Pseudomyxoma peritonei originating from urachus—case report and review of the literature

Abstract

Pseudomyxoma peritonei (pmp) is a rare clinical condition defined as extensive intraperitoneal spread of mucus associated with a variety of mucinous tumours of varying biologic behavior. Although appendix or ovaries have usually been implicated as the primary site, cases have been reported in association with neoplastic lesions of other sites. Pseudomyxoma peritonei originating from urachal remnants is a unique entity, reported only 18 times in the English literature thus far. Considering the rarity of the lesion, we report the case of a 50-year-old man surgically treated for pmp associated with a low-grade mucinous urachal neoplasm. Unique aspects of case are the low histologic aggressiveness of the causative lesion (reported only twice worldwide) and the early stage of the disease, with a relatively small amount of intraperitoneal free mucin. Review of the literature about pmp in general and a collation of previously reported cases of pmp originating from the urachus are presented and discussed.

1. INTRODUCTION

Pseudomyxoma peritonei (pmp) is a rare clinical condition defined as extensive intraperitoneal spread of mucus associated with variety of mucinous tumours of varying biologic behavior^1,2. The incidence of pmp is about 1–2 per million population^3,4. Low incidence forecloses the possibility of large-scale studies, and as a result there is broad diversity in the definitions, pathology, site-of-origin theories, treatment protocols, and prognosis for this disease⁵.

The clinical entity of pmp embraces a wide spectrum of neoplasms from the benign and borderline to malignant lesions with invasive growth capacity^3,6. Ronnett and colleagues⁷ introduced 3 diagnostic categories within this heterogeneous group: disseminated peritoneal adenomucinosis (dpam), including histologically benign peritoneal lesions; peritoneal mucinous carcinomatosis (pmca), with pathologic features of adenocarcinoma; and disease with features intermediate between dpam and pmca. Distinctive for pmp is a slow but relentless accumulation of abundant gelatinous fluid within the peritoneal cavity. Within this mucinous material, neoplastic cells may be bland and very scanty^1,5.

Although the appendix has been implicated as the primary site in most cases, incidences have been reported in association with neoplastic lesions of other sites^1,4,5, including ovary^2,8,9, fallopian tube¹⁰, endocervix¹¹, colorectum¹¹, retained colorectal tissue dislocated after previous surgical interventions^2,12, small bowel¹¹, stomach¹³, gallbladder⁶, lung¹⁴, breast¹⁵, pancreas^16–18, mucinous cysts of spleen^19,20, and extraperitoneal tumours^21,22. The primary site of invasion can also remain unknown^5,11,23. In unusual cases, the urinary tract can also be the primary source of pmp²⁴. To our knowledge, pmp originating from urachal remnants, as in the case we report here, has been reported only 18 times in the English literature thus far^2,25–41.

Clinically, pmp is a slowly progressive disease. Primary cystic tumour gradually grows, filled with a large amount of gelatinous fluid. After wall rupture because of intraluminal pressure, mucus-containing neoplastic cells leak and spread through the abdominal cavity, transported passively by physiologic peritoneal fluid flow. The tumour implants are usually distributed at sites of peritoneal fluid absorption (omentum, subphrenic space, Treitz ligament) and gravity sinks (pelvis, left abdominal gutter). Continuous peristaltic movement of intact small bowel usually protects the intestine wall from neoplastic invasion. Nevertheless, tumour cells can adhere to surfaces damaged during previous operations and to ovaries. This pattern of tumour dissemination, distinctive for pmp, is called “the redistribution phenomenon”^2,34,41.

During the prolonged clinical course of the disease, massive gelatinous ascites causes compression of the intra-abdominal organs, mechanical and functional gastrointestinal obstructions, and dyspnea leading to cachexia and, potentially, death^{2,32,38,39,41}. Pseudomyxoma peritonei often relapses, each time after a shorter interval, and local tumour recurrence can be expected in 60%–91% of the operated population (depending on the report), with a median disease-free interval of only 24 months, often leading to multiple operations^{2,23,33,41,42}.

Repeated intervention is an important aspect of pmp management. Interventions are associated with an increasing rate of mortality (ranging from 0% to 18%), perioperative morbidity (major complications requiring re-operation or intensive care, or causing chronic disability, are reported in 27%–70% of cases), and long-term treatment complications, of which aggregating adhesive disease is central to the debilitated condition of patients^2,39,41–43.

To summarize, although tumour growth usually tends to remain confined to the abdomen for many years, and blood-borne and lymph node metastases are uncommon, the disease has the potential for aggressive clinical behavior, including local tumour recurrence, and is always lethal unless radically treated^{1,5,42,43,47,48}.

2. CASE SUMMARY

A 50-year-old white man with no significant past medical history was admitted to the Second Department of General and Oncological Surgery of Wroclaw Medical University with a tumour of the lower abdomen. The patient reported a 4-month history of intermittent lower abdominal pain radiating to the back. He denied other ailments, recent weight changes, or abdominal distention.

On admission, the patient’s general condition was good. His physical exam was notable only for a palpable tender mass in the central lower abdomen. Laboratory tests revealed mild monocytosis, with 11.4% white blood cells, and an elevated level of fibrinogen. Tumour marker studies were insignificant (carcinoembryonic antigen 0.5 ng/mL, and carbohydrate antigen 19-9 3.72 U/mL).All other blood and urine analyses, and chest radiography completed before surgery, showed no abnormalities.

Ultrasonography revealed a unilocular, solid, heterogenous, hypoechogenic, well-circumscribed tumour with fibrous partitions in the central lower abdomen, measuring 42×44×78 mm and extending from the anterosuperior dome of the urinary bladder to the anterior abdominal wall. Computed tomography imaging demonstrated the presence in the central lower abdomen of a heterogenous, hypodense, irregular polycystic mass with minute peripheral calcifications and without contrast enhancement, compressing and modelling intestine (Figure 1); mesenteric cyst was a primary consideration in the differential diagnosis. Evaluation for distant metastases was negative.

Figure 1.

Abdominal computed tomography reveals a midline suprapubic polycystic mass, with intramural calcification, compressing the intestine.

The patient subsequently underwent laparotomy. Revision of the abdominal cavity disclosed a polycystic mass emanating from the urachal remnant and mucinous material confined to the rectovesical excavation (Figure 2). The appendix was explored and considered to be normal-appearing. Evaluation for distant metastases and lymph node involvement was negative. The tumour was entirely removed within macroscopically healthy margins, including the extended aspect of parietal peritoneum and umbilical ligament. Partial cystectomy was performed. Approximately 150 mL of thick translucent yellow mucinous material was collected from the rectovesical excavation, and thorough lavage was performed. This procedure resulted in a macroscopically complete cytoreduction [Sugarbaker completeness of cytoreduction (cc) score⁴³ of 0].

Figure 2.

Intraoperative picture of polycystic mass emanating from the apex of the urinary bladder.

The postoperative course was uneventful. At the time of article submission, our patient had been referred to long-term follow-up, but considering the low histologic aggressiveness (low-grade mucinous neoplasm, disseminated peritoneal adenomucinosis), the macroscopically complete cytoreduction, and the microscopically negative margins, no adjuvant chemotherapy was administered.

2.1. Pathology Findings

Macroscopic examination of the specimen revealed a well-circumscribed, gelatinous, polycystic mass emanating from the urachal remnant and measuring 8×7×4.5 cm, with abundant mucin within the lumen (Figure 3). In cross-section, the tumour was composed of smooth-walled cysts containing mucin pools. The mass did not include any papillary or solid lesions and did not communicate with the urinary bladder lumen.

Figure 3.

Gross appearance of excised polycystic tumour containing abundant mucin.

Histologically, the cysts were lined by a tall columnar epithelium, with slight cellular crowding and stratification. The epithelium showed features of simple benign columnar epithelium without areas of dysplasia. Cytologically, the lining columnar cells had abundant mucin in the cytoplasm and showed a slight degree of loss of polarity, but no pleomorphism or mitotic figures were present. No stromal invasion of the tumour cells was observed, although mucin was extravasated into the cyst wall. The association of this tumour with the urachal remnant and its location just anterior to the dome of the urinary bladder confirmed the primary urachal origin. The mucinous material collected from the rectovesical excavation was extensively histologically sampled, but no malignant cells were detected in the specimens.

Histopathologic interpretation was consistent with pmp potentially originating from the urachal remnant (World Health Organization classification: low-grade mucinous neoplasm, disseminated peritoneal adenomucinosis). The specimen margins were free of infiltration. No malignant penetration or presence of mucus within the urinary bladder wall was detected. Figure 4 presents selected images from the pathology evaluation.

Figure 4.

Histologic presentation of low-grade mucinous neoplasm. (A) Tumour shows a circumferential growth pattern and areas of mucin extrusion through the wall. (B) The epithelial lining consists of slightly stratified columnar cells containing mucin. (C) The underlying stroma shows extensive mucin extravasations without tumour cells. (D) The tumour cells contain abundant cytoplasmic mucin and enlarged hyperchromatic nuclei that are basally located, with minimal atypia. Hematoxylin–eosin stain, 40× (A and C) and 100× (B and D) original magnification.

3. DISCUSSION

The urachus is a tubular structure extending medially from the apex of the bladder to the allantoid during fetal development; normally obliterating after birth, it converts into the median umbilical ligament. Its lumen is lined with a transitional epithelium that has the potential for focal glandular metaplasia, possibly followed by malignant transformation. Vestigial persistence of this duct is revealed in 30%–70% of autopsies³³. Urachal remnants can cause diverse abnormalities, including congenital anomalies (patent urachus, umbilical–urachal sinus, vesicourachal diverticulum, urachal cyst) and acquired diseases (infection, neoplasia). Tumours are uncommon and may be benign (adenoma, fibroma, fibroadenoma, fibromyoma, hamartoma) or malignant (adenocarcinoma in 90% of cases, usually with intestinal-type histology)⁴⁴. Urachal carcinoma accounts for 0.01% of all malignancies^27,38 and 0.17%–1% of all bladder cancers^27,38,41,44.

Pseudomyxoma peritonei originating from mucinous neoplasm of the urachus is an extremely rare condition. We identified 18 previous cases in the English literature. Table i presents their distinctive features.

Table I.

Reported cases of pseudomyxoma peritonei originating from the urachus

Reference	Sex (M/F)	Age (years)	Symptoms	cea (ng/mL)	ca19-9 (U/mL)	Findings		Surgical procedure	Chemotherapy	Follow-up (months)	Outcome
						Intraoperative	Histologic
Faulkner et al., 195425	M	65	Abdominal pain, weight loss	Not stated		Suprapubic polycystic tumour, 4×3cm	Well-differentiated adenocarcinoma	Tumourectomy	No	—	Not stated
Mendelhoff and McSwain 197126	M	49	Low back pain	Not stated		Large suprapubic polycystic tumour	Mucinous urachal adenocarcinoma	Tumourectomy	No	28	Died of disease
Loggie et al., 199727	M	35	Gross painless hematuria	Not stated		Peritoneal carcinomatosis	Well-differentiated signet-cell adenocarcinoma	Pelvic exenteration, extensive tumour debulking, omentectomy, right hemicolectomy, sigmoidectomy, cholecystectomy, cystectomy	Preoperative systemic cyclophosphamide, doxorubicin, cisplatin, hipec with mitomycin C; adjuvant systemic 5fu, leucovorin, etoposide	22, 31	Metastasis, died of disease
Sasano et al., 199728	M	45	Abdominal distension	5.7	135	Suprapubic cyst, 22×20×20cm; multiple intra-abdominal implants	Invasive moderately differentiated mucinous adenocarcinoma	Tumourectomy	No	—	Not stated
De Bree et al., 20002	M	34	Recurring tumour of urinary bladder	29	81	Multiple intra-abdominal implants, recurrent after previous operation	Low-grade mucinous urachal adenocarcinoma	Extensive peritonectomy, sigmoidectomy, small-bowel segmental resection, omentectomy, partial cystectomy	Preoperative systemic with 5fu and leucovorin; hipec with mitomycin C	—	Not stated
Stenhouse et al., 200329	M	54	Abdominal pain, rectal bleeding	Not stated		Suprapubic ruptured cyst, 14×9.5×7cm	Mucinous urachal adenocarcinoma in situ	Tumourectomy	No	6	Free of disease
Yanagisawa et al., 200330	M	50	Abdominal fullness	27.9	Not stated	Suprapubic ruptured cyst, 3.5×2.6cm, ovarian metastatic polycystic tumour, 16×14×10cm	Mucinous cystadenocarcinoma	Tumourectomy, oophorectomy	Not stated	—	Not stated
Takeuchi et al., 200431	M	82	Abdominal fullness	7.9	38	Extraperitoneal suprapubic cyst, multiple intra-abdominal implants	Mucinous urachal adenocarcinoma	Tumourectomy, omentectomy, appendectomy	No	NS
Shinohara et al., 200632	M	54	Left inguinal hernia	Not stated		Suprapubic ruptured cyst, 9×7×5.5cm	Mucinous urachal cystic tumour of low malignant potential	Tumourectomy, extensive peritonectomy, partial cystectomy, appendectomy	5′-Deoxy-5-fluorouridine	84	Free of disease
Soto Delgado et al., 200633	M	56	Macroscopic hematuria	Not stated		Large suprapubic tubular tumour	Mucinous urachal adenocarcinoma	Tumourectomy, pelvic adenectomy	No	12	Free of disease
	M	47	Mucinuria, abdominal pain and distention	14	594	Multiple intra-abdominal tumours	Well-differentiated mucinous urachal adenocarcinoma	Tumourectomy, extensive peritonectomy, right hemicolectomy, rectosigmoid colectomy, omentectomy, appendectomy	hipec with mitomycin C and doxorubin;	18	Free of disease
Yan et al., 200634									Early postoperative intraperitoneal 5fu; adjuvant systemic 5fu, leucovorin, 5fu
Sugarbaker et al., 200835	F	32	Infertility	4	82	Multiple intra-abdominal tumours, residual after previous operation	Mucinous urachal adenocarcinoma	Tumourectomy, extensive peritonectomy, rectosigmoid colectomy, omentectomy, splenectomy	Early postoperative intraperitoneal mitomycin C and 5fu	24, 132	Recurrence, died of disease
Khalid et al., 200836	F	14	Weight loss, recurrent subacute bowel obstruction	Normal		Extraperitoneal suprapubic cyst, 16×12×10cm	Invasive moderately differentiated mucinous adenocarcinoma	Tumourectomy, cholecystectomy, partial cystectomy, appendectomy	No	6	Free of disease
Sugiyama and Ito, 200937	M	58	Abdominal fullness	41.5	Not stated	Suprapubic ruptured cyst, 11×10×10cm; multiple intra-abdominal implants	Well-differentiated adenocarcinoma	Tumourectomy, extensive debulking of diffuse lesions, omentectomy	No		Not stated
Lamb et al., 201038	M	63	Chronic urinary retention	Not stated		Cystic mass in dome of bladder, omental metastases	Mucinous urachal adenocarcinoma	Tumourectomy, debulking with limited peritonectomy, omentectomy, partial cystectomy	No	18	Recurrence
Nozaki et al., 201139	M	37	Abdominal pain	Not stated		Cystic tumour beneath umbilicus	Mucinous borderline tumour of low malignant potential	Tumourectomy, extensive peritonectomy	No	54	Free of disease
Kebapçı et al., 201240	M	59	Abdominal turgidity and discomfort	Not stated		Suprapubic ruptured cyst, 10×8×5cm	Mucinous adenocarcinoma	Tumourectomy, partial omentectomy	After recurrence: systemic 5fu and mitomycin C	36, not stated	Recurrence, died of disease
Martinez et al., 201241	M	32	Mucinuria	Not stated		Multiple intra-abdominal implants, residual after previous operation	Mucinous urachal adenocarcinoma	Extensive peritonectomy, tumour debulking, right hemicolectomy, omentectomy, partial cystectomy, appendectomy	hipec with oxaliplatin	24	Free of disease
Agrawal et al. (present case)	M	50	Abdominal pain	0.5	3.72	Suprapubic polycystic tumour, 7.8×4.4×4cm	Low-grade mucinous neoplasm	Tumourectomy, partial cystectomy, extended parietal peritonectomy	No	—	—

M/F = male or female; cea = carcinoembryonic antigen; ca19-9 = carbohydrate antigen 19-9; hipec = hyperthermic intraperitoneal chemotherapy; 5fu = 5-flourouracil.

The collected cases present a variety of clinical pictures, stages at time of surgery, histologic types, and outcomes within a single clinical entity. The low number of reported cases and the differences in management and reported follow-up do not permit any generalizations or statistical assessments. However, we agree with the authors of earlier reports, that pmp originating from the urachus probably shares the pathophysiology, clinical behaviour, and prognosis of pmp with an appendiceal origin. Because peritoneal spread and local invasion dominate the clinical picture and present a major therapeutic problem, pmp originating in the urachus requires the treatment approach recommended for pmp arising from appendix rather than that for urachal adenocarcinoma^2,34,35,41.

Reported symptoms (Table i) are diverse, develop slowly, and usually remain unspecific: lower abdominal pain, distention, palpable mass, weight loss, intermittent bowel obstruction, hematuria, and urinary retention. Mucinuria because of persistent connection between the urachal remnant and the urinary bladder is highly distinctive for this disease³⁵, but occurs relatively rarely. Physical examination (abdominal distention with so-called “jelly belly” ascites, and less often fever and peritoneal irritation) and laboratory tests (leukocytosis, anemia) are also not discriminative³³. In an important proportion of cases (42%), elevated serum carcinoembryonic antigen and carbohydrate antigen 19-9 are present. Both markers are not disease-specific, but remain useful and recommended for primal diagnosis, evaluation of cytoreduction, and postoperative follow-up^28,35,45.

Ultrasonography and computed tomography or magnetic resonance imaging, followed by histopathologic verification of extensively sampled tumour, are the preferred way to establish a diagnosis of pmp^37,46. Ultrasonographic findings supporting a diagnosis of pmp of urachal origin are a large collection of intraperitoneal fluid and a midline-situated cystic tumour attached to the dome of the urinary bladder, often of heterogenous echogenicity, with multi-septation and intramural or septal calcification. Computed tomography and magnetic resonance images (especially T2-weighted sagittal images) of linear structure continuing from the tumour toward the umbilicus may complement other data. Scalloping of the visceral surfaces and intestinal loop displacement evidence a large quantity of ascites and is discriminative with pmp^31,38,40. Cytology examination of aspirated mucus has little diagnostic value, because acellular mucin often spreads further than do malignant cells¹. Transurethral biopsies containing limited diagnostic material can provide false results because the tumour is often of heterogeneous architecture with focal invasive malignancy⁴⁷.

The described lack of pathognomonic symptoms in combination with the slow and occult clinical course of this tumour usually results in disease being locally advanced at the time of diagnosis^34,41.

To the best of our knowledge, no generally accepted staging system has been applied in pmp. Among the 18 previously described cases of urachus-origin pmp (Table i), most were at an advanced stage at clinical presentation. Six reports (including that of the present case) identified the presence of a solitary cystic tumour with various amounts of mucinous material containing sparse neoplastic cells, but without invasion into the urinary bladder. In 3 cases, the bladder wall was additionally infiltrated. A single synchronous extra-urachal locus of invasion was reported once. Multiple intra-abdominal tumour implants or peritoneal carcinomatosis was already present in 9 cases at the time of diagnosis.

In contrast to the natural history of urachal adenocarcinoma, pmp hardly ever gives rise to lymphatic and blood-borne distant metastases. However, it does show a strong tendency for local recurrence^2,33,41. Consequently, the stage of local invasion throughout the peritoneal cavity is the first major prognostic factor⁴⁸.

The second independent prognostic factor is the histologic grade of the causative malignant lesion^{2,7,35,41–43,49}. According to data published by Ronnett and colleagues⁷, the 5-year survival rate in patients with pmp of appendical origin is 84% for patients with dpam, 37.6% for patients whose lesions have intermediate features, and only 6.7% for patients with pmca. Sugarbaker⁴³, in presenting treatment results for 385 patients with pmp, reported 5-year survival rates after complete cytoreduction of 86% for patients with dpam and 50% for patients with lesions having intermediate histopathologic features. Miner and colleagues⁴², referring to surgical treatment in 97 patients, observed that 90% of 10-year survivors had low-grade pathologic features. Table i shows great histologic variation in patients with pmp of urachal origin, from mucinous urachal tumour of low malignant potential and mucinous borderline tumour of low malignant potential; to well-, moderately-, and poorly-differentiated urachal adenocarcinoma. According to the classification system proposed by Ronnett and colleagues⁷, 3 of those cases (including the present case) represent benign disseminated peritoneal adenomucinosis (dpam), 5 represent intermediate disease, and 11 demonstrate histologically aggressive pmca.

The third main prognostic factor is completeness of cytoreduction^42,43,48. Table ii presents the cc score published by Sugarbaker⁴³. In pmp, the aim of surgical procedures is to excise all visible tumour, or if full excision is not achievable, to leave residual nodules less than 0.25 cm. The 0.25 cm diameter is considered the maximal achievable penetration distance for locally applied chemotherapy⁴¹.

Table II.

Completeness of cytoreduction score⁴³

Score	Cytoreduction	Size of largest residual tumour nodule
0	En bloc resection	Nodules not visible
1	Complete cytoreduction	Nodules < 0.25 cm
2	Incomplete cytoreduction, moderate residual disease	Nodules 0.25–2.5 cm
3	Incomplete cytoreduction, gross residual disease	Nodules > 2.5 cm

Sugarbaker⁴³ describes 5-year survival rates of only 20% and no patient surviving 10 years after incomplete cytoreduction (cc-2 and cc-3). No significant differences in survival were observed for patients with cc-2 and cc-3 cytoreductions. Miner and colleagues⁴² observed median survivals of 12.8 and 4.2 years after complete cytoreduction and incomplete cytoreduction respectively.

Abdominal distension, weight loss, invasion of major organs¹, and (if prior surgery has been performed) a large extent of earlier surgical intervention⁴³ have also been assumed to be poor prognostic factors.

The optimal treatment for patients with pmp remains controversial. As mentioned earlier, peritoneal spread and local invasiveness are essential and defining for pmp, and surgical management (radical or partial cystectomy with en block resection of tumour, urachal remnant, umbilicus, and posterior rectus abdominus facia) might be insufficient for urachal adenocarcinoma⁴⁹.

Most publications recommend, at least at the first operation, an aggressive approach resulting in complete cytoreduction (cc-0 or cc-1) with radical peritonectomy and resection of involved major organs, followed by perioperative intraperitoneal chemotherapy^{2,5,27,32–35,39,41,43}. That procedure has demonstrated prolonged survival at the cost of associated severe acute toxicity and elevated morbidity. Conversely, given that aggressive procedures reduce quality of life for patients and are usually not curative (high rates of recurrence are reported among long-term survivors), some authors prefer selective debulking. Miner and colleagues⁴² suggest, that in case of advanced intra-abdominal spread, an aggressive surgical procedure does not ensure completeness of cytoreduction. In that group of patients, the authors advise a treatment strategy based on symptom management and preservation of function.

In the treatment protocol for pmp established by the Basingstoke and North Hampshire Foundation Trust Hospital (British National Tertiary Pseudomyxoma Referral and Treatment Centre), the cytoreductive procedure must include radical peritonectomy and removal of involved viscera to extirpate all visible tumour implants. Palliative debulking is performed if complete cytoreductive surgery is not achievable. Additional appendectomy and revision of ovaries to exclude the two main origins of pmp are advised²⁴. Because radical cystectomy does not improve outcomes, a conservative partial cystectomy is usually recommended^2,34,37. Thorough lavage of the abdominal cavity with mucolytic agents (5% dextrose in water or low molecular weight dextran solution) has been suggested to be beneficial³².

The surgical procedure must routinely be followed by perioperative intraperitoneal chemotherapy^{2,5,27,32–35,39,41,43}. Most recent studies suggest an essential advantage for application of hyperthermic intraperitoneal chemotherapy^{24,34,35,43,48,50,51}. In cases of early-stage pmp with low malignant histology, some authors recommend not to dispense with intraperitoneal chemotherapy³⁹. Only a few authors have described some benefit with systemic chemotherapy and radiotherapy. Nevertheless, such treatments can be applicable and useful for palliation in fast-deteriorating patients with recurrent high-grade malignant disease^2,3.

4. SUMMARY

Although increasing numbers of cases of pmp have been reported, this neoplasm remains a diagnostic challenge because of its rarity and lack of discriminative symptoms. Pseudomyxoma peritonei should be considered in the differential diagnosis for abdominal and retroperitoneal tumours, especially with intercurrent ascites, because misdiagnosis delays effective treatment and affects survival.

5. CONFLICT OF INTEREST DISCLOSURES

We certify that there is no financial conflict of interest with any organization concerning the material discussed in this manuscript.