Morphological Methods in the Diagnosis of Mitochondrial Encephalomyopathies: The Role of Electron Microscopy

Abstract

Mitochondrial encephalomyopathies (MEs) encompass a heterogeneous group of disorders that frequently present a diagnostic challenge to clinicians. Historically, MEs were diagnosed by finding ragged red fibers in the muscle biopsy and confirmatory evidence was provided by the presence of numerical and/or ultrastructural abnormalities in mitochondria. In most centers diagnosis involves clinical evaluation and the morphological, histochemical, and biochemical investigation of a skeletal muscle biopsy. However, with the availability of mitochondrial DNA analysis, the necessity and role of morphological methods and, in particular, electron microscopy has been questioned. The aim of this study was to delineate the role of electron microscopy in the diagnosis of MEs.

Investigation of children for mitochondriopathy confirms need for strict patient selection, improved morphological criteria, and better laboratory methods

“…Ultrastructural abnormalities of mitochondria described in classical mitochondriopathies include increased number and/or size (N1 lm) and quantitative abnormality such as pleomorphism (budding, branching), paracrystalline inclusions, circular and fingerprint arrangement of cristae, and abnormal matrix density [10,15,[24][25][26]. Our quantitative approach evaluated only the size range of mitochondria and absolute maximum diameters.…”

Multiple Muscle Cell Alterations in a Case of Encephalomyopathy

“…Mitochondrial myopathies usually are characterized by morphologically altered mitochondria, especially in adults, not so much in children [18,19]. A common mitochondrial feature in such myopathies is the presence of ostensibly matrical crystalloids.…”

Virtual Electron Microscopy

“…The specimens were processed using standard methods, including resin block processing, semithin section microtomy, selection of appropriate blocks for ultrathin sectioning, staining with uranyl acetate and lead citrate, and mounting the ultrathin section in a thin bar (12 µm bar width) grid with square mesh and hole size of 113 µm. The ultrathin sections were examined using a transmission electron microscope model TECNAI G 2 12, FEI Company (Hillsboro, OR), with built-in motorized stage and equipped with a 11 mega pixel side mount digital camera (Morada, Olympus, Munster, Germany).…”

“…[1][2][3] In addition, it can provide important diagnostic information for difficult tumor cases, especially when results of immunohistochemistry are inconclusive or noncontributory, such as for distinction between some difficult cases of mesothelioma and carcinoma and putative extrarenal rhabdoid tumor versus other poorly differentiated neoplasms. 4 However, pathologists who do not perform ultrastructural examination on a routine basis may not be familiar with the practical operation of the electron microscope.…”

“…Although the role of electron microscopy in diagnostic surgical pathology has diminished in recent decades due to advances in immunohistochemistry and molecular genetics, it remains an essential diagnostic tool for many diseases, such as glomerular diseases, mitochondrial diseases, and ciliary dyskinesia. [1][2][3] In addition, it can provide important diagnostic information for difficult tumor cases, especially when results of immunohistochemistry are inconclusive or noncontributory, such as for distinction between some difficult cases of mesothelioma and carcinoma and putative extrarenal rhabdoid tumor versus other poorly differentiated neoplasms. 4 However, pathologists who do not perform ultrastructural examination on a routine basis may not be familiar with the practical operation of the electron microscope.…”