PMC9810838_01
Side-by-side comparison of coronal CT imaging on diagnosis notable for significant ascites and large mass (A), relapse with recurrent ascites (B), and after 5 years on crizotinib therapy without malignant ascites and persistent necrotic mass (C). Red arrows represent areas of tumor, and yellow arrows represent areas of malignant ascites. When both red and yellow arrows are close together, this area represents known tumor that is obscured by malignant ascites in the pelvis.
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At the time of presentation, a large right adnexal mass was identified by computed tomography measuring 15 cm x 11 cm x 13 cm with omental involvement and large-volume ascites present (Figure 1). The patient remained stable for 4 years on crizotinib monotherapy without disease progression based on follow-up imaging, and parents decided to discontinue therapy (Figure 1). The most recent follow-up obtained in July 2022, 6 years after initiation of crizotinib and 18 months off therapy demonstrated ongoing disease stability without symptoms or evidence of progression (Figure 1).
Anaplastic lymphoma kinase immunohistochemistry (IHC) was performed by Paradigm Cancer Diagnostics (PCDx). Appropriately reacting controls have been performed for all immunohistochemical (IHC) stains. The IHC stains were developed and their performance characteristics determined by Paradigm. Paradigm is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) as qualified to perform high-complexity clinical laboratory testing. IHC scoring ranges from 0 to 4+ in intensity and 0% to 100% in percent noted in tumor sample. IHC for ALK demonstrated increased expression throughout tumor samples (2+ staining intensity in 30% of tumor sample). No pathologic mutations or gene rearrangements in ALK were identified on targeted sequencing by Ignyta.
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IHC testing was positive for anaplastic lymphoma kinase (ALK) protein (2+ staining intensity, 30% of tumor sample; see Figure 2) and neurotrophic tyrosine receptor kinase TRK/NTRK (80%), suggesting that either ALK or TRK/NTRK1/2/3 could be a targetable driver in the tumor. With few options remaining, crizotinib was selected as a therapeutic/palliative target based on the increased levels of ALK protein expressed in the patient's tumor (Figure 2).