Fatal posterior reversible encephalopathy syndrome after blood transfusion in a patient with myelodysplastic syndromes.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is known as a transfusion-related complication with typically favorable prognosis and no report fatalities. Pathological evaluation of PRES is also scarce. CASE REPORT: An 88-year-old female with myelodysplastic syndromes (MDS) attended our hospital because of a compression fracture and chronic heart failure with chronic anemia. While her hemoglobin levels improved from 4.6 to 8.0 g/dL and the pleural effusions substantially decreased following six units of red blood cell transfusion and diuretic therapy, a gradual decline in cognitive function and speech reduction was noted. PRES was diagnosed by magnetic resonance imaging of the head. Despite treatment of intensive supportive care, the patient fell into a coma by the 20th day and passed away on the 22nd day. Although the pathophysiological link between blood-transfusion-related PRES and its impact on survival is not fully understood, autopsy findings confirmed the diagnosis of PRES and revealed multiple cerebral hemorrhages that were not detected in earlier imaging studies. CONCLUSION: This case highlights the importance of vigilant monitoring and management of PRES, especially in high-risk populations such as elderly patients with multiple comorbidities or those with thrombocytopenia. Further studies are needed to elucidate the mechanisms of PRES in patients with hematologic diseases.

[Congenital thrombotic thrombocytopenic purpura diagnosed in adulthood after repeated thrombocytopenia since neonatal period].

A 27-year-old woman was diagnosed with idiopathic thrombocytopenic purpura in the neonatal period, and was admitted to our hospital after presenting with impaired consciousness, purpura, nausea and vomiting, with a platelet count of 10×109/l. Congenital thrombotic thrombocytopenic purpura (cTTP) was suspected on the basis of recurrent thrombocytopenia and impaired consciousness, so tests for ADAMTS13 activity and inhibitor were performed. ADAMTS13 activity was severely decreased, ADAMTS13 inhibitor was negative, and platelet count increased after transfusion of fresh frozen plasma. These findings and the results of genetic testing done on all family members led to a diagnosis of cTTP. cTTP requires differential diagnosis even in adults. If a patient diagnosed with ITP in childhood has a history or findings that suggest cTTP during follow-up observation, it is necessary to actively consider ADAMTS13 testing.

[Acute myeloid leukemia with type I CBFB::MYH11 fusion gene not detected by screening test for leukemia-related chimeric genes].

A 27-year-old woman with pancytopenia was admitted to our hospital. Bone marrow aspiration revealed 52.2% myeloperoxidase-positive myeloblasts, leading to a diagnosis of acute myeloid leukemia. While a screening test for chimeric genes related to leukemia initially yielded negative results, including for the CBFB::MYH11 fusion gene, G-banded karyotyping uncovered the presence of inv (16)(p13.1q22). Further investigation by fluorescence in situ hybridization (FISH) confirmed the split signals for CBFB. A second screening test for leukemia-related chimeric genes with different PCR primers revealed the elusive CBFB::MYH11 fusion gene. Subsequently, the type I CBFB::MYH11 fusion gene was identified through exhaustive exploration using RNA sequencing for fusion gene discovery. This exceptional case highlights the existence of a distinctive subtype of CBFB::MYH11 that may yield false-negative results in conventional chimeric fusion screening, thus emphasizing the indispensable utility of PCR primer modification, FISH, and RNA sequencing in the investigative process.

[CD20-negative diffuse large B-cell lymphoma complicated by rheumatoid arthritis].

CD20 antigen is an important marker for diagnosis of B-cell neoplasms that is highly expressed on the surface of neoplastic B lymphocytes. Patients with rheumatoid arthritis (RA) have an increased risk of developing malignant lymphoma, of which diffuse large B-cell lymphoma (DLBCL) is the most common type. We report an unusual case of CD20-negative DLBCL complicated by rheumatoid arthritis. An 81-year old female presented with a left-sided cervical tumor, enlarged tonsil, and polyarticular pain. Pathological findings of the left tonsil showed proliferation of large atypical cells with irregular shaped nuclei. Most large cells were negative for CD3 and CD20. Additionally, these cells were positive for CD79a, BCL2, and MUM1, and negative for CD10, CD138, BCL6, PAX5, EBV-ISH, HHV8, and ALK.. Therefore, she was diagnosed with CD20-negative DLBCL complicated with RA and received dose-modified CHOP that achieved partial remission. Because CD20-negative DLBCL is rare, the identification of the clinicopathological features of this disease is urgently required.

Outcomes of allogeneic stem cell transplantation for patients with hematologic diseases ≥60 years old.

Hematologic diseases frequently affect people >60 years old, and allogeneic stem cell transplantation (allo-SCT) is a potentially curative treatment for these patients. Although several multicenter studies proposed the risk assessment of allo-SCT for the elderly, they receive different treatments and management at each facility. Therefore, accumulating data from institutions that exhibit relatively the same treatment policy and patient care is important. This retrospective study aimed to clarify the prognostic factors of allo-SCT for the elderly in our institution. Of the 104 patients, 51.0% were 60-64 years old, and 49.0% were ≥65 years old. The 3-year overall survival (OS) was 40.9% and 35.7% for patients 60-64 and ≥65 years old, respectively, which is not significant. While the disease status prior to allo-SCT demonstrated strong effects on the 3-year OS for patients that are 60-64 years old (in remission, 76.9%; non-remission, 15.7%, p<0.001), this effect was smaller for patients ≥65 years old (in remission, 43.1%; non-remission, 30.1%, p=0.048). Multivariate analysis revealed that the performance status (PS), not the disease status prior to allo-SCT, was the prognostic risk factor of OS for patients aged ≥65 years. Our data suggest that PS is a useful predictor of better OS following allo-SCT, especially for patients ≥65 years old.

Ephrin-A3 not only increases the density of hair follicles but also accelerates anagen development in neonatal mice.

BACKGROUND: Ephrins are cell-membrane-bound ligands for Eph receptor tyrosine kinases (Eph). Although ephrins are known to regulate a variety of developmental processes, little is known of their role in hair development. Previously, we studied the gene expression of dermal papilla cells from androgenetic alopecia and found that ephrin-A3 was significantly down-regulated. OBJECTIVE: To characterize the expression of ephrin-A3 in the hair cycle and evaluate the effect of ephrin-A3 on hair growth. METHODS: We investigated gene expression and protein expression of each ephrin-As and EphAs in the skin of neonatal mice through the first and second hair cycle using quantitative PCR and immunohistochemical analysis, respectively. We also injected ephrin-A3 protein into the skin of neonatal mice and demonstrated the effect of ephrin-A3 on hair follicle development. RESULTS: Expression of ephrin-A3 revealed a rapid increase at the beginning of the anagen phase, a peak during the mid-anagen, and a rapid fading during the telogen phase. In addition, we found ephrin-A3 protein was expressed in the developing hair follicles with a characteristic spatiotemporal localization. Furthermore, injection of ephrin-A3 into the skin of neonatal mice markedly accelerated the differentiation process of hair follicles. In addition, injection of ephrin-A3 unexpectedly increased the number of hair follicles. CONCLUSION: These findings demonstrated that ephrin-A3 not only accelerates anagen development but also increases the density of hair follicles, and also suggested that an ephrin-A-EphA signal pathway is closely involved in hair follicle development.

Lipid peroxides induce early onset of catagen phase in murine hair cycles.

The precise mechanisms of alopecia, a pathophysiological disorder with negative psychological implications, are unknown. Androgen and hereditary predisposition are major causes, but the condition is also affected by stress, an irregular diet and high levels of sebum secretion. We focused on oxidative stress and analyzed the effect of the lipid peroxides on hair follicles. Our first observation was that the topical application of linolein hydroperoxides, one of the lipid peroxides, lead to the early onset of the catagen phase in murine hair cycles. Furthermore, by using TUNEL staining we found that lipid peroxides induced apoptosis of hair follicle cells. They also induced apoptosis in human epidermal keratinocytes by up-regulating apoptosis-related genes. These results indicated that lipid peroxides, which can cause free radicals, induce the apoptosis of hair follicle cells, and this is followed by early onset of the catagen phase. These observations may provide insight into the mechanisms underlying the development of alopecia in humans.

Different gene expression profile observed in dermal papilla cells related to androgenic alopecia by DNA macroarray analysis.

BACKGROUND: Androgenic alopecia (AGA) is the most common type of baldness in men. Although etiological studies have proved that androgen is one of the causes of this symptom, the defined molecular mechanism underlying androgen-related actions remains largely unknown. OBJECTIVES: To clarify the difference in the gene expression profile of dermal papilla cells (DPCs) in skin affected by baldness. METHODS: DNA macroarray study was carried out on cultured DPCs from AGA skin comparing with DPCs from skin that is not affected by baldness. RESULTS: From DNA macroarray analysis, we observed that 107 of the 1185 analyzed genes had differing expression levels. A marked difference was observed in the decreased gene expression of BMP2 and ephrin A3 and up-regulated in NT-4 gene. In order to clarify the roles of BMP2 and ephrin A3 in the hair follicles, we examined the proliferation of hair follicle keratinocyte and expression of a hair acidic keratin gene. Both BMP2 and ephrin A3 raised the proliferation rate of the outer root sheath cells (ORSCs) and induced gene expression in acidic hair keratin 3-II. CONCLUSION: These results lead us to the hypothesis that both BMP2 and ephrin A3 function as hair growth promoting factors in the hair cycle.