Original Study
Adenocarcinoma of the Rectum—A Composite of Three Different Subtypes With Varying Outcomes?

https://doi.org/10.1016/j.clcc.2015.12.004Get rights and content

Abstract

Introduction

Adenocarcinoma of the rectum has been classified by the World Health Organization into various histologic subtypes. We analyzed the effect of the histologic subtype (classic, signet ring cell, and mucinous) on the clinical outcomes of patients with rectal cancer. We hypothesized that clinicopathologic outcome measures such as tumor margins, tumor regression grade, recurrence rate, and survival would vary with the histologic subtype.

Materials and Methods

We conducted a retrospective analysis of a prospectively maintained database. All patients with stage I-III rectal adenocarcinoma were included.

Results

From May 2010 to August 2013, 273 patients underwent curative resection. Both mucin-secreting variants were more common in younger patients and presented at a more advanced stage. Also, 54% and 48% of those with signet ring cell carcinoma (SRCC) and mucinous adenocarcinoma (MAC) had node-positive disease compared with the rate in the classic variant (30%). Circumferential resection margin positivity was 24% with MAC and 19% with SRCC compared with 4% with the classic variant. Disease-free survival for those with the classic and mucinous variants was 38.5 and 37.4 months, respectively. In contrast, it was 28.6 months in the SRCC group. The overall survival did not differ significantly.

Conclusion

Rectal adenocarcinoma presents as a spectrum of disease, with progressively worsening outcomes from classic to MAC to SRCC. These aggressive variants might warrant more aggressive resection. These data from the Indian subcontinent differ from the published data from Western countries.

Introduction

Considerable confusion exists regarding the terminology of mucin-secreting adenocarcinomas of the rectum. The World Health Organization (WHO) pathologic classification of gastrointestinal tumors has defined mucinous adenocarcinomas and signet ring cell adenocarcinomas as follows. Mucin-secreting adenocarcinomas (MACs) are those tumors in which > 50% of the lesion is composed of mucin. This variant is characterized by pools of extracellular mucin that contain malignant epithelium as acinar structures, strips of cells, or single cells.1 Signet ring cell carcinomas (SRCCs) are defined by the presence of > 50% of tumor cells with prominent intracytoplasmic mucin. The typical signet-ring cell has a large mucin vacuole that fills the cytoplasm and displaces the nucleus.1 With these definitions, however, a third undefined entity has come to the fore—tumors that satisfy both criteria (ie, poorly differentiated carcinoma with > 50% extracellular mucin and > 50% of a signet ring cell component). When analyzing the data from these mucin-secreting tumors of the rectum, it is essential to define all these entities a priori to reduce the confusion between the pathologist and the treating oncologist and also to prognosticate.

A paucity of data is available from the Indian setting regarding the outcomes of patients with these different pathologic features. In the Indian population, in which rectal cancer is seen at a younger age, the incidence of these subtypes could be different from that in other populations.

Both MACs and SRCCs have been associated with a younger patient age and advanced stage at presentation. It has also generally been believed that patients with SRCC or MAC will have a worse prognosis than those with the non–mucin-secreting variants. However, most of the older studies had the inherent drawback of not clearly defining these variants or of including both groups into one. Some studies have reported that those with mucinous tumors have a poor prognosis, but others have reported that those with SRCC have a poor prognosis. The mucinous variant has been shown to be less sensitive to chemoradiation. However, the response to chemotherapy has been shown to vary. Evidence is emerging that these 2 entities have different biologic outcomes and hence should be viewed from different perspectives.2, 3

The purpose of the present study was to analyze the effect of the histologic features on clinical outcome and the response to treatment. Using a prospectively maintained database, we analyzed all patients with nonmetastatic rectal cancer from a tertiary referral hospital in Western India to clarify the prognostic value of MAC and SRCC of the rectum. Our main aim was to determine the prognostic implications of mucinous and signet ring cell histologic features compared with the classic subtype. We hypothesized that the recurrence rates and survival would vary with the histologic subtype.

Section snippets

Materials and Methods

The present study was a retrospective audit of prospectively maintained data from all patients with rectal cancer who had undergone either upfront surgery or surgery after neoadjuvant chemoradiation at Tata Memorial Centre (Mumbai, India), a tertiary cancer referral center. The study period was from May 1, 2010 to August 31, 2013.

All the patients underwent the routine staging workup, including clinical evaluation, complete colonoscopy, magnetic resonance imaging (MRI) of the pelvis for local

Results

A total of 282 patients with adenocarcinoma of the rectum underwent TME during the study period. Of the 282 patients, 37 with early-stage disease underwent upfront surgery, and 245 underwent neoadjuvant chemoradiotherapy followed by resection. However, 9 of these patients, thought to have disease suitable for resection from the imaging findings, were found to have metastatic disease at laparotomy, and resection was abandoned. The remaining 236 patients underwent surgical resection in the form

Discussion

A large national database analysis from the MD Anderson Cancer Center reported that among rectal adenocarcinoma cases, the incidence of MAC is 7.08% and that of SRCC is 0.7%.4 Another single-institution series from China reported an incidence of MAC of 5% and of SRCC of 1.6% among rectal adenocarcinoma cases.5 However, our study found a strikingly different frequency for these variants in our series from a tertiary, referral center in Western India, with 14% of tumors having SRCC histologic

Conclusion

Critically analyzing our results, it is quite evident that a spectrum of rectal adenocarcinoma exists, with those with the mucinous subtype exhibiting clinicopathologic outcomes that are intermediate between the outcomes of those with the classic and signet ring cell variants. Hence, it is essential that clinicians and pathologists clearly identify the 3 variants a priori to prognosticate these patients and tailor the management plan accordingly. These data from the Indian subcontinent differ

Disclosure

The authors have stated that they have no conflicts of interest.

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