Contributed by Alireza Shams, MD and Katherine Schwetye, MD, PhD
Department of Pathology, Saint Louis University, Saint Louis, MO, USA.
The patient was a 68-year-old female with a longstanding history of psoriasis and hypertension, as well as multiple sclerosis since 2013. In October of 2015, she was started on oral methotrexate for treatment of her psoriasis. Due to worsening symptoms, she was started on secukinumab, an interleukin-17 antagonist. After taking secukinumab for 4-5 weeks, large masses developed on her right forearm and buttock. Her dermatologist discontinued the secukinumab and performed a skin biopsy of the lesions on May of 2016, which showed findings consistent with a cutaneous T-cell lymphoma.
In June of 2016, patient presented with seizures. Brain MRI (Fig. 1a) showed gyriform enhancement in the medial aspect of the right frontal lobe, including the right cingulate gyrus, as well as a smaller area of enhancement in the posterior right frontal lobe. PET scan showed high signal in the right medial frontal lobe (Fig. 1b).The patient was started on anti-seizure medications.
In September of 2016, the patient started to have left-sided weakness, difficulty finding words, and difficulty walking. Brain MRI scans (Figs. 1c, 1d)showed increased T2/FLAIR hyperintensity and enhancing lesions in the right frontal and parietal lobes with further extension into the right parietal lobe, corpus callosum and the medial aspect of left frontal lobe, including the left cingulate gyrus. The increased surrounding edema and mass effect resulted in 5 mm right-to-left midline shift. A biopsy of the right frontal lobe lesion was performed in September of 2016.
MICROSCOPIC PATHOLOGY - BIOPSY
Microscopic examination of the right frontal lobe biopsy demonstrated a proliferation of lymphoid cells with very little intact brain parenchyma, consistent with a mass-like, destructive process (Fig. 1e). These cells were frequently clustered around vessels, mostly small to moderate in size with an atypical appearance; the nuclei were round and chromatin frequently arranged in a "soccer-ball" or clock face configuration with some perinuclear haloes (Fig. 1f). Foamy macrophages and scattered, benign-appearing plasma cells interspersed in variable densities. A subset of lymphoid cells showed slightly enlarged, irregular, grooved nuclei and hyperchromatism. Focally, there were increased mitotic figures and apoptotic cells. Tumor necrosis was identified.
Ancillary work-up showed tumor cells to be immunopositive for CD3 (Fig. 1g), CD4 (Fig. 1h), CD7 (Fig. 1i), and CD8 (Fig. 1j) but predominantly negative for CD5 (Fig. 1k). All tumor cells were immunonegative for CD20, PAX-5, in-situ hybridization of Epstein-Barr virus encoding RNA (EBER), and CD30. A Luxol fast blue-periodic acid Schiff stain (LFB-PAS) demonstrated no significant myelinated axons; neurofilament immunostains showed a few interspersed axons among the cellular infiltrate. What is your diagnosis?