Squamous cell carcinoma of the rectum
- 1 Department of Radiation Oncology, King George's Medical University, Lucknow, India
- 2 Department of Pathology, King George's Medical University, Lucknow, India
- 3 Department of Surgical Oncology, King George's Medical University, Lucknow, India
- Correspondence to Deep Chakrabarti; deepchakrabarti.19@gmail.com
Abstract
Lower gastrointestinal cancers are commonly adenocarcinoma in the colon and rectum, and of squamous cell histology in the anal canal. Squamous cell carcinoma of the rectum is a rare disease attributable to squamous metaplasia in the rectum. The tumour location and histopathology should both serve as indicators to planning treatment, and a robust multidisciplinary team meeting forms the backbone of such decisions.
Background
Globally, lower gastrointestinal cancers are a significant cause of cancer-associated mortality. Adenocarcinoma is the predominant histology in the colon and rectum, while squamous cell cancers predominate in the anal canal. Colorectal cancers, when approached with a definitive intent, are treated by surgery with or without adjuvant chemotherapy, along with the addition of neoadjuvant radiotherapy in the event of middle or low rectal disease to achieve a clear resection margin and prevent local recurrences. Anal cancers are amenable to definitive chemoradiotherapy, while early disease can be excised locally. Common histopathologies may, however, occur in uncommon locations which make management decisions difficult. We present the case of a squamous cell carcinoma of the rectum which was treated by neoadjuvant chemoradiotherapy followed by surgery.
Case presentation
We saw a 39-year-old woman in our oncology outpatient clinic with a 2-month history of per rectal bleeding. Her medical history was not significant except for undergoing hysterectomy for a uterine leiomyoma 3 years back. General examination was unremarkable. Complete blood count, coagulation screen, liver and renal chemistries were normal. Per rectally, a growth was just palpable at 7 cm from the anal verge. A colonoscopy was performed, which showed a polypoidal lesion at 8 cm from the anal margin. A biopsy was obtained. Pelvic imaging studies and biopsy images including the panel for immunohistochemistry are shown in figures 1–4.
Contrast-enhanced CT scan showing asymmetric circumferential thickening of the rectal wall with an ill-defined interface with the urinary bladder.
Contrast-enhanced MRI of the pelvis showing irregular rectal wall thickening with abutment of the urinary bladder.
Rectal biopsy showing tissue lined by benign colonic glands (arrow) and nest of tumour cells in lamina propria (arrowhead) (A). These tumour cells are highly pleomorphic with hyperchromatic nuclei, coarse chromatin, inconspicuous nucleoli and moderate eosinophilic cytoplasm (B).
Immunohistochemistry panel shows the tumour cells strongly positive for p40, weakly positive for p63 and negative for CK20.
Investigations
Contrast CT scan of the abdomen (figure 1) showed asymmetric circumferential thickening of the rectal wall with an ill-defined interface with the urinary bladder. Contrast MRI of the pelvis (figure 2) revealed irregular rectal wall thickening with abutment of the urinary bladder. The biopsy showed tissue lined by benign colonic glands (arrow) and nest of tumour cells in the lamina propria (arrowhead)(figure 3A). These tumour cells were highly pleomorphic with hyperchromatic nuclei, coarse chromatin, inconspicuous nucleoli, and moderate eosinophilic cytoplasm (figure 3B). On the immunohistochemistry panel (figure 4), the tumour cells were strongly positive for p40, weakly positive for p63, and negative for CK20. The diagnosis, although somewhat unusual, was a squamous cell carcinoma of the rectum.
Differential diagnosis
Commonly, malignant lesions in the rectum tend to be adenocarcinomas, which had to be excluded as part of our management plan. The patient was taken for a multidisciplinary tumour board meeting where the unanimous decision was a review of the imaging and the biopsy specimens. Our team of radiologists suggested that there was no anal canal extension of the lesion, hence an anal canal primary squamous cell cancer with rectal extension was ruled out. The oncopathologist confirmed the presence of simple columnar epithelial lining of the rectum and colonic glands in the biopsy specimen. The epithelial lining is an essential finding that differentiates the rectum from the anal canal histologically, as the anal canal is lined by stratified squamous epithelium. Thus, a final diagnosis of a primary rectal SCC was arrived at. The overall 2017 UICC TNM stage was cT3N0M0.
Treatment
The next purpose of the discussion was to define the management protocol. It was decided to give the patient neoadjuvant chemoradiotherapy, followed by surgery at 8–12 weeks postradiotherapy completion. The patient was planned by 3D conformal radiotherapy on an Elekta Synergy linear accelerator system to a dose of 50.4 Gy in 28 daily fractions with concurrent capecitabine (1650 mg/m2 in two daily divided doses) and mitomycin C (12 mg/m2, intravenous bolus on D1). At 10 weeks post-treatment, the patient did not have a complete clinical response on preoperative imaging. She underwent an anterior resection, and the postoperative histopathology was a pathological complete response. The final stage was ypT0N0.
Outcome and follow-up
She has been kept on follow-up and is asymptomatic at 1 year following surgery.
Discussion
Primary squamous cell colorectal cancers are sporadic. We have evolved from questioning their mere existence1 to accepting squamous metaplasia, due to either chronic stress or chronic inflammation as their origin.2 While multiple hypotheses exist to explain their aetiology, the most accepted ones include chronic inflammation due to infections, inflammatory bowel disease, chronic mucosal injury or radiation exposure as triggers for squamous metaplasia.3 Human papillomavirus (HPV) infection may also play a role in pathogenesis, and it has been shown in experimental models that HPV transfection into colonic adenocarcinoma cells can induce squamous metaplasia.4
Being a rare disease, most of our evidence in treating them is from small retrospective or prospective cohorts. Three of the largest of these cohorts report reasonable local control with chemoradiotherapy.5–7 The largest population-based analysis, however, contradicts these findings and found that survival outcomes were improved by adding surgery to radiotherapy in regional disease.2 It is important to note that reliable identification of node-negative patients is difficult before surgery, so the categorisation of disease as local or regional is not straightforward. Additionally, one must consider the predominance of lower or lower-middle rectal tumours in these cohorts, and the few relapses reported were usually in the upper-middle tumours. The authors wish to propose decision-making on the location of the tumour as well as the histopathology, thereby offering surgery after neoadjuvant radiotherapy in upper-middle tumours and definitive chemoradiotherapy in lower rectal tumours. This is based on the fact that sphincter preservation is possible in upper-middle tumours vide an anterior resection, while lower tumours will require an abdominoperineal resection with the sacrifice of the sphincter. Hence, surgical intervention can be kept as a salvage option for the latter.
Learning points
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Primary rectal squamous cell carcinoma is a rare malignancy, and its pathogenesis may lie in squamous metaplasia in the rectum.
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A robust multidisciplinary team forms the backbone of management, and all decisions should be taken in a tumour board.
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The tumour location and histopathology should both serve as indicators to planning treatment, with neoadjuvant chemoradiotherapy and surgery for upper-middle rectal tumours and definitive chemoradiation for lower rectal tumours.
Footnotes
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Twitter @deep190690
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Contributors DC, RG: radiotherapy planning and treatment. SQ: histopathological work-up. NA: operating surgeon. DC wrote the manuscript. SQ, NA and RG provided expert insights. All authors have read and approved the final draft.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests None declared.
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Patient consent for publication Obtained.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.
References
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