Thymoma is an uncommon neoplasm with an incidence of 0.13–0.19 cases per 100,000 persons at risk (1, 2). Thymomas arise from the thymic epithelial cells located in the anterior mediastinum and can be benign or malignant. There is a strong association between thymoma and autoimmune disorders (e.g., myasthenia gravis, pure red cell aplasia, and Good syndrome) (3, 4), and may be due to dysfunction of T-cell activity in the context of abnormal maturation and differentiation of thymic cells in the neoplasm.

The incidence of malignant thymoma is rare, and cases with extra-thoracic spread have only been documented in a few case series and reports. Common sites of extra-thoracic metastasis include lymph nodes, liver, bones, and brain (5). Leptomeningeal disease (LMD) in thymic neoplasm represents a late-stage complication and has an extremely poor prognosis. A systematic review from 2017 mentions only 8 to 10 cases ever reported for brain and LMD (6). We report a case of thymomatous LMD presenting with diplopia and multiple cranial neuropathies.

A 53-year-old man presented with acute, binocular horizontal diplopia, right-sided headache, and facial numbness. Past medical history included a diagnosis of malignant thymoma, with extension to the lungs and pleura. Surgical history was non-contributory, as the patient’s thymoma had been deemed unresectable. The patient was taking the following medications: albuterol for asthma, which was well-controlled, and gabapentin for generalized pain and myalgias. Social history included smoking (3.2 pack years), although he had quit 6 years ago; a history of alcohol abuse, with 10 standard alcoholic drinks per week, but none at presentation. The patient developed constitutional symptoms and chest pain. Patient’s family history was unremarkable for thymic epithelial neoplasm.

Chest X-ray, chest computed tomography (CT), and magnetic resonance imaging (MRI) of the chest revealed total collapse of the left lower lobe, extensive mass effect upon the left upper lobe, and bulky lymphadenopathy of the anterior mediastinum consistent with thymoma. Full-body positron emission tomography (PET) scan confirmed hyperavidity in the mediastinal mass, suggestive of malignancy. However, at this stage, no suspicious brain or lymph node uptake in the head and neck region was noted on the PET scan.

Endobronchial ultrasound-guided biopsy showed lymphoepithelial cells consistent with a thymoma. Staging body imaging showed stage 4 thymoma with lung and pleural metastasis. The patient was started on cisplatin, doxorubicin, and cyclophosphamide for six cycles. Follow-up imaging of the lung and pleural metastasis showed a good response to the chemotherapy.

However, two months later, the patient presented to the emergency department with severe right-sided facial pain and lip numbness (cranial nerve V), and bilateral lower extremity discomfort and myalgias. This was followed 2 weeks later by ptosis and double vision. On examination, he was alert and oriented to person, place, time, and situation, and was able to follow complex commands. There was marked numbness in the V1 and V2 distribution of the trigeminal nerve on the right side, with decreased corneal sensitivity. The left eye (OS) showed limited adduction along with limited elevation and depression in abduction, suggestive of a cranial nerve III palsy OS. There was also a lack of torsion in downgaze consistent with concomitant cranial nerve IV involvement OS (Figure 1). Rest of the cranial nerve examination was unremarkable. Motor exam revealed equal and normal muscle bulk, tone and strength in lower as well as upper extremities. Deep tendon reflexes were intact throughout. Sensations were intact and symmetric in all extremities to light touch, pinprick, temperature, vibration, and proprioception.

Laboratory testing for myasthenia gravis was negative. The clinical picture prompted suspicion of intracranial spread that was responsible for the cranial nerve palsies. MR imaging of the head, neck, and spine revealed nodular leptomeningeal enhancement involving the conus medullaris and cauda equina in the spine (purple arrows in Figure 2). In addition, there was abnormal enhancement involving multiple cranial nerves in the posterior cranial fossa, the right Meckel’s cave (orange arrow), and the right cranial nerve V3 segment (blue arrow), as shown in Figure 3. The lower extremity pain was well accounted for by the leptomeningeal disease of the spinal cord. In addition, the patient’s presentation of right sided facial pain and numbness was adequately described by intracranial nodular metastases involving the trigeminal nerve. However, this mass lesion did not adequately account for the cranial nerve palsies seen on the left side. Thereafter, upon detailed review by the neuroradiology team, involvement of multiple cranial nerve palsies (cranial nerves III and IV on the left side) in the absence of a visible mass was deemed more likely due to leptomeningeal metastasis of thymoma. A lumbar puncture was ordered to confirm the diagnosis of leptomeningeal disease in this setting (see Figure 4).

Lumbar puncture revealed a markedly elevated cerebrospinal fluid protein of 593 mg/dL and albumin content measuring 398 mg/dL. The white blood cell count was notably high, at 2,294 cells/mm³ with differential count showing 43% lymphocytes and 57% monocytes. Flow cytometry showed these lymphocytes comprised of 96% immature T-cells, consistent with metastatic thymoma.

Thus, the patient was formally diagnosed with intracranial and spinal metastases of thymoma. Thereafter, because of the need to target specific neoplastic lesions in the brain and spinal cord, the patient underwent whole brain radiation and 10 fractions of 30 Gy radiation to the lumbar spine, which was overseen by the radiation oncology department.

The patient was understanding of the change in therapeutic regimen, from chemotherapy to radiotherapy, and understood that surgery could not be attempted in his case owing to the extensive metastases. His primary concerns were regaining normal vision and relieving the pain. It was explained to him that his presentation was exceedingly rare, and while radiotherapy could ideally help achieve these goals, the outcomes could vary widely.

LMD due to metastatic thymoma is exceedingly rare and based upon our review of the literature has only been described nine times previously (Table 1). However, there have been no prior reports of simultaneous involvement of the brain and spinal cord from thymoma metastasis. The World Health Organization (WHO) classifies thymomas into five types, designated as Type A, AB, B1, B2, and B3, based on cellular morphology and the presence of lymphocytic components (7). According to the National Cancer Collaborative Network (NCCN), diagnostic workup for thymic masses involves screening for paraneoplastic syndromes, chest imaging with CT/MRI and fluorodeoxyglucose PET scan from skull base to mid-thigh (8). Thymoma can produce diplopia from intracranial metastatic disease, LMD, or from thymoma associated myasthenia gravis.

Our case report adds value to current literature on thymoma and its variable presentations by emphasizing the need for extensive imaging in patients at initial presentation. The more common paraneoplastic presentations of thymoma, such as myasthenia gravis, can mask the more malignant manifestations, such as intracranial and spinal metastases. Thus, a comprehensive metabolic, autoimmune, paraneoplastic, and radiographic image should be constructed for such a patient. In our case, the patient had not been seen by a physician in over a decade before presenting with severe chest pain, when he was diagnosed with pleural and pulmonary metastatic disease. Therefore, one of the limitations of our case report is the limited knowledge of the point in time when the patient developed leptomeningeal disease, which would be needed to construct a detailed timeline showing the relation of disease development to presentation.

Clinicians should be aware that thymoma can be benign or malignant and that malignant thymoma can metastasize. Multiple and bilateral cranial nerve presentations (including facial pain and ophthalmoplegia) should prompt consideration for LMD. The prognosis for LMD is generally poor and thymomatous LMD is exceedingly rare.