An Unusual Case of Eosinophilic Chronic Rhinosinusitis With Concurrent Eosinophilic Otitis Media: Limited Responsiveness to Multiple Antibody Therapies and Subsequent Cochlear Implantation.

Eosinophilic chronic rhinosinusitis (ECRS) and eosinophilic otitis media (EOM) are debilitating inflammatory conditions that affect the paranasal sinuses and middle ear, respectively, and are characterized by eosinophilic infiltration. This study describes a rare and intricate case of a 65-year-old male patient concurrently afflicted with ECRS, EOM, and bronchial asthma. Despite the systematic administration of corticosteroids and various antibody drugs, the patient's condition remained unimproved, necessitating a cochlear implant for EOM, which is seldom an aggressive intervention. The patient had a history of symptoms dating back to 2005, with notable exacerbations and treatment resistance over the years. Multiple antibody drugs, including anti-IgE, anti-IL-5, and anti-IL-4α antibodies, failed to ameliorate the patient's condition, presenting a significant clinical challenge. Pathological examination revealed marked eosinophilic infiltration and severe fibrosis, suggesting a possible mechanism underlying the poor response to antibody therapy. Cochlear implantation significantly enhanced the patient's communicative abilities. This case highlights the limitations of the current antibody drugs in managing severely intertwined cases of ECRS, EOM, and bronchial asthma, highlighting the need for novel therapeutic strategies. This case also propounds cochlear implantation as an efficacious intervention for refractory EOM with severe sensorineural hearing impairment, extending the spectrum of treatment modalities for such challenging scenarios. This singular case contributes to the growing body of evidence regarding the management of ECRS and EOM, especially against the backdrop of treatment resistance, and can aid clinicians in identifying and navigating similar complex cases in clinical practice.

Distribution and clinical impact of molecular subtypes with dark zone signature of DLBCL in a Japanese real-world study.

The distribution and clinical impact of cell-of-origin (COO) subtypes of diffuse large B-cell lymphoma (DLBCL) outside Western countries remain unknown. Recent literature also suggests that there is an additional COO subtype associated with the germinal center dark zone (DZ) that warrants wider validation to generalize clinical relevance. Here, we assembled a cohort of Japanese patients with untreated DLBCL and determined the refined COO subtypes, which include the DZ signature (DZsig), using the NanoString DLBCL90 assay. To compare the distribution and clinical characteristics of the molecular subtypes, we used a data set from the cohort of British Columbia Cancer (BCC) (n = 804). Through the 1050 patient samples on which DLBCL90 assay was successfully performed in our cohort, 35%, 45%, and 6% of patients were identified to have germinal center B-cell-like (GCB) DLBCL, activated B-cell-like (ABC) DLBCL, and DZsig-positive (DZsigpos) DLBCL, respectively, with the highest prevalence of ABC-DLBCL, differing significantly from the BCC result (P < .001). GCB-DLBCL, ABC-DLBCL, and DZsigpos-DLBCL were associated with 2-year overall survival rates of 88%, 75%, and 66%, respectively (P < .0001), with patients with DZsigpos-DLBCL having the poorest prognosis. In contrast, GCB-DLBCL without DZsig showed excellent outcomes after rituximab-containing immunochemotherapy. DZsigpos-DLBCL was associated with the significant enrichment of tumors with CD10 expression, concurrent MYC/BCL2 expression, and depletion of microenvironmental components (all, P < .05). These results provide evidence of the distinct distribution of clinically relevant molecular subtypes in Japanese DLBCL and that refined COO, as measured by the DLBCL90 assay, is a robust prognostic biomarker that is consistent across geographical areas.

Pseudo-malignant paranasal invasive aspergillosis showing bone destruction and FDG uptake on PET/CT: A case report.

RATIONALE: Aspergillosis is a rare disease that often occurs in patients with diabetes mellitus or compromised hosts. This study describes a 60-years-old woman with unusual pseudo-malignant paranasal invasive aspergillosis with 18F-fluorodeoxyglucose (18F-FDG) uptake treated by endoscopic sinus surgery. To the best of our knowledge, there are few reported cases of paranasal fungal infection with 18F-FDG uptake. PATIENTS CONCERNS: A 60-years-old woman was presented with headache and nasal obstruction. DIAGNOSES: Computed tomography (CT) showed a shadow with bone destruction in the sinus cavity and accumulation of 18F-FDG uptake. The patient was diagnosed with a malignant tumor or pseudo-malignant paranasal invasive aspergillosis. INTERVENTIONS: The patient underwent endoscopic sinus surgery; no neoplastic lesions were detected in the areas with CT shadows. All the observed fungal mass reservoirs were removed. OUTCOMES: The patient remained hospitalized for 1 week after the surgery with no significant postoperative abnormalities. There was no recurrence of the disease for 6 months, and the patient's symptoms resolved, indicating a good course of follow-up. LESSONS: Invasive aspergillosis should be considered a differential disease when positron emission tomography (PET)/CT scans show FDG uptake, CT shows bone destruction, and T2-weighted MRI scans show a low signal.

Co-Treatment with Steroid and Dupilumab for Eosinophilic Chronic Rhinosinusitis after Eosinophilic Pneumonitis Caused by Dupilumab.

Eosinophilic chronic rhinosinusitis (ECRS) is a Type 2 inflammatory disease that manifests as chronic inflammation of the paranasal sinus. IL-4/IL-13 receptor monoclonal antibodies (dupilumab) to suppress Type 2 inflammation have become a good treatment option for patients who are refractory to surgery. Most patients respond normally, although significant side effects such as eosinophilic pneumonia may occur, requiring discontinuation of dupilumab. Here, we present a case in which dupilumab administration caused a side-effect of eosinophilic pneumonia. A 65-year-old woman presented with nasal obstruction and olfactory dysfunction due to a nasal polyp. Her symptoms temporarily improved with dupilumab; however, dupilumab was discontinued due to eosinophilic pneumonia. Discontinuation of dupilumab resulted in the rapid resolution of eosinophilic pneumonia and reappearance of nasal polyps. We, therefore, resumed dupilumab treatment in combination with low-dose steroids; eosinophilic pneumonia did not flare up, and the nasal polyps shrank steadily. There is no established treatment strategy in cases where a side effect of eosinophilic pneumonia arises while treating ECRS with dupilumab. Based on the described case, we recommend that a combination of a low-dose steroids and dupilumab be considered as a treatment option to counter the side-effect of eosinophilic pneumonia induced by dupilumab alone.

Higher incidence of thrombocytopenia during obinutuzumab plus bendamustine therapy for untreated follicular lymphoma: a retrospective analysis by the Okayama Hematology Study Group.

Progression-free survival in patients with untreated follicular lymphoma (FL) has significantly improved with obinutuzumab plus chemotherapy followed by obinutuzumab maintenance, compared with rituximab plus chemotherapy. However, the survival outcome and adverse event profile in Japanese FL patients treated with obinutuzumab plus bendamustine (GB) therapy are not well investigated. Recently, we encountered some cases of grade 3-4 thrombocytopenia during GB therapy in patients with FL. This retrospective multicenter survey aimed to identify the characteristics of patients who received GB therapy and developed thrombocytopenia. A total of 54 patients with FL treated by GB therapy between August 2018 and December 2020 were investigated. After a median follow-up of 12.6 months, thrombocytopenia of any grade was observed in 48 (88.9%) patients, including 9 (16.7%) patients with grade 3-4 thrombocytopenia. Notably, although eight of nine patients with grade 3-4 thrombocytopenia were female, no patient characteristics (including gender) were significantly associated with grade 3-4 thrombocytopenia. Importantly, grade 3-4 thrombocytopenia frequently occurred in the first GB therapy cycle, which suggests that platelet count should be monitored carefully in patients who have just started GB therapy.

Chronic active Epstein-Barr virus infection presenting as refractory chronic sinusitis.

A 44-year-old Japanese man presented with fever and sore throat. He had a history of refractory chronic sinusitis that did not respond to several years of pharmacotherapy, and underwent endoscopic sinus surgery (ESS) 5 months prior to his presentation, but his symptoms persisted. A biopsy specimen was taken from the right nasal cavity, and extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) was diagnosed. Two years after complete remission was achieved by chemoradiation therapy, he developed hemophagocytic lymphohistiocytosis (HLH) without recurrence of ENKTL. Epstein-Barr virus (EBV)-DNA copy number was relatively high and EBV-infected lymphocytes (CD8 + T cells) were detected in the peripheral blood. Pathological review of the biopsy specimens taken during ESS showed that CD8 + T cells with slightly atypia infiltrating the stroma were EBV positive. These findings suggested that the patient had underlying chronic active EBV infection (CAEBV) that caused the refractory chronic sinusitis, eventually developed into ENKTL, and also caused HLH. Clinicians should consider adult-onset CAEBV in the differential diagnosis of patients with refractory chronic sinusitis.

[Development of Ph negative acute myeloid leukemia in a patient with minor-BCR/ABL positive chronic myeloid leukemia achieving a partial cytogenetic response during tyrosine kinase inhibitor treatment].

A 78-year-old male, who had CKD and chronic heart failure, was referred to our hospital for evaluation of leukocytosis. His bone marrow contained 12% blast cells and chromosome analysis showed the Ph chromosome as well as other changes. The patient was diagnosed with the accelerated-phase CML because FISH and RT-PCR disclosed BCR/ABL fusion signals and minor BCR/ABL, respectively. Imatinib was administered, but the CML was resistant to this treatment. We gave him nilotinib employing a reduced and intermittent administration protocol because of the progression of anemia and heart failure. The patient achieved PCyR in 8 months, but, 12 months later, his WBC count increased and 83% of the cells were blasts. Because the probable diagnosis was the blast crisis of CML, we switched from nilotinib to dasatinib. However, leukocytosis worsened and he died of pneumonia. It was later revealed that he had a normal karyotype and both FISH and RT-PCR analysis of BCR/ABL were negative. His final diagnosis was Ph negative AML developing from Ph positive CML in PCyR. Since there were no dysplastic changes indicative of MDS, it was assumed that the AML was not secondary leukemia caused by the tyrosine kinase inhibitor but, rather, de novo AML.

Dual-time-point F-18 FDG PET/CT for evaluation in patients with malignant lymphoma.

OBJECTIVE: The aim of this study was to evaluate the usefulness of F-18 fluorodeoxyglucose (FDG) dual-time-point (DTP) positron emission tomography (PET)/computed tomography (CT) with semiquantitative analyses for the initial staging in patients with malignant lymphoma. METHODS: Forty-three patients had DTP PET/CT, with 60-min and 2-h scan [n = 8, Hodgkin's lymphoma (HL); n = 12, indolent non-Hodgkin lymphoma (NHL); n = 23, aggressive NHL]. RESULTS: A total of 524 lesions were evaluated (406 lymph nodes and 118 extra-nodal lesions). The maximum standardized uptake value (SUV(max)) on 2-h delayed scan (SUV(2)) was significantly higher than those on 1-h early scan (SUV(1)) for all groups (P < 0.0001 for HL; P < 0.0001 for indolent NHL; P < 0.0001 for aggressive NHL). Significant differences were detected between HL and indolent NHL, between indolent NHL and the aggressive NHL for both SUV(1) and SUV(2) (each P < 0.0001). No significant differences were detected between HL and aggressive NHL for both SUV(1) and SUV(2) (P = 0.6891 for SUV(1); P = 0.8828 for SUV(2)); however, significant differences were detected for the retention index of SUV(max) between these groups (P = 0.0238). CONCLUSIONS: DTP F-18 FDG PET/CT with a semiquantitative technique may have the potential to provide the more accurate diagnoses for the staging of malignant lymphoma and the more important role in predicting the histological grades of malignancy compared with single-time-point F-18 FDG-PET scan.

Optimal cut-off point of waist circumference for the diagnosis of metabolic syndrome in Japanese subjects.

Metabolic syndrome (MetS) has been redefined by a new criterion in Japan, in which waist circumference cut-off points, that is 85 cm for men and 90 cm for women, are used; however, objections are rising against this criterion. The present study examined the criterion for waist circumference to predict the accumulation of the components of MetS. In the present study, we used data for 5972 Japanese people who received annual health examinations, and 621 men (16.3%) and 51 women (2.4%) were diagnosed as having MetS. A cut-off point as a predictor for two or more components of MetS was evaluated by the sensitivity/specificity and a receiver operating characteristic analysis. The optimal point of waist circumference was estimated as being approximately 84 cm for men and 80 cm for women. We therefore recommend revising the cut-off value for the criterion of MetS in women according to our results and studies from other investigators. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00020.x, 2010).

Bone marrow large B cell lymphoma bearing cyclin D3 expression: clinical, morphologic, immunophenotypic, and genotypic analyses of seven patients.

We report seven large B cell lymphoma patients showing the involvement of tumor cells with cyclin D3 (CCND3) expression in bone marrow (BM) at the initial diagnosis. All patients presented with B symptoms, splenomegaly, and anemia/thrombocytopenia lacking hemophagocytosis in the BM. Five of the seven patients had suffered from immunological diseases or cancers. The tumor cells were divided into those with a lymphoplasmacytoid or blastoid appearance. Six cases were confirmed to express CD5 antigen on tumor cells. Three cases presented a chromosomal translocation between CCND3 and the immunoglobulin heavy chain (IGH) loci, t(6;14)(p21;q32). Three and two cases showed unmutated and mutated sequences of the variable region of IGH (VH), respectively, and one case showed deletion of an entire segment of VH. Two cases with t(6;14)(p21;q32) showed an unmutated VH sequence and chromosomal translocation within the switch region of IGH. Further studies are required to determine whether CCND3 expression is associated with a unique subset of diffuse large B cell lymphoma.

Clinicopathological features of lymphoma/leukemia patients carrying both BCL2 and MYC translocations.

BACKGROUND: Lymphoid neoplasm with 18q21.3/BCL2 and 8q24/MYC translocation to immunoglobulin (IG) genes as dual-hit lymphoma/leukemia is very rare and known to have a poor clinical outcome. DESIGN AND METHODS: To clarify the clinicopathological characteristics of this malignancy, we analyzed 27 cases of cytogenetically proven dual-hit lymphoma/leukemia. RESULTS: Dual-hit lymphoma/leukemia was diagnosed at presentation in 22 cases and at relapse or disease progression in 5 cases. At the time of diagnosis of dual-hit lymphoma/leukemia, extranodal involvement was found in 25 cases (93%) and central nervous system involvement occurred in 15 cases (56%). The median survival and 1-year survival rate of the 27 cases were only 6 months and 22%, respectively, after diagnosis of the dual-hit lymphoma/leukemia. Seven cases of triple-hit lymphoma/leukemia (dual-hit lymphoma/leukemia with 3q27/BCL6 translocation) were included; the median survival of these patients was only 4 months from the diagnosis of the dual-hit lymphoma/leukemia. The duration of survival of the patients with a triple-hit malignancy was shorter than that of the other 20 cases of dual-hit lymphoma/leukemia (p=0.02). The translocation partner of MYC subdivided the dual-hit cases into two groups; 14 cases of IGH and 13 cases of IGK/L. The MIB-1 index was investigated in 14 cases with aggressive B-cell lymphoma, and was higher in the group with MYC-IGH translocation (n=7) than in the MYC-IGK/L group (n=7) (p=0.02). Overall survival was not different between the MYC-IGH translocation group (n=14) and the MYC-IGK or MYC-IGL translocation group (n=13). CONCLUSIONS: Dual-hit lymphoma/leukemia is a rare but distinct mature B-cell neoplasm with an extremely poor prognosis characterized by frequent extranodal involvement and central nervous system progression with either of the translocation partners of MYC.

[Acute myelogenous leukemia complicated with severe tumor lysis syndrome after a single day of idarubicin/cytarabine chemotherapy].

We describe a patient with acute myelogenous leukemia (AML) who was complicated with severe tumor lysis syndrome (TLS) after a single day of chemotherapy; a previously unreported occurrence. A 48-year-old man was admitted because of fever and bleeding tendency, and was diagnosed as having AML: M1. His white blood cell count (WBC) was 66, 300/microliter with 96% myeloblasts. Chemotherapy with idarubicin and cytarabine was started. On the second day of the therapy, he developed acute renal failure (ARF) and deterioration of disseminated intravascular coagulation (DIC) with a marked reduction in his WBC (8500/microliter). Immediately after a diagnosis of tumor lysis syndrome (TLS), the following chemotherapy was discontinued. Hemodiafiltration and hemofiltration were initiated to treat the ARF, concomitant with anticoagulant and antifibrinolysis therapy for the DIC. Chemotherapy with daunorubicin and cytarabine was resumed on the 12th day, recognizing a regrowth of leukemic cells. Thereafter a complete remission was achieved without recurrence of the TLS.