Department of Pathology, Sinai Hospital of Baltimore Pathology, Baltimore, MD, USA
KeywordsAdenomaHyperplastic polypSerrated polypUlcerative colitisCrohn’s diseaseMucinous neoplasmAdenocarcinoma
Colon biopsies are most often performed for one of three reasons:
To evaluate a polyp or mass in the setting of screening or obstruction
To diagnose inflammatory bowel disease and monitor dysplasia
To look for an explanation for diarrhea or bleeding
The history is very important; you should not be diagnosing a tubular adenoma when the endoscopist did not see a polyp. Assuming that you have at least a succinct history or description from the endoscopist, therefore, your approach to the biopsy depends on what you are looking for.
Normal colonic mucosa should have a flat surface and nicely parallel crypts, like “test tubes in a rack.” The crypts are lined with goblet cells, endocrine cells, and precursor cells. Paneth cells, which are red granular cells with basal nuclei, are normal in the ascending and transverse colon but abnormal in the left colon. Immediately under the epithelium is the lamina propria, which is separated from the underlying submucosa by the muscularis mucosa (Figure 8.1). Normal constituents of the lamina propria include lymphocytes, plasma cells, and eosinophils. How many lymphocytes are too many? In general, they are assumed to be physiologic unless there is clinical or histologic evidence of chronic damage to the mucosa. Lymphoid aggregates are common and unremarkable.
Normal colon. Section through colonic mucosa showing parallel crypts (C), lamina propria (LP), muscularis mucosa (MM), and submucosal arteries (A), veins (V), and lymphatics (L).
Deep to the submucosa is the thick muscularis propria. Beyond this layer lies the serosal fat. In biopsy or polypectomy tissue, seeing adipose tissue and thick muscularis propria is not normal and means the endoscopist may have taken a full-thickness specimen, in other words, perforated the colon. This should prompt an immediate courtesy call. However, keep in mind that fat can be seen in the submucosa, so just seeing fat without the thick muscular layer of propria is usually not significant.
Polyps and Masses
An adenoma (at least in the tubular-to-villous family) is defined as a polyp with low-grade dysplasia. Low-grade dysplasia in the colon indicates a cytologic change and stands out from the normal colon as looking blue on the slide. The cells lining the crypts and the surface become tall and dark (because of depleted mucin) and have cigar-shaped and/or pseudostratified hyperchromatic nuclei (Figure 8.2). Mitoses may be present but are generally confined to the base of the crypts.
Tubular adenoma . This section shows an early tubular adenoma in which low-grade dysplasia is seen in the surface glands (arrow) while the deeper glands are uninvolved (arrowhead). The adenomatous epithelium is dark due to crowded and hyperchromatic nuclei and loss of mucinous goblet cells. Mitotic activity and neutrophils are common in adenomas but may also be seen in benign epithelium.
The dysplasia must extend all the way to the surface epithelium to qualify as an adenoma ; if the epithelium shows signs of maturing (progressing to more normal-appearing nuclei) as it ascends, it is more likely to be reactive changes.
Adenomas are subdivided by their architecture. The most common type is the tubular adenoma , which has a smooth surface and parallel crypts, similar to normal epithelium. A villous adenoma is covered in fingerlike projections, whereas a tubulovillous adenoma has features of both. These are soft and subjective distinctions, in practice.
Important considerations for sign-out include the following:
Margins: When an entire polyp is plucked off the colon, ideally it is cross-sectioned so that you can see the stalk. Ink on the stalk is helpful, but cautery also identifies your margin. If there are identifiable margins, mention whether or not the adenomatous epithelium extends to the margin.
Dysplasia : By definition, low-grade dysplasia is present and need not be mentioned. However, high-grade dysplasia is equivalent to carcinoma in situ and must be noted. The diagnosis of high-grade dysplasia is made on the basis of architecture AND cytology. The glands become cribriform, fused, or back to back (Figure 8.3). High-grade architecture is also usually accompanied by ugly cytology: total loss of nuclear polarity, significant pleomorphism, atypical mitoses, and large nucleoli. Often the diagnosis of high-grade dysplasia is reserved for areas that look so complex you are worried about carcinoma but cannot put your finger on invasion.
High-grade dysplasia in an adenoma . The diagnosis is largely based on architectural features, such as cribriform growth (arrow).
Carcinoma : All adenomas are considered at least premalignant lesions; sometimes you will find carcinoma arising in a polyp on biopsy. To diagnose carcinoma (as opposed to high-grade dysplasia), you must demonstrate cancer crossing the basal lamina, that is, into the lamina propria. Clues to invasion include a jagged interface with the lamina propria, individual infiltrating cells, desmoplastic response, and a pinking up of the invasive cells (Figure 8.4).
Invasive adenocarcinoma. Poorly formed glands and single cells (arrow) infiltrate through a desmoplastic stroma (arrowhead). Cells show marked pleomorphism and prominent nucleoli.
Invasion: Invasion into the lamina propria alone is called intramucosal carcinoma . This may happen in a large polyp, and excision is still curative if negative margins can be identified. Within the lamina propria, colon cancer has no metastatic potential. However, once malignant cells cross the muscularis mucosa into the submucosa, there is risk of metastasis. The extent of invasion must be noted in the diagnosis, to the degree that it can be assessed on a biopsy.
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The Serrated Polyps Family
Hyperplastic polyps are those in which the epithelial cells, although benign, begin to outgrow their available space. The glands have an increased number of goblet cells and therefore look pale or cleared out next to normal epithelium, and there tends to be a thickened or “sclerotic-appearing” basement membrane under the neoplastic cells. Furthermore, because the surface area is outgrowing the lamina propria, hyperplastic polyps take on a distinctive frilly (like a skirt) or lacy appearance (Figure 8.5). An imaginary cast of the inside of the crypts might look like a flaring fluted vase, narrow at the base. Crypts cut in cross section have a distinctive star-shaped lumen, and this architecture is called “serrated.”
Hyperplastic polyp. The surface of the polyp shows a characteristic “frilly” appearance (arrow), with hyperplastic mucinous epithelium and prominent goblet cells. Deeper crypts (arrowhead) show star-shaped lumens.
A polyp with adenomatous-looking cells at the base of the crypts, and frilly hyperplastic cells at the surface, is still a hyperplastic polyp. Remember that surface maturation is not consistent with a tubular adenoma . However, a true adenoma with a serrated surface profile may be in the serrated adenoma category, below.
Historically, a “serrated adenoma ” was a polyp with low-grade dysplasia extending to the surface, as seen in tubular adenoma , but with serrated architecture. Now a subset of what were once lumped in with hyperplastic polyps, especially in the right colon, are recognized as a distinct type of polyp with malignant potential, associated with the microsatellite instability (MSI) cancer pathway. These polyps, often broad and sessile, are called either sessile serrated adenomas (SSA ) or sessile serrated polyps (SSP ). The crypts have characteristic widening and horizontal branching at the base (“duck feet”), and the epithelial cells may be more eosinophilic (less mucin) and pseudostratified than the usual hyperplastic polyp (Figure 8.6). In addition, the thickened basement membrane seen near the surface in hyperplastic polyps is absent in SSAs. However, mature goblet cells and the serrated profile are still evident.
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