Efficacy and safety of endoscopic ultrasound-guided gallbladder drainage without dilation by using a 0.035-inch stiff guidewire.

Endoscopic ultrasound-guided gallbladder drainage for patients with cholecystitis and high surgical risk is commonly performed by dilating the fistula before inserting the delivery sheath; however, this carries an increased risk of peritonitis. To overcome this problem, we developed a new technique that did not require dilation, using a 0.035-inch stiff guidewire, and retrospectively evaluated the efficacy and safety of this technique. This retrospective case series report collected data on non-surgical patients who underwent endoscopic ultrasound-guided gallbladder drainage for various indications at Steel Memorial Muroran Hospital between November 2020 and October 2022. A total of 71 patients were included (mean age 83 ± 7.6 years; 33 women and 38 men). Breakthrough of the delivery sheath without dilation of the fistula was successful in 97.2% (n = 69) of patients. The success rate of stent placement was 98.6% (n = 70), as was the clinical success rate. Complications occurred in 2.8% (n = 2) of patients. Early and late adverse events occurred in 2.8% (n = 2) and 12.7% (n = 9) of patients, respectively. The mean procedure time was 24.8 ± 9.3 min. If a 0.035-inch stiff guidewire is used, the dilation procedure can be omitted in the endoscopic ultrasound-guided gallbladder drainage using self-expandable metal stents.

Detailed Clinical Characteristics, Interventions, and Long-Term Outcomes of Patients With Gastric Cancer Who Received the Best Supportive Care Without Any Anticancer Treatment.

Background: Due to the lack of studies, the long-term prognoses of unfit patients with gastric cancer (GC) who did not receive any aggressive cancer treatment (best supportive care [BSC] cases) remain unclear, especially for those with potentially curable GC. We conducted this observational study to capture the real-world data of characteristics and outcomes for BSC cases. Method: Consecutive clinical records of patients with GC diagnosed at Steel Memorial Muroran Hospital from January 2017 to December 2021 were analyzed. Result: Of 481 patients diagnosed with GC, 91 (18.9%) were BSC cases. The median overall survival (OS) was 12.4, 8.3, and 2.5 months for clinical stage (cStage) I, II-III, and IV, respectively. Patients with potentially curable GC (cStage I-III) had significantly longer OS than those with incurable disease (cStage IV), with a hazard ratio for death of 0.29 (95% confidence interval: 0.18-0.47). Conclusion: Our report provides useful information for decision-making for unfit patients with GC in daily clinical practice.

Atypical Pseudo-Meigs' Syndrome without Pleural Effusion Due to Ovarian Metastasis from Sigmoid Colon Cancer.

We herein report a case of atypical pseudo-Meigs' syndrome without pleural effusion. A 46-year-old woman was diagnosed with an ovarian tumor and sigmoid colon cancer with massive ascites. She underwent surgical resection of the sigmoid colon and bilateral salpingo-oophorectomy. The pathological diagnosis was sigmoid colon cancer with ovarian metastasis. A few days after the operation, the massive ascites disappeared. Immunostaining for vascular endothelial growth factor (VEGF) suggested its overproduction was involved in the development of the ascites. Although cases of pseudo-Meigs' syndrome without pleural effusion are rare, reporting such cases will facilitate the choice of more appropriate treatment strategies in future.

Fatal Chronic Active Epstein-Barr Virus Infection in a Rheumatoid Arthritis Patient Treated with Abatacept.

Chronic active Epstein-Barr virus (CAEBV) T-cell type infection, systemic form, is characterized by persistent infectious mononucleosis-like symptoms, high Epstein-Barr virus (EBV) DNA levels in the peripheral blood, organ damage, and a poor prognosis. The association between CAEBV and rheumatoid arthritis (RA) is unclear. We report a case of fatal CAEBV T-cell type infection in an RA patient undergoing treatment with cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin fusion protein (abatacept, ABT). CAEBV can rapidly worsen in RA patients receiving ABT. Thus, we should try to establish an early diagnosis in patients with CAEBV infection.

Molecular Signature of Tumors with Monoallelic 13q14 Deletion: a Case Series of Spindle Cell Lipoma and Genetically-Related Tumors Demonstrating a Link Between FOXO1 Status and p38 MAPK Pathway.

Spindle cell/pleomorphic lipomas (SCLs), cellular angiofibromas (CAFs) and mammary-type myofibroblastomas (MFBs) are rare benign mesenchymal tumors with monoallelic 13q14 deletion. They are predicted to have a common pathogenic mechanism due to shared similar histological and immunohistochemical features; however, pathological consequences of monoallelic 13q14 deletion remain unknown. We previously reported a CAF case with monoallelic 13q14 deletion in which the tumor expressed decreased levels of FOXO1 and RB1, both of which were encoded in 13q14, and increased reactive oxygen species (ROS) levels. We further demonstrated the activation of p38 mitogen-activated protein kinase (p38 MAPK) pathway induced by oxidative stress. We hypothesized that SCLs, CAFs and MFBs would share common molecular signatures involving FOXO1, ROS and p38 MAPK and that their expression patterns were different from those tumors without monoallelic 13q14 deletion such as solitary fibrous tumors (SFTs). We compared the expression levels of FOXO1, RB1, ROS markers and several signal transduction factors between SCLs and SFTs. SCLs expressed decreased levels of FOXO1 and RB1, whereas SFTs showed no change. Both tumor types exhibited increased markers of ROS; however, nuclear localization of phosphorylated p38 was significantly more frequent in SCLs than that in SFTs, suggesting p38 MAPK activation by oxidative stress. SFTs showed lower p38 MAPK activity and higher ß-catenin expression, implying that oxidative stress was caused by increased cellular proliferation stress. Finally, CAFs and MFBs showed changes similar to those observed in SCLs. Overall, tumors with monoallelic 13q14 deletion showed shared molecular signatures that might be associated with pathogenesis.

A rare pulmonary hamartoma: fibroleiomyomatous hamartoma.

Pulmonary hamartomas are more common than expected because they are usually asymptomatic and are either discovered on routine chest radiography or when they are noted incidentally in approximately 0.25 % of autopsies. In contrast, pulmonary fibroleiomyomatous hamartoma, which consists of interlacing bundles of smooth muscle cells admixed with fibrous tissue and numerous tubular or cleft-like epithelial inclusions, is a rare type of hamartoma. Controversy exists regarding the pathogenesis of this tumor. We herein present a rare case of a 68-year-old male patient without a pre-existing smooth muscle tumor, who underwent resection for a tumor that was considered to be a true pulmonary fibroleiomyomatous hamartoma.

Immunohistochemical and molecular detection of the expression of FGF23 in phosphaturic mesenchymal tumors including the non-phosphaturic variant.

BACKGROUND: Phosphaturic mesenchymal tumors (PMTs) are rare neoplasms that are often associated with tumor-induced osteomalacia (TIO) due to excessive serum levels of fibroblast growth factor 23 (FGF23). PMTs share overlapping histologic features with other types of tumors; thus, accurate pathological diagnosis may be challenging. We performed an immunohistochemical examination of FGF23 expression in PMTs and other types of tumors, together with pertinent molecular analyses. METHODS: Seven PMTs (5 with TIO and 2 without TIO) and 46 other types of bone and soft tissue tumors were retrieved, and immunohistochemistry was performed using a commercially available anti-FGF23 antibody. In addition, FGF23 mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR), using RNA extracted from formalin-fixed, paraffin-embedded tissues. RESULTS: Immunohistochemical analysis of FGF23 expression showed distinct, punctate staining in the cytoplasm in 5 PMTs with TIO, whereas FGF23 expression was negative in the 2 PMTs without TIO and the other 46 tumors. FGF23 mRNA expression was detected in all 4 PMTs examined, as well as in 1 chondromyxoid fibroma and 1 myxoid liposarcoma. The real-time RT-PCR data showed that the relative expression levels of the FGF23 mRNA tended to be higher in PMTs with TIO than in PMTs without TIO, or in the chondromyxoid fibroma specimen. CONCLUSIONS: Our data suggested that the feasibility of immunohistochemical detection of FGF23 may depend on the level of secreted FGF23 from tumor cells. Thus, immunohistochemistry for FGF23 is an useful diagnostic adjunct for PMT, although its utility appears to be limited in cases without TIO.

Pulmonary Neoplasms in Patients with Birt-Hogg-Dubé Syndrome: Histopathological Features and Genetic and Somatic Events.

Birt-Hogg-Dubé syndrome (BHD) is an inherited disorder caused by genetic mutations in the folliculin (FLCN) gene. Individuals with BHD have multiple pulmonary cysts and are at a high risk for developing renal cell carcinomas (RCCs). Currently, little information is available about whether pulmonary cysts are absolutely benign or if the lungs are at an increased risk for developing neoplasms. Herein, we describe 14 pulmonary neoplastic lesions in 7 patients with BHD. All patients were confirmed to have germline FLCN mutations. Neoplasm histologies included adenocarcinoma in situ (n = 2), minimally invasive adenocarcinoma (n = 1), papillary adenocarcinoma (n = 1), micropapillary adenocarcinoma (n = 1), atypical adenomatous hyperplasia (n = 8), and micronodular pneumocyte hyperplasia (MPH)-like lesion (n = 1). Five of the six adenocarcinoma/MPH-like lesions (83.3%) demonstrated a loss of heterozygosity (LOH) of FLCN. All of these lesions lacked mutant alleles and preserved wild-type alleles. Three invasive adenocarcinomas possessed additional somatic events: 2 had a somatic mutation in the epidermal growth factor receptor gene (EGFR) and another had a somatic mutation in KRAS. Immunohistochemical analysis revealed that most of the lesions were immunostained for phospho-mammalian target of rapamycin (p-mTOR) and phospho-S6. Collective data indicated that pulmonary neoplasms of peripheral adenocarcinomatous lineage in BHD patients frequently exhibit LOH of FLCN with mTOR pathway signaling. Additional driver gene mutations were detected only in invasive cases, suggesting that FLCN LOH may be an underlying abnormality that cooperates with major driver gene mutations in the progression of pulmonary adenocarcinomas in BHD patients.

A striking response of plasmablastic lymphoma of the oral cavity to bortezomib: a case report.

BACKGROUND: Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of non-Hodgkin diffuse large B-cell lymphoma originally with a predilection to the oral cavity of patients infected with HIV. However, PBL of extraoral sites possesses clinicopathological characteristics distinct from oral PBL. Recently, therapeutic approaches using a proteasome inhibitor bortezomib to PBL of extraoral sites have been reported. We present a PBL patient with a bulky tumor of the oral cavity, who dramatically responded to bortezomib. CASE PRESENTATION: The patient was a 58 year-old Japanese male, who presented with a rapidly progressive history of a swelling on his left cheek and restricted mouth opening. He did not have a history or evidence of immunosuppression including HIV infection. A computed tomography demonstrated a bulky tumor in the oral cavity without enlarged lymph nodes. The tumor showed the proliferation of large lymphoid cells with centroblastic morphology, which were positive for CD138, CD38, CD56 and MUM-1, and negative for CD20, CD79a, BCL-6 and HHV8. The Ki-67 proliferation index was almost 100 %. Neither osteolytic lesions nor M-protein was observed. One week after the initiation of bortezomib, a marked regression of the oral tumor was obtained. CONCLUSIONS: Thus, our case demonstrated the effectiveness of bortezomib on PBL of the oral cavity as well as the extraoral sites.

Possible familial case of Birt-Hogg-Dubé syndrome complicated with lung cancer: A possible link between these two disease entities.

A 65-year-old Japanese woman was introduced to our hospital for an examination of multiple pulmonary cystic lesions and a pulmonary nodule in the left lower lobe. She had a smoking history of 25 pack-years, and her two younger brothers had suffered from pneumothorax; one of them additionally had lung cancer with pulmonary multiple cystic lesions. A surgical biopsy specimen obtained from her left lower lobe revealed adenocarcinoma surrounded by a single epithelial layer that was covered with collagen fibers. The pathological features were compatible with the findings of the cystic lesions in the patients with Birt-Hogg-Dubé syndrome (BHDS). A diagnosis of BHDS was eventually made according to the detection of a folliculin gene mutation. This is the first report of a possible familial case of BHDS complicated with primary lung cancer. We herein reviewed the previously reported cases of BHDS with lung cancer and other tumors and discussed a potential mechanism of tumorigenesis and carcinogenesis in the lung in the patients with BHDS.

CAMTA1 is a useful immunohistochemical marker for diagnosing epithelioid haemangioendothelioma.

AIMS: The diagnosis of epithelioid haemangioendothelioma (EHE) is usually straightforward, based on characteristic histological features. However, it is sometimes difficult to differentiate EHE from a variety of other tumours with epithelioid morphology. The WW domain-containing transcription regulator 1-calmodulin-binding transcription activator 1 (WWTR1-CAMTA1) fusion gene, resulting in the overexpression of CAMTA1, is demonstrated in approximately 90% of EHEs, and the yes-associated protein 1-transcription factor E3 (YAP1-TFE3) fusion gene, associated with the strong and diffuse nuclear expression of TFE3, is present in another small subset of EHEs. The aim of our study was to examine CAMTA1 expression in EHEs and a variety of other tumours to evaluate its diagnostic utility, and to analyse TFE3 expression status in EHEs. METHODS AND RESULTS: Immunohistochemistry was performed on 16 EHEs, including five cases with CAMTA1 rearrangement and 276 non-EHE tumours. Fourteen of 16 EHEs and only one case of ductal carcinoma of the breast were positive for CAMTA1 and its expression was focal and weak in the latter (sensitivity 87.5%, specificity 99.6%). TFE3 expression was expressed focally and weakly in three (19%) EHEs (two with the CAMTA1 rearrangement). CONCLUSIONS: Nuclear CAMTA1 expression is sensitive and highly specific for EHE and can be applied to diagnostic immunohistochemistry in epithelioid tumours.

Prognostic significance of WNT signaling in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancies and is associated with a variety of molecular abnormalities. Although WNT signaling through its canonical/non-canonical pathways is one of the major factors involved in oncogenesis or progression of PDA, the prognostic significance of WNT signaling still remains poorly investigated. In this study, the status of the WNT signaling pathways was immunohistochemically analyzed in 101 PDAs, and its potential association with patient postoperative survival was assessed. Nuclear expression of beta-catenin, a hallmark of the activated canonical pathway, was identified in 59 cases, and was associated with reduced survival compared to the patients lacking nuclear beta-catenin expression (P = 0.002). In contrast, activation of the non-canonical pathway (25 cases), as indicated by co-expression of WNT2/5a and nuclear NFATc1, was not correlated with reduced survival (P = 0.268). Co-activation of both pathways (16 cases) was associated with worse prognosis in comparison with cases with an activated non-canonical pathway (P = 0.034). In addition, nuclear beta-catenin expression was an independent unfavorable prognostic factor (P = 0.006). Our data indicate that activated WNT signaling through its canonical pathway has a significantly negative effect on the clinical course of PDA, and the canonical WNT pathway should be considered as a future therapeutic target for PDA.

The combination of CD99 and NKX2.2, a transcriptional target of EWSR1-FLI1, is highly specific for the diagnosis of Ewing sarcoma.

Ewing sarcoma (ES) is a high-grade malignant neoplasm primarily affecting children and young adults. The diagnosis of ES is often difficult because of its broad differential diagnosis comprising a diverse group of small round cell tumors (SRCTs). Although the identification of tumor type-specific fusion genes by molecular testing is the gold standard for the diagnosis of ES, such approaches are not always available in a routine pathology practice. Thus, a reliable immunohistochemical marker is required. A recent study using a limited number of tumor samples has shown that NKX2.2, a putative transcriptional target of EWSR1-FLI1, is a useful marker for the diagnosis of ES. In the present study, the immunohistochemical expression of NKX2.2 was evaluated on 46 genetically confirmed ES and 85 non-ES SRCTs, together with comparative assessment of CD99 and other molecular targets of EWSR1-FLI1, including NR0B1, E2F3, and EZH2. NKX2.2 was expressed in 37 (80 %) of the ES samples with a mostly diffuse and strong staining pattern, and 14 (16 %) of the non-ES SRCTs, including olfactory neuroblastomas, extraskeletal myxoid chondrosarcoma, mesenchymal chondrosarcoma, small cell carcinomas, and Merkel cell carcinoma, also expressed this marker. The sensitivity and specificity of the NKX2.2 expression in this cohort were 80 and 84 %, respectively. The specificity when combined with CD99 was 98 %, with exceptional expression of both markers in only two non-ES SRCTs, including one case each of mesenchymal chondrosarcoma and small cell carcinoma. NR0B1, E2F3, and EZH2 were less sensitive for specific markers for ES when applied singly or in any combination. In conclusion, the study reinforces that NKX2.2 is a useful immunohistochemical marker for ES, and that the combination of CD99 and NKX2.2 is a powerful diagnostic tool that can differentiate ES from other SRCTs.

Desmin-positivity in spindle cells: under-recognized immunophenotype of lipoblastoma.

Lipoblastoma is a distinct benign fatty tumor composed of adipocytes, lipoblasts, and primitive mesenchymal cells with a myxoid stroma. Lipoblastoma harbors characteristic fusion genes involving the PLAG1, resulting in aberrant expression of PLAG1. However, the nature of the primitive mesenchymal cells remains obscure. In our routine pathology practice, we noticed desmin-positive spindle mesenchymal cells in lipoblastomas, which is a hitherto poorly described phenomenon. Thus, we examined the expression of several myogenic markers including desmin in a variety of 95 mesenchymal tumors with fatty elements. Fourteen of the 15 lipoblastomas examined contained desmin-positive spindle cells, which also showed nuclear expression of PLAG1, whereas α-smooth muscle actin, muscle specific actin, h-caldesmon, and myogenin were negative. Some spindle cells in subsets of atypical lipomatous tumors/well differentiated liposarcomas (6/20), dedifferentiated liposarcomas (11/31) and pleomorphic liposarcomas (2/10) were positive for actins and/or desmin, supporting focal myofibroblastic or smooth muscle differentiation. The other tumors, including 11 myxoid/round cell liposarcomas, four spindle cell lipomas, and four lipofibromatoses, were negative for all of the myogenic markers assessed. The almost consistent desmin expression in spindle mesenchymal cells suggests a potential diagnostic utility of this marker and myofibroblastic phenotype of fractions in lipoblastoma cells.