Keywords
pleomorphic adenoma - benign mixed tumor - recurrent pleomorphic adenoma - carcinoma
ex pleomorphic adenoma - intracranial invasion
Case Report
A 53-year-old man presented to the emergency department with a 7-day history of right
ear fullness, otalgia, and hearing loss. He had recently been treated with antibiotics
for sinusitis at an outside hospital but his symptoms failed to resolve. He denied
vertigo, dizziness, otorrhea, or tinnitus. Physical examination demonstrated a mass
behind an intact right eardrum, and tuning fork evidence of a conductive hearing loss.
The remainder of his cranial nerve examination was normal, with the exception of the
long-standing House-Brackmann Grade VI/VI right facial nerve paralysis. Audiogram
demonstrated a right moderate conductive hearing loss with flat (Type B) tympanogram.
The left side was normal.
The patient had a right parotid pleomorphic adenoma 35 years ago, which was treated
by enucleation. He presented with several subcutaneous nodules 7 years after the initial
treatment, which were treated by total parotidectomy. During surgery the facial nerve
was sacrificed due to tumor encasement. Pathology confirmed recurrent pleomorphic
adenoma. Postoperatively the tumor bed was treated with external beam radiotherapy.
After this he remained asymptomatic for nearly 30 years.
Magnetic resonance imaging of the head confirmed a large, irregular, heterogeneous,
and variably enhancing mass in the right mastoid with extension medially along the
floor of the posterior fossa measuring ~5 × 5 × 5 cm ([Fig. 1]). The mass eroded through the mastoid laterally and inferiorly into the upper cervical
soft tissues. The superior portions of the mastoid were opacified with enhancement,
suggesting tumor infiltration. The mass extended inferiorly into the parapharyngeal
space and extrinsically compressed the right sigmoid sinus displacing it medially.
In addition, a 1 × 1 cm enhancing nodule in the right cerebellum medial to the cystic
lesion was observed. The differential diagnosis at this point included carcinoma ex
pleomorphic adenoma, postradiation sarcoma, another parotid gland carcinoma, and recurrent
pleomorphic adenoma.
Figure 1 Preoperative magnetic resonance imaging. (A) Axial T1, (B) axial T2, (C) coronal
T1, and (D) sagittal T1-weighted images reveal a variably enhancing mass in the right
mastoid air cells extending medially along the floor of the posterior fossa, extending
inferiorly into the parotid bed and medially into the cerebellum.
The patient was taken to the operating room for transtemporal resection. Upon entering
the mastoid, tumor was noted completely infiltrating the mastoid cavity. It eroded
through the dura of the posterior fossa medial to the sigmoid sinus and into the cerebellum.
The tumor had also eroded into the fallopian canal, requiring debridement and transection
of the grossly involved facial nerve. The mass infiltrated the posterior semicircular
canal and the aditus ad antrum; however, the middle ear space and facial recess were
free of tumor. After tumor had been removed from these areas, the overlying dura was
resected. Once proximal and distal venous control was achieved, the sigmoid and transverse
sinuses (both involved by tumor) were resected inferior to the vein of Labbé. Finally,
the remaining tumor was removed from the jugular foramen, lateral infratemporal fossa
skull base, and the superior parapharyngeal region.
Throughout the procedure, multiple specimens were collected for intraoperative frozen
sections. All specimens were interpreted as consistent with benign mixed tumor (pleomorphic
adenoma). The remainder of the specimen was examined following standard histological
processing and staining with hematoxylin and eosin. Upon final review, the intraoperative
diagnoses were corroborated. Although there was evidence of destruction of the mastoid
and involvement of the facial nerve, the growth pattern of the tumor was lobulated
and expansile rather than directly infiltrative ([Fig. 2]). The tumor showed areas of cellularity without mitoses or cellular atypia as well
as areas of abundant chondromyxoid matrix. There were numerous foci of squamous metaplasia
and tyrosine crystals were readily identified. There was no indication of malignant
transformation of either the epithelial or mesenchymal components. Immunohistochemistry
performed on the most cellular areas demonstrated a low proliferation rate (<2%) and
diffuse but weak staining with p53. Taken together, these findings excluded the possibility
of a malignancy such as carcinoma ex pleomorphic adenoma, and were highly suggestive
of an aggressive recurrence of an otherwise histologically benign pleomorphic adenoma.
Figure 2 Histological features of recurrent mixed tumor. (A) Expansile growth of tumor extending
into the mastoid causing local destruction, H&E, low magnification. (B) Cellular area
of the tumor showing well-formed tubules in a chondromyxoid matrix, H&E, low magnification.
(C) Paucicellular region of the tumor with abundant chondromyxoid matrix and tyrosine
crystal, H&E, high magnification. (D) K
i-67 immunohistochemistry showing rare positive cell denoting a low proliferation rate.
Postoperatively the patient did well and was discharged on postoperative day 3. He
immediately noted improvement in his hearing, though did have a transient vocal fold
paresis which is currently resolving.
Discussion
Pleomorphic adenoma, also known as benign mixed tumor, is the most common tumor affecting
the parotid gland, but can occur in any major or minor salivary gland as well as extra-salivary
tissue.[1–4] Pleomorphic adenoma is most common in middle age and in women,[5] and although rare in children, it remains the most common solid parotid mass in
the pediatric population.[6–9] These tumors arise directly from salivary gland tissue and consist of epithelial
and mesenchymal cells; the latter can give rise to osseous, cartilaginous, hyaline,
and myxoid elements, hence the name “mixed tumor.” Surgical resection is the treatment
of choice for pleomorphic adenoma due to possible malignant transformation (to carcinoma
ex pleomorphic adenoma) and its potential to reach massive size, causing significant
morbidity and cosmetic deformity. The invasion of bony structures is rare.[10] In this study, we identify a unique pattern of intracranial invasion of a recurrent
pleomorphic adenoma, as there does not exist anywhere in the literature a case reported
with such extensive intracranial spread of this benign tumor.
Recurrence of pleomorphic adenoma after excision is a well-known phenomenon and can
present decades after resection of the primary tumor.[11] The incidence of recurrent pleomorphic adenoma has been reported as high as 17%,
depending on the surgical technique used in the primary excision.[12] Pleomorphic adenomas are not all truly encapsulated; rather some possess “pseudopodia”
that vary in thickness and extend from the tumor surface, contributing to postoperative
recurrence.[13]
Initially believed to be primarily due to tumor spillage during excision, recurrence
may also be due to unique histological and genetic characteristics.[12] Additionally, the presence of microscopic satellite tumors left behind after resection
has been reported to contribute to pleomorphic adenoma recurrence.[13] More recently there has been an interest in determining the expression profile of
various tumor marker genes to determine if particular expression patterns exist between
pleomorphic adenomas and their malignant counterparts. Several studies have demonstrated
that carcinoma ex pleomorphic adenoma has a higher proliferative index, as determined
by the expression of the proliferation marker K
i-67, as well as accumulation of dysfunctional p53, than benign pleomorphic adenomas.[14–17] However, very few studies have examined the genetic differences between nonrecurrent
and recurrent pleomorphic adenomas. Stennert and colleagues studied the expression
of the proliferative marker K
i-67 in both myxoid and cellular types of recurrent pleomorphic adenomas and found
a higher proliferative index in the more aggressive, cellular type recurrences.[18] Hamada and colleagues compared the expression patterns between nonrecurrent and
recurrent pleomorphic adenomas for glycosylated phosphoprotein mucin 1 (MUC1), which
is upregulated in various cancers,[19] and found that high expression of MUC1 was a significant risk factor in developing
recurrence.[20] In our study the tumor showed a low proliferation (Ki-67) rate (<2%) with positive p53. Positive p53 immunohistochemistry has been identified
not only in malignant salivary gland tumors but also in tumors showing classic pleomorphic
adenoma histology, cellular pleomorphic adenomas, and recurrent pleomorphic adenomas.[21–23] More significant is the utility of the nuclear antigen K
i-67 as a predictor of tumor behavior, in malignant tumors a high proliferation rate
is suggestive of more aggressive behavior.[24] The low proliferation rate in addition to classic pleomorphic adenoma histology
with no evidence of malignant transformation of either cellular or stromal components
definitively placed this tumor into the category of a recurrent pleomorphic adenoma.
Clearly, more prospective investigations are needed to determine if immunohistochemical
profiling can reliably predict recurrence. While several characteristics appear to
individually contribute to recurrent disease, it is the combination of surgical technique,
histology, and genetics that conveys the true risk.
Conclusion
We present a unique case of massive transcranial invasion of a recurrent benign mixed
tumor arising from the parotid. In the vast majority of cases reported of recurrent
pleomorphic adenoma, the recurrent tumor is confined to the site of the primary tumor
with some extension into surrounding tissue. While bone changes and destruction have
been reported,[10]
[25] we believe this case represents the most massive and destructive recurrent pleomorphic
adenoma in the literature, and illustrates the point that recurrent pleomorphic adenoma
must be within the differential diagnosis of any patient presenting with a malignant
appearing intracranial lesion and a remote history of pleomorphic adenoma resection.
