Intraluminal Calcium Hydroxyapatite Crystals in Breast Carcinoma: An Ultrastructural Study

Abstract

Sixty-three breast carcinomas were examined by electron microscopy to determine the frequency of calcium hydroxyapatite (apatite) within tumor lumina. Twenty-one adenocarcinomas contained apatite in intracytoplasmic and/or intercellular lumina. Well-differentiated tumors exhibited a higher incidence of apatite (44%), while only 20% of the poorly differentiated tumors contained apatite (gamma = +.22). There was no apparent correlation between the presence of apatite and a positive estrogen receptor assay. Ninety-eight adenocarcinomas of other than breast origin (previously processed for electron microscopy) were examined, revealing 2 cases containing apatite in the appropriate locations. The tissue of origin in one case was determined to be ovarian, while the origin of the second case remains undetermined. The ultrastructural finding of apatite in lumina of adenocarcinoma appears to be unusual in that it has only been observed in breast carcinomas and certain ovarian tumors. The presence of apatite within the lumen in addition to other characteristics of an adenocarcinoma may suggest the breast as the primary site.

Multiple Pathways for Pathological Calcification in the Human Body

“…Breast XRD, [158][159][160][161] EDS, [159,160,[162][163][164] TEM imaging, [ 160,[162][163][164] electron diffraction, [ 164] SEM, [ 160,165,166] Raman, [166][167][168][169] FTIR, [ 165,170] von Kossa staining [ 164,166] Psammoma bodies Thyroid TEM [ 171] Ovaries TEM, [ 172] EDS, [173] XRF, [ 173] FTIR, [ 173] von Kossa staining, [ 172] XRD [ 173] Brain (meningioma) XRD, [ 174] TEM, [ 120] TEM lattice fringes and electron diffraction, [ 175] SEM, [ 175] EDS, [175] Raman [ 176,177] Brain (pineal gland) XRD, [ 174,178,179] SEM, [178,180] TEM, [ 178,180,181] EDS, [ 1...…”

“…In support of a more cellularly regulated process, in addition to necrosis, vesicle involvement in microcalcification formation has been suggested, [164] and intracellular calcifications (nonmitochondrial) in living cells were observed within breast carcinoma cells using TEM (Figure 2d). [163,164,250] One study specifically focused on intra-and intercellular lumina, structures unique to certain types of tumor cells, and found apatite and amorphous calcium phosphate within these structures in one third of the breast cancer patients analyzed. [163] Furthermore, in addition to colocalized mucosubstances, specific mineralization proteins such as OPN, [162,330,334,335] BMP, [162] BSP, [336] and osteonectin [335] have been identified in association with breast microcalcifications.…”

“…[163,164,250] One study specifically focused on intra-and intercellular lumina, structures unique to certain types of tumor cells, and found apatite and amorphous calcium phosphate within these structures in one third of the breast cancer patients analyzed. [163] Furthermore, in addition to colocalized mucosubstances, specific mineralization proteins such as OPN, [162,330,334,335] BMP, [162] BSP, [336] and osteonectin [335] have been identified in association with breast microcalcifications. Breast carcinomas have a significant increase in BSP compared to benign lesions [336] and tumors that express OPN are more likely to be associated with calcifications.…”

“…Figure 2d shows an example of an ex vivo ultrastructural study of breast cancer in which intracytoplasmic membrane bound and free apatite or calcium phosphate crystals were identified. [ 164 ] These crystallization events, occurring within breast cancer‐specific intracytoplasmic lumina, are thought to be distinct from intramitochondrial and necrosis‐based precipitation, [ 163 ] though leukocytic debris (that could conceivably calcify) has been reported within similar structures. [ 252 ] It has also been proposed that excretion of calcium and phosphorus‐rich intracytoplasmic vesicles may be involved in breast microcalcification formation.…”