CASE REPORT

Complete clinical response of a primary squamous cell carcinoma of the rectum

Emiliano Caruso, Mateo Lendoire, Nicolás Rotholtz, Maximiliano Bun

General Surgery Department, Coloproctology Section, Hospital Alemán de Buenos Aires

The authors declare no conflict of interest.

Emiliano Caruso: caruso95611@gmail.com

Received: July 2022. Accepted: October 2022

Emiliano Caruso: 0000-0001-7286-763X

Mateo Lendoire: 0000-0002-7796-3644

Nicolás Rotholtz: 0000-0002-4811-3739

Maximiliano Bun: 0000-0002-2819-819X

Received: July 2022. Accepted: October 2022

ABSTRACT

Primary squamous cell carcinoma (SCC) of the rectum is a rare disease with few cases reported in the literature. We present a 61-year-old woman with 1-month-long diarrhea with hematochezia and mucorrhea due to an exophytic and friable rectal mass 4 cm from the anal margin. The biopsy with immunohistochemistry diagnosed SCC. Nuclear magnetic resonance (NMR) staged the tumor as rmT3dN2aM0 and compromised circumferential margin. Computed tomography did not show distant metastases. The Nigro protocol with chemoradiotherapy was performed. After 12 weeks of treatment, the absence of residual lesion was demonstrated in digital rectal examination, endoscopy, and restaging MRI. After 12 months of follow-up, the complete clinical response persisted. In the literature, primary chemoradiotherapy has shown acceptable oncological results, avoiding primary surgery for this rare disease. Further studies are needed to demonstrate its benefit on safety and survival.

Key words: rectal cancer; Nigro protocol; chemoradiotherapy; rectal squamous cell carcinoma

INTRODUCTION

Squamous cell carcinoma (SCC) of the gastrointestinal tract is an entity that generally affects the esophagus and anus. It is estimated that 90% of rectal neoplasms are adenocarcinomas and the remaining 10% are carcinomas, sarcomas, and lymphoproliferative tumors.1

SCC of the rectum is a rare disease. Its incidence represents approximately 0.1 to 0.25 per 1000 colorectal malignancies.2 Only a few cases have been reported in the literature, making the preferred treatment less clear.

CASE

A 61-year-old woman with no relevant medical history consulted for diarrhea with hematochezia and mucorrhea of 1 month's duration. A digital rectal examination revealed a mass approximately 4 cm from the anal verge on the left lateral wall of the lower rectum.

A diagnostic colonoscopy revealed a 4 cm exophytic friable rectal mass that was biopsied (Fig. 1). Histopathology showed a poorly differentiated neoplasm with extensive necrosis, and immunohistochemical staining (IHC) diagnosed a P63-positive, CK20-negative and AE1-AE3-positive SCC (Fig. 2). Magnetic resonance imaging (MRI) showed invasion beyond the muscularis propria, with a positive circumferential resection margin (CRM) and four lymph nodes with malignant morphological criteria, rmT3dN2aM0 (Figs. 3, 4 and 5. Computed tomography (CT) demonstrated the absence of distant metastases. The carcinoembryonic antigen was 1.8 ng/ml. Gynecological examination and transvaginal ultrasound revealed no abnormalities.

Figure 1. Exophytic lesion on the left lateral aspect of the rectum, with an implantation base 3-4 cm from the anal edge, which occupies the entire circumference.

Figure 2. Histopathology and immunohistochemical profile. A. Squamous cell carcinoma. H&E 40x. B. P63 positive. C. AE1-AE3 positive.

Figure 3. MRI T2 weighted image, axial plane. A. Endophytic tumor measuring 103 x 79 x 94 mm, that invades through the muscularis propria for a total of 52 mm. B. Mesorectal lymph nodes measuring 7.8 mm (a) and 9.8 mm (b).

Figure 4.  Axial, sagittal, coronal and 3D dose distributions of the initial plan.

Figure 5. Absence of residual lesion in the rectum, after chemoradiotherapy treatment.

The case was discussed by the multidisciplinary oncology team that decided to carry out the Nigro protocol. The patient received combination treatment with 5-fluorouracil 4000 mg/m2 total dose (1000 mg/m2/day, 6400 mg on days 1 to 5 and 28 to 32) + mitomycin C 12 mg/m2 on day 19, and three-dimensional conformal radiotherapy (3D-CRT) The total dose of radiotherapy was 45 Gy in the pelvis with a boost of 9 Gy in the rectal tumor, delivered in a fractionated manner over a long period of time (1.8 Gy x 30 fractions for 6 weeks) After delivering 23.4 Gy, a new planning CT scan was performed, which showed a significant reduction in the size of the tumor. The radiotherapy plan was adapted to these changes with greater protection of the organs at risk.

Twelve weeks after chemoradiotherapy, digital rectal examination revealed minimal scarring at the original tumor location, and colonoscopy revealed no residual lesion. MRI showed a complete response (yrmT0N0). A new gynecological examination showed no abnormalities.

The patient remained asymptomatic and maintained a complete clinical response after one year of follow-up, which was performed with clinical examination and high-resolution pelvic MRI every 3 months and annual chest CT.

DISCUSSION

SCC generally occurs in the esophagus or anus and rectal involvement is very rare, representing 0.1-0.25% per 1,000 cases of colorectal carcinoma.^2,3 About 90% of rectal cancer cases are adenocarcinomas.¹ As SCC is a rare entity, there is no standardized therapeutic regimen due to insufficient evidence.

Primary colonic SCC was first described in 1919 by Schmidtmann and in 1933 Raiford reported the first case of primary rectal SCC.

The pathogenesis of SCC is unclear. Studies suggest that inflammation secondary to infection, inflammatory bowel disease, or radiation results in squamous metaplasia from which cancer can arise. Another hypothesis claims that squamous cell differentiation by pluripotent stem cells leads to SCC, supported by the fact that cancerous squamous cells are often among poorly differentiated cells. It is also believed that the coexistence of a squamous component with an adenocarcinoma could be indicative of its potential development from adenomas or adenocarcinomas.¹

Postulated risk factors for the development of rectal SCC include ulcerative colitis, smoking, human immunodeficiency virus, human papillomavirus, and other enteric infections such as amoebiasis or schistosomiasis.² None of them were found in the case presented.

Depending on the location of the tumor, symptoms often include gastrointestinal bleeding (rectal bleeding or hematochezia), abdominal pain or discomfort, weight loss, anorexia, constipation, and diarrhea. It is reported that some cases could be asymptomatic, so the role of regular screening with a highly sensitive fecal occult blood test or colonoscopy is vital.

Endoscopic findings include a polypoid formation or a stenosing ulcerated tumor, but biopsy will yield the pathologic diagnosis. IHC techniques are useful to distinguish from poorly differentiated tumors; the most useful cytokeratins (CK) are CAM 5.2, AE1/AE3, and 34B12, with CAM 5.2 being useful for differentiating between anal and rectal SCC.² SCCs of the anal canal express CK7, CK5/6, p53, and p63 but are negative for CK20. In contrast, anal gland carcinomas are mucin-positive and express CK20 and CK7, but are negative for CK5/6 and p63. Our patient was p63 and AE1-AE3 positive and CK20 negative, confirming the rectal origin of the SCC.

MRI, CT, and endorectal ultrasound are used for imaging staging. Carcinoembryonic antigen is an early tumor marker that could increase in these cases and is useful for prognosis or to monitor response to treatment.^2,3

Williams et al.⁴ established four diagnostic criteria for primary colorectal SCC: 1) there should be no evidence of SCC elsewhere (e.g., cervix, bladder) that could metastasize to the large intestine, 2) the tumor must not have a fistula with squamous epithelium, 3) the tumor must not be a proximal extension of a primary anal SCC, 4) must be confirmed histologically. The patient reported met all of these criteria.

Historically, the surgical approach was considered the first treatment option, followed by adjuvant chemotherapy or radiotherapy.⁵Currently, this classical management has been questioned, based on the promising results of chemoradiotherapy as initial treatment in anal SCC. Although there are no specific treatment guidelines, the current trend is to establish chemoradiotherapy as the first approach, using a combination of mitomycin C with 5-fluorouracil and radiotherapy, with a minimum dose of 45-50 Gy,⁶ as was done in our patient.

The response is evaluated 6-8 weeks after the end of the treatment by means of rectosigmoidoscopy with biopsy, MRI or PET and periodic controls are carried out during follow-up. As in SCC of the anal canal, surgery should be reserved for tumor persistence after treatment, indicating anterior or abdominoperineal resection depending on tumor location, local staging, and patient characteristics.

There are some series in the literature with a low number of cases in which chemoradiotherapy as initial treatment showed a complete response in 66 to 100%, without the need for subsequent surgery.³A 5-year survival of 50% has been reported for the stage II that decreases to 33% with lymphatic involvement.²

CONCLUSION

Primary rectal SCC is a rare disease with no established standard treatment. Chemoradiation therapy has shown acceptable oncologic outcome avoiding primary surgery, but studies with large numbers of patients are needed to demonstrate its benefit on safety and survival, compared with the surgical approach.

REFERENCES

1. Sameer AS, Syeed N, Chowdri NA, Parray FQ, Siddiqi MA. Squamous cell carcinoma of rectum presenting in a man: A case report. J Med Case Rep. 2010; 4:392.

2. Dyson T, Draganov PV. Squamous cell cancer of the rectum. World J Gastroenterol. 2009; 15:4380-86.

3. Rasheed S, Yap T, Zia A, Mcdonald PJ, Glynne-Jones R. Chemo-radiotherapy: An alternative to surgery for squamous cell carcinoma of the rectum - Report of six patients and literature review. Colorectal Dis. 2009; 11:191-97.

4. Williams GT, Blackshaw AJ, Morson BC. Squamous  carcinoma of the colorectum and its genesis. J Pathol. 1979: 129:139-47.

5. Gelas T, Peyrat P, Francois Y, Gerard JP, Baulieux J, Gilly FN, et al. Primary squamous-cell carcinoma of the rectum: Report of six cases and review of the literature. Dis Colon Rectum. 2002; 45:1535-40.

6. Benson AB 3rd, Arnoletti JP, Bekaii-Saab T, Chan E, Chen YJ, Choti MA, et al. Anal carcinoma, version 2.2012: featured updates to the NCCN guidelines.  J Natl Compr Cancer Netw. 2012; 10:449-54.

COMMENT

Squamous cell carcinoma (SCC) of the rectum is a tumor with a very low incidence. It is defined as a squamous cell tumor of the rectum that does not have the presence of fistulous tracts and that is not related to the extension of a squamous cell tumor of anal or gynecological origin. The etiopathogenesis is uncertain.

Although the optimal treatment is not protocolized due to the low incidence of these tumors, the existing therapeutic regimen has been extrapolated from that used for both rectal adenocarcinoma and anal SCC. Currently, all anal SCC have an indication for chemoradiation with the Nigro protocol, with a high rate of satisfactory response. Similarly, adenocarcinoma of the middle and lower rectum has an indication for a chemoradiotherapy regimen, with a high response rate. In SCC of the rectum, the Nigro protocol can be performed because of its favorable response history for anal cancer and the favorable response of rectal cancer to chemoradiotherapy. In SCC of the rectum, the response will depend on the tumor size and biology and the disease progression at the time of diagnosis.

Depending on the therapeutic response observed, surgical treatment or exhaustive periodic follow-up will be indicated. The therapeutic regimen should be discussed by a multidisciplinary team (oncologist-radiation therapist-surgeon coloproctologist-imagenology specialist-pathologist) to decide the appropriate approach. Adequate discussion should be carried out with the patient and relatives to explain the therapeutic, response and prognostic possibilities.

Patients must be strictly monitored both locally and remotely (rectosigmoidoscopy-colonoscopy-MRI of the Pelvis-Computarized Tomography of the Thorax, Abdomen and Pelvis and gynecological check-up)

I congratulate the authors for reporting this case, the only way to disseminate and show the prevalence of the disease.

Marcelo Pollastri

Hospital Privado de Rosario, Santa Fe