G a s t r o i n t e s t i n a l I m a g i n g • R ev i ew

Wnorowski et al.
Imaging Features of Mucin-Containing Rectal Carcinomas

Gastrointestinal Imaging
Review

Mucin-Containing Rectal
FOCUS ON:

Carcinomas: Overview of Unique

Clinical and Imaging Features
Amelia M. Wnorowski1 OBJECTIVE. The purpose of this study is to review the unique clinical and imaging fea-
Christine O. Menias 2 tures of mucin-containing rectal carcinomas.
Perry J. Pickhardt 3 CONCLUSION. Mucinous rectal carcinoma is an uncommon tumor subtype with a
David H. Kim 3 worse prognosis. At MRI, it is marked by T2-hyperintense extracellular mucin. Difficulty in
Amy K. Hara2 distinguishing cellular from acellular mucin and persistent tumor bulk can cause errors at re-
staging. Signet ring cell carcinoma contains intracellular mucin. The classic imaging appear-
Meghan G. Lubner 3
ance is rectal linitis plastica. Both tumor subtypes have a unique metastatic pattern.
Wnorowski AM, Menias CO, Pickhardt PJ, Kim DH,
ucin-containing rectal tumors was first described in 1923 [6] and is defined

M
Hara AK, Lubner MG
can be classified into three dis- by the World Health Organization as great-
American Journal of Roentgenology

tinct types, two of which are un-
common primary subtypes of
rectal carcinoma and one of which is encoun-
tered as a response to treatment. We consider
mucinous carcinoma and signet ring cell car-
cinoma, two separate histologic subtypes of
rectal cancer, as the first two types [1]. Muci-
Keywords: MRI, mucinous rectal carcinoma, rectal nous carcinoma contains extracellular mucin
cancer, signet ring cell carcinoma
at the time of diagnosis, before any treatment,
doi.org/10.2214/AJR.18.20864 whereas signet ring cell carcinoma contains
intracytoplasmic mucin. Mucinous and signet
Received November 7, 2018; accepted after revision ring cell carcinomas are considered distinct
February 10, 2019. histologic entities by the World Health Orga-
P. J. Pickhardt is an adviser to Bracco and a shareholder
nization [1], though signet ring cells can also
in Elucent, SHINE, and Cellectar. D. Kim is a shareholder occur within mucinous carcinomas (i.e., mu-
in Elucent and Cellectar. A. K. Hara has a licensure cinous carcinoma with signet ring cells) [2].
agreement with GE Healthcare for CT colonography This is considered separate from true signet
software. M. G. Lubner has received prior grant funding
ring cell carcinoma, which does not contain
to her institution from Philips and Ethicon.
extracellular mucin [2]. The third type of mu-
Based on a presentation at the Radiological Society of cin-containing rectal tumor encompasses tu-
North America 2017 annual meeting, Chicago, IL. mors that are originally nonmucinous but de-
1
velop acellular mucin pools as a response to
Department of Radiology, University of Maryland School
therapy. The distinctions among these three
of Medicine, 22 S Greene St, Baltimore, MD 21201.
Address correspondence to A. M. Wnorowski types of mucin-containing rectal tumors are
(AmeliaWnorowski@umm.edu).  important because they have varied imaging
appearances and carry varied prognoses. Sig-
net ring cell carcinoma carries the worst
2
Department of Radiology, Mayo Clinic Arizona, Phoenix, AZ. 
er than 50% tumor composition by extra-
cellular mucin [1]. At histopathologic anal-
ysis, these tumors show extracellular mucin
pools surrounded by neoplastic epithelial
cells [7]. The mucinous composition results
in a classic radiologic and histologic appear-
ance. Colorectal mucinous carcinoma most
commonly affects the right colon [8]. It less
commonly occurs in the rectum, with an in-
cidence of 0.8 cases per 100,000 population
according to the U.S. Surveillance, Epide-
miology, and End Results database [1], ac-
counting for 10% of all rectal tumors [9]. It is
associated with a worse prognosis than non-
mucinous rectal adenocarcinoma. Recogni-
tion of this tumor subtype has important pa-
tient care implications in a multidisciplinary
care setting [10].
Mucinous rectal carcinoma is associat-
ed with a unique genetic pattern, suggest-
ing that this histologic type reflects a distinct
pathologic entity [11]. It more commonly has
several genetic aberrations that indicate ag-
gressiveness and therapy resistance, includ-
ing BRAF and KRAS mutations and MUC-2
overexpression [10]. These tumors also more
commonly show microsatellite instability

3
Department of Radiology, University of Wisconsin
prognosis [3], whereas mucin production as a (MSI), which is caused by a defect in DNA
School of Medicine and Public Health, Madison, WI.  response to neoadjuvant chemoradiation is mismatch repair. Colonic tumors with MSI
considered a good prognostic sign [4, 5]. are associated with better prognosis, even af-
AJR 2019; 213:1–9 ter adjusting for tumor stage [12]. The prog-
0361–803X/19/2131–1
Mucinous Rectal Carcinoma nostic significance of MSI in rectal cancer is
Mucinous rectal carcinoma is a distinct less well studied, but MSI in rectal cancers
© American Roentgen Ray Society histopathologic subtype of rectal cancer; it has been linked to a poorer prognosis, unlike

AJR:213, July 2019 1


its colonic counterpart [13]. In one recent
study of over 5000 patients with locally ad-
vanced rectal cancer, MSI was independent-
ly associated with a reduction in pathologic
complete response after neoadjuvant therapy
[14]. Several studies have shown that rectal
tumors with MSI are more often hereditary
and related to Lynch syndrome, rather than
sporadic [13, 15]. Additional tumor screen-
ing and genetic counseling are important in
this patient subgroup.
The prognostic significance of mucinous
histologic type in the rectum was previously
debated. However, older studies often com-
bined tumors that become mucinous after
chemoradiation with true mucinous carci-
nomas, which are now being recognized as
separate entities with different prognoses.
More recent studies have shown that, com-
pared with nonmucinous adenocarcinoma,
mucinous carcinoma of the rectum is asso-
ciated with a higher T category at diagnosis
[11], greater risk of metachronous metastases
[16], and worse survival [17–19]. However,
the difference in survival between patients
American Journal of Roentgenology
with mucinous and nonmucinous rectal can-
cers may be decreasing as a result of modern
advances in imaging, surgical technique, and
neoadjuvant therapy [9].
Signet Ring Cell Carcinoma
Signet ring cell carcinoma is a rare distinct
histopathologic subtype of rectal cancer. It
can develop in other sites of the gastrointes-
tinal tract, most commonly the stomach, but
does also account for 0.1–2.4% of all colorec-
tal tumors [20]. Signet ring cell carcinoma is
defined by the World Health Organization as
a tumor with more than 50% of cells contain-
ing intracytoplasmic mucin [1]. At histopath-
ologic analysis, the intracellular mucin dis-
places the nuclei, resulting in a characteristic
signet ring appearance. It affects younger pa-
tients, is considered undifferentiated and high
grade, and carries a poor prognosis [20–22].
In fact, despite the overall stable incidence
of rectal cancer since 1980, the incidence of
rectal cancer in patients younger than 40 has
quadrupled in this period with an increased
risk of signet ring cell histologic subtype in
this young subgroup [22]. Rectal signet ring
cell carcinomas tend to be larger, later stage,
and lower in location than mucinous carcino-
mas and nonmucinous adenocarcinomas [23].
They also grow in the submucosa, which can
lead to false-negative biopsy [24]. Deeper bi-
opsy or even surgical exploration may be re-
quired to make the diagnosis.
2 AJR:213, July 2019
Wnorowski et al.
The genetic basis of signet ring cell histo-
logic subtype has been better studied in gas-
tric cancer than in colorectal cancer [22].
Gastric signet ring cell carcinoma is associat-
ed with a mutation in the CDH-1 gene, which
leads to E-cadherin deficiency, with germline
mutations predisposing patients to heredi-
tary gastric cancer [22]. Further research is
required to identify potential genetic associ-
ations specific to rectal signet ring cell car-
cinoma, especially in light of its increasing
incidence among young patients. Compared
with colorectal adenocarcinoma, signet ring
cell carcinoma is associated with varied ge-
netic alterations, including MSI, oncogene
(KRAS and BRAF) and tumor suppressor
gene (p53 and p16) mutations, disruption of
cell adhesion–related genes (E-cadherin and
β-catenin), and higher expression of mucin-
related genes [2, 25]. It is hypothesized that
decreased expression of the cell-cell adhesion
molecules may contribute to more aggressive
tumor behavior through increased local and
metastatic spread [2]. Several studies have
shown an association of signet ring cells with
poor prognosis, even at minor (< 50%) tumor
composition of signet ring cells [2, 26].
Tumors With Posttreatment Mucin
Mucinous change can be induced as a re-
sult of neoadjuvant therapy. At imaging, this
is reflected by the development of mucin
pools within a tumor that was not mucinous
before therapy. The mucin pools induced by
therapy are usually acellular. This induced
mucinous change is an indicator of treatment
response and is associated with better prog-
nosis [4, 27]. In one study, tumors with in-
A B
Fig. 1—47-year-old man with mid rectal mucinous carcinoma.
A, Sagittal T2-weighted MR image shows T2-hyperintense mucinous tumor (arrows).
B, Sagittal contrast-enhanced T1-weighted MR image shows heterogeneous and overall decreased
enhancement of mass (arrow).
duced mucinous change had significantly
greater 2-year recurrence-free survival than
did tumors that were mucinous before treat-
ment (91.2% vs 39.3%) [4].
Imaging Features
MRI
Diagnosis of mucinous carcinoma at initial
biopsy is prone to sampling error, with mis-
classification in approximately 25% of cases
[28]. However, this tumor subtype has a clas-
sic appearance at MRI, allowing the radiolo-
gist to diagnose it confidently and accurate-
ly in almost all cases. Extracellular mucin
is T2 hyperintense; thus, mucinous carcino-
mas have significantly higher T2-weighted
signal than do nonmucinous tumors [29]. Us-
ing T2-weighted signal, MRI is 96–97% ac-
curate at predicting the mucinous histologic
type with sensitivities of 94–100% and spec-
ificities of 95–98% [30]. MRI is more accu-
rate than biopsy for the diagnosis of muci-
nous histologic subtype [19] and can predict
histologic quantification of mucin [16]. MRI
has excellent interobserver agreement [30–32]
with rare false-positive cases due to conges-
tion, abscess, necrosis, or mural edema [30].
Furthermore, the presence of T2-hyperintense
mucin within a tumor at pretherapy MRI has
been shown to be an independent biomarker
for poor prognosis and poor therapy response
[19]. Thus, when T2-hyperintense signal is
subjectively assessed as present in greater
than 50% of tumor volume, radiologists can
accurately diagnose mucinous rectal carcino-
ma with important patient care implications.
Because of their overall decreased cellu-
larity, mucinous tumors show less enhance-
(Fig. 1 continues on next page)
 Imaging Features of Mucin-Containing Rectal Carcinomas

Fig. 1 (continued)—47-year-old man with mid rectal

mucinous carcinoma.
C, Axial DW image (left) and corresponding apparent
diffusion coefficient (ADC) map (right) show overall
intermediate-to-high signal throughout mass on DW
image, mostly reflecting T2 signal shine-through on
ADC map (arrow).

ment and diffusion restriction compared

with nonmucinous tumors (Fig. 1). On con-
trast-enhanced images, there is enhancement
of the cellular portions of the tumor with a
predominantly peripheral and heterogeneous
enhancement pattern [32]. At DWI, there
is lower signal on high-b-value images and
higher mean apparent diffusion coefficient
values than for nonmucinous tumors as a re-
sult of the lower cellular density in the mu-
cinous components [16, 33]. If a radiologist
relies heavily on the presence of diffusion re-
striction for tumor identification and assess-
ment of tumor extent in otherwise subtle cas-
es, the lack of diffusion restriction can be a A B
potential pitfall in interpretation.
American Journal of Roentgenology

Fig. 2—34-year-old man with signet ring cell carcinoma of rectum.

The appearance of signet ring cell carcino- A and B, Sagittal (A) and axial (B) T2-weighted MR images show long segment of infiltrative tumor (arrows, A
ma varies, but it is classically a scirrhous tu- and B). Length of involvement and soft-tissue infiltration of submucosa producing malignant target appearance
mor with a submucosal growth pattern and seen on axial image (B) are characteristic of rectal linitis plastica. Note mesorectal and pelvic side wall lymph
node metastases (arrowheads, B). Signet ring cell carcinoma has propensity for lymph node metastases.
is associated with linitis plastica of the rec-
tum. “Linitis plastica” is a term first used to
describe the macroscopic appearance of tu-
mors infiltrating the stomach and resembling
a leather bottle. The term was later applied to
any part of the gastrointestinal tract when in-
filtrative tumor and the associated desmoplas-
tic reaction cause thickening of the wall, rigid-
ity, and lack of distensibility [24, 34, 35]. At
MRI, linitis plastica is characterized by long-
segment thickening and a cross-sectional tar-
get or ring appearance on T2-weighted images
[20, 24, 34] (Fig. 2). The infiltrative and sub-
mucosal growth patterns cause long-segment
strictures without the typical shouldering as-
sociated with most colorectal tumors [24]. The
submucosal growth pattern leads to the imag-
ing appearance of the malignant target sign,
wherein the submucosa is replaced by soft- A B
tissue signal, rather than the signal of edema,
Fig. 3—59-year-old man with obstructing mucinous rectal carcinoma.
and sequentially and progressively enhances A and B, Coronal (A) and axial (B) contrast-enhanced CT images show large high rectal mass (arrows) causing
on the delayed phase contrast-enhanced imag- upstream obstruction. Central mucin is marked by low attenuation at CT.
es, similar to that reported in other scirrhous
tumors of the gastrointestinal tract [36]. have been few reports examining the appear- tion at CT (Fig. 3). Because of this, muci-
ance of mucinous rectal carcinomas at CT. nous colorectal tumors are overall more hy-
CT However, CT remains heavily used in many poattenuating than are nonmucinous tumors
Prior literature has focused primarily on institutions, especially for distant staging. [37, 38]. At CT, mucinous tumors also show
the imaging appearance of mucin at MRI be- Therefore, it is important to recognize fea- more heterogeneous enhancement with less
cause MRI is used more commonly in eval- tures at CT that can indicate the presence of enhancement of the solid tumor components
uation of the primary tumor. Overall, there a mucinous tumor. Mucin has low attenua- overall and more severe and eccentric wall

AJR:213, July 2019 3

 Wnorowski et al.

thickening [37, 38]. Mucin acts as an ion-ex- is a recognized rare complication of chronic Metastasis
change resin, often leading to calcium depo- perianal fistula [46, 47]. This can be a diffi- Mucinous tumors from other sites can
sition in the primary tumor, as well as me- cult diagnosis because of its nonspecific pre- occasionally metastasize to the rectum and
tastases [39]. At CT, mucinous colorectal sentation, chronic symptoms, and misleading mimic a primary mucinous carcinoma. The
tumors show intratumoral calcification more physical examination findings. Cross-section- most common primary sites include the co-
frequently [37, 38]. In one series comparing al imaging has a low sensitivity because the lon, stomach, and ovaries. Peritoneal depos-
86 mucinous colorectal tumors to 105 non- appearance of a mucinous tumor overlaps its within the deep pelvis can involve the an-
mucinous tumors, calcifications were present with that of a perianal abscess. Heterogeneous terior rectal wall. In these cases, the mass
in 21% of the mucinous subtype compared internal enhancement of mucinous carcinoma will be primarily eccentrically located with
with only 5% of the nonmucinous subtype is a clue to differentiate the two entities be- possible growth into the rectal wall (Fig. 5).
[38]. The overall specificity of these findings cause an abscess will more commonly show Secondary linitis plastica of the rectum
is 87% if multiple features are present [38]. peripheral enhancement only [46, 48] (Fig. 4). due to metastatic disease is more common
Signet ring cell carcinoma is more likely
to be concentrically thickened, producing the
malignant target sign, and homogeneously en-
hancing on CT [37] and often shows significant
perirectal infiltration [40]. As in MRI, the di-
agnosis should be considered when CT shows
a long length of concentric thickening and a
target sign; the mean length of involvement
was 6 cm and the mean thickness was 2 cm in
one series [40]. The linitis plastica appearance
can mimic an inflammatory or ischemic pro-
cess [34, 40]. A high level of suspicion must
be maintained because neoplasm is often not
American Journal of Roentgenology

the primary consideration in young patients,

who are, unfortunately, more commonly af-
fected by signet ring cell carcinoma.

PET
Mucinous rectal carcinoma may show vari- A B
able FDG uptake at PET/CT or PET/MRI de-
Fig. 4—61-year-old man with Crohn disease and mucinous carcinoma arising in perianal fistula. Patient
pending on the degree of mucin content. There required seton placement for transsphincteric perianal fistula. Surveillance MRI showed increased size of
is a negative correlation between the amount ischiorectal fossa collection, prompting biopsy that confirmed invasive mucinous carcinoma.
of mucin present and FDG avidity [41]. There- A, Coronal T2-weighted MR image shows T2-hyperintense mucinous mass (arrows) arising in perianal fistula.
Asterisk marks skin drainage site.
fore, the utility of PET may be limited in tumors B, Axial contrast-enhanced T1-weighted MR image shows heterogeneous internal enhancement (arrows).
with a large amount of mucin. However, con-
trary to their mucinous counterpart in the colon,
mucinous rectal carcinomas are more likely to
be as FDG-avid as nonmucinous tumors [16,
42]. Several reports have suggested value in
dual-time-point PET to increase sensitivity [43,
44]. This is thought to be due to different enzy-
matic expression in malignant tumors that leads
to continued FDG accumulation and retention
over time compared with normal tissue, which
more readily clears FDG [45]. This results in
higher contrast of FDG uptake between malig-
nant and benign tissue over time, which could
be helpful in detecting mucinous tumors, which
are classically less conspicuous [43].

Rare Presentations of Mucinous A B

Perirectal Tumors
Complication of Perianal Fistula
Tumors arising within a perianal fistu-
la may be either squamous cell carcinomas
or adenocarcinomas. Mucinous carcinoma
Fig. 5—56-year-old man with mucinous metastasis to rectum from cecal primary tumor.
A, Sagittal T2-weighted MR image shows mass in rectovesical pouch (arrows). Mass is T2-hyperintense and
appears eccentric along anterior rectal wall, which suggests its cause as metastatic deposit rather than
primary rectal tumor.
B, Coronal contrast-enhanced CT image shows T4a mucinous cecal tumor (arrow) that was resected 2 years
earlier. Resection of pelvic mass confirmed metastatic mucinous carcinoma.

4 AJR:213, July 2019

 Imaging Features of Mucin-Containing Rectal Carcinomas

than primary rectal signet ring cell carcino-
ma [49]; however, the imaging findings are
similar. Metastatic linitis plastica can oc-
cur as a result of direct invasion of the rec-
tum by bladder or prostate carcinoma or dis-
tant peritoneal, lymphatic, or hematogenous
spread from a gastric signet ring cell carcino-
ma or breast cancer [34, 50–53]. Distinction
in these cases may be possible because of the
patient’s history and presence of other meta-
static disease elsewhere, especially peritone-
al carcinomatosis.
Local Staging
Local staging is best performed with MRI
via the American Joint Committee on Can-
cer’s TNM system [54]. MRI staging allows
determination of the depth of invasion and
whether the anal sphincter can be spared at
American Journal of Roentgenology
surgery to maintain fecal continence. MRI
has been shown to be highly accurate in pre-
dicting the possibility of complete surgical
resection [55]. The staging of mucin-contain-
ing rectal tumors is no different than that of
nonmucinous adenocarcinoma. T category is
assessed by greatest depth of invasion (Fig.
6). T1 tumors are those that grow through the
muscularis mucosa and extend into the sub-
mucosa. T2 tumors grow through the sub-
mucosa and extend into the muscularis pro-
pria. T3 tumors grow through the muscularis
propria and into the mesorectum. Finally, T4
tumors extend through the mesorectum to
penetrate the visceral peritoneum (T4a) or
adjacent organs or structures (T4b).
N category is determined by regional nod-
al involvement. N0 is defined as no region-
al nodal involvement, N1 as involvement of
one to three regional lymph nodes, and N2 as
involvement of four or more regional lymph
nodes [54]. Nonregional lymph node involve-
ment such as paraaortic adenopathy above
the origin of the inferior mesenteric artery is
designated M1a. Mucinous lymph node me-
tastases may be T2 hyperintense as well.
Assessment of Treatment Response
One of the most important prognostic fac-
tors in rectal cancer is complete surgical re-
section at total mesorectal excision. Neo-
adjuvant chemoradiation is the standard of
care for locally advanced disease. It results
in frequent downstaging and lower local re-
currence rates after subsequent surgery. The
degree of tumor regression after neoadjuvant
therapy correlates with disease-free surviv-
al [56].
At restaging MRI, mucinous composition
should be noted [27]. This may reflect mu-
cinous change in an originally nonmucinous
tumor, an indicator of treatment response
and better prognosis [4, 27]. Mucin seen af-
ter neoadjuvant therapy is most commonly

acellular. Acellular mucin is not considered

residual tumor in the TNM category [57] and
has no effect on disease-free survival [58].
In tumors that are mucinous before treat-
ment, mucin persists despite neoadjuvant
therapy. Restaging MRI is less accurate for
these tumors because of the difficulty in dis-
tinguishing persistent cellular mucin (lack
of response) from acellular mucin (treatment
effect). These tumors will remain T2 hyper-
A B
intense regardless of treatment effect. In ad-
dition, DWI may not be helpful because muci-
nous carcinomas are commonly bright on the
apparent diffusion coefficient map both be-
fore and after treatment [16, 59]. Tumor het-
erogeneity can help distinguish cellular from
acellular mucin. Acellular mucin generally
has more homogeneous T2-weighted signal,
whereas cellular mucin tends to be more het-
erogeneous with areas of intermediate signal
and enhancement [27]. However, cellular and
acellular mucin can be difficult to differenti-
ate at MRI [5] and both are resected.
Mucinous rectal carcinomas are less like-
C D ly to decrease in tumor bulk as a response to
Fig. 6—Four patients with different mucinous rectal tumors. T2-hyperintense signal of each tumor reflects neoadjuvant therapy [5, 60]. This is due to
extracellular mucin. the persistence of acellular mucin and is true
A, 38-year-old man. Axial T2-weighted MR image shows category T2 mucinous low rectal tumor contained
within muscularis propria (arrow). Surgical resection confirmed T2 tumor.
even in cases of complete response [5]. Per-
B, 60-year-old man. Axial T2-weighted MR image shows T3 mucinous anorectal tumor with areas that extend sistent tumor bulk and difficulty differentiat-
through muscularis propria into mesorectal fat (arrows). ing cellular from acellular mucin can result
C, 57-year-old man. Axial T2-weighted MR image shows T4a mucinous mid rectal tumor that extends through in overstaging [5]. Because of the difficulty
mesorectal fat to involve anterior peritoneal reflection (arrow).
D, 45-year-old man. Axial T2-weighted MR image shows T4b mucinous mid rectal tumor (arrow) invading in distinguishing treatment effect and residu-
seminal vesicles (arrowheads). al disease, restaging MRI is more error prone

AJR:213, July 2019 5

 Wnorowski et al.

for mucinous carcinoma than for nonmuci-

nous tumors (Fig. 7). In one study by Allen et
al. [5], accurate prediction of complete resec-
tion was more difficult for mucinous tumors
(82%) than nonmucinous tumors (94%). In
that same study, they found that acellular mu-
cin pools at the resection margin were a fre-
quent confounder and resulted in overstaging.
Similarly, in tumors that develop mucinous
change as a response to neoadjuvant therapy,
the development of acellular mucin pools can
result in erroneous overstaging [61]. Despite A
difficulties with restaging mucinous tumors,
MRI remains useful in this setting to delin-
eate areas of potential residual disease and to
assist in surgical planning.
Mucinous rectal carcinomas are less like-
ly to be downstaged with neoadjuvant ther-
apy, less likely to show pathologic complete
response, and more likely to have positive
resection margins [9, 17–19, 62, 63]. In one
large review of over 85,000 patients with rec-
tal cancer, mucinous and signet ring cell his-
tologic subtype were associated with higher
margin positivity with adjusted odds ratios B C
American Journal of Roentgenology

of 1.51 and 2.49, respectively [64]. In another Fig. 7—55-year-old man with mucinous rectal carcinoma with near-complete treatment response.
study of 88 patients with rectal cancer, mu- A, Axial contrast-enhanced CT image obtained before treatment shows large low rectal mucinous tumor (arrows).
Note low-attenuation mucin at CT.
cinous carcinomas were the only tumors to B, Axial T2-weighted restaging MR image obtained after neoadjuvant chemoradiation shows that mass extends into
show disease progression after neoadjuvant prostate (arrow) and abuts levator musculature (arrowheads).
therapy [60]. This poor response to neoadju- C, Axial DW image (top) and apparent diffusion coefficient map (bottom) show lack of significant diffusion restriction
in bulk of tumor (arrows). Despite persistence of large tumor bulk at imaging, pathologic examination at pelvic
vant therapy is thought to be due to the low- exenteration showed near-complete treatment response with large amount of acellular mucin and rare tumor cells.
er microvascular density within mucinous tu-
mors [65]. Unfortunately, no imaging markers
have yet been shown to predict neoadjuvant
nonresponse in mucinous carcinoma [16].
Patients with rectal signet ring cell carci-
noma generally have a very poor prognosis
despite neoadjuvant therapy. However, sev-
eral studies have noted that some patients
are able to achieve complete response with
chemoradiation [34, 66]. In one series of pa-
tients with rectal signet ring cell carcinoma,
more extensive lymph node involvement (N
category) at pretreatment MRI was associ-
ated with a lack of treatment response [66].

Imaging of Local Recurrence

With optimal oncologic surgical technique
(i.e., total mesorectal excision) and neoadju-
vant chemoradiation, the 10-year cumulative
frequency of local relapse is less than 10%
[67]. Most tumors recur in the first 3 years,
and over 50% of patients have additional met-
astatic disease at the time of recurrence [68].
The risk of local recurrence is greater with
higher original tumor category [68], positive
resection margin [60], and spillage of cellu-
lar mucin at the time of surgery [27]. At MRI,
A B
Fig. 8—64-year-old woman with locally recurrent mucinous rectal carcinoma.
A, Axial T2-weighted MR image at level of bladder and vaginal canal shows infiltrative disease recurrence in
pelvis with innumerable small T2-hyperintense tumor deposits (arrows) that replace vaginal and bladder walls.
B, Axial T2-weighted MR image inferior to image shown in panel A at level of urethra shows additional tumor
deposits encasing urethra (arrow). Patient had history of primary rectal carcinoma with mucinous and signet
ring cell features treated with abdominoperineal resection and adjuvant chemotherapy.
locally recurrent mucinous carcinoma is also at MRI or low attenuation at CT, similar to
T2 hyperintense (Fig. 8). Its appearance may that of fluid. Recurrence may be differentiated
mimic that of postoperative fluid collections by central or peripheral enhancement, FDG
[68] because of their T2-hyperintense signal uptake (Fig. 9), or growth on sequential scans.

6 AJR:213, July 2019

 Imaging Features of Mucin-Containing Rectal Carcinomas

through tissue planes and direct extension

into the peritoneal cavity [69] (Fig. 10). C to-
reductive surgery with hyperthermic intra-
peritoneal chemotherapy has shown promise
in the treatment of patients with colorectal
cancer metastatic to the peritoneal cavity
[76]. However, unfortunately, the signet ring
cell histologic subtype is associated with a
high rate of recurrence [77].

Conclusion
In conclusion, mucinous rectal carcinoma
and signet ring cell carcinoma are uncommon
histologic subtypes of rectal cancer that por-
A B tend a poor prognosis. Mucinous rectal car-
Fig. 9—56-year-old man with local recurrence of mucinous carcinoma 2 years after initial resection. cinoma is defined as greater than 50% tumor
A and B, Restaging contrast-enhanced CT (A) and PET (B) images obtained 2 years after initial surgery reveal composition by extracellular mucin. MRI has
low-attenuation collection in operative bed (arrows) with peripheral enhancement and FDG uptake. This was
confirmed to be mucinous local recurrence.
a high diagnostic accuracy, superior to that of
biopsy. The hallmark of the mucinous histo-
logic subtype is T2-hyperintense signal at
Metastatic Patterns Mucinous rectal and signet ring cell car- MRI. Mucin has low attenuation at CT and
Radiologists need to be aware of the unique cinomas have a higher frequency of both can be a cause of false-negative PET examina-
pattern and appearance of mucinous rectal lymph node and peritoneal metastases [69, tions. Restaging MRI is error prone because
carcinoma metastases. The mucinous histo- 75]. Additional rare metastatic sites, such as of difficulties in distinguishing residual cellu-
logic subtype is associated with an increased the heart, ovary, pancreas, and skin, are also lar from acellular mucin and persistent tumor
American Journal of Roentgenology

risk of metachronous metastases and in- more common in mucinous and signet ring bulk despite potential treatment response. Tu-
creased number of metastatic sites [16, 69]. cell carcinomas. Signet ring cell carcinoma mors with extracellular mucin before thera-
Mucinous metastases usually have imaging in particular has a very high rate of lym- py—that is, true mucinous carcinomas—must
features similar to those of the primary tu- phatic spread. Metastatic disease to the peri- be distinguished from nonmucinous tumors
mor with T2-hyperintense signal at MRI. Im- toneal cavity portends a very poor progno- that develop acellular mucin only as response
portantly, PET may be limited when there are sis. The frequencies of peritoneal spread for to therapy, which is a good prognostic sign.
large amounts of mucin in metastatic lesions, nonmucinous adenocarcinomas, mucinous Signet ring cell carcinoma is diagnosed patho-
and this can lead to false-negative results [70– carcinomas, and signet ring cell carcinomas logically by the presence of intracellular mu-
72]. A high index of suspicion, careful corre- were 20.1%, 48.2%, and 51.2%, respectively, cin. The classic imaging appearance of this
lation with CT or MR images, and lower stan- in one series [69]. The increased frequency subtype reflects its scirrhous morphologic fea-
dardized uptake value cutoffs may increase of peritoneal dissemination in mucinous tu- tures and submucosal growth pattern, giving
the sensitivity of PET in this setting [73]. mors is thought to be due to mucin dissection rise to rectal linitis plastica. The metastatic
In a study of close to 6000 autopsies of pa-
tients with colorectal tumors, compared with
patients with nonmucinous tumors, patients
with mucinous and signet ring cell carcino-
mas more commonly had metastatic disease
(27.6%, 33.9%, and 61.2%, respectively) and
were more likely to have multiple metastatic
sites (49.9%, 58.6%, and 70.7%, respectively)
[69]. Although mucinous and signet ring cell
carcinomas metastasize to the liver less com-
monly than nonmucinous tumors [20, 69], mu-
cinous liver metastases have been shown to be
an independent marker of poor prognosis [74].
Compared with nonmucinous metastases, mu-
cinous liver metastases are more commonly
single, larger, and unilateral [74]. Because of A B
the T2-hyperintense signal of mucinous liver Fig. 10—38-year-old woman with mucinous and signet-ring cell rectal carcinoma.
metastases, they can be confused with cysts or A, Sagittal T2-weighted MR image shows T2-hyperintense rectal mass (arrows) that involves anterior peritoneal
hemangiomas. However, their enhancement reflection (arrowhead). At time of diagnosis, there was peritoneal carcinomatosis with ascites.
B, Coronal T2-weighted MR image shows bilateral heterogeneous T2-hyperintense ovarian masses (arrows),
pattern allows differentiation with very mild consistent with mucinous metastases to ovaries. Neoadjuvant chemotherapy followed by rectosigmoid resection,
and heterogeneous internal enhancement. hysterectomy, bilateral salpingo-oophorectomy, and omentectomy confirmed metastatic mucinous tumor.

AJR:213, July 2019 7


pattern of mucinous and signet ring cell car-
cinoma is unique with increased frequency of
lymph node and peritoneal metastases.
References
1. [No authors listed.] WHO classification of tu-
mours, 4th ed., vol. 3. WHO classification of tu-
mours of the digestive system. In: Bosman FT,
Carneiro F, Huban RH, Theise ND, eds. Paris,
France: World Health Organization, 2010
2. Börger ME, Gosens MJ, Jeuken JW, et al. Signet
ring cell differentiation in mucinous colorectal
carcinoma. J Pathol 2007; 212:278–286
3. Hyngstrom JR, Hu CY, Xing Y, et al. Clinicopath-
ology and outcomes for mucinous and signet ring
colorectal adenocarcinoma: analysis from the Na-
tional Cancer Data Base. Ann Surg Oncol 2012;
19:2814–2821
4. Nagtegaal I, Gaspar C, Marijnen C, Van De Velde
C, Fodde R, Van Krieken H. Morphological
changes in tumour type after radiotherapy are ac-
companied by changes in gene expression profile
but not in clinical behaviour. J  Pathol 2004;
204:183–192
5. Allen SD, Padhani AR, Dzik-Jurasz AS, Glynne-
American Journal of Roentgenology
Jones R. Rectal carcinoma: MRI with histologic
correlation before and after chemoradiation thera-
py. AJR 2007; 188:442–451
6. Parham D. Colloid carcinoma. Ann Surg 1923;
77:90–105
7. Symonds DA, Vickery AL. Mucinous carcinoma
of the colon and rectum. Cancer 1976; 37:1891–
1900
8. Verhulst J, Ferdinande L, Demetter P, Ceelen W.
Mucinous subtype as prognostic factor in colorec-
tal cancer: a systematic review and meta-analysis.
J Clin Pathol 2012; 65:381–388
9. Hugen N, van de Velde CJ, Bosch SL, et al. Mod-
ern treatment of rectal cancer closes the gap be-
tween common adenocarcinoma and mucinous
carcinoma. Ann Surg Oncol 2015; 22:2669–2676
10. Hugen N, Brown G, Glynne-Jones R, de Wilt JH,
Nagtegaal ID. Advances in the care of patients
with mucinous colorectal cancer. Nat Rev Clin
Oncol 2016; 13:361–369
11. Mekenkamp LJ, Heesterbeek KJ, Koopman M, et
al. Mucinous adenocarcinomas: poor prognosis in
metastatic colorectal cancer. Eur J Cancer 2012;
48:501–509
12. Samowitz WS, Curtin K, Ma KN, et al. Microsat-
ellite instability in sporadic colon cancer is asso-
ciated with an improved prognosis at the popula-
tion level. Cancer Epidemiol Biomarkers Prev
2001; 10:917–923
13. Samowitz WS, Curtin K, Wolff RK, Tripp SR,
Caan BJ, Slattery ML. Microsatellite instability
and survival in rectal cancer. Cancer Causes Con-
trol 2009; 20:1763–1768
8 AJR:213, July 2019
Wnorowski et al.
14. Hasan S, Renz P, Wegner RE, et al. Microsatellite
instability (MSI) as an independent predictor of
pathologic complete response (PCR) in locally
advanced rectal cancer: a National Cancer Data-
base (NCDB) analysis. Ann Surg 2018 Sep 13
[Epub ahead of print]
15. de Rosa N, Rodriguez-Bigas MA, Chang GJ, et al.
DNA mismatch repair deficiency in rectal cancer:
benchmarking its impact on prognosis, neoadju-
vant response prediction, and clinical cancer ge-
netics. J Clin Oncol 2016; 34:3039–3046
16. Barbaro B, Leccisotti L, Vecchio FM, et al. The
potential predictive value of MRI and PET-CT in
mucinous and nonmucinous rectal cancer to iden-
tify patients at high risk of metastatic disease. Br J
Radiol 2017; 90:20150836
17. McCawley N, Clancy C, O’Neill BD, Deasy J, Mc-
Namara DA, Burke JP. Mucinous rectal adenocar-
cinoma is associated with a poor response to neo-
adjuvant chemoradiotherapy: a systematic review
and meta-analysis. Dis Colon Rectum 2016;
59:1200–1208
18. Shin US, Yu CS, Kim JH, et al. Mucinous rectal
cancer: effectiveness of preoperative chemoradio-
therapy and prognosis. Ann Surg Oncol 2011;
18:2232–2239
19. Yu SK, Chand M, Tait DM, Brown G. Magnetic
resonance imaging defined mucinous rectal carci-
noma is an independent imaging biomarker for
poor prognosis and poor response to preoperative
chemoradiotherapy. Eur J Cancer 2014; 50:920–
927
20. Lee NK, Kim S, Kim HS, et al. Spectrum of mu-
cin-producing neoplastic conditions of the abdo-
men and pelvis: cross-sectional imaging evalua-
tion. World J Gastroenterol 2011; 17:4757–4771
21. Nagtegaal ID, Hugen N. The increasing relevance
of tumour histology in determining oncological
outcomes in colorectal cancer. Curr Colorectal
Cancer Rep 2015; 11:259–266
22. Tawadros PS, Paquette IM, Hanly AM, Mellgren
AF, Rothenberger DA, Madoff RD. Adenocarci-
noma of the rectum in patients under age 40 is in-
creasing: impact of signet-ring cell histology. Dis
Colon Rectum 2015; 58:474–478
23. Chen JS, Hsieh PS, Hung SY, et al. Clinical sig-
nificance of signet ring cell rectal carcinoma. Int J
Colorectal Dis 2004; 19:102–107
24. Rudralingam V, Dobson MJ, Pitt M, Stewart DJ,
Hearn A, Susnerwala S. MR imaging of linitis
plastica of the rectum. AJR 2003; 181:428–430
25. Gopalan V, Smith RA, Ho YH, Lam AK. Signet-
ring cell carcinoma of colorectum: current per-
spectives and molecular biology. Int J Colorectal
Dis 2011; 26:127–133
26. Inamura K, Yamauchi M, Nishihara R, et al. Prog-
nostic significance and molecular features of sig-
net-ring cell and mucinous components in
colorectal carcinoma. Ann Surg Oncol 2015;
22:1226–1235
27. Patel UB, Blomqvist LK, Taylor F, et al. MRI after
treatment of locally advanced rectal cancer: how
to report tumor response—the MERCURY expe-
rience. AJR 2012; 199:[web]W486–W495
28. Younes M, Katikaneni PR, Lechago J. The value
of the preoperative mucosal biopsy in the diagno-
sis of colorectal mucinous adenocarcinoma. Can-
cer 1993; 72:3588–3592
29. Imai Y, Kressel HY, Saul SH, et al. Colorectal tu-
mors: an in vitro study of high-resolution MR im-
aging. Radiology 1990; 177:695–701
30. Kim MJ, Park JS, Park SI, et al. Accuracy in dif-
ferentiation of mucinous and nonmucinous rectal
carcinoma on MR imaging. J Comput Assist To-
mogr 2003; 27:48–55
31. Kim MJ, Huh YM, Park YN, et al. Colorectal mu-
cinous carcinoma: findings on MRI. J Comput As-
sist Tomogr 1999; 23:291–296
32. Hussain SM, Outwater EK, Siegelman ES. Muci-
nous versus nonmucinous rectal carcinomas: dif-
ferentiation with MR imaging. Radiology 1999;
213:79–85
33. Nasu K, Kuroki Y, Minami M. Diffusion-
weighted imaging findings of mucinous carci-
noma arising in the ano-rectal region: compari-
son of apparent diffusion coefficient with that of
tubular adenocarcinoma. Jpn J Radiol 2012;
30:120–127
34. Boustani J, Kim S, Lescut N, et al. Primary linitis
plastica of the rectum: focus on magnetic reso-
nance imaging patterns and treatment options.
Am J Case Rep 2015; 16:581–585
35. Laufman H, Saphir O. Primary linitis plastica
type of carcinoma of the colon. AMA Arch Surg
1951; 62:79–91
36. Gollub MJ, Schwartz MB, Shia J. Scirrhous me-
tastases to the gastrointestinal tract at CT: the ma-
lignant target sign. AJR 2009; 192:936–940
37. Li ZH, You DY, Gao DP, et al. Role of CT scan in
differentiating the type of colorectal cancer.
OncoTargets Ther 2017; 10:2297–2303
38. Ko EY, Ha HK, Kim AY, et al. CT differentiation
of mucinous and nonmucinous colorectal carci-
noma. AJR 2007; 188:785–791
39. Yu MH, Kim YJ, Park HS, Jung SI, Jeon HJ. Im-
aging patterns of intratumoral calcification in the
abdominopelvic cavity. Korean J Radiol 2017;
18:323–335
40. Kim HJ, Ha HK, Cho KS, et al. CT features of
primary colorectal signet-ring cell carcinoma.
J Comput Assist Tomogr 2001; 25:225–230
41. Berger KL, Nicholson SA, Dehdashti F, Siegel
BA. FDG PET evaluation of mucinous neoplasms:
correlation of FDG uptake with histopathologic
features. AJR 2000; 174:1005–1008
42. Dos Anjos DA, Habr-Gama A, Vailati BB, et al.
 Imaging Features of Mucin-Containing Rectal Carcinomas
18F-FDG uptake by rectal cancer is similar in mu-
cinous and nonmucinous histological subtypes.
Ann Nucl Med 2016; 30:513–517
43. Basu S, Baghel NS. Value of delayed PET imaging
in mucinous adenocarcinoma rectum: should this
be employed while evaluating mucinous tumors
with FDG-PET? Indian J Cancer 2011; 48:374–
375
44. Basu S, Kembhavi S. Unusual isolated perineal
recurrence in mucinous adenocarcinoma of the
rectum after abdominoperineal resection: useful-
ness of dual-time-point FDG PET in evaluating
mucinous tumors. Clin Nucl Med 2012; 37:989–
990
45. Zhuang H, Pourdehnad M, Lambright ES, et al.
Dual time point 18F-FDG PET imaging for differ-
entiating malignant from inflammatory processes.
J Nucl Med 2001; 42:1412–1417
46. Hama Y, Makita K, Yamana T, Dodanuki K. Mu-
cinous adenocarcinoma arising from fistula in
ano: MRI findings. AJR 2006; 187:517–521
47. Surabhi VR, Menias CO, Amer AM, et al. Tumors
and tumorlike conditions of the anal canal and peri-
anal region: MR imaging findings. RadioGraphics
2016; 36:1339–1353
American Journal of Roentgenology
48. Fujimoto H, Ikeda M, Shimofusa R, Terauchi M,
Eguchi M. Mucinous adenocarcinoma arising
from fistula-in-ano: findings on MRI. Eur Radiol
2003; 13:2053–2054
49. Barabino G, Miggino M, Cuilleron M, Abboud K,
Phelip JM, Porcheron J. Rectal linitis. Surgery
2013; 154:641–642
50. Ha HK, Jee KR, Yu E, et al. CT features of meta-
static linitis plastica to the rectum in patients with
peritoneal carcinomatosis. AJR 2000; 174:463–466
51. Venturini F, Gambi V, Di Lernia S, et al. Linitis
plastica of the rectum as a clinical presentation of
metastatic lobular carcinoma of the breast. J Clin
Oncol 2016; 34:e54–e56
52. Dresen RC, Beets GH, Vliegen RF, Creytens DH,
Beets-Tan RG. Linitis plastica of the rectum sec-
ondary to bladder carcinoma: a report of two cas-
es and its MR features. Br  J Radiol 2008;
81:e249–e251
53. Katsinelos P, Papaziogas B, Chatzimavroudis G,
et al. Secondary rectal linitis plastica as first man-
ifestation of urinary bladder carcinoma. Ann Gas-
troenterol 2012; 25:173–175
54. Jessup JM, Goldberg RM, Asare EA, et al. Colon
and rectum. In: Amin MB, Edge S, Greene F, et
al., eds. AJCC Cancer Staging Manual. Basel,
Switzerland: Springer Nature, 2017:251–274
55. MERCURY Study Group. Extramural depth of
AJR:213, July 2019 9
tumor invasion at thin-section MR in patients with
rectal cancer: results of the MERCURY study.
Radiology 2007; 243:132–139
56. Patel UB, Taylor F, Blomqvist L, et al. Magnetic
resonance imaging-detected tumor response for
locally advanced rectal cancer predicts survival
outcomes: MERCURY experience. J Clin Oncol
2011; 29:3753–3760
57. Engstrom PF, Arnoletti JP, Benson AB 3rd, et al;
National Comprehensive Cancer Network. NCCN
Clinical Practice Guidelines in Oncology: rectal
cancer. J Natl Compr Canc Netw 2009; 7:838–881
58. Shia J, McManus M, Guillem JG, et al. Signifi-
cance of acellular mucin pools in rectal carcinoma
after neoadjuvant chemoradiotherapy. Am J Surg
Pathol 2011; 35:127–134
59. Enkhbaatar NE, Inoue S, Yamamuro H, et al. MR
imaging with apparent diffusion coefficient histo-
gram analysis: evaluation of locally advanced rec-
tal cancer after chemotherapy and radiation thera-
py. Radiology 2018; 288:129–137
60. Oberholzer K, Menig M, Kreft A, et al. Rectal
cancer: mucinous carcinoma on magnetic reso-
nance imaging indicates poor response to neoad-
juvant chemoradiation. Int J Radiat Oncol Biol
Phys 2012; 82:842–848
61. Barbaro B, Fiorucci C, Tebala C, et al. Locally
advanced rectal cancer: MR imaging in prediction
of response after preoperative chemotherapy and
radiation therapy. Radiology 2009; 250:730–739
62. Sengul N, Wexner SD, Woodhouse S, et al. Effects
of radiotherapy on different histopathological
types of rectal carcinoma. Colorectal Dis 2006;
8:283–288
63. Miyakita H, Sadahiro S, Ogimi T, et al. Mucinous
components assessed by magnetic resonance im-
aging in primary rectal cancer tissue before and
after chemoradiotherapy and tumor response. Int
J Colorectal Dis 2018; 33:1135–1138
64. Russell MC, You YN, Hu CY, et al. A novel risk-
adjusted nomogram for rectal cancer surgery out-
comes. JAMA Surg 2013; 148:769–777
65. Oberholzer K, Menig M, Pohlmann A, et al. Rec-
tal cancer: assessment of response to neoadjuvant
chemoradiation by dynamic contrast-enhanced
MRI. J Magn Reson Imaging 2013; 38:119–126
66. Bratland A, Vetrhus T, Grøholt KK, Ree AH. Pre-
operative radiotherapy in rectal signet-ring cell
carcinoma: magnetic resonance imaging and
treatment outcome—report of six cases. Acta On-
col 2010; 49:42–49
67. Sauer R, Liersch T, Merkel S, et al. Preoperative
versus postoperative chemoradiotherapy for lo-
cally advanced rectal cancer: results of the Ger-
man CAO/ARO/AIO-94 randomized phase III
trial after a median follow-up of 11 years. J Clin
Oncol 2012; 30:1926–1933
68. Sinaei M, Swallow C, Milot L, Moghaddam PA,
Smith A, Atri M. Patterns and signal intensity
characteristics of pelvic recurrence of rectal can-
cer at MR imaging. RadioGraphics 2013;
33:E171–E187
69. Hugen N, van de Velde CJ, de Wilt JH, Nagtegaal
ID. Metastatic pattern in colorectal cancer is
strongly influenced by histological subtype. Ann
Oncol 2014; 25:651–657
70. Belcher E, Nicholson AG, Hansell DM, Goldstraw
P. Imaging characteristics of a mucinous colorec-
tal pulmonary metastasis. Ann Thorac Surg 2008;
86:1698
71. Whiteford MH, Whiteford HM, Yee LF, et al. Use-
fulness of FDG-PET scan in the assessment of
suspected metastatic or recurrent adenocarcino-
ma of the colon and rectum. Dis Colon Rectum
2000; 43:759–767; discussion, 767–770
72. Sarikaya I, Bloomston M, Povoski SP, et al.
FDG-PET scan in patients with clinically and/or
radiologically suspicious colorectal cancer recur-
rence but normal CEA. World J Surg Oncol 2007;
5:64
73. Yang ZY, Hu SL, Shi W, Zhu BL, Xu JY, Zhang
YJ. The clinical value of fluorine-18 fluorodeoxy-
glucose positron emission tomography/computed
tomography in postoperative patients with gastro-
intestinal mucinous adenocarcinoma. Nucl Med
Commun 2011; 32:1018–1025
74. Lupinacci RM, Mello ES, Coelho FF, et al. Prog-
nostic implication of mucinous histology in re-
sected colorectal cancer liver metastases. Surgery
2014; 155:1062–1068
75. Nozoe T, Anai H, Nasu S, Sugimachi K. Clinico-
pathological characteristics of mucinous carcino-
ma of the colon and rectum. J Surg Oncol 2000;
75:103–107
76. Verwaal VJ, Bruin S, Boot H, van Slooten G, van
Tinteren H. 8-year follow-up of randomized trial:
cytoreduction and hyperthermic intraperitoneal
chemotherapy versus systemic chemotherapy in
patients with peritoneal carcinomatosis of
colorectal cancer. Ann Surg Oncol 2008;
15:2426–2432
77. van Oudheusden TR, Braam HJ, Nienhuijs SW, et
al. Poor outcome after cytoreductive surgery and
HIPEC for colorectal peritoneal carcinomatosis
with signet ring cell histology. J Surg Oncol 2015;
111:237–242