Key-words:
Distant ovarian metastasis - high-grade ovarian carcinoma - intramedullary spinal
cord metastasis - intramedullary spinal tumors
Introduction
Ovarian carcinoma is the 7th most commonly diagnosed and 8th most common cancer associated
with cancer-related death in women.[[1]] Metastatic ovarian carcinoma is associated with poor survival and usually seen
as a disseminated abdominal disease, but very rarely distant hematogenous metastasis
to location like spinal cord is also reported. Metastasis forms a part of spectrum
of rare intramedullary spinal cord tumors after glial tumors and hemangioblastoma.
Lung and breast cancers are the most common primary disease to metastasize to intramedullary
spinal cord, while reports describing solid tumors such as ovarian cancers with such
spread are sparse.[[2]]
We present our experience with one such patient of ovarian carcinoma with isolated
intramedullary metastasis in dorsal spine who received standard treatment and was
believed to be disease free on follow-up visits. To the best of author's knowledge,
this is the third in world literature report describing such disease in dorsal spine.
It also strengthens the idea of keeping metastases as a differential in ovarian cancer
patients who present to clinic with deficits localizing to intramedullary cord levels
so that early diagnosis and stellar care can be given which in turn can have a positive
effect on survival and quality of life of such patients.
Case Report
A 74-year-old female with CA-125 levels of 1991.89 units/ml underwent transabdominal
hysterectomy with bilateral salpingoophorectimy and bilateral pelvic lymph node dissection.
Histopathological examination (HPE) of excised specimen revealed ovarian adenocarcinoma,
and the patient received six cycles of adjuvant chemotherapy with paclitaxel and carboplatin.
On regular follow-up visits, there were no clinicoradiological signs of disease recurrence
and her CA-125 levels were dropped to 2.19 units/ml at 1- year follow-up. Approximately
18 months after the end of treatment patient was referred to neurosurgical outpatient
department with complaints of bilateral lower limb dysaesthetic pain, sensory loss
to pain, and temperature at lower abdomen and asymmetric paraparesis (left −4/5 and
right +4/5) with left extensor plantar response and a clinical localization to intramedullary
D10 spinal cord level was made. The patient was evaluated with magnetic resonance
imaging (MRI) scan of dorsolumbar spine which was suggestive of bulky cord with intramedullary
lesion at D6/D7 vertebral level which was isointense on T1-weighted image, hypointense
on T2-weighted image with hyperintense edema extending craniocaudally from D3 to D10
without any polar cyst or hemosiderin cap, on gadolinium injection the lesion was
avidly enhancing, and a differential diagnosis of metastasis was made based on her
past history [[Figure 1]]. The patient was further evaluated with positron emission tomography-computed tomography
(CT) scan which showed hypermetabolic lesion in spinal cord at D7 vertebral level
without any other fluorodeoxyglucose avid lesions in body and her CA-125 levels were
within normal limits. Based on above findings, expected survival of >6 months and
gradually worsening neurological status of patient, she was advised surgery. Patients
underwent D6–D8 laminectomy and excision of lesion; intraoperatively, a circumscribed
mass was seen with clear tumor-cord interface identified at most of the places and
a gross total resection was achieved with moderate ease. Postoperatively, the patient
was found to have worsening in her paraparesis (right 3/5 and left 1/5), for which
she was treated with oral steroids and physiotherapy with rehabilitation. Over the
course of 2 months, she gradually recovered to her preoperative neurological status
without any untoward new event. Excised tumor on HPE showed small clusters with cribriform
pattern and papillae formation, individual cells had scanty cytoplasm and hyperchromatic
nuclei. Mitotic figures were abundant, and on immunohistochemical (IHC) analysis,
specimens were estrogen receptor/progesterone receptor/PAX-8/WT-1 positive and thyroid
transcription factor/CDX-2negative [[Figure 2]]. Based on HPE and IHC findings, diagnosis of metastatic papillary adenocarcinoma
was made. The patient received adjuvant local radiotherapy to postoperative tumor
bed. Adjuvant chemotherapy was not given as there was no other intracranial or extracranial
lesion. On follow-up visits at postoperative 3 and 6 months, she regained near total
strength in her lower limbs and was able to carry out her activity of daily living
without any assistance. Postoperative 6 months and 1 year MRI [[Figure 3]] showed no recurrence or new disease in craniospinal axis, and the patient was lost
to follow-up after 1 year of disease-free interval.
Figure 1: Preoperative magnetic resonance imaging. (a) T2 fluid.attenuated inversion recovery
showing thickened spinal cord with intramedullary heterogeneous isointense lesion
at D7 with cord edema extending from D3 cranially to D10 caudally, (b) postgadolinium
scan showing a well circumscribed avidly enhancing intramedullary mass at D7
Figure 2: (a) Histopathological examination showing small clusters with cribriform pattern
and papillae formation, individual cells had scanty cytoplasm and hyperchromatic nuclei;
immunohistochemical analysis showing. (b) Estrogen receptor positive. (c) Progesterone
receptor positive. (d) PAX-8 positive. (e) WT-1 positive. (f) Thyroid transcription
factor 1 negative. (g) CDX-2 negative
Figure 3: (a) T1WI. (b)T2WI Postoperative MRI showing gross total resection of IMSCm
Discussion
Intramedullary spinal cord metastases (IMSCm) are rare tumors with the prevalence
of 2.1% of all cancers and 8.5% of cases of metastasis in large autopsy series.[[3]] Neoplasms of lung (40%–60%) followed by breast (14%) are the most common primaries
to metastasize to intramedullary spinal cord.[[2]] Primary ovarian neoplasm with intramedullary metastases is very rare with reported
prevalence of 2.1% of all IMSCm.[[4]] Patients most commonly present with dysaesthetic pain, sensory loss, motor weakness,
and autonomic dysfunction based on the level of cord involvement. Prognosis of such
patient as per literature is highly variable with survival of 10 months to 3 years
and most probably depends on the time of diagnosis from onset of symptom and treatment
received by patient.[[5]] Role of surgery is to achieve cytoreduction, to get an unambiguous diagnosis by
histology and to relieve neurodeficits in patients with expected gross total resection,
i.e., in patients where lesion is well circumscribed in preoperative scans. Another
viable option is oral steroids which may help reduce tumor-associated vasogenic edema
and thus relieve patient symptom or else upfront platinum-based chemotherapy and upfront
radiotherapy alone or in combination.
Till date, only seven cases have described isolated intramedullary metastasis (without
associated cranial and extramedullary metastasis) as a recurrence for primary ovarian
neoplasm, of which four were in cervical spine, one had conus medullaris and cauda
equina involvement, and only two cases were involving thoracic spine; in six cases,
the primary ovarian carcinoma was high grade (≥ Grade III, FIGO) and only one was
Grade IB. In all cases, primary was adequately treated with surgical resection and
systemic chemotherapy, and the patient was on regular follow-up and with normal CA-125
levels in six patients, thus considered disease free until they developed neurological
sequalae. The average time for diagnosis of spinal disease was 24 months after the
diagnosis of primary. Five patients underwent surgical resection for IMSCm with adjuvant
therapies and two patients were treated with upfront radiation. Two patients died
at 5 and 10 months follow-up from disseminated systemic metastasis and rest 5 continued
to be disease free [[Table 1]].[[6]],[[7]],[[8]],[[9]],[[10]],[[11]]
Table 1: Summary of isolated intramedullary metastasis from primary ovarian carcinoma published
in literature till date
Due to sparse literature and incidence of IMSCm from ovarian carcinomas, appropriate
diagnostic strategies and management protocols are less defined. Routine follow-up
of a treated ovarian carcinoma involves contrast CT scans of abdomen and chest as
viscera, omentum, and diaphragm are most likely to get solid tumor metastasis by transcoelomic
peritoneal spread along with serum CA-125 levels which can be misleading as demonstrated
by previously published literature. Mechanism of distant metastasis in ovarian carcinoma
is still unclear, and most probably the cancer cells from involved lymph nodes in
high stage disease reach internal jugular vein through lymphatic drainage and thus
metastasize to distant organs by hematological spread later in the course of disease.
Most significant predictors for distant metastasis include P53 null mutations and
high stage of primary.[[12]]
Based on our experience, we recommend clinicians to have a very low threshold for
diagnosing central nervous system metastasis in patients with high stage ovarian carcinoma
and to perform screening MRI of neuroaxis in follow-up visits even with normal CA-125
values. Regarding treatment, a combination of surgical resection with oral steroids
and adjuvant local radiotherapy alone or in combination should be tailored according
to case. Choice of surgical resection largely depends on status of primary disease,
expected survival, performance status, and most importantly consent of patient and
their relatives to accept risk associated with myelotomy and resection of lesion.
Conclusion
Isolated IMSCm is a very rare clinical entity, and due to sparse literature, it can
present as diagnostic and therapeutic dilemma for treating clinicians worldwide. Early
diagnosis and prompt treatment can give patients with end-stage disease an extended
disease-free survival. It is preferrable to keep all management options open for the
patient and a stellar treatment should be tailored on case-to-case basis after thorough
discussion with neuro-oncologist, medical oncologist, and radiation oncologist with
a common goal of improving the quality of life of the patient.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms.
In the form the patient(s) has/have given his/her/their consent for his/her/their
images and other clinical information to be reported in the journal. The patients
understand that their names and initials will not be published and due efforts will
be made to conceal their identity, but anonymity cannot be guaranteed.
