Morphological and Compositional Analysis of Biomineral Microdeposits in Non-Small Cell Lung Cancer

Lung cancer is the leading cause of death from malignant neoplasms in both men and women [1]. While calcification is a well-researched pathological process in many tumors and lung diseases, its occurrence in lung cancer remains poorly understood, and the prognostic value and impact of calcification on lung cancer are still unclear [2]. Our previous studies on biomineral formations in ovarian, thyroid, and breast tumors identified the prevalence of hydroxyapatite [3-5] and this research aimed to evaluate the composition and morphology of biomineral microdeposits in non-small cell lung cancer (NSCLC).

A total of 49 histological samples were obtained from NSCLC patients treated at the Sumy Regional Oncology Center between 2013 and 2018. The samples were stained with hematoxylin and eosin to assess pathohistological changes, and the presence of calcium compounds was confirmed using alizarin red and von Kossa staining. Transmission electron microscopy (TEM) with electron diffraction (ED) was performed using a PEM-125K microscope (SELMI, Ukraine) to assess the composition of microdeposits.

Calcification was detected in 4 out of 49 cases: 2 cases in squamous cell carcinoma of the basaloid type and 2 in mucinous adenocarcinoma. In squamous cell carcinoma, pathological biomineralization appeared as coarse polycyclic fragments, blocks, and debris among necrotic detritus surrounded by tumor layers of squamous epithelium. In mucinous adenocarcinoma, specific rounded lamellar calcifications, known as psammoma bodies, were observed.

TEM analysis revealed that NSCLC calcifications possess a crystalline structure with a wide range of crystal sizes (7 to 300 nm), with the most common sizes being 7-14 nm. These particles aggregate into conglomerates, with the largest crystals forming the core. Uniform brightness in the micrographs and point reflections in the electronograms indicate that these particles aggregate based on the predominant orientation of crystallographic planes. The crystals are metastable and highly sensitive to electron beam irradiation. Under an 11 μA electron beam, rapid recrystallization occurs, likely due to slight sample heating. Reducing the beam current to 5 μA slows the recrystallization process. Electronogram analysis showed that the calcifications comprise hydroxyapatite with Ca5(PO4)3(OH) formula.

The obtained data suggest the importance of biomineralization and microdeposits in the development of lung cancer, but future research is required to understand their diagnostic potential and role in disease progression.