The hematoxylin–eosin (H&E) stain has stood the test of time as the standard stain for histologic examination of human tissues. This simple dye combination is capable of highlighting the fine structures of cells and tissues. Most cellular organelles and extracellular matrix are eosinophilic, while the nucleus, rough endoplasmic reticulum, and ribosomes are basophilic. This review discusses the spectrum, intensity, and texture of colors observed in H&E-stained slides to illustrate their value in surgical pathology diagnosis. Changes in color of the nuclei occur in the presence of nuclear pseudoinclusions (such as papillary thyroid carcinoma) or inclusions (such as viral infection, surfactant, immunoglobulin, and biotin). The color of the cytoplasm of spindly cells can provide clues to their nature, such as basophilic (fibroblast), eosinophilic (smooth muscle and others), and amphophilic (myofibroblast). Eosinophilic globules have diagnostic value for sclerosing polycystic adenosis of salivary gland, low-grade B-cell lymphoma, solid pseudopapillary tumor of pancreas, and inclusion body fibromatosis. Eosinophilic granules are characteristic of granular cells (lysosome-rich), oncocytic cells (mitochondria-rich), and cells with secretory products (including neuroendocrine cells). Eosinophilic crystals can be diagnostic of lymphoma/plasmacytoma and crystal-storing histiocytosis. Basophilic granules or inclusions are diagnostic of acinic cell carcinoma and malakoplakia (Michaelis–Gutmann bodies). Yellow or brown inclusions are characteristic of hyalinizing trabecular adenoma of thyroid (yellow bodies), brown bowel syndrome, and malignant melanoma. Extracellular eosinophilic deposits can be produced by many conditions, but amyloid and monoclonal immunoglobulin deposition disease are important considerations. Extracellular basophilic deposits may be seen in small cell carcinoma and systemic lupus erythematosus, but they differ in that the former is blue (nuclear material) while the latter is purple (nuclear material plus immunoglobulin).

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