The outcome of double-hit lymphoma (DHL) defined by concurrent rearrangements of MYC and BCL2 and/or BCL6 is extremely poor than that of diffuse large B-cell lymphoma (DLBCL). Patients with DHL are usually resistant to R-CHOP therapy and show a highly aggressive clinical course frequently involving the extranodal sites, such as the bone marrow, peripheral blood, pleural effusion, and central nervous system (CNS). However, several retrospective studies conducted recently have demonstrated a relatively favorable outcome with intensive chemotherapy, such as dose-adjusted EPOCH-R, than those receiving R-CHOP in patients with DHL. “Double expressor status” with concomitant expression of MYC and BCL2 protein by immunohistochemistry in DLBCL is considered a poor prognostic biomarker and has been associated with high risk of CNS relapse. Therefore, to reduce these risks, CNS-directed evaluation and consideration of CNS-prophylactic strategies should be performed in patients with double expressor lymphoma. This chapter reviews the clinical and pathological features, prognosis, treatment strategies, and new insights in MYC-associated B-cell lymphoma, such as Burkitt lymphoma.

Failure of autologous peripheral blood stem cell collection (PBSCH) can affect the treatment modality for patients with hematological malignancies. The clinical efficacy of plerixafor in PBSCH was analyzed in our institution. The medical records of 61 patients were retrospectively reviewed. The use of plerixafor was determined according to the CD34⁺ cell count in the peripheral blood (PB CD34⁺) on day 4 of G-CSF administration and patients’ backgrounds. A total of 47 patients received G-CSF plus plerixafor: 31 with multiple myeloma, 8 with AL amyloidosis or POEMS syndrome, and 8 with non-Hodgkin lymphoma. The median fold increase in PB CD34⁺ following the first dose of plerixafor was 7.18 times. The median number of collected CD34⁺ cells on day 5 was 4.1×10⁶/kg and 5.3×10⁶/kg in total. Among the 47 patients, 44 (93.6%) yielded the minimum required cell collection of 2.0×10⁶/kg within an average of 1.3 days. Plerixafor enables rapid and efficient mobilization, and sufficient numbers of CD34⁺ cells were successfully collected.

Protein S (PS) gene (PROS1) is found on chromosome 3 (3q11.1). To date, the reported detection rate of causative gene mutations in patients suspected of PS deficiency is only approximately 50%. To improve the detection rate of causative mutations, an exhaustive analysis of PROS1 was attempted using the next-generation sequencing method (NGS) to analyze the entire nucleotide sequence of PROS1 without analyzing those affected by pseudogenes. A total of 10 different mutations (three males and six females (52.9%) out of 17 patients (3 males and 14 females) with clinical PS deficiency were identified in this study. Remarkable improvements in the detection rate of causative mutations could not be obtained even with NGS analysis. These results suggested that the rate of diagnosis did not improve even after performing an exhaustive genetic analysis in patients clinically diagnosed with low PS antigen level and/or low PS activity. Although no reports were found on the gender gap in the rate of gene diagnosis for PS deficiency, the fluctuation of estrogen levels especially in women might cause a lower rate of diagnosis.

Intravascular large B-cell lymphoma (IVLBCL) is a rare form of extranodal non-Hodgkin’s lymphoma, and the absence of specific findings makes ante-mortem diagnosis difficult. This study was conducted to identify the clinical findings useful for timely diagnosis of IVLBCL. Ten patients who were diagnosed with IVLBCL in our institute between 2005 and 2017 were retrospectively analyzed. Eight of the 10 cases had fever and 7 cases presented with respiratory symptoms, including cough, sputum, and dyspnea. Cytopenias were noted in all patients, and serum lactate dehydrogenase levels were elevated in 9 of the 10 patients. Arterial partial pressures of oxygen were <80 mmHg in 6 of the 7 patients examined. Computed tomography scanning detected hepatosplenomegaly and chest abnormalities in 7 and 9 cases, respectively. These results suggest that IVLBCL has a higher frequency of lung involvement than those reported previously. Physicians must therefore be vigilant in the identification of IVLBCL in patients who demonstrate respiratory symptoms or hypoxemia of uncertain origin, because early diagnosis can decrease the severity and prevent mortality.

A 56-year-old man who sustained a right waist injury 1 month ago, reported to our department complaining of pain in the right waist and femur for 1 day. In a computed tomography examination, hematoma of the right iliopsoas muscle was revealed, and arterial embolization was immediately performed but was not effective. Laboratory findings showed hemoglobin levels as 5.4 g/dl, platelet of 20.2×10⁴/µl, prothrombine time of 13.1 s, partial thromboplastin time (APTT) of 81.1 s, and a convex upward curve of the APTT cross-mixing test. The activity of the coagulation factor VIII was <1.0%, but its amount was 120%, and the level of factor VIII inhibitor was 130 Bethesda Unit/ml. Disseminated intravascular coagulation was not noted. Under the diagnosis of acquired hemophilia A, treatment with prednisolone and recombinant activated factor VII was initiated. However, APTT remained prolonged, and intubation and mechanical ventilation were required because of right hemothorax. After steroid pulse therapy and plasma exchange, APTT returned to its normal range, and the inhibitor disappeared. Thus, we finally succeeded in extubation. This case indicated that intensive care may be necessary in the early phase treatment for acquired hemophilia A.

The patient was a 73-year-old man diagnosed with low-grade B-cell lymphoma not otherwise specified based on a biopsy of the enlarged cervical lymph nodes. He remained untreated and was monitored during follow-up visits only. Progressive anemia developed after 5 years. Enteroscopy revealed stricture and ulcerative lesions involving the entire circumference of the middle section of the small intestine. Based on the biopsy results, he was diagnosed with enteropathy-associated T-cell lymphoma (EATL). Biopsy of an enlarged axillary lymph node simultaneously revealed Epstein-Barr virus-negative diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma not otherwise specified (PTCL, NOS) as well as rearrangement of immunoglobulin heavy-chain and T-cell receptor beta and gamma chain genes. These findings suggested that the axillary lymph node contained composite lymphoma comprising DLBCL and PTCL and that EATL represented a discordant lymphoma. The present case emphasizes the importance of re-biopsy and genetic analysis following an atypical clinical course.

An 81-year-old woman with type 2 diabetes mellitus presented to our hospital due to anorexia, leg edema, and respiratory distress. Laboratory results revealed anemia, thrombocytopenia, elevated lactate dehydrogenase, and markedly elevated soluble interleukin-2 receptor levels. Computed tomography showed ground-glass opacities and consolidation in both lung fields, but no lymphadenopathy was noted. Intravascular large B-cell lymphoma (IVLBCL) was considered as a differential diagnosis; therefore, bone marrow and random skin biopsy were performed. Her respiratory condition deteriorated, with the occurrence of acute respiratory distress syndrome, disseminated intravascular coagulation, hemophagocytic syndrome, and further alveolar hemorrhage. Methylprednisolone pulse therapy was performed, but did not improve the patient’s condition. On hospital day 6, the acid-fast bacterial smear of the sputum using the Gaffky scale was 2, and on the next day, tuberculosis DNA was detected in the polymerase chain reaction. In the bone marrow biopsy, multiple epithelioid cell granulomas were found; thus, the patient was diagnosed with miliary tuberculosis. Although anti-tuberculosis therapy was started immediately, she died on hospital day 22. The soluble interleukin-2 receptor level increased up to 19,400 U/ml. The differential diagnosis should be cautiously made because miliary tuberculosis can mimic IVLBCL.

A 30-year-old woman who was 14 weeks pregnant was admitted to our hospital due to purpura, nasal bleeding, and abdominal pain. She was diagnosed with acquired thrombotic thrombocytopenic purpura (TTP) based on the presence of hemolytic anemia, thrombocytopenia, decreased ADAMTS 13 activity (<0.01 IU/ml), and high ADAMTS 13 inhibitor levels (4.8 BU/ml). Plasma exchange (PE) and steroid therapy were immediately administered. However, because she did not respond to these therapeutic approaches, rituximab was additionally administered on the sixth day of treatment. The level of ADAMTS 13 inhibitor increased to 12.5 BU/ml on the seventh day. Renal insufficiency, disturbed consciousness, and genital bleeding did not improve in spite of daily PE, steroid therapy, and second dose of rituximab. She finally died after sudden convulsions on the 14th day. Although the treatment outcomes of TTP have remarkably improved, some cases are refractory to therapy. Establishment of adequate treatment strategies for acquired TTP in pregnant women is required.

More than 1,200 hemoglobin variants are identified worldwide, and approximately 200 variants are detected in one of 3,000 Japanese people. Most of these patients are asymptomatic; however, some patients had hemolytic anemia or cyanosis. Herein, we report a case of a 49-year-old woman with prolonged fatigability after experiencing symptoms of common cold and intermittent brown urine. Her clinical data showed mild hemolysis, a disparity between SpO2 (93%) and pO2 (85.2 mmHg), and abnormally low HbA1c levels (3.7%). These findings lead to the diagnosis of unstable hemoglobin variant, Hb Hirosaki. A simple series of tests using pulse oximetry, an arterial blood gas analysis, measurement of HbA1c levels, or identifying the HPLC chromatogram of HbA1c can be the factors associated with the diagnosis of hemoglobinopathy.

Primary effusion lymphoma (PEL) is a rare type of non-Hodgkin lymphoma, usually presenting as serous effusions without detectable tumor masses, and it is universally associated with the human herpesvirus 8 (HHV8). In contrast, cases of HHV8-negative effusion lymphoma have been reported and termed as HHV8-negative PEL-like lymphoma. Here, we have reported a rare case of HHV8-negative PEL-like lymphoma that developed in the left atrium tumor 4 years after the pericardial drainage. A 74-year-old female was admitted due to cardiac tamponade caused by massive pericardial effusion. Pericardial drainage was performed, and cytopathologic examination of the fluid revealed atypical lymphoid cells consistent with an effusion lymphoma of B-cell lineage. The pericardial effusion was completely drained, and complete remission was achieved. After 4 years of the drainage, she developed syncope caused by arrhythmia. A computed tomography scan revealed a large tumor in the left atrium and multiple swollen mediastinal lymph nodes. Biopsy of one of the lymph nodes was performed, and its histology was consistent with diffuse large B-cell lymphoma. She was treated with chemotherapy, including rituximab, and complete remission was achieved again. Thus, our experience suggests that careful follow-up may be required in patients with HHV8-negative PEL-like lymphoma after complete remission has been achieved by the drainage.