PMC7149248_01
Imaging findings. a-c Computed tomography images on the day of admission. a Massive pleural effusion and slightly enlarged axillary lymph nodes are observed (arrows). b Hepatosplenomegaly is seen. c Massive ascites and slightly enlarged para-aortic lymph nodes are observed (arrows). d
18F-fluorodeoxy-glucose positron emission tomography (FDG-PET) images on day 8. Although the findings are poor (FDG uptake is generally weak), FDG uptake is observed in the para-aortic lymph nodes. e Funduscopic evaluation performed on day 10. Bilateral optic disk edema is remarkable. Roth's spots are observed (arrows). Hemorrhage in the fundus of right eye is also observed
41100_2018_157_Fig1_HTML.jpg
PMC7149248_01_41100_2018_157_Fig1_HTML.jpg
Fig1
Computed tomography (CT) performed on the day of admission revealed massive pleural effusions and ascites, generalized mild lymphadenopathy (< 1.5 cm in diameter), and hepatosplenomegaly (Fig. 1a-c). Echocardiography performed on day 2 revealed normal wall motions without any sign of valvular disease, but a collapsed inferior vena cava was observed (maximum diameter < 5 mm). 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) revealed no apparent FDG uptake, except for slight uptake in the para-aortic lymph nodes (Fig. 1d). On ophthalmological examination, keratoconjunctivitis was not observed; however, bilateral optic edema was remarkable (Fig. 1e).
Pathological findings. a, b Pathological evaluation involving bone marrow biopsy in the present case performed on day 9. a Mild increased number of megakaryocytes is observed (hematoxylin and eosin [H&E] staining). b Mild reticulin myelofibrosis in bone marrow is observed (silver impregnation staining). c-h Pathological evaluation of the right neck lymph node in the present case. c, d Atrophic germinal center, vascular invasion with a glomerular-like pattern of vascular endothelial cell proliferation and hyalinization are observed in the follicles (H&E staining). e Dendric proliferation of arterioles and swelling of vascular endothelial cells are observed (H&E staining). f, g Invasion of plasma cells (CD38+) is observed in the intrafollicular space (immunohistochemical staining). h Immunoglobulin G (IgG) 4-positive plasma cells are observed (> 10 IgG4-positive plasma cells/high power field on immunohistochemical staining); however, the IgG4/IgG ratio is 24.2%, and it does not fulfill the criteria for IgG4-related disease (> 40%, data not shown). Human herpesvirus 8 is negative on immunohistochemical staining, and the Epstein-Barr virus-encoded small RNA in situ hybridization is negative in the lymph node (data not shown). These findings are compatible with mixed-type multicentric Castleman disease-like histology
41100_2018_157_Fig2_HTML.jpg
PMC7149248_01_41100_2018_157_Fig2_HTML.jpg
Fig2
Bone marrow aspiration was dry tap, and bone marrow biopsy revealed a mild increase in megakaryocytes and mild reticulin myelofibrosis on silver impregnation staining (Fig. 2a, b). Biopsy of a cervical lymph node was performed on day 10, and the pathological findings were compatible with a mixed-type MCD histology (Fig. 2c-g).
Clinical course of the present case. a, b The patient became afebrile after pulse methylprednisolone therapy. The C-reactive protein (CRP) level decreased to within the normal range with combination therapy involving intravenous glucocorticoid and oral cyclosporine A. However, despite the treatment, the amount of ascites increased gradually and renal impairment did not improve. The CRP and serum creatinine levels were elevated on day 50, and complicated infection was suspected. After the initiation of continuous renal replacement therapy, the patient experienced cardiac arrest on the same day because of myocardial infarction. Despite intensive care, including antibiotics therapy and continuous hemodiafiltration, the patient died on day 52. BT body temperature, Cre creatinine, CRP C-reactive protein, CRRT continuous renal replacement therapy, CsA cyclosporine A, MAP mean arterial pressure, mPSL methylprednisolone, Plt platelet
41100_2018_157_Fig3_HTML.jpg
PMC7149248_01_41100_2018_157_Fig3_HTML.jpg
Fig3
However, the patient's platelet count and serum creatinine level as well as his overall condition did not improve, even after the initiation of immunosuppressive treatment (Fig. 3a). Diuretics, including furosemide, potassium canrenoate, trichlormethiazide, and tolvaptan were administered during hospitalization; however, the amount of ascites did not decrease (Fig. 3b).
Imaging and assessments after treatment. a Computed tomography (CT) images of the chest on day 50. Pleural effusion resolved, but a mass lesion (arrows) is newly observed. b-d CT images of the heart on days 31, 48, and 50. Scattered appearance of high intensity is gradually seen in the cardiac wall. CT performed on day 31 shows no remarkable finding in the myocardium. However, high intensity gradually became apparent on CT images obtained on days 48 and 50 (arrows). e-g Electrocardiogram performed after recovery of spontaneous circulation and coronary angiography (CAG) results on day 50. e ST elevations are observed at leads V2-5 and aVL. Reciprocal changes are observed at leads I, II, and aVF on electrocardiography. f CAG shows complete occlusion of the left descending coronary artery (arrows). g After percutaneous old balloon angioplasty, reperfusion of blood flow is achieved
41100_2018_157_Fig4_HTML.jpg
PMC7149248_01_41100_2018_157_Fig4_HTML.jpg
Fig4
CT of the chest showed a mass in the right lung (Fig. 4a) in addition to scattered appearance of high intensity regions in the myocardium, which were newly observed (Fig. 4b-d). STEMI was suspected from electrocardiography findings obtained immediately after ROSC (Fig. 4e). On CAG, complete occlusion of the left anterior descending coronary artery was observed, and reperfusion was achieved through percutaneous old balloon angioplasty (Fig. 4f, g).
Histological findings on autopsy. a In lymph nodes, infiltration of CD38+ plasma cells was observed in the intrafollicular space (immunohistochemical staining of CD38). However, the number of plasma cells is decreased compared with that before treatment (Fig. 1f). b Double contour of the glomerular basement membrane with mild mesangiolysis is observed in the glomeruli (periodic acid-methenamine silver staining). c Subendothelial swelling is observed (electron microscopy). d Macroscopic appearance of a cross section of the heart revealed necrotic areas with dark reddish-brown color, corresponding to the anterior wall and septum. Left ventricle walls were thickened, and cardiac hypertrophy was observed (weight, 460 g). e Calcification is observed most remarkably in myocardial cells. Some of the myocardial cells are replaced by calcified tissue, and the remaining myocardial cells are intact (hematoxylin and eosin [H&E] staining). f Calcification is also observed in the skeletal muscle cells of the diaphragm (H&E staining). g In the right lung, fungal hyphae are abundant (Grocott staining). h In the lungs, intravascular invasion by fungal hyphae is observed (H&E staining). i Intra-alveolar invasion by fungal hyphae is observed (H&E staining). j Enlarged cells with intra-nuclear inclusion are remarkably observed in the lungs (H&E staining). k These cells are positive for cytomegalovirus (CMV) infection (immunohistochemical staining of CMV). l Subcutaneous tissue of the anterior mediastinum shows that fat tissue is largely replaced by fibrotic tissue. No infiltration of inflammatory cells is observed, and no remarkable finding in tissue of the thymus is noted (H&E staining)
41100_2018_157_Fig5_HTML.jpg
PMC7149248_01_41100_2018_157_Fig5_HTML.jpg
Fig5
The histological findings of autopsy are shown in Fig. 5.