Page 351 - Haematologica Vol. 109 - July 2024

CASE REPORT
neoepitopes. These neoantigens were prioritized based on predicted major histocompatibility complex (MHC) binding affinity (absolute and quantile rank), excess affinity compared with the non-mutated protein, and protein expression in cancer (Protein Atlas). After filtering with these criteria, we retained 84 neo-peptides for further analysis. As expected, the number of potential neo-peptides was much higher in sarcoma than in AML and GCT. Some of these neo-peptides were shared by two tumors, and ten were common to the GCT, AML, and sarcoma. These 84 peptides were synthetized and tested in pools in interferon (IFN)-γ ELISPOT assays with the patient’s peripheral blood mononuclear cells (PBMC) after 1 week of in vitro amplification. PBMC were obtained after complete donor chimerism. Positive response in two pools containing the common interleukin (IL) 36G16-24 YPSMCKPIT peptide was confirmed using the corresponding peptide (Figure 3). This neoantigen was restricted by HLA-B*54:01, an HLA allele shared between the donor and the patient and was detected in the sarcoma but neither in the GCT nor AML. The neoepitope-specific T-cell response was detected
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again in the patient’s PBMC 7 years after HSCT. Association between GCT and hematologic malignancies is a rare condition, occurring in about 2-5% of patients with pri- mary mediastinal non-seminomatous GCT.1 The median time from diagnosis of GCT to hematologic malignancy is 5 months but both tumors are diagnosed simultaneously in 33% of cases, with median survival from GCT diagnosis ranging from 1 to 6 months.1,3 Sarcomas in patients with GCT are also rare. They are observed mainly in the context of primary mediastinal GCT, bear a poor prognosis and are thought to derive from yolk sac tumors.4 We describe here a case of simultaneous AML and mediastinal GCT, followed by a mediastinal sarcoma. Treatment with combined chemotherapy, allogeneic HSCT/ DLI and surgery resulted in a durable complete remission, possibly maintained through immunosurveillance.
A recent study analyzing 15 patients with GCT and as- sociated hematological malignancies demonstrated that these malignancies evolve independently from a common precursor and not from further differentiation of the GCT:1 Indeed, germ cells and hematopoietic cells are both em-
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Figure 1. Histological analysis of the patient’s tumors.
(A-C) Seminomatous component of the mediastinal tu- mor: (A) hematoxilin and eosin (H&E) staining, (B) pla- cental alkaline phosphatase (PLAP) staining, (C) CD61 staining showing the megakaryocytic differentiation. (D, E) Bone marrow biopsy at initial presentation: (D) H&E staining, (E) CD61 staining showing the megakaryocytic differentiation. (F) H&E staining of the sarcoma that developed in the mediastinum following bone marrow transplantation. The vascular differentiation can be seen by the presence of red blood cells in the cytoplasm of certain cells and was confirmed by ERG staining (data not shown). Magnification x400.
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