Primary ovarian fibrosarcomas are very uncommon neoplasms. Since the diagnostic criteria were established in 1981, less than one hundred cases have been reported. This diagnosis can be difficult to establish and other similar appearing  mesenchymal processes must be ruled out. In every case this diagnosis is under consideration. Multiple sections of the specimen and immunohistochemical stains will be necessary to support this diagnosis. The difficulty of recognition in frozen section in the majority of the situations implies that  the diagnosis should be deferred to the definitive study of the permanent sections with immunohistochemical studies. There exists a histological resemblance between a primary ovarian fibrosarcoma and actively mitotic fibroma. In some cases, it can be impossible to separate exactly these two entities. We report a well-differentiated ovarian fibrosarcoma, with less than 1-2 mitosis ×10 HPF and low-grade cytological atypia, similar to active mitotic fibromas, developing liver metastasis one year later. Despite having distant metastasis, some cases with long survival rates have been reported in patients who received chemotherapy after surgery; so that the adjuvant chemotherapy should be considered, especially in young females

Castellví, Josep

Díaz de Corcuera Frutos, Isabela

García Jiménez, Angel

Pérez Benavente, Assumpció

Ramón y Cajal, Santiago

English

PubMed

Primary ovarian fibrosarcomas are very uncommon neoplasms. Since the diagnostic criteria were established in 1981, less than one hundred cases have been reported. This diagnosis can be difficult to establish and other similar appearing  mesenchymal processes must be ruled out. In every case this diagnosis is under consideration. Multiple sections of the specimen and immunohistochemical stains will be necessary to support this diagnosis. The difficulty of recognition in frozen section in the majority of the situations implies that  the diagnosis should be deferred to the definitive study of the permanent sections with immunohistochemical studies. There exists a histological resemblance between a primary ovarian fibrosarcoma and actively mitotic fibroma. In some cases, it can be impossible to separate exactly these two entities. We report a well-differentiated ovarian fibrosarcoma, with less than 1-2 mitosis  HPF and low-grade cytological atypia, similar to active mitotic fibromas, developing liver metastasis one year later. Despite having distant metastasis, some cases with long survival rates have been reported in patients who received chemotherapy after surgery; so that the adjuvant chemotherapy should be considered, especially in young females

Angel García Jiménez

Josep Castellví

Assumpció Pérez Benavente

Isabela Díaz de Corcuera Frutos

Santiago Ramón y Cajal

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Case Reports in Medicine

Ovarian Fibrosarcoma: Clinicopathologic Considerations about the Intraoperative and Post-Surgical Procedures

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Hindawi Publishing Corporation
Case Reports in Medicine
Volume 2009, Article ID 802817, 4 pages
doi:10.1155/2009/802817
Case Report
Ovarian Fibrosarcoma: Clinicopathologic Considerations about
the Intraoperative and Post-Surgical Procedures
Angel Garcı´a Jime´nez,1 Josep Castellvı´,1 Assumpcio´ Pe´rez Benavente,2
Isabela Dı´az de Corcuera Frutos,3 and Santiago Ramo´n y Cajal1
1Department of Pathology, University Hospital Vall d’Hebron, Passeig Vall d’Hebron, 119-129, 08035 Barcelona, Spain
2 Service of Gynecology, University Hospital Vall d’Hebron, Passeig Vall d’Hebron, 119-129, 08035 Barcelona, Spain
3 Service of Medical Oncology, University Hospital Vall d’Hebron, Passeig Vall d’Hebron, 119-129, 08035 Barcelona, Spain
Correspondence should be addressed to Angel Garcı´a Jime´nez, angarcia@vhebron.net
Received 7 October 2009; Accepted 15 December 2009
Recommended by Herman Yee
Primary ovarian fibrosarcomas are very uncommon neoplasms. Since the diagnostic criteria were established in 1981, less than one
hundred cases have been reported. This diagnosis can be diﬃcult to establish and other similar appearing mesenchymal processes
must be ruled out. In every case this diagnosis is under consideration. Multiple sections of the specimen and immunohistochemical
stains will be necessary to support this diagnosis. The diﬃculty of recognition in frozen section in the majority of the situations
implies that the diagnosis should be deferred to the definitive study of the permanent sections with immunohistochemical studies.
There exists a histological resemblance between a primary ovarian fibrosarcoma and actively mitotic fibroma. In some cases, it
can be impossible to separate exactly these two entities. We report a well-diﬀerentiated ovarian fibrosarcoma, with less than 1-2
mitosis ×10 HPF and low-grade cytological atypia, similar to active mitotic fibromas, developing liver metastasis one year later.
Despite having distant metastasis, some cases with long survival rates have been reported in patients who received chemotherapy
after surgery; so that the adjuvant chemotherapy should be considered, especially in young females.
Copyright © 2009 Angel Garcı´a Jime´nez et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
1. Introduction
In Gynecology there is a wide spectrum of ovarian spindle
cell lesions developing from stromal fibroblasts located at
the periphery of ovarian follicles. Amongst these lesions
there are fibromas, thecomas, mitotically active fibromas,
and fibrosarcomas. The primary ovarian fibrosarcomas
are extraordinarily rare neoplasm; the diagnostic criteria
include a mitotic index higher than 4 × 10 HPF and
atypical cytology. Necrosis and haemorrhage are frequently
associated in these cases. Because they are uncommon
and can look like other malignant spindle cell pro-
cesses, the criteria of diﬀerentiation sometimes are not
clear, especially between mitotically active fibromas and
fibrosarcoma. Therefore these lesions may be prone for
misdiagnosis leading to in appropriate therapy especially
if intraoperative studies with frozen sections are used
primarily.
2. Clinic Case
A 55-year-old woman, without significant pathologic
antecedents, had vaginal bleeding associated with notable
pelvic swelling. A giant heterogeneous ovarian mass of
23 × 15 cm, without lymphadenopathy, was discovered by
ultrasound and CT scan image studies (Figure 1). The
patient underwent surgical excision of the mass. Ovarian
tumour removal was extremely diﬃcult due to the vast
adhesions to the anterior abdominal wall as consequence of
infiltrative margins. The uterine annexal tumour was sent
to the Department of Pathology with the aim to analyze
and rule out malignancy by means visual assessment of
frozen sections during intraoperative study. The lesion was
considered as a spindle cell tumour with no clear signs of
atypia, and with final diagnoses deferred to histopatholog-
ical examination of the permanent sections. Because there
were grossly extensive necrotic areas, capsular disruption
2 Case Reports in Medicine
R
A
10 cm
Figure 1: CT scanner image. Huge ovarian mass involving the
anterior abdominal wall can be appreciated.
Figure 2: Giant ovarian tumour with capsular disruption and
strong red surface colour due to haemorrhaging.
and many adhesions with other organs, excision using an
ovarian cancer protocol was performed. As a result, surgery
was completed with bilateral iliac and paraaortic lymph
node dissection, omentectomy, and cytological analysis of
peritoneal washings.
3. Pathologic Study
Grossly, the ovarian tumour measured 23 × 15 cm, with
capsular disruption and a strong red external surface colour
(Figure 2). The cut surface of ovary showed multiple blood
filled cysts and solid but necrotic areas. Only 10%–20% of
the total of tumour consisted of viable tumour. The spec-
imen was sampled exhaustively. Microscopically, necrosis
and haemorrhage were reflected as major components. A
proliferation of spindle cells was found, frequently adopting
a storiform pattern. The cellular appearance consisted of
homogeneously appearing spindle-shaped cells and nuclei
with scant amounts of cytoplasm and ill-defined margins
(Figure 3). Only a few of mitotic figures was found, with a
rate less than 1-2 × 10 HPF. Even though the viable tumour
was mainly homogeneous with low number of mitotic
figures, the diagnosis of malignancy was rendered due to
other factors, such as necrosis, haemorrhage, ovarian cap-
sular disruption, and invasion of the neighbouring tissues.
Immunohistochemical stains only revealed a strong expres-
sion of vimentin. In order to rule out other mesenchymal
entities (GIST, leiomyosarcoma, dendritic cell proliferations,
and sarcomatoid carcinomas) other immunostains were
performed, such as cocktails of cytokeratins, CD117 (c-
kit), smooth muscle actin, H-caldesmon, neuron specific
enolase, CD21, CD22, and CN4A. All of these antibofies
stained negative in the tumour cells. On the other hand,
a nuclear expression for Ki 67 (MIB-1) was seen in more
than 60% of total cells, despite the infrequent number of
mitotic figures. In the complementary specimens (uterus,
lymph nodes, omentum, peritoneum) there was no definitive
evidence of malignancy. The case was diagnosed as ovarian
fibrosarcoma, stage pT1c No Mo/I C (FIGO).
After the diagnosis, the patient underwent adju-
vant chemotherapy. A combination of 4′-epidoxorubicin
60 mg/m2 on days 1 and 2 and ifosfamide 1.8 g/m2 on
days 1 through 5, with hydration, mesna, and granulocyte
colony-stimulating factor were administrated, according to
the Italian co-operative study with adjuvant chemotherapy
for soft tissue sarcoma [1]. After a disease free interval of
14 months, one metastatic liver nodule was detected. The
hepatic lesion was removed and the histology was identical
to the primary ovarian tumour.
4. Discussion
Primary ovarian fibrosarcoma is an extremely rare entity
[2, 3]. They are considered to have originated directly
from stromal cells around the sex cord of ovarian follicles.
Alternatively, a malignant transformation of a previous
fibroma is also believed to be a potential origin as well. These
tumours occur at any age although most of them appear
in menopausal and postmenopausal women. Clinically, the
patients note abdominal swelling as a result of large pelvic
mass with accelerated growth. The majority of tumours show
areas of necrosis and haemorrhage, capsular disruption as
well as infiltrative margins that make adhesions with other
pelvic organs. Microscopically, similar to fibrosarcomas in
other locations, there is a high cellularity often there is a
moderate cellular pleomorphism and an average of 4 or
more mitotic figures × 10 HPF [3]. In some cases, trisomy
12 or 18 has been reported in these neoplasms [4]. Usually,
the prognosis is poor, with early distant metastases, show-
ing resistance to some adjuvant chemotherapy regiments,
although recently several cases have been reported with long
posttreatment survival rates [5].
Diagnosis is diﬃcult because there are not specific
patterns of immunohistochemical staining or molecular
studies for this sort of neoplasm. Before making a diagnosis
of primary ovarian fibrosarcoma, other spindle cell lesions
should be ruled out. In this sense, some Krukenberg’s
tumours have a large component of spindle cells, and
in some cases the epithelial cells can be identified only
after an extensive sampling [6, 7]. Similarity, sarcomatoid
carcinomas might have similar histology as fibrosarcoma
Case Reports in Medicine 3
(a) (b)
Figure 3: (a) Spindle cells appear with relatively homogeneous nuclei and scant cytoplasm. Low-grade atypia and few number of mitosis
can be observed. H/E 400X. (b) the ki-67 immunostain shows a 60% nuclear expression of all spindle cells among the interstitial collagen.
[6] and require immunohistochemical stains or ultrastruc-
tural study to demonstrate their epithelial nature. Primary
ovarian leiomyosarcomas and ovarian invasion from uterine
origin might be mistaken as fibrous neoplasms. However,
leiomyosarcomas tend to show a higher grade of cellular
pleomorphism and immunostains with specific markers
for smooth muscle. Sometimes, ovarian sex cord tumours
are also associated with a vast spindle cell component,
mimicking sarcomatoid lesions. In these cases it is necessary
to make an exhaustive sampling to minimize misdiagnosis,
and in some cases stain for inhibin, although some stromal
cells can be positive as well [8].
In the diﬀerential diagnosis of these spindle-shaped
lesions, we should also consider the possibility of gastroin-
testinal stromal tumours involving the ovary; in these cases,
immunostain for CD117 or molecular studies, evaluating c-
kit mutations, would be essential [9, 10]. Other processes
that eventually aﬀect the ovary are endometrial stromal
sarcomas which must be taken into account, especially
those with a spindle shaped cell pattern. These cases will
need immunohistochemistry with CD10 to demonstrate
their stromal nature [11]. More rarely, some tumours with
occasional spindle cell or sarcomatoid pattern can involve
the ovary such as dendritic cell neoplasms and melanomas,
where immunohistochemical stains will be also necessary
[12, 13]. Finally, ovarian metastases of sarcomas originating
in other locations should also be ruled out.
Generally, the spectrum of ovarian fibrous tumours is
wide and the diagnostic criteria are not always clear and
therefore the management of these patients may not be
appropriate. There are no problems distinguishing a fibroma
from fibrosarcoma; however, the recognition of a mitotically
active fibroma is not clear. Mitotically active fibromas have
been defined as spindle cell tumours with low mitotic rate
(less than 4×10 HPF), without atypical cytology, necrosis, or
infiltrative margins. On the contrast, ovarian fibrosarcomas
usually have higher mitotic rate and have atypical cytology
[3]. Usually, these criteria should not give rise to any
problems, but Irving et al. recently reported that the mitotic
activity was not the unique criteria of malignancy [9].
These authors studied 75 ovarian fibrosarcomas, including
45 mitotically active fibromas. Ovarian fibrosarcomas fre-
quently show cellular atypia or pleomorphism besides a high
mitotic activity. In addition, they considered that fibrosar-
comas usually had a short history of accelerated growth and
were tumours with adhesions, necrosis, and haemorrhage. In
contrast, mitotically active fibromas had no cellular atypia,
their gross sizes were smaller and adhesions, necrosis or
haemorrhage were absent in their series. However, not all of
these histological diﬀerences can be discriminatory between
a fibrosarcoma and mitotically active fibromas. In our case,
despite having low degree of atypical cytology and few
numbers of mitotic figures, this tumour metastasized to the
liver one year later. A discrepant clue in our case leading
to our diagnosis of malignancy was the discrepant Ki-67
staining compared to the visual assessment of mitotic figures.
Several diﬀerent series with several tumours with criteria
of fibrosarcomas had a good survival outcome and long
unexpected survivals after adjuvant chemotherapy have been
reported [5]. These experiences bring us the hypothetical
idea that mitotically active fibroma and fibrosarcoma could
be the same neoplasm with diﬀerent degree of evolution. In
other words, there still exists an overlapping between several
ovarian spindle cell tumours that may complicate the suitable
management of these patients.
In conclusion, these findings imply that we still have
no clearly defined morphologic criteria to diﬀerentiate these
proliferative spindle shaped cell processes. The histology
is diﬃcult, and there are no specific immunostains or
molecular factors capable of identifying the biological behav-
ior. More studies will be necessary to identify predictive
factors of behavior. Moreover, the intraoperative studies with
frozen sections, that are useful in epithelial tumours, can be
extraordinarily diﬃcult to read, and in this sense, no cases
4 Case Reports in Medicine
of ovarian fibrosarcoma have been reported yet. We recom-
mend caution in the diagnosis by frozen sections. In these
situations, we prefer make the diagnosis only as proliferative
spindle cell tumour, without excluding a malignant nature
and wait to definitive study of permanent sections from
extensive sampling. Under these circumstances, gynecolog-
ical surgeons need to evaluate other additional parameters
intraoperatively, such as the existence of capsular disruption,
necrosis, or haemorrhage that allows a greater suspicion
of malignancy. In these tumours, not only the histological
appearance should prevail but the clinical signs (accelerated
growth, adhesions) and direct exam of surgical specimen
(necrosis, haemorrhage) have to be evaluated as well. In
addition, high rates for antigen of proliferation Ki67 (MIB-
1), as in our case (above 60%), could contribute to the
diagnosis of malignancy, despite having a low visual mitotic
rate.
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A z o u r ya n dJ .D .W o o d r u ﬀ, “Primary ovarian sarcomas.

Adjuvant chemotherapy for adult soft tissue sarcomas of the extremities and girdles: results of the Italian randomized cooperative trial,”

An immunohistochemical analysis of endometrial stromal and smooth muscle tumors of the uterus: a study of 54 cases emphasizing the importance of using a panel because of overlap in immunoreactivity for individual antibodies,”

Cellular ﬁbromas and ﬁbrosarcomas of the ovary: a comparative clinicopathologic analysis of seventeen cases,”

Cellular ﬁbromas of the ovary: a study of 75 cases including 40 mitotically active tumors emphasizing their distinction from ﬁbrosarcoma,”

Clusterin expression distinguishes follicular dendritic cell tumours from other dendritic cell marker and clinopathologic data on 12 additional follicular dendritic cell tumours and 6 additional interdigitating dendritic cell tumour,”

From Krukenberg to today: the ever present problems posed by metastatic tumors

Gastrointestinal stromal tumors metastatic to the ovary: a report of ﬁve cases,”

K r a e m e r ,E .G .S i l v a ,a n dN .S n e i g e ,“ F i b r o s a r c o m ao f ovary: a new component in the nevoid basal-cell carcinoma syndrome,”

Krukenberg tumors of the ovary: a clinicopathological analysis of 120 cases with emphasis on their variable pathologic manifestations,”

Malignant ﬁbrothecomatous tumour of the ovary: diagnostic value of anti-inhibin immunostaining,”

Primary ovarian ﬁbrosarcoma with long-term survival: a report of two cases,”

Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classiﬁcation from

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2820290

Ovarian Fibrosarcoma: Clinicopathologic Considerations about the Intraoperative and Post-Surgical Procedures

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