Description of a case report of an intestinal-type ... - Cancer Therapy

Cancer Therapy Vol 6, page 1005
Cancer Therapy Vol 6, 1005-1010, 2008
Description of a case report of an intestinal-type
mucinous borderline ovarian tumor
Case Report
Raffaele Longo 1, *, Irnerio Angelo Muttillo 2 , Francesca Cacciamani 1 , Giuseppe Dal
Sasso 2 , Lisa Luzzatto 2 , Mauro Simone 2 , Palmiro Masci 3 , Francesco Torino 1 ,
Giampietro Gasparini 1 , Alessandro Mero 2
1 Division of Medical Oncology, “San Filippo Neri” Hospital Rome, Italy
2 Division of Surgery and Emergency, “San Filippo Neri” Hospital Rome, Italy
3 Division of Anathomy and Pathology, “San Filippo Neri” Hospital Rome, Italy
__________________________________________________________________________________
*Correspondence: Raffaele Longo, MD, Division of Medical Oncology ‘San Filippo Neri’ Hospital, Via Martinotti 20, 00135 Rome,
Italy; Tel: +39-06-33062272; Fax: +39-06-33062414; E-mail: raflongo@libero.it
Key words: ovarian mucinous borderline tumors, ovarian surgery, adnexal masses, tumors of low malignant potential
Abbreviations: Borderline ovarian Tumors, (BOTs); intraoperative frozen section, (IFS); Mucinous Borderline Ovarian Tumor,
(MBOT)
Received: 27 October 2008; Revised: 24 November 2008
Accepted: 3 December 2008; electronically published: December 2008
Summary
We report the case of a 53 year-old woman hospitalized for an intestinal subocclusion syndrome due to a very large,
multicystic mass occupying the whole abdominal cavity and compressing the other intrabdominal organs. The
patient underwent surgical tumor resection with a radical hysterectomy and bilateral salpingo-oophorectomy.
Histology showed an intestinal-type mucinous borderline tumor (MBT) of the left ovary (diameter of 33x29x27cm;
weight of 17 Kg) containing focal areas of “in situ” adenocarcinoma. After a follow-up of 19 months, the patient is
now alive and disease-free. Intestinal-type mucinous borderline ovarian tumors (MBOTs) are uncommon tumors of
large dimensions and good prognosis. Surgery is the cornerstone in their management. However, many issues
remain unmet, including the extent of the staging procedure and the optimal surgical approach, such as the use of
laparoscopy, conservative surgery, and retroperitoneal lymph nodes dissection. Chemotherapy should be reserved
only for progressive disease or in case of invasive peritoneal implants that may not be surgically resected.
I. Introduction
Borderline ovarian Tumors (BOTs) were first
described by Taylor in 1929 and account for 10-20% of all
epithelial ovarian cancers (Wong et al, 2007). They are
characterized by a degree of cellular proliferation and
nuclear atypia without aspects of infiltrative growth or
stromal invasion. BOTs are typically present in younger
women compared with invasive carcinomas, and they are
mostly diagnosed at an earlier stage, resulting in an
excellent prognosis. The 5-year overall survival rate for
early-stage disease is approximately 98% and varies
between 86% and 92% for more advanced disease (Hart,
2005a,b; Wong et al, 2007).
Histologically, BOTs can be divided according to
their epithelial characteristics as serous (50%), mucinous
(46%), and mixed, endometrioid, clear cell, or Brenner
tumors (3.9%) (Hart, 2005a,b; Wong et al, 2007).
We report the case of a large Mucinous Borderline
Ovarian Tumor (MBOT) in a post-menopausal woman
treated with a radical hysterectomy and bilateral salpingooophorectomy.
II. Case Report
In March 2007, a 53 year-old post-menopausal woman was
hospitalized for abdominal distension and pain, vomiting and
constipation.
Physical examination revealed a large abdominal mass.
Over the last year she had progressively gained weight despite a
decreased appetite without any other clinical sign or symptom of
the underlying disease.
Whole body CT scan (Figure 1A-D) and transabdominal
ultrasound showed the presence of a massive and multicystic
ovarian lesion occupaying the whole abdominal cavity and
compressing the other intrabdominal organs, associated with a
small amount of ascites. Blood chemistry documented low levels
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Longo et al: Description of a case report of an intestinal-type mucinous borderline ovarian tumor
of total proteins with hypoalbuminemia. The serum level of CA-
125 was 120 U/ml (normal range < 35 U/ml).
The patient underwent surgical resection of the tumor with
hysterectomy, bilateral salpingo-oophorectomy, appendectomy
and infracolic omentectomy (Figure 2A). A careful inspection of
the peritoneum, associated to multiple random biopsies,
documented the absence of peritoneal tumor implants. Peritoneal
cytology was negative and no enlarged retroperitoneal lymph
nodes were also detected. Histology documented an intestinaltype
MBT of the left ovary (diameter of 33x29x27cm; weight of
17 Kg) (Figure 2B) containing focal areas of “in situ”
adenocarciroma (Figure 2C, small arrows) and aspects of early
stromal desmoplastic reaction (Figure 2C, big arrows).
The postoperative course was uneventful and the patient
was discharged 10 days post-operatively. After a follow up of 19
months, the patient is alive, in good clinical conditions, and
disease-free as documented by a whole body CT scan and serum
level of CA-125 that returned to within normal ranges.
III. Discussion
BOTs represent approximately 10% to 20% of all
ovarian malignancies and can be quite large in size,
particularly mucinous histotype. In 1988, two MBOT
subtypes have been described: the intestinal-type (85%)
and the endocervical-like (Mullerian) type (15%) (Acs,
2005; Hart, 2005a,b; Wong et al, 2007). MBOTs,
particularly the intestinal-type, can be associated with
pseudomyxoma peritonei (10%) and necessitates a
thorough investigation of the gastrointestinal tract with
special attention to the appendix (Acs, 2005; Hart, 2005a;
Vang et al, 2006).
The endocervical-like type is clinically and pathologically
related to serous borderline tumors with which it is often
mixed and it is usually associated with endometriosis
(Acs, 2005; Hart, 2005a; Vang et al, 2006). The intestinaltype
is much more common and occurs over a very wide
age range (9-70 years), with a mean age of 35 years (Acs,
2005; Hart, 2005a,b; Wong et al, 2007). Typically, it is
characterized by large multicystic masses (mean diameter,
17 cm) with smooth outer surfaces like benign mucinous
cystadenomas (Acs, 2005; Hart, 2005a,b; Wong et al,
2007). Over 90% of these tumors are unilateral and may
have an heterogeneous composition, with coexisting areas
of cystadenoma, noninvasive carcinoma, and sometimes
occult areas of invasive carcinoma. For this reason, an
adequate sampling is particularly important (Acs, 2005;
Hart, 2005a,b; Vang et al, 2006; Wong et al, 2007).
Figure 1. Whole body CT scan showed a massive and multicystic ovarian lesion (arrows) occupaying the whole abdominal (A-C) and
pelvic (D) cavity and compressing the other intrabdominal organs, such as liver, spleen, and kidneys.
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Cancer Therapy Vol 6, page 1007
Figure 2. At surgical abdominal examination, a very large left ovarian tumor was documented (diameter of 33x29x27cm; weight of 17
Kg) (A). Histology showed an intestinal-type Mucinous Borderline Ovarian Tumor (B) containing focal areas of “in situ”
adenocarciroma (C, small arrows) and aspects of early stromal desmoplastic reaction (C, big arrows).
Histologically, MBOTs are composed of multiple
cysts and glands of various sizes that are lined by a
mixture of cell types, including endocervical-, gastric- and
goblet-type mucinous cells, which are generally stratified
into no more than two or three layers and have slight-tomoderate
nuclear atypia (Lee and Scully, 2000; Acs, 2005;
Hart, 2005a,b; Vang et al, 2006; Wong et al, 2007).
Mitotic figures may be easily found and areas of necrosis
and acute inflammation may be present (Lee and Scully,
2000; Acs, 2005; Hart, 2005a,b; Vang et al, 2006; Wong
et al, 2007).
One or multiple tiny foci of stromal invasion have
been documented in up to 9% of MBOTs (Hart, 2005a,b).
In most cases, individual microinvasive foci are less than
1-2 mm and may have several histological patterns (Hart,
2005a,b).
Small or large areas of noninvasive mucinous
carcinoma occur in about 15-55% of otherwise typical
MBOTs (Acs, 2005; Hart, 2005a,b). In this case,
additional sampling is required to exclude overtly invasive
areas of carcinoma that usually are related to a poor
prognosis (Hart, 2005a).
After a complete surgical treatment, almost all
intestinal-type MBOTs are Stage I and have an excellent
prognosis with reported metastatic rates of 0-7% and 0-3%
for tumors with or without noninvasive carcinoma areas,
respectively (Kliman et al, 1986; Watkin et al, 1992;
Kaern et al, 1993; Guerrieri et al, 1994; Nayar et al, 1996;
Lee and Scully, 2000; Rodriguez and Prat, 2002; Ludwick
et al, 2005; Kikkawa et al, 2006). In one of the largest
reported series of Stage I pure MBOTs, actuarial survival
rates were 98% at 5 years and 96% at 10 years (Lee and
Scully, 2000). More than half of the tumors were treated
by unilateral salpingo-oophorectomy.
Tumors with noninvasive carcinoma also have a
favorable prognosis (Kliman et al, 1986; Watkin et al,
1992; Kaern et al, 1993; Guerrieri et al, 1994; Nayar et al,
1996; Lee and Scully, 2000; Rodriguez and Prat, 2002;
Ludwick et al, 2005; Kikkawa et al, 2006). They are
usually Stage I tumors, although up to 7.2% of reported
cases in one literature review have been Stage II or III, and
almost 6% of 208 Stage I patients with noninvasive
carcinoma recurred (Lee and Scully, 2000).
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Longo et al: Description of a case report of an intestinal-type mucinous borderline ovarian tumor
Surgery is the cornerstone in the management of
BOTs, but many issues exist on the extent of the staging
procedure and the optimal surgical approach, including the
use of laparoscopy, conservative surgery, and
retroperitoneal lymph nodes dissection. Considering the
clinical relevance of the stage in deciding treatment
options, a careful inspection of the entire abdominal cavity
with peritoneal washing, infracolic omentectomy, removal
of all macroscopic suspicious peritoneal lesions, multiple
peritoneal biopsies, and, for MBOTs, appendectomy, are
mandatory (Cadron et al, 2007). Unfortunately, complete
staging is only performed in 50% or fewer patients, even
though the pelvic peritoneum and abdominal peritoneum
are involved in 58% and 48% of patients, respectively
(Menzin et al, 2000; Cadron et al, 2007). Furthermore,
invasive implants are present in pelvic peritoneum and
abdominal peritoneum in 9% and 14% of patients,
respectively. The omentum is involved in 39% of patients,
and in 9% of patients, these implants are invasive (Jones,
2006; Cadron et al, 2007).
Because younger women are more likely to develop
BOTs, an important issue is the appropriateness of
conservative surgery with fertility preservation for stage I
disease or for BOTs with noninvasive implants. According
to results of retrospective studies comparing conservative
vs more radical approach, it seems reasonable to perform
conservative surgery (ie, salpingo-oophorectomy with
infracolic omentectomy and multiple peritoneal biopsies
and cytology) only for stage I disease (Cadron et al,
2007).Considering the increased risk of developing
persistent invasive implants or recurrence, patients with
invasive implants should be treated with radical surgery.
In case of extraovarian recurrence with invasive implants
after conservative therapy, extensive cytoreductive surgery
remains the treatment option of choice (Cadron et al,
2007). The advantage of retroperitoneal lymph node
sampling is questionable in patients with BOTs and
lymphadenectomy can be omitted, even for the advanced
disease, because it does not affect the recurrence or
survival rate (Cho et al, 2006; Cadron et al, 2007). A
recent prospective study conducted in 57 women with
BOTs, para-aortic and pelvic node dissection was not
correlated to any survival advantage (Pirimoglu et al,
2008).
Laparoscopy seems to be feasible in BOTs of
moderate size (diameter below 10 cm), to give fewer
complications and a shorter hospitalization (Cadron et al,
2007; Daraï et al, 2007; Ødegaard et al, 2007). However,
many potential concerns remain unmet, including the
chance of tumor rupture, the development of port site
metastases, and finally a potentially increased number of
patients with unstaged or inappropriately staged tumors.
Future, prospective studies with a long-term follow-up are
needed to determine the ultimate recurrence risk as well as
fertility rates of this procedure as compared to laparotomy
(Cadron et al, 2007).
Chemotherapy should be reserved only for
progressive disease that does not respond to surgical
management (Cadron et al, 2007).
Finally, another important issue is the intraoperative
frozen section (IFS) diagnosis of BOTs. A recent
retrospective analysis comparing IFS analysis and
definitive histology showed an agreement between these
two procedures in 69/96 (71.9%) patients, yielding an
overall sensitivity and a positive predictive value of 75.0%
and 94.5%, respectively. Underdiagnosis and
overdiagnosis occurred in 27/96 (28%) and 0/96 (0%)
patients, respectively. The authors concluded that surgical
management based on IFS diagnosis should be used with
caution in BOT patients (Tempfer et al, 2007).
In our case, considering tumor dimensions, the
menopausal status and the lack of peritoneal implants and
locoregional lymph nodes involvement, the patient
underwent radical surgical tumor resection without other
adjuvant treatments. After a follow up of 19 months, the
patient is alive, in good clinical conditions, and diseasefree
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