PMC10004274_01
Histologic sections showed a highly cellular glial tumor with a solid growth pattern, brisk mitotic activity, microvascular proliferation, and palisading necrosis (A). Immunohistochemistry revealed high Ki-67 expression (B) and strong cytoplasmic ALK expression (C).
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A panel of immunohistochemistry supported the diagnosis of HGG (Figure 1).
Schematic of ATIC-ALK fusion. Diagram showing chromosome 2 (courtesy of UCSC genome browser; ; with approximate locations of ALK (2p23) and ATIC (2q35). The inversion and subsequent fusion between the 5' end of ATIC to the 3' end of ALK leads to activation of the ALK kinase. For our patient, the fusion is noted specifically between exon 7 of ATIC and exon 20 of ALK.
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ATIC (exon 7) and ALK (exon 20) (Figure 2). Additional (Ashion) testing through the precision medicine program at our center confirmed the ATIC-ALK fusion at both the DNA and RNA level.
Pre (A, D, G), Post 1 (10 weeks) (B, E, H) and Post 2 (6 months) (C, F, I) ALK inhibitor administration. Pre-treatment images demonstrate nodular lesions near the splenium of the corpus callosum (arrows in D, G) and along the floor of the third ventricle (arrow in A). Post-treatment images (Post 1) demonstrate substantial decrease in size of both lesions (arrows in B, E, H). Continued decrease in lesion size is seen on Post 2 images (arrows in C, F, I).
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Subsequent brain MR imaging after 10 weeks of daily lorlatinib treatment revealed a partial response in the largest residual tumor lesion and complete response on the smaller tumor nodules (Figure 3) and 6 months after starting lorlatinib, near complete response on all the residual tumor nodules (Figure 3).
Timeline of major clinical events since diagnosis to present day.
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At the time of this report, the patient continues on daily lorlatinib therapy (See timeline Figure 4).