ABSTRACT
Objective: To analyse the relationship between peritumoural oedema volume and tumour volume in relation to the impact of
metastatic posterior fossa tumour survival rates.
Study Design: An observational study.
Place and Duration of Study: Umraniye Training and Research Hospital, İstanbul, Turkey, from 2011–2021.
Methodology: Fifty-six cancer patients who had been operated upon for cerebellar metastases were analysed retrospectively. To
investigate the effect of oedema on survival, patients with a single cerebellar metastasis were evaluated retrospectively. Those patients
had a single metastasis located in the cerebellum and did not receive radiotherapy or corticosteroids before surgery. OsiriX MD DICOM

viewer was used to calculate the volumes of the tumour and the oedema using fluid-attenuated inversion recovery (FLAIR) and contrast-
enhanced magnetic resonance imaging (MRI). The patients were separated into two groups, and the cut-off limit for the oedema to-tu-
mour ratio was set to two. Survival analysis was performed on the two groups.

Results: When the primary sites of the tumours were evaluated, 60.7% were located in the lungs (n = 34), 10.7% were located in the
breasts (n = 6), 10.7% were located in the gastrointestinal tract (n = 6), 7.1% were located in the renal region (n = 4), 5.4% were
located in the gynaecologic tract (n = 3), and 5.4% were located in other parts of the body (n = 3). A univariate analysis showed that
overall survival duration was significantly longer in the subgroup with breast cancer (83.3%) and in those patients with a peritumoural

oedema volume to tumour volume ratio of less than two (27.6%, p <0.05). Negative prognostic factors were lung cancer and high peritu-
moural oedema volume.

Conclusion: Significant peritumoural oedema was linked to a poor prognosis for cancer patients with a single cerebellar metastasis,
especially with lung cancer as the primary source.
Key Words: Cerebellar metastases, Cerebellum, OsiriX MD, Tumour volume.
How to cite this article: Ramazanoglu AF, Varol E, Avci F, Etli MU, Aydin S, Yaltirik CK. Peritumoural Oedema as a Predictor of Overall
Survival for Patients with Posterior Fossa Metastases. J Coll Physicians Surg Pak 2023; 33(02):136-140.

INTRODUCTION

Intracranial metastases are the common complication in cancer

patients, and 30–40% of cancer patients develop brain metas-
tases at some point during the course of their disease.1

A total of
20% of brain metastases occur in the posterior fossa.2
If the

metastasis remains untreated, the patient runs the risk of devel-
oping serious conditions such as acute hydrocephalus, brain-
stem compression, cerebellar tonsillar herniation, and falling

into a coma.2

There are various factors that affect the overall

survival rates for intracranial metastases patients,3,4 with func-
tional impairment (measured using the Karnofsky Performance

Scale Index), the occurrence of extracranial metastases, and
adjuvant chemotherapy or radiotherapy being the primary
factors that affect life expectancy.1,5,6

Correspondence to: Dr. Cumhur Kaan Yaltirik, Depart-
ment of Neurosurgery, Umraniye Training and Research

Hospital, Istanbul, Turkey
E-mail: dr_cky@yahoo.com
……………………………………………..
Received: July 30, 2022; Revised: December 11, 2022;
Accepted: January 03, 2023
DOI: https://doi.org/10.29271/jcpsp.2023.02.136

However, there are only a few studies in literature on the radiolog-
ical factors impacting the estimated survival rates of patients

with posterior fossa metastasis.7

In this study, the aim was to find
the correlation between peritumoural oedema volume and
tumour volume in relation to the impact of metastatic posterior
fossa tumours on patient survival rate.
In this study, 172 patients who had been operated on at the
Ümraniye Research and Training Hospital, between 2011 and
2021 were studied retrospectively using their hospital records.
To investigate the effect of oedema on survival, patients with a
single cerebellar metastasis were evaluated retrospectively.
The patients had a single metastasis located in the cerebellum
and did not receive radiotherapy or corticosteroids before
surgery. The pathology report was compatible with metastasis,
and the preoperative magnetic resonance imaging (MRI)
included both contrast-enhanced images and fluid-attenuated
inversion recovery (FLAIR) sequences, which were included in
the study. Patients who did not have a brain MRI prior to surgery,

whose clinical information could not be obtained, who had multi-
focal cerebral or cerebellar metastasis, who did not have a

primary focus of cancer, who were diagnosed with a neurodegen-
erative disease, and who received corticosteroid therapy for any

reason were excluded from the study. Following these criteria,

Ali Fatih Ramazanoglu, Eyup Varol, Furkan Avci, Mustafa Umut Etli, Serdar Aydin and Cumhur Kaan Yaltirik

Journal of the College of Physicians and Surgeons Pakistan 2023, Vol. 33(02): 136-140 137
56 patients were retrospectively analysed. All study participants
had undergone surgical resection and received radiotherapy
during the postoperative period. Thirty-four patients with a score
of less than two and twenty-two patients with a score of more

than two were included in the study. The cut-off limit for the oede-
ma-to-tumour ratio was two. The participants were divided into

two groups, and survival analysis was performed on two groups.
OsiriX MD is cleared by the FDA as a class II medical device for
diagnostic imaging. Hence, OsiriX MD software was used to
calculate tumour volume and peritumoural oedema volume.8
The tumours were viewed on T1 contrast-enhanced MRI
images, and a region of interest9

was marked around the tumour
tissue. Peritumoural oedemas were viewed via MRI, ROIs, and
FLAIR sequences were marked around the peritumoural
oedema tissue. The markings were made on every section of the

MRI images, and the peritumoural oedema volume was calcu-
lated using OsiriX software. To isolate the peritumoural oedema

volume from the tumour volume, the tumour volume was
subtracted from the total volume, and the peritumoural volume
was obtained. The ratio of peritumoural oedema volume to
tumour volume was then calculated (Figures 1a-1c). The
measurements were performed by two different researchers

simultaneously; there were no statistically significant interob-
server differences between the measurements.

Figure 1 (a,b,c): Calculation of tumour volume and peritumoural oedema
volume using OsiriX MD. (d,e): Kaplan–Meier survival analysis of the
study groups.
Statistical Package for the Social Sciences (SPSS) version 25.0

(IBM Corp., Armonk, NY, USA) was used for the statistical anal-
ysis of the results. Descriptive statistics, including numbers,

percentages, and mean and standard deviation (SD) were used
to evaluate the results of the study. The Kaplan–Meier analysis
method was used to calculate survival. The effects of prognostic

factors on survival were evaluated using Cox regression anal-
ysis. The results were evaluated with 95% confidence interval

and p <.05 was considered significant.
RESULTS

The median age of the participants was 62 (30–87), and 50%
were 63 years or older (n = 28). A total of 69.6% (n = 39) of the

patients were male, and 30.4% (n = 17) were female. When the
primary sites of the cancer tumours were evaluated, 60.7%
were located in the lungs (n = 34), 10.7% were located in the
breasts (n = 6), 10.7% were located in the gastrointestinal tract
(n = 6), 7.1% were located in the renal region (n = 4), 5.4% were
located in the gynaecologic tract (n = 3), and 5.4% were located
in other areas (n = 3). The median volume of the tumours
viewed in T1 contrast-enhanced MRI images was 9.54 cm3
(0.28–30.1 cm3), and the median volume of the peritumoural
oedemas, which was calculated using the total peritumoural
oedema volume in FLAIR sequences—was 92.99 cm3
(11.99–130.85 cm3). The peritumoural oedema volume to
tumour volume was less than two in 60.7% of the participants (n
= 34) and greater than two in 39.3% (n = 22, Table I).
Twenty-two of the 56 study participants (39.2%) had systemic
metastases, four (18.18%) had adrenal gland metastases, four
(18.18%) had lung metastases, and four (18.18%) had spinal
distant metastases. Hydrocephalus was observed in 16 (29%)
participants, while only four (7.1%) participants became

ventriculoperitoneal shunt-dependent. Twelve study partici-
pants (75%) recovered from hydrocephalus after being treated

with an external ventricular drainage system.

During follow-up, 73.2% of the participants (n = 41) experi-
enced death related to intracranial tumours (mean: 14.14 ±

24.62 months, median: 4.3 (1–124) months), and 60.7% of the
deaths occurred within a year. The one and three-year survival
rates were 36.7% and 21.9%, respectively, based on a
Kaplan–Meier survival analysis (Figure 1d and 1e). A univariate
analysis showed that overall survival was significantly longer in
the breast cancer subgroups, and the peritumoural oedema
volume to tumour volume ratio was less than two (27.6%, p <
0.05). It was found that the negative prognostic factors
impacting overall survival were of lung cancer [HR: 7.71
(1.04–57.32), p = 0.046], and the presence of other metastatic
tumours [HR: 11.56 (1.51–88.57), p = 0.018]. Based on the

results of the multivariate Cox regression analysis, the indepen-
dent factors affecting overall survival were lung cancer [HR:

12.98 (1.51–111.64), p = .020], multiple cancer diagnoses [HR:
10.27 (1.23–86.04), p = .032], and an oedema to tumour ratio
greater than two [HR: 2.13 (1.01–4.52), p = .048].
Compared to breast cancer patients as a reference, overall
survival was 12.98 times more negative in lung cancer
patients, 10.27 times more negative in patients with multiple
cancer diagnoses, and 2.13 times more negative in patients
whose peritumoural oedema volume to tumour volume ratio
was greater than two (Table II).
DISCUSSION

Davis et al. found that the most common primary site of malig-
nancy for brain metastases are the lungs (20–40%).9

However,
60.7% of the posterior fossa metastases in this study originated

from a lung. The lung cancer metastases in this study is signifi-
cantly greater than in other studies.10

Peritumoural oedema as a predictor of overall survival with posterior fossa metastases

138 Journal of the College of Physicians and Surgeons Pakistan 2023, Vol. 33(02): 136-140
Table I: Demographic Information (n = 56).
Variable N % Mean (SD) Median (range)
Age 56 100 60.59 (11.11) 62.5 (30–87)
Age group
<63 28 50
≥63 28 50
Gender
Female 17 30.4
Male 39 69.6
Tumour localisation
Lung 34 60.7
Breast 6 10.7
Gastrointestinal tract 6 10.7
Renal region 4 7.1
Gynaecologic tract 3 5.4
Other 3 5.4
Tumour volume (cm3) 56 100 9.83 (6.50) 9.54 (0.28–30.1)
Peritumoural oedema
volume (cm3)

56 100 16.42 (12.82) 16.57
(0.14–70.48)

Ratio of peritumoural
oedema volume to
Tumour volume

56 100 3.22 (3.77) 1.71 (0.01–16.85)

Ratio of peritumoural
oedema volume to tumour
volume
≤2 34 60.7

2 22 39.3
Systemic metastasis
Yes 22 39.3
No 34 60.7
Systemic metastasis type
Adrenal gland metastases 4 18.2
Lung metastases 4 18.2
Spinal distant metastases 4 18.2
Other 10 45.5
Hydrocephalus
complication
Yes 16 28.6
No 40 71.4
Ventriculoperitoneal shunt
Yes 4 7.1
No 52 92.9
SD: Standard deviation.

Magnetic resonance (MR) examinations, which were adopted
for clinical use in the 1980s, have taken the place of computed
tomography (CT) examinations in diagnosing primary brain
tumours and evaluating patient response to treatment.11
Contrast-enhanced MRI, which is widely used in metastasis
screening, facilitates detailed evaluation of parenchymal
metastases and structures such as the calvarium, diploic
distance, meninges, choroid plexus, and pituitary gland.11

FLAIR sequences suppress the T2-hyperintensity of cere-
brospinal fluid surrounding the brain parenchyma and in the

ventricles, permitting a clearer assessment of oedema adja-
cent to the lesion.12 MRI has a higher sensitivity than CT scans

and positron emission tomography PET-CT scans for detecting
small metastases.13,14

Advanced MRI imaging methods are frequently used in metas-
tasis examinations.15 MRI perfusion examination provides

information on the blood flow to the lesion.9

In this study,
volume measurements performed on acoustic neuromas by
Kollman et al. using Brainlab software, ITK-Snap, and the OsiriX
radiological DICOM viewer system were tested on acoustic
neuromas.16 OsiriX MD has been shown to be faster and more
reliable for volume measurements than other systems.16

The main purpose of this study is to understand whether peritu-
moural oedema of posterior fossa metastatic tumours impacts

the overall survival of cancer patients. The peritumoural
oedema volume to tumour volume ratio has recently been
investigated for diagnostic purposes by other researchers. The
literature review revealed that this study is the third research
evaluating survival in cerebellar metastasis patients. Calluaud
et al. found that peritumoural oedema is highly significant to
the overall survival of patients with metastatic posterior fossa
tumours.17 The authors divided the patients in their study into
four groups based on peritumoural oedema volume to tumour
volume ratio and found that overall survival was significantly
low with a cut-off ratio of two—a result that is in line with
authors study. They also simultaneously investigated patients
with supratentorial metastasis and posterior fossa metastasis,

while the authors excluded patients with supratentorial metas-
tasis from the study.

Kaya et al. found that carcinoma metastases have larger peritu-
moural oedema volumes than non-carcinoma metastase;

overall. However, the survival rates reported were not signifi-
cantly different in that study.18 Here, only cerebellar metas-
tases and the effect of oedema around the tumour on the

survival of the patient were evaluated. Patients with a peritu-
moural oedema volume to tumour volume ratio greater than

two had significantly shorter overall survival than patients with
a lower ratio. The authors used OsiriX MD software for
measurements, and Kaya et al. and Calluaud et al. also
used the same OsiriX software to measure tumour and
metastasis volumes.17,18

Ali Fatih Ramazanoglu, Eyup Varol, Furkan Avci, Mustafa Umut Etli, Serdar Aydin and Cumhur Kaan Yaltirik

Journal of the College of Physicians and Surgeons Pakistan 2023, Vol. 33(02): 136-140 139
Table II: Factors affecting overall survival (univariate and multivariate Cox regression analysis results).

Univariate
overall survival analysis

Multivariate
overall survival analysis

Factor Category % HR (95%CI) p-value HR (95%CI) p-value
Age <63 33.9

≥63 0.07 1.77 (0.94–3.32) 0.077 1.33 (0.69–2.55) 0.395

Gender Female 35.3

Male 14.5 1.25 (0.62–2.51) 0.533 1.99 (0.87–4.55) 0.104

Tumour location Breast 83.3

Lung 12.8 7.71 (1.04–57.32) 0.046* 12.98 (1.51–111.64) 0.020*
Other 12.5 11.56 (1.51–88.57) 0.018* 10.27 (1.23–86.04) 0.032*

Ratio of peritumoural
oedema volume to
Tumour volume

≤2 27.6

2 13.9 2.07 (1.10–3.88) 0.023* 2.13 (1.01–4.52) 0.048*

*p <0.05, Cox regression analysis, (Method = Enter), HR: Hazard ratio, CI: Confidence interval.
Previous studies have reported that 8% of cancer patients
develop hydrocephalus.2,19 In this study, 28.5% of the
studied patients developed hydrocephalus (n = 16). Only

25% of the study participants who developed hydro-
cephalus required a ventriculoperitoneal shunt operation,

and 75% went through the perioperative period using an
external ventricular drainage catheter; there was no shunt
dependency.

Limitations of this study overall survival investigated in rela-
tion to only peritumoural oedema volume to tumour volume

and not adjuvant radiotherapy or chemotherapy. Moreover,
the impact of other known factors on overall survival was
not investigated, e.g., graded prognostic assessment (GPA);

resection rates, preoperative comorbidities such as hydro-
cephalus, and molecular variations were not considered in

the statistical analysis. In future studies, peritumoural
oedema should be examined together with these factors,
and prognostic algorithms should be created. The method

used in this study allowed the authors to find the correla-
tion between preoperative neuroimaging findings and

overall survival, revealing that a significant peritumoural
oedema, as indicated by a high oedema volume to tumour
volume ratio, is linked to a poor prognosis.
CONCLUSION

Significant peritumoural oedema is linked to a poor prog-
nosis for cancer patients with a single cerebellar metas-
tasis, particularly in patients with primary lung cancer.

ETHICAL APPROVAL:
The study was approved by the ethical committee of the
Umraniye Training and Research Hospital. (Reference No.
B.10.1. TKH.4.34.H.GP.0.01/221).
PATIENTS’ CONSENT:
Informed consents were obtained from all patients included
in the study.
COMPETING INTEREST:
The authors declare that there are no conflicts of interest
concerning the materials or methods used in this study or
the findings reported in this paper.
AUTHORS’ CONTRIBUTION:
AFR, MUE, CKY: Contributed to the conception and design of
the study.
AFR, EV, FA, MUE, SOA, CKY: Contributed to patient inclusion
and follow-up.

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1
Department of Pathology, Umraniye Training
and Research Hospital, University of Health
Sciences, Istanbul, Turkey
2
Department of Neurosurgery, Health
Sciences University Umraniye Training and
Research Hospital, Istanbul, Turkey
3
Department of Radiation Oncology, Health
Sciences University Umraniye Training and
Research Hospital, Istanbul, Turkey
4
Department of Radiology, Health Sciences
University Umraniye Training and Research
Hospital, Istanbul, Turkey
5
Department of Radiology, Health Sciences
University Umraniye Training, and Research
Hospital, Istanbul, Turkey
Correspondence
Ali Koyuncuer, Department of Pathology,
Health Sciences University Umraniye Training
and Research Hospital, Istanbul, Turkey.
Email: alikoyuncuer@hotmail.com and
alikoyuncuer@gmail.com

Abstract

Metastases from ovarian cancer to the central nervous system (CNS) are rare, in par-
ticular, isolated leptomeningeal metastases (LM) are extremely rare. The gold stan-
dard in the diagnosis of leptomeningeal carcinomatosis (LC) is the detection of

malignant cells in cerebrospinal fluid (CSF) cytology. A 58-year-old woman diagnosed
with ovarian cancer 2 years ago underwent lumbar puncture and CSF cytology in
recent months due to new weakness, loss of strength in the lower extremities, and
speech disorders. Magnetic resonance imaging CNS was simultaneously visualized
and linear leptomeningeal enhancement was demonstrated. CSF cytology showed

tumor cells as isolated cells or small clusters of tumor cells with large, partially vacuo-
lated, and abundant cytoplasm, mostly with centrally located nuclei. Given her history

of high-grade clear cell ovarian cancer,CSF cytology was positive for malignant cells and

a diagnosis of leptomeningeal carcinomatosis was made by the neuro-oncology multidis-
ciplinary tumor board. Since LM also implies a systemic disease, the prognosis is very

poor, CSF cytology will play an important role in rapid diagnosis and will be useful both
in the right choice of treatment and in the early initiation of palliative care.
KEYWORDS
carcinoma, cytology, leptomeningeal carcinomatosis, metastasis, ovarian cancer

1 | INTRODUCTION
Metastases to the central nervous system are usually caused by lung
cancer, breast cancer, and malignant melanomas.1 Brain metastases from
ovarian cancers are very rare, accounting for about 1%–2% of all brain
metastases.1 In the literature, brain metastases have been reported in
521 patients in 38 clinical studies including ovarian carcinomas with brain
metastases, and 413 cases (1.19%) in 29 clinical series including 34.728
cases of ovarian carcinoma.2 Compared to epithelial carcinomas of the
ovary, ovarian clear cell carcinoma (OCCC) has a poorer prognosis and
the number of OCCC with brain metastasis is very few in the literature,
with 13 cases so far, with our case as the 14th case.3–5 Carcinomatous
meningitis (CM) or leptomeningeal carcinomatosis (LC) occurs when

tumor cells spread away from the primary tumor sites into the subarach-
noid, pia mater and cerebrospinal (CSF) fluid of the brain and spinal

cord.6 CM was first described by Beerman in 1912 for the metastasis of
cancer cells to the meninges without the presence of cancer cells in the
parenchyma of the central nervous system.7,8 The reported cases of

ovarian cancer with leptomeningeal metastasis without brain paren-
chyma in isolation are very limited.9

2 | CASE REPORT
A 58-year-old woman was operated on for a left ovarian mass about
twoyears ago. On histopathologic examination, ovarian clear cell

Received: 14 March 2023 Revised: 5 April 2023 Accepted: 10 April 2023
DOI: 10.1002/dc.25145

Diagnostic Cytopathology. 2023;1–4. wileyonlinelibrary.com/journal/dc © 2023 Wiley Periodicals LLC. 1

carcinoma was diagnosed and chemotherapy (Topotekan 4 mg/4 mL

infusion 2 day, Filgrastim 30 MIU/0.5 mL infusion 9 week, Grani-
setron 2 mg tablets 6 months) were administered regularly for

7 months. However, a cytologic examination of cerebrospinal fluid
performed at an outside hospital where she had been admitted for
the last forty-five days due to increasing weakness and weakness in

the lower extremities was found to be non-diagnostic/inadequate and

no diagnosis was made. Magnetic resonance imaging (MRI) was per-
formed and brain parenchyma and meninges were evaluated. No

gross tumor was observed in the parenchyma, but the thickening of
the dura, which showed faint appearances without increased
perfusion (Figure 1A,B), was found to be significant in terms of

FIGURE 1 (A, B) Brain
magnetic resonance imaging

(MRI): T1-weighted contrast-
enhanced cranial MRI shows dural

thickening with diffuse
enhancement, and linear and
nodular leptomeningeal
enhancement (black arrow).

FIGURE 2 (A–D) Leptomeningeal carcinomatosis (LC): Cerebrospinal fluid (CSF) cytology showed tumor cells as isolated cells or small clusters
(2A, D, Papanicolaou stain 400) of tumor cells with large, partially vacuolated (2B, black arrow Papanicolaou stain 400) and abundant
cytoplasm with centrally located nuclei. Numerous imbibed polys within the cytoplasm (2C, black arrow, Papanicolaou stain 400), and tumor
diathesis were observed among tumor cell groups (red arrow).
2 KOYUNCUER ET AL.
10970339, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/dc.25145 by Turkey Cochrane Evidence Aid, Wiley Online Library on [29/05/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

leptomeningeal involvement, and CSF cytology was recommended for
early examination. Two preparations prepared with an automatic
Thin-Prep device from the material sent in 20 milliliters of Thin-Prep
solution were stained with a special Thin-PrepPAP staining set.
Scanned in “integrated imager” system. CSF cytology showed clusters
and dispersed single tumor cells. Some of these cells had abundant
clear pale vacuolated cytoplasm and centrally located moderately

pleomorphic nuclei. Nuclei showed binucleation and prominent nucle-
olus. Numerous imbibed polys within the cytoplasm and tumor diathe-
sis were observed among tumor cell groups. It was considered

positive for malignant cells (Figure 2A–D). In our case, adenocarci-
noma cells, reactive macrophages and infectious meningitis, intracra-
nial infarction, or hemorrhages were included in the differential

diagnosis of CSF cytology. Based on the clinical history, previous his-
tological diagnosis, and clinicopathological findings, the case was

accepted as leptomeningeal involvement of OCCC by the Neuro-
Oncology Multidisciplinary Tumor Board. Whole brain RT (WBRT)

with 30 Gy in 10 fractions was planned.

3 | DISCUSSION
The incidence of ovarian cancer ranks second among all gynecologic
malignancies and first in mortality.10 Mortality is high because the
overwhelming majority of ovarian cancers present with extensive

metastases to the abdominal cavity. Cancer can spread by direct inva-
sion of nearby organs and structures, or the shed cancer cells can

spread through the peritoneum with peritoneal fluid and ascitic fluid.
Unlike other cancers, metastasis via vascular channels is rare, but
spread to pelvic and para-aortic lymph nodes is common.11 The most
common distant metastases from epithelial ovarian cancer are pleural,
followed in descending order by liver, lung, pelvic/para-aortic lymph

node chains, skin, pericardial, brain, and bone metastases.2 Leptome-
ningeal metastases from gynecological cancers are extremely rare.

While disease-free life expectancy has been prolonged due to the
advances in chemotherapy, metastasis of these tumors to the central
nervous system has also increased. Yano et al. reported that of

24 gynecologic cancers with CNS metastases, five patients hadlepto-
meningeal metastasis (LM).12 The incidence of LC in ovarian cancer is

exceedingly rare, usually occurring in cases of disseminated disease or
advanced stages.2 Our patient was admitted to the intensive care unit
due to a deteriorating clinical condition and liver and lung metastases
were identified. In their retrospective study, Pectasides et al. found
CNS metastases in only 17 (1.17%) of 1450 patients with primary
malignant ovarian tumors and could not detect LC in any of these
patients.13,14 In a study by Cormio et al. leptomeningeal metastases
were found in only one case out of 23 patients with epithelial ovarian
carcinoma with CNS metastases. Only one case had histology of clear

cell carcinoma. Unlike in this study, the histology of the surgical re-
section specimen was confirmed in only 5 patients and a CSF diagno-
sis was made in only one patient. A clinical-radiological metastasis

was diagnosed in 17 patients.15 Sanderson et al. reported cerebral
metastases in 13 (1.1%) of 1222 cases of ovarian cancer based on

computed tomography (CT) and magnetic resonance imaging (MRI)
findings. The histopathologic diagnosis of two of these cases was

clear cell carcinoma, the remainder being serous carcinoma, endome-
trioid, and small cell carcinoma.16 Leptomeningial carcinomatosis can

cause symptoms by obstructing CSF flow, infiltrating nerves in the

subarachnoid space, occluding pial blood vessels, or invading or irritat-
ing the brain parenchyma. Clinical manifestations include increased

intracranial pressure, neurological deficits, radiculopathies, stroke-like

symptoms, encephalopathy, and epileptic seizures.17 Because follow-
up of epithelial ovarian cancer focuses primarily on intra-abdominal

recurrences, CT scans of the brain parenchyma and meninges are gen-
erally not recommended. However, a CT or MRI scan for LM is war-
ranted if neurological symptoms develop.14 Given the multifocal

spread to LC, leptomeninges, and CSF, the sensitivity of the MRI
imaging technique is high.18 Although CSF cytology is tumor negative

in some patients with LC (about 10%), it is still one of the most com-
mon diagnostic methods.17,19 Hyun et al. reported that 22% of

519 patients with LM were diagnosed by CSF cytology, 35% by MRI,
and 42% by both MRI and CSF cytology. CSF cytology is a very useful
diagnostic tool to establish the diagnosis of LM, particularly when
MRI is negative or has pitfalls and when LC is suspected, even when
the CSF cell count is biochemically normal.20 Both diagnostic methods
were synchronously positive in our case. Serum CA-125 levels have
been observed to increase (>35 U/mL) in a significant proportion, but
not all, of ovarian cancer with brain metastases.2,21,22 In our patient,
the last test showed a serum value of 492.There are currently several
treatment modalities for LM. Intrathecal chemotherapy, whole-brain
radiation therapy (WBRT), radiation therapy for spinal cord disease
(RT), and CNS-sensitive chemotherapy regimens can be selected.23
LM represents an advanced disease with a short survival time and an
aggressive clinical presentation. The median progression-free survival
after diagnosis of LM is 3.4 months and the median overall survival is
2.8 months.24

4 | CONCLUSION
Metastasis of ovarian cell carcinoma OCCC to the brain parenchyma
and leptomeninges is extremely rare. Since the prognosis of brain

metastases from ovarian cancer is very poor, CSF cytology examina-
tion is very important for rapid diagnosis and treatment and can have

a positive effect on the prognosis.
AUTHOR CONTRIBUTIONS

Ali Koyuncuer: writing and revision of manuscript, cytological evalua-
tion; Eyup Varol: detailed clinical history; Bengul Seraslan: conception

and design; Yas ̧ar Bükte: helped to collect clinical and follow-up data
of the case.
FUNDING INFORMATION
This research did not receive any specific grant from funding agencies
in the public, commercial, or not-for-profit sectors (no specific funding
was disclosed).

KOYUNCUER ET AL. 3
10970339, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/dc.25145 by Turkey Cochrane Evidence Aid, Wiley Online Library on [29/05/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

CONFLICT OF INTEREST STATEMENT
It is declared that all authors have no conflicts of interest to disclose.
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the
corresponding author upon reasonable request.
ORCID
Ali Koyuncuer https://orcid.org/0000-0002-0994-1275
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How to cite this article: Koyuncuer A, Varol E, Serarslan
Yagcio

glu B, Bükte Y, Sakcı Z. Cerebrospinal fluid-
dissemination of a ovarian clear cell carcinoma: A

leptomeningial carcinomatosis with diagnostic challenges.
Diagnostic Cytopathology. 2023;1‐4. doi:10.1002/dc.25145