PMC6437980_01
Skin lesions on trunk and upper limb. a Cutaneous eruption on trunk. b Vesiculo-bullous elements within scattered erythematous plaques, lacking Nikolsky's sign, on trunk
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Fig1
Hodgkin lymphoma, treated with 12 different therapeutic regimens due to multiple relapses, including successively ABVD, radiotherapy, cisplatin containing regimen and autologous stem cell transplantation after BEAM conditioning regimen (year 4) (Additional file 1: Figure S1). He relapsed again, and was treated successively by bendamustin, FMS tyrosine kinase inhibitor, ICE, holoxan; bendamustin, and a first allogeneic stem cell transplantation from one of his HLA-matched sister (year 9) (conditioning regimen: Fludarabine 30 mg/m2 day 1-5; busulfan 3.2 mg/kg day 3 and 4; antithymocyte globulin 2.5 mg/kg day 5 and 6. 98% donor-type chimerism was achieved after this first allo-SCT. There were remaining patches of unaffected skin (Fig. 1).
Progression to heart block. Electrocardiography showing regular rhythm at a rate of 55 bpm with normal QRS complex duration and morphology. AS atrial rate (70 bpm) was faster than the ventricular rate (55 bpm), and PP interval was constant with no relationship between the P waves and QRS, demonstrating atrioventricular dissociation
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Fig2
Moreover, troponin was elevated (4 microg/L) without any evidence of myocardial infarction; ECG (Fig. 2) showed regular rhythm at a rate of 55 bpm with normal QRS complex duration (< 0.12 s) and morphology. PD-L1 was found to be expressed on inflammatory cells, as well as on Kupffer and endothelial cells (Additional file 2: Figure S2).
Extensive immune infiltrate in skin biopsies. Skin biopsies were fixed in formal acetic alcohol and included in paraffin. a HES staining at low magnification (x100). b HES at high magnification (x400), lymphocytes CD3 + (c), CD4 + (d), CD8 + (e) located along the dermoepidermal junction, at low magnification (x100) (f) and g immune cells and keratinocytes PD-L1 + at low (e x100) and high magnification (f x400)
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Fig3
A skin biopsy was analyzed by HES coloration (Fig. 3a, b) after hospitalization, 3 months after the second allograft. Immunohistochemistry revealed the presence of numerous CD3 + lymphocytes, with similar proportions of CD4 + and CD8 + lymphocytes (Fig. 3c-e). PD-L1 was found to be expressed in the inflamed dermoepidermal junction and in the epidermis both on immune cells and on keratinocytes (Fig. 3f, g). 
Immune infiltrate in muscle tissue. HES staining and immunohistochemistry analysis on muscle biopsy frozen in isopentan. a HES staining at low (x100) and b moderate magnification (x200) showing an important inflammatory endomysial infiltrate. Images of myophagia are seen. c HLA class I (x100) and d HLA class II (x100) stainings show a diffuse pattern with strong sarcoplasmic membrane positivity. Lymphocytic infiltration was also assessed. e Some CD68 + histiocytes are seen (x200), while a predominant CD3 + lymphocyte infiltration (x100) was observed (f), consisting mostly of CD4 + (x100) (g) but few CD8 + lymphocytes (h x100). i) to k) PD-L1 expression is shown at low (i x100), moderate (j x200) and high magnification (k x400). PD-L1 was found to be expressed in the inflamed area, both on immune cells and myocytes
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Fig4
A muscular biopsy was performed 3 months after the haplo-SCT, and showed foci of endomysial inflammation (Fig. 4a, b). There was evidence of acute necrotizing myositis characterized by several foci of necrotic muscle fibers, macrophage activity and some regenerative fibers (Fig. 4b arrows highlight some basophilic fibers with nuclear internalizations). There was massive lymphoid-histiocytic infiltration of muscle fibers (Fig. 4b). The infiltrating cells were mostly CD3 + , although some CD68 + macrophages were present (Fig. 4e, f). In the endomysium, CD4 + lymphocytes were in higher density than CD8 + (Fig. 4g, h). The expression of both HLA molecules was also sarcoplasmic in the inflammatory foci (Fig. 4c, d), confirming the diagnosis of myositis. PD-L1 was found to be expressed in the inflamed area, both on immune cells and myocytes (Fig. 4i-k).