Paraneoplastic limbic encephalitis secondary to sertoli cell testicular tumor: A case report

Abstract

Paraneoplastic Limbic Encephalitis (PLE) is a neurocognitive condition caused by an immune response to neuronal proteins linked to malignancy, such as testicular cancer. We report a 25-year-old male with cognitive and personality changes. His initial MRI showed vasogenic edema. A subsequent CT scan revealed bilateral hydroceles, and a follow-up scrotal US uncovered a right testicular mass, leading to a radical orchiectomy that confirmed a Sertoli cell tumor. Following orchiectomy and immunomodulating therapy, the patient’s symptoms showed near-complete resolution within a year. This is the first documented case of PLE resulting from a non-germ cell testicular tumor.

1 Introduction

Although initially thought to be a rare condition, paraneoplastic limbic encephalitis (PLE) is now a relatively frequent autoimmune disorder often associated with small cell lung carcinoma, ovarian malignancies, Hodgkin’s lymphoma, and testicular germ cell tumors. ^, Proposed etiologies to the disorder include immune cross-reactivity against tumor antigens that have structural similarity to neurologic antigens, mounting a T-cell mediated response at a site distant from the cancer. Advancement in the detection of paraneoplastic and anti-neuronal antibodies has led to greater identification of PLE. Known associations exist between certain antibodies and specific cancers, such as anti-Hu and small cell lung carcinoma or anti-Ma2 and testicular germ cell tumors. As such, early identification of paraneoplastic antibodies can help identify the primary malignancy causing PLE. In fact, 90 % of patients with paraneoplastic neurologic diseases will have their cancer diagnosed within a year of presentation, underscoring the potential opportunity to identify and treat a previously undiagnosed malignancy in these patients.

Symptoms of PLE include short-term memory loss, personality change, and seizures with symptom severity proportional to the degree of inflammation and edema. In a recent systematic review by Deol et al., 96 cases of paraneoplastic encephalitis secondary to testicular tumors were identified. Notably, all cases were associated with germ cell tumors. PLE secondary to germ cell testicular tumors is well documented and associated with a variety of autoantibodies such as anti-Ma1/2, anti-KLHL11, and anti-TA. Using both PubMed and Ovid MEDLINE, we searched the keywords “Sertoli cell tumor,” “non-germ cell tumor,” and “paraneoplastic limbic encephalitis” to assess previous cases examining the association between PLE and non-germ cell tumors. Our search included the time frame from January 1st, 1946 to February 14th, 2025 and included all forms of publication types. To date, there has not been a reported case of PLE secondary to a non-germ cell testicular tumor. Here, we present the first description of PLE secondary to a non-germ cell tumor, specifically a Seritoli cell tumor.

1.1 Case presentation

A 25-year-old male with a past medical history significant for Bell’s Palsy presented to the ED with a one-month history of syncope, short-term memory loss including an inability to recognize family, personality changes, irritability, and aphasia. The patient had a baseline degree of mental disability of unknown origin but was able to live and work independently prior to symptom onset. He was initially seen at an outside hospital, where he received a course of empiric antibiotics and steroids with no immediate improvement in his neurological symptoms.

At presentation, the patient reported intermittent headaches and neck stiffness concerning for meningitis. An infectious workup, which included testing for HIV, syphilis, COVID-19, and HSV-1 & 2, was negative. Routine blood work revealed no metabolic source of his encephalopathy. The differential diagnosis was broadened with further testing revealing normal vitamin B12 and folate levels, mildly increased inflammatory markers including ESR and CK. Initial MRI revealed nonspecific vasogenic edema in the medial temporal and occipital lobe with the left side worse than the right ( Fig. 1 ), new from prior imaging 3 weeks earlier at the outside hospital. As his symptoms continued to progress and without a clear etiology, the patient was started on quetiapine for significant agitation and valproate for seizure prophylaxis.

As his initial workup was non-contributory, his workup continued with an EEG, which revealed generalized delta and theta slowing indicating diffuse cerebral dysfunction, however, no epileptiform activity was seen. A lumbar puncture was performed and showed lymphocytosis, oligoclonal bands, and elevated protein. Complete infectious testing of the CSF was altogether negative and included: Cryptococcus, CMV, HSV, Enterovirus, E coli K1, Haemophilus influenzae, HIV, Leptospira, Neisseria gonorrhoeae, Listeria, GBS, Streptococcus Pneumoniae, and Varicella. Additionally, a bacterial culture of the CSF showed no growth. A comprehensive paraneoplastic and infectious disease panel was negative.

In an effort to further assess for a source of the patient’s encephalopathy, a CT scan of the chest, abdomen, and pelvis was ordered to assess for malignancy. While no acute malignant changes were identified, bilateral hydroceles were visible and prompted a testicular ultrasound, which revealed a 1.5 cm by 1.1 cm by 1.5 cm right testicular mass ( Fig. 2 ). At this point, the patient was urgently referred to urology, and a comprehensive genitourinary physical exam showed a right-sided posterior testicular mass, confirming the scrotal ultrasound findings. A more focused review of his CT did not reveal evidence of metastasis including no retroperitoneal lymphadenopathy and tumor markers AFP, LDH, and b-hCG were all within normal range. Three days later, an uncomplicated right radical orchiectomy with right testicular implant was performed under general anesthesia, and pathology characterized the mass as a sclerosing Sertoli cell tumor with negative margins. Immunohistochemistry was positive for vimentin, beta-catenin, and synaptophysin, which was further suggestive of a neoplasm of Sertoli cell origin.