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A case of an asymptomatic 19-year-old woman with Kimura disease presenting with a nodule in the right parotid gland is presented. She had a medical history of atopic dermatitis and noticed a mass on her right-side neck. Cervical lymphadenopathy was clinically diagnosed. The initial management plan was to observe the lesion, which had enlarged from 1 cm to 2 cm in diameter 6 months later. An excisional biopsy was performed, and the pathology confirmed an eosinophil-containing inflammatory parotid gland lesion with many squamous nests and cysts, mimicking a parotid gland tumor. High serum immunoglobulin E levels, peripheral blood eosinophilia, and pathological and genetic diagnoses confirmed Kimura disease. The lesion tested negative for human polyomavirus 6. No recurrence was observed 15 months after the biopsy. The prognosis of Kimura disease without human polyomavirus 6 infection may be favorable; however, further validation of this hypothesis is required as only 5 or 6 cases of Kimura disease have been evaluated for this viral infection. Proliferative squamous metaplasia occurring in parotid gland lesions of Kimura disease is rare and may complicate the diagnostic imaging and pathological diagnosis.

DOI： 10.1016/j.radcr.2023.02.027

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It is difficult to histologically differentiate extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) from chronic gastritis (CG)/ reactive lymphoid hyperplasia (RLH). To determine whether immunohistochemistry for IRTA1 and MNDA can differentiate gastric MALT lymphoma from CG/RLH, we investigated 81 stomach biopsy specimens [Wotherspoon grade (WG) 1, 11 cases; WG 2, 9 cases; WG 3, 20 cases; WG 4, 31 cases; and WG 5, 10 cases]. According to a previously reported algorithm involving PCR for immunoglobulin heavy (IgH) chain locus rearrangement, all 81 cases were divided into three groups: CG/RLH (55 cases), MALT lymphoma (19 cases) groups, and IgH undetectable group (7 cases). We analyzed the CG/RLH and MALT lymphoma groups. The median percentage of IRTA1-positive cells was 0% (range 0%-90.6%) in the CG/RLH group and 43.5% (range 0%-97.6%) in the MALT lymphoma group (p < 0.0001). The median percentage of MNDA-positive cells was 32.4% (range 0%-97.6%) in the CG/RLH group and 55.1% (range 0%-97.6%) in the MALT lymphoma group (p = 0.0044). These results indicate that immunohistochemistry for IRTA1 and MNDA can help differentiate gastric MALT lymphoma from CG/RLH.

DOI： 10.3960/jslrt.22021

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A 52-year-old man presented with palatine tonsillar swelling caused by follicular lymphoma. His tumor burden was low, but exacerbation of snoring and dysphagia was observed. Considering the first wave of coronavirus disease 2019 (COVID-19) pandemic, he received palliative 4-Gy irradiation to the tonsils in 2 fractions, which induced partial regression of tonsillar swellings and eradication of the circulating lymphoma cells. We suggest that low-dose radiotherapy triggered an abscopal effect of lymphoma, which allowed the patient time to receive COVID-19 vaccination before starting immunosuppressive chemo-immunotherapy.

DOI： 10.2169/internalmedicine.8968-21

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BACKGROUND: Intestinal grafts are susceptible to ischemia-reperfusion injury, resulting in the loss of mucosal barrier function and graft failure. Biliverdin is known to exert a variety of cytoprotective functions against oxidative tissue injury. Because the mucosal layer is the primary site of ischemia-reperfusion injury, mucosa-targeting strategies by luminal delivery of reagents might be beneficial. We tested whether intraluminal administration of biliverdin as an adjuvant to standard preservation solutions protected against ischemia-reperfusion injury. METHODS: Orthotopic syngeneic intestinal transplants were performed on Lewis rats after 6 hours of cold preservation. Saline containing biliverdin (10 μM) or without biliverdin was introduced into the lumen of the intestinal grafts immediately before cold preservation. RESULTS: Damage to the intestinal mucosa caused by ischemia-reperfusion injury resulted in severe morphological changes, including blunting of the villi and erosion, and led to significant loss of gut barrier function 3 hours after reperfusion. These changes to the mucosa were notably ameliorated by intraluminal administration of biliverdin. Biliverdin also effectively inhibited upregulation of messenger RNAs for interleukin-6, inducible nitric oxide synthase, and C-C motif chemokine 2. Additionally, biliverdin treatment prevented the loss of expression of claudin-1, a transmembrane, tight-junction barrier protein. The 14-day survival of recipients of biliverdin-treated grafts was significantly improved as compared with the recipients of saline-treated control grafts (83.3% vs 38.9%, P = .030). CONCLUSION: This study demonstrated that luminally delivered biliverdin provides beneficial effects during the transplant of rat small intestinal grafts and could be an attractive therapeutic option in organ transplantation.

DOI： 10.1016/j.surg.2022.07.021

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BACKGROUND: Brain-dead donors are susceptible to pulmonary atelectasis (AT). In procurement surgery, lung recruitment under circulatory conditions and cold-flushing for atelectatic donor lungs often provoke graft injury due to the acute blood inflow. We hypothesized that lung recruitment without blood circulation can mitigate graft injury. This study aimed to examine the benefits of lung recruitment subsequent to cardiac arrest using a porcine lung-transplant model. METHODS: Thirteen donor pigs were categorized into the non-atelectatic (No-AT) group (n=3) representing a healthy control group; AT-BCR group (n=5), in which AT was reverted by conventional blood-circulated recruitment (BCR); and AT-no-BCR group (n=5), in which AT was reverted by no-BCR following circulatory arrest. In the atelectatic donor models, the left main bronchus was ligated for 24 hours prior to lung procurement. Left lung transplantation (LTx) was subsequently performed in the thirteen recipient pigs. After 6 hours evaluation, the recipients were euthanized and the lung grafts were excised. RESULTS: The post-transplant PaO2/FiO2 ratio was significantly higher in the AT-no-BCR group than in the AT-BCR group (P=0.015). Wet/dry ratio, histological findings of graft injury and tissue interleukin-8 expression in the AT-no-BCR group were similar to those of the No-AT group. CONCLUSIONS: Lung recruitment without circulation after circulatory arrest could be more protective for atelectatic donor lung than the conventional procedure.

DOI： 10.21037/jtd-22-226

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BACKGROUND: The protective effects of carbon monoxide (CO) against ischemia/reperfusion (IR) injury during organ transplantation have been extensively investigated. Likewise, CO-releasing molecules (CORMs) are known to exert a variety of pharmacological activities via liberation of controlled amounts of CO in organs. Therefore, we hypothesized that intraluminal administration of water-soluble CORM-3 during cold storage of intestinal grafts would provide protective effects against IR injury. METHODS: Orthotopic syngeneic intestinal transplantation was performed in Lewis rats following 6 h of cold preservation in Ringer solution or University of Wisconsin solution. Saline containing CORM-3 (100 µmol/L) or its inactive counterpart (iCORM-3) was intraluminally introduced in the intestinal graft before cold preservation. RESULTS: Histopathological analysis of untreated and iCORM-3-treated grafts revealed a similar erosion and blunting of the intestinal villi. These changes in the mucosa structure were significantly attenuated by intraluminal administration of CORM-3. Intestinal mucosa damage caused by IR injury led to considerable deterioration of gut barrier function 3 h postreperfusion. CORM-3 significantly inhibited upregulation of proinflammatory mRNA levels, ameliorated intestinal morphological changes, and improved graft blood flow and mucosal barrier function. Additionally, CORM-3-treated grafts increased recipient survival rates. Pharmacological blockade of soluble guanylyl cyclase activity significantly reversed the protective effects conferred by CORM-3, indicating that CO partially mediates its therapeutic actions via soluble guanylyl cyclase activation. CONCLUSIONS: Our study demonstrates that luminally delivered CORM-3 provides beneficial effects in cold-stored rat small intestinal grafts and could be an attractive therapeutic application of CO in the clinical setting of organ preservation and transplantation.

DOI： 10.1097/TP.0000000000004007

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BACKGROUND: The protective effects of carbon monoxide (CO) against ischemia/reperfusion (IR) injury during organ transplantation have been extensively investigated. Likewise, CO-releasing molecules (CORMs) are known to exert a variety of pharmacological activities via liberation of controlled amounts of CO in organs. Therefore, we hypothesized that intraluminal administration of water-soluble CORM-3 during cold storage of intestinal grafts would provide protective effects against IR injury. METHODS: Orthotopic syngeneic intestinal transplantation was performed in Lewis rats following 6 h of cold preservation in Ringer solution or University of Wisconsin solution. Saline containing CORM-3 (100 µmol/L) or its inactive counterpart (iCORM-3) was intraluminally introduced in the intestinal graft before cold preservation. RESULTS: Histopathological analysis of untreated and iCORM-3-treated grafts revealed a similar erosion and blunting of the intestinal villi. These changes in the mucosa structure were significantly attenuated by intraluminal administration of CORM-3. Intestinal mucosa damage caused by IR injury led to considerable deterioration of gut barrier function 3 h postreperfusion. CORM-3 significantly inhibited upregulation of proinflammatory mRNA levels, ameliorated intestinal morphological changes, and improved graft blood flow and mucosal barrier function. Additionally, CORM-3-treated grafts increased recipient survival rates. Pharmacological blockade of soluble guanylyl cyclase activity significantly reversed the protective effects conferred by CORM-3, indicating that CO partially mediates its therapeutic actions via soluble guanylyl cyclase activation. CONCLUSION: Our study demonstrates that luminally delivered CORM-3 provides beneficial effects in cold-stored rat small intestinal grafts and could be an attractive therapeutic application of CO in the clinical setting of organ preservation and transplantation.

DOI： 10.1097/TP.0000000000004007

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The diagnosis of leptomeningeal metastases is sometimes difficult when the cytology of cerebrospinal fluid is negative. We report a rare case of leptomeningeal metastases that required differentiation from paraneoplastic limbic encephalitis. A 67-year-old man with extensive-stage small cell lung cancer was admitted for a sudden decrease in the level of consciousness. He suffered memory disturbances that began the day before admission. Diffusion-weighted and fluid-attenuated inversion recovery images of brain magnetic resonance imaging (MRI) showed bilateral symmetric areas of hyperintensity in the hippocampus, amygdala, insular cortex, and medial temporal lobe; contrast enhancement was positive. Cytology of the cerebrospinal fluid (CSF) was negative. Anti-N-methyl-d-aspartate receptor antibody and herpes simplex virus DNA were not detected in the CSF. Paraneoplastic Limbic encephalitis was suspected due to his symptoms and brain MRI scan. The patient developed generalized seizures after admission. High-dose methylprednisolone and intravenous immune globulin were administered, but his condition did not improve. Uncontrollable seizures persisted and he died in the hospital at day 13. Autopsy revealed leptomeningeal metastasis and invasion of cancer cells into the limbic system. Contrast-enhanced MRI should be performed even if limbic encephalitis is suspected, and leptomeningeal metastases should be suspected if the lesions are enhanced.

DOI： 10.1016/j.rmcr.2021.101417

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Plasma cell type idiopathic multicentric Castleman disease (PC-iMCD) occasionally manifests as parenchymal lung disease. This study aimed to elucidate the detailed clinicopathological features of lung lesions in PC-iMCD and compare the findings with those in immunoglobulin (Ig) G4-related disease (IgG4-RD), the most difficult differential diagnosis of PC-iMCD. We analyzed the clinicopathological findings and immunohistochemical expression patterns of interleukin-6 (IL-6) and Igs in lung specimens from 16 patients with PC-iMCD and 7 patients with IgG4-RD. Histologically, pulmonary PC-iMCD could not be differentiated from IgG4-RD based on lesion distribution patterns, the number of lymphoid follicles and obliterative vasculitis, or fibrosis types. The eosinophil count was higher in the IgG4-RD group than in the PC-iMCD group (p = 0.004). The IgG4/IgG-positive cell ratio was significantly higher in the IgG4-RD group (p < 0.001). The IgA-positive cell count and IL-6 expression intensity were higher in the PC-iMCD group than in the IgG4-RD group (p < 0.001). Based on these findings, we proposed a new diagnostic approach to differentiate lung lesions of PC-iMCD and IgG4-RD. Our approach can be utilized to stratify patients with suspected lung-dominant PC-iMCD to identify candidates for strong immunosuppressive treatment, including IL-6 blockade, at an early stage.

DOI： 10.3390/jpm10040269

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Authorship：Corresponding author   Language：English  

DOI： 10.1111/pin.13022

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Breast involvement of Adult T-cell leukemia-lymphoma (ATLL) is extremely rare, and the data on the characteristics are limited. We herein describe a 49-year-old woman who presented with skin involvement of ATLL. Positron emission tomography/computed tomography showed bilateral breast lesions. Although the patient once achieved a complete metabolic response, a relapse of her ATLL occurred. The patient received subsequent allogeneic hematopoietic stem cell transplantation (HSCT). To our knowledge, only four cases of ATLL with breast involvement have previously been reported, and the prognoses have generally been poor. Breast lesions of ATLL have aggressive features, and intensive systemic chemotherapy and HSCT are required to improve survival.

DOI： 10.2169/internalmedicine.5077-20

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Prolonged intestinal cold storage causes considerable mucosal breakdown, which could bolster bacterial translocation and cause life-threatening infection for the transplant recipient. The intestine has an intraluminal compartment, which could be a target for intervention, but has not yet been fully investigated. Hydrogen gas exerts organ protection and has used been recently in several clinical and basic research studies on topics including intestinal transplantation. In this study, we aimed to investigate the cytoprotective efficacy of intraluminally administered hydrogen-rich saline on cold IR injury in intestinal transplantation. Isogeneic intestinal transplantation with 6 hours of cold ischemia was performed on Lewis rats. Hydrogen-rich saline (H2 concentration at 5 ppm) or normal saline was intraluminally introduced immediately before preservation. Graft intestine was excised 3 hours after reperfusion and analyzed. Histopathological analysis of control grafts revealed blunting of the villi and erosion. These mucosal changes were notably attenuated by intraluminal hydrogen. Intestinal mucosa damage caused by IR injury led to considerable deterioration of gut barrier function 3 h post-reperfusion. However, this decline in permeability was critically prevented by hydrogen treatment. IR-induced upregulation of proinflammatory cytokine mRNAs such as IL-6 was mitigated by hydrogen treatment. Western blot revealed that hydrogen treatment regulated loss of the transmembrane protein ZO-1. Hydrogen-rich saline intraluminally administered in the graft intestine modulated IR injury to transplanted intestine in rats. Successful abrogation of intestinal IR injury with a novel strategy using intraluminal hydrogen may be easily clinically applicable and will compellingly improve patient care after transplantation.

DOI： 10.1111/petr.13848

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Classic Hodgkin lymphoma (CHL) is a lymphoid neoplasia characterized by the presence of large tumor cells, referred to as Hodgkin and Reed-Sternberg (HRS) cells, originating from B-cells in an inflammatory background. As the clinical significance of B-cell markers has yet to be fully elucidated, this study aimed to clarify the clinicopathological significance of CD79a in 55 patients with CHL. They were immunohistochemically divided into two groups, comprising of 20 CD79a-positive and 35 CD79a-negative patients. There was no significant correlation between CD79a and CD20 expression (rs = 0.125, P = 0.362). CD79a-positive patients were significantly older at onset (P = 0.011). There was no significant correlation between CD79a-positivity and clinical stage (P = 0.203), mediastinal involvement (P = 0.399), extranodal involvement (P = 0.749), or laboratory findings, including serum levels of lactate dehydrogenase (P = 1) and soluble interleukin-2 receptor (P = 0.251). There were significant differences in overall survival (OS) (P = 0.005) and progression-free survival (PFS) (P = 0.007) between CD79a-positive and CD79a-negative patients (5-year OS: 64.6% and 90.5%; 5-year PFS: 44.0% and 76.6%, respectively). Five patients in whom the majority (> 80%) of HRS cells expressed CD79a consisted of 4 males and 1 female aged between 52 and 81 years; 4 of them were in a limited clinical stage. We concluded that CD79a-positive CHL may have unique clinicopathological features.

DOI： 10.3960/jslrt.20010

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Plasma cell-type Castleman disease (PCD) is a rare idiopathic atypical lymphoproliferative disorder. It is difficult to differentiate between PCD and IgG4-related disease (IgG4-RD) based on histology alone. As PCD often presents with abundant hemosiderin deposition, lymph node lesions obtained from 22 PCD patients and 12 IgG4-RD patients were analyzed using Prussian blue staining to clarify whether hemosiderin deposition is effective in distinguishing between these two diseases. The analysis disclosed that hemosiderin was more densely deposited in PCD than in IgG4-RD. The median number of Prussian blue-positive cells ± standard deviation (SD) in PCD and IgG4-RD cases was 13 ± 36 cells/3HPFs and 4 ± 8 cells/3HPFs (P = 0.034), respectively. In addition, we analyzed the relationship between hemosiderin deposition and levels of serum interleukin (IL)-6, serum C-reactive protein (CRP), and anemia-related biomarkers. We found that hemosiderin deposition was significantly correlated with the level of serum CRP (P = 0.045); however, no significant correlation was observed between hemosiderin deposition and serum IL-6 levels (P = 0.204). A non-significant positive correlation was observed between hemosiderin deposition and serum hemoglobin levels (P=0.09). Furthermore, no significant correlation was observed between hemosiderin deposition and serum iron levels (P = 0.799). In conclusion, hemosiderin deposition characteristically observed in PCD may be related to the inflammatory aggressiveness of the disease and could be used for its differential diagnosis.

DOI： 10.3960/jslrt.19037

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Pleomorphic lobular carcinoma (PLC) is a histological variant of invasive lobular carcinoma (ILC) and is associated with worse prognosis than classical ILC. It exhibits a greater degree of cellular atypia and pleomorphism and is occasionally accompanied with apocrine morphology. We investigated the immunohistochemical characteristics of samples from 31 Japanese patients with PLC to elucidate the clinicopathological characteristics of PLC including androgen receptor (AR) immunoreactivity. The surrogate molecular subtypes were luminal A-like, luminal B-like, luminal B-like/HER2, HER2-type, and triple-negative in 5, 4, 3, 5, and 14 cases, respectively. AR was positive in 92.8% (13/14) of the triple-negative PLC cases and 100% (10/10) of the non-triple-negative PLC cases. Disease-specific survival was worse in patients with histological grade 3 PLCs than in those with histological grade 2 PLCs (p = 0.007). However, there was no significant difference in the progression-free survival between the two groups (p = 0.152). No other clinicopathological characteristics were associated with prognosis. These results reveal that PLC exhibits various surrogate molecular subtypes and that the triple-negative subtype frequently expresses AR. The observed molecular apocrine differentiation implicates that triple-negative PLC can be categorized into the luminal AR subtype. Furthermore, AR-targeted therapy might be useful for patients with triple-negative PLC.

DOI： 10.1371/journal.pone.0235790

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Castleman-Kojima disease, also known as idiopathic multicentric Castleman disease with TAFRO syndrome (iMCD-TAFRO), is a recently recognized systemic inflammatory disorder with a characteristic series of clinical symptoms, including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O). Patients with iMCD-TAFRO often develop severe abdominal pain, elevated alkaline phosphatase levels, and systemic inflammation, but the etiological factors are unknown. To investigate the potential role of bacterial infection in the pathogenesis of iMCD-TAFRO, we performed polymerase chain reaction (PCR) for the bacterial 16S rRNA gene with DNA extracted from liver specimens of three patients with iMCD-TAFRO, four patients with amyotrophic lateral sclerosis, and seven patients with inflammatory conditions. Sequencing of the PCR product showed 99% DNA sequence identity with Campylobacter jejuni in all three patients with iMCD-TAFRO and in two patients with inflammatory conditions. Immunohistochemical and electron microscopy analyses could not identify C. jejuni in patients with iMCD-TAFRO. The findings indicated that C. jejuni infection is not the pathological cause of iMCD-TAFRO; however, this ubiquitous bacterium may play a role in uncontrolled systemic hypercytokinemia, possibly through the development of cross-reactive autoantibodies.

DOI： 10.1111/pin.12856

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DOI： 10.1136/jclinpath-2017-204973

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Language：Japanese  

Distinguishing between IgG4-related disease (IgG4-RD) and hyper-interleukin (IL) -6 syndrome, such as immune mediated conditions, autoimmune diseases, and idiopathic multicentric Castleman disease (iMCD) is challenging. Here, we report the case of a 69-year-old man with cervical lymphadenopathy who was admitted to our hospital and histologically diagnosed with hyper-IL-6 syndrome mimicking IgG4-RD phenotypically. Laboratory data detected polyclonal hypergammaglobulinemia comprising IgG, including IgG4 (2,350 mg/dl). Computed tomography revealed presence of systemic lymphadenopathy, enlarged bilateral submandibular glands, and infiltrative shadow in the right lower lung. Magnetic resonance imaging revealed diffusely enlarged pancreas the size of a sausage and hypointense rim on T2, suggesting autoimmune pancreatitis as part of IgG4-RD. Biopsy of the cervical lymph node revealed proliferation of IL-6-positive mature plasma cells in the expanded interfollicular area with an elevated IgG4+/IgG+ cell ratio (approximately 70%). These histological findings were consistent with hyper-IL-6 syndrome rather than IgG4-RD; however, the serum IL-6 level was slightly elevated. Bone marrow aspiration detected both IgG4- and IL-6-positive mature plasma cells. Although this case cannot be diagnosed as IgG4-RD because it failed to meet its diagnostic criteria, administration of oral prednisolone (0.5 mg/kg) resulted in rapidly improved lymphadenopathy, enlarged pancreas, and serological findings. This report can be helpful for the diagnostic assessment of polyclonal hypergammaglobulinemia conditions.

DOI： 10.11406/rinketsu.60.392

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BACKGROUND: Multicentric Castleman disease (MCD) is an uncommon lymphoproliferative disease characterized by systemic inflammatory reactions associated with the dysregulated production of interleukin-6 (IL-6). In patients with MCD, renal involvement is uncommon, with only one report published regarding kidney transplantation (KTx) to treat end-stage renal disease (ESRD) secondary to MCD. Recent clinical observations have shown that IL-6 production is implicated in allograft rejection, while IL-6 receptor blockade (with tocilizumab [TCZ]) reduces alloantibody generation and thereby improves graft survival; however, the efficacy and safety of TCZ in MCD patients undergoing KTx is still unknown. CASE PRESENTATION: Herein, we describe the case of a 50-year-old man with MCD who received living-donor KTx for ESRD. Post-operative immunosuppression consisted of a triple-drug regimen (tacrolimus, mycophenolate mofetil and methylprednisolone) with TCZ that was administered intravenously every 2 weeks. At 17 months post-transplantation, the patient remains asymptomatic, and the allograft pathology has shown no evidence of rejection and no development of de novo donor-specific antibody (DSA). CONCLUSIONS: To our knowledge, this is the second reported case of an MCD patient with ESRD who underwent successful KTx. TCZ safely supported the patient during the perioperative period, and this drug may be useful for blocking the generation of donor-specific antibodies and reducing the risk of rejection episodes. KTx in combination with TCZ is thus considered a viable treatment option for ESRD due to MCD.

DOI： 10.1186/s12882-018-1065-4

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TAFRO syndrome is a newly recognized variant of idiopathic multicentric Castleman disease (iMCD) that involves a constellation of syndromes: thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O). Thrombocytopenia and severe anasarca accompanied by relatively low serum immunoglobulin levels are characteristic clinical findings of TAFRO syndrome that are not present in iMCD-not otherwise specified (iMCD-NOS). Lymph node biopsy is recommended to exclude other diseases and to diagnose TAFRO syndrome, which reveals characteristic histopathological findings similar to hyaline vascular-type CD. TAFRO syndrome follows a more aggressive course, compared with iMCD-NOS, and there is no standard treatment.

DOI： 10.1016/j.hoc.2017.09.009

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Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by overexpression of cyclin D1 resulting from t(11;14)(q13;q32) translocation. Herein, we report 3 cases of MCL with features of plasma cell-type Castleman disease (CD). The 3 patients were all men, ranging from 51 to 74 years in age, and they all presented with systemic lymphadenopathy with anemia, hypoalbuminemia, elevated serum levels of C-reactive protein, and polyclonal hypergammaglobulinemia. Lymph node biopsy specimens of the 3 cases showed histological features of plasma cell-type CD, including atrophic germinal centers and interfollicular plasmacytosis, with no light chain restriction. However, flow cytometric analysis demonstrated an abnormal B-cell population with CD5 expression, and further analysis using cyclin D1 immunostaining highlighted a neoplastic component that was restricted to the mantle zone. These neoplastic cells were immunohistochemically positive for CD20, CD5, and SOX11, and negative for CD3, CD10, and HHV8. The Ki67 index was low. All patients were finally diagnosed with MCL. This rare type of MCL can be misdiagnosed clinically and histologically as CD. Therefore, it is important to recognize this rare type of MCL, and careful examination is required using both histological and flow cytometric analyses.

DOI： 10.1016/j.prp.2017.09.015

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We herein report a case of primary parotid extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) with Dutcher bodies. An 82-year-old man presented with a 4 cm × 2.5 cm mass in the left parotid region. Positron emission tomography/computed tomography (PET/CT) showed localized abnormal fluorodeoxyglucose (FDG) uptake in the left parotid gland and lymph nodes of the left cervical region. Fine needle aspiration (FNA) cytology of the left parotid gland showed lymphoplasmacytoid cells with periodic acid-Schiff (PAS)-positive Dutcher bodies. A subsequent excisional biopsy showed sheets of small- to medium-sized neoplastic B cells with abundant IgM in the cytoplasm as detected by immunohistochemistry. A diagnosis of stage II MALT lymphoma was made, but the patient did not receive therapeutic intervention. As previously reported, Dutcher bodies are mainly observed in B-cell neoplasms with IgM production. Because these characteristic intranuclear inclusions can be easily observed by PAS staining, the presence of PAS reaction-positive Dutcher bodies in FNA cytology can serve as a clue to differentially diagnose MALT lymphoma from plasmacytoma. Diagn. Cytopathol. 2017;45:547-551. © 2017 Wiley Periodicals, Inc.

DOI： 10.1002/dc.23691

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Plasma cell-type Castleman disease (PCD) is often encountered when differentiating IgG4-related disease (IgG4-RD). Given that serum IgA is often elevated in Castleman disease, we investigated whether IgA expression levels in histological specimens can be used to differentiate between the two diseases. Lymph node lesions obtained from 12 IgG4-RD and 11 PCD patients were analysed by immunohistochemistry with anti-IgG, -IgG4, and -IgA antibodies. In addition to all 12 cases of IgG4-RD, 8/11 cases (72.7 %) of PCD also met the diagnostic criteria of IgG4-RD (serum IgG4 ≥135 mg/dl and IgG4/IgG-positive cells ≥40 %). IgA-positive cells were sparsely and densely distributed in IgG4-RD and PCD cases, respectively. The median number of IgA-positive cells ± SD in all 12 cases of IgG4-RD was 31 ± 37 cells per three high-powered fields (3HPFs) (range 4-118 cells/3HPFs). In contrast, the median number of IgA-positive cells, which was significantly higher in all 11 cases of PCD, was 303 ± 238 cells/3HPFs (range 74-737 cells/3HPFs) (P < 0.001). In conclusion, our findings indicate that in cases where serum analysis-based data are unavailable, anti-IgA immunostaining can be used for differential diagnosis of IgG4-RD.

DOI： 10.1007/s00795-016-0145-4

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We herein report a case in which an IgG4-producing lymphoma arose in a patient with a previous diagnosis consistent with an IgG4-related disease. A 43-year-old man presented with enlarged cervical lymph nodes and was treated with steroids and radiation for what was initially assumed to be Kimura's disease, although the lesions were later histologically re-diagnosed as IgG4-related lymphadenopathy. Fourteen years later, when the patient was 58-years-old, he presented with retroperitoneal fibrosis and swollen lymph nodes. The suspicious lesions were not histologically examined as the patient did not give consent. However, the serum IgG4 concentration was high (1400 mg/dL) and he was clinically diagnosed with systemic IgG4-related disease. Although steroid administration reduced the size of the lesions, tapering the dose finally resulted in systemic, prominently enlarged lymph nodes. Analysis of the biopsy specimen revealed that these multiple lymph node lesions were marginal zone B cell lymphomas that themselves expressed IgG4. Complete remission was achieved after a total of six courses of chemotherapy including rituximab. This case suggests that the infiltrating IgG4-expressing cells observed in IgG4-related disease can clonally expand to malignant lymphomas.

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Plasmablastic lymphoma (PBL) is an aggressive lymphoma commonly associated with human immunodeficiency virus (HIV) infection. Herein we describe a rare case of PBL that spontaneously regressed. An 80-year-old man was referred to our hospital owing to an exophytic gingival tumor in the right maxillary second molar region. He had no significant past medical history, and a screening test for HIV was negative. Imaging showed that the tumor measured 26 × 23 × 16 mm and was confined in the alveolar bone. The tumor was histologically comprised of highly proliferative immunoblastic cells positive for CD138 and Epstein-Barr virus (EBV)-encoded RNA. Monoclonal IgH chain gene rearrangement was detected via polymerase chain reaction. After biopsy and diagnosis of PBL, the tumor began to decrease in size and had apparently disappeared at the time of surgery. There was no histological evidence of a residual lesion in the surgical specimen. In conclusion, a minority of immunosenescence-associated PBLs in the elderly should be recognized as a unique clinicopathological entity distinct from common aggressive PBL.

DOI： 10.1186/s13000-015-0421-y

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

A second-generation direct-acting antiviral agent, simeprevir, now provides a new treatment option for hepatitis C virus (HCV) infection with good safety profile in combination with pegylated interferon and ribavirin. We herein report a rare case of severe liver injury under simeprevir plus pegylated interferon/ribavirin therapy. We initiated this therapy in a 65-year-old male with treatment-naïve genotype 1b HCV. On day 28, the patient's HCV-RNA was successfully eliminated, and his liver function was fully restored. However, on day 49, the serum alanine aminotransferase level was elevated at 700 IU/L. The HCV-RNA titer was still undetectable and the involvement of other possible viruses was negligible. A liver biopsy performed on day 60 showed an acute hepatitis pattern. The discontinuation of therapy alone successfully improved his liver damage on day 84. No other treatments such as steroids were required. According to the diagnostic criteria for drug-induced liver injury in Japan (DDW-J2004), the liver injury observed in this case can be associated with the administration of simeprevir plus pegylated interferon/ribavirin therapy. In conclusion, simeprevir plus pegylated interferon/ribavirin should be used with caution, as these agents may cause unreported serious adverse events including severe liver injury, despite their clinical safety profile.

DOI： 10.1007/s12328-014-0527-x

PubMed

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

UNLABELLED: D cyclins positively regulate the cell cycle and mediate the pathogenesis of some lymphomas. Cyclin D1 overexpression is the hallmark of mantle cell lymphoma, whereas cyclins D2 and D3 are reportedly not as specific to certain lymphomas as cyclin D1. In this study, cyclin D2 was found to be overexpressed in 98% of de novo CD5-positive diffuse large B-cell lymphomas (DLBCLs) (50/51) and in 28% of CD5-negative DLBCLs (14/51). A statistically significant difference was observed between these two groups (p<0.0001). In contrast, no statistical difference was found in the cyclin D3 expression between CD5-positive (18/51) and CD5-negative (24/51) DLBCLs (p=0.23). Based on these findings, cyclin D2 is therefore considered to be closely associated with de novo CD5-positive DLBCLs. This insight may be useful for overcoming the inferior survival of this aggressive lymphoma. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1382856320966453.

DOI： 10.1186/1746-1596-8-81

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

Sonography-guided cutting needle biopsy for the diagnosis of malignant lymphoma has recently come into wide use. However, surgery is sometimes unavoidable for the diagnosis of malignant lymphoma, particularly for low-grade malignant lymphoma such as extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, because cutting needle biopsy offers limited diagnostic accuracy for low-grade malignant lymphoma. Of course, unnecessary invasive procedures like open biopsy should be avoided wherever possible, given the cosmetic problems and burden on the patient. We tried to diagnose malignant lymphoma using the combination of cutting needle biopsy, flow cytometry and polymerase chain reaction to identify monoclonal rearrangement of immunoglobulin heavy chain genes. We have used this method in two cases in whom malignant lymphoma was suspected in the head and neck region, allowing diagnosis of mucosa-associated lymphoid tissue lymphoma in both cases. One case involved a 23-year-old woman with mucosa-associated lymphoid tissue lymphoma in the parotid glands, and the other involved a 77-year-old man with mucosa-associated lymphoid tissue lymphoma in the thyroid. The combination of cutting needle biopsy, flow cytometry and immunoglobulin heavy chain gene rearrangement testing might offer a useful alternative to open biopsy for the diagnosis of mucosa-associated lymphoid tissue lymphoma. We recommend this procedure, particularly for young women or patients with poor performance status in whom malignant lymphoma is suspected.

DOI： 10.1093/jjco/hys011

PubMed

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

The D cyclins are important cell cycle regulatory proteins involved in the pathogenesis of some lymphomas. Cyclin D1 overexpression is a hallmark of mantle cell lymphoma, whereas cyclins D2 and D3 have not been shown to be closely associated with any particular subtype of lymphoma. In the present study, we found that cyclin D2 was specifically overexpressed in the proliferation centers (PC) of all cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) examined (19/19). To examine the molecular mechanisms underlying this overexpression, we immunohistochemically examined the expression of nuclear factor (NF)-κB, p15, p16, p18, and p27 in the PC of six patients. Five cases showed upregulation of NF-κB expression, which is known to directly induce cyclin D2 by binding to the promoter region of CCND2. All six PC examined demonstrated downregulation of p27 expression. In contrast, upregulation of p15 expression was detected in five of six PC examined. This discrepancy suggests that unknown cell cycle regulatory mechanisms involving NF-κB-related pathways are also involved, because NF-κB upregulates cyclin D2 not only directly, but also indirectly through c-Myc, which is believed to downregulate both p27 and p15. In conclusion, cyclin D2 is overexpressed in the PC of CLL/SLL and this overexpression is due, in part, to the upregulation of NF-κB-related pathways.

DOI： 10.1111/j.1349-7006.2011.02046.x

PubMed

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

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Language：English   Publisher：(一社)日本リンパ網内系学会  

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Language：Japanese   Publisher：(一社)日本リンパ網内系学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：English   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：English   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：岡山県臨床細胞学会  

背景:左腋窩リンパ節生検において、捺印細胞診が診断の契機となったALK(Anaplastic lymphoma kinase)陽性ALCL(Anaplastic large cell lymphoma)の一例を経験したので報告する。症例:40代、女性。近医にて、発熱および左腋窩リンパ節腫大で経過観察していたが、痛みが出現し、当院血液内科に紹介された。血液検査で可溶性IL-2レセプターが6,764U/mLと高値であり、リンパ節生検が施行された。組織像ではリンパ節の構造は破壊され、中型主体のリンパ腫様細胞が出現し、一部で大型異型細胞が見られた。免疫染色の結果よりT-cell lymphomaが疑われた。リンパ節生検時に作製した捺印細胞診標本では、馬蹄形核やドーナッツ状細胞など多形性に富んだ大型異型細胞が少数孤立散在性に観察された。いわゆるhallmark cellと考えられ、ALCLを疑う所見であった。これを受けて組織標本にて追加免疫染色を施行したところ、CD30、ALK、TIA/GranzymeBが広く陽性を呈した。フローサイトメトリー(以下FCM)および染色体G-band検査の結果と総合し、ALK陽性ALCLと診断された。まとめ:本症例では、組織標本ではALCLに特徴的な異型細胞が少数で観察しづらかったが、捺印細胞診では個々の細胞を詳細に観察することができ、少数であってもhallmark cellと考えられる異型細胞が確認できた。それによりALCLを疑い、FCMや免疫染色などの追加検索に繋がり、診断確定への一助となった。細胞診断を併用することの有用性が改めて認識できた一例であった。(著者抄録)

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Language：Japanese   Publisher：(一社)日本リンパ網内系学会  

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Language：English   Publisher：(一社)日本血液学会-東京事務局  

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Language：Japanese   Publisher：(一社)日本リンパ網内系学会  

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Language：English   Publisher：(一社)日本リンパ網内系学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：(一社)日本リンパ網内系学会  

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Language：English   Publisher：(一社)日本リンパ網内系学会  

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Language：Japanese   Publisher：(一社)日本リンパ網内系学会  

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Language：English   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：広島医学会  

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Language：Japanese   Publisher：広島医学会  

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Language：Japanese   Publisher：広島医学会  

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Language：English   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：広島医学会  

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Language：Japanese   Publisher：広島医学会  

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Language：Japanese   Publisher：広島医学会  

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Language：Japanese   Publisher：(一社)日本リンパ網内系学会  

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Language：English   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(有)科学評論社  

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