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).
Practice Point
The spleen is an unusual site for metastatic cancer of any origin, and splenic invasion by PMP is quite rare.
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).
Practice Point
Treatment includes surgical cytoreduction with or without intraperitoneal or systemic chemotherapy.
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.
Disclosure
The authors have no relationship with any commercial entity that might represent a conflict of interest with the content of this article and attest that the data meet the requirements for informed consent and for the Institutional Review Boards.
References
- Shimoyama S, Kuramoto S, Kawahara M, et al. A rare case of pseudomyxoma peritonei presenting as an unusual inguinal hernia and splenic metastasis. J Gastroenterol Hepatol. 2001;16(7):825-829.
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- Mets T, Van Hove W, Louis H. Pseudomyxoma peritonei. Report of a case with extraperitoneal metastasis and invasion of the spleen. Chest. 1977;72(6):792-794.
- 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.
- Karak PK, Vashisht S, Berry M. Pseudomyxoma peritonei with splenic invasion. Trop Gastroenterol. 1991;12(4):195-198.
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- Ronnett BM, Zahn CM, Kurman RJ, et al. Disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis. A clinicopathologic analysis of 109 cases with emphasis on distinguishing pathologic features, site of origin, prognosis, and relationship to "pseudomyxoma peritonei." Am J Surg Pathol. 1995;19(12):1390-1408.
- 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.
