Pineal and leptomeningeal metastases from a parotid carcinoma ex pleomorphic adenoma: a case report

Abstract

Carcinoma ex pleomorphic adenoma (CEPA) is an uncommon complication of an untreated pleomorphic adenoma (PA), but one that has a life-threatening significance. This case report documents the clinical, radiological and histopathological features of an extremely rare case of biopsy-proven pineal metastasis, with cerebellopontine and leptomeningeal spread, from CEPA of the parotid gland in spite of the patient having undergone parotidectomy, ipsilateral neck dissection and adjuvant radiotherapy. In spite of the current surgical and oncological treatment of CEPA, the rates of recurrence and distant metastases are high, with a subsequently poor prognostic outcome in most patients. Distant spread is usually to the bones and the lungs; however, more unusual locations have been documented. Our finding of pineal metastasis from CEPA has not previously been reported in the literature. Although this is a rare complication of an unusual condition, the aggressive behaviour of these malignancies warrants close clinical follow-up, with a low threshold for re-imaging and investigation if indicated.

Full text

Received:
11 July 2015
Revised:
12 October 2015
Accepted:
10 November 2015
Cite this article as:
Francies O, Paraskevopoulos D, Narenthiran G, Piper K, Sibtain A, Offiah C, et al. Pineal and leptomeningeal metastases from a parotid
carcinoma ex pleomorphic adenoma. BJR Case Rep 2016; 2: 20150279.
CASE REPORT
Pineal and leptomeningeal metastases from a parotid
carcinoma ex pleomorphic adenoma
1
OLIVIA FRANCIES, BSc, MBChB,
2
DIMITRIOS PARASKEVOPOULOS, MD, MSc,
2
GANESALINGAM NARENTHIRAN, FRCS(SN),
3
KIM PIPER, PhD, FRCPath,
4
AMEN SIBTAIN, MD, FRCR,
1
CURTIS OFFIAH, FRCS, FRCR and
1
ANANT S KRISHNAN, PhD, FRCR
1
Imaging Department, Barts Health NHS Trust, London, UK
2
Department of Neurosurgery, Barts Health NHS Trust, London, UK
3
Department of Cellular Pathology, Barts Health NHS Trust, London, UK
4
Department of Radiation Oncology, Barts Health NHS Trust, London, UK
Address correspondence to: Dr Anant Krishnan
E-mail: Anant.Krishnan@bartshealth.nhs.uk
ABSTRACT
Carcinoma ex pleomorphic adenoma (CEPA) is an uncommon complication of an untreated pleomorphic adenoma (PA),
but one that has a life-threatening significance. This case report documents the clinical, radiological and histopathological
features of an extremely rare case of biopsy-proven pineal metastasis, with cerebellopontine and leptomeningeal spread,
from CEPA of the parotid gland in spite of the patient having undergone parotidectomy, ipsilateral neck dissection and
adjuvant radiotherapy. In spite of the current surgical and oncological treatment of CEPA, the rates of recurrence and
distant metastases are high, with a subsequently poor prognostic outcome in most patients. Distant spread is usually to
the bones and the lungs; however, more unusual locations have been documented. Our finding of pineal metastasis from
CEPA has not previously been reported in the literature. Although this is a rare complication of an unusual condition, the
aggressive behaviour of these malignancies warrants close clinical follow-up, with a low threshold for re-imaging and
investigation if indicated.
CLINICAL FINDINGS
We present the case of a 62-year-old female with a high-
grade parotid carcinoma ex pleomorphic adenoma (CEPA)
that was initially treated with left parotidectomy and ipsi-
lateral neck dissection. The patient originally presented
with a 1-year history of a left parotid region mass and co-
existing ipsilateral facial nerve palsy, with the diagnosis
confirmed using ultrasound, MRI (Figure 1a,b) and core
biopsy of the lesion (Figure 2a,c). At the time of surgery,
there was no evidence of direct extracapsular spread of
the tumour. However, multiple anterior cervical lymph
nodes were infiltrated and the tumour was staged at
pT4apN2bM0. Adjuvant radiotherapy was commenced
immediately after surgery.
The patient was well at initial follow-up, with no clinical or
radiological evidence of recurrence. However, approxi-
mately 6 months after completing radiotherapy, she started
experiencing tinnitus as well as feelings of “drunkenness”.
Fine needle aspiration cytology was performed on a suspi-
cious left supraclavicular fossa lymph node during an out-
patient visit to the head and neck one-stop clinic. This
demonstrated features consistent with a poorly differenti-
ated metastatic malignancy, likely adenocarcinoma. An
audiogram performed at the same time confirmed com-
plete hearing loss in the left ear.
A subsequent urgent MRI demonstrated an avidly enhanc-
ing, large pineal region tumour with resulting obstructive
hydrocephalus (Figure 3a). Additionally, abnormal lepto-
meningeal enhancement was shown extending from the
mass over the folia of the superior cerebellar parenchyma
(Figure 3b). A small, discrete, enhancing lesion was also
present in the left cerebellopontine angle (Figure 3c). The
MRI also showed disease progression within the left supra-
clavicular fossa, although there was no evidence of recur-
rence within the parotid bed. This was confirmed on
subsequent whole body 2-deoxy-2-[
18
F]-fluoro-D-glucose
(
18
F-FDG) positron emission tomography/CT (PET/CT)
imaging, which also revealed multiple bone metastases and
bilateral metabolically active hilar lymph nodes, also suspi-
cious for metastases (Figure 3d).
The patient was discussed at the head and neck oncology
and neuro-oncology multidisciplinary meetings. The most
likely differential diagnoses for the pineal mass at this stage
included metastases, a high-grade pineal parenchymal
tumour or a germ cell tumour. Metastases from a primary
tumour other than a parotid tumour was thought to be
BJR|case reports doi: 10.1259/bjrcr.20150279
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more likely, as the pattern of intracranial spread observed in this
case had not been previously reported in relation to a CEPA.
There was a further deterioration in the patient’s symptoms,
although she did not experience any nausea, vomiting or head-
aches. On examination, her Glasgow coma score was 15 and,
apart from the pre-existing left facial nerve palsy, she had no
motor deficit. The patient was admitted under the neurosurgeons
and underwent an endoscopic third ventriculostomy and biopsy
of the pineal region lesion with a free-hand technique and an Aes-
culap endoscopy kit (MINOPÒInVent, Aesculap, B. Braun
Medical Ltd., Sheffield, UK) via a right frontal pre-coronal burr
hole. A pale pink rounded mass was seen suspended in the poste-
rior part of the third ventricle, overhanging the cerebral aqueduct.
Tumour and cerebrospinal fluid samples were sent intraopera-
tively. There were no perioperative complications and the patient
was discharged home on the third postoperative day.
Histological analysis of the pineal tumour determined conclu-
sively that the lesion was not a primary brain malignancy or germ
cell tumour, but a metastatic carcinoma. The immunoprofile
combination of CK7-positive and CK20-negative was suggestive
of salivary gland tumour metastasis. The gross cystic disease fluid
protein-15 marker was also identified, and although it is usually
expressed in breast carcinomas, its appearance has also been
reported in salivary duct carcinomas.
1
In this case, when the his-
tology from the pineal gland was compared with the original his-
tology, the intracranial lesion was consistent with a metastatic
adenocarcinoma from the parotid gland (Figure 4a,b).
Although the patient was neurologically intact at her next
follow-up appointment, and the ventricular system had been
successfully decompressed, the contrast-enhanced MRI demon-
strated that the leptomeningeal enhancement had progressed
dramatically and now extended throughout the neuraxis
(Figure 5a,b). There was further rapid deterioration in the
patient’s condition and she subsequently died.
DISCUSSION
Pleomorphic adenoma (PA) is the most common non-malig-
nant tumour to affect the salivary glands, usually involving
the parotid glands and less commonly the submandibular and
other minor salivary glands, as well as the lacrimal glands.
2
Although benign, it has been reported that as many as 25% of
primary and recurrent PAs undergo carcinomatous transfor-
mation into CEPA if left untreated.
2,3
The carcinomatous
component is usually adenocarcinoma, not otherwise speci-
fied, or salivary duct carcinoma.
1
The other rarer malignant
subsets associated with PAs are carcinosarcoma, which com-
prises both the epithelial and mesenchymal components of
PA, and metastasizing PA (metastatic foci of benign PA).
2,4
Malignant degeneration should be suspected in lesions that
appear infiltrative with an irregular contour on imaging.
Ultrasound evaluation of the cervical lymph nodes is also
vital in identifying any evidence of local lymphatic
dissemination.
CEPAs comprise approximately 12% of all malignant salivary
gland neoplasms, usually occurring in the sixth to eighth deca-
des of life.
2–4
Although often asymptomatic, they most com-
monly present as a firm mass in the parotid region. The patients
may also present with facial nerve palsy owing to deep parotid
Figure 1. (a) Ultrasound image (longitudinal) demonstrating a
poorly defined, irregular, hypoechoic lesion that corresponds to
the primary parotid tumour, within the superficial parotid gland
extending towards the deeper lobe. (b) Coronal T
2
weighted
craniofacial MRI image demonstrating a low signal lesion within
the left parotid gland, adjacent to the mandible (black arrow),
which corresponds to the primary parotid tumour.
ba
Figure 2. (a) H and E-labelled section (10magnification) of the parotid tumour demonstrating tumour invasion of the normal
serous acini of the parotid gland. The tumour cells have eccentrically-placed nuclei consistent with plasmacytoid morphology seen
frequently in PAs. (b) H and E-labelled section (10magnification) of the parotid tumour demonstrates an area of myxoid stroma
(black arrow), which is further evidence that the tumour arose from a pre-existing PA. (c) H and E-labelled section (10magnifica-
tion) of the parotid tumour showing hyalinization (black arrow), which occurs more frequently in PAs that undergo malignant trans-
formation. Extensive perineural invasion (black arrowhead) is also shown, highlighting the aggressiveness of the tumour. (All
histological images were provided courtesy of Dr Reshma Agrawal, Specialist Registrar in Oral Pathology, Division of Cellular Pathol-
ogy at The Royal London Hospital, London, UK.) H and E, haematoxylin and eosin; PA, pleomorphic adenoma.
bca
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lobe invasion involving the facial nerve, a finding that should
raise the suspicion for malignant degeneration in patients with
PA. Transformation into CEPA has been linked to an increased
pre-operative duration of a PA.
3
Local and regional surgical resection followed by radiotherapy is
the most recognized appropriate treatment in cases of high-
grade CEPA, although there are no standardized treatment
protocols.
2,3,5,6
MRI is the imaging modality of choice for post-
treatment follow-up of salivary gland neoplasms, with PET/CT
being invaluable for the assessment of suspected recurrence and
disseminated disease.
7
CEPAs are aggressive malignancies with high rates of recurrence
and metastases. Owing to the limited number of cases and the
variability in histological and radiological staging, survival rates
in these patients vary but are regularly reported as less than
1 year.
3,4
Zhao and colleagues
5
demonstrated an overall 5-year
survival of approximately 50% in a study of 51 patients with
CEPA, who were treated with curative intent.
Regional and distant metastases from CEPA appear to occur
with an equivalent frequency.
6
The histological grade of the pri-
mary tumour, local invasiveness and cervical lymph node
involvement are all important prognostic factors, the latter is rec-
ognized as the most reliable feature in predicting recurrence or
metastasis.
5
In this case, although there was no extracapsular
extension of the lesion, the tumour was high-grade with multiple
cervical lymph nodes also involved. Distant metastases are usu-
ally to the lungs and bones, with renal, hepatic and splenic
metastases also rarely reported.
4–6
Intracranial or spinal
Figure 3. (a) Axial gadolinium-enhanced T
1
weighted MRI demonstrating the large pineal region tumour obstructing the cerebral
aqueduct and giving rise to acute hydrocephalus. (b) Sagittal gadolinium-enhanced T
1
weighted MRI demonstrating the pineal
region tumour as well as contrast enhancement along the folia of the superior cerebellar parenchyma (black arrow) in keeping
with leptomeningeal spread of the tumour. (c) Axial gadolinium-enhanced T
1
weighted MRI of the posterior fossa demonstrating
the left cerebellopontine angle deposit (black arrow) that extends into the left internal auditory meatus. (d) Whole body
18
F-FDG positron emission tomography scan (posterior view) demonstrating the FDG-avid left supraclavicular fossa lymph
nodes, as well as metabolically active bilateral hilar lymph nodes and widespread metastatic bony infiltration. FDG, 2-deoxy-2-
[
18
F]-fluoro-D-glucose.
a b cd
Figure 4. (a) H and E-labelled section (20magnification) of
the primary parotid tumour demonstrating cells with
eccentrically placed nuclei consistent with plasmacytoid mor-
phology (black arrows). (b) Magnified H and E-labelled section
(10magnification) from the pineal tumour biopsy demon-
strating cells with a plasmacytoid morphology (black
arrows) that are analogous to those demonstrated within the
parotid gland tumour. H and E, haematoxylin and eosin.
ab
Figure 5. (a) Coronal gadolinium-enhanced T
1
weighted MRI
demonstrating progression of the leptomeningeal disease
along the superior cerebellar folia. The pineal region tumour is
also demonstrated but the hydrocephalus has resolved after
ventriculostomy. The shallow right subdural and subgaleal col-
lections are post-procedural. (b) Sagittal gadolinium-
enhanced T
1
weighted MRI demonstrating the posterior fossa
leptomeningeal enhancement as well as the meningeal
enhancement along the anterior cervical spinal cord (black
arrow). Also the widespread abnormal bone marrow signal
within the vertebral bodies in keeping with metastatic
deposits is noteworthy.
a b
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metastatic spread is exceptionally rare, with only very few cases
reported in the literature. Sheedy et al
2
reported a case of biopsy-
proven metastases from CEPA of a parotid primary tumour
affecting the brain and intramedullary spinal cord, which they
believed to be the first reported case of its kind at the time. Ahn
and colleagues
8
have reported intracranial and spinal metastases
from a lacrimal gland CEPA, with recurrent primary tumour
directly extending into the cavernous sinus with leptomeningeal
deposits also identified. Our case is exceptional in that, to our
knowledge, a pineal gland metastasis from a distant CEPA has
never been reported. The presence of a metastatic deposit within
the cerebellopontine angle from this primary lesion has also not
been previously described. The intracranial and spinal leptome-
ningeal disease, which rapidly progressed in our patient, has only
previously been documented in the report by Ahn et al,
8
indicat-
ing that this is also a remarkably rare finding.
Overall, the pineal gland is an unusual location for metastatic
spread, with many cases discovered incidentally at autopsy:
reports have indicated that there is a prevalence of 0.4–3.8% in
patients with solid tumours.
9
There are few cases of symptom-
atic pineal region metastases reported in the literature; however,
a case reported by Nemoto et al
10
of a patient with an isolated
pineal region metastasis from lung adenocarcinoma also pre-
sented with obstructive hydrocephalus. As in our case, there was
an indolent clinical course, with little in the way of examination
findings and no evidence of raised intracranial pressure. The
limited literature available documents that the most common
primary tumour site for spread to the pineal gland is the lungs,
with other primaries including breasts, malignant melanoma
and kidneys also cited.
9,10
Pineal metastasis from a salivary
gland neoplasm has not, to the best of our knowledge, been
reported in the literature.
Although this is an extremely rare case report of a pineal gland
metastasis, with a cerebellopontine angle deposit and leptome-
ningeal spread, from a parotid CEPA, it serves to demonstrate
how aggressively this primary tumour can behave, as well as
serve to illustrate the diagnostic dilemmas that the clinical team
may face. A strong, collaborative effort on the part of the multi-
disciplinary team looking after these patients is key to the diag-
nosis and effective treatment of these challenging cases.
LEARNING POINTS
1. There is an uncommon yet significant risk of PAs
undergoing malignant transformation, particularly if
untreated. As such, they should be considered as
premalignant conditions.
2. CEPA behaves unpredictably but has high rates of
recurrence and metastases, and the discovery of involved
lymph nodes is strongly regarded as a poor
prognostic sign.
3. Utilization of a variety of imaging modalities in the
management of CEPA is strongly recommended.
Ultrasound ±needle aspiration or biopsy, MRI and
PET/CT investigations will aid in the definitive
evaluation of recurrence at the surgical bed, confirmation
of local lymph node involvement or
distant metastatic spread, and the suspected
complications of disease progression.
4. Intracranial metastases are extremely rare in salivary
gland tumours and there needs to be close collaboration
between clinicians, radiologists and pathologists in
ensuring timely diagnosis and treatment.
5. Although an unusual entity, metastases should be a
differential diagnosis for any patient with a
known malignancy who presents with a pineal
region tumour.
CONSENT
Informed consent could not be given by the patient as she was
deceased at the time of writing this case report. This could not
be obtained from the next of kin or a family member despite
exhaustive attempts to contact them.
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