Myeloid Sarcoma of the Breast as Blast Phase of JAK2-Mutated (Val617Phe Exon 14p) Essential Thrombocythemia: A Case Report and a Systematic Literature Review.

INTRODUCTION: Myeloid sarcoma (MS) is a mass-forming proliferation of myeloid blasts. Frequently, it arises as blast phase of pre-existing myeloproliferative, myelodysplastic disorders or consequent to bone marrow transplant. Its molecular characterization has become an increasingly important requirement for the diagnostic definition of this solid leukemia. CASE PRESENTATION: Our case report concerns an MS arising in the breast of a woman with a previous diagnosis of JAK2-mutated essential thrombocythemia (Val617Phe exon 14p) mimicking, on histology, a lobular carcinoma of the breast. The immunohistochemical study of the neoplasm provided the key that solved the diagnostic doubt and the immunohistochemical evaluation of NPM protein expression, which turn out to be negative, provided a clear indication on the molecular status and prognosis of the disease. A year later, the neoplasm relapsed in the pelvic area. DISCUSSION: This diagnostic challenge led us to review the literature of the past 10 years concerning MS of the breast. To the best of our knowledge, this was the first case of MS of the breast occurring in a patient with a history of essential thrombocythemia and recurred in the pelvic region.

Odontogenic keratocystic can be misdiagnosed for a lateral periodontal cyst when the clinical and radiographical findings are similar.

Lateral periodontal cyst (LPC) and odontogenic keratocystic (OK) are two osteolytic lesions of the jaw with different local invasiveness and percentage of recurrence. The aim of this study was to highlight the attention on the differential diagnosis of these lesions that sometimes can have unexpected location and can lead doubts on diagnosis, therapy, and follow-up. A 34-year-old man presented to our department with a complaint of soft pain in the vestibular aspect of left mandibular second premolar and left mandibular first molar. Vital teeth in the left mandible, no mucosal swelling, and no drainage were observed. The CBCT showed a well circumscribed hypodensity area, extending between 3.5 and the apex of mesial root of 3.6. No displacement and no resorption of the roots were notified. Upon clinical and radiographical examination, a provisional diagnosis of LPC was made and enucleation of the lesion and histological examination were planned. Histologically, a cystic wall partially lined by a keratinizing squamous epithelium was observed. Surrounding and within the lesion, there was a chronic inflammatory infiltrate also of granulomatous type and with cholesterol clefts. Based on these findings, the diagnosis of odontogenic keratocystic was done. Radiolucent lesions in the premolar and canine region are frequently clinically and radiographically misdiagnosed. The identification of keratocyst in a location preoperatively favoring a lateral periodontal cyst should be suspected and biopsy must be considered in all cases to establish the nature of the lesion, the best surgical treatment, and the follow-up appointments.

Proliferation in pleomorphic adenoma: Lights and shadow on this parameter, in a neoplasm showing unpredictable behavior-An immunohistochemical study and review of the literature.

BACKGROUND: Pleomorphic adenoma accounts for the majority of benign tumors of the salivary gland. It is also called mixed tumor because it is composed by ductal epithelial and myoepithelial cells, variably intermixed within a chondromyxoid stroma. The recurrence rate is around 3.4% and 6.3%, respectively at 5 and 10 years and, to date, there are no valuable predictive factors. Aim of our study was to assess the role of Ki67 proliferative index in our cases and through meta-analysis. METHODS: Immunohistochemistry with Ki67 antibody was performed on 28 cases. A manual count of the signal was performed, to establish the proliferative activity. Statistical tests were applied to assess the correlation between the score and clinico-pathologic parameters. Further data were extrapolated from studies published on Pubmed, Cochrane and Web of Science database. RESULTS: Higher values of Ki67 were found among cases with larger size (p value = 0.0061) and showing greater cellularity (p value=0.0004). 19 papers were selected from the bibliographic search, concerning a total of 1187 patients affected by pleomorphic adenoma. In most of them, a higher Ki67 was detected among relapsing forms but results were controversial. In each study, several count methods were applied. CONCLUSION: The role of Ki67 in pleomorphic adenoma of the salivary glands remains unclear. The lack of homogeneity of the data makes it very difficult to standardize them in order to draw a conclusion. It would therefore be desirable to carry out a comparison study of the various possible methods of Ki67 counting.

Malignant intraventricular meningioma: literature review and case report.

Malignant intraventricular meningiomas (IVMs) are very rare with only a few reported cases. A midline search up to December 2020 selected 40 articles for a total of 65 patients. The inclusion criteria were series and case reports in English language, as well as papers written in other languages, but with abstracts written in English. Malignant IVMs at the first diagnosis (group A, 50 patients) and those with anaplastic transformation from previous WHO grades I and II tumors (group B, 15 patients) were separately analyzed. The unique personal case among 1285 meningiomas (0.078%) is also added. Malignant IVMs mainly occur in women (61%) with a median age of 45 years and are mainly located in the lateral ventricle (93%) and trigonal region (74%), with no cases in the fourth ventricle. Irregular borders (80%), heterogeneous enhancement (83%), and perilesional edema (76%) are the most frequent radiological findings. The histology was mainly pure anaplastic (85%), whereas papillary (7%), rhabdoid (5%), and mixed forms (3%) are very rare. The CSF spread was found in 60% of the cases. The prognosis is very dismal, with an overall median survival of 17.5 months after surgery for the anaplastic forms. Malignant IVMs at initial diagnosis (group A) show better overall survival (25 months) than those occurring from anaplastic transformation of lower grade tumors (group B) (10.1 months).

Evaluation of MGMT Gene Methylation in Neuroendocrine Neoplasms.

Unresectable neuroendocrine neoplasms (NENs) often poorly respond to standard therapeutic approaches. Alkylating agents, in particular temozolomide, commonly used to treat high-grade brain tumors including glioblastomas, have recently been tested in advanced or metastatic NENs, where they showed promising response rates. In glioblastomas, prediction of response to temozolomide is based on the assessment of the methylation status of the MGMT gene, as its product, O 6-methylguanine-DNA methyltransferase, may counteract the damaging effects of the alkylating agent. However, in NENs, such a biomarker has not been validated yet. Thus, we have investigated MGMT methylation in 42 NENs of different grades and from various sites of origin by two different approaches: in contrast to methylation-specific PCR (MSP), which is commonly used in glioblastoma management, amplicon bisulfite sequencing (ABS) is based on high-resolution, next-generation sequencing and interrogates several additional CpG sites compared to those covered by MSP. Overall, we found MGMT methylation in 74% (31/42) of the NENs investigated. A higher methylation degree was observed in well-differentiated tumors and in tumors originating in the gastrointestinal tract. Comparing MSP and ABS results, we demonstrate that the region analyzed by the MSP test is sufficiently informative of the MGMT methylation status in NENs, suggesting that this predictive parameter could routinely be interrogated also in NENs.

Qualitative Heterogeneous Signal Drop on Chemical Shift (CS) MR Imaging: Correlative Quantitative Analysis between CS Signal Intensity Index and Contrast Washout Parameters Using T1-Weighted Sequences.

The aim of this study was to calculate MRI quantitative parameters extracted from chemical-shift (CS) and dynamic contrast-enhanced (DCE) T1-weighted (T1-WS) images of adrenal lesions (AL) with qualitative heterogeneous signal drop on CS T1-WS and compare them to those of AL with homogeneous or no signal drop on CS T1-WS. On 3 T MRI, 65 patients with a total of 72 AL were studied. CS images were qualitatively assessed for grouping AL as showing homogeneous (Group 1, n = 19), heterogeneous (Group 2, n = 23), and no (Group 3, n = 30) signal drop. Histopathology or follow-up data served as reference standard to classify AL. ROIs were drawn both on CS and DCE images to obtain adrenal CS signal intensity index (ASII), absolute (AWO), and relative washout (RWO) values. Quantitative parameters (QP) were compared with ANOVA analysis and post hoc Dunn's test. The performance of QP to classify AL was assessed with receiver operating characteristic analysis. CS ASII values were significantly different among the three groups (p < 0.001) with median values of 71%, 53%, and 3%, respectively. AWO/RWO values were similar in Groups 1 (adenomas) and 2 (benign AL) but significantly (p < 0.001) lower in Group 3 (20 benign AL and 10 malignant AL). With cut-offs, respectively, of 60% (Group 1 vs. 2), 20% (Group 2 vs. 3), and 37% (Group 1 vs. 3), CS ASII showed areas under the curve of 0.85, 0.96, and 0.93 for the classification of AL, overall higher than AWO/RWO. In conclusion, AL with qualitative heterogeneous signal drop at CS represent benign AL with QP by DCE sequence similar to those of AL with homogeneous signal drop at CS, but different to those of AL with no signal drop at CS; ASII seems to be the only quantitative parameter able to differentiate AL among the three different groups.

Progesterone Receptor Expression in Meningiomas: Pathological and Prognostic Implications.

BACKGROUND: The progesterone receptor (PR) is variably expressed in most meningiomas and was found to have prognostic significance. However, the correlation with patient age, tumor location, time to recurrence, and pattern of regrowth has scarcely been discussed. METHODS: A surgical series of 300 patients with meningiomas is reviewed. The PR expression was classified as: 0. absent; 1. low (<15%); 2. moderately low (16-50%); 3. moderately high (51-79%); 4. high (≥80%). The PR values were correlated with the patient age and sex, meningioma location, WHO grade, Ki-67 MIB1, recurrence rate, pattern of recurrence (local-peripheral versus multicentric diffuse), and time to recurrence. RESULTS: The PR expression has shown lower rate of high expression in the elderly group (p = 0.032) and no sex difference (including premenopausal versus postmenopausal women), higher expression in medial skull base and spinal versus other locations (p = 0.0036), inverse correlation with WHO grade and Ki67-MIB1 (p < 0.0001). Meningiomas which recurred showed at initial surgery higher rates of low or moderately low PR expression than the non-recurrent ones (p = 0.0004), whereas the pattern of regrowth was not significant. Higher rates of PR values ≥80% were found in cases with time to recurrence >5 years (p = 0.036). CONCLUSION: The higher PR expression in medial skull base meningiomas, the significant correlation with the time to recurrence, the lack of difference of PR expression between premenopausal and postmenopausal women and between local-peripheral versus multicentric-diffuse recurrences are the most relevant unreported findings of this study. The rate of PR expression must be included in the routine pathological diagnosis of meningiomas because of its prognostic significance.

Cavernous Malformations to Be Investigated for Familiarity: The Role of Ki67 MIB1.

BACKGROUND: Familial forms of cavernous malformations (CMs) often occur as multiple lesions. Nevertheless, the presence of a single CM does not exclude the familiarity. The aim of this study is to establish which patients who undergo surgery for a single cerebral cavernous malformation (CCM), with no family history at initial diagnosis, should be investigated for familiarity through genetic testing and counseling. METHODS: Eight families with 2 or more members affected by CCM have been studied. A control group of sporadic cases operated on, with no family history and followed up 10 years or more, was also included. Analyzed factors were patient age and sex, location, number and size of the lesions, associated developmental venous anomaly, presence of epileptic seizures, symptomatic hemorrhage, focal neurological deficits, and documented growth of the malformation and Ki67 MIB1 proliferation index. RESULTS: The familial group of CCMs showed higher incidence of pediatric patients (P = 0.01), more frequent occurrence of multiple lesions (P = 0.0004), higher rate of large CCMs, and symptomatic hemorrhage; besides, all 3 cases with documented growth belonged to the familial group (14%). The expression of Ki67 MIB1 was positive in 79% of the familial cases versus 0% in the sporadic ones (P < 0.00001). CONCLUSIONS: Patients with CCM and no known family history at the time of the initial diagnosis who present specific features should be studied by genetic screening. The Ki67 MIB1 is a useful biomarker in favor of familial occurrence and may be studied in all patients with CMs to define the indication to the genetic tests.

Endoscopic resection of a large polypoid gastric heterotopia of duodenum: a case report.

This report shows a rare case of gastric heterotopia in the duodenum presented as a large polypoid lesion, differently from data reported in literature, which enters into differential diagnosis with other duodenal lesions that are not always benign.

Diagnostic Utility of the Immunohistochemical Expression of Serine and Arginine Rich Splicing Factor 1 (SRSF1) in the Differential Diagnosis of Adult Gliomas.

BACKGROUND: The aim of this study was to investigate the immunohistochemical expression and distribution of serine and arginine rich splicing factor 1 (SRSF1) in a series of 102 cases of both diffuse and circumscribed adult gliomas to establish the potential diagnostic role of this protein in the differential diagnosis of brain tumors. METHODS: This retrospective immunohistochemical study included 42 glioblastoma cases, 21 oligodendrogliomas, 15 ependymomas, 15 pilocytic astrocytomas, 5 sub-ependymal giant cell astrocytoma and 4 pleomorphic xanthoastrocytomas. RESULTS: Most glioblastoma (81%), oligodendroglioma (71%), sub-ependymal giant cell astrocytoma (80%) and pleomorphic xanthoastrocytoma (75%) cases showed strong SRSF1 immunoexpression, while no detectable staining was found in the majority of ependymomas (87% of cases) and pilocytic astrocytomas (67% of cases). CONCLUSIONS: The immunohistochemical expression of SRSF1 may be a promising diagnostic marker of astrocytomas and oligodendrogliomas and its increased expression might allow for excluding entities that often enter into differential diagnosis, such as ependymomas and pilocytic astrocytomas.

Does endometrial morular metaplasia represent odontogenic differentiation?

The nature of endometrial morular metaplasia (MorM) is still unknown. The nuclear ß-catenin accumulation and the not rare ghost cell keratinization suggest a similarity with hard keratin-producing odontogenic and hair matrix tumors rather than with squamous differentiation. We aimed to compare MorM to hard keratin-producing tumors. Forty-one hard keratin-producing tumors, including 26 hair matrix tumors (20 pilomatrixomas and 6 pilomatrix carcinomas) and 15 odontogenic tumors (adamantinomatous craniopharyngiomas), were compared to 15 endometrioid carcinomas with MorM with or without squamous/keratinizing features. Immunohistochemistry for ß-catenin, CD10, CDX2, ki67, p63, CK5/6, CK7, CK8/18, CK19, and pan-hard keratin was performed; 10 cases of endometrioid carcinomas with conventional squamous differentiation were used as controls. In adamantinomatous craniopharyngiomas, the ß-catenin-accumulating cell clusters (whorl-like structures) were morphologically similar to MorM (round syncytial aggregates of bland cells with round-to-spindled nuclei and profuse cytoplasm), with overlapping squamous/keratinizing features (clear cells with prominent membrane, rounded squamous formations, ghost cells). Both MorM and whorl-like structures consistently showed positivity for CD10 and CDX2, with low ki67; cytokeratins pattern was also overlapping, although more variable. Hard keratin was focally/multifocally positive in 8 MorM cases and focally in one conventional squamous differentiation case. Hair matrix tumors showed no morphological or immunophenotypical overlap with MorM. MorM shows wide morphological and immunophenotypical overlap with the whorl-like structures of adamantinomatous craniopharyngiomas, which are analogous to enamel knots of tooth development. This suggests that MorM might be an aberrant mimic of odontogenic differentiation.

Handcrafted MRI radiomics and machine learning: Classification of indeterminate solid adrenal lesions.

PURPOSE: To assess a radiomic machine learning (ML) model in classifying solid adrenal lesions (ALs) without fat signal drop on chemical shift (CS) as benign or malignant. METHOD: 55 indeterminate ALs (21 lipid poor adenomas, 15 benign pheocromocytomas, 1 oncocytoma, 12 metastases, 6 primary tumors) showing no fat signal drop on CS were retrospectively included. Manual 3D segmentation on T2-weighted and CS images was performed for subsequent radiomic feature extraction. After feature stability testing and an 80-20% train-test split, the train set was balanced via oversampling. Following a multi-step feature selection, an Extra Trees model was tuned with 5-fold stratified cross-validation in the train set and then tested on the hold-out test set. RESULTS: A total of 3396 features were extracted from each AL, of which 133 resulted unstable while none had low variance (< 0.01). Highly correlated (r > 0.8) features were also excluded, leaving 440 parameters. Among these, Support Vector Machine 5-fold stratified cross-validated recursive feature elimination selected a subset of 6 features. ML obtained a cross-validation accuracy of 0.94 on the train and 0.91 on the test sets. Precision, recall and F1 score were respectively 0.92, 0.91 and 0.91. CONCLUSIONS: Our MRI handcrafted radiomics and ML pipeline proved useful to characterize benign and malignant solid indeterminate adrenal lesions.

Periprostatic adipose tissue promotes prostate cancer resistance to docetaxel by paracrine IGF-1 upregulation of TUBB2B beta-tubulin isoform.

Growing evidence supports the pivotal role played by periprostatic adipose tissue (PPAT) in prostate cancer (PCa) microenvironment. We investigated whether PPAT can affect response to Docetaxel (DCTX) and the mechanisms associated. Conditioned medium was collected from the in vitro differentiated adipocytes isolated from PPAT which was isolated from PCa patients, during radical prostatectomy. Drug efficacy was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide citotoxicity assay. Culture with CM of human PPAT (AdipoCM) promotes DCTX resistance in two different human prostate cancer cell lines (DU145 and PC3) and upregulated the expression of BCL-xL, BCL-2, and TUBB2B. AG1024, a well-known IGF-1 receptor inhibitor, counteracts the decreased response to DCTX observed in presence of AdipoCM and decreased TUBB2B expression, suggesting that a paracrine secretion of IGF-1 by PPAT affect DCTX response of PCa cell. Collectively, our study showed that factors secreted by PPAT elicits DCTX resistance through antiapoptotic proteins and TUBB2B upregulation in androgen independent PCa cell lines. These findings reveal the potential of novel therapeutic strategies targeting adipocyte-released factors and IGF-1 axis to overcome DCTX resistance in patients with PCa.

From microbiota toward gastro-enteropancreatic neuroendocrine neoplasms: Are we on the highway to hell?

Gut microbiota is represented by different microorganisms that colonize the intestinal tract, mostly the large intestine, such as bacteria, fungi, archaea and viruses. The gut microbial balance has a key role in several functions. It modulates the host's metabolism, maintains the gut barrier integrity, participates in the xenobiotics and drug metabolism, and acts as protection against gastro-intestinal pathogens through the host's immune system modulation. The impaired gut microbiota, called dysbiosis, may be the result of an imbalance in this equilibrium and is linked with different diseases, including cancer. While most of the studies have focused on the association between microbiota and gastrointestinal adenocarcinomas, very little is known about gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). In this review, we provide an overview concerning the complex interplay between gut microbiota and GEP NENs, focusing on the potential role in tumorigenesis and progression in these tumors.

Neuroinvasive potential of SARS-CoV2 with neuroradiological and neuropathological findings: is the brain a target or a victim?

Coronaviridae family includes pathogen viruses for humans, that lead to clinical conditions with main respiratory involvement; many of these viruses have notoriously a neuroinvasive potential, as demonstrated by published data on SARS-CoV and MERS-CoV epidemics, as well by results obtained in experimental models. During pandemic of coronavirus disease 2019 (COVID-19), it is noticed that the central nervous system involvement represented a truly significant moment in the history of some COVID-19 patients; indeed, clinical and radiological features published in literature regarding COVID-19 disease are consistent with a neurological involvement. It is also known that histopathological data related to SARS-CoV2 infection have been published with considerable delay, which was even greater for neuropathological information. Moreover, many published data are incomplete, and often the lesions described are not directly related to the action of the virus. In this review, we collected the available radiological and neuropathological information, in order to delineate a more complete picture of the relationship between SARS-Cov2 and brain, focusing our attention on the two most important neuroinvasion routes for the virus. We also highlighted what we consider methodological mistakes both in the autopsy procedures and brain study in COVID-19 deaths. We emphasize the need for a complete study of all the organs in case of autopsy. It is important that through this experience, we no longer do the mistake of neglecting the brain.

Extraovarian dysgerminoma in a pregnant woman: an extremely rare finding.

Extraovarian germ cell tumors are very rare and their occurrence during pregnancy is exceptional. In this case report an abdominal mass was shown by ultrasonography, during a routine monitoring of a 26-year-old pregnant woman. The patient was left under radiological control in the following months in order to bring the pregnancy to term. A few months after the delivery, the patient underwent surgery and a diagnosis of extraovarian (abdominal) dysgerminoma was made. To the best of our knowledge, there are only 3 other case reports describing an extra-gonadal dysgerminoma occurring during pregnancy. The aim of this study was to report an extremely rare tumor, whose management can be challenging first because this neoplasm has some differences from its ovarian and testicular counterparts. Furthermore, the occurrence during pregnancy makes the multidisciplinary approach mandatory since 3 distinct but not independent entities are involved (tumor, mother and fetus).

Fractional Microablative CO2 Laser-Related Histological Changes on Vulvar Tissue in Patients With Genitourinary Syndrome of Menopause.

BACKGROUND AND OBJECTIVES: Fractional CO2 laser has been proposed as an effective treatment for the genitourinary syndrome of menopause (GSM). However, the effects of laser treatment on vulvar tissue have never been assessed. We aimed to assess histological changes related to fractional CO2 laser in vulvar tissue from GSM patients. STUDY DESIGN/MATERIALS AND METHODS: A single-center observational prospective cohort study was performed enrolling all GSM patients from July 2017 to October 2018. Patients underwent three outpatient vulvovaginal applications of fractional CO2 laser and vulvar biopsy before and after treatment. Rates of histological changes in vulvar tissue, the difference in means of Vulva Health Index (VuHI), Vaginal Health Index (VHI), Visual Analogue Scale scores for GSM symptoms, and procedure-related pain, and rate of patient's overall satisfaction with treatment were assessed. Univariate comparisons between continuous variables were performed by using the paired t-test (α error = 0.05). RESULTS: Of 20 enrolled patients, 18 underwent all laser applications, and 15 underwent both vulvar biopsies. 93.3% of patients showed remodeling of vulvar connective tissue; 80% showed improvement in vulvar epithelium trophism and 86.7% showed neovascularization. Differences in means between before and after treatment were significant for VuHI, VHI, and all GSM symptoms. Means ± standard deviation of the degree of pain at each laser application were 4.4 ± 0.9, 3.7 ± 1.6, and 2.9 ± 1.9. The rate of overall satisfaction with the treatment was 72.2%. CONCLUSIONS: Fractional CO2 laser leads to a restoration of the normal architecture of vulvar tissue, with significant improvement in GSM-related signs and symptoms, and overall satisfaction with the treatment in most GSM patients. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Meningiomas in Premenopausal Women: Role of the Hormone Related Conditions.

BACKGROUND: Several epidemiological and pathological findings suggest that the female sex hormones may influence the development of meningiomas. However, the role of pregnancy, oral contraceptives, and fertilization therapies is still controversial. METHODS: From the surgical series of 354 patients with meningiomas operated between 2006 and 2019, the group of 72 premenopausal women was separately considered. The tumor location, WHO grade, Ki67-labeling index (LI), progesterone receptor (PR) expression, and histological types were studied in premenopausal women with and without hormone-related conditions were compared. RESULTS: In this premenopausal group, 24 patients had hormone-related conditions, including use of oral contraceptives in 16, intrauterine fertilization in one, pregnancy in three, and tumors of the female reproductive system in four. The group of patients with hormone-related conditions, as compared to that with no hormone related conditions, showed slightly lower median age (38 versus 43 years) and no significant difference of meningioma location WHO grade, Ki 67-Li, PR expression and histological type. The clinical onset during pregnancy in three patients and tumor growth during contraceptive progesterone therapy in two others were evidenced. CONCLUSION: The biological behavior of meningiomas and their pathological findings, including PR expression, are not correlated with the different hormone related conditions in premenopausal female patients. Contraceptives and fertilization therapies, mainly with progesterone, should be avoided in patients with meningiomas.

Serrated lesions of the colon and rectum: Emergent epidemiological data and molecular pathways.

In 2010, serrated polyps (SP) of the colon have been included in the WHO classification of digestive tumors. Since then a large corpus of evidence focusing on these lesions are available in the literature. This review aims to analyze the present data on the epidemiological and molecular aspects of SP. Hyperplastic polyps (HPs) are the most common subtype of SP (70-90%), with a minimal or null risk of malignant transformation, contrarily to sessile serrated lesions (SSLs) and traditional serrated adenomas (TSAs), which represent 10-20% and 1% of adenomas, respectively. The malignant transformation, when occurs, is supported by a specific genetic pathway, known as the serrated-neoplasia pathway. The time needed for malignant transformation is not known, but it may occur rapidly in some lesions. Current evidence suggests that a detection rate of SP ≥15% should be expected in a population undergoing screening colonoscopy. There are no differences between primary colonoscopies and those carried out after positive occult fecal blood tests, as this screening test fails to identify SP, which rarely bleed. Genetic similarities between SP and interval cancers suggest that these cancers could arise from missed SP. Hence, the detection rate of serrated-lesions should be evaluated as a quality indicator of colonoscopy. There is a lack of high-quality longitudinal studies analyzing the long-term risk of developing colorectal cancer (CRC), as well as the cancer risk factors and molecular tissue biomarkers. Further studies are needed to define an evidence-based surveillance program after the removal of SP, which is currently suggested based on experts' opinions.