CD8-positive T-cell lymphoproliferative disorder associated with Epstein-Barr virus-infected B-cells in a rheumatoid arthritis patient under methotrexate treatment.

We report a 48-year-old female who developed lymphoproliferative disorder (LPD) during treatment of rheumatoid arthritis (RA) with methotrexate (MTX). She presented with multiple tumors in the cervical lymph nodes (LNs), multiple lung shadows and round shadows in both kidneys with pancytopenia and a high CRP level. The LN showed CD8-positive T-cell LPD associated with Epstein-Barr (EB) virus-infected B-cells. Clonality assays for immunoglobulin (Ig) heavy chain and T-cell receptor gamma (TCRγ) were negative. The cessation of MTX without chemotherapy resulted in the complete disappearance of the tumors and abnormal clinical features. We compared this case with previously published ones and discuss the pathological findings, presuming that the proliferation of CD8 T-cells was a reactive manifestation to reactivated EB virus-infected B-cells.

Fluorodeoxyglucose (FDG) uptake in pulmonary rheumatoid nodules diagnosed by video-assisted thoracic surgery lung biopsy: two case reports and a review of the literature.

Two cases of rheumatoid nodules evaluated by fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and video-assisted thoracic surgery (VATS) biopsy are reported. The first case was that of a 44-year-old woman who presented with a cavitated nodule with intense standardized uptake values (SUVs) both in the early (max 3.4) and delayed (max 4.4) phases, suggesting malignancy. However, after VATS biopsy, she was diagnosed as having a rheumatoid nodule with vasculitis. The second case was that of a 74-year-old woman admitted with bilateral lung nodules, two of which showed intense early (max 2.2) and delayed (max 6.0) phase SUVs, and mild early (max 0.6) and delayed (max 0.9) phase SUVs. These two nodules were finally proven to be a lung cancer and rheumatoid nodule without vasculitis, respectively. These cases show that rheumatoid nodules with an enhanced inflammatory process, such as vasculitis, can appear false-positive for malignancy on FDG-PET/CT scan images.

Cardiac swinging calcified amorphous tumors in end-stage renal failure patients.

We recently encountered 2 patients with mobile cardiac calcified amorphous tumors who were successfully treated by surgery. Both patients had mitral annular calcification and were on hemodialysis. These tumors showed swinging motion on echocardiography and they grew rapidly. Intraoperatively, the tumors were found to be fragile and they easily detached from their origin. The histologic findings were thrombus with angiogenesis, fibrin, and calcium deposition. This rapid-growing mobile tumor in end-stage renal failure patients is speculated to increase the risk of embolic events and should be included as a special entity of cardiac amorphous tumors.

Classification of clinical subtypes, patient survival, kidney prognosis, and relapse in patients with MPO-ANCA-associated vasculitis: a single-center experience.

Myeloperoxidase-type antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis may manifest various organ symptoms. Treatment allows recovery from early, but severe, organ involvement. However, the relationship between the initial organ involvement and the eventual clinical course has not been studied in this disease. Therefore, the current study evaluated 30 patients who were hospitalized and then categorized into ten clinical subtypes based on organ involvement. The relationship of these subtypes to development of clinical features, patient survival, kidney prognosis, and relapse were evaluated over an average observation period of 4.3 years. During this study, the most common clinical features were lung and kidney involvement. Twenty-one patients already manifested clinical features around the time of admission and did not commonly present new symptoms as long as they were receiving the treatment for vasculitis. In contrast, as far as pulmonary involvement type at the initial time was concerned and in those not being treated for vasculitis, 7 of the 12 patients progressed to pulmo-renal involvement and 5 of them went onto renal failure. Progression to renal failure also occurred frequently in patients with pulmo-renal type manifesting at the initial time. Thirteen patients died, including three patients due to vasculitis of systemic type, seven due to infections, and three due to malignancy. Death due to vasculitis occurred in the early phase of treatment and was associated with either pulmonary hemorrhage or gastrointestinal bleeding. Infectious death occurred throughout the entire course of treatment, mostly in patients with pulmo-renal or pulmonary type, and tended to be associated with opportunistic organisms. Death with malignancy was observed after several years of treatment. Regarding renal prognosis, ten patients underwent hemodialysis. At initiation of hemodialysis, nine patients had pulmo-renal type and only one had renal type. A relapse was observed in ten patients, mainly in patients with pulmo-renal or pulmonary type, and it occurred after about 2.7 years, even with treatment. Such relapses manifested in a similar manner to their initial clinical subtypes. These results suggest that pulmo-renal type as well as pulmonary type have a high chance to progress to renal failure or systemic type, and they were fairly commonly associated with vasculitic or infectious death. Therefore, classification of clinical subtypes at the initial time and on admission is meaningful to some extent for predicting patient survival, kidney prognosis, and relapse, in addition to indicating the appropriate treatment regimen.

Tubulointerstitial nephritis without glomerular lesions in three patients with myeloperoxidase-ANCA-associated vasculitis.

BACKGROUND: Myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis frequently induces crescentic glomerulonephritis. However, a few cases have so far been reported to have only tubulointerstitial (TI) nephritis without any apparent glomerular lesions. We recently treated three similar cases. Therefore, their pathological features as well as clinical manifestations were studied in detail. METHODS: The pathological study was performed with immunohistochemical staining using various antibodies to the vascular endothelial cell surface markers, von Willebrand factor, type IV collagen, cytokeratin, E-cadherin, and MPO in addition to the routine histochemical examination. RESULTS: The study disclosed the loss of CD34 endothelial cell surface markers with and without the destruction of type IV collagen (capillary basement membrane) in the peritubular capillaries, even though the glomeruli showed good staining of these factors. Electron microscopy showed breaks in the capillary basement membrane. The loss of CD34 staining was associated with the infiltration of a few mononuclear cells and neutrophils in the lumen of peritubular capillaries and the surrounding interstitial tissues. The cytokeratin staining in the tubular epithelial cells was also diminished around these areas. Tubulitis was demonstrated with or without the destruction of the tubular basement membrane. The clinical manifestations of these three cases were only a few red blood cells and granular casts in the urinary sediment as well as slightly increased beta2-microglobulin in the urine, but no proteinuria. CONCLUSION: Based on these findings, the loss of CD34 vascular endothelial markers occurs in the early phase of the disease because of the MPO, which is presumed to have burst out from the infiltrated, activated neutrophils. This MPO, which releases proteolytic enzymes and radical oxygen species, acts on tissue destruction, namely the lysis of endothelial cell membranes as well as vascular basement membranes in the peritubular capillary. This mechanism eventually proceeds to the destruction of the peritubular capillary walls (vasculitis). This pathogenesis is thought to play an important role in the pathogenesis of TI nephritis, which is associated with MPO-ANCA vasculitis.

DMRT-1 expression during NEC8 human embryonic carcinoma cell differentiation.

To elucidate the relationship between dsx and mab-3 related transcription factor 1 (Dmrt-1) and differentiation, alteration in mRNA levels during differentiation of NEC8 human embryonic carcinoma cells was investigated. After stimulation with 50 nM phorbol 12-myristate 13-acetate (PMA), the cells differentiated into cells with mesenchymal characteristics and upregulated Dmrt-1 mRNA, possibly through the protein kinase C/mitogen-activated protein kinase/activated protein-1 signaling pathway. Conversely, knockdown of Dmrt-1 by small interfering RNA resulted in cell morphology that was different from that after PMA treatment. These results indicated that Dmrt-1 expression was apparently associated with the differentiation of NEC8, and this cell line may be a helpful in vitro tool to clarify the role of Dmrt-1 in the differentiation process.