Pseudomyxoma Peritonei: A Challenging Clinical Diagnosis. Case Report and Review of the Literature

Abstract

Background

Pseudomyxoma peritonei (PMP) is a clinical entity of subtle onset abdominal pain, ascites, and distention associated with characteristic imaging. In most cases, laparoscopic exploration will give the definitive diagnosis and histopathologic verification. However, usually there are difficulties in the diagnosis of this disease.

Case Report

Herein, we present a case of a 51-year-old female who developed ascites over 5 months. An investigational laparotomy established the diagnosis of PMP, after the discovery of a mucinous, grey-brown tumor that was CK20 positive and CK7 negative. Subsequently, chemotherapy with oxaliplatin combined with 5-FU (FOLFOX4 regimen), was initiated and the patient survived for 30 months. We also present a comprehensive review of the English literature concerning the different symptoms and radiological findings of this rare entity. According to the literature review, 35 cases of PMP with different clinical and radiological findings have been described. In the majority of the cases, ultrasound, computed tomography or magnetic resonance imaging was orientating towards a proper diagnosis before a diagnostic laparotomy.

Conclusion

The combination of a clinical picture with the characteristic imaging findings enables a prompt diagnosis of PMP, making prognosis more favorable.

Pseudomyxoma peritonei (PMP) is a rare disorder within the abdomen clinically presented with abdominal pain and mass, fatigue, and weight loss. It is characterized by progressive accumulation of mucin in the peritoneal cavity and the presence of gelatinous ascites and peritoneal implants. Due to the fact that the symptoms are not specific, it is usually incidentally discovered during surgery for other reasons (1).

PMP is commonly associated with malignant tumors in the appendix, but there is a controversy regarding the epithelium from which it originates (2,3). Theories of ovaries being an alternative primary site of PMP origin are considered to be convincing, although not fully explained when it comes to immunochemistry. The term is still being applied for a wide range of diseases and some oncologists and pathologists apply PMP to any condition with gelatinous material in the abdomen and pelvis (4).

The disease is three to four times more common in females than males and its incidence estimated at 1-2 per million per year (5,6). This case report presents the challenging clinical diagnosis of a PMP and the intriguing effect that it had on the choice of treatment.

Case Report

A 51-year-old female presented to the emergency department with a five month history of gradually deteriorating abdominal pain, abdominal distension and ascites. The clinical examination did not reveal any palpable masses of the abdomen beyond marked ascites. The computed tomography (CT) scan of the upper and lower abdomen revealed an ovary enlargement and ascites. Serum tumor markers were also measured to be as follows: CEA=312.9 ng/ml, CA125=72.9 IU/ml, CA19-9=520.6 ng/ml.

The patient underwent an investigational laparotomy, and a tumor was found in the right iliac fossa, infiltrating the right ovary, right fallopian tube, and omentum. A second tumor was found in the left ovary as well.

An extrafascial total abdominal hysterectomy along with bilateral salpingo-oophorectomy and resection of the infracolic omentum was performed. Macroscopically, the right iliac tumor was described as having a mucinous, cystic form (5×5×3cm) with an irregular inner surface and a multilobar, mucinous, grey-brown outer surface. The second tumor sallied out from the left ovary, laterally, towards the fallopian interspace, infiltrating almost the entire left fallopian tube. It was a multilobar, mucinous, grey-brown tumor (3×3×2.5cm). The histopathology and immunohistochemistry report (CK20 positive and CK7 negative) confirmed the diagnosis of a mucinous adenocarcinoma, in the context of PMP.

Although the extensive sampling of the surgical specimen did not reveal histological evidence of appendix residue (CK20 positive rather than CK7) and elevated CEA, the patient was treated with oxaliplatin combined with 5-FU (FOLFOX4 regimen), as first line treatment for stage IV colorectal cancer. The re-evaluation after six cycles showed virtually stable disease and it was decided that she should continue with second line chemotherapy, using the combination of irinotecan and 5-FU (FOLFIRI regimen).

Three months later, the patient was stable and underwent plastic surgery for omphalocele and white line hernia. The pathology report showed infiltration with mucinous cystadenocarcinoma, with extracellular and intracellular mucin production (signet-ring cells). Palliative treatment was offered, however, the patient died 30 months after the primary diagnosis.

Review of the literature. We searched MEDLINE for papers using the following key words: “pseudomyxoma peritonei”, “cancer”, “malignancy”, “presenting symptoms” and “laparatomy”. Reference lists in the retrieved papers were checked to identify any other published data. Cases were included if there was both clinical and histological evidence of PMP. Only papers written in the English language and cases with patients older than 14 years were included in the analysis. Data regarding the primary tumor, age, sex, presenting symptoms, and the clinical and diagnostic work up were analyzed.

Table I summarizes the 35 cases, including ours, that were identified in the literature review for patients experiencing symptoms of “pseudomyxoma peritonei”, presented with a variety of clinical pictures, stages at time of surgery, and histologic types.

Table I. Patients with pseudomyxoma peritonei (PMP).

Duration: Duration of symptoms; CT: computed tomography; F: female; M: male; MRI: magnetic resonance imaging; N/A: not assessed; u/s: ultrasound; IHC: immunohistochemistry.

Discussion

This report describes the clinical experience of managing a rare PMP case. The correct diagnosis of the disease is considered of high importance since the discovery of the origin indicates the appropriate treatment regimen. It is emphasized that even with no histological evidence of appendix residue; we must consider the primary origin as colorectal cancer (7). In this case, the immunohistochemistry findings (positive CK20 and negative CK7) and elevated tumor markers (CA19-9 and CEA) strongly supported the colorectal origin of this PMP. What merits a particular mention is the classification that pathologists have compiled for PMP subtypes, with different prognosis for each one: disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and an intermediate PMCA type (PMCA-1) (7).

PMP is a slowly progressive disease that can be presented with a variety of symptoms. Usually, PMP exhibits the characteristic “jelly belly”, as the amount of mucoid fluid fills the peritoneal cavity. Symptoms that have been described are abdominal pain, nausea, vomiting, fatigue, and urinary abnormalities. It can also be presented with local symptomatology, mirroring the location of the primary or metastatic tumor, like appendicitis (38).

In the majority of cases as we can see in Table I, the diagnosis was made only by CT (11 cases) with the assistance of ultrasound (u/s) or magnetic resonance imaging (MRI), followed by histopathologic verification of an extensively sampled tumor. In six cases, only u/s was performed (10,12,20,32,36,37), but in two of them (36,37), u/s misled the diagnosis, resulting in delayed treatment. Thus, CT or MRI would be probably the most appropriate imaging option, offering accurate and prompt diagnosis. Ultrasound usually describes cystic masses and mucinous substance as retroperitoneal fluid. CT and MRI will differentiate the fluid (watery vs. mucinous) and confirm the cystic nature of the masses.

Another important aspect for the diagnosis and follow-up of PMP patients is the assessment of serum tumor markers CEA and CA19-9. CEA has been reported to be increased in 56% to 75% of patients and CA19-9 in 58% to 67% respectively, whilst the baseline tumor marker values seem to be related to the extent of tumor and completeness of resection (39,40).

Analysis of immunohistochemical markers' expression, such as cytokeratin (CK) 7, 20, CEA, and CDX-2 is very useful in characterizing the origin of tumors. Positive expression of CK20, CEA, and CDX-2 imply primary colorectal or appendiceal origin while CK7 and CA125 indicate a primary ovarian origin (41).

There is currently no consensus regarding the optimal treatment for progressive PMP. Cytoreductive surgery, with or without hyperthermic intraperitoneal chemotherapy (HIPEC), despite possible concomitant morbidity is considered the proper treatment (42). Although several approaches have been described so far, the radical removal of all intra-abdominal and pelvic disease and the administration of intraperitoneal heated chemotherapy (mitomycin, 5-FU) have been adopted by most clinicians (43,44).

Conclusion

To conclude, the reported symptoms for PMP vary, the clinical course is vague, and there is no certain pathognomic signs that can lead to the prompt diagnosis and management of this clinical entity. Therefore, clinicians should demonstrate high index of clinical suspicion, as to discover this medical entity without delay.

Conflicts of Interest

No potential conflicts of interest exist in relation to this study.

Authors’ Contributions

All Authors equally contributed to this study regarding the conception and design of the study, literature review and analysis, drafting, critical revision, editing, and final approval of the final version.