Our patient is a 43-year-old lady diagnosed with a right parasagittal brain glioblastoma five years ago. The glioblastoma was WHO (World Health Organization) grade 4 with an unmethylated MGMT (methylguanine-DNA methyltransferase) mutation. She underwent gross resection in July 2016 and received concurrent chemoradiotherapy, which was completed in October 2016. In addition, she received adjuvant TMZ (temozolomide) and high-dose atorvastatin as per KFMC ART study protocol, completed in March 2017. Unfortunately, her glioblastoma recurred in February of 2018, for which she underwent reresection and received bevacizumab for five months. Despite these interventions, she developed a third recurrence and required resection in November of 2018, and received bevacizumab and irinotecan for six months. In September 2019, she had a fourth recurrence, which was resected, but she had rapid disease progression and was treated with surgical resection and 35 Gy in 10 fractions of radiation therapy. In December 2019, CT scans showed a fifth recurrence of her disease, which was resected again and treated with reirradiation 35 Gy in 10 fractions until February 2020, when her disease progressed again, and she received bevacizumab and lomustine until August 2020. However, her disease progressed again. She had another surgical resection in September 2020 with reirradiation with 35 Gy in 10 fractions in November 2020. She was maintained on bevacizumab and dose dense temozolomide until May 2021, when she complained of shortness of breath.
The patient was referred to our emergency room for admission. She gave a two-week history of shortness of breath associated with productive cough and right-sided pleuritic chest pain. Before coming to the clinic with her new symptoms, she sought medical advice in a nearby clinic and was given a course of antibiotics with no significant improvement in her condition. Her symptoms progressed to the extent that she had severe dyspnea at rest, could not lie flat, and her cough was worse with blood-tinged sputum. She lost her appetite and had a 6-kilogram unintentional weight loss over two months. She did not have any history of fever or exposure history of note. Subsequently, she presented to our emergency department and was found tachypneic, and her other hemodynamics were normal. The patient looked fatigued, and her physical examination was significant for decreased air entry over the right side on chest auscultation with a dull percussion note in the right lower zone.
Her laboratory investigations showed a WBC (white cell count) of 5.7 x 103/muL and two negative COVID-PCR swabs. Her chest computed tomography showed multiple enlarged necrotic mediastinal and bilateral hilar LN, the largest measuring 4.1 x 2.4 cm. She had a moderate right-sided pleural effusion with multiple bilateral pulmonary nodules, with the largest one in the left lower lobe, measuring 2.4 cm. Multiple lytic lesions in the dorsal vertebrae and a sclerotic focus in the manubrium sternum were identified (Figures 1 and 2).
Bedside thoracentesis was done, draining around 1.2 L of clear yellow fluid initially. The pleural fluid cell count showed 723 x 103/UL WBC with a lymphocytic predominance (78% lymphocytes). Gram stain showed no acid-fast bacilli, and the polymerase chain reaction for mycobacterium DNA was not detected. Pleural fluid cytology showed highly atypical cells, and after sometime, GFAP (glial fibrillary acidic protein) immune staining was positive in some atypical cells. After pleural fluid drainage, the patient's symptoms improved, and she was able to lie flat.
The patient underwent EBUS-TBNA the following day as this case was time-sensitive and to confirm wether she has LN metastasis (which is very rare as mentioned) vs. another primary malignancy or other cause. Five and six needle passes were performed from the right lower paratracheal and right interlobar LNs, respectively. The rapid onsite examination from both stations was consistent with adequate lymph node tissue aquisition and highly suspicious for malignancy, and the samples were sent for further pathological examination and cultures. Cytological smears and cellblock demonstrate clusters of hyperchromatic neoplastic cells with small nucleoli and oval to elongated nuclei in a necrotic background. Cytoplasmic extensions were appreciated in some areas (Figure 3). The tumor cells were negative for broad-spectrum epithelial markers (a panel of keratins was employed). All site-specific epithelial markers were negative. Tumor cells, however, were immunoreactive for GFAP, synaptophysin, and S100 protein (Figure 4). Due to the patient's prior history and immunohistochemical results, the findings were considered consistent with metastatis from the patient's known glioblastoma.
A trial of carboplatin/etoposide was entertained, and the patient received 2 cycles before her extraneural disease progressed. Next-generation sequencing (NGS) was performed on the tissue samples, but no actionable mutations were found. Her performance status declined, and she was transferred under the care of the palliative team in July 2021. Unfortunately, she passed away after several months. Treatment timeline is shown in Figure 5.