PMC5977423_01
Pathologic findings and immunohistochemical staining for the mTOR pathway using paraffin embedded sections of the patient's tumor tissue. (a) Diffusely proliferating spindle neoplastic cells are merging with sporadical glomeruloid structures. Dilated lymphatic channels are in the periphery of the tumor nodule beneath the epidermis. (b) Neoplastic cells are forming compressed vessels with brown stippled hemosiderin. (c) D2-40 is identified in the neoplastic cells sparing central area of a glomeruloid structure. D2-40 is densely expressed in the surrounding lymphatic channels. The sections have also been stained for primary antibodies to (d) mTOR, (e) phospho-mTOR, (f) AKT1, and (g) phospho-AKT. The endothelial cells of stromal vessels in the KHE tissue (black arrows) expressed AKT and mTOR proteins that are also positive when probed with anti-phosphoprotein AKT (p-AKT), and anti-phosphoprotein mTOR (p-mTOR) antibodies.
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Tissues were sliced in 4-mum sections and then stained with hematoxylin and eosin (Figure 1(a), x7 and (b), x40). Immunohistochemical analysis revealed that the neoplastic cells were positive for CD31, CD34, and D2-40 (Figure 1(c)). AKT and mTOR, using paraffin embedded sections of the patient's tumor tissue. AKT and mTOR proteins were positive in the cytoplasm of endothelial cells that lined stromal vessels in KHE tumor tissue and these cells were also positive when probed with anti-phosphoprotein AKT (p-AKT) and mTOR (p-mTOR) antibodies (Figure 1(d)-(g)), indicating constitutive activation of the AKT/mTOR signaling pathway in the KHE.
Clinical course.. VCR: vincristine; RCC: red cell concentrates; PC: platelet concentrates.
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Ten years after the initial diagnosis, the patient presented with painful facial ecchymosis with subcutaneous induration (Figure 2). Magnetic resonance imaging (MRI) revealed that the KHE infiltrated the subcutaneous tissue with deterioration of KMP (Figure 2). Two weeks after the patient was started on sirolimus, the hemoglobin level had increased from 8.5 to 10.1 g/dL, and after 3 weeks, the platelet count had increased from 24 x 103/microL to 44 x 103/microL (Figure 2). After 2 months, MRI showed marked shrinkage of the vertebral KHE lesions demonstrated as high-intensity areas on T2-weighted imaging (Figure 2). The patient was then treated with sirolimus alone for 23 months and further improvements were identified on blood tests, MRI (at 9 months), and physical examination (at 36 months) without side effects (Figure 2).