An unusual aetiology in a patient with increasing abdominal girth

Ms Jenna Lyttle


Ms Jenna Lyttle
Monash University

Jenna is a final year MBBS (Hons.) student at Monash University in Melbourne. Before studying Medicine, she worked in the Allied Health sector as a physiotherapist. She has a keen interest in women's health, clinical research and bioethics.


Pseudomyxoma peritonei (PMP) is a rare, slow growing mucinous ascites, typically associated with primary appendiceal or ovarian neoplasm [1]. Mucinous material fills the peritoneal cavity, causing enlargement of the abdomen and has been described as “jelly belly”, due to its appearance at laparotomy [2]. The symptoms of PMP are often non-specific and vague, causing difficulties in diagnosis. Further, diagnostic imaging is not always able to detect the disease prior to surgery. The clinical implications of this are that PMP is not commonly considered a differential diagnosis in patients with these symptoms, which may then delay the diagnosis being made. This causes a potential delay in treatment, which has been shown to worsen the morbidity and mortality associated with PMP [3,4].

Introduction

Pseudomyxoma peritonei (PMP) is a rare, slow growing mucinous ascites, typically associated with primary appendiceal or ovarian neoplasm [1]. Mucinous material fills the peritoneal cavity, causing enlargement of the abdomen and has been described as “jelly belly”, due to its appearance at laparotomy [2]. The symptoms of PMP are often non-specific and vague, causing difficulties in diagnosis. Further, diagnostic imaging is not always able to detect the disease prior to surgery. The clinical implications of this are that PMP is not commonly considered a differential diagnosis in patients with these symptoms, which may then delay the diagnosis being made. This causes a potential delay in treatment, which has been shown to worsen the morbidity and mortality associated with PMP [3,4].

Case

A 48-year-old female presented to her general practitioner with a two-month history of increasing abdominal girth and a feeling of pelvic “fullness”. Importantly, she had not been unwell, did not have any infective symptoms, no loss of weight or appetite, and no nausea or vomiting. Her bladder and bowel function was normal, her periods were regular, and her Pap smears were up to date and normal.

The patient had a past medical history of primary hypothyroidism and depression, both of which were clinically stable. She had no known allergies. Her regular medications were Fluoxetine (20 mg daily) and thyroxine sodium (100 mg daily). She lived with her 16-year-old daughter, and worked full time in a delicatessen. Her family history included bowel, prostate, and breast cancer.

Her GP ordered various investigations (Table 1). Her borderline high CA-125 level (38 kU/L, reference range < 36 kU/L) and the imaging findings suggested a possible gynaecological malignancy.

Table 1: Initial investigation results

Full blood examination Normal
UEC Normal
Ca125^ 38 (RR* < 36 kU/L)
CEA^ 7.2 (RR* < 2.5 mg/L in non-smokers)
Ca19.9^ 12 (RR* < 31 kU/L)
Trans-abdominal ultrasound
  • Normal-sized, anteverted uterus.
  • Right adnexa: large complex-appearing mass lesion associated with ascites. Right ovary not able to be visualised.
  • Left adnexa: left ovary slightly bulky but unremarkable.
CT chest/ abdomen/ pelvis Relevant features:

  • Multiloculated cystic lesion noted within the right side of the pelvis that measures 9 cm in maximum diameter.
  • Thin septa with associated calcifications are noted.
  • Ascites is present in the peritoneal cavity and there is streaking of the omentum. Some of this streaking is suspicious for omental seeding.
  • There is no retroperitoneal lymphadenopathy seen

Conclusion: right-sided pelvic lesion consistent with ovarian mucinous cystadenomatous-type lesion. The presence of ascites and possible omental caking suggests adenocarcinoma.

  • *RR: reference range
  • ^Ca125: cancer antigen 125, CEA: carcinoembryonic antigen, Ca19.9: cancer antigen 19.9. These are common tumour markers used in conjunction with clinical examination and other investigations to aid cancer diagnosis.

She was referred to an outpatient gynaecological oncology clinic for further evaluation and formulation of a management plan. On examination in the clinic, the patient looked well and was afebrile. Her abdomen was distended, with a palpable, non-tender mass in the right iliac fossa. Mild ascites was present. She was also obese (BMI 37). Per vaginal examination revealed a palpable mass, with noted fixation of the right adnexa. Her uterus was mobile, non-tender, and of normal size and morphology.

The patient was discussed at the multidisciplinary team meeting where it was recommended that she undergo a laparotomy for total abdominal hysterectomy, bilateral salpingo-oophrectomy, and omentectomy. At the time of the surgery, she was noted to have extensive mucinous material throughout her peritoneum, and within her uterus and cervix. The mass seen on imaging was found to be an enlarged appendix, which required concurrent general surgical consultation for removal. The specimens were sent to pathology for analysis (Table 2).

Table 2: Formal pathology results

Cytology
  • Smears are mildly cellular, with abundant thick mucin, in keeping with peritoneal mucinosis or pseudomyxoma peritonei.
  • No overt malignant cells identified.
Histopathology Macroscopic
  • Uterus, tubes and ovaries: serosal surface of the uterus appears haemorrhagic, with multiple mucin-containing cystic lesions. No mass lesion is identified. The left ovary is haemorrhagic with a disrupted cyst present. The right ovary is partially covered in mucinous material and cysts. Unremarkable myometrium.
  • Appendix: large specimen (9 cm x 6 cm x 5 cm) that is disrupted, cystically-dilated and containing mucin. The surface is congested, with mucin extravasation present.
Microscopic
  • Uterus, tubes and ovaries: all sections of the serosa have organising mucinous exudate present. No tumour cells are seen in the serosal mucous. No neoplasia is seen in either ovary.
  • Appendix: dilatation of the proximal lumen, with marked fibrosis and patchy calcifications. Distally the lumen is distended by mucin, with tall columnar epithelium showing basophilic hyperchromatic nuclei and suprabasaloid mucin production. Some of these atypical cells are spread over the surface of the luminal mucus. The mucin has dissected through the appendix muscularis to rupture into the peritoneal cavity.

The subsequent histopathological diagnosis was of a primary appendiceal malignancy, with rupture and extensive mucin extrusion into the peritoneal cavity.

She had an unremarkable post-operative course, and was discharged home on day 4. She was to be followed up with the pathology results for relevant discussion regarding her ongoing treatment, management, and prognosis.

Discussion

Pathology

The underlying pathology in PMP has been a controversial area for some time [6]. The pathological process was originally thought to be due to a foreign body reaction after mucus containing cysts ruptured into the peritoneum [7]. However, it has now been re-defined to embrace a spectrum of cells from benign to malignant that produce abundant mucinous fluid. Within the ascitic fluid, there may be a few, if any, neoplastic cells seen, as the mucinous exudate is believed to spread further than any potential malignant cells within the peritoneum [8]. Malignant cells that produce PMP are often described as histologically borderline, as they do not show invasion of surrounding structures since they adhere rather than invade. Haematogenous or lymphatic metastasis is unusual, and most cases are found to originate from the appendix, with the most common being primary appendiceal mucinous neoplasia [6]. Rarely, however, the origin may be from the ovary, stomach, gallbladder, pancreas, urinary bladder, uterus, or fallopian tubes [1]. The mucinous tumour cells form cysts that increase intraluminal pressure within the organ of origin, and eventually cause the luminal wall to rupture [8]. The cells are then able to leak into the peritoneum. They are transported passively by peritoneal fluid flow and absorption, and by gravity to adhere to both abdominal and pelvic structures. Even if PMP is of a benign cell origin, the slow but relentless increase of gelatinous fluid in the peritoneal cavity causes compression of intra-abdominal organs, and mechanical and functional gastrointestinal obstruction [8].

Clinical presentation

Symptoms of PMP vary and will depend on the extent of the disease. Most commonly, patients report increasing abdominal girth or enlarging incisional, umbilical, or inguinal hernias [2]. Women may be diagnosed incidentally during routine pelvic examination or may present with infertility [2]. Patients may also report early satiety, as the space within the peritoneal cavity for the stomach to expand decreases, or with a clinical picture of acute appendicitis [9]. However, PMP is still often diagnosed incidentally at laparotomy, with symptoms sometimes inaccurately labeled as irritable bowel syndrome for years prior to diagnosis [1,2].

Utility of diagnostic imaging in PMP

Multiple imaging modalities have been reviewed with regard to PMP. Plain abdominal x-rays have been found to be of little diagnostic use, however, it may help to diagnose intestinal obstruction, a late complication of PMP [10]. Ultrasound may be utilised, with reported findings including homogenous tumour deposits, separated ascites, scalloping of the liver edges, and echogenic masses [11]. CT scans are the most widely used imaging technique for intra-abdominal pathology. Findings suggestive of PMP include scalloping of organs, ascitic septations and loculi, curvilinear calcifications, and omental thickening [10].

A review of CT scan use in 17 cases of PMP reported that early disease is easier to diagnose than more advanced disease. The authors urged radiologists to look for a pattern of mucinous ascites accumulation, rather than the appearance of individual deposits of disease on the image [12]. These authors were based at a surgical hospital and had experience with PMP. It may be difficult to expect a radiologist to detect this diagnosis without having had a similar level of experience. Ultrasound requires similar expertise, where it has been reported that familiarity with the features of PMP are required for accurate diagnosis [13].

Clinical implications

Despite being uncommon, PMP is a possible diagnosis that may occur in patients. It is worth keeping this disease as a differential diagnosis for patients that present with abdominal fullness. Imaging may help with the diagnosis but is not definitive. Without treatment, the prognosis for this condition is poor, with a ten-year survival rate of approximately 32% [14]. Treatments such as peritonectomy, intra-peritoneal chemotherapy at the time of surgery, and radical de-bulking of tumour deposits have been shown to improve the recurrence free survival time in these patients and decrease overall mortality [3,4]. Further, surgery that does not definitively de-bulk the condition contributes to increased difficulty in managing PMP effectively later on, through the creation of adhesions that can facilitate spread of PMP to the small bowel [3]. Early diagnosis is therefore important to help expedite care, allow for appropriate surgical and oncology management to occur, and improve outcomes in patients with PMP.

This case highlights that although it is most commonly horses when you hear hooves, very occasionally, it may actually be a zebra.

Consent declaration

Informed consent was obtained from the patient for publication of this case report.

Conflicts of interest

None declared.

References

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