Can low grade PMP be divided into prognostically distinct subgroups based on histological features? A retrospective study and the importance of using the appropriate classification

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Abstract

Introduction

The pathological classification of PMP of appendiceal origin has prognostic and treatment implications. Our goals were to

• Classify low grade mucinous carcinoma peritonei (LGMCP) into prognostically distinct subgroups based on histological features.

• Compare the reproducibility of the WHO and the PSOGI classifications for both PMP and the appendiceal primary tumor.

Patients and methods

A retrospective analysis of patients undergoing CRS and HIPEC or debulking surgery was done. All the tumors were re-classified according to the PSOGI classification. LGMCP was further classified into three histological subgroups and the impact on survival was evaluated.

Results

From Jun 2011 to June 2016, 101 patients underwent CRS with HIPEC (n = 89) or debulking surgery (n=12). The median PCI was 28 (3–39) and 74.1% patients had CC-0/1 resections. Of the 76.2% patients who had LGMCP, 4 patients (5.1%) were classified as group 1, 54 (70.1%) as group 2 and 19 patients (24.6%) as group 3. At a median follow up of 21 months, the disease free survival was not reached, 30 months and 14 months for groups 1, 2 and 3 respectively (p = 0.09). There was no difference in overall survival. Using the WHO classification, there was a discordance in the grade of the primary tumor and the peritoneal lesions in 19.8% and conflicting terminology was used in 62% of patients.

Conclusions

The subgroups of LGMCP described here are prognostically different though this needs further prospective evaluation in larger series. The PSOGI classification is more uniformly reproducible and should be preferred to the WHO classification.

Introduction

The grade of pseudomyxoma peritonei (PMP) of appendiceal origin has prognostic and treatment implications [1]. The first classification developed by Ronnet and collaborators fell out of use because PMP was considered a benign condition and the current consensus is that given its propensity for relentless growth and ability to spread and invade organs, it is a malignant condition [2]. Currently, the World Health Organization (WHO) classification and the peritoneal surface oncology group international (PSOGI) consensus classification are the most commonly used classifications [3], [4]. PMP of appendiceal origin represents a unique clinical condition where the primary tumor and the peritoneal lesions are graded separately [5]. The PSOGI classification is only for PMP of appendiceal origin whereas other classifications do not make this distinction.

For mucinous appendiceal tumors, the main difference between the two classifications is the definition of invasion. The WHO classification considers tumor extension beyond the muscularis mucosa as invasion whereas in the PSOGI classification only lesions showing infiltrative invasion are considered invasive [3], [4]. Similarly, for the peritoneal lesions, in the WHO classification, which retains the term PMP, tumors with bland epithelium with minimal or no atypical and low cellularity (<10%) are classified as low grade PMP and all others as high grade PMP. Involvement of the surface of organs like the ovaries and the spleen is classified as high grade PMP. The description of this classification also states that low grade PMP represents a very well differentiated adenocarcinoma and subsequent publications have used the terms ‘low grade mucinous adenocarcinoma (LGMAC)’ and ‘high grade mucinous adenocarcinoma (HGMAC)’ for low grade and high grade PMP respectively [5], [6]. This leads to the use of the term ‘low grade mucinous adenocarcinoma’ to describe low grade PMP which represents a high grade disease process leading to confusion among the clinicians [7]. The PSOGI classification divides PMP into four groups namely acellular mucin, low grade mucinous carcinoma peritonei (LGMCP) - synonymous with diffuse peritoneal adenomucinosis- (DPAM) in the Ronnet classification, high grade mucinous carcinoma peritonei (HGMCP)- synonymous with peritoneal mucinous carcinomatosis (PMCA) and high grade mucinous carcinoma peritonei with signet ring cells (HGMCP-S). In most cases making a distinction between LGMCP and HGMCP is relatively straightforward for a pathologist. However, there are situations in which overlapping pathological features are present and the classification in these situations becomes subjective. This is partly due to the fact that LGMCP itself includes a broad spectrum of tumors with varied pathological features and secondly, the division into high and low grade is not completely objective. The goals of performing this study were.

  • 1.

    To classify low grade mucinous carcinoma peritonei (LGMCP) into prognostically distinct subgroups based on histological criteria

  • 2.

    To compare the reproducibility and clinical implications of the WHO and the PSOGI classifications for both PMP and the appendiceal primary tumor.

Section snippets

Methods

This is a retrospective study of patients of PMP of appendiceal origin undergoing CRS and HIPEC or debulking surgery at two peritoneal surface malignancy units in India. The slides of patients treated from June 2011 to June 2016 were retrospectively reviewed. Institutional permission was obtained.

Results

From Jun 2011 to June 2016, 101 patients underwent CRS with HIPEC (n = 89) or debulking surgery (n = 12). The characteristics of the patients are listed in Table 1. 66/89 patients (74.1%) had a CC-0/1 resection. The median PCI was 28 (range 3–39; mean 26.3).

Discussion

An essential component of the multidisciplinary team for the management of peritoneal metastases is the pathologist both for providing the correct diagnosis in case of rare tumors and for an accurate assessment of the tumor biology in others. In PMP, there is a significant difference in the long term outcomes in patients with low and high grade disease [11]. In non-specialized and emerging centers on the learning curve, the pathologists are faced with two challenges-selecting the appropriate

Conclusions

The use of the WHO classification led to a discrepancy of 19.8% % in the grade of the peritoneal lesions and primary tumors and the use of conflicting terminology in 62% of the patients. The PSOGI classification classifies both the primary and peritoneal lesions more accurately, is uniformly reproducible and should be preferred over the WHO classification. Criteria for classifying PMP into various groups should be made more objective by an expert consensus. Using the histological criteria

Conflicts of interest statement

All authors declare no conflicts of interest.

Acknowledgement

The authors thank Prof. Frederic Bibeau for his insights and inputs on the subject.

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