| Nuclear Shapes: Artefactual / Degenerate / Physiological / Mechanical NOTE: Normal and abnormal nuclei are subject to the same processes and forces. Interpretation of nuclear shape must be cautious in the presence of degeneration or distortion. 
Shrinkage due to alcohol fixation Can be seen in normal and abnormal cells. This effect is often extreme in normal intermediate cell nuclei. Sharp outward points are separated by shallow smoothly concave or flat areas (‘beaches and headlands’). This is not to be confused with abnormal nuclear irregularity. | |
Degenerate shrinkage Degenerate condensed and shrunken nuclei can take any shape, mimicking abnormality. Shape is unreliable when chromatin is condensed and smudged. | |
Nipple nuclear protrusions Are seen in normal and abnormal cells of glandular and metaplastic origin. Condensed nuclear material forms a bulging, nipple-like protrusion on one end of the nucleus. The protrusion may be large and irregular when the nucleus is shrunken. | |
Distortion by vacuoles Degenerate and secretory vacuoles often distort nuclei. | |
Mechanical forces distorting nuclei Nuclei may mould or flatten to adjacent cell borders and other nuclei.
Nuclei may stretch and distort due to shearing forces during sampling or smearing. Nuclear Structures: Degenerate NOTE: Normal and abnormal nuclei can show the same degenerate changes. Interpretation must be cautious in the presence of degeneration.
Degenerate coarse structure The nucleus has many crowded condensed dark elements, clear in between. The border is crenated; interrupted by small gaps. | |
Chromatin condensation Nuclei are dark, blue-black, with a smudged structure. Chromatin bands are indistinct and not sharply defined. Shrunken nuclei are darker. | |
Pyknosis The nucleus is brown or black, rounded, 1/3 its original diameter and lacks an internal structure. | |
Karyorrhexis Pyknotic nuclear fragments occupying the original nuclear area. No nuclear border. | |
Shotholes The nucleus has condensed, smudged chromatin with many small round cleared spaces. It may resemble the Coarse nuclear structure, but lacks distinct chromatin granules, and the paler areas are not connected. | |
Nuclear Shapes: Stromal or Histiocytic If all nuclear shapes are from this list, nuclear size and structure are predictable, and cytoplasm is consistent with stromal or histiocytic origin, then one can be confident that the cells are benign non-epithelial cells. | Round, oval | | Flattened oval | | Pointed oval, triangle | | | | Bean, kidney | | Comma, footprint | | Rectangle, dumbbell | CAUTION: Any of these shapes can occur in abnormal cells. However, in an abnormal cell population, these shapes will not represent the whole range of nuclear shapes, and shapes below the dotted line will occur only occasionally. Nuclear Structures: Abnormal NOTE: Any normal nuclear structure can also occur in abnormal cells.
Fine, evenly granular The chromatin is evenly distributed, fine grained, and has a granular texture. There are many small chromatinic elements densely crowded throughout the nucleus with lighter elements of similar size. Nuclei can be hyperchromatic, or appear with normal density. This abnormal structure varies from normal in that the small chromocentres are more numerous, crowded together and often distinct. | |
Few clumps Occasional (5-10) larger chromocentres or clumps in an otherwise fine grained, even nucleus. | |
Coarse A great many distinct chromatinic elements, with similar sized paler parachromatin spaces between them. This structure may occur with different levels of overall density – hyperchromatic, or paler with normal density. | |
Speckled or stippled Similar to the Coarse nuclear structure except that fewer, more widely separated but distinct chromocentres are scattered through the paler parachromatin. | |
Very coarse - ‘Granite’ Numerous large, prominent chromatinic elements crowded throughout the nucleus, with parachromatin elements of similar size between them. When parachromatin is pale, nuclear structure is open and transparent. The pattern resembles granite. Very coarse nuclei may have different levels of overall chromasia. Pale and open, coarse or very coarse abnormal nuclei may mimic benign reactive changes. Reactive nuclei almost invariably have a prominent nucleolus. Absence of a nucleolus strongly suggests abnormality in this nuclear type. However, presence of a nucleolus is not useful diagnostically, as high grade abnormal cells of this type often have a nucleolus. | |
Leopard spots Many (20–50) evenly spaced, similar sized, very prominent chromocentres with distinctly pale or cleared parachromatin between them.
When the nuclear border is absent or not sharply defined, this nuclear structure may be similar to degeneration, or prophase of mitosis. | |
Panther spots A panther is like a leopard, but the fur between the spots is black.
A highly abnormal structure. Similar to leopard spots but parachromatin is densely hyperchromatic. Distinct chromocentres indicate that the nucleus is not degenerate or smudged. | |
Clumped chromatin Several large chromocentres with irregular shapes and varied sizes. | |
Clearing Angular, irregular areas of bright clearing in the parachromatin. | |
Clumping and clearing A combination of parachromatin clearing with irregularly clumped chromatin. | |
Irregular distribution of chromatin within the nucleus Different parts of the nucleus may have a different density, or chromocentres may be more or less crowded, or of a different general size. Imagine the nucleus divided into four. Does one quadrant have a markedly different structure or level of chromasia? | |
‘Empty’ nucleus Fine, evenly pale internal nuclear structure, with a distinct border. Common in adenocarcinoma. A prominent round nucleolus, irregular thickening of the border or irregular shape adds suspicion. | |
Diffuse irregular distribution Diffuse irregular distribution of very fine or homogeneous chromatin. May be hyperchromatic. Occasionally seen in adenocarcinoma. | |
Irregularly thickened border Thick and thin areas along the border, or clumps of chromatin attached to it. | |
No discernable nuclear border The internal nuclear structure just stops at the border, without a defined, pencil line boundary. | |
Nuclear Shapes: Abnormal NOTE: Abnormal nuclei can be any normal shape. Absence of abnormal shape does not suggest benign. Indeed in many abnormal conditions, such as crowded sheets of HSIL, abnormal nuclear shapes are rare. Specific nuclear shapes that suggest abnormality:
Undulating Wavy, undulating nuclear outline, with rounded convexities and without any sharp points. | |
Indented and bulging One or more convex bulging areas, and/or indentations. Indentations between bulges point sharply inwards. The more bulges and indentations, the greater the suspicion of abnormality. Note: One small notch on the side of a nucleus near the cell centre is normal (centriole). | |
Position of irregularities Irregularity on the side of the nucleus that is away from the bulk of the cytoplasm is more significant than an irregularity facing the main body of the cytoplasm. The latter may be physiological. A notch on the end of a nucleus is significant. | |
Abnormal angularity Points may face outwards, but unlike fixation artefact, they are not separated by smooth concave depressions in the nuclear border. Indentations are also pointed. | |
Abnormal moulding Adjacent abnormal nuclei may retain some irregularities that do not flatten out between the nuclei, or one nucleus may distort its neighbour without itself deforming. | |
Architectural Features of Adenocarcinoma-in-situ The classic architectural features of AIS are best displayed in the endocervical subtype. In other subtypes these features are developed to a lesser extent.
Palisading Elongated cells and nuclei align parallel, like palings in a fence. This may be seen in strips of cells or at group edges. | |
Pseudostratification Squamous epithelium is stratified, or multi layered, but glandular epithelium, including AIS, is only one cell thick. In AIS, nuclear crowding gives an impression of multiple layers of cells and so it is termed pseudostratification. This is best appreciated in strips. Each nucleus is set back a different distance from the common luminal edge. | |
Feathering Cells attached to a group project separately from the cell group, in a pattern like feathers on the wing tips of a large bird. | |
Radial Polarity Cells appear to spray out from a point. | |
Curved strip A curved strip of cells, which may show feathering, radial polarity, palisading and pseudostratification, forms an arc with a smooth common luminal cytoplasmic border on the inner aspect of the arc. The outside of the arc is more ragged, with wisps of cytoplasm and part-bare nuclei. | |
Strip-off sheet A short strip with nuclei on one side and cytoplasm on the other may project from the edge of a larger, disordered, crowded cell sheet. | |
Rosette A strip curved right round in a circle. The outside of the circle is ragged, with part-bare nuclei, wisps of cytoplasm and perhaps feathering. Inside the circle there is either a pool of cytoplasm, or cytoplasm around a gland opening. | |
Gland openings in sheets Large crowded sheets of AIS may contain groups of cells arranged in a circle around a pool of cytoplasm or a
glandular lumen. |
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