A case of successful CAR-T cell therapy for early isolated CNS recurrence of DLBCL with persistent CAR-T cells.

Secondary central nervous system (CNS) lymphomas typically require CNS-penetrating drugs; however, the available agents are limited with temporary effects and poor outcomes. Chimeric antigen receptor T (CAR-T) cell therapy (lisocabtagene maraleucel; liso-cel) has been used to treat a few cases of isolated secondary CNS lymphoma. Herein, we report the case of a 66-year-old male diagnosed with diffuse large B-cell lymphoma (Ann Arbor grade IV; R-IPI, good risk; CNS IPI: Intermediate risk) who achieved complete remission (CR) after six courses of R-CHOP therapy. Three months later, he presented with ptosis and eye movement disorder. Systemic CT and bone marrow examination revealed no lymphoma. Although cranial-enhanced MRI showed normal findings, an increased number of B-cells (51/µL) with the original lymphoma phenotype (CD19+CD79a+CD5-CD10-CD20-Igλ+) was detected in cerebrospinal fluid (CSF), indicating an isolated CNS relapse. Seven high-dose methotrexate courses led to partial response. Subsequently, the patient received CAR-T cell therapy with tolerable adverse events - cytokine release syndrome treated with tocilizumab, no immune effector cell-associated neurotoxicity syndrome, and bone marrow failure treated with granulocyte-colony stimulating factor and eltrombopag. Sequential flow cytometry revealed a high peak of CAR-T cells and the presence of residual CAR-T cells in the peripheral blood, indicating immune surveillance of CNS lymphoma by CAR-T cells. This treatment led to a second CR. This case is the first to validate the efficacy and safety of CAR-T cell therapy for isolated secondary CNS lymphoma in clinical practice. Future accumulation of evidence on the efficacy and safety of CAR-T cell therapy is essential.

The clinical impact of the ratio of C-reactive protein to albumin (CAR) in patients with acute- and lymphoma-type adult T-cell leukemia-lymphoma (ATL).

Recently, the ratio of C-reactive protein to albumin (CAR) is used as an inflammatory marker that has been demonstrated to be a simple and reliable prognostic factor in solid tumors and hematological malignancy. However, no studies of the CAR have been performed in patients with adult T-cell leukemia-lymphoma (ATL). We retrospectively analyzed the clinical features and outcomes in 68 newly diagnosed acute- and lymphoma-type ATL [(acute-(n=42) or lymphoma-type (n=26)] patients in Miyazaki Prefecture from 2013 to 2017. Furthermore, we investigated correlations between pretreatment CAR levels and clinical features. The median age was 67 years (range, 44 - 87). Patients were initially treated by either palliative therapy (n=14) or chemotherapy [n=54; CHOP therapy (n=37)/ VCAP-AMP-VECP therapy (n=17)], and showed median survival durations of 0.5 months and 7.4 months, respectively. The factors affecting OS by multivariate analysis were age, BUN, and CAR. Importantly, we revealed that the high CAR group (optimal cut-off point; 0.553) was a significant indicator of worse OS by multivariate analysis (p< 0.001, HR; 5.46). The median survival of patients with a CAR< 0.553 was 8.37 months, while patients with a CAR>0.553 had a median survival of 3.94 months. The different clinical features between high CAR and low CAR groups were hypoproteinemia and the implementation of chemotherapy. Furthermore, in the chemotherapy group, but not the palliative therapy group, CAR was a significant prognostic marker. Our study indicated that CAR may be a new simple and significant independent prognostic marker in acute- and lymphoma-type ATL patients.

An Extragastrointestinal Tumor Diagnosed as a Vaginal Mass during Pregnancy.

We report a case of an extragastrointestinal stromal tumor diagnosed as a vaginal mass during pregnancy. The mass was detected during routine examination at 24 weeks of gestation. At 26 weeks, the patient underwent transvaginal ultrasonography and magnetic resonance imaging, which revealed a blood flow-rich mass of approximately 50 × 30 mm in the rectovaginal septum. At 29 weeks of gestation, we resected the mass vaginally and the pathological diagnosis was a gastrointestinal stromal tumor. Chemotherapy was withheld until after full-term birth because the proliferation index of the tumor cells was low. The patient delivered a healthy infant. Imatinib was commenced at 1 month postpartum, with no recurrence or metastasis after 2.5 years. An extragastrointestinal stromal tumor as a vaginal mass in pregnancy has not been reported; however, our case suggests that the tumor should be considered a differential diagnosis of a vaginal mass in pregnancy.

[Analysis of Prognostic Factors Considering Absolute Lymphocyte Count of Metastatic Breast Cancer Patients with Eribulin Mesylate Therapy-A Retrospective Study in a Single Institution].

Recently, a study for eribulin mesylate(ERI), which is a useful drug for metastatic and recurrent breast cancer, reported that the absolute lymphocyte count(ALC)before administration is a useful prognostic factor. We retrospectively examined whether the results were reproducible in the patients with ERI. We examined the effect of ERI on the overall survival(OS)in 21 patients with HER2-negative metastatic and recurrent breast cancer who underwent treatment with ERI at our hospital. The clinical benefit ratio(CBR)was 57.1%. The median time to treatment failure(TTF)was 5.8 months and median OS was 19.9 months, showing a positive correlation between the TTF and OS. The factors that significantly prolonged the OS in univariate analysis were the TTF(<3 months vs ≥3 months, p<0.001), NLR(<3 vs ≥3, p=0.037), and ALC(<1,000/ µL vs ≥1,000/µL, p=0.008). In the multivariate analysis, TTF and ALC were the prognostic factors. The ERI outcome at our institution was good regardless of the subtype. The results of the multivariate analysis showed that TTF and ALC were factors that prolonged OS, and patients who received ERI for >3 months had good OS. Long-term administration of ERI was assumed to affect the immune microenvironment and prolong OS. Additionally, our data showed that the lymphocyte count before ERI administration is a simple and useful prognostic factor.

Postpartum regression of human papillomavirus-related vulvar cancer: A case report.

We report a case of a 23-year-old pregnant woman (gravida 2 para 0, pregnancy 33 weeks and 3 days) with a history of laser ablation for cervical intraepithelial neoplasia-3 at 22 years. At initial visit, a 2 × 2 × 1-cm elevated mass was found on right labia majora. Biopsy results revealed squamous cell carcinoma of right labia; immunostaining revealed p16 positivity. Patient was diagnosed with human papillomavirus-related vulvar cancer. Selective cesarean section was performed at 36 weeks and 4 days of gestation. Postoperative histopathological diagnosis of squamous cell carcinoma, and 1.7-mm deep infiltrations led to vulvar cancer stage IB diagnosis. Reduction operation was performed, and postoperative follow-up of 1 year and 8 months revealed no recurrence. These results emphasize that small vulvar tumors during pregnancy should not be underestimated and histological examinations should be performed without hesitation. Careful observation and evaluation of tumors is necessary during pregnancy and after delivery because they may shrink postdelivery.

A rare case of synchronous multiple primary malignancies of breast cancer and diffuse large B-cell lymphoma that responded to multidisciplinary treatment: a case report.

BACKGROUND: Multiple primary malignancies of breast cancer and diffuse large B-cell lymphoma (DLBCL) are rare. Here, we report a case of advanced breast cancer and DLBCL managed with multidisciplinary therapy preceded by surgery with a successful outcome. CASE PRESENTATION: During a medical examination, a 71-year-old woman was diagnosed with a right breast mass, enlarged lymph nodes throughout the body, and a splenic tumor. The results of the clinical examination and imaging were suggestive of widely spread breast cancer with lymph node metastasis and malignant lymphoma with systemic metastasis. The histological evaluation of the biopsied breast tissue revealed human epidermal growth factor receptor 2 (HER2)-positive breast cancer, whereas the histological evaluation of the excised inguinal lymph node revealed DLBCL. 18F-FDG PET/computed tomography was performed, and it was determined that both breast cancer and DLBCL were in an advanced stage. Thus, mastectomy was performed, and the axillary lymph nodes showed mixed metastasis of breast cancer and DLBCL. Soon after, the R-CHOP therapy was initiated (375-mg/m2 rituximab, 2-mg/m2 vincristine, 50-mg/m2 doxorubicin, 750-mg/m2 cyclophosphamide, and 125-mg methylprednisolone). After irradiation of the spleen, trastuzumab was administered for 1 year. CONCLUSIONS: We experienced a case of combined breast cancer and DLBCL, which was difficult to treat because both were in advanced stages. Thorough staging of the malignancy and discussion by a multidisciplinary team are necessary to determine the optimal treatment strategy.

Immunohistopathological Analysis of Extramedullary Hematopoiesis and Angiogenesis of Spleen in a Case of Primary Myelofibrosis with Huge Splenomegaly.

Although splenomegaly is one of the important signs of primary myelofibrosis, the differential diagnosis varies from malignant disorders to benign disorders, including malignant lymphoma and sarcoidosis. The patient was a 67-year-old male who developed anemia and huge splenomegaly. The laboratory findings include human T-cell leukemia virus type 1 (HTLV-1) antibody, elevated soluble interleukin-2 receptor, hypocellular bone marrow, and uptake in the spleen on positron emission tomography/computed tomography scan. Additionally, we performed laparoscopic splenectomy to alleviate the clinical symptoms and to rule out malignant lymphoma. Histological findings revealed extramedullary hematopoiesis, characterized by the presence of erythroid islands and clusters of dysplastic megakaryocytes with increased reticulin fibrosis. Immunohistochemical staining revealed the presence of von Willebrand factor, dysplastic megakaryocytes, myeloperoxidase, myeloid-predominant proliferations, and CD34 immature myeloid cells. Furthermore, regarding the angiogenesis in the spleen, the endothelial cells of the capillaries and those of the sinusoidal vascular system that were reactive for CD34 and CD8, respectively, were also detected. Consequently, the histological findings revealed both extramedullary hematopoiesis and angiogenesis in spleen. Based on the histological findings and the identification of Janus activating kinase 2 (JAK-2) mutation, the patient was diagnosed with primary myelofibrosis. Splenectomy reduces blood transfusion requirements after surgery. The patient was carefully followed-up without further treatments. Thus, primary myelofibrosis is the crucial differential diagnosis of huge splenomegaly.

Pneumocystis Pneumonia in a Patient with Ovarian Cancer Receiving Olaparib Therapy.

We herein report a case of pneumocystis pneumonia (PCP) in a 77-year-old woman with ovarian cancer who was receiving olaparib therapy. After the patient's second relapse of ovarian cancer, she was administered olaparib as maintenance therapy following successful completion of docetaxel and carboplatin therapy. On receiving olaparib, she showed symptoms of a fever and malaise. Based on laboratory and imaging findings, she was diagnosed with PCP. After treatment with corticosteroids and trimethoprim/sulfamethoxazole followed by atovaquone, the patient's general condition improved. The lymphocytopenia observed after olaparib administration may have been associated with the development of PCP.

Tracheal Mucoepidermoid Carcinoma Mimicking Deteriorated Bronchial Asthma during Pregnancy.

Primary bronchial tumors are extremely rare. However, symptoms, such as coughing and wheezing, are not specific to this disease, and primary bronchial tumors are often misdiagnosed as bronchial asthma. This report describes the case of a pregnant patient with a bronchial tumor that mimicked deteriorating bronchial asthma. A 37-year-old female patient suffered from repeated episodes of pneumonia since 26 weeks of gestation. Despite treatment, she suffered from another episode of pneumonia at 28 weeks of gestation. This was considered as deteriorating asthma. Bronchoscopy performed at 34 weeks of gestation showed a tumor in the left main lung bronchus, obstructing nearly 100% of the trachea. After cesarean delivery at 34 weeks, she underwent endoscopic bronchial tumor resection. Because of recurrent bronchial obstruction and the possibility of malignant disease, subsequent left main lung bronchial resection and bronchoplasty were performed. The pathological diagnosis was low-grade mucoepidermoid carcinoma. In conclusion, if pneumonia develops repeatedly during pregnancy, the possibility of bronchial tumor should be considered.

Snowball-like appearance on radial endobronchial ultrasonography in a patient with invasive mucinous adenocarcinoma.

Invasive mucinous adenocarcinoma (IMA), which is a relatively rare lung adenocarcinoma, is considered a high-grade subtype and is associated with a poor prognosis. IMA is difficult to diagnose by computed tomography because it requires differentiation from inflammatory diseases, such as atelectasis, infectious pneumonia, and organizing pneumonia. Thus far, no reports of radial endobronchial ultrasonography (EBUS) findings in IMA have been published. This article presents a case of IMA with a characteristic shadow, snowball-like appearance on radial EBUS in a 67-year-old Japanese man.

Clozapine-induced antineutrophil cytoplasmic antibody-associated vasculitis: a case report.

Clozapine is the most effective antipsychotic medication for refractory schizophrenia, but it has many possible serious side effects, including antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, the rare case reports available have not presented sufficient characteristic features of drug-induced AAV. Herein, we report a case of a 48-year-old Japanese woman with schizophrenia who presented with fever, arthralgia, myalgia and skin rash after 2 years of clozapine treatment. Her C-reactive protein (CRP) level increased, myeloperoxidase ANCA was positive and skin biopsy revealed leukocytoclastic vasculitis. Initially, steroid administration achieved remission, but her symptoms and high CRP levels relapsed every time the steroid dosage was tapered down. Upon discontinuation of clozapine, her symptoms and elevated CRP level immediately improved and the steroid was successfully tapered and discontinued. This outcome suggested that clozapine was the main cause of AAV.

Endobronchial metastasis of ovarian cancer rescued by tumor ablation and a self-expanding hybrid stent: A case report and review of the literature.

Tracheal stenosis caused by malignancy is a life-threatening complication. Herein, we performed tumor ablation and airway stenting using a hybrid stent on a patient with upper tracheal stenosis caused by endobronchial metastasis of ovarian cancer. To date, only 9 cases of endobronchial metastasis of ovarian cancer have been reported. This is the first reported case of endobronchial metastasis in the upper part of the trachea, which had a favorable outcome after tumor ablation as a sequential treatment and use of a hybrid stent. In addition, 10 cases of endobronchial metastasis of ovarian cancer, including ours and other case reports, were reviewed.

Bronchial mucoepidermoid carcinoma, recurrent asthmatic symptoms, and pneumonia presenting in pregnancy.

We report the case of a 37-year-old pregnant Japanese woman (34th week of gestation) with a left main bronchus mucoepidermoid carcinoma. She had left lower lung pneumonia episodes for eight weeks that had been associated with bronchial asthma. Bronchoscopy revealed a membranous endobronchial tumour obstructing most of the left main bronchus. We delivered the baby without any problems by caesarean section, followed by tumour cauterization using a rigid bronchoscope under general anaesthesia. After that, we performed a sleeve resection of the main left bronchus. At one-year follow-up, the patient was disease-free and her baby was growing well.

Severe tracheal stenosis after first administration of pembrolizumab rescued by Dumon Y-stent in a lung cancer patient.

A 70-year-old woman diagnosed with advanced, non-resectable programmed cell death ligand 1-positive-non-small-cell lung carcinoma was treated with pembrolizumab as first-line therapy. Soon after therapy initiation, she presented with severe dyspnea, and chest computed tomography revealed a soft tissue mass in the lower trachea of the right main bronchus. During bronchoscopy, she became severely hypoxic, and we performed endoscopic tumor ablation and Dumon Y-stent placement. We considered this severe deterioration caused by pseudoprogression, and suggest that it is necessary to perform bronchoscopy and to prepare for the bronchial intervention when treating patients with immune checkpoint inhibitors.

Clinical Features, Pathological Features, and Treatment Outcomes of 22 Patients with Aggressive Adult T-cell Leukemia-lymphoma Treated with a Humanized CCR4 Antibody (Mogamulizumab) at a Single Institution during a 6-year Period (2012-2018).

Objective To elucidate the clinical impact of humanized CCR4 antibody (mogamulizumab) on adult T-cell leukemia-lymphoma (ATL), we retrospectively analyzed the clinical and pathological features and treatment outcomes of aggressive ATL. Methods Twenty-two patients (median age: 65 years) with aggressive ATL [acute- (n=16) or lymphoma-type (n=6)] had their characteristics analyzed. All cases were treated with mogamulizumab at our institution from 2012 to 2018. In addition, we subjected 14 specimens of ATL to histological, immunological, and genetic analyses. Results Regarding the patient outcomes, the overall response rates were 68.1% and 31.8% after 4 and 8 courses (or after the final courses), respectively. The median overall survival (OS) was 95.5 days, while the OS rates at 6 and 12 months were 31.5% and 21.1%, respectively. Concerning patient pathological characteristics, 6 of the 14 patients examined (42.9%) had CCR4 mutations. Regarding the clinicopathological findings related to the mogamulizumab response, notably, the cases with somatic CCR4 mutation tended to have a poorer response (16.7%) than those with wild-type CCR4 (62.5%) after 4 cycles of mogamulizumab. Furthermore, the CCR4 global score tended to be higher in the responder cases than in the non-responder cases. Conclusion The present findings suggest that the CCR4 expression may be related to the mogamulizumab response, although no other significant predictive markers were identified in this study. Further studies will be needed in order to identify more markers related to the mogamulizumab response.

Giant serous cystadenoma of the pancreas appearing sonographically as a remote pararenal mass.

Macrocystic serous cystadenoma (MSC) of the pancreas is a rare benign neoplasm with varied imaging appearances. We describe an intriguing case of a surgically resected and histologically proven giant MSC, developed in the pararenal space. Ultrasonography (US) revealed a large, oligocystic mass around the lower pole of right kidney. Like US, computed tomography, and magnetic resonance imaging were unable to detect the origin of the lesion, which was only verified at surgical exploration. A bizarre finding was the unusual location of the pancreatic tumor growing seemingly apart from the pancreas itself, with no obvious connection to it.

The clinical impact of human T-lymphotrophic virus type 1 (HTLV-1) infection on the development of adult T-cell leukemia-lymphoma (ATL) or HTLV-1-associated myelopathy (HAM) / atypical HAM after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and renal transplantation.

Because there are limited clinical reports on the impact of human T-lymphotropic virus type 1 (HTLV-1) on organ transplantation, its effects on the development of adult T-cell leukemia-lymphoma (ATL), post-transplantation lymphoproliferative disorder (PTLD) and HTLV-1-associated myelopathy (HAM) or atypical HAM after organ transplantation remain unclear.We retrospectively analyzed the impact of HTLV-1 in 54 allogeneic hematopoietic stem cell transplantation (allo-HSCT) cases and 31 renal transplantation cases between January 2006 and December 2016.Among the 54 allo-HSCT cases, nine recipients with ATL tested positive for HTLV-1, and one was found to be an HTLV-1 carrier. All donors tested negative for HTLV-1. Only one HTLV-1 carrier did not present with ATL or HAM development after allo-HSCT. Among nine ATL cases after allo-HSCT, four eventually relapsed due to proliferation of recipient-derived ATL cells. However, in one ATL case, atypical HAM developed rapidly at 5 months after allo-HSCT.Among the 31 renal transplantation cases, all donors tested negative for HTLV-1, and only recipients tested positive. Only one HTLV-1 carrier recipient did not present with ATL or HAM development after renal transplantation. However, one HTLV-1-negative recipient developed PTLD in the brain 10 years after renal transplantation.In clinical practice, careful follow-up of HTLV-1 infected recipients after organ transplantation is important because atypical HAM can develop in ATL patients after allo-HSCT. Furthermore, to clarify the risk of ATL or HAM development in HTLV-1 infected recipients, we prospectively followed up our cohort.

Early/prefibrotic primary myelofibrosis in patients who were initially diagnosed with essential thrombocythemia.

A new entity, namely early/prefibrotic primary myelofibrosis (PMF), was introduced as a subtype of PMF in the 2016 revised World Health Organization (WHO) criteria for myeloproliferative neoplasms (MPN). It was diagnosed based on histopathological features of bone marrow (BM) biopsy specimens together with clinical parameters [leukocytosis, anemia, elevated lactate dehydrogenase (LDH) values, and splenomegaly]. The aim of this study was to evaluate the prevalence of early/prefibrotic PMF in patients who were previously diagnosed with ET, and to compare clinical features at diagnosis and outcomes between early/prefibrotic PMF and essential thrombocythemia (ET) patients. BM biopsy samples obtained at the time of ET diagnosis were available in 42 patients. Sample reevaluation according to the 2016 revised WHO criteria revealed that early/prefibrotic PMF accounted for 14% of patients who were previously diagnosed with ET, which was comparable to the rates in previous reports. Compared to patients with ET, patients with early/prefibrotic PMF had higher LDH values and higher frequencies of splenomegaly. Overall, myelofibrosis-free and acute myeloid leukemia-free survivals were comparable between the 2 groups. Accurate diagnosis is required to clarify the clinical features of Japanese ET patients.

Endobronchial Mucosa-associated Lymphoid Tissue Lymphoma: A Report of Two Cases and a Review of the Literature.

Primary endobronchial mucosa-associated lymphoid tissue lymphoma (EML) is rare. We reviewed 20 cases of EML, including ours and case reports. We found that the location of tumor in 70% of these cases was limited to the trachea and main bronchus, and the form of tumor in 61% of these cases was several nodular protrusions. If a patient exhibits these characteristics, adequate specimen collection on bronchoscopy is important. Because the prognosis for patients with EML is good, tumors on the trachea and main bronchus should be treated, while those on the peripheral airway can be watched carefully.