A malignant polyp (MP) 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. Lesions without submucosal invasion, even in the presence of high-grade dysplasia (HGD), 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 HGD. 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.
Malignant polyps constitute less than 5% of all colorectal adenomas and approximately 40–60% of stage I colorectal cancers. 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 MP 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.
Overview of evidence (non-systematic literature review)[edit source]
Endoscopic considerations[edit source]
Invasive disease is rare in polyps < 10mm. Recognising the endoscopic appearances of early submucosal invasion (SMI) is important to optimise treatment outcomes. Suspicion of SMI 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 (ESD) 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.
In overview, lesions are classified according to the Paris system 1 and surface morphology which allows broad stratification for the risk of SMI. Homogeneous flat (0–11a) granular lesions have a low risk of SMI 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 SMI, generally >20%. Gross features that suggest SMI include presence of ulceration, firm or hard surface, friability and effacement or distortion of the surrounding colonic folds. Increasing size is generally associated with an increased risk of SMI, 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 SMI one may identify a demarcated zone of altered or disrupted pit or microvascular pattern (e.g. Kudo pit pattern type V). Approximately 50% of large sessile and laterally spreading polyps with cancer do not disclose overt features of SMI, so called “covert SMI”. In a large multicentre Australian study of over 2000 lesions, once overt SMI cases were excluded, features associated with covert SMI were rectosigmoid location, protuberant morphology (Paris 0-Is and 0-IIa+Is) and increasing size (>40mm). Lesions suspected of harbouring SMI may not be suitable for endoscopic excision. Piecemeal resection prevents histopathological assessment of complete excision and interferes with the prediction of lymph node metastasis. In experienced hands, ESD 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.
Pathologic considerations[edit source]
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. Consistently, the most important parameters suggesting a risk of lymph node involvement are an inadequate margin, poorly differentiated carcinoma grade and lymphovascular invasion. 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. 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.
Who needs formal surgical resection?[edit source]
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. 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. 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 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.
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, an English series found depth of invasion, but not lymphovascular invasion, to be important, a Japanese series did not find depth of invasion per se to be important and a population-based series from Modena found lymphovascular invasion to be important. Tumour budding was considered an important risk factor in a single-centre Polish study 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.
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. 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). The series from England also found that 1% of MP cases already had distant metastases at diagnosis.
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. Whilst a US population-based series using the Surveillance, Epidemiology and End Results (SEER) database showed surgery to improve cancer-free survival compared to endoscopic therapy alone, no difference in overall survival was seen in an earlier population-based series with the SEER database involving a different patient set or in a Korean series. 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, 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 Colorectal Physiologic and Operative Severity Score for the Enumeration of Mortality and Morbidity (CR-POSSUM) and Association of Coloproctology of Great Britain and Ireland (ACPGBI) 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.
Surveillance for malignant polyps[edit source]
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. If there is uncertainty about endoscopic clearance and surgery is not performed, a reasonable interval for reinspection is at 3 months.
Future directions[edit source]
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 DNA 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.
Practice Points[edit source]
Endoscopists should be familiar with endoscopic appearances suggestive of a malignant polyp.
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.
Tattoos should be applied 2–3cm distal to the polypectomy site if future site localisation or surgery is necessary.
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).
Cases considered for surgery must have an assessment of surgical risk using validated surgical risk scoring systems, e.g. Risk Prediction in Surgery.
A discussion of risk of residual cancer balanced against risk of surgery must occur with the patient to determine ultimate management choice.
Multi-disciplinary management and audit are important.
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.
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.
- Williams JG, Pullan RD, Hill J, Horgan PG, Salmo E, Buchanan GN, et al. Management of the malignant colorectal polyp: ACPGBI position statement. Colorectal Dis 2013 Aug;15 Suppl 2:1-38 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23848492.
- Rex DK, Hassan C, Bourke MJ. The colonoscopist's guide to the vocabulary of colorectal neoplasia: histology, morphology, and management. Gastrointest Endosc 2017 Aug;86(2):253-263 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28396276.
- Gill MD, Rutter MD, Holtham SJ. Management and short-term outcome of malignant colorectal polyps in the north of England(1). Colorectal Dis 2013 Feb;15(2):169-76 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22709241.
- Reggiani-Bonetti L, Di Gregorio C, Pedroni M, Domati F, Barresi V, Marcheselli L, et al. Incidence trend of malignant polyps through the data of a specialized colorectal cancer registry: clinical features and effect of screening. Scand J Gastroenterol 2013 Nov;48(11):1294-301 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24073745.
- Belderbos TD, van Erning FN, de Hingh IH, van Oijen MG, Lemmens VE, Siersema PD. Long-term Recurrence-free Survival After Standard Endoscopic Resection Versus Surgical Resection of Submucosal Invasive Colorectal Cancer: A Population-based Study. Clin Gastroenterol Hepatol 2017 Mar;15(3):403-411.e1 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27609703.
- Burgess NG, Hourigan LF, Zanati SA, Brown GJ, Singh R, Williams SJ, et al. Risk Stratification for Covert Invasive Cancer Among Patients Referred for Colonic Endoscopic Mucosal Resection: A Large Multicenter Cohort. Gastroenterology 2017 Sep;153(3):732-742.e1 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28583826.
- Moss A, Bourke MJ, Williams SJ, Hourigan LF, Brown G, Tam W, et al. Endoscopic mucosal resection outcomes and prediction of submucosal cancer from advanced colonic mucosal neoplasia. Gastroenterology 2011 Jun;140(7):1909-18 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21392504.
- Ferlitsch M, Moss A, Hassan C, Bhandari P, Dumonceau JM, Paspatis G, et al. Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy 2017 Mar;49(3):270-297 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28212588.
- Klein A, Bourke MJ. Advanced polypectomy and resection techniques. Gastrointest Endosc Clin N Am 2015 Apr;25(2):303-33 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25839688.
- Burgess NG, Bahin FF, Bourke MJ. Colonic polypectomy (with videos). Gastrointest Endosc 2015 Apr;81(4):813-35 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25805461.
- Davenport A, Morris J, Pritchard SA, Salmo E, Scott M, Haboubi NY. Interobserver variability amongst gastrointestinal pathologists in assessing prognostic parameters of malignant colorectal polyps: a cause for concern. Tech Coloproctol 2016 Sep;20(9):647-52 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27522597.
- Benson AB 3rd, Bekaii-Saab T, Chan E, Chen YJ, Choti MA, Cooper HS, et al. Rectal cancer. J Natl Compr Canc Netw 2012 Dec 1;10(12):1528-64 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23221790.
- Aarons CB, Shanmugan S, Bleier JI. Management of malignant colon polyps: current status and controversies. World J Gastroenterol 2014 Nov 21;20(43):16178-83 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25473171.
- Butte JM, Tang P, Gonen M, Shia J, Schattner M, Nash GM, et al. Rate of residual disease after complete endoscopic resection of malignant colonic polyp. Dis Colon Rectum 2012 Feb;55(2):122-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22228153.
- Naqvi S, Burroughs S, Chave HS, Branagan G. Management of colorectal polyp cancers. Ann R Coll Surg Engl 2012 Nov;94(8):574-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23131228.
- Kim JB, Lee HS, Lee HJ, Kim J, Yang DH, Yu CS, et al. Long-Term Outcomes of Endoscopic Versus Surgical Resection of Superficial Submucosal Colorectal Cancer. Dig Dis Sci 2015 Sep;60(9):2785-92 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25586088.
- Nałęcz-Janik J, Zagórowicz E, Bartnik W, Jarosz D, Pachlewski J, Butruk E, et al. Outcomes of colonoscopic polypectomy for malignant adenomas: a prospective 30‑year cohort study from a single center (STROBE 1a). Pol Arch Med Wewn 2015;125(4):272-81 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25764127.
- Brown IS, Bettington ML, Bettington A, Miller G, Rosty C. Adverse histological features in malignant colorectal polyps: a contemporary series of 239 cases. J Clin Pathol 2016 Apr;69(4):292-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26424814.
- Yoshii S, Nojima M, Nosho K, Omori S, Kusumi T, Okuda H, et al. Factors associated with risk for colorectal cancer recurrence after endoscopic resection of T1 tumors. Clin Gastroenterol Hepatol 2014 Feb;12(2):292-302.e3 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23962552.
- Di Gregorio C, Bonetti LR, de Gaetani C, Pedroni M, Kaleci S, Ponz de Leon M. Clinical outcome of low- and high-risk malignant colorectal polyps: results of a population-based study and meta-analysis of the available literature. Intern Emerg Med 2014 Mar;9(2):151-60 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22451095.
- Bosch SL, Teerenstra S, de Wilt JH, Cunningham C, Nagtegaal ID. Predicting lymph node metastasis in pT1 colorectal cancer: a systematic review of risk factors providing rationale for therapy decisions. Endoscopy 2013 Oct;45(10):827-34 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23884793.
- Fischer J, Dobbs B, Dixon L, Eglinton TW, Wakeman CJ, Frizelle FA, et al. Management of malignant colorectal polyps in New Zealand. ANZ J Surg 2017 May;87(5):350-355 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27062541.
- Mounzer R, Das A, Yen RD, Rastogi A, Bansal A, Hosford L, et al. Endoscopic and surgical treatment of malignant colorectal polyps: a population-based comparative study. Gastrointest Endosc 2015 Mar;81(3):733-740.e2 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25708762.
- Cooper GS, Xu F, Barnholtz Sloan JS, Koroukian SM, Schluchter MD. Management of malignant colonic polyps: a population-based analysis of colonoscopic polypectomy versus surgery. Cancer 2012 Feb 1;118(3):651-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21751204.
- Calderwood AH, Lasser KE, Roy HK. Colon adenoma features and their impact on risk of future advanced adenomas and colorectal cancer. World J Gastrointest Oncol 2016 Dec 15;8(12):826-834 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28035253.