PMC9207126_01
(A) Microscopic appearance of the tumor characterized by solid sheets of highly atypical cells (H&E x600). (B) Immunohistochemistry stain against TTF-1 shows strong nuclear positivity (immunohistochemistry x400). (C) Immunohistochemistry stain against napsin-A shows strong cytoplasmic positivity (immunohistochemistry x400). (D) Immunohistochemistry stain against PD- L1 shows a negative staining (immunohistochemistry x400).
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Pathological sections showed fragments of skeletal muscle fibers and fibroadipose tissue infiltrated by a tumor characterized by ill-defined glandular structures as well as showing solid sheets of pleomorphic polygonal cells some with cytoplasmic mucin (Figure 1A). PAPH and PSA. PD-L1 (TPS) is negative (Figure 1D).
Axial post contrast fat saturated images of the brain: before (A) and 14 days (B), and three months (C) post-osimertinib. (A) Before treatment showing multiple small enhancing foci in the left cerebellar hemisphere (blue arrow), abnormal enhancement involving the perimesencephalic cistern (yellow arrow) and abnormal enhancement of the trigeminal nerve bilaterally (red arrows). (B) After treatment showing almost complete clearance of the abovementioned nodules in left cerebellar hemisphere, the abnormal enhancement in the perimesencephalic cistern and the trigeminal nerves. (C) After three months treatment showing persistent improvement with no detected nodules or meningeal enhancement.
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Magnetic resonance imaging (MRI) of the brain showed abnormal sulcal and cisternal enhancement representing extensive leptomeningeal metastases, with small cerebellar and cerebral cortical metastases (Figure 2A). Furthermore, a decrease in the leptomeningeal regions (Figure 2B). A month later, November 2019, a follow-up PET scan showed favorable response (Figure 3), and in January 2020 a follow-up MRI for brain and spine showed regression of the tiny cerebral enhancing metastatic lesions (Figure 2C).
18F-FDG PET/CT maximum intensity projection (MIP) images and sagittal fused PET/CT images. Staging 18F-FDG PET/CT maximum intensity projection (MIP) image (left side) showing FDG-avid left lung, adrenal lesion and some bone metastases (left humerus, right iliac wing). Sagittal fused PET/CT image (middle image) showing no evidence of meningeal involvement. Follow-up PET/CT MIP image (right side) demonstrates near complete resolution of lung, adrenal and right iliac wing lesion as well as decreasing uptake in the left humerus.
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PET scan showed disease progression (Figure 3). Patient refused a lumbar puncture. A month later, November 2019, a follow-up PET scan showed favorable response (Figure 3), and in January 2020 a follow-up MRI for brain and spine showed regression of the tiny cerebral enhancing metastatic lesions (Figure 2C). PET scan showed practically stable presentation (Figure 3).
Real time-PCR analysis for EGFR hotspots, real time-PCR results of EGFR gene for L858R and T790M. The DNA was extracted from FFPE using Promega kit following manufacturer instructions (Cat No: AS1130) and the results obtained using Entrogen kit for EGFR mutation analysis (EGFR-RT52) and analyzed by Quant Studio Dx in accordance with CAP guidelines for molecular genetics laboratory.
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The T790M-mutation was not detected in this biopsy (Figure 4).
(A) Axial CT scan of the brain without IV contrast (patient cannot do MRI and cannot receive IV contrast because of rising creatine), this limited study shows thickening of the right tentorium in comparison to left one suggesting meningeal involvement (arrow in A). (B) Axial CT scan of the brain without IV contrast (patient cannot do MRI and cannot receive IV contrast because of rising creatinine), shows almost complete clearance of the thickened right tentorial leaflet (arrow in B).
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In April, the patient showed up following a syncope and fall, CT scanning was performed for the head and showed changes related to the leptomeningeal metastasis with thickening of the tentorium cerebelli and along the right greater wing of sphenoid (Figure 5A). In July, while presenting with seizures, CT scanning of the head showed reduction in the leptomeningeal and tentorium cerebelli thickening (Figure 5B).