Pseudomyxoma peritonei (PMP), a rare syndrome first described by Karl F Rokitansky in 1842, is an enigmatic, often fatal intraabdominal disease characterized by dissecting gelatinous ascites and multifocal peritoneal epithelial implants secreting copious globules of extracellular mucin.1 In majority of the cases it originates from ruptured appendiceal mucocoeles.

A 59 year old male presented with gradual distension of abdomen for eight months with loss of weight and appetite, not accompanied by abdominal pain, jaundice, haematemesis or melaena. He had undergone diagnostic laparoscopy elsewhere which showed serosanguinous ascites, multiple omental and peritoneal nodes. However, the mesentery and small bowel biopsy did not show any abnormality.

Per abdomen examination revealed multiple ill-defined lumps palpable all over the abdomen, enlarged liver and free fluid. A film of the abdomen showed opaque flanks suggestive of ascites. Ultrasonography (USG) showed cirrhotic liver, massive ascites and multiple gllstones. Other viscera appeared normal. A computed tomography (CT) scan after oral and intravenous contrast showed high attenuation in greater and lesser omenta with ascites and a sub-centimeter simple cyst in left kidney.

Subsequently, the patient underwent repeated ascitic fluid tappings and its cytology revealed lymphocytic effusion with reactive mesothelial cells. Ultrasound guided biopsy of abdominal and liver masses was also done but pathologist found the material, sent for biopsy, insufficient to conclude any diagnosis. Polymerase chain reaction (PCR) of sputum and ascitic fluid was positive for Mycobacterium tuberculosis. In view of the above findings, a diagnosis of tuberculous peritonitis was made and anti-tubercular treatment was started. Gradually the patient recovered and was discharged.

He again presented, after five months of discharge, with abdominal pain for 2-3 months. On examination, the patient had an enlarged liver with multiple, hard, not freely mobile masses in the epigastrium. USG showed cirrhotic liver, multiple gallstones, multiple echogenic mass like areas in the peritoneal cavity, which were difficult to identify separately from the bowel loops and ascites with multiple bands (tubular type) and a provisional diagnosis of PMP was made (Fig. 1). A CT scan of abdomen and pelvis with intravenous contrast was done to confirm the USG diagnosis and it showed scalloping of the hepatic, splenic and omental surfaces, high density ascites with mass effect on the peritoneum and bowels and 1 cm bilateral diaphragmatic lymph nodes (Figs. 2 and 3). Both USG and CT scan findings were thus suggestive of PMP. Subsequently mini-laparotomy was done which revealed jelly-like material filling the whole abdomen. About 465 gms of material was removed and sent for biopsy. The biopsy revealed pools of mucin separated by thick fibrous tissue with hyalinization and a few lymphocytes in the wall, the picture consistent with PMP.

Patient was advised repeat laparotomy, intra and postoperative heated intraperitoneal chemotherapy, which the patient said he will consider but did not follow up.

PMP is a very rare disease occurring in 2 of 10,000 laparotomies.2,3 It is mostly prevalent in women aged between 50 and 70.

In large majority of cases (80%), PMP arises from appendicular disease and not ovarian disease although ovarian seeding, observed in nearly 90% of the female patients may be misleading.3 Christine Szych et al have reported that mucinous tumours involving the appendix and ovaries in women with PMP are clonal and derived from a single site, most likely the appendix, based on the analysis of k-ras mutations and allelic losses of chromosomes of 18q, 17p, 5q and 6q in a substantial number of morphologically uniform cases of PMP.4

PMP arising from colon, breast, endometrium, pancreas, common bile duct carcinoma and urachus have also been reported.

Its biology is characterized by a redistribution phenomenon with large amount of extra cellular mucin. The mucin producing cells in PMP are poorly adherent and circulate with peritoneal fluid. They are easily dislodged from the surface of the bowel by constant peristalsis. They only seed at sites of relative stasis. This process has been termed the ‘redistribution phenomenon’.6

It is characterized by the presence in the peritoneal cavity of three elements-mucinous neoplastic cells, mucinous ascites and diffuse mucinous implants.7

It can be classified into three histologic groups: disseminated peritoneal adenomucinosis (DPAM)- the one present in our case, peritoneal mucinous carcinomatosis (PMCA) and intermediate group.8,9

O’Connell JT et al have reported that PMP is a disease of MUC 2- expressing goblet cells. MUC 2- expression accounts for voluminous deposits of extra cellular mucin (mucin: cell ratios exceeding 10:1). Because mucinous tumours of the appendix similarly express MUC 2, MUC 2 expression profile also supports an appendiceal rather than ovarian origin for PMP.

The common presentation of PMP is pain in abdomen, distension of abdomen and/or lump in abdomen. Fever, anorexia, nausea, vomiting and weight loss may be associated. Thus the clinical features are vague and in our country could be mistaken for abdominal tuberculosis.5

The common sites of tumour load are the greater omentum (omental cake), the undersurface of the right hemidiaphragm, the right retrohepatic space, the left abdominal gutter, at the ligament of Treitz and pelvic spaces. Peritoneal surfaces of bowel are spared. The tumour progresses by the production of mucus, exfoliation of tumour cells and redistribution of these cells around abdomen.5

Despite the presence of distended abdomen with nonshifting ascites on physical examination, diagnosis is seldom absolute until laparotomy is performed. Laboratory tests are of little help but fortunately over the past few years, radiological imaging techniques are proving to be extremely useful in reaching diagnosis of PMP.

The pertinent cytological features of PMP include a mucinous background with mesothelial cells and histiocytes. The well-differentiated columnar epithelial cells producing mucin usually display minimal nuclear features of malignancy.

Plain abdominal X-rays taken during the later stages of the disease show central displacement of bowels with obliteration of the psoas muscle border. When used in conjunction with barium studies, the proximal extent of the disease can be assessed and a possible extrinsic tumour causing large bowel obstruction can be ruled out.

USG shows septated ascites with numerous suspended echoes that do not move as the patient changes position (these were seen in our case) and scalloping of the liver.5,13

CT scan shows four basic patterns-scalloping of intra abdominal organs due to extrinsic pressure of adjacent peritoneal implants (diagnostic signs that distinguishes mucinous from fluid ascites on CT and which was seen in our case), diffuse peritoneal infiltration appearing similar to ascites with separated fluid pockets filling the peritoneal cavity, posterior displacement of the intestines with numerous low density masses and calcifications and intrahepatic low density attenuated lesions. PMP is not characterized by haematogenous or lymphatic metastases, so the presence of lymphadenopathy should bring the diagnosis of PMP into question.6,13 But in our case CT showed bilateral diaphragmatic lymph nodes, which were probably concurrently involved.

Finally, MRI, which is still being investigated, may prove more helpful than CT especially in assessing the rare visceral invasion by mucinous tumours. One major disadvantage is the poor cost effectiveness compared with CT.13

In summary, preoperative diagnosis could therefore be made with careful physical examination in conjunction with USG and CT. However, explorative laparotomy still remains the main diagnostic tool of choice. A positive finding is indicated by the presence of litres of yellowish grey mucoid material involving both the omental and peritoneal surfaces.

The goal of therapy should be a multimodal concept combining complete cytoreduction (defined as tumour nodules less than 2.5 mm in diameter remaining after surgery) with the use of peritonectomy procedures and peri and postoperative intraperitoneal chemotherapy. Aggressive and “repetitive debulking” surgery including appendicectomy, bilateral oophorectomy and omentectomy at the initial procedure should be undertaken. Surgical peritonectomy aims to achieve the complete removal of tumour cells at the macroscopic level.5,10,11

Subsequently intraoperatively or in the immediate postoperative phase when the absence of adhesions allows for a homogeneous intra abdominal spread of cytotoxic drugs, heated intraperitoneal chemotherapy with 5 - fluorouracil (5FU) and mitomycin C (MMC) represents the most solidly established treatment designed to treat residual microscopic disease. Hyperthermia enhances the penetration of cytostatic drugs into tumour tissue and also shows synergism with various cytostatic drugs. As the penetration depth of drugs into tissue is limited, therefore intraperitoneal chemotherapy can only be effective in patients with minimal disease after aggressive surgery.10,11

Intra peritoneal chemotherapy may cause systemic toxicity, dependant on the drug used. Systemic chemotherapy is rarely indicated. Abdominal CT is an excellent technique to follow up these patients for recurrence.5 Radiotherapy of the abdomen with pelvic boost can be given in cases unresponsive to chemotherapy.

The clinical features, which correlate significantly with therapy failure, are tumour site, histopathological grade, preoperative cancer volume and completeness of cancer removal by cytoreductive surgery. Advancing abdominal disease caused by intestinal obstruction account for the majority of patients' morbidity and mortality.

Tumour markers are also useful for diagnosis and follow up. The measurement of the tumour marker Carbohydrate Antigen 19.9 (CA 19.9) is useful in evaluating therapy in patients with PMP treated with cytoreductive surgery and heated intraperitoneal chemotherapy. It is a prognostic factor for predicting recurrent disease.12

In 1996, Kairemo KJ et al stated that immunohisto chemistry based on digital quantitative autoradiography utilizing radio labelled monoclonal antibody B 72.3 (Mo Ab) recognizing TAG - 72 antigen on pseudomyxoma tumours, can be used for earlier diagnosis and more accurate location of residual disease after operations and evaluating treatment response.14

Although diagnostic modalities like USG, CT and MRI can give supportive evidence in favour of PMP but the definitive diagnosis can only be made by explorative laparotomy. In this context, improving the rate of detection of this elusive condition demands a high degree of suspicion on the part of treating physician and the radiologist. The diagnostic CT features like scalloping of intraabdominal organs due to extrinsic pressure of adjacent peritoneal implants alert the radiologist of its presence.

There are advantages and disadvantages of available investigation techniques and treatment regimens but their use continues to be invaluable in patients with pseudomyxoma peritonei. This seems to be particularly true for postoperative use of chemotherapy, which has been shown to improve prognosis in some patients.