Woman with pulmonary lesions presents with ptosis

Ocular motility exam revealed near complete loss of supraduction, infraduction and adduction of the right eye.

Issue: September 10, 2018

ByLaurel N. Vuong, MD

BySarah E. Thornton, MD

A 65-year-old woman was referred to the New England Eye Center with a 6-week history of throbbing right brow pain and 4 weeks of progressive right upper lid ptosis with diplopia when the ptotic lid was lifted.

Five months earlier, she had presented to her primary care physician with a 2-month history of non-productive cough and weight loss. A chest X-ray revealed scattered soft tissue nodules throughout both lungs with an 8-cm right lower lobe mass suspicious for malignancy (Figure 1). CT of the chest and abdomen confirmed the presence of pulmonary lesions and showed a lesion at the T10 vertebral body that raised concern for metastatic disease. PET/CT demonstrated additional lesions in the right sacrum and right inferior pubic ramus. The patient underwent CT-guided fine needle aspiration biopsy of the right lower lobe lung mass, and pathology returned non-small cell carcinoma with a staining pattern suggestive of adenocarcinoma. She received a final diagnosis of stage 4 lung adenocarcinoma with bone metastasis. The decision regarding her treatment course had not yet been established when her ocular symptoms manifested.

Before her diagnosis of metastatic adenocarcinoma, the patient’s medical history had included hypertension and non-insulin-dependent type 2 diabetes. Her ocular history and family history were unremarkable. She had no smoking history. She had immigrated to the United States from China in 2010.

Examination

Upon examination, the patient’s best corrected visual acuity was 20/40 in the right eye and 20/25 in the left eye. Her pupils were symmetric, and she had no afferent pupillary defect. IOPs were within normal limits. Color plates were full in both eyes. On external examination, she had complete ptosis of the right upper eyelid (Figure 2). There was no proptosis. Ocular motility examination revealed near complete loss of supraduction, infraduction and adduction of the right eye (Figure 3). Abduction of the right eye was preserved. There was no intorsion of the right eye on attempted downgaze. Motility in the left eye was full.

Figure 1. Upright, lateral and posteroanterior chest radiograph showing scattered soft tissue nodules throughout both lungs with an 8-cm right lower lobe mass.

Figure 2. External photograph showing complete ptosis of the right upper eyelid.

Figure 3. External photograph showing near complete loss of supraduction, infraduction and adduction of the right eye. Abduction of the right eye is preserved. Motility in the left eye is full.

On slit lamp examination, the anterior segment was unremarkable in both eyes. Fundus examination revealed no abnormalities including disc edema, cotton wool spots or vessel occlusion. Cranial nerve examination was significant for right-sided hyperesthesia in the V1 distribution. Strength and sensation were intact in upper and lower extremities bilaterally.

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Cranial neuropathies

The patient’s constellation of clinical findings including right-sided ptosis, ophthalmoplegia and trigeminal neuralgia suggests a process involving cranial nerves III (oculomotor nerve), IV (trochlear nerve) and V1 (ophthalmic nerve). The differential diagnosis for multiple cranial neuropathies is broad but can be narrowed by identifying the likely anatomic site of involvement. In this case, the pattern of cranial neuropathies localizes to the right cavernous sinus.

The cavernous sinus contains important neurovascular structures including a venous plexus, the internal carotid artery, sympathetic nerve fibers, and portions of cranial nerves III, IV, V1, V2 (maxillary nerve) and VI (abducens nerve). The oculomotor nerve, trochlear nerve, ophthalmic nerve and maxillary nerve travel in the lateral aspect of the cavernous sinus while the abducens nerve is found medially (Figure 4). Cavernous sinus syndrome (CSS) arises when pathology affects intracavernous segments of cranial nerves. CSS can have variable clinical presentations depending on the structures involved, but common findings include ophthalmoplegia, Horner’s syndrome, proptosis, pain and sensory abnormalities of the trigeminal nerve. The oculomotor and abducens nerves are most frequently involved in CSS while the trochlear nerve may be spared.

Figure 4. Anatomy of the cavernous sinus. The oculomotor, trochlear, ophthalmic and maxillary nerves can be seen passing along the lateral aspect of the cavernous sinus. The abducens nerve passes more medially.

Figure 5. Sagittal T1-weighted brain MRI showing a 2- to 3-mm focus of enhancement within the left inferior cerebellar hemisphere.

Figure 6. Coronal (left) and axial (right) T1-weighted brain MRI showing a mass lesion of the right cavernous sinus that can be seen invading local structures including the right superior orbital fissure and optic canal. The mass also encases the cavernous segment of the internal carotid artery.

The differential diagnosis for CSS includes infectious, inflammatory, neoplastic and vascular etiologies. Infectious CSS may result when fungal or bacterial pathogens invade from paranasal sinuses and should be considered in immunocompromised patients. Inflammatory causes of CSS include Tolosa-Hunt syndrome, which causes a painful ophthalmoplegia that tends to have a relapsing-remitting course. Neoplastic involvement of the cavernous sinus can occur with meningioma, schwannoma, nasopharyngeal carcinoma, pituitary adenoma, leukemia or lymphoma, and metastatic disease. Vascular lesions such as aneurysm of the internal carotid artery or traumatic carotid-cavernous fistula may also be implicated in CSS.

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Workup and management

Given the patient’s history of metastatic disease, a neoplastic etiology of CSS was high on the differential diagnosis. The patient was sent for brain MRI, which was notable for a 3-mm focus of enhancement within the left inferior cerebellar hemisphere concerning for metastatic disease (Figure 5). Enlargement of the right cavernous sinus was also noted on MRI (Figure 6). This asymmetry was caused by a mass lesion within the right cavernous sinus that invaded local structures including the right superior orbital fissure and optic canal. The mass also encased the cavernous segment of the right internal carotid artery.

The patient followed up with Hematology/Oncology at Tufts Medical Center. Given her symptomatic brain metastasis, she underwent whole brain radiation therapy. She also initiated chemotherapy with carboplatin and pemetrexed. She tolerated treatment well with significant improvement of her ptosis and diplopia. After 4 months of treatment, she remains clinically stable.

Discussion

Cavernous sinus metastasis is an uncommon event. When parasellar metastasis does occur, it is associated with breast or lung cancer in two-thirds of cases. Less commonly, lymphoma, prostate cancer, renal cell cancer and colon cancer may spread to this region. Most patients who present with cavernous sinus lesions already carry a diagnosis of metastatic disease, often with prior osseous involvement. However, in rare situations, CSS may be the initial presentation of an unknown malignancy.

When suspicion is high, MRI or CT can help confirm the presence of cavernous sinus lesions. MRI may show cavernous sinus widening with outward displacement of the lateral wall. Homogenously enhancing soft tissue masses may be seen in Meckel’s cave. On CT, bone destruction or lesions may be apparent. In the case described, the cavernous sinus lesion was initially overlooked by the interpreting radiologist, which highlights the importance of careful clinical exam and personal review of imaging.

The prognosis of cavernous sinus metastasis is poor with an average survival of less than 2 years. Treatment options are generally palliative and may include chemotherapy, radiation therapy or surgical resection. Conventional radiation may be effective for symptom control in up to 78% of patients. Radiosurgery, although limited by potential side effects, may have a role in controlling tumor burden in cavernous sinus metastasis. Surgical resection, if possible, may also be considered as a palliative measure.

References:
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For more information:
Sarah Thornton, MD, and Laurel N. Vuong, MD, can be reached at New England Eye Center, Tufts University School of Medicine. 800 Washington Street, Box 450, Boston, MA 02111; website: www.neec.com.
Edited by Adam T. Chin, MD, and Omar Dajani, MD. They can be reached at the New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.

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