The ovary is a frequent metastatic site for primary
gastrointestinal malignancies (colon and gastric
carcinomas); primary cancers of breast, uterus and
cervix; and haematologic malignancies (lymphomas
and leukaemias).[1-3] Secondary ovarian malignancies are
relatively common ovarian cancers with prevalence
range of 5% to 30%. This appears to be related to the
frequency and patterns of dissemination of the primary
cancers.[2,4] In addition, secondary ovarian cancers also
infrequently arises from metastasis of malignancies of
the appendix, biliary tract, pancreas and the lungs.[1]
Metastatic ovarian cancers arises through spread from
the primary malignancies via lymphatic or haematogenous
or through transperitoneal or direct spreads.[2-3]Krukenberg tumour had been inappropriately used
to typify secondary ovarian neoplasm of gastrointestinal
tract primary or all secondary ovarian cancers by some
authors.[1] Krukenberg tumour in the strict sense refers
to metastatic ovarian cancers morphologically characterised by moderate multinodular growth and
histopathological feature of diffusely infiltrating signet
ring cells.[2] Krukenberg tumours comprise of
carcinoma arising from the stomach, colon, breast and
other sites and are often bilatera[l-2,3,5]The works by Yakushiji et al and Fukuda et al suggested
the likelihood of secondary ovarian cancer occurring
in younger individuals in comparison to primary
ovarian malignancy as the average age of the affected
patients was about a decade less than that of patients
with primary ovarian malignancy[5,6-7]. Studies by Odone
et al from the USA also reported increased frequency
(18-27%) of metastasis of colorectal carcinomas to
the ovaries in younger women (i.e. below 40 years)
than in older patients.[8] This is probably because gastric
carcinomas have a typical propensity to metastasize to
the ovary during pregnancy, with concomitant
aggressive growth post-delivery.[2-3] This could partly
have accounted for the increased incidence of
secondary malignancy in pre-menopausal women
unlike in primary ovarian cancers.Metastatic ovarian cancer may be suspected based on
detailed clinical history, however, symptoms related
to ovarian metastasis may sometimes be the first clinical
manifestation of the primary malignancy, especially for
gastrointestinal malignancies.[3] Morphologic features
that suggest secondary ovarian neoplasm include,
bilaterality, small tumour size (i.e. <10cm), ovarian
surface and superficial cortex involvement and
histological features inconsistent with a primary ovarian
malignancy.[9-10] However, it must be noted that some
primary ovarian malignancy such as serous papillary
and endomerioid carcinoma can involve both ovaries.[11]
Ovarian endometrioid carcinoma and primary ovarian
mucinous adenocarcinomas may share close histological
features with a metastatic colorectal carcinoma.[3,12-13]
Tumour marker such as CA-125 and immunohistochemistry
especially cytokeratin 7 and cytokeratin 20
may help in differential diagnosis of some secondary
ovarian tumours. However, the interpretation of such
results requires circumspection and due cognizance of
the clinical details and total morphological pictures.[14]
Therefore, correct and precise diagnosis of secondary
ovarian malignancy is critical because it has significant
implication on the patients' choice of management and
prognosis since metastatic ovarian cancer signifies an
advanced disease.[14]Secondary ovarian neoplasm has a typically poor
prognosis with median survival ranging from 1-3years
depending on the primary malignancy.[15] Hence, the
purpose of this study is to review the histopathological
pattern of secondary ovarian neoplasm at the
University College Hospital, Ibadan, South- western
Nigeria over a twenty-two and half year period.To the best of our knowledge, there has been no
published local study in the available literature on this
subject in our environment. Therefore, this study may
serve to provide the first documented baseline data
on the histopathological pattern of secondary ovarian
neoplasm at the University College Hospital, Ibadan,
and South- western Nigeria.
MATERIALS AND METHOD
This was a retrospective study. All histologically
confirmed cases of metastatic neoplasms of the ovary
in the records and files of the Department of Pathology,
University College Hospital (UCH), Ibadan between
January 1991 and June 2013 were used for the study.
These were cases diagnosed following total abdominal
hysterectomy, total abdominal hystero-salpingooophorectomy,
bilateral salpingo-oophorectomy,
omentectomy, and multiple peritoneal biopsies and postmortems
at the University College Hospital between
January 1991 and June 2013. Cases with inadequate
clinical data and those with missing slides and tissue
blocks were excluded from this study. The
haematoxylin and eosin stained histopathology slides
of the available cases were reviewed and where
necessary, new haematoxylin and eosin stained sections
were obtained from archival paraffin blocks. Cases
were re-classified to determine the histological subtypes
according to the 2014 WHO histological classification
of tumours of the ovary. The cases were all reviewed
independently by two Histopathologists. The data
obtained were analysed using the Statistical Package
for Social Sciences version 20. Ethical clearance for
the study was obtained from the Joint University of
Ibadan/University College Hospital Ethical Review
Committee. (Ethical approval number: UI/EC/12/
0380)
RESULTS
In this study, forty-six cases of metastatic tumours of
the ovary were seen accounting for 5.3% of the
histologically diagnosed cases of ovarian neoplasm (i.e.
868 cases) at the University college Hospital between
January 1991 and June 2013.The commonest secondary ovarian neoplasm in this
study was metastatic carcinoma which constituted 30
(65.2%) cases. Nineteen out of which were from
adenocarcinoma of colon. 6 cases were from the
gastric carcinoma while the remaining five cases were
from the squamous carcinoma of the uterine cervix.
Secondary Burkitt lymphoma constituted 14 (30.4%)
cases. Primary ovarian Burkitt lymphoma was ruled
out by evidence of documented clinical history and histologically diagnosed extra ovarian Burkitt
lymphoma and secondly by evidence of systemic
Burkitt lymphoma with secondary ovarian involvement
such as bone marrow infiltration. Other secondary
ovarian neoplasms were Malignant Mixed Mullerian
Tumour and metastatic leiomyosarcoma which
constituted 1 (0.1%) each. The overall peak age of
occurrence of secondary ovarian neoplasms was in
the 4th decade. Metastatic carcinomas were found
between 20-79 years with 30-39 years being the age
group with maximum tumours. Secondary Burkitt
lymphoma cases were found between 0-39 years with
the peak age of occurrence at the 2nd decade. The
only case of metastatic carcinosarcoma and metastatic
leiomyosarcoma were found in the 3rd and 4th
decades of life respectively. (Table 1). Of 46 (5.3%)
of secondary ovarian tumours, half (50.0%) of the
cases were bilateral,
Table 1:
Age Distribution of 46 patients with secondary ovarian neoplasms (p=0.001)
Age (years)
Metastatic Carcinoma
Burkitt Lymphoma
Carcino-Sarcoma
Metastatic Leiomyosarcoma
Total (%)
0-9
0
2
0
0
2 (4.3)
10-19
0
9
0
0
9 (19.6)
20-29
2
2
1
0
5 (10.9)
30-39
9
1
0
1
11(23.9)
40-49
7
0
0
0
7 (15.2)
50-59
6
0
0
0
6 (13)
60-69
2
0
0
0
2 (4.3)
70-79
4
0
0
0
4 (8.7)
Total (%)
30 (65.2)
14 (30.4)
1 (2.2)
1 (2.2)
46 (100)
DISCUSSION
In this study, 40.6% of the ovarian tumours were
malignant while 58.8% .6% were benign. This findings
were in agreement with those of similar studies by
Sabageh et al and Onyiaorah et al from Ile Ife and
Lagos respectively in South Western Nigeria who
reported 69.6% benign ovarian tumours, 30.4%
malignant ovarian neoplasms, and 80.3% benign, 19.7
malignant ovarian neoplasms respectively.[16-17] The
finding from this study also correlated with that of
Obed et al from Maiduguri, North Eastern Nigeria
who reported 79.3% of benign ovarian tumours and
29.7% malignant ovarian neoplasm.[18]Secondary ovarian tumours constituted 13.1% of
malignant ovarian tumours similar to study by Lee et al from North Korea, Asia who reported that
secondary ovarian malignancy accounted for 13.6%
of malignant ovarian neoplasm[4]Secondary ovarian tumours accounted for 5.3% of
all ovarian tumours in this study in concordance with
Swamy and Satyanarayana[19] in Chitwan, Nepal who reported 5.0%. However, similar studies by Sabageh
et al.[16] and Onyiaorah et al.[17] reported 4.3% and 3.9%
respectively. Similar foreign studies by Pradhan et al. [20]
from Dharan, Nepal; Abdullah et al.[21] from Jedda,
Saudi Arabia; Ahmad et al.[22] from Uttarakhand,
Pakistan; Jha et al.[23] from Nepal; Makwana et al.[24] from
Gurarat, India; and Gupta et al.[25] from Meeru, India
reported slightly less incidence rates of secondary
ovarian tumours namely 3,6%, 3.4%, 2.5%, 2.4%, 2.1%
and 2.0% respectively. Other similar foreign studies
by Ashraf et al.[26] from Lahore, Pakistan; Pilli et al.[27]
from India; Yasmin et al.[28] from Peshawar, Pakistan;
Nabi et al.[29] from Lahore, Pakistan reported a
comparatively lesser incidence rates of 0.8%, 0.7%,
0.7% and 0.7%. respectively.Metastatic carcinoma was the commonest secondary
ovarian tumour constituting 30 (65.2%) of secondary
ovarian tumour and 3.5% of total ovarian neoplasm
similar to some studies.[16,22,30] The primary sites of
tumours were predominantly from the colon, closely
followed by the stomach and uterine cervix. These
findings correlate closely with that of Lee et al who
reported similar spread patterns of the primary
tumours in Korean women[4,31-32]Unlike in similar study by Lee et al from North Korea
that reported extremely small proportions of secondary
ovarian neoplasms of extra gastrointestinal and nongynaecological
origins, secondary Burkitt lymphoma
accounted for 30.4% (14) of secondary ovarian
tumour and 1.6% of total ovarian neoplasm.[4] This
might not be unconnected with the overall incidence
and ethnic variations of the primary malignancy.[4]There is a significant variation in the disease
progression and survival rate between primary and
secondary Burkitt lymphoma with worse and less
favourable outcome in secondary Burkitt lymphoma
as it represents an advanced stage of the disease.
Therefore, accurate diagnosis of Burkitt lymphoma is
crucial for appropriate treatment.[33] The diagnostic criteria for primary ovarian lymphoma as
recommended by Fox et al include; the confinement
of the disease to the ovary or adjacent lymph nodes
or structures, absence of the disease in blood or bone
marrow and appearance of remote involvement at
least 60 months following earlier diagnosis of ovarian
lymphoma.[33]The peak age of occurrence of metastatic carcinoma
was 30-39 years age group younger than those with
primary malignant epithelial tumours. This finding was
corroborated by Young and Scully[2], and McCluggage
and Wilkinson3 respectively who noted that,
gastrointestinal carcinomas have a typical propensity
to metastasize to the ovary during pregnancy, with
concomitant aggressive growth post-delivery. This
could partly have accounted for the increased incidence
of secondary malignancy in pre-menopausal women
unlike in primary ovarian cancers.[16,18,24,30]
CONCLUSION
This study has revealed the occurrence of secondary
malignant ovarian neoplasms in younger age groups.
Therefore this study emphasizes that in young females
with ovarian mass, the possibility of secondary ovarian
tumour types should not be overlooked. Although
ovarian neoplasms can be diagnosed clinically and
radiologically, a histological diagnosis is inevitable for
a definitive diagnosis of ovarian tumours because it
has significant implication on the patients' choice of
management and prognosis since metastatic ovarian
cancer signifies an advanced disease relative to primary
ovarian cancers.