Autoimmune Hemolytic Anemia Associated with Mature Ovarian Cystic Teratoma Containing Monoclonal Immunoglobulin G: A Case Report and Review of Literature.

Background: Autoimmune hemolytic anemia (AIHA) associated with solid tumors such as mature cystic teratomas is rare and poorly understood. Here, we report a successfully treated case of secondary AIHA in a mature cystic teratoma containing antibodies against red blood cells. Case description. A 22-year-old woman was referred to our hospital with progressive anemia. Laboratory findings revealed hemolysis with a positive direct and indirect antiglobulin test. Imaging studies identified a left ovarian mass, suspected to be a mature cystic teratoma, which was later confirmed by histopathology after laparoscopic oophorocystectomy. The patient was treated with prednisolone, resulting in improved anemia. To examine the relationship between the tumor and AIHA, an indirect antiglobulin test was performed on the tumor contents. Stronger aggregations were observed at any concentration diluted by 10 times from 10 to 10,000 times of the tumor contents compared to the patient's serum. Additionally, immunofixation electrophoresis of the tumor contents revealed the presence of monoclonal immunoglobulin G-κ. Conclusion: The presence of monoclonal IgG-κ in the tumor suggests intratumoral antibody production as a possible mechanism. Further research is necessary to elucidate the pathogenic relationship between such tumors and AIHA. The report also highlights the importance of considering secondary AIHA in patients with unexplained anemia and solid tumors.

Non-nodal mantle cell lymphoma mimicking hairy cell leukemia.

This case of non-nodal mantle cell lymphoma (MCL) showcases atypical hairy cell-like features, distinguishing it via next-generation sequencing. Despite a TP53 mutation indicating poor prognosis, our case followed an indolent course, highlighting the importance of genetic testing and phenotypical examination in MCL.

A Novel SPTA1 Mutation in a Patient with Hereditary Spherocytosis without a Family History and Coexisting Gilbert's Syndrome.

Most patients with hereditary spherocytosis (HS) have a family history of disease, while those without such a history are difficult to diagnose. We herein report a case of HS with no family history harboring a novel heterozygous mutation of SPTA1, c.2161G>A (p.E721K), and a homozygous polymorphism of UGT1A1*6. In silico analyses suggested that the mutation might contribute to the pathogenesis of HS. The coexistence of HS and Gilbert's syndrome increases the risk of gallstones. Therefore, splenectomy, alone or in combination with cholecystectomy, is recommended. The determination of genetic diathesis provides useful information for the management of hemolytic anemia.

An experience with ibrutinib monotherapy for Richter's syndrome isolated in the central nervous system.

Richter's syndrome (RS) of the central nervous system (CNS) is known to have an extremely poor prognosis. Ibrutinib has been reported to have some activity in patients with RS, despite its poor prognosis. Although ibrutinib crosses the blood-brain barrier, its efficacy in RS patients with CNS involvement remains unknown. Here, we report a case of RS isolated in the CNS that was confirmed to be clonally related to chronic lymphocytic leukemia (CLL) by immunoglobulin heavy chain gene analysis. Although the median survival of patients with RS clonally related to CLL was significantly shorter than that of patients with RS clonally unrelated to CLL, the patient received ibrutinib monotherapy without experiencing any significant adverse events, and the disease remained stable with ibrutinib until 6 weeks later. Following whole-brain radiation therapy (40 Gy in 20 fractions) with dexamethasone, the patient has survived for five months after diagnosis. Thus, ibrutinib may be a safe and effective therapeutic option for patients with RS and CNS involvement.

[Acute promyelocytic leukemia complicated with central nervous system involvement successfully treated with all-trans retinoic acid via nasogastric tube].

At initial diagnosis, central nervous system (CNS) involvement in acute promyelocytic leukemia (APL) is rare. Here, we report a case of newly diagnosed APL with CNS involvement that was successfully treated with all-trans retinoic acid (ATRA)-combined chemotherapy. A 64-year-old woman was referred to our hospital to evaluate a bleeding tendency, and she was diagnosed with APL. Induction chemotherapy with ATRA via a nasogastric tube was initiated under mechanical ventilation because of respiratory failure and disturbance of consciousness. Although her respiratory condition improved a few days after initiating treatment, the disturbance of consciousness remained. Brain magnetic resonance imaging showed mixed signals of tumor infiltration and acute cerebral infarction with a focus on the right cerebellum. The patient was diagnosed with CNS involvement of APL and acute cerebral infarction. Three months after the initiation of induction therapy, her consciousness improved along with the reduction in CNS involvement, and complete molecular remission was achieved. Thus, patients with APL can have CNS involvement at initial diagnosis. Administering ATRA via nasogastric tube can be a good therapeutic option in patients with difficulty swallowing due to disturbance of consciousness.

Sézary Syndrome with CD4/CD8 Double-Negative Neoplastic T Cells in Peripheral Blood.

Sézary syndrome is a rare leukemic type of cutaneous T-cell lymphoma characterized by the presence of neoplastic T cells with cerebriform nuclei (Sézary cells) in the skin, lymph nodes, and peripheral blood. Typical Sézary cells have a CD3+CD4+CD8- phenotype; however, in cases of the aberrant loss of antigens on Sézary cells, especially the loss of critically important T-cell antigens such as CD4, there is a possibility of misdiagnosing the disease or underestimating the tumor burden of the disease. Here, we report a rare case of Sézary syndrome with CD4/CD8 double-negative Sézary cells in the peripheral blood. Most of the Sézary cells in the peripheral blood had lost CD4 expression, and we diagnosed the disease and evaluated the tumor burden by multicolor flow cytometry. Intriguingly, the Sézary cells showed a typical CD4+CD8-CD7- phenotype in the skin even though the cells in the peripheral blood lacked CD4. The patient responded well to treatment with bexarotene and narrow-band ultraviolet B therapy. Analysis by multicolor flow cytometry is essential to diagnose this rare type of Sézary syndrome and evaluate the tumor burden.

[Successful treatment with cyclosporine in a patient with rituximab-refractory thrombocytopenic purpura].

Acquired thrombotic thrombocytopenic purpura (aTTP) is a life-threatening systemic thrombotic microangiopathy characterized by the presence of anti-ADAMTS13 antibodies (inhibitor). Here we report the case of a patient with refractory aTTP successfully treated with cyclosporine. A 69-year-old man presenting with hematuria and petechiae was referred to our hospital; he was disoriented and febrile. Laboratory results revealed Coombs-negative hemolytic anemia, thrombocytopenia, and renal failure. Undetectable ADAMTS13 activity and presence of anti-ADAMTS13 antibodies (inhibitor) confirmed the diagnosis of aTTP. Despite performing plasma exchange and administering prednisolone and rituximab (375 mg/m2), we were unable to restore his platelet counts to the normal level. Therefore, he was treated with cyclophosphamide (500 mg/bodyweight), vincristine (1.4 mg/m2), bortezomib (1.3 mg/m2), and cyclosporine (2.5 mg/kg). After the cyclosporine therapy, his platelet counts gradually normalized. Continuous cyclosporine maintenance therapy led to complete disappearance of the inhibitor. Therapeutic strategies for refractory aTTP have not yet been established. Further investigations are warranted to establish a therapeutic strategy for refractory aTTP.

Early central nervous system relapse of monomorphic epitheliotropic intestinal T-cell lymphoma after cord blood transplantation.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare subtype of intestinal T-cell lymphoma that occurs mostly in Asia. CHOP-like therapy is usually selected, but the prognosis is very poor. This report concerns a 43-year-old woman with newly diagnosed stage IVA MEITL. The patient obtained a partial response after 4 cycles of GDP (gemcitabine, dexamethasone, cisplatin) and achieved a complete response (CR) after cord blood transplantation (CBT) conditioned with total body irradiation, cyclophosphamide, and cytarabine. Seven months after transplantation, the patient experienced cognitive impairment. Magnetic resonance imaging of the brain showed a high-intensity lesion in the right cerebral peduncle and internal capsule. A cerebrospinal fluid examination confirmed central nervous system (CNS) relapse of MEITL. After 3 cycles of MPV (methotrexate, procarbazine, vincristine) followed by whole-brain radiotherapy, her cognitive impairment improved. Due to disease progression, she died 6 months after CNS relapse. Given the CNS relapse after achieving a CR with GDP and CBT in this patient, CNS prophylaxis during first-line therapy may be beneficial in the treatment of MEITL.

[Therapy-related acute promyelocytic leukemia with complex karyotype accompanied by cryptic PML/RARA on chromosome 15 by metaphase FISH].

A 53-year-old male presented with pancytopenia for 13 months. He had a past history of follicular lymphoma and hypopharyngeal cancer, which was treated via chemotherapy and radiotherapy. Bone marrow aspiration biopsy of the patient revealed a hypocellular marrow with 32% of hypergranular blasts without Auer bodies. There were also erythroid and megakaryocytic dysplasia in the bone marrow. Although the PML/RARA transcript was detected by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction (RT-PCR), the G-banding karyotype analysis showed a complex karyotype without t (15;17). The PML/RARA fusion signal was identified on chromosome 15 by metaphase FISH. The patient was diagnosed of therapy-related acute promyelocytic leukemia (t-APL) with cryptic PML/RARA. He successfully attained molecular complete remission with all-trans retinoic acid (ATRA) and two courses of arsenic trioxide (ATO). He was subsequently administered nivolumab without ATRA maintenance therapy because of a progressing metastasis of a hypopharyngeal cancer to the lung. The patient had a relapse of t-APL following nine courses of nivolumab, 8 months after ending consolidation therapy with ATO. Reinduction therapy with ATRA was not effective for the relapsed t-APL that was accompanied by del (5q) and monosomy 7. Little has been previously reported on t-APL with cryptic PML/RARA. Therefore, the clinical course of this patient may provide useful insights about the characteristics of t-APL with cryptic PML/RARA.

[Successful treatment with a combination of elotuzumab, lenalidomide and dexamethasone of extramedullary disease in a patient with refractory multiple myeloma].

A 56-year-old man diagnosed with multiple myeloma was treated with CBD (cyclophosphamide, bortezomib, and dexamethasone; DEX), which was discontinued because of bortezomib-associated adverse events. Thereafter, he was treated with Ld (lenalidomide; LEN+DEX) followed by high-dose chemotherapy with autologous stem cell rescue, resulting in a complete response. Ld as maintenance therapy was discontinued because of immune thrombocytopenia, resulting in disease progression. Although treatment was switched to Pd (pomalidomide+DEX), DLd (daratumumab+LEN+DEX), and IRd (ixazomib+LEN+DEX); the patient's M protein level continued to increase and the extramedullary disease expanded despite radiotherapy. He was treated with E-Ld (elotuzumab+LEN+DEX) after 3 cycles of short VAD (vincristine, doxorubicin, and DEX). The extramedullary disease disappeared after 8 cycles of E-Ld. To the best of our knowledge, this is the first report showing the effectiveness of E-Ld treatment for extramedullary disease of a heavily treated patient for multiple myeloma. We believe that the clinical course of this patient provides useful insights about the antimyeloma mechanism of elotuzumab.