Approaching the Unknown Glass Slide
Ed Friedlander MD

This website collects no information. If you e-mail me, neither your e-mail address nor any other information will ever be passed on to any third party, unless required by law.

This page was last modified December 19, 2011.

I have no sponsors and do not host paid advertisements. All external links are provided freely to sites that I believe my visitors will find helpful.

This guide will help you stay focused when you do your mock signout. "Pathology" must include some traditional classroom / reading / exam work. But learning is most meaningful and effective when you are practicing a skill, with supportive guidance and feedback. It is our intention that everybody come away from this exercise with a genuine feeling of satisfaction and accomplishment.

We will tell you the organ. You may use the histology textbooks in the office while you are working. if none of the familiar histologic structure is present, this must be a tumor.

Find the epithelium. Is it normal for that organ? If it is gone, and replaced by an inflamed crater, you are looking at an ulcer. If there is anaplasia confined to a portion of the epithelium, it is dysplasia / carcinoma in situ / intraepithelial neoplasia.

Look for other landmarks in the organ. Is something too thick? Too thin? Absent? Is the change focal or generalized?

Look for pigments. Black is probably carbon. Brown is probably melanin, hemosiderin, bile, or lipofuscin. WARNING: Brown pigment among red cells (and identical pigment appearing on the same slide) is an artifact. Ignore it. Cholesterol needles usually come from atherosclerotic plaque but can occur in necrotic areas. If it stains dark blue but isn't a nucleus / nuclear dust, it's bacteria or calcium.

Look for hyaline. Inflamed hyaline is probably fibrin. Non-inflamed extracellular hyaline is probably collagen or amyloid. Intracellular hyaline can be diagnosed based on its context.

Look for necrosis. Unless there is advanced coagulation necrosis (i.e., eosinophilic cell ghosts), your best tipoff will be nuclear dust and/or totally-pyknotic nuclei. If you can still see the outlines of cells, it is coagulation necrosis. If it's fine-granular and fairly homogeneous, it's caseous necrosis. If a portion of the tissue is absent, it's probably undergone liquefaction necrosis. Dead fat with a blue tinge is enzymatic fat necrosis.

Look for inflammatory cells. Distinguish neutrophils (acute inflammation), lymphocytes and plasma cells (lymphoid tissue or chronic inflammation), and eosinophils (less helpful in this exercise). Look for pus (neutrophils with little or nothing else). Giant cells are your best sign of a granuloma. Parallel small blood vessels are your best sign of granulation tissue. With acute inflammation, there is likely to be edema. With chronic inflammation, there is likely to be fibrosis.

Red cells outside of vessels are hemorrhage. Look at how it is positioned relative to the normal architecture or tumor architecture -- and think how the hemorrhage must have occurred. Inside a vessel or cardiac chamber, a thrombus can usually be recognized by lines of Zahn -- alternating erythrocyte-rich (red) and erythrocyte-poor (pink) layers.

If a portion of the tissue (or all of it) lacks the architectural features you remember from "Histology", this is a tumor. If a tumor exhibits anaplasia (i.e., cells with dark, oversized, irregular nuclei), necrosis, easy-to-find mitotic figures, hemorrhage, and/or obvious invasion (i.e., tentacles, or epithelial elements where they couldn't possibly belong), this is probably cancer. Otherwise, it is probably a benign tumor. A benign tumor with glands is an adenoma. A benign tumor with melanin in its cells is probably a nevus. And so forth.

If it is cancer, try to tell the kind. Cells lining up, adhering to one another, and moulding one another indicates carcinoma. Papillae, signet ring cells, lumens, back-to-back glands (swiss-cheese; it must be easy to find cells that are part of two different glands), and lakes of mucin say adenocarcinoma. Squamous pearls, desmosomes, and lone apoptotic cells say squamous cell carcinoma. Spindle-cell cancers (i.e., those with lots of nuclei oriented parallel) are often sarcomas. Melanin in cancer cells says melanoma. The infamous oat cell carcinoma features small blue cells, about 20 microns across, moulding each other, without a visible stroma. Lymphoma features sheets of relatively uniform round cells, not moulding each other but effacing the architecture of a lymphoid organ.

This will enable you to make a diagnosis on most of your mock-signout cases. There will be a few which will require you to recognize something more. But if you can recognize these key features on a slide, you will get credit for the slide even if you cannot exactly put the diagnosis together.

Ed's Pathology Pages

Meet Ed
Write to Ed

New visitors to
reset Jan. 30, 2005: