A Case of Relapsed/Refractory CD56-Positive Acute Promyelocytic Leukemia, in Which Complete Molecular Remission Was Achieved Following Combination Therapy with Venetoclax and Azacitidine.

An 84-year-old woman was diagnosed as having acute promyelocytic leukemia(APL)in July Year X-3. The test for promyelocytic leukemia- retinoic acid receptor alpha(PML-RARA)mRNA was positive, while that for CD56 was negative. Since her white blood cell( WBC) count was <3,000/µL, with a count of APL cells of <1,000/µL, she was started on monotherapy with all-trans retinoic acid(ATRA). In September Year X-3, complete hematological remission(CHR)was confirmed. she refused to provide consent for receiving consolidation therapy. In February Year X-2, hematological relapse occurred. She was started on re-induction therapy with arsenite(ATO), and in June Year X-2, complete molecular remission(CMR)was achieved. She was started on post-remission therapy with ATO. In August Year X-1, she developed molecular relapse and was started on tamibarotene(Am80). In October Year X-1, hematological relapse was detected, and the test for CD56 was positive. She was started on combined venetoclax(VEN)+azacitidine(AZA)(VEN+AZA). After completion of 1 course of treatment, CMR was achieved, but she developed hematological relapse after 5 courses of treatment. She died of gastrointestinal hemorrhage. This is considered a valuable case for accumulating information on the treatment of CD56-positive APL resistant to ATRA and ATO.

Possible New Histological Prognostic Index for Large B-Cell Lymphoma.

We conducted a retrospective analysis of GRP94 immunohistochemical (IHC) staining, an ER stress protein, on large B-cell lymphoma (LBCL) cells, intracellular p53, and 15 factors involved in the metabolism of the CHOP regimen: AKR1C3 (HO metabolism), CYP3A4 (CHOP metabolism), and HO efflux pumps (MDR1 and MRP1). The study subjects were 42 patients with LBCL at our hospital. The IHC staining used antibodies against the 17 factors. The odds ratios by logistic regression analysis used a dichotomous variable of CR and non-CR/relapse were statistically significant for MDR1, MRP1, and AKR1C3. The overall survival (OS) after R-CHOP was compared by the log-rank test. The four groups showed that Very good (5-year OS, 100%) consisted of four patients who showed negative IHC staining for both GRP94 and CYP3A4. Very poor (1-year OS, 0%) consisted of three patients who showed positive results in IHC for both GRP94 and CYP3A4. The remaining 35 patients comprised two subgroups: Good (5-year OS 60-80%): 15 patients who showed negative staining for both MDR1 and AKR1C3 and Poor (5-year OS, 10-20%): 20 patients who showed positive staining for either MDR, AKR1C3, MRP1, or p53. The Histological Prognostic Index (HPI) (the four groups: Very poor, Poor, Good, and Very good) is a breakthrough method for stratifying patients based on the factors involved in the development of treatment resistance.

Eosinophil-rich variant of nodal marginal zone lymphoma: a clinicopathological study of 11 cases.

AIMS: Tissue eosinophilia is commonly observed in T-cell and classic Hodgkin lymphomas, but rarely in B-cell lymphomas. Herein, we present the first report of a case series on nodal marginal zone lymphoma (NMZL) with tissue eosinophilia. METHODS AND RESULTS: All 11 patients in this study had nodal disease at primary presentation. The mean age at diagnosis was 64 years. The mean follow-up period was 39 months, and all patients were alive. Nine of the 11 patients (82%) showed no recurrence, but the other two patients experienced recurrence in the lymph nodes or skin. Marked eosinophilic infiltration was observed in all biopsied lymph nodes. Nine of the 11 patients had a preserved nodular architecture with expanded interfollicular areas. The other two patients showed diffuse lymphoma cell infiltration with effacement of nodal architecture. One of them was diagnosed as having diffuse large B-cell lymphoma transformed from NMZL because large cells accounted for >50% of the lymphoma cells and formed sheet-like patterns. Cells were positive for CD20 and BCL2 and negative for CD5, CD10, and BCL6. Some patients showed myeloid cell nuclear differentiation antigen (MNDA) positivity. All patients showed B-cell monoclonality via flow cytometry, southern blotting, and/or polymerase chain reaction (PCR). CONCLUSION: All patients showed distinctive morphological features and could be misdiagnosed with peripheral T-cell lymphoma due to their eosinophil-rich backgrounds. The predominance of B cells, absence of histiocytes, and high endothelial venules in the interfollicular areas are key factors for diagnosis. B-cell monoclonality is the most reliable evidence of differentiation. We designated this type of lymphoma as an eosinophil-rich variant of NMZL.

Role of TGF-beta1 and TNF-alpha1 produced by neoplastic cells in the pathogenesis of fibrosis in patients with hematologic neoplasms.

We conducted this study with the objective of elucidating the mechanism of development of fibrosis in hematologic neoplasms and develop treatments for these patients. Among the suggested mechanisms of development of fibrosis is cases of hematologic neoplasms is the production of TGF-beta1 (transforming growth factor-beta-1) and TNF-alpha1 (tumor necrotizing factor-alpha-1) by the tumor cells, both of which are fibrosis-stimulating cytokines that act on fibroblasts to promote fibrosis. However, there are few reports based on human clinical pathology studies. We conducted an immunohistochemical study on paraffin-embedded formalin-fixed specimens obtained from 104 patients with various pathologic conditions (acute leukemia, malignant lymphoma, inflammation, cancer, etc.). The association of tissue fibrosis with positive immunohistochemistry for TGF- beta1 and/or TNF-alpha1, TGF-beta1 was found to be strongly associated with tissue fibrosis, and in cases with positive immunohistochemistry for TGF-beta1, the odds ratio for fibrosis was 12.8, which was significantly high. Combined positivity for TGF-beta1 and TNF-alpha1 was also associated with a significant odds ratio for fibrosis of 3.4, suggesting that TGF-beta1 expression is an important prerequisite. TGF-beta1 has been suggested as playing a relatively important role in tissue fibrosis. Future clinical application of these cytokines for both diagnosis and treatment is expected.

Clinical characteristics of Japanese patients with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis.

Myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) is a rare disease, which presents with features of myelodysplastic syndromes with ring sideroblasts and essential thrombocythemia, as well as anemia and marked thrombocytosis. SF3B1 and JAK2 mutations are often found in patients, and are associated with their specific clinical features. This study was a retrospective analysis of 34 Japanese patients with MDS/MPN-RS-T. Median age at diagnosis was 77 (range, 51-88) years, and patients had anemia (median hemoglobin: 9.0 g/dL) and thrombocytosis (median platelet count: 642 × 109/L). Median overall survival was 70 (95% confidence interval: 68-not applicable) months during the median follow-up period of 26 (range: 0-91) months. A JAK2V617F mutation was detected in 46.2% (n = 12) of analyzed patients (n = 26), while an SF3B1 mutation was detected in 87.5% (n = 7) of analyzed patients (n = 8). Like those with myelodysplastic syndromes or myeloproliferative neoplasms, patients often received erythropoiesis-stimulating agents and aspirin to improve anemia and prevent thrombosis. This study, which was the largest to describe the real-world characteristics of Japanese patients with MDS/MPN-RS-T, showed that the patients had similar characteristics to those in western countries.

Development of rapidly fatal TAFRO syndrome-like features in a patient with essential thrombocythemia.

TAFRO syndrome is a rare systemic inflammatory disease characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly. We encountered a case of calreticulin mutation-positive essential thrombocythemia (ET) with TAFRO syndrome-like features, followed by a rapid fatal course. The patient had been on anagrelide therapy for approximately three years for management of ET; however, she suddenly stopped going for follow-up and discontinued the medicine for a year. She presented with fever and hypotension, suggestive of septic shock, and was transferred to our hospital. The platelet count at the time of admission to another hospital was 50 × 104 / µL; however, it decreased to 25 × 104 / µL upon transfer to our hospital and further decreased to 5 × 104 / µL on the day of her death. In addition, the patient showed remarkable systemic edema and progression of organomegaly. Her condition suddenly worsened and led to her death on the 7th day of hospitalization. Postmortem, serum and pleural effusion interleukin (IL)-6 and vascular endothelial growth factor (VEGF) levels were significantly increased. Consequently, a diagnosis of TAFRO syndrome, since she met the diagnostic criteria for clinical findings and had high cytokine concentrations. Dysregulation of cytokine networks has also been reported in ET. Therefore, concurrent ET and TAFRO syndrome may have further triggered cytokine storms and contributed to the aggravation of the disease on development of TAFRO syndrome. To the best of our knowledge, this is the first report of complications seen in a patient with TAFRO syndrome due to ET.

Refractory Primary Vitreoretinal Lymphoma Involving the Spinal Cord with a Temporary Complete Response to Tirabrutinib.

Many patients with primary vitreoretinal lymphoma (PVRL) exhibit central nervous system (CNS) involvement either at the diagnosis or during follow-up. The prognosis in the patients of PVRL with relapsed or refractory CNS remains extremely poor. We herein report a patient with refractory PVRL who had recurrence in the spinal cord despite receiving high-dose methotrexate-based chemotherapy and whole-brain radiotherapy. The patient surprisingly responded to tirabrutinib temporarily. We believe that this case suggests the utility of this new target therapy.

Factors Associated With Survival in Patients With End-of-Life Hematological Malignancies Who Received Chemotherapy: A Retrospective Single-Institution Study.

BACKGROUND: Clinicians can appropriately terminate treatment or reduce treatment intensity by determining prognostic factors of end-of-life chemotherapy. In particular, it provides important information for patients with hematological malignancies who receive chemotherapy until near-the-end of life compared with patients with solid tumors. This study aimed to clarify whether existing prognostic tools are associated with the survival in patients with end-of-life hematological malignancies who received chemotherapy. METHODS: We retrospectively reviewed the records of 247 patients diagnosed with hematological malignancies and died at our university hospital hematology ward between May 2015 and May 2021. We performed multivariate analysis in 82 (33.2%) patients who received end-of-life chemotherapy using the Palliative Prognostic Index (PPI) and inflammation-based prognostic models, such as the Glasgow Prognostic Score (GPS), Prognostic Nutritional Index (PNI), and Controlling Nutrition Status (CONUT). RESULTS: On comparing 82 patients who received end-of-life chemotherapy with 165 patients who did not, the proportion of patients with PPI group A, GPS score = 0, and CONUT normal/mild was significantly higher among patients who received chemotherapy. In multivariate analysis, we identified PPI groups B (2.0 < PPI ≤ 4.0) and C (PPI > 4.0) [hazard ratio (HR) 2.1290, 95% CI 1.1830-3.828, P = .01166, respectively] and age ≥ 65 years (HR 2.0170, 95% CI 1.1280-3.607, P = .01805) were associated with overall survival. CONCLUSION: PPI use and age were independent associating factors for patients with hematological malignancies receiving end-of-life chemotherapy. PPI, a popular prognostic tool may be helpful for patients and hematologists to make decisions about end-of-life care.

Hodgkinoid histiocytosis: an atypical nodal CD30 and S100-positive histiocytosis with eosinophilia.

Histiocytes and dendritic cells may display cytological atypia and an aberrant immunophenotype even in reactive processes. Herein, we describe two cases of "Hodgkinoid histiocytosis" that show distinctive clinicopathological features, mimicking morphologically classic Hodgkin lymphoma (CHL), but suggesting reactive histiocytic/dendritic cell proliferation in lymph nodes. Both the patients presented with peripheral lymphadenopathy and blood eosinophilia with skin manifestations. Lymph node biopsy revealed scattered large histiocytes resembling Hodgkin cells with a round or stellate shape, abundant cytoplasm, and distinct nucleoli admixed in a predominant inflammatory background. The Hodgkinoid histiocytes occasionally showed emperipolesis. They expressed CD30, S100, and PD-L1 proteins but lacked PAX5 and CD1a expressions, Epstein-Barr association, BRAF V600E mutation, and PD-L1 gene amplification. Neither of the patients showed overt progression to malignant haematopoietic neoplasms during the disease course. An identical case series of four patients has been reported to date. Both these series highlight the potential of being interpreted as CHL due to the presence of Hodgkinoid histiocytes with CD30 positivity.

Poorly Differentiated Neuroendocrine Carcinoma of Unknown Primary with Metastasis to the Testis: A Case Report.

Neuroendocrine neoplasms are rare epithelial neoplasms with neuroendocrine differentiation. Few cases of primary testicular poorly differentiated neuroendocrine carcinomas (PD-NECs) have been reported, and secondary testicular neoplasms are rare. A 61-year-old man with a chief complaint of left testicular swelling was referred to our hospital. An orchiectomy was performed in order to determine the pathological diagnosis. Pathological examination showed diffuse sheets of highly atypical cells that were positive for neuroendocrine markers and a Ki-67 proliferation index of 80%. The patient was diagnosed with poorly differentiated small-cell NEC. Contrast-enhanced computed tomography revealed multiple metastases to the pancreas, adrenal glands, and lymph nodes. Esophagogastroduodenoscopy showed multiple gastric metastases, and biopsy revealed the same histological findings as observed for the testicular tumor. Contrast-enhanced magnetic resonance imaging of the head also revealed multiple brain metastases. The confirmed diagnosis was PD-NEC of unknown primary with metastases to the testis, stomach, pancreas, adrenal glands, brain, and lymph nodes. We started the first-line chemotherapy with etoposide and cisplatin. Stereotactic radiotherapy for the brain metastases was administered between the first and second cycles. After five cycles, a partial response was observed; however, disease progression was observed after seven cycles with recurrence of the brain metastases and enlargement of all tumors. To our knowledge, this is the first report of an unknown primary PD-NEC with metastasis to the testis.

A Case of EBER Positive Angioimmunoblastic T-cell Lymphoma Combined with Myxofibrosarcoma of the Pleura.

A 76-year-man presented with generalized lymphadenopathy. Lymph node biopsy led to the diagnosis of Epstein-Barr virus-encoded small RNA in situ hybridization (EBER)-positive angioimmunoblastic T-cell lymphoma (AITL). He was initiated on treatment with oral prednisolone (PSL) at the dose of 50 mg/day; however, he was diagnosed as having right pleural effusion. He was started on treatment with cyclophosphamide, doxorubicin, vincristine and PSL (CHOP therapy). However, the right pleural effusion increased in size, and thoracentesis was performed. The aspirated pleural fluid was bloody, and since only a very small number of atypical cells were found, no definitive diagnosis could be made. CT revealed multiple nodular lesions in the pleura, and thoracoscopy was performed, which revealed jelly-like white lesions in the right parietal pleura. Biopsy raised the suspicion of undifferentiated pleomorphic sarcoma (UPS). Treatment with carboplatin and pemetrexed was started, but his respiratory symptoms worsened and he died. Autopsy revealed evidence of complete remission of AITL and myxofibrosarcoma (MFS) of the pleura. This is the first reported case of AITL combined with MFS.

Prognostic Value of Palliative Prognostic Index for Hospitalized Patients With End-of-Life Hematologic Malignancies in a Japanese University Hospital.

PURPOSE: Uncertainty of prognosis is one reason patients with hematologic malignancies receive aggressive therapy near end of life more often than those with advanced solid tumors. It is unknown whether end-of-life prognosis prediction models are useful for patients with hematologic malignancies, especially hospitalized patients receiving chemotherapy, because most prognostic models were developed for patients with solid tumors. The purpose of this study was to evaluate the prognostic accuracy of the Palliative Prognostic Index (PPI) for end-of-life patients with advanced hematologic malignancies. METHODS: We retrospectively reviewed the records of 143 patients who became resistant to standard chemotherapy and died of disease progression in our university hospital hematology ward between May 2015 and November 2019. Patients were classified according to PPI scores (groups: A, PPI ≤ 2.0; B, 2.0 < PPI ≤ 4.0; and C, PPI > 4.0) based on their clinical charts at admission. The median overall survival for each patient (95% confidence interval) was calculated using the Kaplan-Meier method. Log-rank tests were used to determine significant differences between survival curves. RESULTS: Median patient age was 76 years (range: 39-92 years), and 59% were men. Median overall survival times in the PPI groups A, B, and C were 58 days, 36 days, and 10 days, respectively. Statistically significant differences in survival time were observed between the groups (P < .01); prediction accuracy was similar to that for patients with different diagnoses. CONCLUSION: The usefulness of PPI was validated for near-end-of-life hospitalized patients with hematologic malignancies.

Two autopsy cases of pulmonary leukemic infiltration mimicking severe pneumonia in patients with acute myeloid leukemia.

Although a previous autopsy series demonstrated that pulmonary leukemic infiltration (PLI) is a major pulmonary complication in patients with acute myeloid leukemia (AML), an antemortem diagnosis of PLI is rare. Diverse pulmonary complications cause acute respiratory failure (ARF) in patients with AML undergoing chemotherapy. This article reports two elderly patients with AML who presented with ARF due to PLI mimicking severe pneumonia during induction chemotherapy. Accurate antemortem diagnosis of PLI was almost impossible without pathological examination since the clinical course was not typical of PLI. We recommend considering PLI in patients with AML who have an unknown etiology of ARF.

Chronic active Epstein-Barr virus-associated secondary hemophagocytic lymphohistiocytosis in pregnancy: a case report.

BACKGROUND: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a rare and fatal disease characterized by uncontrolled immune cell activation that can lead to a cytokine storm. Unfortunately, this condition can occur even during pregnancy, threatening both maternal and fetal lives. CASE PRESENTATION: A 23-year-old nulliparous woman at 26 weeks of gestation presented with continuous fever, coughing, and sore throat. Upon arrival at our hospital, her temperature was >38°C and laboratory findings indicated cytopenia (neutrophil count, 779/µL; hemoglobin level, 10.2 g/dL; platelet count, 29,000/µL), elevated ferritin level (1,308 ng/mL), and elevated soluble interleukin-2 receptor level (11,200 U/mL). Computed tomography showed marked splenomegaly. Bone marrow examination revealed hemophagocytosis, and blood examination showed a plasma Epstein-Barr virus (EBV) DNA level of 8.9 × 105 copies/µg. The monoclonal proliferation of EBV-infected T cells was confirmed by Southern blotting, and the patient was diagnosed with chronic active EBV-associated sHLH and T-cell lymphoproliferative disease. Immediately after admission, the patient's condition suddenly deteriorated. She developed shock and disseminated intravascular coagulation, requiring endotracheal intubation along with methylprednisolone pulse and etoposide therapy. Although the patient recovered, she delivered a stillborn baby. After delivery, she was treated with reduced-dose dexamethasone, etoposide, ifosfamide, and carboplatin (DeVIC) and steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapies. Five months after diagnosis, she received human leukocyte antigen-haploidentical allogeneic bone marrow transplantation from her sister. She remains in remission for 5 months from the time of transplantation to the present. CONCLUSIONS: sHLH, which may cause maternal and fetal death, should be carefully considered in critically ill pregnant women, particularly those presenting with continuous fever and cytopenia.

Need to Inspect the Total Gastrointestinal Tract of Patients With Malignant Lymphomas.

BACKGROUND/AIM: Malignant lymphoma (ML) cases with overlapping gastrointestinal (GI) lesions are often encountered. We aimed to elucidate the importance of examining the GI tract in patients with ML and assess the overlap rate. PATIENTS AND METHODS: We analysed 190 patients diagnosed with GI MLs. We compared the overlap rates among the different histopathological types. RESULTS: Twenty-five (13.2%) patients had overlapping GI lesions in more than two segments. The overlap rates were 100% in mantle cell lymphomas (MCL), 27.6% in follicular lymphomas (FL), and 16.3% in diffuse large B-cell lymphomas (DLBCL). MCL, FL, and DLBCL cases showed significantly higher overlap rates than mucosa-associated lymphoid tissue lymphoma cases (p<0.01). About 64.0% of cases of ML with overlapping lesions involved the small intestine. CONCLUSION: In GI ML cases, it is ideal to examine the entire GI tract by esophagogastroduodenoscopy, colonoscopy, and capsule endoscopy and/or balloon-assisted endoscopy, especially in MCL, FL, and DLBCL.

Use of Ibrutinib in 10 Patients with Treatment-Naïve or Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma in Real-World Clinical Practice -A Report from a Single Medical Institution.

In Japan, ibrutinib has been approved as both a front-line and later-line treatment for chronic leukemia/small lymphocytic lymphoma(CLL/SLL). However, little is known about the actual outcomes and adverse events(AEs)associated with the use of ibrutinib in Japanese patients. OBJECTIVE: The outcomes and AEs of patients treated with ibrutinib in a real-world setting were investigated. METHODS: A retrospective cohort study of all patients with CLL/SLL who were treated with ibrutinib at a single institution was conducted. RESULT: In total, 10 patients, including 5 treatment-naïve patients(50%), were enrolled. The median follow-up period was 9.8 months(range, 0.2-21.6 months), and the estimated overall response rate (ORR: complete remission plus partial remission)was 60%. The median overall survival and progression-free survival outcomes were not reached. During the follow-up period, 4 patients(40%)had at least one AE and 1 patient(10%)had at least one grade≥3 AE. Ibrutinib was discontinued in 4 patients(40%)because of AEs in 2 patients(20%), the progression of CLL in 1 patient(10%), and financial reasons in 1 patient(10%). Richter's transformation did not occur in any of the cases. CONCLUSION: The ORR was lower(60%)than that observed in clinical trials. The frequency and severity of AEs were both relatively low, although the discontinuation rate was high(40%). Patient education and medication adherence were considered important.

Small Neuroendocrine Tumors of the Whole Gastrointestinal Tract Performed Endoscopic or Surgical Resections Also Show Positive for Lymphovascular Invasion.

BACKGROUND AND AIMS: In gastrointestinal neuroendocrine tumors (GI-NETs), tumor size and grading based on cellular proliferative ability indicate biological malignancy but not necessarily clinically efficient prognostic stratification. We analyzed tumor size- and grading-based prevalence of lymphovascular invasion in GI-NETs to establish whether these are true biological malignancy indicators. METHODS: We included 155 cases (165 lesions), diagnosed histologically with GI-NETs, that had undergone endoscopic or surgical resection. Patient age, sex, method of treatment, tumor size, invasion depth, lymphovascular invasion positivity according to Ki-67 index-based neuroendocrine tumor grading, distant metastases, and outcome were evaluated. The primary endpoints were the prevalence of lymphovascular invasion according to tumor size and grading. RESULTS: Overall, 24.8% were positive for lymphovascular invasion. There was a high rate of lymphovascular invasion positivity even among grade 1 cases (22.8%). The rate of lymphovascular invasion was 3.4% for grade 1 cases <5 mm, with a lymphovascular invasion rate of 8.7% for those 5-10 mm. Lymphovascular invasion ≤10% required a tumor size ≤8 mm, and lymphovascular invasion ≤5% required a tumor size ≤6 mm. A cutoff of 6 mm was identified, which yielded a sensitivity of 79% and a specificity of 63%. Even small GI-NETs grade 1 of the whole GI tract also showed positive for lymphovascular invasion. CONCLUSIONS: GI-NETs ≤10 mm had a lymphovascular invasion prevalence exceeding 10%. The lymphovascular invasion impact in GI-NET development is incompletely understood, but careful follow-up, including consideration of additional surgical resection, is crucial in cases with lymphovascular invasion.

Hemophagocytic lymphohistiocytosis associated with Epstein-Barr virus-positive diffuse large B-cell lymphoma, NOS of bone marrow-liver-spleen type: an autopsy case report.

Lymphoma-associated hemophagocytic lymphohistiocytosis (HLH) has a significantly poor prognosis among secondary HLH. We describe the rare case of a 74-year-old female with secondary HLH presenting with a rapidly fatal course. Post-mortem examination revealed Epstein-Barr virus (EBV) -positive diffuse large B-cell lymphoma (DLBCL). We were unable to make a definite antemortem diagnosis because the patient did not exhibit lymphadenopathy and bone marrow biopsy demonstrated hemophagocytosis without evidence of lymphoma. She died of multiple organ failure on the twelfth day of hospitalization despite a temporary response to steroids. Autopsy revealed diffuse lymphoma cell infiltration of the bone marrow, liver and spleen, suggesting "bone marrow-liver-spleen" (BLS)-type large B-cell lymphoma (LBCL). BLS-type LBCL is a rare and clinically aggressive lymphoma, usually associated with fever, cytopenia and HLH. The disease has a high mortality rate due to the delay in diagnosis and a highly aggressive clinical course. Further studies are required to improve our understanding of this rare extranodal DLBCL.

Low‒Risk Essential Thrombocythemia Who Presented with Recurrent Episodes of Cerebral Hemorrhage during Pregnancy and Developed Cerebral Infarction during Puerperium.

A 42‒year‒old woman. At week 27 of pregnancy, she developed subcortical hemorrhage and underwent open cranial surgery for hematoma evacuation. The platelet(Plt)count was 297,000/µL. At week 34 of pregnancy, she developed subcortical hemorrhage again. The Plt count was 429,000/µL. At week 35 of pregnancy, the ventricular rupture and she underwent drainage and emergency cesarean section. The Plt count was 687,000/µL. Two days after delivery, hemorrhage was detected. The Plt count was 815,000/µL. Six days after delivery, she developed infarction. The Plt count was 915,000/µL. MRI revealed no evidence of aneurysm, arteriovenous malformations or tumor. Ten days after delivery, the Plt count was 1,173,000/µL. Bone marrow examination led to the diagnosis of essential thrombocythemia(ET). JAK2, CARL and MPL was negative. She was rated as"low‒risk"by IPSET‒thrombosis, and as"ultralow"risk by revised IPSET‒thrombosis. von Willebrand factor(VWF)activity was as high as 247%. The bleeding time and platelet aggregation activity were normal. There was no evidence of disseminated intravascular coagulation(DIC)or hypertensive disorders of pregnancy(HDP). She died of cerebral hemorrhage and infarction, 26 days after delivery.