A tissue biopsy becomes a slide through formalin, wax and a blade
Before a pathologist can spot cancer under a microscope, a lump of tissue must be preserved in formaldehyde, soaked in alcohol, packed in hot wax and shaved into slices a few thousandths of a millimetre thick. Then it gets dyed, because living tissue has almost no natural contrast. That craft is histology.
Histology is the study of tissues too small to see with the naked eye, the microscopic partner to gross anatomy. It once had separate branches for organs, tissues and cells, but now covers all three. Animal tissues fall into four families: muscle, nerve, connective and epithelial. Blood counts as connective tissue, since its cells float in a liquid matrix, the plasma. Histopathology, the medical offshoot, examines diseased tissue and underpins most cancer diagnoses.
Preparation starts with fixation. The standard for light microscopy is 10% neutral buffered formalin, which locks proteins together with chemical bridges, hardening tissue enough to cut; electron microscopy usually uses glutaraldehyde. The trade-off is that fixation damages enzymes and degrades DNA and RNA, though special methods can still recover them. Because wax will not mix with water, samples then pass through ever stronger alcohol baths, a clearing agent such as xylene, and finally molten paraffin that sets into a block.
A blade in a microtome then cuts slices, typically 5 to 15 micrometres thick for light microscopes, while electron microscopy needs diamond or glass knives producing sections of 50 to 150 nanometres. Staining brings out detail. The workhorse, haematoxylin and eosin, colours nuclei blue and the rest of the cell in shades of pink. More targeted methods pick out single substances, such as Perls' Prussian blue for iron deposits, and antibodies tagged with fluorescent labels can light up specific proteins. Surgeons sometimes need answers mid-operation, so tissue is frozen and sliced on the spot to check whether a tumour's edges are clear.
The field's roots go back to the 17th century and Italian anatomist Marcello Malpighi, whom some call its founder. Peering at the lungs of animals, he saw the tiny air sacs and the fine vessels linking arteries to veins, which he named capillaries, revealing how inhaled oxygen reaches the blood.
Source: Histology
