Calcium pyrophosphate dihydrate crystal deposition disease: a review of the literature and a light and electron microscopic study of a case of the temporomandibular joint with numerous intracellular crystals in the chondrocytes

The pathogenesis of calcium pyrophosphate dihydrate (CPPD) crystal deposition disease of synovial joints is still unclear, although overproduction of extracellular pyrophosphate (PPi) is thought to play a key role. We studied the light and electron microscopic appearances of a case of CPPD crystal deposition disease of the temporomandibular joint (TMJ) in search of new clues for its pathogenesis. Light microscopic examination of CPPD-containing material from the joint space revealed cartilaginous nodules with various degrees of crystallization. Transmission electron microscopic examination revealed numerous extra- as well as intracellular crystals and crystal shaped spaces in the chondrocytes. Other striking ultrastructural features of the chondrocytes included the presence of many mitochondria, frequently containing crystalline material, and the presence of highly dilated rough endoplasmic reticulum and large glycogen islands. The presence of intramitochondrial crystals may hypothetically imply a derangement in mitochondrial adenosine triphosphate or PPi metabolism. The finding of intracellular CPPD crystals in chondrocytes points to the existence of an intracellular pathway of CPPD crystal formation in CPPD crystal deposition disease of the TMJ and possibly in CPPD crystal deposition disease in general.