Malignant polyps

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Definition

A malignant polyp (MPMalignant polyp) is an adenoma in which neoplastic cells have invaded through the muscularis mucosa into the submucosa. It is therefore a colorectal cancer, and such invasion is associated with the possibility of spread to locoregional lymph nodes and distant organs.[1] Lesions without submucosal invasion, even in the presence of high-grade dysplasia (HGDHigh grade dysplasia), have negligible potential for distant spread and are not considered MPs.

Previously, terms such as ‘intramucosal carcinoma’ and ‘carcinoma in situ’ were occasionally used to describe HGDHigh grade dysplasia. These terms should no longer be used, due to the therapeutic confusion they may create and the potential for unnecessary surgery and over-surveillance. Such lesions are not MPs.[2]

Background

Malignant polyps constitute less than 5% of all colorectal adenomas and approximately 40–60% of stage I colorectal cancers.[3][4][5] Their occurrence is expected to rise as the proportion of stage I cancer increases, in the setting of the National Bowel Cancer Screening Program. The clinicopathological significance of the MPMalignant polyp usually arises after endoscopic polypectomy, when histology confirms invasive malignancy. The question becomes whether endoscopic resection alone is sufficient treatment or if surgical resection of the affected bowel segment with lymph node clearance is necessary. Ultimately, the treatment decision is based on an estimated risk of residual cancer, risk of surgical complications and informed patient choice.

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Overview of evidence (non-systematic literature review)

Endoscopic considerations

Invasive disease is rare in polyps < 10mm. Recognising the endoscopic appearances of early submucosal invasion (SMISubmucosal invasion) is important to optimise treatment outcomes. Suspicion of SMISubmucosal invasion may dictate a change in the therapeutic strategy to optimise the possibility of en-bloc and R0 excision, including endoscopic mucosal resection, endoscopic sub-mucosal dissection (ESDEndoscopic submucosal dissection) or surgery. Whilst large pedunculated polyps may contain cancer, this is often not evident or recognised prior to endoscopic resection and because the lesion’s pedicle provides a natural resection margin, conventional polypectomy proceeds as it generally would, ensuring adequate clearance from the neoplastic head of the lesion. Lesion assessment is thus most important for flat and laterally spreading lesions. It is divided into an overview and focal interrogation phase.[6]

In overview, lesions are classified according to the Paris system 1 and surface morphology which allows broad stratification for the risk of SMISubmucosal invasion. Homogeneous flat (0–11a) granular lesions have a low risk of SMISubmucosal invasion of <1%, whilst the less frequent flat non-granular lesions with a depressed component (0–11a + c) or nodule (0–11a + 1s) are at increased risk for SMISubmucosal invasion, generally >20%. Gross features that suggest SMISubmucosal invasion include presence of ulceration, firm or hard surface, friability and effacement or distortion of the surrounding colonic folds.[7][1][8] Increasing size is generally associated with an increased risk of SMISubmucosal invasion, but the use of this parameter alone is too simplistic and even very extensive lesions can be non-invasive, for example, homogeneous granular 0–11a laterally spreading lesions (LSLs) of the proximal colon.

Once overview assessment is complete, focal interrogation is used to examine areas of depression or nodularity looking for a disruption in the mucosal pit or microvascular pattern. Benign lesions should generally have a homogeneous surface pattern. With SMISubmucosal invasion one may identify a demarcated zone of altered or disrupted pit or microvascular pattern (e.g. Kudo pit pattern type V).[9][10] Approximately 50% of large sessile and laterally spreading polyps with cancer do not disclose overt features of SMISubmucosal invasion, so called “covert SMISubmucosal invasion”. In a large multicentre Australian study of over 2000 lesions, once overt SMISubmucosal invasion cases were excluded, features associated with covert SMISubmucosal invasion were rectosigmoid location, protuberant morphology (Paris 0-Is and 0-IIa+Is) and increasing size (>40mm).[6] Lesions suspected of harbouring SMISubmucosal invasion may not be suitable for endoscopic excision. Piecemeal resection prevents histopathological assessment of complete excision and interferes with the prediction of lymph node metastasis.[9] In experienced hands, ESDEndoscopic submucosal dissection may be an option but formal surgical resection is often required.

If malignant histology is suspected, tattoo placement to enable precise future localisation of the polypectomy site is recommended. Tattoo placement may also be useful for hard-to-see polyps being referred for expert endoscopic removal; in this instance, the tattoo must be sufficiently distant to avoid encroachment and potential fibrosis at the polyp base.

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Pathologic considerations

Although the endoscopist decides if endoscopic/macroscopic resection is complete at the time of polypectomy, histological features are the most important determinant of the risk of residual disease. Given evidence of significant interobserver variation, review by a second pathologist with special interest in gastrointestinal pathology should be considered, especially where the diagnosis is unclear or difficult.[11] Consistently, the most important parameters suggesting a risk of lymph node involvement are an inadequate margin, poorly differentiated carcinoma grade and lymphovascular invasion.[1][12][13] Each of these factors alone may confer a risk of 5-20% for lymph node involvement. Other parameters reported to be important include depth of invasion (especially for sessile lesions), tumour width, tumour budding, cribriform architectural pattern, distal location (distal colon and rectum) and mucinous histology. Multiple high-risk features often coexist in a given case. Assessment of high-risk parameters can be especially difficult with sessile polyps, which present difficulties with orientation and are often fragmented. Many of the important parameters (e.g. depth of invasion by Haggitt classification for pedunculated polyps and Kikuchi classification for sessile polyps), are not routinely reported by all laboratories, yet are prognostically important.[3] Synoptic reporting assists standardisation. Variation amongst reported series means estimating absolute risk based on histopathologic findings is also difficult, but co-existent unfavourable features increases risk.

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Who needs formal surgical resection?

The evidence basis for managing MPs relies entirely on retrospective series, with no available randomised trials. Nonetheless, low-risk lesions, characterised by superficial submucosal invasion (<1000 microns), clear resection margins, well- or moderate- degrees of histological differentiation (i.e., not poor) and absence of lymphovascular invasion, are best served by endoscopic resection alone, which is almost always curative.[1][13] In these cases, the risks of surgical complications far outweigh the chance of residual lymph node involvement. There is significant recent support for a resection margin of ≥1mm (as opposed to ≥2mm) as being adequate.[3][14][15][16][17] However, there remains controversy in cases where clearance at the margin is uncertain; a population-based series from The Netherlands found the only independent risk factor predicting long term cancer recurrence to be a positive resection margin[5] whilst a Brisbane series found that in the absence of other high risk histological factors, a positive resection margin may only require further local excision rather than oncological colonic resection.[18]

Whilst defining low risk MPs is now clear, the recent literature continues to show some variation in identifying high risk factors for residual cancer. For instance, the Brisbane series identified greater width and depth of malignant invasion, poor differentiation and a cribriform architecture as high risk features,[18] an English series found depth of invasion, but not lymphovascular invasion, to be important,[3] a Japanese series did not find depth of invasion per se to be important[19] and a population-based series from Modena found lymphovascular invasion to be important.[20] Tumour budding was considered an important risk factor in a single-centre Polish study[17] and a systematic review found lymphatic invasion, depth of invasion, tumour budding and poor differentiation all to be important factors, each with a relative risk of approximately 5-fold for lymph node invasion.[21]

Even in the presence of high risk pathological criteria, over 70-85% of surgical resections will offer no clinical benefit as the absolute risk of residual cancer is small. In the Brisbane series of 239 consecutive MPs, 59% of cases ultimately underwent surgical resection due to high risk indications and, of these, only 6.4% had residual disease in bowel wall and 8.6% were found to have lymph node involvement (1% had disease in both bowel wall and lymph nodes). Thus, approximately 85% of operated cases may not have needed surgery.[18] Furthermore, a proportion of cases, who undergo surgery and presumably adjuvant therapy, will still develop metastatic cancer, as can be expected for nodal colorectal cancer (stage III).[5][20] The series from England also found that 1% of MPMalignant polyp cases already had distant metastases at diagnosis.[3]

The recommended surgery when high-risk pathologic criteria are identified is a complete oncological resection with appropriate lymph node clearance. However, the decision for surgery must balance the risk of residual cancer, which only involves the minority of cases, with patient co-morbidities. Cardiopulmonary factors are an important cause of mortality in long term follow-up of patients treated for MPs as shown in New Zealand.[22] Whilst a US population-based series using the Surveillance, Epidemiology and End Results (SEERSurveillance, Epidemiology and End Results) database showed surgery to improve cancer-free survival compared to endoscopic therapy alone,[23] no difference in overall survival was seen in an earlier population-based series with the SEERSurveillance, Epidemiology and End Results database involving a different patient set[24] or in a Korean series.[16] However, selection bias does not permit accurate causal attribution of survival to any therapeutic strategy per se, especially as surgery is likely to be avoided in patients with substantial co-morbidities.

In the most comprehensive review to date,[1] estimates of the risk of residual cancer are presented in tabular form and include resection margin <1mm (>20% risk), deep invasion (>20% risk), poor differentiation (8–15% risk), lymphovascular invasion (5-10% risk) and tumour budding (<5% risk). Online risk calculators are available, examples of which can be found at Prediction in Surgery (St Mark's Lymph Node Positivity Model) or the T1 Colorectal Cancer Working Group. Estimations such as these are necessary to counterbalance surgical risk. An excellent set of online surgical risk assessment calculators can also be found at Prediction in Surgery and includes the ColorectalReferring to the large bowel, comprising the colon and rectum. Physiologic and Operative Severity Score for the Enumeration of Mortality and Morbidity (CR-POSSUM) and Association of Coloproctology of Great Britain and Ireland (ACPGBIAssociation of Coloproctology of Great Britain and Ireland) calculators. A particularly difficult surgical decision arises for very low rectal lesions, where the appropriate oncological operation is an abdominoperineal resection necessitating a permanent colostomy. In such cases, a compromise is an extended local excision (e.g. transanal endoscopic microsurgery) if the only issue is an inadequate clearance margin without any other high risk feature.

Thus, the management of MPs requires review by a multidisciplinary team consisting of endoscopist, pathologist and surgeon as a minimum. In the private setting this may still occur, albeit potentially on a less formal basis. Ideally, individuals and institutions should contribute to a national prospective database. Risks of residual and nodal cancer must be estimated, surgical risk needs to be assessed and final decisions only made after open discussion with the patient.

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Surveillance for malignant polyps

Post-polypectomy colonoscopic surveillance for MPs is based on limited evidence. If the resection margin is clear, follow up should not be for local recurrence but for detection of metachronous adenomas and cancer. Hence, surveillance should be consistent with that for post-operative surveillance after curative surgery.[25] If there is uncertainty about endoscopic clearance and surgery is not performed, a reasonable interval for reinspection is at 3 months.[1]

Future directions

A substantial majority of MPs with high risk criteria do not have residual or nodal cancer at surgery. For these patients, endoscopic polypectomy alone would have sufficed and most of these cases have therefore undergone “unnecessary” surgery. Histopathological assessment alone has been unable to differentiate those who do and do not have residual cancer. It is unlikely that prospective randomisation will add much further insights given that patients refusing or unsuitable for surgery have already provided some understanding of the natural history of high risk cases. Technological advances such as functional (not anatomical) imaging or molecular techniques (e.g. circulating tumour DNADeoxyribonucleic acid detection) will be needed to improve patient selection for further surgery.

Improved endoscopic prediction of MPs with technological advances in endoscopic instruments and techniques may enable more successful en-bloc endoscopic polypectomies and better preservation of resection margins. Appropriate patient selection for more complex endoscopic submucosal dissection rather than the more common endoscopic mucosal resection may also improve pathological confirmation of clear resection margins.

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Practice Points

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

Endoscopists should be familiar with endoscopic appearances suggestive of a malignant polyp.

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

Removal of polyps likely to be malignant should be en-bloc or patients should be referred to a centre specialising in endoscopic excision of large and flat polyps.

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

Tattoos should be applied 2–3cm distal to the polypectomy site if future site localisation or surgery is necessary.

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

Malignant polyps should be reviewed by a second pathologist with a specialist gastrointestinal interest where histological diagnosis is unclear or difficult. Multidisciplinary review and management (endoscopist, pathologist and surgeon as a minimum) is appropriate in public and private settings although the nature may differ.

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

Standardised synoptic reporting should be used to assist clinical decision making (structured reporting protocols are available at the Royal College of Pathologists of Australasia website).

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

Low-risk malignant polyps have all of the following features: superficial submucosal invasion (<1000 microns), moderate or well differentiated histology, no lymphovascular invasion, clear margins and no other risk features. In these cases, where the endoscopist is certain that the lesion has been completely removed, then the neoplasm should be considered cured by endoscopic polypectomy.

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

Polyps that do not satisfy low risk criteria or have other histological risk features (often not routinely reported) including: malignant invasion depth >2mm, invasion width >3mm, tumour budding and cribriform architecture, should be considered at risk of harbouring residual bowel wall cancer or lymph node metastases. A magnitude of the risk should be estimated and the need for formal surgical resection considered.

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

Cases considered for surgery must have an assessment of surgical risk using validated surgical risk scoring systems, e.g. Risk Prediction in Surgery.

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

A discussion of risk of residual cancer balanced against risk of surgery must occur with the patient to determine ultimate management choice.

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

Multi-disciplinary management and audit are important.

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

Surveillance recommendations for a T1 adenocarcinoma as per 2017 Australian Clinical practice guidelines for the prevention, early detection and management of colorectal cancer should be followed for completely resected malignant polyps.

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

A patient who has had potential incomplete endoscopic resection of a malignant polyp not undergoing surgery should undergo repeat colonoscopy to assess recurrence at an interval of 3 months.

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References

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