Clinical features

Hyperplastic polyps are the most commonly encountered polyp in the adult colorectum. They are found with increasing frequency in individuals older than 40 years of age, are more common in men than in women, and are more common in westernized populations. Because of their small size, hyperplastic polyps are asymptomatic and often detected incidentally at sigmoidoscopy or colonoscopy.

Most patients with adenomatous polyps have coexistent hyperplastic polyps. This observation has prompted the suggestion that hyperplastic polyps are a biomarker of an increased risk for neoplasia. However, the vast amount of evidence to date indicates that conventional hyperplastic polyps have no preneoplastic potential, and the finding of a hyperplastic polyp during sigmoidoscopy is not an indication for colonoscopic examination. Patients with adenomatous or carcinomatous transformation occurring in a hyperplastic polyp have been reported, usually in association with large polyp size (> 1 cm), or location within the proximal colon. However, recent data indicate that these lesions are most likely the result of sporadic microsatellite instability (MSI), and are better classified as sessile serrated adenomas (SSAs), a distinct form of colorectal neoplasm that does have neoplastic potential.

Pathologic features

Microscopic findings

Hyperplastic polyps contain elongated colonic crypts lined by epithelial cells with a pseudopapillary configuration and are composed of well-differentiated goblet and absorptive cells ( Fig. 13-1 ). The papillary infoldings are most prominent in the upper half of the crypts, resulting in the characteristic “saw-toothed” or serrated appearance. The number of absorptive cells lining the crypts is greater than the number of goblet cells, and these crypts contain ample eosinophilic cytoplasm and a prominent brush border. Apical mucin vacuoles may be present within the absorptive cells. Mitoses are not uncommon but are confined to the bottom half of crypts. The subepithelial collagen layer is thickened, best appreciated at the polyp surface. At the crypt base, the muscularis mucosa often shows splaying of the muscle fibers, with fibers extending into the lamina propria and surrounding individual crypts. The nuclei of epithelial cells range from small and hyperchromatic to slightly enlarged with a prominent nucleolus. Scattered Paneth or endocrine cells may also be seen within the crypt bases ( Fig. 13-2 ).

Hyperplastic polyp. A, Low-power view, microvesicular type. The serrated appearance of the upper crypts is evident at low power. The lamina propria is normal. B, High-power view of polyp surface. The nuclei are small and basally located, and the cytoplasm of the lining epithelium has a “frothy” appearance resulting from mucin-containing vesicles. Scattered goblet cells are also present, but account for the minority of epithelial cells within the polyp. C, High-power view of polyp base showing mild nuclear enlargement, prominent nucleoli, and scattered mitoses. Note that the crypt bases are smaller in diameter than the crypt surfaces.

Hyperplastic polyp. Mild nuclear atypia may be present in a hyperplastic polyp, seen as enlarged nuclei with fine chromatin pattern and one or more prominent nucleoli. However, crowding of nuclei is minimal. At the base of crypts, scattered endocrine cells are also present.

Three histologic subtypes of hyperplastic polyp have been described. They include the microvesicular cell type (see Fig. 13-1 ), the goblet cell type ( Fig. 13-3 ), and the mucin-poor type ( Fig. 13-4 ). Microvesicular type hyperplastic polyps are the most common, and likely equate to the classically recognized hyperplastic polyp. They are best distinguished by their microvesicular mucin with few goblet cells, some dystrophic goblet cells, and mild nuclear atypia. Goblet cell type polyps are noted by elongated crypts with prominent goblet cells and minimal serrations of the epithelium (see Fig. 13-3 ). Finally, mucin-poor polyps are the least common and have features suggestive that they are regenerative in nature (see Fig. 13-4 ). The epithelial cells are small with minimal cytoplasm, lack neuroendocrine cells, and show varying amounts of crypt dilatation. However, as a result of their crypt dilatation, some investigators have regarded mucin-poor hyperplastic polyps as morphologic variants of SSAs. At this time, however, there is no evidence that a distinction among these types of hyperplastic polyp has any clinical significance. The most important features to distinguish conventional hyperplastic polyps from an SSA are the lack of architectural distortion and the normal distribution of proliferating epithelial cells.

Goblet cell hyperplastic polyp. In this morphologic variant, the crypts are elongated and the epithelium is composed predominantly of goblet cells. Serrations of the epithelium are minimal, mostly present at the polyp surface.

Mucin-poor hyperplastic polyp. In this morphologic variant, the crypts are uniformly dilated from surface to base, with the serrated epithelium lining the crypts composed of small cells with minimal intracytoplasmic mucin and rare goblet cells. Mild nuclear atypia is present. The epithelial changes are reminiscent of regenerative changes following mucosal injury.

HYPERPLASTIC POLYPS—PATHOLOGIC FEATURES

Gross findings

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  Small sessile polyp (< 5 mm) grossly indistinguishable from a small tubular adenoma

  
  
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  Rectosigmoid colon most common location

Microscopic findings

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  Crypt elongation with micropapillary appearance of epithelium

  
  
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  Well-differentiated goblet and absorptive cells

  
  
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  Mitoses restricted to crypt bases

Differential diagnosis

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  Mucosal prolapse

  
  
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  Reactive epithelial changes

  
  
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  Tubular adenoma

Differential diagnosis

Other lesions with serrated epithelial features can mimic a hyperplastic polyp, including inflammatory cloacogenic polyps (ICPs), which often show prominent serrated epithelial changes of the surface epithelium. Features to distinguish ICPs from hyperplastic polyps include the polyp location at the anal verge, presence of smooth muscle ingrowth, reactive epithelial changes, and lamina propria hemorrhage and fibrosis. In some cases, a hyperplastic polyp may show areas of erosion with associated reactive epithelial changes, also raising the concern of a sessile serrated adenoma. The presence of surface maturation and lack of cytologic atypia should rule out this possibility.

Prognosis and therapy

Hyperplastic polyps do not have malignant potential. Because they may be endoscopically similar in appearance to small adenomatous polyps, hyperplastic polyps are often removed by polypectomy solely to distinguish them on histologic grounds from adenomatous polyps.

Clinical features

Sessile serrated adenomas are an entity that has been recognized only within the past decade as a pathologic lesion distinct from hyperplastic polyps. Recognition of these lesions has largely stemmed from the observations that (1) patients with hyperplastic polyposis, a disorder characterized by numerous hyperplastic polyps, have an increased risk for colorectal neoplasia and (2) sporadic right-sided hyperplastic polyps more commonly contain a variety of genetic alterations, including MSI and increased gene methylation, than their left-sided counterparts. Part of the reason for discrepancies in the literature are that these lesions have been called by a variety of names, including serrated polyp with atypical proliferation, giant hyperplastic polyps, large hyperplastic polyps, mixed hyperplastic/adenomatous polyps, sessile serrated polyps, serrated adenomas, and inverted hyperplastic polyps.

Formal evaluations of the clinical features of SSAs indicate that they represent approximately 10% of all lesions with serrated epithelial architecture encountered at endoscopy. The most common age at diagnosis is in the sixth to seventh decade of life, similar to that for classic adenomatous polyps.

Pathologic features

Microscopic findings

Two major morphologic features distinguish SSAs from conventional hyperplastic polyps: architectural distortion and abnormal proliferation. Architectural features that are characteristic of SSAs include crypt dilatation, horizontal orientation of deep crypts, serrations of crypt epithelium extending to the crypt bases, and inverted crypts ( Fig. 13-5 ). Abnormal proliferation in SSAs is characterized by nuclear atypia that extends to the mid and upper crypts (as opposed to conventional hyperplastic polyps where atypia, if present, is confined to the crypt base), asymmetric proliferation within crypts, prominent nucleoli, and mitoses in upper crypts ( Fig. 13-6 ). The basement membrane is not thickened, and the muscularis mucosa does not extend into the lamina propria as described for conventional hyperplastic polyps. Both neuroendocrine cells and Kulchitsky cells are decreased to absent. Cytologic features are less of a distinguishing feature of SSAs than of conventional hyperplastic polyps and include dystrophic goblet cells, irregular distribution of goblet cells, increased apoptosis, and excessive luminal mucin.

Sessile serrated adenoma. Unlike conventional hyperplastic polyps shown in Figure 13-1 , sessile serrated adenomas show widening of the crypt bases relative to the surface, complexity of crypts including papillary structures, and serrated epithelial changes extending to the crypt bases.

Sessile serrated adenoma. A, Nuclear atypia may be seen as enlarged nuclei with a fine chromatin pattern and one or more prominent nucleoli. In the absence of true adenomatous features, the atypia is not unlike that encountered in a conventional hyperplastic polyp. B, Asymmetric proliferation demonstrated by Ki-67 immunostain. In the crypt noted by an asterisk, nuclear staining extends more than halfway up the left side of the crypt in contrast to the right side, in which nuclear staining is confined to the base.

Mixed hyperplastic/adenomatous polyps are thought to represent conventional epithelial dysplasia arising within an SSA and thus are part of a histomorphologic continuum of these lesions. In these cases, the serrated changes of an SSA are present but with clear cytologic evidence of conventional epithelial dysplasia, including nuclear enlargement, loss of polarity extending to the polyp surface, and nuclear pleomorphism ( Fig. 13-7 ).

Conventional epithelial dysplasia arising in a sessile serrated adenoma. Low-power (A) and high-power (B) views of conventional epithelial dysplasia arising in a large sessile serrated adenoma, recognized by its nuclear crowding, nuclear enlargement, pencillate nuclei, loss of nuclear polarity, and loss of differentiation.

Ancillary studies

Immunohistochemical labeling does not have a routine role in the diagnosis of SSAs at this time, in that as no markers have demonstrated the appropriate sensitivity to discriminate a small SSA from a hyperplastic polyp. MUC6 has been reported to be a marker of SSAs, although this finding has not been validated in independent studies. By contrast, abnormal nuclear labeling for beta-catenin has been shown to be specific marker of serrated polyps with neoplastic potential ( Fig. 13-8 A). However, because nuclear labeling is only found in 29% of SSAs compared with 100% of SSAs with foci of conventional epithelial dysplasia, its role is limited as a diagnostic tool in early polyps. Similarly, some SSAs have been shown to have loss of hMLH1 protein expression, consistent with the increased rate of MSI reported for these polyps, although the loss of hMLH1 expression also occurs in the setting of conventional epithelial dysplasia or carcinoma arising in an SSA, limiting its utility as a diagnostic marker (see Fig. 13-8 B).

Immunohistochemical labeling for beta-catenin and hMLH1 in sessile serrated adenomas. A, Nuclear accumulation of beta-catenin protein within the epithelial cells of a sessile serrated adenoma. This polyp did not have associated conventional epithelial dysplasia. B, Loss of hMLH1 protein labeling within regions of conventional epithelial dysplasia and infiltrating carcinoma arising in a sessile serrated adenoma. Note the retention of hMLH1 labeling in the residual sessile serrated adenoma in the left side of the image.

Differential diagnosis

The main entity in the differential diagnosis of an SSA is a conventional hyperplastic polyp or a traditional serrated adenoma, particularly for left-sided lesions. Recognition of a lack of cytologic atypia, normal proliferation, thickened subepithelial basement membrane, and presence of neuroendocrine cells should aid in diagnosis as a hyperplastic polyp. Traditional serrated adenomas have a polypoid or villiform growth pattern, as well as ectopic crypt formations.

Prognosis and therapy

Recognition and differentiation of an SSA from a hyperplastic polyp are of clinical importance, because SSAs are associated with an increased risk for colorectal neoplasia, while hyperplastic polyps are not. The absolute risk for neoplastic transformation in an SSA remains an area of uncertainty. However, an association is recognized between MSI colorectal cancers and serrated adenomas, with up to 6% of colorectal cancers found in association with these lesions. The need for SSAs to be diagnosed and reported is thus of critical importance to aid in the development of management guidelines. In the absence of these data, management as for classic adenomatous polyps is likely the most appropriate course of action.

Clinical features

Traditional serrated adenomas (TSAs) are a subset of colorectal polyps with the architectural and cytologic features that overlap both tubular adenomas and hyperplastic polyps. Whereas the initial descriptions of these polyps likely also included SSAs, leading to diagnostic confusion, more recent evidence has definitely shown that they are a pathologically and genetically distinct entity from both tubular adenomas and sessile serrated adenomas. For this reason, the clinical features and incidence of TSAs at endoscopy are unknown but will likely be revealed in the coming years. It is estimated that TSAs are less prevalent than SSAs, with an average age at diagnosis in the seventh decade of life, similar to that for classic adenomatous polyps and SSAs. They are slightly more common in males, and there is no racial predominance.

Pathologic features

Microscopic findings

TSAs have features of both a classical tubular adenoma and a serrated polyp. The architectural features that are similar to tubular adenomas include polypoid or villiform growth of tubular glands with an intervening normal lamina propria. Cytologic features that are similar to tubular adenomas include nuclear enlargement, nuclear crowding, pencillate nuclei, loss of nuclear polarity, and loss of goblet cells and apical mucin. In addition, TSAs have a pronounced serrated epithelial architecture, ectopic crypt formations, and eosinophilic cytoplasm. Ectopic crypt formations followed by cytoplasmic eosinophilia are the most specific features of a TSA ( Fig. 13-9 ).

Traditional serrated adenoma. A, In addition to the serrated appearance of the epithelium, there is clear evidence of adenomatous change characterized by nuclear enlargement, crowding, pseudostratification, and atypia. Ectopic crypt formations are also a prominent feature. B, High-power view of ectopic crypt formations, seen as the abnormal development of crypts specifically within the epithelium, with the base of the crypt juxtaposed to the basement membrane. C, In this example of a traditional serrated adenoma, the adenomatous features are particularly prominent and are associated with eosinophilia of the neoplastic epithelium.

SESSILE SERRATED ADENOMAS—PATHOLOGIC FEATURES

Gross findings

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  Polypoid growth

  
  
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  Size ranges up to 2 cm

  
  
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  Left colon distribution

Microscopic findings

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  Villiform growth

  
  
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  Serrated epithelium in association with nuclear and cytologic atypia

  
  
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  Ectopic crypt formations

  
  
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  Eosinophilic cytoplasm

Differential diagnosis

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  Sessile serrated adenoma

  
  
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  Tubular adenoma

Differential diagnosis

The main entities in the differential diagnosis of a TSA are sessile serrated adenomas and classical tubular adenomas. Sessile serrated adenomas can be recognized by their sessile growth pattern and the presence of crypt dilatation, horizontal orientation of deep crypts, serrations of crypt epithelium extending to the crypt bases, and inverted crypts. Sessile serrated adenomas are also more commonly located in the right colon. Tubular adenomas can be recognized by their lack of serrated epithelium. Neither sessile serrated adenomas nor classical tubular adenomas have ectopic crypt formations that are a specific feature of TSAs.

Prognosis and therapy

The absolute risk for neoplastic transformation in a TSA is unknown. However, as high-grade dysplasia or carcinoma has been found in association with TSAs, they are best managed as for classic adenomatous polyps.