysis of its calcifying
process and pathogenesis. Am. J. Surg. Path. 17: 788-802, 1993.
PubMed ID : 8338191
26. Steinherz, R.; Chesney, R. W.; Eisenstein, B.; Metzker, A.; DeLuca, H. F.;
Phelps, M. :
Elevated serum calcitriol concentrations do not fall in response to
hyperphosphatemia in familial tumoral
calcinosis. Am. J. Dis. Child. 139: 816-819, 1985.
PubMed ID : 3839626
27. Teutschlaender, O. :
Ueber progressive Lipogranulomatose der Muskulatur. Klin. Wschr. 14:
451-453, 1935.
28. Teutschlaender, O. :
Die Lipoidocalcinosis oder Lipoidkalkgicht (Lipocalcinogranulomatose).
Beitr. Path. Anat. 110: 402-432, 1949.
29. Thomson, J. G. :
Calcifying collagenolysis (tumoural calcinosis). Brit. J. Radiol. 39:
526-532, 1966.
30. Viegas, S. F.; Evans, E. B.; Calhoun, J.; Goodwiller, S. E. :
Tumoral calcinosis: a case report and review of the literature. J. Hand
Surg. 10A: 744-748, 1985.
31. Wilber, J. F.; Slatopolsky, E. :
Hyperphosphatemia and tumoral calcinosis. Ann. Intern. Med. 68:
1044-1049, 1968.
32. Witcher, S. L.; Drinkard, D. W.; Shapiro, R. D.; Schow, C. E., Jr. :
Tumoral calcinosis with unusual oral dental findings. Oral Surg. Oral
Med. Oral Path. 68: 104-107, 1989.
33. Zerwekh, J. E.; Sanders, L. A.; Townsend, J.; Pak, C. Y. C. :
Tumoral calcinosis: evidence for concurrent defects in renal tubular
phosphorus transport and in 1-alpha,
25-dihydroxycholecalciferol synthesis. Calcif. Tissue Int. 32: 1-6, 1980.
PubMed ID : 6775776
CLINICAL SYNOPSIS
View Clinical Synopsis Entry
CREATION DATE
Victor A. McKusick : 6/3/1986
EDIT HISTORY
alopez : 6/10/1997
mark : 4/30/1996
terry : 4/22/1996
davew : 7/11/1994
carol : 4/19/1994
terry : 4/18/1994
warfield : 4/15/1994
carol : 10/20/1993
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Dr. G. Christian Overton
Center for Bioinformatics email: coverton at pcbi.upenn.edu
University of Pennsylvania tel: 215-573-3105
1312 Blockley Hall fax: 215-573-3111/215-573-4792
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