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Mu et al. Microstructures 2023;3:2023030 https://dx.doi.org/10.20517/microstructures.2023.05 Page 11 of 21

Figure 5. Crystal deposition in the urinary system (Reproduced with permission from Evan et al. [150] . Copyright 2005, Elsevier). (A) The
initial sites of the deposition of kidney stones in transmission electron microscopic images and (B) immunogold staining showed the
localization of osteopontin in the plaque.

Ocular
Ocular mineralization can be found in the cornea, retina, optic nerve, and Bruch’s membrane [92,174-176] . In the
aging eye, the accumulation of protein- and lipid-containing deposits external to the retinal pigment
epithelium (RPE) can lead to macular degradation and, consequently, blindness [92,177] . Three types of
structures of minerals have been found in age-related macular degradation, spherules (whitlockite), plaques
(amorphous apatite), and nodules (apatite) [20,21] . However, the mechanism of the formation of calcified
nodules remains unknown.

Breast
Breast mineralization, also called microcalcification, has been suggested to be a consequence of either injury
or diseases, such as chronic kidney disease, hypertension, or metabolic syndrome [178,179] . The formation of
microcalcification is related to the acquisition of mesenchymal characteristics in breast cancer cells, affected
by transforming growth factor beta (TGF-β) or nuclear factor kappa-light-chain-enhancer of activated B
cells (NF-κB) [180,181] . Multiple phases of breast microcalcifications have been identified: CaPs (such as
carbonate HAp and whitlockite), amorphous CaP, and, less commonly, CaO x [182-185] . However, the exact
origins of minerals remained unclear. Nevertheless, the screening and evaluation of the morphology and
distribution of microcalcification aid in determining the likelihood of whether the calcifications are benign,
intermediate, or necessitate further investigation . For instance, CaOx (type I calcification) is detected in
[17]
benign breast lesions or lobular carcinoma, whereas HAp calcification (type II calcification) is detected in
both benign and malignant breast tissues [18,19] . Compared to those formed in malignant ducts, type II
microcalcification formed in benign ducts was found to contain a higher amount of CaCO and a lower
3
[186]
[187]
amount of protein . In some malignant specimens, Mg and Na have also been detected . Elevated Na
levels have been found in malignant specimens, but no correlation has been found between the level of Mg
and malignancy .
[187]