Results and Discussion
According to the 2019 WHO classification, intestinal serrated lesions are classified
as hyperplastic polyps (HPs), serrated lesions with and without dysplasia, traditional
serrated adenomas (TSAs), and unclassified serrated adenomas.[9] The nomenclature of these lesions in classifications and diagnostic criteria has
undergone changes in the last three decades and, and, in order to better understand
taht, it is necessary to review the definitions adopted in the first published studies.
In 1990, Longacre and Fenoglio-Preiser[6] described some polyps of serrated architecture that presented characteristics common
to conventional adenomas (CAs) and HPs, and named them as mixed hyperplastic/adenomatous
polyps – serrated adenomas. In 1996, Torlakovic and Snover[7] described a group of serrated lesions, in a case of serrated polyposis syndrome
(SPS), which showed abnormal architecture and cytological dysplasia, defined as “sessile
serrated adenomas (SSAs),” currently considered precursor lesions for CRC with MSI.[8] The prevalence of SSAs was underestimated for years, corresponding from 0.1% to
14.7% of all colorectal polyps. The differentiation of these from other conventional
polyps and adenomas became fundamental, since the identification of a morphological
and molecular profile related to the serrated carcinogenesis pathway was described,
with different prognosis, follow-up and response to treatment when compared to traditional
CRCs.[9]
[10]
[11] For the first time in 2000, the WHO[12] described two main types of serrated lesions: HPs (metaplastic) and serrated adenomas,
as well as mixed hyperplastic/adenomatous polyps. In 2010, the WHO[3] classified serrated lesions into three main categories: 1) HPs, microvesicular HPs
(MVHPs), goblet cell-rich HPs (GCRHPs) and mucin-poor HPs (MPHPs); 2) sessile serrated
adenomas/polyps (SSA/Ps), with and without cytological dysplasia, conventional (similar
to conventional, non-serrated adenomas), or serrated (pencillate nuclei and eosinophilic
cytoplasm); and 3) TSAs. The WHO classification also considered the diagnostic criteria
of mixed polyps (MPs), which contain alterations of more than one type of serrated
lesion, but which could represent collision lesions or a possible progression from
one lesion to another, and recommended that the terminology should be used with caution.[3] In 2019, the WHO[9] published the 5th edition of its classification: 1) MVHPs and GCRHPs; 2) sessile
serrated lesions (SSLs), with and without cytological dysplasia (conventional and/or
serrated); 3) TSAs; and 4) unclassified serrated adenomas, described as lesions with
intermediate characteristics between SSLs and TSAs, in addition to “serrated tubulo-villous
adenomas”. The latter category apparently replaces the previous nomenclature of “mixed
polyps”. The denominations adopted by the 2019 WHO classification were already recommended
by the 2017 British Society of Gastroenterology's[5] position statement, which used the terms “hyperplastic polyp, sessile serrated lesions
with and without dysplasia, traditional serrated adenoma, and mixed polyps”. [Table 1] shows the main classifications of serrated lesions in the past thirty years, based
on the last three WHO classifications and original descriptions from Longacre and
Fenoglio-Preiser[6] and Torlakovic and Snover.[7]
Table 1
Evolution in the classification of serrated lesions
|
Main authors and publications
|
Classification of serrated lesions
|
|
Longacre and Fenoglio-Preiser
[6]
|
• Hyperplastic polyp.
• Mixed hyperplastic adenomatous polyp/serrated adenoma.
|
|
Torlakovic and Snover
[7]
|
• Hyperplastic polyp.
• Sessile serrated adenoma.
• Mixed hyperplastic adenomatous polyp.
|
|
World Health Organization (WHO) 2000
[12]
|
• Hyperplastic polyp (metaplastic).
• Serrated adenoma.
• Mixed polyp (hyperplastic/adenomatous).
|
|
WHO 2010
[3]
|
• Hyperplastic polyp (microvesicular, globet cell-rich and mucin-poor).
• Sessile serrated polyp/adenoma (with or without dysplasia).
• Traditional serrated adenoma.
• Mixed polyp.
|
|
WHO 2019
[9]
|
• Hyperplastic polyp (microvesicular, globet cell-rich and mucin-poor).
• Sessile serrated lesion.
• Sessile serrated lesion with dysplasia.
• Traditional serrated adenoma.
• Unclassified serrated polyp.
|
Current Overview of Serrated Lesions
The morphological characteristics of each serrated lesion will be addressed briefly.
[Figure 1] and [Table 2] show the main histological differences between the serrated lesions.
Table 2
Serrated lesions and main and minor histological characteristics
|
Serrated lesions
|
Main histological characteristics
|
Minor histological characteristics
|
|
Hyperplastic polyps
|
• Proliferative zone confined to crypt base.
• Proximal crypt serration.
• Straight crypts, without distortion.
• More than one type of epitelial cell according to the polyp type.
|
• Localized basement membrane thickening.
• Individual crypt branching may eventually exist.
• Small, round and basally-located nuclei.
|
|
Traditional serrated adenoma
|
• Eosinophilic cytoplasm and pencillate nuclei.
• Formation of ectopic crypt.
• Villous architecture.
• Slit-like serration.
|
• Flat-type traditional serrated adenoma may show a few or no formation of ectopic
crypts.
• A few globet cells may be present, except in the mucin-rich type, in which they
are predominant.
• In up to 50% of the cases, a serrated precursor may be found.
|
|
Sessile serrated lesions
|
• Assymetric crypt dilation and/or branching.
• Luminal crypt serration throughout the entire extension, including its base.
• Horizontal branching of the base of the crypt in J, L or inverted-T pattern.
• Crypt herniation through the muscularis mucosa.
|
• Microvesicular and globet cells.
• Proliferative zone in the middle and base of the crypt.
• Most lesions do not exhibit epithelial dysplasia.
|
Fig. 1 (A) Hyperplastic polyp. Rounded glands with superficial and regular crypt serrations
(arrows); (B) sessile serrated lesion with complete (including distal) crypt serration and characteristic
lateral branching of the base of the crypt (arrows); (C) sessile serrated lesion with irregular (assymetric) crypt serration and lateral
branching of the base of the crypt and dilatation (arrows); (D) traditional serrated adenoma, showing slit-like serration and eosinophilic cytoplasm.
Staining method: Hematoxilin-Eosin. (Magnification: A and C – 200 X; B and D – 100
X).
Hyperplastic Polyps
Hyperplastic polyps are the most commonly observed type of serrated lesion, corresponding
to between 24% and 42% of all intestinal polyps, and 83% to 96% of serrated lesions.[5]
[10]
[11] They are usually small, measuring less than 5.0 cm, and with a sessile pattern,
containing glands with columnar epithelium, goblet cells, and elongated and dilated
crypts. They have straight crypts that extend symmetrically from the polyp surface
to the muscularis mucosa, with greater luminal distension and serration in its proximal
portion, without important architectural distortion, horizontal or irregular branching
pattern.[11] The basal membrane may be thickened; reactive epithelial alterations and mitotic
figures may be present, and should not be confused with dysplasia.[5] Currently, two morphological types of HPs are recognized. The most common is the
MVHP, composed of glands with epithelial cells containing mucus, apical serration
and goblet cells in lower frequency; it is more often located in the left colon and
rectum, although 10% to 15% of them may be located in the right and transverse colons.[13] The second type, corresponding to one third of the total, the GCRHP, exhibits numerous
goblet cells and lower apical serration, being more commonly found in the left colon
and rectum. The MVHP most often has mutations in the BRAF gene, and the GCRHP may
exhibit KRAS mutations, suggesting that they may be in different parts of the serrated
pathway. A third type, rarely identified, described in previous publications,[3]
[12] the MPHP, was excluded from the 2019 WHO classification; little is known about the
molecular characteristics related to this subtype, and one theory is that it would
correspond to the MVHP with reactive epithelial alterations secondary to inflammation.[13]
Sessile Serrated Lesions
Sessile serrated lesions and TSAs generally have in common the serrated appearance
of their crypt lumens. They are larger than HPs and, most SSLs occur in the right
colon. The diagnosis is based on the distorted and disorganized pattern of the crypts,
mainly in the basal portion, with serration along the whole extension of the crypt,
including its base, which is dilated, and with horizontal branches forming a “J,”
“L” or “Inverted T” pattern. Superficial biopsies may represent a greater challenge
in the differentiation from MVHPs. The crypts of the SSLs tend to be arranged parallel
to the muscularis mucosa and sometimes herniated through it, not necessarily representing
invasion. They show clear columnar cells with a less eosinophilic cytoplasm than those
observed in TSAs. The presence of mucinous cells in the base of the crypts can lead
to mucus accumulation and dialtion of the luminal gland, differently from HPs, which
show narrow lumens in their bases, and proliferative cells.[4] Another important issue is whether SSLs arise de novo or originate from HPs, particularly
MVHPs. The identification of most of pure SSLs at the right colon and MVHPs at the
left colon support the de novo theory. However, the frequent identification of areas
of MVHPs in large SSLs, associated with the presence of hypermethylation and BRAF
mutations observed in ∼ 66% to 75% of MVHPs, and ∼ 85% of SSLs, suggests that SSLs
may in fact represent advanced forms of MVHPs.[14] Sessile serrated lesions were defined in the 2010 WHO[3] classification as lesions presenting the aforementioned characteristics in at least three crypts (or two adjacent crypts). However, according to the criteria of the American Gastroenterology Association (AGA),
the presence of these alterations in only one crypt would be enough for the diagnosis.[13] Divergences in established criteria may justify the difficulties to make an adequate
diagnosis; it is estimated that ∼ 20% to 30% of lesions previously classified as HPs
currently correspond to SSLs and TSAs, as observed in studies[4]
[8]
[15] on the reclassification of these lesions. The 2019 WHO classification[9] considers a minimum criterion “the presence of at least one serrated crypt containing unequivocal architectural distortions”. Sessile serrated lesions may exhibit nuclear and cytoplasmic atypia similar to
that of low- and high-grade dysplasia observed in CAs; in these situations, well-defined
areas of cytological dysplasia are often identified in SSLs without dysplasia. These
areas are almost always related to the loss of immunoexpression of MHL1 due to the
inactivation of the gene, common in the MSI pathway, but unusual in the classic carcinogenesis
scheme[15]; at the same time, foci of dysplasia retain the BRAF gene mutation observed in the
remainder of the SSL. The identification of dysplasia is considered a marker of progression
to CRC, associated with rapid increase in size. In addition, the focus of dysplasia
in SSLs with malignant transformation is often identified, and identification of SSLs
with cytological dysplasia in polyps of individuals without a history of CRC is infrequent.[13]
[15]
More than one type of dysplasia is described in SSLs; however, the importance of differentiation
and graduation is still an issue to be defined. The most common type, conventional
dysplasia (similar to that of adenomas), is characterized by the presence of elongated
cells with pseudostratified and hyperchromatic nuclei, amphophilic cytoplasm, and
increased number of mitoses. Although graduation into low and high grades is performed
in CAs, the importance of the graduation of SSL dysplasia is not clear, and the recommendation
is to consider lesions with cytological dysplasia as a polyp of greater risk (advanced),
with management similar to that of high grade adenomas.[16] A second, less described type of dysplasia is the “serrated dysplasia,” rarely observed
in SSLs, characterized by the proliferation of more cuboidal atypical cells, with
eosinophilic cytoplasm, increased nuclear size with vesicular chromatin and prominent
nucleolus, as well as an increased number of mitoses; this pattern is considered by
some authors a marker of tumor progression.[13]
Traditional Serrated Adenoma
The third type of serrated polyp is the TSA, which usually exhibits a protuberant
exophytic configuration, villous architectural pattern with rounded ends, coated by
large numbers of columnar cells with eosinophilic cytoplasm, and elongated and pseudostratified
nuclei. A usual characteristic is the presence of so-called “ectopic crypts,” whose
formation seems to be related to the loss of their normal anchorage to the muscularis
mucosa. Both types of dysplasia can be found in TSAs; however, it is discussed whether
the serrated pattern represents a real dysplastic alteration or a metaplastic one,
since it differs from the cytological and architectural pattern of conventional dysplasia.
The overall prevalence of this type of condition is of 0.6%.[4]
[13] With neoplastic progression, TSAs are believed to have increased levels of cytological
atypia prior to the development of carcinoma. There is no consensus regarding the
identification or graduation of dysplasia in TSAs, and the recommendation is that
should be graded similarly to CAs (low and high grades). A recent study[8] showed that 25% of the TSAs studied had high-grade dysplasia, and 8% presented intramucous
carcinomas. The risk of malignancy in TSAs and the time of progression are yet to
be defined.[13]
[17] The molecular profile described for TSAs exhibits great heterogeneity, which can
be partially attributed to the confusing terminology and difficulty in diagnosing
serrated lesions.[15] The data available suggest that TSAs are not part of the serrated pathway, at least
regarding SSLs, since they do not always present MLH1 hypermethylation and BRAF mutations,
and may also exhibit KRAS and p53 mutations. Despite all these controversies, it is
believed that they are better managed, in terms of follow-up and treatment, such as
tubular adenomas of the same size.[13]
Non-classifiable Serrated Adenoma
This was a category introduced in the 2019 WHO classification,[9] with the purpose of including serrated polyps of difficult distinction, especially
TSAs and SSLs with dysplasia. The newly described serrated tubullo-villous adenoma
(TVA) is also included in this group.[9] Possibly, given the uncertainty regarding the characteristics of this group of lesions,
the microscopic criteria for this category were not described in this edition.
Reproducibility and Interobserver Agreement in the Histopathological Diagnosis of
Serrated Lesions
The detection of serrated lesions depends mainly on the examiner'' experience; approximately
half of the lesions in the proximal colon go unnoticed during the endoscopic examination,
which contributes to the lower detection rates of proximal colon cancers compared
with distal lesions.[16] The surveillance and treatment of serrated lesions, within each histological type,
diverge from those of conventional adenomas, based on the 2012 consensus recommendations
of the American Society of Gastrointestinal Endoscopy (ASGE), the AGA, and the American
College of Gastroenterology (ACG). In general, serrated lesions larger than 10 mm
and/or presenting cytological dysplasia, as well as TSAs, have a surveillance periodicity
of 3 years, lower than that of tubular adenomas with low-grade dysplasia.[16] Despite the existing recommendations, the strategies for the surveillance of serrated
lesions can only be adequately used after the proper histological diagnosis. However,
the literature[14]
[18]
[19]
[20]
[21]
[22] highlights a great difficulty related to the adoption and interpretation by the
pathologists of the criteria for the classification of serrated lesions. Part of this
difficulty is probably related to the different denominations applied, as well as
to the subjectivity of the existing histological criteria. Moreover, each type of
polyp has peculiarities, which lead to confusion between one or more histological
types (not necessarily only with serrated polyps). The related studies addressing
this issue consider two main points: the percentage of HP reclassifications to SSA,
MP, SSA/P and TSA, and the IOC or intraobserver concordance based on the kappa coefficient,
according to the classifications, denominations and criteria presented in the 2000[12] and 2010[3] WHO classifications (depending on the year of the paper). As an example, a study[20] conducted in 2014 shows that 41 (20.5%) among 200 polyps (serrated and conventional)
presented discordant diagnoses, and that the use of the 2010 WHO[3] classification, led to a reduction in the diagnosis of SSA/Ps and an increase in
the detection of HPs, due to the adoption of more rigid criteria. Currently, with
the change in diagnostic criteria for “only one crypt” containing the histological
characteristics of SSLs, this will probably lead to new IOC profiles, even though
there does not seem to be yet a published study on this topic.
One of the most cited studies was performed in 2007.[22] In it, an online quiz was conducted with microphotographs of 20 lesions and 168
observers from different countries, for which 4 diagnoses were admitted (HP, TVA,
SSA and TSA). The denominations most used by the participants were investigated, resulting
in more than 19 different terms used, such as: serrated polyp with anomalous proliferation, traditional mixed serrated adenoma, sessile serrated adenoma, hyperplastic-adenomatous mixed polyp, among others.[22] It also should be pointed out from this study that the mean agreement percentage
was ∼ 48%, with SSAs being more confused with HPs and TSAs, and TSAs more confused
with TVAs. It is noteworthy that 9.4% of the participants claimed to have never used
the term serrated adenoma as a diagnosis.
Another frequently cited study[23] was conducted in 2009, containing 40 HPs diagnosed in 2001 by pathologists with
no experience in gastrointestinal-tract pathology (GITP). It was proposed that the
cases were reviewed by 3 GITP specialists in 2007, based on the current knowledge
of that time (probably aligned with the guidelines later published in 2010 by the
WHO[3]). The authors demonstrated that ∼ 30% to 85% of HPs were reclassified as SSAs, with
a kappa coefficient of 0.16 (very poor or poor agreement).
In 2009, a study[18] described a general agreement of 42% and a kappa coefficient of 0.49 (moderate)
for all types of polyps, and 0.38 (fair) for SSAs and 0.53 (moderate) for HPs. However,
this study does not distinguished between TSAs and SSA/Ps. Compared with this study,
another one from 2008[21] presented an almost perfect IOC (kappa coefficient > 0.80) for the diagnosis of
TSAs; however, it did not include in its case series CAs or MPs, which probably reduced
the possibility of disagreement among observers; the kappa values were also obtained
for the other categories, which ranged from 0.45 to 0.47 for SSAs; from 0.42 to 0.52
for HPs; and from 0.46 to 0.58 for all lesions in general (moderate agreement).
In 2013, 2 studies[24]
[25] described the review and reclassification of cases previously diagnosed as HPs in
the right colon from 2009 to 2012, using, however, the criteria of the AGA,[13] (minimum of 1 crypt containing the characteristic histological changes), currently
adopted in the 2019 WHO classification.[3] The studies found a percentage reclassification range, in each year, of 30% to 64%
of cases (average of 42% over the 4 years), mainly for the diagnosis of SSA/Ps; as
an example, in 2009, there was no record of diagnosis of any SSA/P, and 66 HPs in
the right colon. Of these, 30% of the cases were reclassified as SSA/Ps, and 1%, as
TSAs. The percentage of reclassification of SSA/Ps observed was of up to 5% of the
cases, suggesting that the greatest difficulty lied in the differentiation of HPs
from SSLs, not the contrary. The kappa value was not calculated in these studies.[24]
[25]
Two other studies[19]
[20] show important data on this topic: the first of them, from 2014,[20] evaluated 200 lesions with diagnoses of CA, SSA, HP and MP. The general IOC was
moderate to good (kappa: 0.56 and 0.68), but the agreement in the use of cytological and architectural
criteria for diagnosis was analyzed, with large variations and low levels, especially
between the SSA and TSA criteria, such as crypt inversion (kappa: 0.25) and crypt
dilation (kappa: 0.38), formation of ectopic crypts (kappa: 0.25) and eosinophilic
cytoplasm (kappa: 0.06). Variations in diagnosis were also calculated in different
scenarios: A (before the disclosure of the diagnostic criteria), B (after the disclosure
of age, gender and location of the lesion) and C (after the disclosure of the consensus
on criteria). The greatest change observed in the diagnosis of SSAs and HPs occurred
mainly in scenario C, associated with greater difficulty in the application of semiquantitative
criteria, situations that had already been addressed in another study,[24] in which the use of criteria such as one or two crypts for the diagnosis seem to lead to significant changes in the trend of one or another
diagnosis. Another study,[19] performed in 2012 with 70 cases and conducted in two stages, one before the consensus
discussion and another after the definition of criteria based on the 2010 WHO classification,[3] showed an agreement of 0.318 and 0.557 (fair to moderate) for each stage respectively.
It is noteworthy that, after the definition of criteria, the agreement regarding the
diagnosis of HPs, SSLs and TSAs increased from 0.415, 0.301 and 0.433 to 0.977, 0.912
and 0.845 respectively; the global kappa coefficient, however, remained 0.557, possibly
due to the very poor agreement regarding MPs (0.158), which even decreased after the
disclosure of the criteria. Moreover, it is important to say that there were no cases
of CA in this study,[19] which could possibly reduce the chance of misdiagnosis with MPs and serrated adenomas
with dysplasia (in this study considered equivalent to SSL with dysplasia). This study[19] also evaluated the concordance between histological criteria, similarly to the previously
mentioned 2014 study,[20] in which serrated superficial crypts (kappa coefficient: 0.97), serrated superficial
epithelium (0.83), mitoses in the basal portion (0.79), goblet cells in the superficial
crypts (0.77), and dilation in the superficial portion of the crypts (0.72) showed
higher levels of agreement. The criteria with better discrimination capacity for each
diagnostic category were: serration, dilatation and goblet cells in the superficial
crypts in HP; horizontal dilatation of basal crypts and vesicular nuclei with nucleoli
in SSA; and formation of ectopic crypts, cytoplasmic eosinophilia, pseudostratification,
hyperchromasia, and nuclear elongation in TSA. Thus, it is suggested that architectural
criteria present greater discriminatory capacity for HP and SSA, and cytological criteria
contribute more to the diagnosis of TSA.
Finally, a 2015 study[26] showed 27 HPs reclassified as SSAs (SSLs and TSAs) among 310 polyps studied, resulting
in a total of 31 SSAs, from 3 SSAs initially identified, and a kappa coefficient of
0.102 (very poor agreement). Over the years, other studies[27]
[28] have shown similar results. [Table 3] summarizes the main studies on the subject in the literature.
Table 3
Interobserver variability in different series
|
Authors
|
Number of cases
|
Interobserver concordance
|
|
Baldin et al.,
[26]
2015
Rau et al.,
[20]
2014
|
n = 310 (HP/SSA/CA)
n = 200 (HP/ SSA/TSA/MP/CA/OL)
|
Very poor
Fair to good
|
|
Gill et al.,
[24]
2013
|
n = 797 (HP/SSA)
|
30% to 64% of HPs reclassified as SSAs, over 4 years (kappa not calculated)
|
|
Ensari et al.,
[19]
2012
|
n = 70 (HP/SSA/TSA/MP)
|
Good (in general) and very good for HP, SSA and TSA
|
|
Gunia et al.,
[27]
2011
|
n = 19 (SSA/TSA/ IP)
|
Poor to fair
|
|
Bustamante-Balén et al.,
[28]
2009
|
n = 195 (HP/SSA)
|
Very poor
|
|
Wong et al.,
[18]
2009
|
n = 60 (HP/SSA/MP/CA/OL)
|
Poor
|
|
Khalid et al.,
[23]
2009
|
n = 40 (HP/SSA)
|
Very poor
|
|
Farris et al.,
[21]
2008
|
n = 185 (HP/SSA/TSA)
|
Good
|
CA, conventional adenoma; HP, hyperplastic polyp; IP, inflammatory polyp; MP, mixed
polyp; OL, other lesions; SSA, sessile serrated adenoma; TSA, traditional serrated
adenoma.
Considering all of these studies, it was possible to observe that those including
lesions other than serrated ones, such as CAs, and lesions of other nature (inflammatory,
reactive or normal mucosa lesions), showed higher levels of reclassification and lower
IOC. This data suggests that when the study included a lower variety of lesions or
restricted evaluation criteria, the chances of discordances in the evaluation were
reduced. For example, CAs usually do not pose great diagnostic difficulty regarding
HPs and SSLs; however, they can be easylly mistaken for TSAs, which are rare lesions
with a frequency ∼ 1%,[22]
[24]
[25] whose difficulty to diagnose may not be clear if there is not a representative number
of TSAs in the study.
A condition little addressed in reclassification studies of serrated polyps, but frequent
in the pathologist routine, is the difficulty that sometimes exists to differentiate
an HP from a reactive lesion. A possible explanation might be the presence of microscopic
features of crypt hyperplasia and polypoid aspect observed in colonoscopies, in reactional
or inflammatory lesions, acting as a confounding factor. Another possibility that
could justify it, is the lack of recognition of the neoplastic potential of HPs by
pathologists, as a lesion of the serrated carcinogenesis pathway, who might tend to
opt for this diagnosis at the time of evaluation of a suspected lesion (both on colonoscopy
and microscopic analysis) in case of doubt, since they may consider it as an innocuous
or without carcinogenic potential.
Finally, the great variation in the rates of diagnostic agreement for SSLs and TSAs
reflects the magnitude of the problem regarding the diagnosis of these lesions, which
end up being confused with each other and with other colorectal polyps. Regarding
HPs, it is recognized that they are the main simulators of SSLs, and that, in the
past, most SSLs were diagnosed as HPs or MPs.[20]
[21]
[23]
[24] Although there are not many reports in the literature about the diagnostic difficulty
in differentiating between CAs with SSLs and HPs, it is worth mentioning the perception
by the pathologists that SSLs and TSAs are lesions with dysplasia, probably due to
previous denominations as serrated adenomas and mixed polyps, when in fact the presence of dysplasia in these lesions is not so frequent, corresponding
only to ∼ 5% of cases of SSL, for example.[21] Moreover, the presence of hyperplastic changes in the crypts of conventional adenomas
is not infrequent, often leading the pathologist to resort to the old term “hyperplastic-adenomatous
mixed polyp”. This term, which was no longer used since the 2010 WHO classification[3] as a specific type of serrated lesion, apparently came to be considered again in
the new classification,[9] under the term non-classified serrated polyp, whose frequency and minimum microscopic criteria have not yet been defined.
