case_images: PMC10030599_01
case_images: PET/CT image of 18F-deoxyglucose (FDG) uptake in the patient (male, 45 years of age) with multiple lymph node enlargement. (A). PET/CT maximum intensity projection (MIP) image displaying multiple groups of metabolically elevated lymph nodes throughout the body, with bilaterally general symmetry and mildly increased splenic metabolism. (B-G). Cross-sectional images in PET/CT showing generalized multiple enlarged lymph nodes, hepatosplenomegaly, and bilateral abnormally enlarged tonsils together with increased metabolism; and active involvement of generalized bone metabolism.
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case_images: Subsequent hybrid imaging with 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) revealed generalized and multiple enlargements of the lymph nodes, hepatosplenomegaly, and bilateral tonsillomegaly:with augmented glucose metabolism throughout the body ( Figure 1 ).
case_images: Pathologic histology of histiocytic sarcoma. (A), Structural disruption of the lymph nodes under the microscope, along with marked proliferation of small vessels and a diffuse distribution of cells with slightly larger nuclei and abundant cytoplasm (H&E staining, x100). (B), Severe inflammatory cell infiltration in the alternating bright and dark areas; distribution of lymphocytes and plasma cells around the vessels in a target ring-like pattern (H&E staining, x400). Immunostaining of tumor cells with positive staining for (C), CD68 and (D), S-100, respectively (IHC, x 400). (E), Membrane staining for the most specific histiocytic marker, CD163+ (IHC, x 400). (F), Diffuse staining for PD-L1+ in the tumor cells (IHC, x 400).
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case_images: Biopsy of the right supraclavicular lymph node was ultimately performed on September 3 after a general surgery consultation, and the final pathologic diagnosis was consistent with primary HS ( Figure 2 ). The sections for hematoxylin-eosin (H&E) staining ( Figures 2A, B ) revealed structural disruption of the lymph nodes with patches of large neoplastic cells that were markedly atypical cytologically, proliferation of small vessels, and diffusely distributed cells with slightly larger nuclei and abundant cytoplasm. Extensive immunohistochemical studies ( Figures 2C-E ) showed that the tumor cells were positive for CD163, CD68, S100, Lys, and CD34; and negative for CD1a, CD207, HMB45, MPO, and CD30. Further immunostaining for PD-L1 was positive as over 80% of the tumor cell membranes were stained ( Figure 2F ).
case_images: The clinical process comprising the patient's treatment. Supportive therapy: anti-infective therapy, anti-allergic therapy, dexamethasone to reduce fever, and blood transfusion. PD-1 inhibitor, sintilimab; AEVD, epirubicin (50 mg on d 1), etoposide (100 mg on d 1), vincristine (3 mg on d 1) and dexamethasone (15 mg on d 1); ID, intravenous drip; DEC, dexamethasone (10 mg on d 0-14), etoposide (100 mg on d 1-2 and d 8) and chidamide (20 mg biw; i.e., every Wednesday and Saturday); PD, progressive disease; and PR, partial response.
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case_images: A combination chemotherapeutic regimen of PD-1 inhibitor + AEVD (epirubicin/etoposide/vincristine/dexamethasone) was implemented on September 15 ( Figure 3 ) that consisted primarily of sintilimab (200 mg on d 0), epirubicin (50 mg on d 1), etoposide (100 mg on d 1), vincristine (3 mg on d 1), and dexamethasone (15 mg on d 1) in a 21-d course:supplemented by supportive treatment.
case_images: Gene mutations detected in the patient: (A). IDH2, (B). RHOA, and (C). TET2. (D). Specific information on the primary mutated genes provided by the sequencing company. NS mutation, non-synonymous mutation; FS deletion, frame-shift deletion; SA, spliceosome abnormalities; TA, terminator acquisition.
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case_images: TET2 ( Figure 4 ). A novel missense mutation [c.50G>T, p.Gly17Val (NM_001664)] was also found in RHOA gene; non-synonymous mutation [c.515G>A, p.Arg172Lys (NM_002168)] in IDH2 gene; and c.3344delC, p. Pro1115fs (NM_001127208) in TET2 gene, with a frame-shift deletion mutation and a splicing mutation at c.3501-2A>C (NM_001127208). These mutations are known to be damaging mutations associated with high response to drugs classified in the epigenetic modification category, i.e., histone deacetylase inhibitors (HDACis).