PMC6377617_01
Overview of the case, including targeted response of a metastatic MPTT to PI3K inhibition. a Timeline of the patient's course of disease starting with her neck dissection at a tertiary care center. Note: as detailed in the text, the patient had a recurrent posterior scalp lesion treated with local excisions for many (10+) years prior to her neck dissection. b Hematoxylin and eosin (H&E) stain of original diagnostic biopsy (4x). Note: (1) the dermal proliferation of convoluted lobules that infiltrate the deep dermis and subcutis, with tricholemmal type keratinization typical of PTT (dashed ellipse); and, (2) in the deeper sheets of cells there is cytologic atypia, increased mitoses, and infiltrating margins diagnostic for MPTT (dashed box). c CT scans of patient demonstrating radiographic response of MPTT to BYL719 (alpelisib). Left images = patient after six cycles of chemotherapy (largest paratracheal mass diameter = 13 mm; largest subcarinal mass diameter = 19 mm); right images = patient after 3 months of treatment with alpelisib (largest paratracheal mass diameter = 4 mm; largest subcarinal mass diameter = 9 mm). LN = lymph node. d Molecular response of MPTT to alpelisib. H&E and Ki67 (a marker of cellular proliferation) of tumor tissue before alpelisib treatment (top) and after 3 months of alpelisib treatment (middle). Nearby healthy skin (bottom) was also biopsied 3 months after initiation of alpelisib treatment and demonstrates normal proliferation of stratum basale. e) Quantification of tumoral Ki67 positive nuclei before and during treatment with alpelisib. Data are presented as mean +- standard deviations (n = 3 separate sections of >=100 nuclei). **p = 0.0036 by unpaired t-test
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Fig1
SCC to MPTT (Fig. 1b). Subsequently, the patient was referred to a head and neck surgeon for modified radical posterior neck and lymph node dissection. After 3 months of treatment, she demonstrated a partial response per RECIST (Fig. 1c and S1). Additionally, an on-treatment research biopsy, obtained 3 months after the start of alpelisib, demonstrated a significant reduction in proliferation as assessed by Ki67 staining (Fig. 1d, e).
Genomic characterization of a metastatic MPTT. CIRCOS-style plot demonstrating the position of mutations, CNVs, and SVs found in a metastatic MPTT by WGS. Each chromosome is delineated by the appropriate letter or number and the corresponding color-matched segments of the concentric rings. The segments of the outermost ring represent the normal relative length along/of each chromosome. Points and text along each of the chromosomes indicate the position of the 43 non-silent coding mutations identified in the tumor. The segments of the inner ring represent CNVs along the length of each chromosome. The outer boundary of these segments is the baseline copy number of 2 (diploid), and the inner boundary is scaled to a copy number of 10. Bars in each of these segments indicate copy number loss or gain, with the size and direction of the bar correlating with the magnitude of gain or loss. The center of the plot displays any/all SVs, including inter and intra-chromosomal translocations, insertions, and deletions
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Fig2