mucinous carcinoma of the rectum: a distinct

REVIEW

Mucinous carcinoma of the rectum: a distinctclinicopathological entity

M. Chand • S. Yu • R. I. Swift • G. Brown

Received: 16 June 2013 / Accepted: 18 November 2013 / Published online: 11 December 2013

� Springer-Verlag Italia 2013

Abstract

Purpose The definition of mucinous tumours relies on

quantification of the amount of mucus produced by neo-

plastic cells within the rectum. This has changed over the

years to include varying degrees of mucin production. The

inconsistency of diagnosis has led to conflicting reports in

the literature regarding clinical outcomes and treatment

response. A universally accepted definition and improved

imaging and surgical techniques in the last decade are now

challenging the traditional view of these tumours. The aim

of this review was to present the current evidence on the

clinicopathological characteristics of mucinous tumours of

the rectum.

Methods A systematic review was conducted using Pre-

ferred Reporting for Systematic Reviews and Meta-Anal-

yses guidelines. A literature search was performed using

the Ovid SP to search both EMBASE and MEDLINE

databases, Google Scholar and PubMed to find all studies

relating to mucinous carcinoma of the rectum. The search

dates were between 1 January 1965 and 1 March 2013.

Results Mucinous tumours comprise 5–20 % of all rectal

cancers and commonly present at a more advanced stage

and in younger patients. They are readily identified on

MRI, and the diagnosis is confirmed on histological ana-

lysis, demonstrating more than 50 % of extracellular mucin

within the tumour complex. They carry an overall worse

prognosis compared to adenocarcinoma of the same stage.

The response to oncological treatment remains

controversial.

Conclusion Mucinous tumours of the rectum are less well

understood than non-mucinous adenocarcinoma. This is

due to the inconsistent histopathological definitions of the

past making comparison of clinical outcome data difficult.

They remain challenging to treat and are associated with a

poor prognosis. A universally accepted definition and the

role of imaging techniques such as MRI to accurately

detect mucinous tumours are likely to lead to a better

understanding of these cancers.

Keywords Mucinous carcinoma � Rectum �Magnetic resonance imaging � Histopathology �Neoadjuvant chemoradiotherapy � Rectal cancer

Introduction

Mucinous carcinoma is a specific morphological subtype of

rectal cancer. It is characterised by an abundance of

extracellular mucin secreted by overactive neoplastic aci-

nar cells. Mucin-producing tumours have been described in

other sites such as breast, prostate, ovary and pancreas and

share some generic characteristics [1]. The abundance of

mucin within the tumour complex gives it a unique

appearance both histologically and radiologically. Contrast

this with signet cell carcinomas, which are a specific type

of mucin-producing tumour in which single neoplastic cells

demonstrate large amounts of intracytoplasmic mucin that

results in displacement of the nuclei.

Over the years, there has been debate on the precise

histological definition of mucinous tumours, which has

M. Chand (&) � S. Yu � G. Brown

Royal Marsden Hospital, Downs Road, Sutton SM2 5PT, UK

e-mail: [email protected]; [email protected]

M. Chand � G. Brown

Royal Marsden Hospital, Fulham Road, London, UK

M. Chand � R. I. Swift

Croydon University Hospital, London Road,

Croydon CR7 7YE, UK

123

Tech Coloproctol (2014) 18:335–344

DOI 10.1007/s10151-013-1099-3

made interpretation of studies problematic. The current

accepted definition, initially proposed by Jass, is based on

the presence of a minimum of 50 % of mucin to tumour

volume [2]. Previous studies have used varying propor-

tions of mucin to define these tumours [3, 4]. They rep-

resent 5–20 % of all colorectal cancers [5–8] and are

generally considered to have a worse prognosis than non-

mucinous tumours of the rectum. Furthermore, they are

also suggested to have a limited response to oncological

treatments.

This paper reviews the clincopathological characteristics

of mucinous rectal cancer and presents the evidence on

treatment response to determine whether these tumours

may be considered as a unique entity.

Methods

Identification of studies

An electronic search was carried out using MEDLINE

(1965–2013), EMBASE (1980–2013), CINAHL (1982–

2013) and the Cochrane library databases. The following

medical subject heading (MeSH) terms and keywords were

used as follows: The keywords ‘‘mucinous’’; ‘‘mucoid’’;

‘‘colloid’’; ‘‘colorectal’’; ‘‘rectal’’; ‘‘tumours/tumors’’;

‘‘cancer’’ were used in combination. The ‘‘related articles’’

function was used to broaden the search, and all

abstracts, studies and citations retrieved were scanned for

subject relevance. The latest date of this search was 1

March 2013.

Complete articles of all potentially relevant manuscripts

were retrieved and evaluated for inclusion. To be included

in this review process, additional references from the col-

lective libraries of the senior authors were identified.

Reference lists of all relevant publications were hand-

searched for additional studies missed by the search strat-

egy, and this cross-referencing continued until no further

relevant publications were identified.

Study inclusion criteria and data extraction

Study methodology was carried out in accordance with

the ‘‘Preferred Reporting for Systematic Reviews and

Meta-Analyses’’ (PRISMA) recommendations for

improving the standard of systematic reviews. Where

multiple studies describing the same patient population

were identified, the most recent publication was used

unless additional information was imparted by earlier

work (Fig. 1).

Fig. 1 Flowchart showing the

systematic methodology used to

extract articles for review

336 Tech Coloproctol (2014) 18:335–344

123

Results

Epidemiology and clinical characteristics

Mucinous carcinoma accounts for between 5 and 20 % of

all colorectal cancers [5–8]. It is relatively rare to find such

tumours in the rectum, being most commonly found in the

proximal colon. One of the largest studies examining the

outcomes of mucinous tumours investigated 16,991

patients and found that just over 18 % of all mucinous

tumours were found in the rectum compared with 29 % of

non-mucinous tumours [9]. A recent meta-analysis of

outcomes in mucinous colon cancer, which included some

studies with rectal tumours, reported that mucinous

tumours were more frequently found proximal to the

splenic flexure compared to non-mucinous adenocarcinoma

[10]. Conversely, mucinous tumours are more common

than non-mucinous in the proximal colon. A study using

the National Cancer Database in the USA reported that

60 % of mucinous tumours were right-sided compared to

42 % of non-mucinous tumours [11]. Consorti et al. [12]

conducted a prospective study of mucinous and non-

mucinous tumours and reported 31 % of mucinous tumours

in the rectum compared to 44.3 % non-mucinous.

There is a higher incidence in younger patients [13–15].

A study by Dozois et al. [16], which investigated the

characteristics of colon and rectal cancer in patients below

the age of 50, found that patients with mucinous tumours

had a mean age at presentation of 42.2 years. Furthermore,

rectal cancers were found to be more common below the

age of 50 (49.1 vs. 21.9 %). Other studies have shown

similar results [17, 18]. Wu and colleagues used a cut-off

of 39 years in their comparison of mucinous and non-

mucinous tumours, and although this included patients with

colonic cancer as well, they found mucinous tumours more

commonly in patients \39 years old [19]. A further study

of 2,089 patients (of which 144 had mucinous tumours)

reported a mean age at presentation of 54.2 ± 16.25 years.

This was statistically less than patients with non-mucinous

adenocarcinoma who had a mean age at presentation of

58.73 ± 13.62 years [20].

Morphology and pathological characteristics

Histological diagnosis remains the ‘‘gold standard’’. Mucin

produced by the tumour cells aggregates into ‘‘pools’’ or

‘‘lakes’’, which produce a distinctive pattern on haema-

toxylin and eosin stain (H&E stain). Although histopa-

thological detection of the mucinous component of

tumours is not particularly challenging, sufficient tissue is

required to make a diagnosis. Therefore, there may be

under-reporting using biopsy specimens due to insufficient

tissue [21], and definitive diagnosis is confirmed on ana-

lysis of the resection specimen (Fig. 2).

Although most tumours have the propensity to produce

some mucin, Parham was one of the first to describe

mucinous or colloid carcinoma in detail as a separate entity

defined by the amount of mucin produced by the tumour

cells [22]. He found that these tumours were associated

with a more aggressive behaviour and pattern of spread

than non-mucinous adenocarcinoma. A further study by

Fig. 2 a Histological micrograph showing areas of mucin within

tumour complex. The mucinous areas are seen as large vacuoles in

relation to the bowel wall and tumour. b Histological micrograph

showing a large mucin pool amongst the tumour complex

Tech Coloproctol (2014) 18:335–344 337

123

Symonds and Vickery reviewed the pathological charac-

teristics of mucinous tumours and found that the micro-

scopic appearance of these tumours is of particular interest

with regard to their behaviour [5]. They found that mucin

deposits comprise the main bulk of the tumour complex

and are lined by epithelial cells around their perimeter.

They proposed that the spread of mucin separated the

muscle bundles but upon reaching the perirectal fat showed

pooling. This may explain the perceived aggressiveness of

these tumours. One theory is that the tumour cells have the

ability to imbibe water causing swelling of the tumour

complex. As they splay the muscle structure and pass

through the layers of the bowel wall, they disseminate

tumour cells. This is similar to the pressure theory put

forward by Sugarbaker whereby the mucin exerts a pres-

sure effect on the bowel wall structure, thus disseminating

cancer cells into the peritoneal cavity that are taken up into

lymphatics [23].

Clinical outcomes and survival

Survival outcomes between mucinous and non-mucinous

tumours have been much studied. A recent meta-analysis of

mucinous cancers of the colon and rectum showed a worse

prognosis for mucinous cancers compared with non-

mucinous types, even when corrected for stage at presen-

tation [10]. Previously, suggestions had been made that any

difference in clinical outcomes between mucinous and non-

mucinous carcinomas were attributed to a more advanced

stage at presentation. There is a higher incidence of stage III

and IV disease associated with mucinous tumours. They are

more likely to have lymph nodes involvement in addition to

increased tumour penetration [11, 20, 24]. The association

with lymph node involvement has led to suggestions of

more radical dissections for this tumour subtype [25].

A study by Hyngstrom et al. [11] found that mucinous

subtype was only associated with worse survival outcomes

when the tumour was located in the rectum. The hazard

ratio (HR) of death was 1.22 (95 % CI 1.16–1.29), for

rectal cancers but a HR of 1.03 (95 % CI 1.00–1.06), for

colonic cancers. This contrasts with signet cell tumours (a

special type of mucinous tumour) who had an increased

risk of death regardless of tumour location.

In a study of 97 patients with mucinous colorectal

cancer who underwent surgery with curative intent, the

clinically significant predictive factors on multivariate

analysis included stage at diagnosis, mucinous histology,

tumour location, gender and age [26]. Mucinous tumours

were found to have a worse survival independent of other

factors. Curative surgery was defined as obtaining a mar-

gin-free resection; however, details on surgical technique

and whether surgery was based on principles of total

mesorectal excision (TME) were not provided.

One of the largest studies into the outcomes of

mucinous tumours that looked at over 160,000 patients did

show a survival advantage for non-mucinous tumours [9].

Overall, for all locations of colorectal cancer, mucinous

tumours had a significantly worse 5-year survival (58.1 vs.

62.9 %), and this was also apparent for rectal cancers

specifically.

One study found a difference in 5-year survival in stages

II and III but not for stages I and IV. Further, when com-

paring patients of all stages who had undergone supposed

‘‘curative’’ resection, the 5-year survival was 70 % for non-

mucinous tumours and 62 % for mucinous tumours; this

was considered statistically significant [20].

However, there are reports that have showed no survival

differences between mucinous and non-mucinous adeno-

carcinomas of the rectum. A prospective, case–control

study comparing survival outcomes of Dukes C or stage III

tumours showed that there was no significant difference in

overall survival at 5 years. For both groups, this was

approximately 50–55 % [12]. Although the study included

colon and rectal cancers, the survival analysis was pre-

dominantly rectal tumours.

A Canadian study also found no difference in survival

between mucinous and non-mucinous tumours independent

of tumour location [27]. However, a sub-analysis per stage

of presentation found that stage III mucinous tumours did

have a worse overall survival compared with non-mucinous

tumours of the same stage.

Radiological diagnosis and measuring response

Magnetic resonance imaging (MRI) has the ability to dif-

ferentiate mucinous tumours from non-mucinous tumours.

This is advantageous in being able to diagnose mucinous

carcinoma early in the treatment pathway rather than

relying on histological diagnosis following surgery. The

signal characteristics depend on imaging protocol—T1-

weighted images show low signal intensity, whereas on T2-

weighted images, there is a significant hyper-intense signal.

In contrast, non-mucinous tumours demonstrate interme-

diate signal intensity on T2 imaging. The difference in

signal characteristics is due to the abundant mucin com-

position [28, 29].

The signal and enhancement characteristics on MRI may

make it difficult to distinguish mucinous tumours from other

fluid-containing pathologies such as cysts, fluid collections

and even necrotic tumours [30]. Although it is unusual to

confuse these benign conditions with cancer during pre-

liminary imaging of the pelvis, the difficulty arises during

follow-up imaging after treatment. Figure 3 shows the signal

characteristics of mucinous tumour on MRI.

Allen et al. [31] studied the MRI features of rectal can-

cers and the changes following chemoradiotherapy. They


123

defined mucinous tumours on T2-weighted images as high

signal intensity, similar to that of obturator internus muscle.

The same areas showed a uniform hyper-intensity after

chemoradiation on T2-weighted images. However, there

were no other morphological changes or shrinkage seen

radiologically with persistent areas of high signal intensity.

Oberholzer correlated the radiological changes on MRI

following CRT with pathology in order to describe the

accuracy of MRI in predicting response in mucinous

tumours [32]. They found that more advanced mucinous

tumours (CRM to tumour distance of \5 mm) showed a

worse response to CRT in terms of down-staging than non-

mucinous tumours leading to increased rates of R1

resections. In addition, there was also disease progression

in mucinous tumours only (Fig. 4).

A sub-classification of mucinous tumours

Mucinous tumours may fall into one of three categories.

There are those tumours, which are diagnosed as mucinous

prior to any treatment and remain mucinous throughout

their course. For example, they are identified as mucinous

on biopsy and/or MRI as well as on the surgical resection

specimen. These tumours appear to have the worst prog-

nosis and increased risk of local recurrence [33, 34]. The

documentation of the extent of residual cellular mucin is

Fig. 3 a, b MRI showing a rectal cancer with focal areas of mucin. There is a difference in signal characteristics between the tumour itself and

the areas of mucin which have a higher signal. The heterogeneous nature of the signal is indicative of cellular mucin

Fig. 4 a, b MRI showing areas of mucin which have responded to chemoradiation. The homogeneous signal characteristics as depicted by the

arrow suggest an acellular component to the mucin which is thought to represent tumour response


123

important since the risk of tumour spillage from such

mucin pools will increase the risk of local recurrence.

A second group of tumours exist, which become

mucinous during treatment. These tumours may have

started out as non-mucinous and subsequently show mor-

phological change as a consequence of either natural dis-

ease progression or chemoradiotherapy. This group is of

particular interest as it may represent a specific type of

tumour, which behaves as non-mucinous adenocarcinoma

despite having the phenotype of mucinous carcinoma.

Nagtegaal et al. [35] studied a number of mucinous

tumours and found that those tumours that had become

mucinous following short-course radiotherapy (SCRT) had

a better prognosis than those tumours that were mucinous

prior to treatment.

Post-therapeutic change leading to mucinous differen-

tiation has previously been well documented; however, the

clinical significance of this is now better understood. For

example, on baseline imaging, such as MRI, this corre-

sponds to a tumour that is of entirely intermediate signal

intensity with no areas of high signal intensity mucin. After

neo-adjuvant chemoradiation or radiotherapy alone,

necrosis of the tumour can result in mucinous degeneration.

In such cases, degeneration of the tumour results in high

signal intensity pools within the previously documented

intermediate signal intensity tumour stroma, and can

therefore be interpreted as evidence of treatment response.

In a further study by Allen et al. [31] in which the MRI

features of rectal carcinoma were studied before and after

chemoradiation, an additional 4 tumours were added to the

original 7 tumours, which were identified as mucinous by

MRI. Tumours were classified as mucinous on signal

intensity of the supposed mucinous area having greater

signal intensity than the obturator internus muscle. Inter-

estingly, although chemoradiation may increase the degree

of mucinous differentiation, these tumours do show a

response to treatment. They show tumour regression and

down-staging, meaning that induced mucinous change does

not appear to be a poor prognostic factor. The European

Organisation for Research and Treatment of Cancer (EO-

RTC) trial investigated the effect of adding chemotherapy

to pre-operative radiotherapy and the role of adjuvant

chemotherapy in stages II and IV rectal cancer. As part of

the analysis, they found that in addition to there being an

increased proportion of mucinous tumours found following

neo-adjuvant treatment, this was further enhanced in the

group with chemo- and radiotherapy than just pre-operative

radiotherapy alone [36]. This phenomenon is not fully

understood; however, one explanation offered by the Col-

lege of American Pathologists is that mucinous change is a

feature of response to pre-operative treatment [33].

The final group of mucinous tumours are those that

demonstrate acellular mucin on histological analysis. The

relevance of acellular mucin remains controversial. A

recent analysis of 108 prospectively collected post-treat-

ment specimens showed acellular mucin pools in 16 cases.

The presence of acellular mucin pools had no impact on

recurrence-free survival [37]. Acellular mucin may be

regarded as a type of treatment response and not as residual

tumour although this is still contentious. Cellular mucin on

T2 imaging is hyper-intense but contains areas of more

intermediate signal corresponding to the histologically

demonstrated malignant cells, cords and vessels. After

treatment, the necrosis of these morphological features

results in the formation of acellular mucin—namely pools

of featureless high signal intensity fluid-like signal on the

T2-weighted images which when compared with pre-

treatment scans contain no or minimal intermediate signal

intensity. The clinical outcomes of these tumours that show

colloid or mucin pools with little or no tumour activity

have been studied by Rullier et al. [38]. They differ in

behaviour and morphology from pre-existing mucinous

tumours and commonly have a much greater component of

mucin in the tumour complex, sometimes as much as 80 %.

The pools of mucin are also less basophilic than pre-

existing mucin. The debate as to whether this variant of

mucin should be considered as complete response—

ypT0N0; or consider these mucin pools to contain residual

tumour continues. Rullier showed some similarities with

tumours that have shown down-staging and some similar-

ities with tumours that have shown no response at all. It

may be prudent not to consider mucin response as complete

response.

The effect of chemo/radiotherapy

Neo-adjuvant chemo/radiotherapy (CRT) is an integral part

of the management of rectal cancer. CRT may be given for a

combination of reasons based on the evidence of poor

prognostic factors. Several studies have shown that patients

with mucinous tumours respond more poorly to radiotherapy

than non-mucinous tumours. One such study of 136 patients

compared the outcome of 25 mucinous tumours with 111

non-mucinous tumours. Although the results showed

decreased down-staging in the mucinous group, this was not

seen to affect overall survival or disease-free survival [39].

Interestingly, there was a benefit for the mucinous tumours

that received neo-adjuvant CRT. None of the mucinous

tumour achieved complete response, but almost half were

down-staged by one stage. Sengul et al. [40] reported a sta-

tistically significant difference in tumour regression grade

(TRG) between the two subtypes and a much smaller

decrease in T and N staging. However, only 16 patients were

studied and the small numbers may account for the results.

The underlying biology of these tumours may explain their

different responses to oncological therapy.


123

Shin et al. [41] reported on the effectiveness of pre-

operative CRT on 23 patients with mucinous rectal cancer.

Seven patients showed minimal down-staging of one stage,

and one patient showed disease progression. There were no

cases of pathological complete response unlike the non-

mucinous group where this was the case in 16 % of

patients. Recurrence was not statistically significant, but

there was a difference in 5-year survival (64.8 vs. 79.8 %).

This was more apparent in more advanced stages of dis-

ease. They compared the response to CRT of 23 mucinous

tumours with 345 non-mucinous tumours. T-stage down-

staging was much worse in the mucinous group although

there was no difference in nodal down-staging. However,

the numbers of mucinous tumours in this study were again

small. A study by Qiu found that mucinous type along with

T4 stage on multivariate analysis negatively affected

tumour response [42]. These findings may be explained by

underlying gene expression which results in chemo-resis-

tivity. Enzymes that interfere with pyrimidine and plati-

num-based compounds are overexpressed in mucinous

tumours [43].

Mucin or colloid production by a tumour may represent

a measure of response to neo-adjuvant treatment. The

production of mucin without the presence of tumour cells is

a common phenomenon after radiotherapy in particular

[32, 37, 44–46]. Rullier et al. [38] found that 39 patients

out of 200 demonstrated a colloid response to pre-operative

radiotherapy, of which the vast majority (n = 34) showed

no regression in tumour grade. But this is a separate phe-

nomenon to radiation causing mucinous tumours. A sig-

nificant proportion of tumours that arise following pelvic

irradiation for other cancers are seen to be mucinous—

approximately 25 % [47].

Yet the role of adjuvant therapy in the treatment for

mucinous tumours may be changing. Previous studies have

suggested that mucinous tumours do not response well to

5-FU-based chemotherapy after surgery [48, 49]. Negri

et al. [49] studied the effect of 5-FU-based adjuvant

chemotherapy on survival in colorectal cancers. Median

overall survival was 11.8 vs. 17.9 months, which showed

statistical significance on multivariate analysis. The view

had been that mucinous tumours show little response to

adjuvant therapy, but this may have been due to inade-

quate oncological surgery. The acceptance of TME in

rectal cancer has changed outcomes for all stages of dis-

ease. More recent studies have accounted for this factor as

a reason for local, and in the case of nodal disease, distant

recurrence. A recent report by Catalano studying the

outcomes of mucinous colon cancer in stage II and stage

III disease has shown a survival benefit for patients with

mucinous tumours that are offered adjuvant chemotherapy.

This was shown on multivariate analysis with a hazard

ratio of 2.73 [50].

The biology of mucinous rectal cancer

Cancer of the colon and cancer of the rectum demonstrate

many biological and molecular differences. This raises the

possibility of different pathways governing tumorigenesis

in these malignancies. The differences in clinicopatholog-

ical such as location of tumour may be a reflection of the

underlying molecular profiles or different embryological

origin of the different parts of the gut.

Mucin is produced as a protein by a group of specific

mucin-producing genes, which are prefixed by the name—

‘‘MUC’’. There are several genes within this family, and

they are able to produce two distinct types of mucin—a

transmembranous type and a secretory type. These genes

are not part of a gene family in the truest sense of the term as

their gene products vary dramatically in their structure and

function. However, it is the characterisation of specific parts

of the gene products, which have led to them sharing the

name ‘‘MUC’’. The two types of mucins are classified

according to whether they are secreted mucins or trans-

membranous mucins. MUC1 produces a transmembranous

mucin, which is associated with a poor prognosis. MUC1

expression is low in mucinous tumours but in those tumours

that show overexpression, there is an association with worse

prognosis and chemoresistivity to certain chemotherapy

agents [51]. Conversely, the MUC5 gene has been shown to

confer a survival benefit [52] and unusually is overexpres-

sed in some mucinous tumours. However, MUC5 also

shows a greater association with proximal location of the

colorectum, which may explain the poor prognosis of

mucinous rectal cancer; that this may be due to relative

underexpression of MUC5. MUC2 on the other hand is

almost exclusively associated with mucinous tumours. It

may play a role in p53 mutation. There are also reports of

MUC2 and liver metastases [53]. Kim et al. [54] studied the

prevalence and expression of specific mucin core proteins in

a variety of colorectal polyps in addition to mucinous and

non-mucinous tumours. MUC2 and MUC5 were most fre-

quently found in mucinous tumours and villous adenomas.

In addition to the pattern of mucin gene expression,

mucinous tumours also express other distinct genetic features.

For example, there is a lower frequency of p53 mutations and

conversely a higher frequency of K-Ras mutations [55]. p53

mutations are interesting as they are associated with rectal

cancers but not common in mucinous subtype [56, 57]. There

may be heterogeneity in p53 mutations that accounts for dif-

ferent phenotypic effects on individual tumours.

Discussion

The results of this study have highlighted specific charac-

teristics of mucinous rectal cancer, which distinguishes it


123

from non-mucinous disease. These tumours are more

commonly found in the proximal colon; however, when

present in the rectum, they appear to behave more

aggressively. The location of tumours may reflect the

underlying molecular profile although this has not been

definitively proven. It is also unclear as to whether fair

comparisons can be made between the clinical outcomes of

colon and rectal cancer; the survival outcomes, response to

chemotherapy and ability of the tumour to metastasise are

not immediately comparable between non-mucinous

tumours. The more aggressive behaviour of mucinous

rectal, rather than colonic tumours, may simply be due to

anatomical location and that the mechanism of spread

described above has a more immediate effect in the narrow

confines of the pelvis.

The results of the demographic profile of mucinous

tumours consistently showed that they are more common in

younger patients. Different studies used varying cut-offs;

however, the trend was that these tumours manifest earlier in

younger patients. Whilst the explanation to this observation

will most likely lie in the genetic make-up of these tumours,

this may simply reflect their aggressive nature. Whilst non-

mucinous tumours may take longer to progress through

carcinogenesis, mucinous tumours may accelerate through

this pathway and thus present earlier. Another explanation

may be related to the stage at presentation. Early tumours that

are confined to the bowel wall may not present with symp-

toms compared to more locally advanced tumours. Mucin-

ous tumours are more commonly seen at an advanced stage,

which may be due to aggressive spread through the bowel

wall causing symptoms requiring investigation.

The actual response of these cancers to oncological

treatment is becoming clearer. The challenge over the years

in both mucinous and non-mucinous tumours with regard

to survival outcomes following varying types of oncolog-

ical treatment has been interpreting the results in the light

of pathological scrutiny of the surgical technique. Several

of the historical studies did not include operative details or

grade the quality of the specimens. The importance of this

has been highlighted by Quirke [58]. Therefore, attempting

to apply the results of these studies, which do not describe

surgical technique and histopathological audit, may not be

relevant to today’s practice. However, more recent studies,

which include TME surgery and note the importance of a

positive CRM, have challenged the traditional view of

chemoresistance. And whilst the survival benefit of adju-

vant chemotherapy has not been specifically documented in

any high-quality randomised trial for this type of rectal

cancer, it is becoming clear that adjuvant chemotherapy

may indeed have a role to play in mucinous cancer.

Equally, whether pre-operative radiotherapy leads to down-

staging is another issue, which must be resolved with

greater accuracy. If these issues do become clearer, it will

allow clinicians to decide whether and when radio- or

chemotherapy should be given and what the survival ben-

efit will be.

The acceptance of TME as the optimal surgical tech-

nique for rectal cancer has helped standardise practise. A

discussion on the modifications of this technique is beyond

the scope of this review; however, the association of an

increased nodal burden in mucinous disease should not

impact on technique. If the principles of TME are followed

and the mesorectal nodes are removed en-bloc with the

specimen, there should be prognostic relevance to local

recurrence although this may be a stronger indication for

adjuvant chemotherapy.

Conclusion

Mucinous tumours of the rectum remain difficult to treat

and are still associated with worse survival outcomes than

non-mucinous tumours. However, with a universally

accepted definition, better pre-operative detection using

MRI and high-quality oncological surgery, we may see

improvement in outcomes in the future. This will aid fur-

ther study of these subtypes and allow clinicians to risk

stratify patients in terms of oncological treatment.

Acknowledgments Authors received fund from NIHR BRC Pro-

gramme Grant Royal Marsden Hospital.

Conflict of interest None.

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