Pseudomyxoma peritonei extending to the lower extremity: a case report

An 80-year-old woman presented to our institution with odorous discharge from an opening
in her swollen right thigh. In the previous 4 years, her right thigh had swollen up.
Three months prior to her visit, an opening formed spontaneously at the medial aspect
of the thigh, and jelly-like material began to ooze steadily. Two months before her
visit, an odorous discharge began to exude from the opening. Physical examination
revealed fluctuation in the right lower quadrant of the abdomen, the medial aspect
of the right thigh, and the posterior aspect of the right calf.

Fourteen years previously, the patient had undergone an operation for an intra-abdominal
mass at another institution. The operation record mentioned a bilateral salpingo-oophorectomy
with massive adhesiolysis and excision of a large 20?×?19?×?18-cm mass in the retroperitoneal
space. There was no mention of the appendix in the record, and the patient had not
undergone appendectomy before the operation. The pathological record reported a mucinous
borderline left ovarian tumor with extensive pseudomyxoma ovarii and severe tubo-ovarian
adhesion. Although the patient had noted progressive abdominal expansion with dull
pain in the right lower quadrant 8 years previously, diagnostic studies such as computed
tomography (CT) and ultrasonography (US) 16] were not performed.

A magnetic resonance image of the right thigh showed a fluid-containing lesion in
contact with the surface and an opening in the medial compartment. In addition, there
was a multiloculated, lobulated lesion mainly involving the anterior and medial compartment
of the thigh and extending distally along the fascia of the hamstring muscles (Fig 1a, b). A magnetic resonance image of the calf also revealed a similar lesion chiefly involving
the posterior compartment along the deep fascia (Fig 1c, d). An abdominal CT scan showed a large multiloculated cystic mass occupying the right
retroperitoneal space and extending to the right thigh (Fig 1e). There were no definite abnormal findings on the chest CT scan. Together, these
imaging studies revealed extension of the lesion from the abdomen to the calf. The
patient’s initial blood tests revealed abnormal results including a white blood cell
(WBC) count of 11,820/mm
³
, 87.5 % segmented neutrophil, an erythrocyte sediment rate of 96 mm/h, 5.89 mg/dL
C-reactive protein, 178 mg/dL fasting blood sugar, 4.5 g/dL total protein, 2.4 g/dL
albumin, and 50 U/L aspartate transaminase. The urine analysis and sediment examination
noted abnormal results including leukocytosis, a positive occult blood, and WBC and
red blood cell count of 30 to 49 and 20 to 29 per high-power field.

Fig 1. Image findings. a A T2-weighted coronal view magnetic resonance image (MRI) of the right thigh shows
a cystic lesion mainly involving the anterior compartment, especially the sartorius
muscle (an arrowhead). b A T2-weighted axial view MRI reveals lesions mainly involving the medial compartment
along the fascia of the hamstring muscles (an arrowhead). c A T2-weighted coronal view of MRI of the right calf shows multiloculated and lobulated
lesions mainly involving the posterior compartment (arrowheads). d A T2-weighted axial view MRI reveals a lesion along the superficial fascia (arrowheads). e A coronal view abdominal computed tomography scan shows a large multiloculated cystic
mass occupying the right retroperitoneal space (arrowheads)

Immediately after admission, we started intravenous antibiotic administration, which
included 2.25 g of piperacillin and tazobactam four times a day and 1 g vancomycin
once every 96 h. Two weeks after admission, a suspected infected portion of the thigh
lesion was excised, and tracks connecting from the thigh to the peritoneum were ligated.
After the operation, administration of 2.25 g of piperacillin and tazobactam four
times a day was continued. Staphylococcus epidermidis grew when mucinous material
obtained intra-operatively from the lesion was cultured. Pathological examination
of the excised specimen demonstrated acellular mucinous materials with a carcinoembryonic
antigen-positive immunoreaction (Fig 2a).

Fig 2. Pathologic findings. a Mucinous material obtained from the right thigh shows a carcinoembryonic antigen-positive
immunoreaction (carcinoembryonic antigen antibody stain, original magnification ×200).
b A pathology slide demonstrates low-grade pseudomyxoma peritonei. The malignant epithelium
appears bland, and tumor cells look deceptively bland with papillary tufting (hematoxylin
and eosin stain, original magnification ×200). c Dissecting mucin without tumor cells was observed in the soft tissue of the right
thigh (hematoxylin and eosin stain, original magnification ×40). d A previous pathology slide demonstrates pseudomyxoma ovarii. The malignant epithelium
appears bland, and tumor cells look deceptively bland with papillary tufting

Two weeks after the first surgery, follow-up blood test results demonstrated improvement
of the infectious condition in the thigh. The WBC count, segmented neutrophil, erythrocyte
sediment rate, C-reactive protein, fasting blood sugar, total protein, albumin, and
aspartate transaminase were 4640 /mm
³
, 51.8 %, 11 mm/h, 1.09 mg/dL, 112 mg/dL, 5.7 g/dL, 2.9 g/dL, and 24 U/L, respectively.
On urine analysis and sediment examination, the WBC and red blood cell count were
1 to 3 and 4 to 9, respectively, per high-power field.

A second operation was performed for all the lesions from the abdomen to the calf
by a collaborative team of orthopedic surgeons and gynecologists. No bowel obstruction
was observed, and the appendix was not seen. A large volume of mucinous material was
suctioned from the abdominal lesion (Fig 3a). Multiple intra-muscular and interfascial connections between the abdomen and lower
extremity were observed at the level of the inguinal ligament (Fig 3b). Cytoreductive surgery with peritonectomy was performed for the intra-abdominal
lesion. The lower extremity lesion was marginally removed; it had a thin capsule and
was mostly composed of mucinous material (Fig 3c). Four hours after the operation, the patient underwent cardiopulmonary resuscitation
following a hypovolemic shock due to massive intra-operative bleeding. She recovered
with proper management without any acute sequelae.

Fig 3. Intra-operative findings. a Mucus ascites is seen gushing from the abdominal lesion. b Multiple intra-muscular and interfascial connections were observed at the level of
the inguinal ligament. c A huge cystic lesion with mucus was observed in the calf

Five days after the second surgery, no bacterial growth was observed in a culture
of intra-operatively obtained mucinous material. Pathological examination showed low-grade
mucinous carcinoma peritonei with the lining epithelium in the intra-abdominal lesion
(Fig 2b) and only acellular mucinous material in the lower extremity lesion (Fig 2c). The patient’s postoperative course was uneventful, and she was discharged 2 weeks
after the definitive operation. Thereafter, she sent us the pathology slides from
14 years previously, which were re-examined by pathologists at our institution. They
revealed pseudomyxoma ovarii (Fig 2d). The patient did not report any abdominal symptoms or swelling in the lower extremity
at the most recent follow-up, which was 2 years after the final operation. She was
able to walk with a cane, and the Musculoskeletal Tumor Society functional rating
for the lower extremity was 73 %.

Discussion

The origin of PMP is still controversial. PMP is currently thought to be associated
mainly with mucinous epithelial neoplasms of the appendix 3]–9]. However, several convincing cases have been published with a different primary organ
of origin, such as the ovary, urachus nest, or colon 10], 11]. Because our patient had not undergone an appendectomy before the operation in 1999
and there was no mention on the appendix in the operation record, we could not confirm
the appendix as the origin of PMP on histological grounds. Despite the previous pathological
report, the ovaries were normal and did not appear to be the origin of the tumor based
on the review of the previous slides. We, therefore, assume that the appendix was
the organ of origin in this case.

PMP usually manifests with tumor deposits throughout the entire peritoneal cavity.
This characteristic pattern of dissemination can be explained by the redistribution
phenomenon, which is associated with the intra-peritoneal fluid current and gravity
13]. In the end stage of disease, PMP engulfs the entire peritoneal cavity. Intestinal
movement becomes limited because of an excessive amount of mucinous tumor mass, and
bowel obstruction becomes imminent. Patients ultimately die of cachexia when untreated
3], 14], 15].

CT and US have been reported to be useful in detecting PMP 3], 17], 18]. While CT remains the gold standard for diagnostic imaging, US is inexpensive, readily
available, well tolerated, and can identify most common PMP findings such as ascites
and omental caking. Our patient did not have any diagnostic examination despite abdominal
symptom, and a relapse was diagnosed barely after development of the lower extremity
lesion.

In 1995, Ronnett et al 10] described three distinct categories of PMP, namely, diffuse peritoneal adenomucinosis
(DPAM), PMCA, and an intermediate/discordant subtype (PMCA-I/D) on the basis of pathological
findings. They reported that 5-year overall survival rates of 75 % in DPAM, 50 % in
PMCA-I/D, and 14 % in PMCA when the same surgeon treated PMP tumor patients uniformly.
Recently, Chua et al. 12] examined the outcome of nearly 2300 patients from 16 institutions worldwide who were
treated uniformly over an 18-year period and confirmed the paramount importance of
the histopathological subtype with respect to outcome. Five-year overall survival
rates were 81 % for DPAM, 78 % for hybrid tumors, and 59 % for PMCA. Multivariate
analysis showed that the PMCA subtype was an independent predictor of poor overall
survival.

Although the intra-peritoneal lesion in this case was diagnosed as low-grade PMCA
and optimal treatment was not performed for a long time, our patient did not report
any symptoms associated with bowel obstruction. Despite a huge lesion, her clinical
course was modest over a long period, and death by cachexia was avoided. We assume
that the extension of the intra-peritoneal lesion to the lower extremity acted as
an expansion of the peritoneal cavity and prevented such an outcome. When PMP is progressing,
the characteristic visceral and mesenteric sparing of PMP becomes visible intra-operatively
and is related to a favorable prognosis after surgery 19], as in our case.

The proper treatment for PMP remains uncertain; however, the combination of aggressive
cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy seems to improve
the outcome 20]. Nevertheless, extensive surgical resections to achieve complete tumor eradication
are associated with high morbidity and mortality rates and may decrease the quality
of life without any survival benefit, particularly in cases of extensive high-grade
diseases 21]–23]. In contrast, less aggressive surgery may be optimal in cases of extensive low-grade
disease, as in the extremity lesion of our patient if the benefit compensates for
surgical morbidity 24]. Chemotherapy may cause side effects, particularly surgical complications, as a result
of bone marrow toxicity 25]. As in the case of peritoneal lesions, we had to consider balancing treatment benefit
and morbidity in the extremity lesion. A wide excision encompassing large areas of
muscle and parts of neurovascular structures could have rendered the extremity nonfunctional,
especially with adjuvant treatments. In addition, it may have caused more severe hypovolemia.
Even if we had chosen more aggressive management with careful support from anesthesiologists,
it would have been difficult to achieve R0 margin because the mucinous contents and
thin capsule extended from the abdomen to the calf. The first surgery had already
contaminated the thigh area. The advanced age of the patient also added complexity;
therefore, we performed less extensive surgery without any adjuvant treatment for
the extremity lesion.

Although the cause of PMP extension to the lower extremity has an important clinical
significance, we could not explain why the extension occurred only in this case. The
fluidity of mucinous contents and the gravity might have contributed to the formation
of the lower extremity lesions as an extension of tuberculous psoas abscess into the
thigh. Further studies to elucidate the mechanism are required.