[Hemophagocytic lymphohistiocytosis following mRNA-1273 COVID-19 vaccination].

A 34-year-old man with no medical history presented with fever 4 days after receiving the first dose of mRNA-1273 coronavirus disease 2019 (COVID-19) vaccine. He had no prior clinical evidence of severe acute respiratory syndrome coronavirus 2 infection and was negative for serial polymerase chain reaction testing. Ten days after vaccination, he was referred to our hospital because of no response to antibiotics and the emergence of neutropenia, thrombocytopenia, and liver dysfunction. Blood tests also showed elevated serum ferritin and plasma soluble interleukin-2 receptors. Serological and PCR testing excluded active infections of cytomegalovirus, Epstein-Barr virus, and hepatitis viruses. Blood culture yielded no growth. Computed tomography revealed mild hepatosplenomegaly and porta hepatis lymphadenopathy but no focus on infection. Bone marrow aspiration demonstrated hemophagocytosis but no infiltrating lymphoma cells. Immediately, 2-mg/kg intravenous methylprednisolone was commenced based on the presumptive diagnosis of hemophagocytic lymphohistiocytosis (HLH), leading to the rapid and durable improvement of his symptoms and laboratory data. Later, without other causes triggering hemophagocytosis, and with the close link between vaccination and disease onset, the final diagnosis of vaccination-induced secondary HLH was made. HLH after COVID-19 vaccination, though extremely rare, can occur regardless of the vaccine type. Therefore, clinicians should recognize and deal with this occasionally fatal adverse event.

[Chronic myeloid leukemia with an in-frame exon 4 deletion in ABL1 with acute abdomen due to an intrapelvic bulky mass as the initial symptom].

A 23-year-old woman was admitted to our hospital because of rapidly developing lower abdominal pain. Computed tomography revealed ascites, splenomegaly, and a huge mass that occupied the pouch of Douglas and surrounded her uterus. A markedly elevated white blood cell count of 495×109/l and the identification of the BCR-ABL1 fusion gene led to the diagnosis of chronic myeloid leukemia (CML). Although neither an increase in the blast percentage nor any additional chromosomal abnormality was observed in the patient, CML was considered in the blast phase because of extramedullary disease infiltration. Dasatinib was administered with the temporal use of hydroxyurea and VP-16, which resulted in rapid disappearance of her intrapelvic mass and complete hematologic response within 1 month. She refused to undergo allogeneic hematopoietic stem cell transplantation and continued to take dasatinib, achieving complete cytogenetic and major molecular responses within 5 and 11 months, respectively. CML cases initially presenting with extramedullary tumors are rare. Furthermore, in our case, a mutational analysis at diagnosis revealed an in-frame exon 4 deletion in ABL1, which is reported to decrease cell proliferation. This fact is intriguing because her clinical outcome was relatively favorable.

[Follicular lymphoma with nodular lesions mimicking gallbladder carcinoma].

A 68-year-old female was diagnosed with follicular lymphoma (FL) grade 2, based on the excisional biopsy of her enlarged left cervical lymph node. Positron-emission tomography/computed tomography (PET/CT) revealed the 18F-fluoro-deoxyglucose-avid lesions in the sigmoid colon and at the fundus of the gallbladder, besides those in the left neck. A sigmoid colon polyp, which was endoscopically resected, proved histologically to be a well- to moderately-differentiated tubular adenocarcinoma with deep invasion into the submucosa. In addition, nodular lesions of the gallbladder were enhanced on dynamic CT, markedly suggesting gallbladder carcinoma. Among FL, colorectal cancer, and presumed gallbladder adenocarcinoma, FL was considered having the lowest priority of treatment because of its indolent nature and low tumor burden. We performed laparoscopic-assisted sigmoid colectomy, followed by gallbladder bed resection on the same day. Unpredictably, gallbladder lesions were histologically revealed to be FL. Often, FL involves extranodal sites such as the gastrointestinal tracts. However, the gallbladder involvement is extremely rare, and preoperative distinction from gallbladder adenocarcinoma remains challenging to date; this report discusses its characteristics along with the literature review. Furthermore, our case, in which another malignant neoplasm coexisted, needed histological identification of the gallbladder lesions to ascertain the therapeutic strategy.

[Systemic lupus erythematosus with marked eosinophilia and clinical features mimicking TAFRO syndrome].

A 76-year-old woman was referred to our hospital because of fever, hemorrhagic skin lesion with pruritus, and severe thrombocytopenia. Anemia; marked eosinophilia; and elevated ALP, CRP, and soluble IL-2 receptor levels were observed on admission. Both anti-nuclear antibody and Coombs tests were positive. Computed tomography revealed bilateral pleural effusion, ascites, abdominal lymphadenopathy, and mild hepatosplenomegaly. A thorough examination for the initial differential diagnoses excluded the possibility of myeloid/lymphoid neoplasms with eosinophilia and gene rearrangement, infectious diseases, and eosinophilic granulomatosis with polyangiitis. Remaining possibilities included angioimmunoblastic T-cell lymphoma (AITL) and systemic inflammatory disorders. Although AITL was plausible, there was no histological evidence to support the diagnosis. The patient was then administered prednisolone alone, which led to a lasting resolution of her symptoms. The atypical AITL course raised the suspicion of a misdiagnosis; thus the possibility of an inflammatory disease was reconsidered. TAFRO syndrome was suspected owing to its characteristic clinical features (thrombocytopenia, anasarca, fever and organomegaly). Since a definitive diagnosis required the exclusion of systemic lupus erythematosus (SLE), anti-double-stranded DNA antibody was tested in the initial frozen serum sample. An unexpected positive result led to the final diagnosis of SLE. Here, we report a rare case of SLE lacking typical symptoms and exhibiting various hematological abnormalities, such as eosinophilia.

[Neutrophil recovery by eltrombopag treatment in a patient with adult-onset autoimmune neutropenia and immune thrombocytopenia].

Adult-onset autoimmune neutropenia (AIN) is rarely self-limiting, unlike infant-onset AIN. Although several therapeutic agents have been reported, including corticosteroids, more effective treatment options may exist. Here, we describe neutrophil recovery by eltrombopag in a 52-year-old male AIN patient with immune thrombocytopenia (ITP) who was referred to our hospital with severe neutropenia. Within a year of referral, he developed moderate thrombocytopenia. He was diagnosed with AIN and concurrent ITP, based on the detection of antineutrophil antibodies and bone marrow aspiration, respectively. Further platelet count reduction and the appearance of purpura prompted an initial treatment of 0.5 mg/kg prednisolone. Thrombocytopenia remission was prompt but transient, with platelet counts rapidly declining before initiating prednisolone tapering. Similarly, absolute neutrophil counts (ANCs), after a shorter recovery period, returned to the baseline level below 2×108/l. Further platelet reduction was prevented by eltrombopag administration. Intriguingly, the ANCs recovered following platelet recovery and remained above 5×108/l for > three months despite prednisolone dosage tapering. To our knowledge, this is the first report describing the effectiveness of eltrombopag in AIN.

Tumour-associated macrophages in diffuse large B-cell lymphoma: a study of the Osaka Lymphoma Study Group.

AIMS: To evaluate the role of tumour-associated macrophages (TAMs) of the M1 and M2 types in the behaviour of diffuse large B-cell lymphoma (DLBCL). METHODS AND RESULTS: Double immunohistochemical staining of HLA-DR/CD68 (M1) or CD163/CD68 (M2) was performed in 101 cases of DLBCL. CD68+ cells represent the total number of TAMs. The average number of double-positive cells was counted, and the cut-off value was set at the mean number of counts, i.e. 30.7 and 27.0 for M1 TAMs and M2 TAMs, respectively. That for total TAMs was set at the 90th percentile number of total counts, i.e. 132.3. Cases were categorized into three pairs: high (34 cases) and low (67 cases) M1 TAM groups, high (39 cases) and low (62 cases) M2 TAM groups, and high (10 cases) and low (91 cases) total TAM groups. The difference in overall survival rates was statistically significant between the high and low M2 TAM groups (P < 0.01) and between the high and low total TAM groups (P < 0.05). Multivariate analysis revealed that the presence of a bulky mass and a higher number of M2 TAMs were significant factors for poor prognosis (P < 0.05). CONCLUSIONS: Estimation of specific type of macrophages, of the M1 and M2 types, is superior to the estimation of TAMs as a whole (CD68+ cells) for prediction of the prognosis of DLBCL patients.

Wilms tumor gene peptide-based immunotherapy for patients with overt leukemia from myelodysplastic syndrome (MDS) or MDS with myelofibrosis.

The Wilms tumor gene, WT1, is overexpressed not only in leukemias and myelodysplastic syndrome (MDS) but also in various types of solid tumors, including lung and breast cancer, and the WT1 protein is a tumor antigen for these malignancies. In clinical trials of WT1 peptide-based cancer immunotherapy, patients with overt leukemia from MDS or MDS with myelofibrosis were injected intradermally with 0.3 mg of an HLA-A*2402-restricted, 9-mer WT1 peptide emulsified with Montanide ISA51 adjuvant. Only a single dose of WT1 vaccination resulted in an increase in WT1-specific cytotoxic T-lymphocytes, which was followed by a rapid reduction in leukemic blast cells. Severe leukopenia and local erythema at the injection sites of WT1 peptide were observed as adverse effects. These results have provided us with the first clinical evidence suggesting that WT1 peptide-based immunotherapy is an attractive treatment for patients with leukemias or MDS.