OR IG INAL ARTICLE
Aggressive papillary tumor of the
middle ear: A true entity or an
endolymphatic sac neoplasm?
Jam es R. Tysome, MA, MRCS; lo nny Harcourt, MA, FRCS; Ma nish C. Patel, FRCR;
Ann Sandison, FRCPath ; Leslie Michaels, MD, FRCPath
Abstract
Aggressive papillary tumors of the middle ear are rare,
and their true origin is not clear. We describe the clini-
cal, radiologic, genetic, and histopathologic features of a
papillary epithelial tumor filling the middle ear of a 68-
year-old woman. Imagingrevealed no evidenceofpetrous
temporal bone apex involvement, nor did geneticstudies
demonstrate the von Hippel-Lindau mutation. A litera-
turesearch revealed 24 previously reported cases ofsucha
papillary epithelial tumor of the middle ear. All except 2
casesdemonstrated apical petroustemporal boneinvasion
on imaging, and it hasbeensuggested that they arosefrom
a primary endolymphattcsac tumor, which hasa similar
papillary epithelialhistology. Substantialnumbers ofcases
ofpapillaryepithelialtumorsinvolvingthemiddleearare
reported to beassociated with vonHippel-Lindaudisease,
as are known cases of endolymphatic sac tumor. This is
the thirdreportedcase ofpapillaryepithelial tumorof the
middleearthatdoes notshowapicalpetroustemporalbone
invasion onimaging,suggesting thatsuch neoplasms donot
always arise from a primary in the endolymphatu: sac.
Introduction
Aggressive papillary tumors of the middle ear are rare. It
has been suggested that these tumors mayarise from a pri-
marypapillaryendolymphatic sac tumor (ELST) because
of the frequency of their concomitant petrous temporal
From the Depa rtme nt of Otolaryngology-Head and Neck Surgery (Mr.
Tysorn e, Mr. Harcourt), th e Depa rt me nt of Radiology (Dr. Patel),
and the Depa rtmen t of Histopath ology (Dr. Sandi son ), Cha ring
Cross Ho spit al; and th e Department of Histop ath ology, University
College (Prof. Michaels), Lond on, U.K.
Correspond ing autho r: Mr. Jam es R. Tysorne, 33 Burn ey St., Lond on,
SElO 8EX, UK. Phone: 44-780-37 1-0935; fax: 44- 163-482-505 5;
e-mail: jamest ysome @yahoo.com
378' www.entjournal.com
bone involvemen t,I the similarity of the histopath ologic
appearances,' and the association of some tu mors of both
regions with von Hippel-Linda u (VHL) disease." ? We
present the third case in which, to our knowledge, there
was no invasion of the petrous temporal bone.
Case report
A 68-year-old woman presented with an I8-month his-
to ry of otalgia, hearing loss, and an offensive-smelling
discharge from her right ear. Otoscopy revealed a poly-
poid growth emanating from a right central tympanic
membrane perforation . The facial ne rve was intact.
Pure-tone audiometry showed a severe mixed hearing
loss on the right. Nasoendoscopy was normal.
A biopsy of the polyp was taken under topical local
anest hesia. Histology revealed inflam ma tory tissue with
no unusual features . Comp uted tomography (CT) of th e
temporal bo nes showe d a soft-tissue opacity filling th e
right middl e ear bu t no erosion of the apica l porti on of
the petrous tem poral bone (figure 1). The coch lea and
semicircular canals were intact, and there was no dilata-
tion of the endo lymphatic duct .A provisional diagnosis
of active mucosal chronic otitis media was made.
The patient was managed with topical antibiotics
and steroids. She underwent a second polypectomy
under local anaesthesia 6 months later. Histology again
confirmed inflammatory tissue. Since her ear rem ained
active after 1year,the patient agreed to undergo a cortical
mastoidectomy and tympanoplasty. Operative findings
were free fluid and a soft, greyish vascular mass filling
the mastoid segment of the middle ear. The ossicular
chain and all bony structures were intact. Postoperative
recovery was uneventful.
H istopath ology revea led an aggressive papillary
tumor of the m iddle ear (figure 2, A). The tissue was
com posed of papillary epithelial outgrowths with a
ENT·Ear, Nose & Throat Journal ' July2008
 AGGR ESSIV E PAPI LLARY TUMOR OF THE MI DDLE EAR: A TRUE ENTITY OR AN END OLYM PHATIC SAC NEO PLASM?

fibrovascular stro ma and an

epithelial covering that was
cuboidal to columnar (figure
2, B). Im munohi stochemical
staining showed expression
of pa ncytokeratin AE/AE3,
which confirmed th e epithe-
lial nature of the neoplasm.
Expressio n of glial fibrillary
acidic prot ein was weak, and
th e presenc e ofKi- 67 prot ein
demon st rated a low prolif-
eration ra te (figur e 2,C). Ge-
netic studies demonstrated
th at the pa tient did not have
th e VHL gene m utation or
deletions on the short ar m
of chromosome 3. Figure 1. Axial (top row) and coronal (bottom row) CT imagesof the temporalbonesshowa soft-
tissue opacity filling the right middle ear and /10 erosion of the petrous temporal bone.
The patient had no fur ther
in tervention an d re mains
symptom-free 12 mon th s postoperatively (figure 3),
without signs of recurrence on clinical examination or
magnetic resonance imagi ng (MRI) .
Discussion
A pap illary epithelial tu mor filling the middle ear and
invading th e adjacent petro us temporal bon e has been
called a "primary aggressive papillary tumor of th e
middle ear" by Gaffey et al." This is a rare tumor. We
reviewed th e literature on such a primary neopl asm ,
selecting only tho se cases in which th ere was definite
evidence of middle ear involvement by th e neopl asm.
We found 24 repo rt ed cases, involving 17 fem ale and 7
male patients.v -":" Th is is considerably fewer than the
46 literature cases ofprimary aggressive pap illary tumor
of the middle ear referred to by Gaffey et aJ,3 because
of the care we took to select on ly those cases with bona
fide invo lvemen t of th e middle ear.
The range of age at diag nos is in the group we selected
was 16 to 55 years, with a med ian age of 33 years. The
present case represents th e oldest at presentation, at 68
years of age. In many of the cases, however, th e pat ient
ha d already suffered symptoms for some years, subse-
quen tly ascr ibable to the tumor when the diagn osis was
made, so th at the real age at onset may be cons iderably
younger tha n is suggested . In the prese nt case, the tru e
diagnosis was not apparent from the first two biopsies,
and th e histop ath ologic findings after th e patient 's
ma stoid ectom y were un expected.
In all of th e previou sly reported cases except 2, there
was extensive invasion of the apical portion of thepetrous
tem poral bone, demonstrated as lytic lesions by CT.20-21
In some cases, the tumor reached the cerebellopontine
ang le or invaded the cerebellum . 10
It has bee n suggested that aggressive papillary middle
ear tumors with involvement of th e temporal bon e may
ar ise from a primary papillary ELST.I Th e endo lym -
pha tic sac develops from the otocyst and lies between
th e int ern al auditory cana l and sigmo id sinus. ELSTs
show two histop athol ogic patt ern s: colloid- filled cysts
or a papillary pattern.' Because of th e position of th e
endo lympha tic sac, ELSTs pr im ar ily invade the petrous
temporal bon e and may extend into th e posterior cra-
nial fossa.I There is always bony erosion or dilat ati on
of either the endo lym phatic sac or vestibular aqueduct
on CT in patient s with ELST. MRI cha racteristically
shows a mixtur e of hyperintense and isointense foci on
T2-weighted images, with a heterogen ous enhancement
patte rn." Mid dle ear invasion is prob ably a late occur-
rence in the grow th of this neoplasm .
Increasing evidence po ints to an associa tion between
both aggressive pap illary tumors of the mi ddle ear and
ELST with VHL disease. VHL is a gene tic abnorma lity
on the short arm of chro mosome 3 inher ited as an
autosomal-do minant trait. It predisposes patien ts to
m ultip le hemangioblastom as of th e central nervou s
system, ph eochromocytom as, renal cysts, renal cell and
other carcinomas, and pan creatic cysts.
Man ski et al found radiologic evidence of ELST in 11%
of 121 patient s with VHL. 5 Gaffey et al found that 15%

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 TYSOME, HARCOURT, PATEL, SANDISON, MICHAELS
of 46 patients reported in the literature with aggressive
papillary middle ear/temporal bone tumors had VHL,3
Four reports have demonstrated the VHL mutation in
patients with ELST.6-9 One report demonstrated the
VHL mutation in a patient with an aggressive papillary
middle ear tumor," but in our patient, genetic studies
did not demonstrate this mutation.
380· www.entjournal.com
Figure 3. The patient's right ear is symptom-free 12 months after
cortical mastoidectomy and tympanoplasty (original tnagnijica-
tion x lO).
The frequency of petrous temporal bone involvement,
the similarity of the histopathologic appearances, and tne
association of some tumors of both regions with VHL
disease support the possibility that aggressive papillary
middle ear tumors may arise from a primary papillary
ELST. However, an origin in the middle ear in some cases
of this neoplasm has not been definitely excluded. Both in
our case and 2 others reported, there was no involvement
of the petrous temporal bone at al1,20,21MRI in our case
also did not demonstrate dilatation of the endolymphatic
sac, supporting the possibility that aggressive papillary
tumors of the middle ear may be an entity separate from
the ELST. In a description of the pathologic changes of
an aggressive papillary tumor of the middle ear in an
autopsy temporal bone, widespread deposits of tumor
were found at inner ear sites, but no mention was made
of involvement of the endolymphatic sac or duct. "
Whatever the site of origin of this rare tumor, it should
be recognized that a papillary epithelial tumor of the
middle ear may be an aggressive neoplasm, in contrast
to the nonpapillary adenoma of the middle ear, which
is common and benign." The present case raises the
possibility that aggressive papillary tumors of the middle
ear may be a separate entity from ELST. In view of the
association ofsome cases of aggressive papillary middle
ear tumors with VHL, consideration should be given to
performing genetic studies for the VHL gene mutation
in all patients with this neoplasm.
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ENT·Ear, Nose & Throat Journal· July 2008
 CAVERNOUS HEMANGIOMA OF THE MIDDLE TURBINATE : A CASE REPORT
App ropriate management of a nasal hemangioma
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AGGRESSIVE PAPILLARY TUMOR OF THE MIDDLE EAR: A TRUE ENTITY OR AN ENDOLYMPHATIC SAC NEOPLASM?
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