Christopher J. Myers, MD
Chief Resident
Department of General Surgery
The Mercy Hospital of Pittsburgh
Pittsburgh, PA

Viven B. Valdez, BS
Medical Student IV
Lake Erie College of Osteopathic Medicine
Erie, PA

John M. Sundermann, MD
Attending Pathologist
Department of Laboratory Medicine
The Mercy Hospital of Pittsburgh
Pittsburgh, PA

Harry W. Sell Jr., MD
Chairman
Department of Surgery
Chief
Division of General Surgery
The Mercy Hospital of Pittsburgh
Pittsburgh, PA

ABSTRACT
Introduction: Pseudomyxoma peritonei (PMP) is a rare tumor that is characterized by its production of extensive gelatinous fluid and surface implants within the abdominal cavity. PMP typically originates from a cystadenoma or cystadenocarcinoma of the appendix or ovaries. In many cases, these tumors are discovered incidentally during surgery for other conditions. Despite its sometimes malignant nature and tendency to spread, solid organ invasion is rare, especially of the spleen. Only 20 cases of splenic invasion have been reported worldwide, with 6 appearing in the English-language literature.
 

Results and discussion: The authors report a case of PMP involving a 42-year-old woman who presented to the hospital with abdominal distention and generalized abdominal pain. They discuss the classification, diagnosis, and treatment of these tumors and provide an analysis of their patient?s case. They also examine the significance of splenic involvement.

Conclusion: PMP tumors are rare and consequently poorly understood. Currently, PMPs are classified according to the tumor?s characteristics and extent of spread. Surgical debulking is the mainstay of treatment, with chemotherapy offered to patients whose tumors demonstrate malignant characteristics.

Figure 1—Pathology image from the patient?s 1988 laparoscopic procedure showing appendiceal tumor with microcalcification and mucin spillage into the periappendiceal area (hematoxylin and eosin staining, magnification x100).

Pseudomyxoma peritonei (PMP) is an extremely rare tumor that is generally discovered intraoperatively, with an incidence of 2 in every 10,000 laparotomies.¹ It is characterized by the accumulation of extensive gelatinous fluid and implants within the abdominal cavity. Current evidence suggests that PMP results from the rupture of a mucinous cystadenoma or mucinous cystadenocarcinoma of the ovaries or appendix, with appendiceal involvement being more common.² We report a case of splenic invasion by PMP in a woman who had been found to have a mucinous cystadenoma 8 years before she presented to our institution. We could find only 6 previous cases in the English-language literature that detailed splenic invasion by PMP.^1-5

CASE REPORT

A 42-year-old white woman presented to the hospital reporting a 2-week history of vague left-sided abdominal pain and generalized distention. The patient had experienced minor weight gain despite a decreased appetite. Her surgical history was significant for laparoscopy and ablation of endometriosis, which a gynecologist from an outside institution had performed 8 years earlier. During the procedure, adhesions and mucinous pools were found in the patient's pelvis, and her appendix was noted to be thickened and edematous. A general surgeon was brought in to remove the appendix, which measured 6.0 cm in length and 1.5 cm in diameter. Macroscopic examination revealed an enlarged, edematous, red, soft-tissue mass in the distal half of the specimen. Serial sections of the appendix showed a dilated lumen that contained thick tenacious mucus, findings which were reported grossly as a mucocele. Microscopic evaluation suggested a mucinous cystadenoma with spillage of mucin into the periappendiceal area (Figure 1).

Computed tomography (CT) scans obtained during the patient's current presentation revealed ascites; two coarse, calcified, round masses between the liver and abdominal wall; and an enlarged spleen, which was inferiorly replaced by a complex, cystic, partially calcified, 10-cm mass (Figure 2). Surgical exploration found mucinous ascites filling the abdominal cavity and three peritoneal implants above the liver on the right hemidiaphragm (Figure 3A). The spleen appeared cystic, and a large, deep hole was located inferiorly, suggestive of parenchymal invasion (Figure 3B). The omentum and left ovary appeared abnormal and were encased in mucin. The right diaphragmatic peritoneal implants were excised, and diaphragmatic repair, splenectomy, omentectomy, left salpingo-oophorectomy, and aggressive peritoneal irrigation were undertaken. All peritoneal implants were resected using peritonectomy procedures. At the conclusion of the operation, no macroscopic evidence of residual disease was found, suggesting adequate debulking of the tumor.

Figure 2—Abdominal CT scan showing a large calcified cyst in the spleen, perihepatic ascites, and two calcified peritoneal implants above the liver.

The right hemidiaphragm implants, liver tissue, spleen, omentum, and left adnexa were sent for pathological evaluation. The three peritoneal implants measured 4.5 x 3.0 x 1.5 cm, 6.0 x 4.0 x 1.5 cm, and 9.0 x 5.0 x 2.5 cm, and were predominantly cystic, gray-tan masses containing gelatinous, yellow-pink material. The implants were subsequently identified as organizing mucinous ascites that had extensive chronic inflammation, adhesions, and calcification. The spleen weighed approximately 407 g, and its outer surface was coated with mucinous material up to 0.3 cm thick (Figure 4). Approximately 50% of the spleen consisted of cystic mucinous tumor. These cysts ranged from 0.3 cm to 9.0 cm in diameter and contained an abundance of yellow, mucinous material; the cyst walls showed extensive fibrosis and focal calcification (Figure 5). The left ovary measured 3.5 x 3.0 x 2.0 cm, demonstrated physiological changes, and contained a 1-cm benign cyst. The outer surfaces of both the left adnexa and omentum contained mucin but, as expected, no gross evidence of tumor invasion. The cystic nature of these specimens and the presence of mucinous ascites suggested a diagnosis of low-grade mucinous tumor, consistent with disseminated peritoneal adenomucinosis (DPAM). Immunohistochemical staining (negative cytokeratin 7, positive cytokeratin 20, and positive carcinoembryonic antigen) was consistent with PMP originating from an appendiceal adenoma.

The patient's postoperative recovery was complicated by a small right pneumothorax, which resulted from excision of the tumors on the right hemidiaphragm. The pneumothorax was treated conservatively, and the patient was discharged to home on postoperative day 5. At 8-month follow-up, she was doing well and her functional capacity was nearly back to its preoperative state. Medical oncology did not recommend any further treatment.

DISCUSSION

Figure 3—Intraoperative photograph demonstrating three, large calcified peritoneal implants above the liver on the right hemidiaghram (A). The spleen appears cystic, demonstrating invasion by mucinous ascites, and has a large, deep hole inferiorly, suggesting parenchymal invasion (B).

In 1884, Werth coined the term pseudomyxoma peritonei to describe the mucinous material that had spread throughout a patient's peritoneal cavity in association with a ruptured cystadenoma of the ovaries. Werth theorized that metaplasia of the peritoneum resulted from an inflammatory reaction to the contents of the ruptured cyst.³ Evidence now suggests that PMP is not an inflammatory reaction but a consequence of a ruptured mucinous cystadenoma or mucinous cystadenocarcinoma of the appendix or ovaries, with appendiceal involvement being more common.² Fraenkel discovered PMP to be associated with a ruptured mucocele of the appendix in 1901.⁶

PMP is a rare tumor that is generally discovered incidentally during approximately 2 of every 10,000 laparotomies.¹ PMP appears to have a female predominance and patients usually present with an increase in abdominal girth. Extravasation from PMP causes mucin to migrate diffusely throughout the abdominal cavity, seeding the peritoneal surfaces of the viscera, abdominal wall, and peritoneum. The gelatinous material is mainly confined to a superficial level, and direct invasion is rare. Hematogenous or lymphatic spread is even less common.

Diagnosis and treatment

CT scanning is the radiographic modality of choice in illustrating intra-abdominal mucinous ascites in association with calcified cysts or masses. PMP is confirmed intraoperatively with the observation of extensive gelatinous fluid and implants throughout the abdominal cavity. Once diagnosed, treatment may consist of repeated abdominal explorations for radical cytoreduction. These procedures are debilitating and may eventually result in the patient's death. In addition to surgical debulking, heated intraperitoneal chemotherapy (IPHC) and systemic chemotherapy may be offered, depending on the type and amount of residual tumor.⁷

Classification

Since the time of Werth and Fraenkel, numerous researchers have attempted to classify PMP. Most recently, these tumors have been divided into two categories: DPAM and peritoneal mucinous carcinomatosis (PMCA). PMCA is subdivided into PMCA-I/D, which is defined as DPAM with focal areas of well-differentiated mucinous carcinoma (intermediate or discordant).

DPAM tumors are peritoneal lesions comprising extracellular mucin that contains simple, proliferative mucinous epithelium and demonstrates little cytologic atypia or mitotic activity; an associated appendiceal mucinous adenoma may or may not be present. The spread of DPAM, also known as the "redistribution phenomenon," is characterized by superficial, noninvasive involvement of the omentum, undersurface of the diaphragm, pelvis, right retrohepatic space, left pericolic gutter, and ligament of Treitz. The peritoneal surfaces of the bowel are spared. DPAM is benign in nature and has a 5-year survival rate of approximately 75%.⁷

PMCA is characterized by peritoneal lesions composed of more abundant mucinous epithelium and demonstrating cytologic features of carcinoma; an associated appendiceal primary mucinous adenocarcinoma may or may not be present. PMCA tumors have malignant characteristics and demonstrate lymphadenopathy and invasive implantation on the bowel and other organs. The malignant features of PMCA contribute to its lower 5-year survival rate of 26%.⁷ PMCA-I/D, which shares some characteristics with DPAM, has a 5-year survival rate between 38% and 50%.⁷

Splenic involvement

Figure 4—Gross pathology image of the sectioned spleen showing massive cystic replacement of the parenchyma and coated with a layer of mucinous material up to 0.3 cm thick.

Splenic metastases from mucinous neoplasms of the appendix are uncommon. The spleen is an unusual site for metastatic cancer of any origin, and splenic invasion by PMP is quite rare. One theory postulates that in these rare cases, mucin-producing epithelial cells become trapped in the trabeculae of the splenic capsule, congenital clefts, or microfissures, and they continue to produce mucin that can then expand inward into the soft splenic parenchyma.⁸

Clinical observations regarding our patient

Our case demonstrates some interesting pathological features of PMP. First, following the patient's appendectomy 8 years earlier, the appendix specimen was found to contain a cystadenoma, and a pelvic biopsy was positive for mucin. These findings may have constituted early signs of PMP and raise the question as to whether the patient should have returned to the operating room for open exploration with aggressive washout and possible right colectomy. Whether this would have prevented tumor spread is unknown. Second, the final classification of this tumor was unclear. Thorough evaluation of the pathological specimens showed no evidence of vascular or lymphatic spread, which would be consistent with DPAM, yet there was gross splenic involvement that seemed to indicate a more malignant property, possibly consistent with PMCA. The tumor's spread was reminiscent of the "redistribution phenomenon," however; it acted like DPAM but with splenic involvement and was likely a variant of DPAM.

We decided to treat our patient's tumor as DPAM. Both IPHC and systemic chemotherapy were discussed with the patient, but after consulting with the oncologist, she decided to forego these treatments. Because the tumor had grossly involved the spleen (which was removed), acted clinically and pathologically like DPAM, and had been adequately debulked, it was decided that chemotherapy was unnecessary. The patient showed no evidence of recurrence 8 months after surgery.

CONCLUSION

Figure 5—Pathology image of the spleen illustrating parenchymal invasion with cystic mucinous tumor; the cyst walls demonstrate extensive fibrosis and focal calcification (hematoxylin and eosin staining, magnification x100).

PMP defines the rare intraoperative discovery of extensive gelatinous fluid and implants within the abdominal cavity, typically originating from a cystadenoma or cystadenocarcinoma of the appendix or ovaries. These tumors are classified according to specific pathological findings and patterns of tumor spread. Treatment includes surgical cytoreduction with or without intraperitoneal or systemic chemotherapy. Our case is interesting because our patient had demonstrated evidence of an appendiceal cystadenoma with pelvic mucin 8 years before presenting to our institution. Her tumor featured some of the common characteristics of PMP, such as mucinous ascites and the "redistribution phenomenon," yet had uncommon splenic invasion. Comprehensively, these findings demonstrate qualities of both DPAM and PMCA; thus, chemotherapy was not advised.

PMP is a rare disease that is poorly understood. As more cases are reported in the literature, perhaps knowledge of this disease will increase, corresponding to less debilitating treatment and improved patient survival rates.

References

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4. Holder PD, Fehir KM, Schwartz MR, et al. Primary mucinous cystadenocarcinoma of the appendix with pseudomyxoma peritonei manifested as a splenic mass. South Med J. 1989;82(8):1029-1031.
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6. Fraenkel E. Ueber das sogennante pseudomyxoma peritonei [in German]. Muench Med Wschr. 1901;48:965-971.
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8. Cabanas J, Gomes da Silva R, Zappa L, et al. Splenic metastases from mucinous neoplasms of the appendix and colon. Tumori. 2006; 92(2):104-112.