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Ancillary to standard techniques (i.e., light microscopy) to resolve diagnostic difficulties in human histopathology through examination of ultrastructural findings at the cellular and organelle level

  • Unclassifiable, undifferentiated neoplasms

  • Supporting a diagnosis from a list of differential diagnosis

  • Supporting a light microscopic diagnosis

  • Determination of the primary site in metastatic neoplasms

  • Medical disease of kidney

  • Metabolic storage diseases

  • Other congenital disorders

  • Infectious agents

  • Autoimmune diseases

  • Certain cutaneous diseases

  • Identification of foreign material in tissues


  • Tissue preparation is similar to conventional wax embedding light microscopy: aldehyde fixation, dehydration, embedding, sectioning, and examination of sections exposed to some form of radiation

  • Electron microscopy differences include

    • Image is formed by the scattering of electrons by heavy metal atoms (introduced as solutions of uranyl acetate and osmium tetroxide or lead citrate) selectively adherent to tissue sections

    • Tissue is embedded in epoxy, allowing for sectioning to a thickness of 100 nm

    • Tissue should be submitted in appropriate media (i.e., 2.5% glutaraldehyde; Karnovsky's [universal] solution)

  • Fixation with glutaraldehyde provides the best structural preservation; unlike formaldehyde, glutaraldehyde is slowly penetrating. Therefore, only very small pieces of tissue are processed (i.e., 0.5–1 mm3 or 2–3 mm2 and thickness of about 0.5 mm)

  • Although processing and staining are labor intensive, turn around time can be as short as 24 to 48 hours

  • Electron microscopy may also be performed on formalin fixed material from deparaffinizing a wax block. Preservation may be sufficient for diagnostic purposes although results may be variable


Langerhans Cell

  • Bone marrow–derived (Fig. 34-1)

  • Antigen-processing and -presenting cells

  • Indented nucleus with ropey nucleolus

  • Rod- and racket-shaped (terminal expansion) cytoplasmic granules (Birbeck granules) with central dotted line

  • Often seen at the cell surface when membrane-bound antigen is internalized by endocytosis

  • Cytoplasm contains dispersed vimentin intermediate filaments


Langerhans cell. (© 1967 Wolff. The Journal of Cell Biology, 1967, 35: 468–473. doi:10.1083/jcb.35.2.468.)

Merkel Cell

  • Slowly adapting type I mechanoreceptors located in sites of high tactile sensitivity (Fig. 34-2)

  • Present among basal keratinocytes

  • Nucleus is lobulated

  • Cytoplasm is electron lucent with prominent Golgi

  • Margins of cells project cytoplasmic spines toward keratinocytes

  • Typical granules (80–200 nm) have a dense core, halo, and a slightly ruffled membrane

  • Granules contain neurotransmitter-like substances

  • Intermediate filaments are numerous and assume a parallel or whorled arrangement near the nucleus (dot-like pattern)


Merkel cell. (Reprinted with permission from Goldsmith LA et al. Fitzpatrick's Dermatology in General Medicine, 8th Ed. New York: McGraw-Hill; 2012.)

Lamellar Granules

  • In the ...

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