Cancer-related thrombotic microangiopathy and disseminated intravascular coagulation in a patient with bone marrow carcinomatosis of unknown primary origin: A case report.

BACKGROUND: Cancer-related thrombotic microangiopathy (CR-TMA) is a rare type of Coombs-negative hemolytic anemia, which is caused by malignancy and has a poor prognosis. CASE: A 76-year-old female was referred to our hospital due to Coombs-negative hemolytic anemia, which was causing fatigue and dyspnea on exertion, accompanied by schistocytosis. A bone marrow examination demonstrated bone marrow carcinomatosis, and the tumor cells were morphologically suspected to be signet-ring cell carcinoma cells. As we failed to find the primary tumor site before the patient died, she was diagnosed with CR-TMA due to bone marrow carcinomatosis of unknown primary origin. Thrombotic thrombocytopenic purpura (TTP) was rapidly ruled out based on her PLASMIC score. In addition, immunohistochemical staining of a clot section of the bone marrow and tumor marker data were useful for narrowing down the likely primary tumor site. CONCLUSION: Although CR-TMA is an extremely rare phenomenon, clinicians who suspect CR-TMA should quickly rule out TTP and decide whether to provide appropriate chemotherapy or plan for palliative care.

Acute myeloid leukemia post­cytotoxic therapy following chemotherapy for thymoma: A case report.

The present study reports the case of a patient with acute myeloid leukemia post-cytotoxic therapy (AML-pCT) that developed following chemotherapy for thymoma. A 64-year-old female patient underwent surgical resection for a mediastinal tumor and was diagnosed with stage IVa thymoma. She received chemotherapy, including carboplatin/etoposide, carboplatin/paclitaxel and amrubicin monotherapy. At 56 months following surgery, she developed blastosis and was diagnosed with AML-pCT. As demonstrated herein, although treatment for thymoma is associated with a markedly lower frequency of myeloid neoplasms post-cytotoxic therapy (MN-pCT) than treatment for other malignancies, such as breast carcinoma, it is important to be aware that MN-pCT may occur as a late complication of thymoma treatment.

Significance of Circulating Remnant Lipoprotein Cholesterol Levels Measured by Homogeneous Assay in Patients with Type 2 Diabetes.

Remnant lipoproteins (RLs), which are typically present at high concentrations in patients with type 2 diabetes mellitus (T2DM), are associated with cardiovascular disease (CVD). Although an RL cholesterol homogeneous assay (RemL-C) is available for the measurement of RL concentrations, there have been no studies of the relationship between RemL-C and clinical parameters in T2DM. Therefore, we evaluated the relationships between RemL-C and CVD-related parameters in patients with T2DM. We performed a cross-sectional study of 169 patients with T2DM who were hospitalized at Kumamoto University Hospital. Compared with those with low RemL-C, those with higher RemL-C had higher fasting plasma glucose, homeostasis model assessment for insulin resistance (HOMA-R), total cholesterol, triglyceride, small dense low-density lipoprotein cholesterol (sdLDL-C), and urinary albumin-creatinine ratio; and lower high-density lipoprotein cholesterol, adiponectin, and ankle brachial pressure index (ABI). Multivariate logistic regression analysis showed that sdLDL-C and ABI were significantly and independently associated with high RemL-C. Although LDL-C was lower in participants with CVD, there was no difference in RemL-C between participants with or without CVD. Thus, RemL-C may represent a useful index of lipid and glucose metabolism, and that may be a marker of peripheral atherosclerotic disease (PAD) in male patients with T2DM.

[Onset of Testicular Plasmacytoma in a Patient with Refractory Multiple Myeloma].

A 72-year-old male patient, who had been on chemotherapy for the treatment of IgG-λ multiple myeloma, presented an enlargement of the testis 3 years and 5 months after the diagnosis. High orchiectomy was then performed, leading to the diagnosis of plasmacytoma. Due to residual disease, treatment with a combination of isatuximab and dexamethasone was initiated. The patient is currently under follow-up without recurrence. While testicular tumors are difficult to diagnose by imaging studies alone and extramedullary plasmacytomas rarely occur in the testis, pathological assessment is critical for treatment planning.

Prevalence and factors related to hypouricemia and hyperuricemia in schoolchildren: results of a large-scale cross-sectional population-based study conducted in Japan.

Hypouricemia in children including renal hypouricemia, which is a major cause of exercise-induced acute renal injury (EIAKI), is an important clinical problem, in addition to hyperuricemia. However, no large-scale studies of serum uric acid (UA) concentrations in the general pre-adolescent population have been carried out. We conducted a population-based cross-sectional study to measure the prevalences of hypouricemia and hyperuricemia and identify the associated factors. We analyzed 31,822 (16,205 boys and 15,617 girls) 9-10-year-old children who underwent pediatric health check-ups in Kagawa prefecture between 2014 and 2018. Hypouricemia and hyperuricemia were defined using serum UA concentrations of ≤ 2.0 mg/dL and ≥ 6.0 mg/dL, respectively. The prevalence of hypouricemia was 0.38% in both 9- and 10-year-old boys and girls, and was not significantly associated with age, sex, or environmental factors, including overweight. The prevalence of hyperuricemia was significantly higher in boys (2.7%) than in girls (1.9%), and was significantly associated with age, overweight, future diabetes risk, hypertriglyceridemia, low high-density lipoprotein-cholesterol, and liver damage, but not with high low-density lipoprotein cholesterol. Therefore, some pre-adolescent children in the general population in Japan showed hypouricemia. A means of identifying children with hypouricemia and lifestyle guidance measures for the prevention of EIAKI should be established.

Co-occurrence of JAK2 V617F-mutated essential thrombocythemia and chronic lymphocytic leukemia harboring der(8;17)(q10;q10).

BACKGROUND AND CASE: We herein present a case of the co-occurrence of JAK2-mutated essential thrombocythemia (ET) with chronic lymphocytic leukemia (CLL) harboring the recurrent and rare whole-arm translocation, der(8;17)(q10;q10). The co-existence of lymphoproliferative neoplasms and myeloproliferative neoplasms is suggested to be a rare event. Under this condition, the lymphoproliferative disorder presents a clinically indolent course with a low-risk biological profile. However, the present case showed aggressive disease progression, reflecting a poor prognostic factor; that is, the loss of 17p caused by the whole-arm der(8;17)(q10;q10) translocation. CONCLUSION: The present case report emphasizes the importance of considering the involvement of a genetically poor prognostic factor, regardless of the co-occurrence of CLL and ET.

Selective targeting of multiple myeloma cells with a monoclonal antibody recognizing the ubiquitous protein CD98 heavy chain.

Cancer-specific cell surface antigens are ideal therapeutic targets for monoclonal antibody (mAb)-based therapy. Here, we report that multiple myeloma (MM), an incurable hematological malignancy, can be specifically targeted by an mAb that recognizes a ubiquitously present protein, CD98 heavy chain (hc) (also known as SLC3A2). We screened more than 10,000 mAb clones raised against MM cells and identified R8H283, an mAb that bound MM cells but not normal hematopoietic or nonhematopoietic cells. R8H283 specifically recognized CD98hc. R8H283 did not react with monomers of CD98hc; instead, it bound CD98hc in heterodimers with a CD98 light chain (CD98lc), a complex that functions as an amino acid transporter. CD98 heterodimers were abundant on MM cells and took up amino acids for constitutive production of immunoglobulin. Although CD98 heterodimers were also present on normal leukocytes, R8H283 did not react with them. The glycoforms of CD98hc present on normal leukocytes were distinct from those present on MM cells, which may explain the lack of R8H283 reactivity to normal leukocytes. R8H283 exerted anti-MM effects without damaging normal hematopoietic cells. These findings suggested that R8H283 is a candidate for mAb-based therapies for MM. In addition, our findings showed that a cancer-specific conformational epitope in a ubiquitous protein, which cannot be identified by transcriptome or proteome analyses, can be found by extensive screening of primary human tumor samples.

[Primary Diffuse Large B-Cell Lymphoma of the Testis Developed during the Course of Mycosis Fungoides-A Case Report].

We report the case of an 84-year-old man who developed primary diffuse large B-cell lymphoma of the testes during the course of mycosis fungoides treated with topical medication. He was referred to our hospital due to bilateral testicular masses, and bilateral high orchiectomy was performed. A pathological diagnosis of diffuse large B-cell lymphoma was made after an examination of the surgical specimen. Rituximab-combined miniCHOP chemotherapy with prophylactic intrathecal injection resulted in complete remission without recurrence 1 year after diagnosis. People with mycosis fungoides are known to be at a higher risk of secondary malignancies than healthy individuals; hence, a pathological examination is important to confirm the diagnosis.

Sea-blue histiocytosis in a patient with acute myeloid leukemia with myelodysplasia-related changes harboring isolated trisomy 9: pathognomonic or a coincidence?

Although isolated trisomy 9, a form of chromosome aneuploidy, is rare in acute myeloid leukemia (AML), up to 30 cases of AML involving isolated trisomy 9 have been reported to date. We report the case of a 77-year-old female with AML, in which trisomy 9 was detected as an isolated aberration. In addition, the patient's bone marrow displayed so-called sea-blue histiocytosis. The accumulation of further cases of isolated trisomy 9-harboring AML involving sea-blue histiocytosis is necessary to determine whether the coexistence of these findings is pathognomonic or a coincidence.

[Bacteremia Due to Edwardsiella tarda Emerging after Chemotherapy for Recurrent Ph-Positive Acute Lymphoblastic Leukemia].

We report the case ofa 76-year-old man who had bacteremia due to Edwardsiella tarda during the course ofchemotherapy, including ponatinib, for the treatment of recurrent Philadelphia-positive acute lymphoblastic leukemia. Treatment with cefepime improved his general condition. The number ofreported cases ofbacteremia due to Edwardsiella tarda is limited. Further accumulation ofcases is necessary to obtain accurate data such as the risk factors of Edwardsiella tarda bacteremia.

An isolated der(1;21)(q10;q10) translocation in a patient with myelodysplastic syndrome: a case report.

Whole-arm translocations are relatively rare among hematological malignancies. There are a few reports on myeloid malignancies harboring der(1;21)(q10;q10). A 65-year-old male was referred to our hospital due to squamous cell carcinoma of the lung. Pembrolizumab monotherapy resulted in progression, and so chemotherapy involving nab-paclitaxel and carboplatin was administered thereafter. The patient developed cytopenia, and his bone marrow exhibited dysplasia. Chromosomal analysis revealed a whole-arm translocation, der(1;21)(q10;q10). Thus, the patient was diagnosed with myelodysplastic syndrome. The der(1;21)(q10;q10) translocation is a rare variant of the der(1;7)(q10;p10) translocation, which is an adverse prognostic factor for myeloid neoplasms. Clarifying the clinical features of myeloid neoplasms in patients with der(1;21)(q10;q10) would facilitate the elucidation of their tumorigenic mechanisms.

[Septic shock due to Citrobacter braakii following high-dose cytosine arabinoside therapy in a patient with acute myeloid leukemia].

Here, we report a case of a 67-year-old man who had septic shock due to Citrobacter braakii infection during the course of chemotherapy with high-dose cytosine arabinoside for acute myeloid leukemia. Treatment with cefepime rapidly improved his condition. The number of reported cases of sepsis due to Citrobacter braakii is limited. Further accumulation of cases is necessary to obtain accurate data such as the risk factors for Citrobacter braakii infections.

Trisomy 6 as the sole stemline abnormality in a patient with acute monocytic leukemia: a case report.

It is rare for trisomy 6 to occur as the sole autosomal anomaly in hematological malignancies, but this finding has been reported to be associated with a hypoplastic bone marrow. We report the case of a 75-year-old male with acute monocytic leukemia, in which trisomy 6 was detected as the sole stemline abnormality. We also summarize the 26 published cases of acute myeloid leukemia involving isolated trisomy 6.