Tumoral calcinosis--a pathogenetic overview: a histological and ultrastructural study with a report of two new cases, one in infancy

Abstract

Tumoral calcinosis occurs as a well-defined pathologic entity in 3 heterologous groups of diseases--hyperphosphatemic familial tumoral calcinosis, normophosphatemic tumoral calcinosis, and secondary tumoral calcinosis. The histological lesion is stereotypic developing from the concurrence of a juxta-articular injury with an elevated calcium-phosphorus product. The reparative response to injury is histiocytic featuring synovial metaplasia forming bursa-like structures that create the characteristic compartmentalization of the lesion. Histiocytic-derived osteoclastogenesis occurs as a response to the calcifying process initiated in the mitochondria of necrotic histiocytes forming the bursa-like structures. These calcifications, propelled by a gamut of conditions elevating serum phosphorus, facilitate the further nucleation of hydroxyapatite in mitochondria, matrical lipidic debris located in the cytoplasm and lysosomes of osteoclasts and in the locular contents, and on collagen and other extracellular matrix materials. The lesions enlarge because of new locule formation and failure to reduce the calcified burden by the compartment lining histiocytes and dysmorphic osteoclasts that are unable to solubilize the hydroxyapatite. The histological landmarks of tumoral calcinosis may be lost when its development becomes quiescent. The classic calcifying classifications are inadequate for tumoral calcinosis requiring creation of a new category for this entity.