Epstein-Barr Virus-Positive Cutaneous and Systemic Plasmacytosis with TAFRO Syndrome-like Symptoms Successfully Treated with Rituximab.

Histopathologic findings in the lymph nodes of patients with thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome are similar to those of idiopathic multicentric Castleman's disease (iMCD), but TAFRO syndrome is different from iMCD in how it can progress rapidly and be fatal. These patients present scarce lymphadenopathy and low immunoglobulin levels. We present a case of cutaneous and systemic plasmacytosis (C/SP) that caused TAFRO syndrome-like symptoms which were successfully treated with rituximab. A 67-year-old woman presented with fever and a pruritic skin rash. Numerous plasma cells were observed in the peripheral blood and imaging revealed organomegaly, anasarca, and generalized lymphadenopathy. Subsequently, she rapidly developed thrombocytopenia as well as renal and heart failure. She tested positive for the Epstein-Barr virus (EBV), elevated immunoglobulins, and C/SP, which are also atypical for TAFRO syndrome, thereby complicating the diagnosis. However, after using the Japanese TAFRO Syndrome Research Group diagnostic criteria, we promptly administered rituximab to treat the C/SP with TAFRO-like symptoms and saved her life. Finally, histopathological observations of the lymph node biopsy helped confirm EBV-positive hypervascular-type iMCD. Therefore, diagnosing TAFRO-like syndromes based on the Japanese diagnostic criteria and following the associated treatment even without a confirmed diagnosis is crucial to improving the patient outcomes.

[Autoimmune hemolytic anemia complicated with acute kidney injury and tubulopathy due to hemoglobin casts].

A 62-year-old male patient was admitted for close monitoring of anemia (hemoglobin level, 8.2 g/dl). Hemolytic anemia was observed; however, the direct antiglobulin test (DAT) result (standard tube method) was negative. Nevertheless, autoimmune hemolytic anemia (AIHA) was still suspected; therefore, a DAT (Colum method) and quantifying levels of red-blood-cell bound immunoglobulin G were performed, resulting in a definite diagnosis of warm AIHA. The patient also had an acute kidney injury (AKI) from the time of admission, which was poorly improved by supplemental fluids therapy alone. Therefore, renal biopsy was performed. Renal biopsy revealed acute tubular injury due to hemoglobin columns, and a diagnosed AKI caused by hemolysis due to AIHA. Following the definitive diagnosis of AIHA, the patient was treated with prednisolone, and after approximately 2 weeks, the anemia and nephropathy completely improved, which is maintained to this day. We report this case as a rare case of AKI induced by hemolysis of AIHA and a successful case of renal salvage by early administration of steroid.

[Successful treatment with ponatinib in combination with hyper-CVAD for chronic myeloid leukemia in the lymphoid blastic phase].

The prognosis of chronic myeloid leukemia (CML) has improved dramatically with the introduction of tyrosine kinase inhibitors. Although the use of second-generation tyrosine kinase inhibitors is now available for initial cases, a small number of patients with CML unfortunately still experience progression to the accelerated or blastic phase of the disease. We recently managed a patient with chronic-phase CML, who developed a T315 mutation early in the course of treatment with dasatinib and progressed to the lymphoid blastic phase. The patient responded quickly to ponatinib therapy in combination with hyper CVAD, leading to cord blood transplantation. We report here the first case of a patient with CML in the lymphoid blastic phase treated with ponatinib in combination with hyper CVAD, which was tolerable despite adverse events such as infection, bilirubin elevation, and hypertension, and who was able to proceed to transplantation after achieving a complete molecular response.

Discontinuation of sorafenib can lead to the emergence of FLT3-ITD-positive acute myeloid leukemia.

A 69-year-old woman who had been diagnosed with unresectable papillary thyroid cancer was referred to our hospital. We initially treated her with sorafenib, but she subsequently developed erythema multiforme, which was suspected to be a drug rush due to sorafenib; therefore, sorafenib was discontinued. At the time of discontinuation, immature blast cells were detected in her peripheral blood. Approximately two weeks later, her skin rash improved substantially, but the proportion of blasts in the peripheral blood increased. We performed a bone marrow examination, and she was diagnosed with FLT3-ITD-positive acute myeloid leukemia. FLT3-ITD expression is found in 20-25% of AML and is a known independent poor prognostic factor. To overcome the poor prognosis associated with FLT3-ITD, molecular drugs targeting FLT3-ITD are attracting much attention. Sorafenib, a multi-kinase inhibitor, also has an effect on FLT3-ITD. Although primary disease flares after tyrosine kinase inhibitor discontinuation have been reported, this is the first report to describe discontinuation of sorafenib treatment as a potential trigger of FLT3-ITD-positive acute myeloid leukemia in papillary thyroid cancer.

[9th Decade Female with Dementia, Who Had Anemia Pointed Out on a Routine Laboratory Check].

In this report, we reviewed the results of RCPC held at the 63rd national congress of the Japanese Society of Laboratory Medicine. The case was a 9th decade female with dementia, who had anemia pointed out on a routine laboratory check. The type of anemia was macrocytic(MCV>130 fL). The serum Vit.B12 and folate levels were markedly decreased. However, her anemia was not improved despite supplementation with Vit.B12 and folate (data on MCV were improved). The WBC increased gradually, but she subsequently died. Laboratory data were assessed by three doctors (DN, NM, and TT: blood cell counts, smear morpholo- gy of peripheral blood cells, and clinical chemistry, respectively). They diagnosed the patient with a hema- tological disorder, probably neoplastic hematological diseases; however, it was very difficult to make a further clinical diagnosis because of the necessary data not presented at this meeting. The final diagnosis was acute myeloid leukemia (AML-M4). The direct cause of death was rupture of her spleen due to the massive infil- tration of neonlastic cells. rReviewl.

Cytomegalovirus Oophoritis Mimicking Burkitt's Lymphoma Recurrence: A Case Report and Literature Review.

Cytomegalovirus (CMV) oophoritis is an extremely rare and fatal condition. We encountered a 63-year-old woman with CMV oophoritis who had been treated for Burkitt's lymphoma. Positron emission tomography/computed tomography performed after chemotherapy showed a high 18F-fluoro-2deoxy-D-glucose uptake in both ovaries, which required distinguishing relapse. CMV oophoritis was diagnosed on histology following bilateral salpingo-oophorectomy. Although the patient later developed recurrent episodes of CMV antigenemia, after which complications of CMV retinitis appeared, and she ultimately died of CMV meningitis, surgical resection with antiviral medication resolved her abdominal symptoms and cleared CMV antigenemia for several weeks. It is therefore worth considering surgical resection in combination with antiviral drugs as a treatment option.

Immune thrombocytopenia associated with Pfizer-BioNTech's BNT162b2 mRNA COVID-19 vaccine.

The recent global pandemic of coronavirus disease 2019 (COVID-19) has led to vaccination in many parts of the world for herd immunity, and as vaccination has progressed, several rare adverse events have been reported. Immune thrombocytopenia (ITP) has been reported to be one of the rare adverse events caused by vaccination with MMR (measles-mumps-rubella) vaccine and influenza vaccine. In addition, ITP has been reported to occur in a small number of cases associated with the COVID-19 messenger ribonucleic acid (mRNA) vaccine. However, there are few reports on the details of the treatment and clinical course; optimal treatment has not yet been established. We report the case of a 20-year-old woman who developed ITP after receiving Pfizer-BioNTech's BNT162b2 vaccine. She had generalized subcutaneous hemorrhage, 14 days after vaccination. At the time of our visit, she had marked thrombocytopenia and intraoral bleeding; she was diagnosed with ITP. Treatment with oral steroids was started and the platelet count promptly improved after 4 days of treatment. Since the response to treatment was very good, we tapered off the steroids. As these vaccines will be increasingly used in the future, it is important to recognize ITP as a possible adverse event.

Autoimmune Myelofibrosis in Sjögren's Syndrome: Report of a Case.

BACKGROUND Autoimmune myelofibrosis (AMF) is a rare clinicopathologic entity of bone marrow fibrosis that occurs in association with autoimmune disorders. Steroids are very effective for treatment of AMF and the disease has a good prognosis and should be distinguished from primary myelofibrosis. CASE REPORT A 49-year-old man with bleeding and petechial hemorrhage of the extremities presented to our institution. His platelet count was 1×109/L. Bone marrow aspiration revealed a dry tap, and bone marrow biopsy confirmed small lymphocyte infiltration and increased reticular fibers, consistent with immune thrombocytopenia. Testing for mutations in JAK2, MPL, and CALR was negative. Because the patient had a history of Raynaud's phenomenon, he was suspected to have collagen disease. Anti-Sjögren's-syndrome-related antigen-A antibody testing, Schirmer's test, and fluorescein staining all came back positive, which led to a diagnosis of Sjögren's syndrome. Given the bone marrow findings, the patient also was diagnosed with AMF. Treatment with steroids resulted in an immediate improvement in his platelet count. CONCLUSIONS In the present case, treatment with steroids resulted in prompt improvement in platelet counts and subsequent marrow biopsy showed MF-0 reticulin fibrosis. Bone marrow fibrosis rarely is seen in association with autoimmune disease, and its significance and mechanism are still to be determined.

Case Report: Composite Angioimmunoblastic T-Cell Lymphoma and Epstein-Barr Virus-Positive B-Cell Lymphoproliferative Disorder as Other Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorders.

Immunosuppressants are widely used to treat patients with rheumatoid arthritis (RA), and their adverse effects have been known to cause other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPDs). We report a patient with RA who had been treated with methotrexate (MTX) and tacrolimus (TAC) and who developed whole body lymphadenopathy. We simultaneously confirmed angioimmunoblastic T-cell lymphoma (AITL) through a right cervical lymph node biopsy and Epstein-Barr virus-positive B-cell lymphoproliferative disorder (EBV-positive B-LPD) through a bone marrow examination. After cessation of immunosuppressant therapy, both LPDs completely disappeared. Patients with AITL are occasionally reported to develop B-cell lymphoma through reactivation of the EBV, which leads to clonal expansion in the microenvironment. Immunohistochemistry results revealed that both LPD components were positive for EBV-encoded RNA. Moreover, in this patient, the plasma EBV DNA level was found to be high; therefore, EBV infection was a probable etiology. Synchronous coexistence of AITL and B-LPD as an OIIA-LPD has rarely been reported. This case report is the first to discuss the disappearance of both LPDs on withdrawal of immunosuppressants only. AITL occasionally accompany B-LPD; however, this composite lymphoma comprised AITL and B-LPD, and OIIA-LPDs should not be overlooked.