Primary Bone Lymphoma of the Spine: A Case Report Highlighting Diagnostic Complexities and Treatment.

The diagnosis of primary bone lymphoma (PBL) of the spine is challenging due to its nonspecific symptoms and radiographic features. This report details the case of an 81-year-old female who presented with lower limb weakness and thoracic pain, consequent to a vertebral pathological fracture and spinal cord compression. The initial surgical intervention revealed granulomas with caseous necrosis; however, a definitive diagnosis remained elusive. Following a third surgical procedure and further histopathological examination, the patient was finally diagnosed with diffuse large B-cell lymphoma. The therapeutic course following diagnosis involved chemotherapy, resulting in a marked improvement of the symptoms. Previous studies have highlighted the diagnostic difficulties associated with PBL, reporting the frequent need for multiple biopsies to confirm the diagnosis due to the prevalence of necrosis, crush artifacts, or inadequate sample volume. While PBL of the spine has shown responsiveness to chemotherapy and radiation therapy, early surgical intervention is advocated in cases of severe spinal cord compression or vertebral instability. The presented case highlights the importance of making a definitive pathology diagnosis in cases of suspected PBL of the spine.

Secondary aneurysmal bone cyst of the frontal bone with fibrous dysplasia showing rapid expansion: a case report.

A 19-year-old woman presented with swelling of the left forehead without pain. She did not have any relevant past or family history. Computed tomography showed destruction of the outer cortex of the frontal bone. A solitary mass lesion with a fluid collection was detected with magnetic resonance imaging. Because the swelling of the left forehead had enlarged rapidly with osteolytic changes, surgical removal of the lesion was performed. The lesion appeared to be enveloped in a fibrous capsule. The soft lesion was removed from the frontal bone. The outer frontal bone was absent, although the inner frontal bone was preserved. Then, the frontal bone was resected with margins from the edge of the erosion. The dura mater under the lesion was intact. A cranioplasty was performed using titanium mesh. On histological examination, the trabecular bones revealed irregular shapes and arrangements, indicating fibrous dysplasia. There was a continuous high-cell-concentration pathological lesion outside the fibrous dysplasia. There were numerous cells, such as mononuclear cells, osteoclast-like multinucleated giant cells, foam cells, and red blood cells. The osteoclast-like multinucleated giant cells and other cells did not show significant nuclear atypia. Immunostaining with H3.3G34W was negative, and the ubiquitin-specific peptidase 6/Tre-2 gene showed no rearrangements. The histopathological diagnosis was secondary aneurysmal bone cyst with fibrous dysplasia. Additional postsurgical therapy was not performed. There has been no evidence of recurrence of the lesion for two years.

NKX3.1 Expression in Salivary Gland "Intraductal" Papillary Mucinous Neoplasm: A Low-Grade Subtype of Salivary Gland Mucinous Adenocarcinoma.

BACKGROUND: Salivary gland intraductal papillary mucinous neoplasm (SG IPMN) is a recently proposed entity characterized by a papillary-cystic proliferation of mucin-producing cells. Because of overlapping histologic features and a clonal AKT1 p.E17K variant, SG IPMN has been presumed to be a precursor or a low-grade subtype of mucinous adenocarcinoma. NKX3.1 is a tumor suppressor gene located on chromosome 8p and is a known immunohistochemical marker of prostate epithelium and mucinous acinar cells of the intraoral salivary glands. METHODS: We retrieved 12 SG IPMN cases, and performed histologic and genetic analysis. Given the association of SG IPMN with mucinous acinar cells, we also investigated the performance of NKX3.1 as a marker of this tumor entity. RESULTS: Diffuse and strong NKX3.1 expression was observed in all SG IPMN cases (12/12, 100%) as well as in normal mucinous acinar cells. In contrast, mucoepidermoid carcinoma and pancreatic IPMN cases as well as normal serous acinar cells were negative for NKX3.1. Genetically, 11 of 12 cases (92%) harbored an AKT1 p.E17K variant. A novel PTEN frameshift deletion (p.G36Dfs*18) was detected in the other single case. At least one of the histologic features implying malignant tumors, such as severe cellular atypia, brisk mitotic activity, high Ki-67 proliferating index, lymphovascular invasion, and lymph node metastasis, was detected in 6 SG IPMN cases (50%). CONCLUSION: The findings suggest that SG IPMN is a low-grade subtype of mucinous adenocarcinoma which may be derived from mucinous acinar cells of the minor salivary gland.

Primary Dural Mucosa-associated Lymphoid Tissue Lymphoma Mimicking Falx Meningioma: A Case Report.

An 85-year-old woman presented with ataxia and deterioration of cognitive functions. She had no history of autoimmune diseases or viral infections. Magnetic resonance imaging showed a solitary mass lesion at the cerebral falx on contrast-enhanced T1-weighted imaging. Gross total resection of the lesion involving the dura mater was performed by bifrontal craniotomy. Histological examination showed diffuse infiltration of small lymphocytes and plasma cells. There was also some proliferation of large lymphocytes with folded nuclei, high-density chromatin, and inconspicuous nucleoli. The large atypical B lymphocytes did not demonstrate diffuse dense sheet findings. Meningothelial components were not detected. Immunohistochemistry was positive for pan B-cell antigens. The analysis of the kappa/lambda ratio indicated kappa immunoglobulin light chain-restricted B-cell proliferation. The final histopathological diagnosis was mucosa-associated lymphoid tissue lymphoma. Systemic screening examinations were then performed. Histological findings of the bone marrow showed normal findings without atypical lymphocytes. A chromosomal study of the bone marrow showed 46, XX. 18F fluoro-2-deoxyglucose positron emission tomography showed high accumulations at the left pterygoid muscle and the right transverse processes of the thoracic vertebrae, and mild accumulation at the right ilium bone, which indicated disseminated lesions. One year later, thickening of the dura mater was detected. Therefore, gamma knife surgery was performed. Two years later, she was alive without neurological deterioration, and magnetic resonance imaging showed no evidence of recurrence.

Adenomatoid tumor of the mediastinum.

Adenomatoid tumors are relatively uncommon benign tumors of mesothelial origin, usually occurring in the male or female genital tracts. Extragenital adenomatoid tumors are quite rare. Here, we report a very rare case of adenomatoid tumor of the mediastinum. A 67-year-old woman was admitted to our hospital with an abnormal shadow that appeared on a routine chest radiograph. After further radiological evaluation suggested a diagnosis of thymoma, surgical resection was performed, and histologic and immunohistochemical examination yielded a definitive diagnosis of adenomatoid tumor. The patient remained clinically free of disease at follow-up, 19 months later.

Retrospective analysis of safety and efficacy of insulin-to-liraglutide switch in Japanese type 2 diabetes: A caution against inappropriate use in patients with reduced ß-cell function.

AIMS/INTRODUCTION: The safety and efficacy of insulin-to-liraglutide switch in type 2 diabetes has not been studied adequately. Here, we retrospectively characterize clinical parameters that might predict insulin-to-liraglutide treatment switch without termination due to hyperglycemia, and examine the effects of switching the therapies on glycated hemoglobin (HbA1c) and bodyweight in Japanese type 2 diabetes. MATERIALS AND METHODS: Japanese type 2 diabetes patients who underwent the switch of therapy were evaluated for their clinical data including ß-cell function-related indices, such as increment of serum C-peptide during glucagon stimulation test (GST-ΔCPR). HbA1c and bodyweight were analyzed in patients continuing with liraglutide after switching from insulin for 12 weeks. RESULTS: Of 147 patients, 28 failed in the switch due to hyperglycemia, nine failed because of other reasons and 110 continued with liraglutide for the 12-week period. Patients failing in the switch due to hyperglycemia showed longer duration and higher daily insulin dose, as well as lower GST-ΔCPR. Receiver-operating characteristic analysis showed that GST-ΔCPR of 1.34 ng/mL is a cut-off point for insulin-to-liraglutide switch without termination due to hyperglycemia. In patients continuing liraglutide for 12 weeks, the switch significantly reduced HbA1c and bodyweight with no severe hypoglycemia, irrespective of sulfonylurea co-administration, body mass index, duration and total daily insulin dose. The switch also significantly reduced the percentage of body fat and visceral fat areas. CONCLUSIONS: Insulin-to-liraglutide switch can improve glycemic control and reduce bodyweight in Japanese type 2 diabetes patients. However, caution must be taken with the switch in patients with reduced insulin secretory capacity as predicted by GST-ΔCPR.

Plasmablastic lymphoma of the stomach in an HIV-negative patient.

Plasmablastic lymphoma (PBL) is a rare B-cell neoplasm with an aggressive clinical behavior that predominantly occurs in the oral cavity of human immunodeficiency virus (HIV)-positive patients. However, it has recently been recognized that PBLs can also affect individuals without HIV infection, and suggested that these neoplasms show different clinicopathological characteristics between HIV-positive and -negative patients. Herein we describe a case of gastric PBL in a female HIV-negative patient. The tumor was composed of a diffuse and cohesive proliferation of large neoplastic cells, which resembled immunoblasts or plasmablasts with a starry sky appearance. Immunophenotypically, the neoplastic cells were diffusely positive for CD138, MUM1, IgM, and BOB-1, and negative for CK, LCA, CD3, CD20, CD79a, Pax5, kappa, lambda, CD30, ALK, S-100, HMB-45, MPO, and HHV-8. The MIB-1 index was nearly 100%. Epstein-Barr virus-encoded RNA in situ hybridization was negative. A monoclonal immunoglobulin heavy chain gene rearrangement was detected in polymerase chain reaction (PCR) and heteroduplex analyses. A combination of PCR-based analysis of immunoglobulin gene rearrangement and immunohistochemistry can be useful to substantiate the diagnosis by utilizing routine paraffin-embedded tissue sections, because PBL in the setting of extra-oral localization and immunocompetence is a diagnostic challenge, given its rarity, morphology, and absence of CD20 expression.

Comparison of incretin immunoassays with or without plasma extraction: Incretin secretion in Japanese patients with type 2 diabetes.

UNLABELLED: Aims/Introduction: The effectiveness of incretin-based therapies in Asian type 2 diabetes requires investigation of the secretion and metabolism of glucose-dependent insulinotropic polypepide (GIP) and glucagon-like peptide 1 (GLP-1). Plasma extractions have been suggested to reduce variability in intact GLP-1 levels among individuals by removing interference that affects immunoassays, although no direct demonstration of this method has been reported. We have evaluated the effects of ethanol and solid-phase extractions on incretin immunoassays. We determined incretin levels during meal tolerance tests in Japanese patients with type 2 diabetes and characterized predictors for incretin secretion. MATERIALS AND METHODS: Japanese patients with type 2 diabetes (23 anti-diabetic drug-naïve and 18 treated with sulfonylurea [SU] alone) were subjected to meal tolerance tests, and incretin levels were determined by immunoassays with or without extraction. RESULTS: Intact GLP-1 levels determined by an intact GLP-1 immunoassay with ethanol and solid-phase extractions were lower than those determined without extraction. Intact GLP-1 levels determined by the extractions were highly correlated with each other, much more so than the levels with and without extraction. Total GLP-1 was unaffected by extractions, showing that extractions remove interference only in the case of intact GLP-1. Incretin secretion after meal ingestion was similar between drug-naïve and SU-treated patients. Fasting and postprandial GLP-1 levels were correlated positively with fasting free fatty acids and negatively with dipeptidyl peptidase-4 activity. CONCLUSIONS: Ethanol and solid-phase extractions remove interference for intact GLP-1 immunoassay. SU showed little effect on incretin secretion. GLP-1 and GIP secretion were predicted by different factors. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00141.x, 2012).

[Multiple glomus tumors in chest wall and buttocks].

We report a case of a 50-year-old man with multiple glomus tumors of the chest wall and buttocks. He was admitted to our hospital because of right chest pain for 10 years. The chest pain was lancinating and gradually increasing. A computed tomography (CT) showed a mass in the right 3rd intercostal space and a mass in the right buttocks. The chest tumor was enhanced with contrast medium on chest CT. Two tumors were resected completely including the 4th rib. Histological examination showed numerous vascular space lined with sheets of epithelial cells (glomus cells), so they were diagnosed as glomus tumor. The postoperative course was well, and the pain disappeared after resection. The glomus tumor of chest wall could be diagnosed as malignant tumor, based on the criteria of the size more than 2 cm and deep location. The glomus tumors which occurred in the chest wall and buttocks were very rare. We presented the case with reference to the literature.

4-Hydroxynonenal modifies IgA in rat intestine after lipopolysaccharide injection.

The lipid peroxide 4-hydroxynonenal (HNE) was measured in rat intestinal mucosa after lipopolysaccharide (LPS) injection (0.5 mg/kg, ip) by a highly sensitive time-resolved fluoroimmunoassay. HNE was increased, with a small peak at 20 min followed by a sustained elevation at 2-4 h, after injection of LPS. Immunohistochemistry demonstrated enhanced labeling with anti-IgA and anti-HNE antibodies in the plasma cells followed by diffusion of the labeled materials into the submucosal tissue after LPS injection. Immunoprecipitation with anti-IgA antibody and Western blotting with anti-HNE antibody showed that IgA is modified with HNE after LPS injection. The HNE (5 microM-5 mM) modification in vitro reduced the bactericidal activity of IgA and anti-Escherichia coli serum. The HNE modification in vitro also promoted polymerization of IgA as shown by nondenaturing gel electrophoresis. This is the first demonstration of the modification of IgA with HNE in an in vivo model of intestinal inflammation as well as in vitro effects of HNE on bactericidal activity and polymerization of IgA. These findings will help in understanding the involvement of oxidative stress in the IgA-mediated immune response exerted by plasma cells in early intestinal inflammation.

Primary poorly differentiated monophasic synovial sarcoma of the lung. A case report with immunohistochemical and genetic studies.

We describe a case of a poorly differentiated monophasic synovial sarcoma arising in the lung of a 50-year-old man. The tumor, which was located in the right upper lobe, was lobulated, relatively well-circumscribed, and whitish to yellowish in color. Microscopically, it was composed exclusively of ovoid to polygonal or short spindle cells, with a high nuclear to cytoplasmic ratio and relatively scant cytoplasm, arranged in solid sheets or in a hemangiopericytomatous pattern with intervening wiry collagen fibers. At the periphery of the tumor, entrapped benign alveolar epithelium produced a pseudo-biphasic appearance. In some areas, an abundance of keloidal collagen imparted a close resemblance to a solitary fibrous tumor, making it difficult to establish the diagnosis on the initial needle biopsy, although the malignant nature of the tumor was suggested because of nuclear anaplasia. Immunohistochemically, the tumor was positive for cytokeratin AE1/AE3, CAM5.2, EMA, vimentin, bcl-2 protein, calretinin, and CD34. The reverse transcriptase-polymerase chain reaction (RT-PCR), using RNA extracted from fresh-frozen tissue, demonstrated SYT/SSX-1 fusion transcripts, confirming the diagnosis of synovial sarcoma. Microscopic examination demonstrated metastatic deposits in hilar lymph nodes. This case indicates that a primary pulmonary synovial sarcoma, particularly in its poorly differentiated form, is a diagnostically challenging and highly aggressive neoplasm typically found at an advanced stage.