Familial tumoral calcinosis. A clinical, histopathologic, and ultrastructural study with an analysis of its calcifying process and pathogenesis.
We describe histopathologic and ultrastructural changes in tumoral calcinosis (TC) occurring in seven siblings from a single family. Tumoral calcinosis appears to be 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--the lesion resembling adventitious bursae. Movement and friction, forces generated from the periarticular location of the TC lesions, putatively are key to this transformation. Concomitantly, two calcifying events develop, possibly driven by concurrent hyperphosphatemia or endogenous hypervitaminosis D. One occurs on membranous fragments in antiprotease-containing large cytoplasmic vesicles within osteoclast-like giant cells and mononuclear cells lining the TC cavities; the second, in the TC locules on membranous and cellular debris derived from cavity-lining cells and erythrocytes. The TC cavities ultimately fill with calcified material, losing their synovial-like lining, become encapsulated by fibrous tissue, and ossify. Hydroxyapatite may gain entrance to capillary lumens and embolize to the lung. We conclude that TC represents a disordered reparative process that often is exaggerated because episodes of bleeding, caused by TC-induced vascular injury, provoke development of new lesions. The capricious response of TC to treatment is correlated with its morphologic features.
Slavin
R E
RE
Department of Pathology, University of Texas Medical Branch, Galveston.
Wen
J
J
Kumar
D
D
Evans
E B
EB
D000328:Adult; D002114:Calcinosis / Q000209:etiology / Q000235:genetics / Q000473:pathology; D002467:Cell Nucleus / Q000648:ultrastructure; D003094:Collagen / Q000032:analysis; D005260:Female; D015726:Giant Cells / Q000473:pathology; D006644:Histiocytes / Q000473:pathology; D006801:Humans; D006882:Hydroxyapatites / Q000032:analysis; D007150:Immunohistochemistry; D007592:Joint Diseases / Q000209:etiology / Q000235:genetics / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D009369:Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology; D000514:alpha 1-Antichymotrypsin / Q000032:analysis; D000515:alpha 1-Antitrypsin / Q000032:analysis
D006882:Hydroxyapatites; D000514:alpha 1-Antichymotrypsin; D000515:alpha 1-Antitrypsin; D003094:Collagen