PMC5896417_01
Sagittal T1 postcontrast image of the lumbar spine with multiple rim-enhancing lesions as indicated by white arrows.
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fig1
Magnetic resonance imaging (MRI) of the thoracolumbar spine to evaluate low back pain showed pathologic process involving the marrow of all visualized osseous structures (Figure 1) which prompted a BM biopsy.
Immunohistochemical stain of bone marrow core biopsy with extensive involvement by poorly differentiated high-grade malignant neoplasm. Positive MART1 stain (a) and positive S100 stain (b).
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Cytogenetic analysis revealed a hypertriploid karyotype with multiple numerical and structural chromosome abnormalities. This cell demonstrates many, but not all, of the abnormalities designated in the composite karyotype, which was based on examination of twenty metaphase cells. Such complex karyotypes are common in high-grade malignancies, including metastatic melanoma.
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fig3
TTF1, AE1/3, HepPar1, Glypican3, PAX8, HCG, CK5/6, P63, and OCT3/4, thus excluding other solid malignancy. Conventional cytogenetic analysis of the bone marrow biopsy revealed an abnormal complex hypertriploid karyotype with 77-79 chromosomes in 18/20 metaphase cells. The composite karyotype was designated as follows: 77-79(3n)XX, -X, add(2)(p21), +add(2)(q11.2), +4, add(5)(q11.2), +add(5)(q11.2), add(6)(q12), +7, +7, +8, +8, +9, -10, -11, +13, +15, +16, -19, +20, +21, +22[cp18]/46, XX (2) (Figure 3).
Immunohistochemical stain of the scalp lesion. Positive S-100 (a) 20x, SOX-10 (b) 20x. S-100 is a cytoplasmic stain, proving the malignant cells are originating from the neural crest derived tissue (melanocytes, glial cells, and Schwann cells). SOX-10 is a nuclear stain, confirming that the malignant cells are melanocytes.
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Biopsy of the scalp lesion (Figure 4) revealed prominent intraepidermal atypical melanocytes with pagetoid spread, as well as the presence of well-formed junctional melanocytic nests, characteristic for malignant melanoma with superficial spreading pattern and stained positive for S-100 and SOX-10.
FDA-approved immunohistochemical stain for PD-L1, clone 28-8, (OPDIVO ) positive in 10.0% tumor cells with weak intensity.
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fig5
Tumor cells had 10% PD-L1 expression on formalin-fixed-paraffin embedded tissue sections using the United States Food and Drug Administration (FDA) approved programmed death ligand 1 (PD-L1) Immunohistochemical (IHC) stain 28-8 pharmDx, a monoclonal rabbit anti-PD-L1 (Figure 5).
Trend of hemoglobin (a) and platelet (b) lab values. Week 0: at diagnosis. Treatment was initiated on Day 3 and patient was transfusion-independent by Week 8.
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The patient had an excellent response to the combined immune-checkpoint inhibitors, becoming transfusion-independent after 2 treatment cycles followed by complete resolution of bicytopenia (Figure 6).