Is formalin-fixed paraffin embedded tissue good enough for studies of transmission electron microscopy of tumors? a comparative study with wet tissue

Transmission electron microscopy (TEM) has historically been pivotal in diagnosing neoplasms with challenging histopathology. However, its use has declined due to cost and the advent of ancillary techniques like immunohistochemistry. This study compares the diagnostic utility of formalin-fixed paraffin-embedded (FFPE) tissue versus wet glutaraldehyde-paraformaldehyde fixed tissue (WT) for TEM in neoplasms. A retrospective analysis of 746 cases (2014-2023) from the National Cancer Institute of Mexico - Instituto Nacional de Cancerología de Mexico (INCan) was performed. Cases were divided into Group A (FFPE, <i>n</i> = 270) and Group B (WT, <i>n</i> = 476). Diagnostic utility was assessed based on ultrastructural preservation and concordance with histopathological reports. Key ultrastructural features, such as microvilli in mesothelioma, cytoplasmic organelles in chondroblastoma, luminal microvilli in secretory breast carcinoma, continuous basal lamina in schwannoma, and abundant rough endoplasmic reticulum in fibroblastic tumors were identifiable in both groups despite artifacts in FFPE. Exact Fisher's test showed no significant difference in diagnostic utility between groups (<i>p</i> = .0548), with 87.03% (235/270) of FFPE cases and 88.66% (422/476) of WT deemed diagnostically useful. Specificity for WT was 100% versus comparable values for FFPE. This study challenges the notion that paraffin embedding severely compromises TEM diagnostic value. FFPE allows precise sampling of archived tissues, expanding TEM's applicability in retrospective studies. Further validation is warranted to confirm these findings.