Clinical Case Report

Signet ring cell carcinoma of the rectal stump in a known ulcerative

colitis patient
Asmanaz Nadaf1 , Ibrahim Hassan Al Haddabi1 , Ramesh Babu Telugu1 ,
Mansour S Al Moundhri2 
How to cite: Nadaf A, Al Haddabi IH, Telugu RB, Al Moundhri MS. Signet ring cell carcinoma of the rectal stump in a known
ulcerative colitis patient. Autops Case Rep [Internet]. 2023;13:e2023418. https://doi.org/10.4322/acr.2023.418

ABSTRACT

Colorectal carcinoma (CRC) is the third most commonly diagnosed cancer worldwide and is the second most common
cause of cancer-related deaths. However, the Omani population shares the major burden as the most prevalent
carcinoma. The disease is comparatively higher in males than females. Patients with pre-existing risk factors, including
inflammatory bowel disease, are at increased risk of developing neoplasia. Among the various histopathological subtypes
of adenocarcinoma in the rectum, signet ring cell carcinoma is the rarest and accounts for approximately 1% of the
cases. Given the aggressive nature of this tumor, advanced presentation, stage, and poor prognosis, regular endoscopic
surveillance is essential. Hereby, we report a rare case of signet ring cell carcinoma arising in the rectal stump in an already
diagnosed and operated patient of Ulcerative colitis.

Keywords
Colon; Carcinoma; Ulcerative Colitis; surveillance; Rectum

INTRODUCTION

Colorectal carcinoma (CRC) is the third most most common cancer in males and the 4th most
commonly diagnosed cancer worldwide and is in females. The incidence has increased in the last
the second most common cause of cancer-related 15 years. The rectum is the most common site of
deaths. 1 The incidence of this cancer is higher in colorectal cancer, followed by the sigmoid colon,
younger patients, with the incidence rate increasing
ascending colon, descending colon, and transverse
by 1.5% in males and 1.6% in females.2 Patients with
colon. 3 The main risk factors for ulcerative colitis-
inflammatory bowel disease (IBD) are at increased risk
associated colorectal cancer, include age at onset,
for colorectal cancer. The risk factors include extensive
colonic disease, the severity of colonic disease, duration, the extent of disease, active smoking history,
long disease duration, and the presence of primary family history of CRC, and concomitant diagnosis of
sclerosing cholangitis (PSC).1 primary sclerosing cholangitis. Patients with risk factors
The Omani population witnesses colorectal require regular screening and preventing exposure to
cancer as the most common cancer. It is the second risk factors.4

1
Sultan Qaboos Comprehensive Cancer Care and Research Centre, Department of Pathology, Laboratory Services, Muscat, Oman
2
Sultan Qaboos Comprehensive Cancer Care and Research Centre, Department of Medical Oncology, Muscat, Oman

Copyright © 2023 The Author(s). This is an Open Access article distributed under the terms of the Creative
Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly cited.
Signet ring cell carcinoma of the rectal stump in a known ulcerative colitis patient

The pathogenesis of IBD-CRC is related to bilateral external iliac, bilateral internal iliac, bilateral
cellular damage that interacts with tumorigenesis common iliac and aortocaval and paraaortic lymph
transcription factors leading to dysplasia and nodes, likely metastatic.
adenocarcinoma.5 Among the various histopathological The lesion was biopsied and sent for
subtypes of rectal adenocarcinoma, signet ring cell histopathological examination. The microscopic
carcinoma is the rarest and accounts for approximately evaluation showed ulcerated mucosa with reactive
1% of all cases. Due to intrinsic tumor biology, this epithelial changes and the lamina propria distended
subtype is characterized by aggressive biological with signet ring cells exhibiting typical morphology of
behavior and poor prognosis. Signet ring cell carcinoma peripherally pushed eccentric nuclei and a large mucin
is commonly seen in young individuals and is associated vacuole (Figure 1A).
with unique molecular profiles like microsatellite Immunohistochemistry shows the tumor cells were
instability and BRAF mutations.6 The present article positive for CDX-2 (Figure 1B), CK20 (Figure 1C), Cam
reports a rare case of signet ring cell carcinoma arising 5.2, and focally for CK-7. Additionally, the neoplastic
in the rectal stump in an already diagnosed patient cells were strongly positive for p53, and the Ki67 index
with ulcerative colitis. was 40% (Figure 1D). There was retained nuclear
expression for all the Mismatch repair (MMR) proteins
CASE REPORT (Figure 2A to 2D). The diagnosis of poorly cohesive
carcinoma with signet ring cells- MMR proficient was
A 40-year-old gentleman with comorbidities signed out. The molecular profile showed RAS and
like hypertension, chronic kidney disease, and IBD RAF Wild Type.
was referred to our institution for further treatment. The patient did not undergo surgery for the
The patient had a history of ulcerative colitis with rectal stump due to the fluctuating renal function
recurrent severe bouts for long-standing for about and to preserve the sphincter function. Hence
13 years and underwent surgery (subtotal colectomy only biopsy was performed for tissue diagnosis.
and Ileostomy). The histopathological examination 6 cycles of mFOLFOX (folinic acid, fluorouracil and
of the colectomy specimen performed in outside oxaliplatin) chemotherapy were administered after the
hospital was reported as severe pancolitis favoring confirmation of adenocarcinoma in the rectal stump
ulcerative colitis and polyps with low-grade dysplasia. biopsy. The follow-up PET scan showed complete
The medical management of ulcerative colitis and its resolution of the enlarged nodes and a significant
clinical and endoscopic response to the medications reduction in the FDG rectal uptake. The patient is under
used was not documented in our medical records as follow-up with a good response to chemotherapy.
the patient was referred from outside the hospital.
The possible risk factors for the development of
DISCUSSION
ulcerative colitis-associated colorectal cancer in this
patient include long-standing duration of disease for Compared to the general population, the incidence
about 13 years and severe pancolitis. of colorectal cancer was found to increase among
The patient was subjected to surveillance before and patients with ulcerative colitis.1 Many risk factors,
after the surgery as per medical records. The patient was such as the long duration of the disease, ongoing
on regular follow-up for his fluctuating renal function. inflammation, extensive mucosal involvement, backwash
The proctoscopy performed in-house showed a rectal ileitis, and concomitant sclerosis, increase the risk of
stump mass with stricture located at 3 cm from the anal neoplasia.4,7 The associated dysplasia with ulcerative
verge, through which the scope couldn’t be passed. colitis mostly occurs in the left colon/distal colon, with
Positron Emission tomography (PET) fluorodeoxyglucose 44 to 72% of the cases occurring in the recto-sigmoid
(18F-FDG) whole body scan showed increased metabolic region.8,9 However, the risk increases with pancolitis
activity in the rectum with mildly FDG avid perirectal compared to left-sided colitis.1 Precisely in the present
fat stranding with thickening of mesorectal fascia with case report, ulcerative pancolitis prevailed for a longer
mildly FDG avid perirectal, presacral, inferior mesenteric, duration of 13 years with the existence of pancolitis.

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 Nadaf A, Haddabi IHA, Telugu RB, Al Moundhri MS

Figure 1. Photomicrographs of the colon. A – Signet ring cell carcinoma in colonic mucosa (H&Ex200); B –
Immunohistochemical positive staining for CDX2 (X200); C – CK20 (X200); and D - Ki-67 (X200).

The pathogenesis of the development of surveillance is decided on the basis of the patient’s risk
neoplasia in IBD is attributed to repeated cycles of factors. A new technique, chromoendoscopy, proved
inflammation leading to the initiation and progression to be highly effective for monitoring programs and
of carcinogenesis.1 Chronic inflammation often results suggested its use with targeted biopsy.7
in re-epithelization of cells, increased cell turnover in It is a fact that the risk of neoplasia exists in the
colonic mucosa and heightened risk of errors in the cell rectal stump. However, postoperative endoscopic
cycle repair in association with oxidative stress and low surveillance could detect dysplasia/cancer at an early
internal defense mechanism for detoxification, which stage. Patients with ileorectal anastomosis (IRA) had
has a cumulative effect to promote the progression to a greater risk of developing neoplasia than those with
neoplasia.5 Primarily, changes occurring at the molecular ileal pouch-anal anastomosis (IPAA).9
level are TP53 mutations, microsatellite instability, and In a study done by Belli et al.10 it is highlighted that
CPG island hypermethylation. In addition, the variations primary signet ring cell carcinoma is (i) an aggressive
in the microbiota have also been attributed to the cause tumor, (ii) frequently seen in the younger age group at
of the development of neoplasia in ulcerative colitis.1 around 40 years, (iii) advanced stages of presentation
Adequate surveillance of patients identified and (iv) poor prognosis. In the present case, the patient
as at-risk patients might significantly improve the was found to be in a similar age group.
management of IBD-CRC risk. Current evidence-based Signet ring cell carcinoma is defined as > 50%
guidelines recommend surveillance colonoscopy for of the tumor cells with prominent intracytoplasmic
patients with colitis 8 to 10 years after diagnosis; further mucin, typically with displacement and molding of the

Autops Case Rep (São Paulo). 2023;13:e2023418 3-6

Signet ring cell carcinoma of the rectal stump in a known ulcerative colitis patient

Figure 2. Photomicrographs of the colon. Immunohistochemical reactions positive for: A – MSH6 (X200); B – PMS2
(X200); C – MLH1(X200); and D – MSH2 (X200).

nucleus. This subtype has a very low (1%) incidence In the present case, the distinction from benign
rate in the rectum and is more common in the right signet ring cell change was made based on single-cell
colon.8 In the present case, the origin was on the left infiltration in the lamina propria and cytological atypia.
side at the ileostomy site in the rectal stump. However, this is quite challenging in some cases.
The histopathological diagnosis of signet ring cell The Immuno-markers routinely used to differentiate
carcinoma is sometimes challenging due to the presence between benign mimics and true signet ring cell
of benign signet ring cell change. This was first described carcinomas are p53 and Ki-67. In a study done by
as a pseudo-neoplastic phenomenon seen commonly Khan et al.11, it was found that the benign signet ring
in gastric xanthomas and transurethral prostatectomy cells were found to be 100% negative for p53 and
specimens. However, in the gastrointestinal tract (GIT), Ki67. However, in our case, the tumor cells displayed
most benign signet ring cell changes are reported in strong positivity for p53 and ki-67 with the labeling
areas of injury or ischemia and are usually limited to index of 40%, indicating malignant signet ring cells.
the mucosa. The morphological features that favor Signet ring cell carcinomas are usually associated with
benign signet ring change are circumscription and microsatellite instability and BRAF mutations.6 In the
lobulated appearance, absence of single-cell infiltration present case, MMR proteins were intact and proficient,
and bland cytological features.11 while RAS and RAF showed wild type.

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 Nadaf A, Haddabi IHA, Telugu RB, Al Moundhri MS

In conclusion, signet ring cell carcinoma is 5. Sunkara C, Swanson G, Forsyth CB, Keshavarzian A.
a very aggressive and rare subtype of colorectal Chronic inflammation and malignancy in ulcerative
colitis. Ulcers, 2011;2011:714046. https://doi.
adenocarcinoma. Its occurrence at the rectal stump
org/10.1155/2011/714046.
region is rare. Owing to its advanced presentation stage
and dismal prognosis, regular endoscopic surveillance 6. Nitsche U, Zimmermann A, Späth C, et al. Mucinous and
signet-ring cell colorectal cancers differ from classical
must be undertaken in patients with ulcerative colitis, adenocarcinomas in tumor biology and prognosis.
irrespective of surgical status. Further studies are Ann Surg. 2013;258(5):775-82, discussion 782-3.
encouraged because there is a lack of literature on the http://dx.doi.org/10.1097/SLA.0b013e3182a69f7e.
development of neoplasia after colectomy. PMid:23989057.

7. Fornaro R, Caratto M, Caratto E,  et al. Colorectal

cancer in patients with inflammatory bowel disease: the
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This study was carried out at the Sultan Qaboos Comprehensive Cancer Care and Research Centre, Department
of Pathology, Muscat, Oman.

Authors’ contributions: Asmanaz Nadaf was responsible for data collection and manuscript preparation,
Ibrahim Hassan Al Haddabi, Ramesh Babu Telugu and Mansour S Al Moundhri were responsible for manuscript
preparation and review.

Ethics statement: We hereby state that an informed consent authorizing data publication was taken from the
patient. The manuscript has been cleared by the institutional Ethics Committee (IRB & EC Project ID: CCCRC-
40-2022).

Conflict of interest: The authors do not have any conflict of interest to disclose.

Financial support: The authors declare that no financial support was received.
Submitted on: November 17th, 2022
Accepted on: December 23rd, 2022

Autops Case Rep (São Paulo). 2023;13:e2023418 5-6

Signet ring cell carcinoma of the rectal stump in a known ulcerative colitis patient

Correspondence
Ramesh Babu Telugu
Sultan Qaboos Comprehensive Cancer Care and Research Centre, Department of Pathology, Laboratory
Services
P.O. Box 566, P.C: 123, SQU Street Al Khoud, Muscat, Sultanate of Oman
Phone: +0 (968) 2277-4131
[email protected]

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