Salivary Gland Adenocarcinoma of the Sphenoid Sinus Causing Compressive Optic Neuropathy

Hashemi N, Billah S, Conderman CP, Alava I, Supsupin EP Jr, Chevez-Barrios P, Adesina OO

Journal of Neuro-Ophthalmology, 2017 · DOI: 10.1097/WNO.0000000000000504

A case report of a 59-year-old man whose sphenoid sinus mass was initially misidentified as arrested pneumatization, delaying diagnosis of a minor salivary gland adenocarcinoma that caused compressive optic neuropathy and vision loss.

7 min read

This case report describes a minor salivary gland adenocarcinoma arising from the sphenoid sinus that initially mimicked a benign fibro-osseous lesion on imaging, leading to delayed diagnosis and subsequent compressive optic neuropathy. Published in the Journal of Neuro-Ophthalmology in 2017, this case highlights the diagnostic challenges of skull base tumors that can masquerade as benign findings and the immunohistochemical pitfall of salivary duct carcinomas staining positive for prostate markers.

Key Findings

Initial MRI misinterpreted a sphenoid sinus mass as arrested pneumatization, delaying the correct diagnosis by several months
Rapid tumor growth over 6 months produced a 3.2 x 3.8 x 2.1 cm skull base mass compressing the right optic nerve and displacing the optic chiasm
Immunohistochemistry was misleading as the tumor stained positive for PSA, PSAP, and androgen receptor, initially suggesting metastatic prostate cancer
CK7 positivity was the key distinguishing marker, favoring salivary gland origin over prostate adenocarcinoma, which is typically CK7-negative
Normal prostate exam and low serum PSA (3.54 ng/mL) helped clinically exclude a prostatic primary
PET/CT revealed diffuse hypermetabolic osteoblastic metastases with maximum standardized uptake values of 5 in the skull base lesion
Final diagnosis: adenocarcinoma of minor salivary gland origin, stage T4dN0M1, with poor long-term prognosis

Background

Minor salivary glands are distributed throughout the paranasal sinuses, and malignant tumors can arise from these glands in locations including the sphenoid sinus. These tumors are rare and can be diagnostically challenging because they may present as subtle lesions on initial imaging. Salivary duct carcinomas are known to express androgen receptor, prostate-specific antigen (PSA), and prostate-specific acid phosphatase (PSAP)--markers more commonly associated with prostatic adenocarcinoma. This immunohistochemical overlap creates a significant diagnostic pitfall, particularly when a skull base mass is discovered in a male patient.

The prognosis for minor salivary gland malignancies depends on histologic subtype, tumor site, grade and stage at diagnosis, patient age, and whether surgical intervention is performed. Tumors in the nasal cavity and paranasal sinuses carry a worse cause-specific survival across all histologic subtypes.

The Patient

A 59-year-old Hispanic man initially presented to the emergency room with:

A painful, neurologically isolated, pupil-sparing right third nerve palsy
The palsy spontaneously resolved and was attributed to a microvascular etiology
Past medical history included hypertension, type 2 diabetes mellitus with diabetic nephropathy, nonproliferative diabetic retinopathy, and a tubular adenoma of the colon

Four months later, he presented to the neuro-ophthalmology clinic complaining of 1 month of progressive blurry vision in the right eye. Examination revealed:

Visual acuity: counting fingers OD, 20/20 OS
A right relative afferent pupillary defect (RAPD)
Intact ocular motility
Right optic disc pallor with a normal left fundus

Diagnostic Workup

Initial Imaging and Laboratory Studies

At the time of the third nerve palsy, a comprehensive workup was performed:

Contrast-enhanced MRI showed only an abnormality of the posterior right sphenoid sinus, interpreted as arrested pneumatization
MR angiography was unremarkable
Lumbar puncture: normal opening pressure; CSF protein elevated at 111 mg/dL (normal: 15-45 mg/dL); normal glucose and white blood cell count
Blood tests: CRP, ESR, TSH, ACE levels were normal; ANA, Lyme, and Sjogren antibodies were negative

Follow-Up Imaging at 6 Months

Repeat contrast-enhanced MRI of the brain and orbits showed dramatic interval change:

An expansile 3.2 x 3.8 x 2.1 cm central skull base mass involving the clivus
The mass partially encased the right cavernous internal carotid artery
It displaced the optic chiasm and extended into the orbital apex, compressing the right optic nerve
In retrospect, this mass corresponded to the lesion initially thought to be arrested pneumatization

Maxillofacial CT demonstrated:

A predominantly hyperdense mass infiltrating the central skull base and sphenoid sinus
Extension anteriorly into the ethmoid sinuses bilaterally (right greater than left)
An appearance consistent with a bony matrix
Findings most concerning for a malignant neoplasm, either primary or metastatic

PET/CT Staging

Diffuse hypermetabolic osteoblastic metastatic disease
The largest and most FDG-avid lesion was in the central skull base with maximum standardized uptake values of 5
Bony metastases in the spine, scapula, and proximal femur
No soft tissue lesions or masses to suggest a primary source, including the prostate

Findings

Histopathology

Nasal endoscopy with sphenoidotomy and biopsy revealed:

Bony trabeculae with an infiltrate of neoplastic cells within the marrow
Glands and solid sheets of intermediate-sized cells with abundant cytoplasm and bland nuclei
Occasional prominent nucleoli and rare cells with intracytoplasmic mucin

Immunohistochemistry

The tumor cells were:

Positive for: cytokeratin AE1/AE3, CAM 5.2, androgen receptor, PSA, PSAP, and focally positive for CK7
Negative for: vimentin, CD31, CD34, PAX-8, TTF-1, p63, S100, cytokeratin 5/6, chromogranin, synaptophysin
Ki-67: moderate proliferative index

Clinical Correlation

Serum PSA was normal at 3.54 ng/mL (normal < 4.0 ng/mL)
Clinical prostate exam: 35-gram gland without nodularity
Urology did not consider the findings consistent with a primary prostate tumor
Multidisciplinary tumor board concluded the tumor was an adenocarcinoma of minor salivary gland origin arising from the sphenoid sinus

Final diagnosis: Adenocarcinoma of minor salivary gland origin, arising from the sphenoid sinus, stage T4dN0M1, causing compressive optic neuropathy.

Clinical Significance

This case illustrates several important lessons for clinicians:

Sphenoid sinus lesions that appear benign on initial imaging can represent early malignancy. The mass initially mimicked arrested pneumatization, a common and benign finding. A high index of suspicion and close imaging follow-up are essential when clinical symptoms do not fully resolve.
Salivary duct carcinomas can express prostate markers (PSA, PSAP, androgen receptor), creating a diagnostic pitfall. Pathologists and clinicians must be aware that these markers are not specific to prostatic adenocarcinoma.
CK7 positivity is a critical differentiating marker. Prostate adenocarcinoma tends to be CK7-negative, whereas salivary gland carcinomas may show focal CK7 positivity. This immunohistochemical finding, combined with clinical context, was essential for reaching the correct diagnosis.
A transient, pupil-sparing third nerve palsy may be the earliest sign of a skull base tumor, even when initially attributed to microvascular ischemia in patients with vascular risk factors.

Diagnostic pitfall: Salivary duct carcinomas can stain positive for PSA, PSAP, and androgen receptor, closely mimicking metastatic prostate adenocarcinoma. In male patients with a skull base mass positive for prostate markers, always consider salivary gland origin--especially when the prostate exam is normal, serum PSA is low, and the dominant mass is in the paranasal sinuses. Focal CK7 positivity strongly favors salivary gland over prostatic origin.

Clinical pearl: A spontaneously resolving third nerve palsy in a patient with vascular risk factors is often attributed to microvascular ischemia. However, if follow-up imaging or new symptoms develop, the initial imaging should be re-reviewed carefully for subtle findings that may have been dismissed, such as small sphenoid sinus lesions. In this case, the initial "arrested pneumatization" was actually an early malignancy.

Citation

Hashemi N, Billah S, Conderman CP, Alava I, Supsupin EP Jr, Chevez-Barrios P, Adesina OO. Nothing to spit at. J Neuroophthalmol. 2017;37(4):440-443. doi:10.1097/WNO.0000000000000504.

References

Was this article helpful?