Current Status of Distress Screening in Designated Cancer Hospitals: A Cross-Sectional Nationwide Survey in Japan.

BACKGROUND: The purpose of this study was to investigate the current status of distress screening implementation in Japanese designated cancer hospitals. SUBJECTS AND METHODS: This was a cross-sectional observational study. Palliative care team representatives in all designated cancer hospitals in Japan completed an ad hoc questionnaire. Demographic data in 2014 were obtained from the Ministry of Health, Labour and Welfare in Japan. RESULTS: Of 422 institutions, 389 responded (92%) and data were obtained from 379 (90%). Approximately 90% of institutions had implemented a distress screening program at some level, and approximately 60% had just started screening. Among those institutions that screened, 77% provided individualized triage to specialized services within the institutions, whereas 60% did not routinely follow-up with patients who had positive screening results. The estimated median percentage of screened patients referred to palliative care teams was 0.4% in outpatient settings and 6.3% in inpatient settings. Although 68% of respondents perceived that screening was useful overall, they also reported difficulties when conducting screening with patients, reporting "no established effective treatment for problems screened" (66%), "patients complain it is difficult to express their distress using scales" (58%), and that it was "difficult to manage screened problems because of lack of time" (49%). Eight perceived barriers to implementing distress screening programs in hospitals were identified; a lack of human resources ranked highest. CONCLUSIONS: Implementation of distress screening in designated cancer hospitals in Japan has just begun. Policymakers should acknowledge that screening can be beneficial for patients when it is implemented with appropriate resources and established methods.

Occurrence of Carcinoma of the Pancreas Following Nilotinib Therapy for Chronic Myeloid Leukemia: Report of a Case with Review of the Literature.

The patient, a 79-year-old Japanese man, was diagnosed with the chronic phase of chronic myeloid leukemia and begun on nilotinib therapy in April 2011. The therapeutic response was major molecular response in August. About 19 months after the start of nilotinib therapy at 400 mg/day (November 2012), an adenocarcinoma (24 x 20 mm) confined to the head of the pancreas developed. In February 2013, a pancreaticoduodenectomy was performed. The therapy regimen was switched to dasatinib at 100 mg/day, beginning in April. The response was still major molecular response with no recurrence of pancreatic carcinoma in July 2013. There have been 29 reported cases of secondary neoplasms associated with nilotinib therapy. These secondary neoplasms were characterized by relatively frequent occurrence of papilloma (6 cases), gastric cancer (3 cases), fibroma (3 cases), and thyroid neoplasms (2 cases). The present case, however, is the first to be reported as carcinoma of the pancreas. This report describes the case.

Peripheral T cell lymphoma, not otherwise specified with myelofibrosis: report of a case with review of the literature.

A 68-year-old man presented to us with pancytopenia, erythroderma, and multiple lymphadenopathies. Lymph node biopsy led to the diagnosis of peripheral T-Cell lymphoma-not otherwise specified (PTCL-NOS). Immunostaining of the lymph node biopsy specimens for cytokines revealed that the tumor cells were positive for plated-derived growth factor (PDGF), basic fibroblast growth factor (b-FGF), vascular endothelial growth factor (VEGF), tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ), interleukin-1ß (IL-1ß), interleukin-2 (IL-2), and transforming growth factor-ß (TGF-ß). Bone marrow biopsy revealed infiltration by the PTCL-NOS and myelofibrosis (MF). Bone marrow blood was negative for JAK-2V617F. Bone marrow immunostaining for cytokines showed that the tumor cells were positive for PDGF, b-FGF, VEGF, TNF-α, IFN-γ, IL-1ß, IL-2, and TGF-ß. The patient was initiated on treatment, and after the first course of CHOP therapy, the bone marrow infiltration by the PTCL-NOS and MF improved. Repeat immunostaining of bone marrow biopsy specimens for cytokines showed that the tumor cells had become negative for PDGF, VEGF, TNF-α and TGF-ß. However, after the second course of CHOP therapy, the bone marrow infiltration by the PTCL-NOS and MF worsened. Immunostaining of bone marrow specimens for cytokines again revealed positive staining results of the tumor cells for PDGF, TNF-α, and TGF-ß. At the completion of the first course of treatment, the infiltration by the PTCL-NOS improved, but not the pancytopenia.

Epstein-Barr virus-positive multiple myeloma developing after immunosuppressant therapy for rheumatoid arthritis: a case report and review of literature.

A 61-year-old woman was diagnosed as having rheumatoid arthritis (RA) and began treatment with salazosulfapyridine (SASP) and methotrexate (MTX) in 2008; the administration of concomitant tacrolimus (TAC) was initiated in 2010. She subsequently developed concurrent multiple myeloma (MM), immunoglobulin G (IgG)-κ type, in 2012. A portion of the tumor cells tested positive for Epstein-Barr virus-encoded small RNA (EBER). MTX treatment was discontinued in 2014, and the exacerbation of MM ensued. The patient received two cycles of bortezomib plus dexamethasone (BD) therapy and attained a complete response (CR). She then underwent an autologous peripheral blood stem cell transplantation. The Epstein-Barr (EB) virus infection arising from the increased RA disease activity and immunosuppressant medication might have influenced the development of MM in this case. Most reported patients with EB virus-positive plasmacytoma are in a state of immunosuppression, and this condition may fall within the category of other iatrogenic immunodeficiency-associated lymphoproliferative disorders. No other reports of plasmacytoma occurring in a background of RA or after TAC or MTX therapy have been made, and the present case is the first such report.

CD56-positive adult T-cell leukemia/lymphoma: a case report and a review of the literature.

A 67-year-old woman presented with a swelling on both sides of the neck. Biopsy of an enlarged cervical lymph node on the left side and flow cytometric analysis revealed CD56-positive CD4(+)CD8(+) abnormal NK/T cells. A Southern blot analysis of the cervical lymph node biopsy specimen showed a human T-cell leukemia virus type 1 provirus DNA monoclonal band. Based on these findings, the patient was diagnosed with CD56-positive adult T-cell leukemia/lymphoma. After five cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, the general condition of the patient gradually declined, indicating resistance to treatment, and approximately 9 months after the onset of symptoms, the patient died. CD56 is recognized as an unfavorable prognostic marker in cases of acute myeloid leukemia with t(8;21), acute promyelocytic leukemia, and anaplastic large cell lymphoma. Only eight cases of CD56-positive adult T-cell leukemia/lymphoma have been reported so far in the literature. Most of these cases were in the advanced stage at diagnosis and had poor outcomes. It appears that the correlation between CD56 expression and outcomes in patients with adult T-cell leukemia/lymphoma should be clarified by investigating a larger number of cases in the future.

A Case of Advanced Primary Thyroid Double-Hit B Cell Lymphoma in Which Complete Remission has been Maintained After High-Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation Performed During the Second Remission, with a Review of the Literature.

A 50-year-old woman who presented with a mass in the thyroid gland was diagnosed as having diffuse large B-cell lymphoma (DLBCL) by biopsy in August 2011. The tumor had a complex chromosomal karyotype, including 8q24 (C-MYC) and 18q21(BCL-2), and fluorescence in situ hybridization confirmed split signals of C-MYC and BCL-2. BCL-2/IgH and C-MYC/IgH fusion signals were also observed. Three courses of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP) therapy were given, followed by thyroid gland irradiation. She was achieved complete remission (CR). In January 2012, a mass appeared in the right breast, which was diagnosed as relapse by biopsy. CR was achieved again after the 4th course of R-CHOP therapy, and one course of rituximab, etoposide, methylprednisolone, cytarabine, cisplatin (R-ESHAP) therapy was given. Thereafter, CR has been maintained after high-dose chemotherapy and autologous peripheral blood stem cell transplantation. There have been only 3 reported cases of primary thyroid C-MYC and BCL-2 double-hit lymphoma, including the present case; 2 of the cases were cases of DLBCL. R-CHOP therapy, irradiation and autologous peripheral blood stem cell transplantation are expected to be effective for such patients.

Patient with refractory multiple myeloma developing eosinophilia after lenalidomide treatment and lung cancer 9 months later: case report and review of the literature.

A 78-year-old man was diagnosed as having advanced symptomatic IgG multiple myeloma in June 2008. Melphalan-prednisolone therapy was effective, however, relapse occurred in January 2011 after 21 courses of melphalan-prednisolone therapy. Addition of bortezomib and dexamethasone led to partial remission, but the treatment needed to be discontinued due to autonomic dysfunction. Combined therapy with lenalidomide and dexamethasone was started in May 2012, which resulted in partial remission. The patient had a persistently elevated eosinophil count (2,350/µL) and increased serum IL-6 level. Pleuritis carcinomatosa developed in January 2013. Lenalidomide was discontinued, which was followed by rapid improvement of the eosinophilia. The patient died of respiratory failure in March 2013. There have been only five reported cases of eosinophilia caused by lenalidomide used for the treatment of multiple myeloma. In these cases, lenalidomide has been speculated to activate cytotoxic T cells to control the plasmacytoma. It would be of interest, therefore, that eosinophilia could serve as a new indicator.

Acquired factor v inhibitor developing after treatment with dabigatran etexilate methanesulfonate: a case report and review of the literature.

A 90-year-old man presented with subcutaneous ecchymoses. He had been under treatment with dabigatran etexilate methanesulfonate (DEM). Prolonged APTT and decreased PT was developed 2 months after the start of DEM, more prolonged 6 months later. DEM was discontinued, the coagulopathy did not improve. Factor V activity was decreased, along with appearance of coagulation factor V inhibitor (FVI). He did not have antiphospholipid syndrome or malignancy. He was diagnosed as having acquired FVI caused by DEM. Steroid pulse therapy was effective. There have been 74 reported cases of AFVI induced by drug treatment, but none after treatment with DEM.

Spontaneous regression of a clinically-advanced histologically low-grade follicular lymphoma involving the breast: case report and review of the literature.

A 68-year-old woman was diagnosed as having grade 1 follicular lymphoma of the left breast in November 2012. Bone marrow infiltration was noted histologically and confirmed by Southern blot analysis of the IgHJH locus. The clinical stage was IVA, advanced stage. According to the Follicular Lymphoma International Prognostic Index, the patient was classified into the high risk group. The general condition was good and there were no organ symptoms, therefore, the patient was kept under observation without treatment. After one year and 2 months of follow up, The mass was regressed spontaneously. As previous studies have suggested a poor prognosis of patients with an advanced clinical stage of the disease, careful follow-up of our patient is necessary.

A case of post-mogamulizumab relapse of acute-type adult T-cell leukemia/lymphoma successfully treated with mogamulizumab and etoposide.

A 70-year-old man presented to us with the chief complaints of a generalized rash and a mass in the right clavicular region that he first noticed in the year 2012. Biopsy of the mass led to the diagnosis of cutaneous nodular mass-type adult T-cell leukemia/lymphoma (ATLL) in March 2013. Phototherapy was started, and the symptoms improved temporarily. However, in late June 2013, the serum lactate dehydrogenase (LDH) level increased to 358 IU/L, which was 1.6 times higher than the upper limit of the reference range; based on the findings, transformation of the disease to the acute type was diagnosed. The patient was treated with 6 courses of CHOP therapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone), which resulted in complete remission (CR). However, the rash recurred in late October 2013, and treatment with mogamulizumab was initiated. A total of 8 courses of mogamulizumab were administered, which resulted in CR. The rash and cutaneous nodular masses recurred again in January 2014, and a total of 8 courses of mogamulizumab were administered again starting in February 2014. However, the patient's symptoms began to worsen gradually. Phototherapy was also initiated, but had to be discontinued due to the development of photosensitivity. Treatment with the combination of mogamulizumab and etoposide (25 mg/day for 21 days) was started in May 2014. The nodular mass rapidly decreased in size. The rash or cutaneous nodular mass had not recurred as of August 2014. Thus, combined therapy with mogamulizumab plus etoposide is considered to be effective for resolution of the cutaneous nodular masses in patients with ATLL.

A case of secondary plasma cell leukemia resistant to novel agents, in which stringent complete remission was achieved and maintained for a long period of time after VAD therapy and tandem autologous transplantation.

A 61-year-old woman was diagnosed in June 2011 as having immunoglobulin G (IgG) ĸ-type multiple myeloma (MM), stage II, according to the International Staging System (ISS). Chromosome analysis showed a complex karyotype, including t(11;14) and del 13q. Analysis of the cell surface markers revealed that the cells were positive for mature plasma cell-1 (MPC-1), and negative for cluster of differentiation (CD) 45 and CD49e, suggestive of an intermediate level of maturity of the cells. The disease was refractory to bortezomib-dexamethasone (BD) therapy and progressed to plasma cell leukemia despite the treatment. Treatment was therefore switched to lenalidomide-dexamethasone (RD) therapy, however, the condition again proved to be refractory to this therapy. A partial response (PR) was achieved with vincristine-doxorubicin-dexamethasone (VAD) therapy. The residual plasma cells became CD45-positive, suggesting a change of the cells from an intermediate level of maturity to mature cells. In December, autologous peripheral blood stem cell transplantation (Auto-PBSCT) was performed after high-dose melphalan therapy (melphalan 200 mg/m(2)) as pretreatment. PR was observed and a second Auto-PBSCT was performed in July 2012. Stringent complete remission (sCR) has been maintained for 2 years since, without any further treatment. This is the first reported case of secondary plasma cell leukemia (sPCL) resistant to new drugs that was successfully treated by high-dose melphalan in combination with VAD therapy and Auto-PBSCT.

Primary platelet-derived growth factor-producing, spindle-shaped diffuse large B-cell lymphoma of the skull: a case report and literature review.

A 39-year-old woman with a right frontal mass underwent a cranial bone tumor biopsy. Histopathologic examination of hematoxylin and eosin-stained slides showed spindle-shaped tumor cells in a storiform pattern, appearing somewhat like a sarcoma. However, the tumor cells were CD20-positive by immunohistochemical staining. Therefore, a diagnosis of spindle-shaped diffuse large B-cell lymphoma (Sp-DLBCL) was made. There have been at least 35 cases of Sp-DLBCL documented in the literature, and most were of the germinal center type, while the present case is the first report of a vimentin-positive primary Sp-DLBCL of the skull. The DLBCL in this case was immunohistochemically stained for six representative cytokines that might give rise to fibrosis, due to the evidence of fibroblastic proliferation. The DLBCL cells were positive for platelet-derived growth factor (PDGF), and some cells were also positive for tumor necrosis factor (TNF) α. Based on these findings, it was inferred that the PDGF and TNFα produced by DLBCL cells induced fibroblastic proliferation. The resultant conspicuous fibrosis caused interfibrous impingement on the DLBCL cells, which deformed them into a spindle shape. The present case is the first reported case of a PDGF-producing Sp-DLBCL.

Intravascular large B-cell lymphoma with pontine involvement successfully treated with R-CHOP therapy and intrathecal administration: a case report and review of literature.

A 46-year-old man developed a fever and cough, and computed tomography showed multiple, nodular infiltrative shadows in lungs. He was diagnosed as having intravascular large B-cell lymphoma (IVLBCL). Brain magnetic resonance imaging (MRI, T2W1) showed an abnormal signal area in the pons, which was IVLBCL involvement. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy and intrathecal (I.T.) injection of methotrexate, cytarabine and prednisolone were selected. Complete remission (CR) was achieved and pontine involvement disappeared. A total of 8 courses of R-CHOP therapy and 4 courses of I.T. were performed. CR has been maintained for 1 year and 2 months.

T-cell lymphoblastic leukemia/lymphoma with t(7;14)(p15;q32) [TCRγ-TCL1A translocation]: a case report and a review of the literature.

A 22-year-old man sought medical advice for a swelling in the right side of the neck in December 2011. Histopathological examination of the lymph node biopsy initially suggested reactive lymphadenitis, on account of the only sparse presence of tumor cells. Bone marrow examination was performed in February 2012 revealed findings consistent with a diagnosis of T-cell lymphoblastic leukemia/lymphoma (T-LBL), and the patient was begun on remission induction therapy. The bone marrow showed an immature thymocytic pattern: cytoplasmic CD3+, surface CD3-, CD5+, CD4-, and CD8-. Re-assessment of the lymph node specimens revealed the same phenotype of the cells in the lymph node as that of the blasts in the bone marrow. In addition, a chromosomal aberration t(7;14)(p15;q32) was noted. The lymph node biopsy specimens were examined by paraffin-embedded tissue section-fluorescence in situ hybridization (PS-FISH), which revealed a fusion signal of T-cell receptor (TCR)γ gene (7p15) with T-cell leukemia/lymphoma 1A (TCL1A) gene (14q32.13). There have been at least 10 reported cases of T-LBL with t(7;14)(p15;q32), including the present case. However, this is the first reported case in which TCRγ-TCL1A translocation was confirmed by FISH.

A case of recurrent autoimmune hemolytic anemia during remission associated with acute pure red cell aplasia and hemophagocytic syndrome due to human parvovirus B19 infection successfully treated by steroid pulse therapy with a review of the literature.

The patient was a 47-year-old man diagnosed as having autoimmune hemolytic anemia (AIHA) in April 2011. He also had a congenital chromosomal abnormality, a balanced translocation. Treatment with prednisolone (PSL) 60 mg/day resulted in resolution of the AIHA, and the treatment was completed in November 2011. While the patient no longer had anemia, the direct and indirect Coombs tests remained positive. In May 2013, he developed recurrent AIHA associated with acute pure red cell aplasia (PRCA) and hemophagocytic syndrome (HPS) caused by human parvovirus B19 (HPV B19) infection. Tests for anti-erythropoietin and anti-erythropoietin receptor antibodies were positive. Steroid pulse therapy resulted in resolution of the AIHA, PRCA, as well as HPS. The serum test for anti-erythropoietin antibodies also became negative after the treatment. However, although the serum was positive for anti-HPV B19 IgG antibodies, the patient continued to have a low CD4 lymphocyte count (CD4, <300/µL) and persistent HPV B19 infection (HPV B19 DNA remained positive), suggesting the risk of recurrence and bone marrow failure.

A probable identical Epstein-Barr virus clone-positive composite lymphoma with aggressive natural killer-cell leukemia and cytotoxic T-cell lymphoma.

The patient was a 52-year old woman with a history of mosquito-bite hypersensitivity since childhood. In July 2011, she developed pyrexia, headaches, and nausea, and Epstein-Barr virus (EBV)-positive aggressive natural killer leukemia (ANKL) was diagnosed on the basis of both a peripheral blood and bone marrow examination. An inguinal lymph node biopsy, on the other hand, revealed EBV-positive cytotoxic T-cell lymphoma plus the presence of a small number of EBV-positive ANKL cells, and a diagnosis of EBV-positive composite lymphoma was made. Both the cytotoxic T-cell lymphoma and ANKL exhibited EBV terminal repeat (Southern blot analysis) monoclonal patterns, and they were almost the same size, approximately 9.0 kb. If it was the identical EBV clone, it is possible that EBV infected progenitor cells common to both NK cells and T cells, that the progenitor cells then differentiated into NK cells and T cells, a chronic active Epstein-Barr virus infection developed, and neoplastic transformation occurred. If it was not the identical EBV clone, fairly similar EBVs must have infected NK cells and T cells separately, and they then underwent neoplastic transformation. Because the mechanism by which EBV infects NK cells or T cells is still unknown, we concluded that this case is also important from the standpoint of elucidating it. We are currently in the process of conducting gene analyses to determine whether the fairly similar EBVs that infected the ANKL and cytotoxic T-cell lymphoma are the identical clone.

Primary gingival diffuse large B-cell lymphoma: a case report and a review of the literature.

The patient was a 73-year-old male who came to our hospital with a chief complaint of pain and swelling of the left side of his jaw. Computed tomography revealed a mass in his left gingiva but no bone destruction. No lesions were observed at any other sites, and an incisional biopsy was performed on the gingival mass on the left side. Histologically, the mass was a diffuse large B-cell lymphoma (DLBCL), and it was CD20-positive, and CD5-negative, CD10-negative, surface immunoglobulin-negative, and Epstein-Barr virus-encoded RNA (EBER)-negative. A serum Human immunodeficiency virus (HIV)-antibody test was negative. A complete remission was achieved after 6 courses of systemic combination chemotherapy, and the complete remission has been maintained for approximately 3 years. According to the literature, primary gingival DLBCL have a high Ki-67-positive rate and many of the cases are stage I and international prognostic index low-risk. However, HIV patients have a high EBER-positive rate and a high risk of developing a CD20-negative, CD138-positive plasmablastic lymphoma, and they have a poor prognosis. By contrast, limited-stage primary gingival lymphomas whose data can be used have been rare in human immunodeficiency virus-negative patients, and only 12 cases, including our own, have ever been reported. Many of the patients have been around 65 years of age, and all of the cases have been CD20-positive, CD138-negative DLBCLs, and the CD5-negative, Epstein-Barr virus-positive rate has been low, with most cases having been non-germinal-center B-cell-like. The prognosis for relapse-free survival has been favorable.

Diffuse large B-cell lymphoma solely involving bilateral adrenal glands and stomach: report of an extremely rare case with review of the literature.

A 60-year-old man complained of nausea, vomiting, decreased appetite, and a feeling of abdominal fullness in August 2013. Based on biopsy findings from an upper gastrointestinal endoscopy examination, a diagnosis of non-Hodgkin's lymphoma (NHL), diffuse large B-cell lymphoma (DLBCL), non-GC type, was made. F18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) revealed abnormal accumulations solely in the gastric wall (SUVmax = 14.5), the left adrenal gland (SUVmax = 14.3), and the right adrenal gland (SUVmax = 8.5). The clinical stage (Ann Arbor) was IVA, the serum LDH level was within the reference range, and the International Prognostic Index (IPI) was low-intermediate. The serum soluble IL-2 receptor level was within the reference range, and there was no evidence of HIV, EB virus, or autoimmune disease. After the completion of 4 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and 2 parallel cycles of prophylactic intrathecal (I.T.), an upper gastrointestinal endoscopy and a FDG-PET/CT examination showed complete remission (CR). The patient received 8 cycles of ritsuximab therapy, 6 cycles of CHOP, and 3 cycles of I.T. The patient has maintained a CR for about 14 months. A literature search revealed that malignant lymphoma with involvement confined to the adrenal gland and gastrointestinal tract is exceedingly rare, and only 3 cases of malignant lymphoma have been reported, with involvement of the stomach in 2 cases and the duodenum in 1 case. All of the cases were diagnosed as DLBCL. The case described herein represents the third case with involvement of the stomach.

IgG3 subclass-positive primary thymic MALT lymphoma without trisomy 3 and trisomy 18: report of a case and review of literature.

The patient, a 42-year-old man, was diagnosed as having an anterior mediastinal tumor. Examination of the resected tumor showed findings consistent with a primary thymic mucosa-associated lymphoid tissue lymphoma, stage IA. Postoperative (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography demonstrated fluorodeoxyglucose accumulation at the site of tumor excision. This accumulation was interpreted as representing a residual lesion, and the patient was treated with rituximab. The patient has since been in a state of complete remission for about 3 years. Sporadic mucosa-associated lymphoid tissue lymphoma cells that appeared to have a propensity for differentiating into plasma cells in this case were analyzed for IgG and IgG subclass expression by immunohistochemical staining. The mucosa-associated lymphoid tissue lymphoma cells that showed a propensity for differentiating into IgG-positive plasma cells were IgG3-positive and IgG1-, IgG2- and IgG4-negative. An increase in IgG3 or IgG1 expression in immune cells has been previously demonstrated in immune responses to continuous exposure to the same proteins or peptide antigens and most mucosa-associated lymphoid tissue lymphomas show increased IgG3 and/or IgG1 expression. It is consistent with the fact that inflammation due to stimulation by a pathogenic antigen is considered to be etiologically responsible for the development of mucosa-associated lymphoid tissue lymphoma.