case_images: PMC11021630_01
case_images: Brain, eye orbit, and paranasal sinus MRI and bilateral lower eyelid edema. (A) MRI of brain, eye orbits, and paranasal sinuses showing bilateral obliteration of the ethmoid-maxillary sinuses, an inflammatory thickening of the periorbital subcutaneous adipose tissue, hypointense in T2 in both orbits, but more evident in the right orbit and brain atrophy and fuzzy T2 hyperintensity of the peritrigonal white matter and corpus callosum. (B) Bilateral lower eyelid edema at admission (top panel) and during the following weeks before rituximab treatment (bottom panel).
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case_images: Brain imaging was performed to exclude neurological involvement, revealing atrophy and fuzzy T2 and FLAIR hyperintensity of the peritrigonal white matter and corpus callosum ( Figure 1A ). The bilateral lower eyelid edema ( Figure 1B ) was suggestive of pre-septal orbital cellulitis and was initially treated with local steroids and systemic antibiotics, based on the eye swab culture, positive for Staphylococcus hominis. In both orbits, but more evident in the right one, there was an inflammatory thickening of the periorbital subcutaneous adipose tissue, hypointense in T2 ( Figure 1A ). No bony discontinuity was detected ( Figure 1A ), and this was also confirmed at the CT scan (not shown).
case_images: Histological examination of the lower right eyelid incisional biopsy. (A) Dense lymphohistiocytic infiltrate extending throughout the biopsy (hematoxylin and eosin staining, original magnification 20x). (B) The infiltrate is composed mainly of T-lymphocytes (CD3+) and (C) histiocytes (CD68+) (CD3 and CD68 immunohistochemical staining, original magnification 10x). (D) Positive signal upon in situ hybridization for EBV (EBER) (EBER immunohistochemical staining, original magnification 4x).
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case_images: The biopsy revealed a marked lymphohistiocytic infiltrate within the fibrous tissue, also characterized by some foci of necrosis and a vascular network consisting of branching vessels, with a slightly thickened wall ( Figure 2A ). T lymphocytes, small and medium-sized cells with irregular nuclei, positive for CD2, CD3 ( Figure 2B ), CD5, and CD8 and a few B-lymphocytes. The staining for CD68 revealed many histiocytes ( Figure 2C ), negative for protein S100 and CD1a. TDT, CD30, pan-cytokeratin, and desmin were also negative. On in situ hybridization with EBER probe, many lymphocytes/macrophages were positive ( Figure 2D ).
case_images: Changes in the main laboratory parameters of peripheral hemophagocytic lymphohistiocytosis (HLH) and plasma EBV-DNA levels over time. A therapy based on dexamethasone and anakinra was established to treat HLH, and an initial decrease in both biochemical values and EBV titer with an increase in hemoglobin levels was obtained by the second week of therapy. At week 4, when an increase in EBV-DNA level and persisting hypertransaminasemia were detected, rituximab was started, and a dramatic improvement was achieved. Hemoglobin levels are shown in green and are referred to the left Y axis. The remaining values are indicated with different symbols, as specified in the legend, and are shown on the right Y axis.
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case_images: After 2 weeks of treatment, we observed a resolution of fever and splenomegaly and a significant increase in hemoglobin and decrease in ferritin levels ( Figure 3 ) and total lymphocyte count. However, after an initial decrease, EBV titer increased up to 50,000 IU/mL and hepatomegaly and hypertransaminasemia persisted under steroid therapy ( Figure 3 ). Figure 3 ). Finally, the patient underwent a successful hematopoietic stem cell transplant (HSCT).