CSF Rhinorrhea: a Rare Clinical Presentation of Choroid Plexus Papilloma

Case Report CSF Rhinorrhea: A Rare Clinical Presentation of Choroid Plexus Papilloma

Layth Mula-Hussain 1,* , Julia Malone 1, Marlise P. dos Santos 2, John Sinclair 3 and Shawn Malone 1

1 Radiation Oncology Division, The Ottawa Hospital—University of Ottawa, Ottawa, ON K1H 8L6, Canada; [email protected] (J.M.); [email protected] (S.M.) 2 Department of Medical Imaging, The Ottawa Hospital—University of Ottawa, and Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; [email protected] 3 Neuro-Surgery Division, The Ottawa Hospital—University of Ottawa, Ottawa, ON K1Y 4E9, Canada; [email protected] * Correspondence: [email protected]

Received: 6 November 2020; Accepted: 27 January 2021; Published: 31 January 2021

Abstract: Choroid plexus papilloma (CPP) is a rare brain tumour occurring mostly in infants and children. Most CPPs are intraventricular and present with symptoms and signs of increased intracranial pressure (ICP). This case report describes a middle-aged female who presented with spontaneous cerebrospinal ﬂuid (CSF) rhinorrhea from a tumour located in the cerebellopontine angle (CPA). She underwent craniotomy with subtotal tumour resection and remained progression and rhinorrhea-free for several years. Upon clinical progression, the patient was treated with Cyberknife stereotactic radiosurgery. The patient clinically improved and demonstrated a favourable radiologic response to radiosurgery.

Keywords: choroid plexus tumour; cerebellopontine angle; CSF rhinorrhea; stereotactic radiosurgery

1. Introduction Choroid plexus tumour (CPT) is a rare epithelial intracranial extra-axial brain tumour that usually grows inside ventricles and is connected to the choroid plexus or near the natural openings of the ventricles. The annual incidence is 0.3 cases per million [1], and they account for about 0.5% of all intracranial neoplasms. CPT can be classified as choroid plexus papilloma (CPP, WHO grade I) or choroid plexus carcinoma (CPC, WHO grade III), with a ratio of 5:1, respectively. Approximately 80% of CPCs occur in children [2]. The most common location of CPTs in adults is the fourth ventricle, followed by the cerebellopontine angle (CPA) [3,4]. Clinically, CPT tends to cause hydrocephalus, and patients present with symptoms of raised intracranial pressure. The treatment of choice is gross total resection (GTR) [5], when clinically feasible. Neurosurgeons must assess the pros and cons of GTR versus the potential morbidity of complete excision. Historically, radiotherapy has been used in cases where surgery is not possible or ended up with subtotal resection, after local recurrence, or in high-grade CPC [6]. Adjuvant chemotherapy has been used in CPC; however, its benefit is not clear. The five-year survival rates are reported to be as high as 100% in CPP following complete resection, with low local recurrence rates. CPC grows more rapidly and has a less favourable outcome, with a 5-year survival rate of 26–40% [2]. Improvements in surgical techniques and post-operative care have improved survival [7].

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2.2. CaseCase StudyStudy AA 43-year-old 43-year-old woman woman presented presented in in January January 20072007 withwith cerebrospinalcerebrospinal fluid fluid (CSF) (CSF) rhinorrhea rhinorrhea from from thethe left left nostrilnostril onon bendingbending forward, headache,headache, and later later on on with with ataxia. ataxia. There There was was no no prior prior history history of ofskull skull trauma trauma or orsurgery surgery and and no nosignificant significant past past medical medical hist history.ory. After After the theconfirmation confirmation of a ofCSF a CSF leak leakwith with a β-2 a tβransferrin-2 transferrin test, a test, CT scan a CT of scan the ofparanasal the paranasal sinuses sinuses on December on December 2007 showed 2007 showed the enlarge- the enlargementment of the right of the foramina right foramina rotundum rotundum and ovale and ( ovaleFigure (Figure 1 A, B1).A,B).

A B

C D

FigureFigure 1. 1.Coronal Coronal plane, plane unenhanced, unenhanced CT CT scan scan of theof the paranasal paranasal sinuses sinuses obtained obtained with with bone bone window window and inand prone in prone position. position. (A–D ,( Dec.A – D 2007)., Dec. ( A2007).): prominent (A): prominent right (arrow) right and(arrow normal) and left normal (triangle) left foramen(triangle) rotundum;foramen rotundum; (B): prominent (B): prominent right (arrow) right and (arrow normal) and left normal foramen left ovale foramen (triangle); ovale ((Ctriangle): prominent); (C): prom- right sphenoidalinent right arachnoidsphenoidal pits arachnoid (dashed pits circle); (dashed (D): circle focal); defect (D): focal of the defect left planum of the left sphenoidale planum sphenoidale (chevron) and(chevron adjacent) and opacification adjacent opacification of the left ethmoid of the left sinus ethmoid and upper sinus nasal and cavityupper (CSFnasal leak,cavity triangles). (CSF leak, triangles). An MRI of the brain on May 2008 (Figure2A,B) revealed an enhancing, T1-isointense and T2-hyperintenseAn MRI of extra-axialthe brain o CPAn May mass 2008 lesion (Figure measuring 2 A, B) r 24evealed24 an30 enhancing, mm, associated T1-isointense with prominent and T2- × × flow-voidshyperintense and extra causing-axial mass-e CPAff ectmass on thelesion lower measuring pons and 24 the × medulla24 × 30 oblongata.mm, associated The mass with encroached prominent onflow the-voids cisternal and segments causing of mass the-effect right 7th on and the 8th lower canal pons nerves and complex. the medulla Inferiorly, oblongata. the mass The extended mass en- upcroached to the level on the of cisternal the foramen segments magnum. of the Our right retroactive 7th and 8th reassessment canal nerves of complex. the CT scan Inferiorly, of the paranasal the mass sinusesextended identified up to the multiple level of unilaterally the foramen prominent magnum. aberrant Our retroactive arachnoid reassessment granulations of (arachnoid the CT scan pits) of the of theparanasal right sphenoid sinuses identified bone and multiple the focal unilaterally disruption prominent of the left planumaberrant sphenoidale, arachnoid granulations contiguous (arach- to an abnormalnoid pits) opacification of the right sphenoid of the medial bone left and ethmoid the focal sinus disruption and upper of the nasal left cavity,planum in sphenoidale keeping the, sourcecontig- ofuous a CSF to an leak abnormal with high opacification intracranial of pressure the medial features left ethmoid (Figure sinus1C,D). and The upper retrospective nasal cavity, review in keeping of the abovethe source mentioned of a CSF MRI leak showed with ahigh very intracranial mild compensated pressure communicating features (Figure hydrocephalus 1 C, D). The retrospective (Figure2B). reviewIn September of the above 2008, mentioned the patient MRI underwent showed a very a right mild posterior compensated fossa craniotomy communicating with hydrocepha- facial nerve monitoring.lus (Figure 2 AB). frozen section of the tumour revealed a CPP. The tumour was extremely vascular, soft, friable,In September and adherent 2008, the to somepatient cranial underwent nerves. a Aright subtotal posterior excision fossa of craniotomy the tumour with was fac performedial nerve inmonitoring. an attempt A tofrozen preserve section cranial of the nerve tumour function. revealed Final a CPP. pathology The tumour revealed was extremely a WHO vascular, grade 1 CPP. soft, Histologically,friable, and adherent the tumour to some tissue cranial had nerves. a papillary A subtotal structure excision with aof fibrovascular the tumour was backbone performed and in was an coveredattempt by to cuboidalpreserve tocranial low columnar nerve function. cells. Postoperatively, Final pathology her revealed headache a WHO and CSF grade rhinorrhea 1 CPP. Histolog- stopped, butically, she the developed tumournew tissue vocal had cord a papillary palsy and structure partial with right a hearing fibrovascular loss and backbone her ataxia and continued. was covered MRI atby eightcuboidal weeks to postoperativelylow columnar cells. revealed Postoperatively, encephalomalacia her headache and an 11 and9 CSF mm rhinorrhea residual enhancing stopped, tumourbut she × developed new vocal cord palsy and partial right hearing loss and her ataxia continued. MRI at eight weeks postoperatively revealed encephalomalacia and an 11 × 9 mm residual enhancing tumour in the right internal auditory canal extending into the right CPA without mass effect and resolution of

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Curr. Oncol. 2021, 28, 3 in the right internal auditory canal extending into the right CPA without mass eﬀect and resolution of the hydrocephalus (Figure 22C,D). C, D). She She was was kept kept on on annual annual clinical clinical and and radiologic radiologic follow-up follow-up forfor overover four years, till December 2012, where her annual follow up was discontinued as she was feeling better with stable radiological residual disease.disease.

Figure 2. PrePre-operative-operative ( ((AA, axial) axial,, and and B, ( Bcoronal)) coronal) and and 2 months 2 months post post-operative-operative (C, axial ((C) axial,, and D and, coro- (D) coronal)nal) postpost-gadoliniumgadolinium T1-W T1-W MRI MRIsequences. sequences. The CPA The CPAtumour tumour measured measured 24 × 24 24 × 3024 mm30 and mm 11 and × 9 × × 11mm, 9respectively. mm, respectively. × Several years later, in mid-2015,mid-2015, she presented with headaches, worsening ataxia ataxia,, and new new-onset-onset facial palsy. Her Her physical physical exam exam revealed revealed asymmetric asymmetric pupils pupils (right (right 5 mm 5 mm and and left left 3 mm), 3 mm), reactive reactive to lightto light with with a horizontal a horizontal beat beat (gaze (gaze-evoked),-evoked), nystagmus nystagmus,, and anddiplopia diplopia on lateral on lateral gaze. gaze.She had She right had- sideright-side hearing hearing loss and loss andan absent an absent gag gag reflex. reflex. A n Aew new MRI MRI revealed revealed the the residual residual tumour's tumour’s progression progression (14 14 17 mm) with central cystic degeneration/necrosis. The tumour extended further into the (14 × 14 × 17 mm) with central cystic degeneration/necrosis. The tumour extended further into the right internalinternal auditoryauditory canal,canal, causingcausing a a mild mild mass mass e ffeffectect on on the the brainstem. brainstem. The The patient patient was was reluctant reluctant to toconsider consider further further surgical surgical intervention. intervention. Three Three subsequent subsequent MRIs MRIs performed performed in 2015in 2015 demonstrated demonstrated the thecontinued continued slow slow growth growth of the of residualthe residual tumour tumour (Figure (Figure3). 3). The case was discussed at neuro-oncology rounds. The multidisciplinary consensus was to offer the patient a course of stereotactic radiosurgery (SRS) using the frameless CyberKnife® (CK) as a non-invasive method of tumour control while allowing function preservation. The patient underwent CT/MR simulation and received treatment in January 2016. The gross tumour volume (GTV) was 3.5 cc and was treated to 3000 cGy in 5 fractions (GTV covered by the 99.8% isodose line), with no treatment margin. Treatment was delivered in five daily fractions over one week. A planning target volume was strictly used for treatment planning purposes. The brainstem doses were as follows: Dmax was 3045 cGy, D0.03cc was 2942 cGy, and the D1cc was 2157 cGy (Figure4).

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the hydrocephalus (Figure 2 C, D). She was kept on annual clinical and radiologic follow-up for over four years, till December 2012, where her annual follow up was discontinued as she was feeling better with stable radiological residual disease.

Figure 2. Pre-operative (A, axial, and B, coronal) and 2 months post-operative (C, axial, and D, coronal) post-gadolinium T1-W MRI sequences. The CPA tumour measured 24 × 24 × 30 mm and 11 × 9 mm, respectively.

Several years later, in mid-2015, she presented with headaches, worsening ataxia, and new-onset facial palsy. Her physical exam revealed asymmetric pupils (right 5 mm and left 3 mm), reactive to light with a horizontal beat (gaze-evoked), nystagmus, and diplopia on lateral gaze. She had right- side hearing loss and an absent gag reflex. A new MRI revealed the residual tumour's progression (14 × 14 × 17 mm) with central cystic degeneration/necrosis. The tumour extended further into the right internal auditory canal, causing a mild mass effect on the brainstem. The patient was reluctant

Curr.to con Oncol.sider2021 further, 28 surgical intervention. Three subsequent MRIs performed in 2015 demonstrated753 the continued slow growth of the residual tumour (Figure 3).

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Figure 3. T1-W post-gadolinium MRI at 7 years post-op on axial (A) and coronal (B) planes. The CPA tumour measured 16 × 15 × 17 mm.

The case was discussed at neuro-oncology rounds. The multidisciplinary consensus was to offer the patient a course of stereotactic radiosurgery (SRS) using the frameless CyberKnife (CK) as a non- invasive method of tumour control while allowing function preservation. The patient underwent CT/MR simulation and received treatment in January 2016. The gross tumour volume (GTV) was 3.5 cc and was treated to 3000 cGy in 5 fractions (GTV covered by the 99.8% isodose line), with no treatment margin. Treatment was delivered in five daily fractions over one week. A planning target. vol- umeFigure was strictly 3. T1-W used post-gadolinium for treatment MRI planning at 7 years purposes. post-op on The axial brainstem (A) and coronal doses ( Bwere) planes. as follows: The CPA Dmax was tumour3045 cGy, measured D0.03cc 16 was15 294217 mm.cGy, and the D1cc was 2,157 cGy (Figure 4). × ×

FigureFigure 4.4. CKCK SRSSRS treatmenttreatment planplan (January(January 2016)2016) withwith thethe axialaxial andand coronalcoronal sections,sections, thethe dose–volumedose–volume histogramhistogram (DVH)(DVH) and and the the dose dose statistics statistics table table of of the the pertinent pertinent volumes. volumes.

TheThe patientpatient toleratedtolerated SRSSRS well,well, withwith nono acuteacute oror latelate toxicity.toxicity. OverOver thethe nextnext ﬁvefive years,years, sheshe hadhad gradualgradual clinicalclinical improvement improvement in in her her gait, gait, swallowing swallowing and and facial facial palsy. palsy. Additionally, Additionally she, hadshe completehad com- resolutionplete resolution of her headachesof her headaches and improvement and improvement in her voice in her function. voice function. Serial MRIs Serial revealed MRIs revealed her tumour her regressiontumour regression with the reliefwith the of massrelief eofﬀect mass on theeffect brainstem on the brainstem (Figure5). (Figure There were5). There no T2 were/Flair no changes T2/Flair (acutechanges or late(acute edema) or late in edema) the brainstem in the brainstem post-treatment. post-treatment.

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Figure 5. PostPost-gadolinium-gadolinium T1 T1-W-W MRI at four years post CK, on axial (A)) andand coronalcoronal ((BB)) planes.planes. TheThe CPA tumour shrank to 12 12 mm. CPA tumour shrank to 12×12 mm. 3. Discussion 3. Discussion This is a rare case of CPA choroid plexus papilloma presenting with CSF rhinorrhea. Initial imaging This is a rare case of CPA choroid plexus papilloma presenting with CSF rhinorrhea. Initial im- revealed a non-specific right CPA tumour and features for long-standing intracranial hypertension. aging revealed a non-specific right CPA tumour and features for long-standing intracranial hyper- The patient underwent craniotomy and the subtotal excision of her tumour. Pathology revealed a WHO tension. The patient underwent craniotomy and the subtotal excision of her tumour. Pathology re- grade I CPP. Seven years after initial surgery, there was a radiologic progression of her tumour, and she vealed a WHO grade I CPP. Seven years after initial surgery, there was a radiologic progression of developed headaches, worsening ataxia, and new-onset facial palsy. Following a multidisciplinary her tumour, and she developed headaches, worsening ataxia, and new-onset facial palsy. Following tumour board, she was treated with salvage CK-based SRS (3000 cGy in 5 fractions). Over the next a multidisciplinary tumour board, she was treated with salvage CK-based SRS (3000 cGy in 5 frac- five years, the patient had gradual subjective clinical improvement. Serial MRIs revealed objective tions). Over the next five years, the patient had gradual subjective clinical improvement. Serial MRIs radiological response to SRS. This case highlights two interesting clinical findings: CSF rhinorrhea is a revealed objective radiological response to SRS. This case highlights two interesting clinical findings: rare presentation from CPP, and CK SRS resulted in the durable local control of this rare tumour. CSF rhinorrhea is a rare presentation from CPP, and CK SRS resulted in the durable local control of CPT usually presents with symptoms of raised intracranial pressure (ICP) due to obstructive this rare tumour. hydrocephalus or from CSF overproduction [7]. Hosmann et al. reported that adult CPT present CPT usually presents with symptoms of raised intracranial pressure (ICP) due to obstructive with the following symptoms: headache (68%), gait disturbance (53%), vertigo (37%), diplopia (32%), hydrocephalus or from CSF overproduction [7]. Hosmann et al. reported that adult CPT present with incidental finding (21%), increased ICP (16%), paresis (11%), and behavioural changes (5%) [5]. In our the following symptoms: headache (68%), gait disturbance (53%), vertigo (37%), diplopia (32%), inci- case report, the patient presented with CSF rhinorrhea due to CPP in the CPA region, which to our dental finding (21%), increased ICP (16%), paresis (11%), and behavioural changes (5%) [5]. In our knowledge, is the first-ever reported presentation in the literature. case report, the patient presented with CSF rhinorrhea due to CPP in the CPA region, which to our CSF leak is caused when there are combined bony and dural defects and a sufficient pressure knowledge, is the first-ever reported presentation in the literature. gradient that allows CSF to drain externally [8]. This can occur at multiple sites, and the predisposing CSF leak is caused when there are combined bony and dural defects and a sufficient pressure causes include trauma, prior skull base or sinus surgery, chronic increased ICP, and arachnoid gradient that allows CSF to drain externally [8]. This can occur at multiple sites, and the predisposing granulations [9]. CSF leak has been rarely reported in other CPA tumours, such as schwannomas [10]. causes include trauma, prior skull base or sinus surgery, chronic increased ICP, and arachnoid gran- Fluid should be collected and sent for β-2 Transferrin, a protein found almost exclusively in CSF, ulations [9]. CSF leak has been rarely reported in other CPA tumours, such as schwannomas [10]. to confirm the presence of a CSF leak. A thin-section multidetector CT scan is used to detect the Fluid should be collected and sent for β-2 Transferrin, a protein found almost exclusively in CSF, to bony breach’s site and the source of the leak. CT or MR cisternography can also be used to identify confirm the presence of a CSF leak. A thin-section multidetector CT scan is used to detect the bony the location of a fluid leak. The most common site for spontaneous CSF leak is the cribriform plate, breach’s site and the source of the leak. CT or MR cisternography can also be used to identify the followed by the ethmoid roof/planum sphenoidale. Primary CSF leaks can also involve the sphenoid location of a fluid leak. The most common site for spontaneous CSF leak is the cribriform plate, fol- sinus, peri sella, and pterygoid recesses [11]. In this case report, the CSF leak site was at the ethmoid lowed by the ethmoid roof/planum sphenoidale. Primary CSF leaks can also involve the sphenoid roof/planum sphenoidale. Due to the constellation of osseous abnormalities found in the CT scan sinus, peri sella, and pterygoid recesses [11]. In this case report, the CSF leak site was at the ethmoid and absence of a history of trauma, we think that the CPP led to over-production of CSF, similar to roof/planum sphenoidale. Due to the constellation of osseous abnormalities found in the CT scan and what Eisenberg et al. reported [12], which caused chronic increased ICP that overtime, remodeled the absence of a history of trauma, we think that the CPP led to over-production of CSF, similar to what skull base and caused erosions that led to the CSF leak through the ethmoid roof with CSF rhinorrhea. Eisenberg et al. reported [12], which caused chronic increased ICP that overtime, remodeled the skull We think that the unilateral aberrant arachnoid pits/granulations [13], foramen ovale and rotundum base and caused erosions that led to the CSF leak through the ethmoid roof with CSF rhinorrhea. We result from the chronically increased ICP due to the long-standing CSF overproduction by the CPP. think that the unilateral aberrant arachnoid pits/granulations [13], foramen ovale and rotundum result from the chronically increased ICP due to the long-standing CSF overproduction by the CPP.

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Gross total or safe-maximal resection is the gold standard of care in the treatment of this benign tumour. At operation, the tumour was compressing the brainstem and cerebellum and extended into the internal porus acusticus. The tumour was adherent to several cranial nerves, including CN VII through CN X. As a result, the patient developed some cranial nerve injuries with clinical deficits, including hearing loss (CN VIII), swallowing dysfunction (CN VII, IX and X), impaired voice function (CNX), impaired gag reflex (CN IX and X) and facial palsy (CN VII). Her voice and swallowing function gradually improved, indicating that these deficits were not permanent. Wolff et al. reported on 566 patients with CPP [3]. Following complete resection, the 10-year survival rate was 85%, compared to 56% with subtotal excision and a one-year survival rate of 50% in patients after biopsy alone (P = 0.002). In that study, CPT in the CPA region was associated with older age, benign histology, and female gender [3]. Our patient achieved so far more than twelve years from her initial diagnosis (seven years from her subtotal open surgical resection, with an additional five years from her salvage radiosurgery, to date). The utility of radiation with conventional techniques and dose fractionation is not well documented in the literature [4,14]. SRS has been used to treat CPP for patients with inoperable tumours or following local recurrence. Duke reported the effective use of SRS in pineal CPP with a frame-based Gamma-Knife in 1997 [15]. Over the last two decades, SRS has been an effective strategy to manage resistant CCP, including tumours in the CPA [16]. The optimal SRS dose and fractionation remained to be defined as do rates of long-term tumour control [5]. In-Young Kim et al. reported tumour control in 8 of 11 tumours (73%) after one or more Gamma Knife SRS procedures. In the series, the longest follow-up post-SRS was 41 months [16]. In our case, durable tumour control was achieved over 60 months of follow-up, with no evidence of acute or late SRS toxicity. CK was a safe, well-tolerated, and effective option in recurrent CPP at CPA.

4. Conclusions CSF rhinorrhea is a rare presentation of CPP in the CPA. CPP is usually managed with a definitive maximal-safe surgical resection. Our patient developed clinical and radiologic progression following the subtotal excision of the tumour. Salvage CK resulted in a significant improvement in the patient’s neurologic deficits and durable local tumour control.

Author Contributions: The first author collected the scientific material, wrote the first draft and finalized all the edits by the co-authors and completed the submission of the manuscript. The co-authors shared in writing, editing and approving the first and final drafts of the manuscript. All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding.

Institutional Review Board Statement: Not required.

Informed Consent Statement: The patient authorized the authors to publish this rare case report.

Data Availability Statement: Not available. Acknowledgments: The authors acknowledge Janice Doody, for her preparation of the dosimetry figure and its statistics. Conflicts of Interest: The authors declare no conflict of interest.

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