A 78-years-old lady presented with productive cough, hoarseness, swallowing impairment, and recurrent episodes of fever (40° C; 104° F), which started 1 month prior to hospitalization. There were no further B symptoms like night sweats or weight loss. Past medical history was unremarkable except for mild hypothyroidism and recent hospitalization for syncope two weeks prior to admission. A cranial computed tomography (CT) scan had been performed in a primary care hospital two weeks prior to admission, which retrospectively revealed a nodular mass in the middle cranial fossa restricted to the sellar region. An empiric antibiotic treatment with ceftriaxone and metronidazole was previously initiated due to elevated serum inflammation markers without significant improvement. Clinical examination on admission revealed left-sided glossopharyngeal and recurrence nerve palsies.
Cranial magnetic resonance imaging (MRI) revealed a contrast enhancing (CE) solid mass in the sellar region with both-sided signal alterations of the optic tract beneath the optic chiasm (Figure 1 A) as well as a CE lesion in the left jugular foramen (Figure 1 B) on T1-weighted imaging. Spinal MRI with CE did not show any further dissemination. CT of thorax, abdomen and pelvis with CE was unremarkable except for a left-sided kidney cyst. Electroencephalography (EEG) revealed a poorly modulated alpha rhythm without epileptogenic potentials.
Pituitary function tests on admission indicated a reduced cortisol serum level (0.7 µg/dl; ref: 10-25 µg/dl) and moderately elevated prolactine levels (178 ng/ml; ref: <23 ng/ml). The patient was substituted with hydrocortisone. Differential blood counts were normal. Except for an elevated lactate dehydrogenase (404 U/l) and a slightly elevated C-reactive protein (CRP) of 5,5 mg/dl, the routine laboratory results were normal. Diagnostic cerebrospinal fluid (CSF) puncture showed mixed pleocytosis with increased lymphocytic cell count (170 cells/µl), but no atypical cells were found. Elevated Epstein-Barr virus (EBV) counts (2,1x105 Geq/ml) were detected by polymerase chain reaction (PCR) of CSF, however serologic markers did not indicate a manifest EBV infection (negative EBNA-1 IgG and VCA IgM). Herpes simplex virus (HSV) and human immunodeficiency virus (HIV) serologies were also negative.
During further course of treatment, the patient developed elevated sodium levels (165 mmol/l) with high urine output and osmolality (339 mosmol/k). However, sodium serum level did not normalize until we started desmopressin medication indicating a diabetes insipidus. Antibiotic and antiviral treatment with ceftriaxone/ampicillin and ganciclovir was initiated on day 6 after admission. Due to sustained elevated inflammation markers antibiotic treatment was escalated with piperacillin/tazobactam on day 12. An episode with respiratory insufficiency due to glossopharyngeal nerve palsy occurred on day 13 and the patient was intubated and transferred to the intensive care unit. Once again antibiotic treatment was escalated with meropenem due to suspected urosepsis caused by vancomycin resistant enterococcus faecalis. Microbiological CSF cultures were negative for bacterial or fungal infection so ceftriaxone and ganciclovir were discontinued.
On day 19 an open tumor biopsy was performed through a right-sided pterional craniotomy with optic nerve decompression. Histopathological evaluation revealed a diffuse infiltrate of medium-sized to large lymphoid cells with irregular folded nuclei, granular chromatin, small nucleoli and a narrow to moderate rim of pale to clear cytoplasm (Figure 3A, hematoxylin/eosin, 400x). Mitotic figures were readily found. There was some geographic necrosis and angiocentric growth. By immunohistochemistry, the lymphoid cells stained positive for the T-cell markers CD2 and CD3 (Figure 3B), the NK-cell marker CD56 (Figure 3C) and the cytotoxic marker granzyme B (Figure 3D), whereas CD20 (Figure 3F), CD138 and Mum1 were negative. The proliferative fraction, as demonstrated by Ki-67 immunostaining was > 90 %. EBV in situ hybridisation was strongly positive in the tumor cells (Figure 3E) and the diagnosis of an EBV-associated lymphoma of the NK/T-cell phenotype was made. Due to limited tissue, neither further immunohistochemical stainings nor molecular studies could be performed.
On day 26 a left-sided hygroma, which was detected on postoperative imaging (Figure 2A), was evacuated through a frontal burr hole in local anaesthesia. Cranial MRI +/- CE additionally indicated growing lesions in the sellar and suprasellar region with compression of the optic chiasm (Figure 2A) and progressive lesions at the right-sided oculomotor nerve (Figure 2C). The tumor mass in the jugular foramen also progressed over time (Figure 2B,C). A dilative tracheotomy was performed since the patient developed ongoing aspiration due to glossopharyngeal palsy. After tapering sedation, we noticed a new right-sided oculomotor palsy. Due to a reduced state of consciousness, we were not able to examine visual acuity and visual fields throughout treatment.
Ultimately therapy with dexamethasone 40 mg daily was initiated and the patient was transferred to the oncologic department for further treatment. Despite corticosteroid medication, her status deteriorated rapidly preventing additional diagnostics and chemotherapy. The patient died due to respiratory insufficiency 37 days after admission.