Abnormal expression of LCA and CD43 in SCLC: a rare case report and brief literature review.

BACKGROUND: To present an unusual case of abnormal LCA expression and CD43 in SCLC and to review the reported literature to avoid potential diagnostic pitfalls. CASE PRESENTATION: A 73-year-old male patient suffered from persistent back pain for more than one month. MRI revealed a compression fracture of the L1-L5 vertebra. A CT scan revealed multiple nodules and masses at the left root of the neck, lung hilum and mediastinum, and multiple areas of bony destruction of the ribs. Histology of the tumor revealed that small and round cells were arranged in nests with areas of necrosis. The tumor cells were round to ovoid with scant cytoplasm and indistinct cell borders. The nuclear chromatin was finely granular, and the nucleoli were absent or inconspicuous. Immunohistochemically, the tumor cells were positive for cytokeratin, TTF-1, POU2F3, LCA, and CD43. CONCLUSION: This report highlights a potential diagnostic pitfall in the diagnosis of SCLC, urges pathologists to exercise caution in cases of LCA and CD43 positivity and illustrates the need for further immunohistochemical studies to avoid misdiagnosis.

POU2F3-positive small cell carcinoma of the bladder: A clinicopathologic analysis of 4 cases and literature review.

POU class 2 homeobox 3 (POU2F3)-positive small cell bladder carcinoma (SCBC) is an extremely rare entity, and its clinicopathologic features have not been fully described. Here, we investigated the clinicopathologic features of 4 cases of POU2F3-positive small cell bladder carcinoma (SCBC) and reviewed the literature. We collected 12 cases of SCBC from our departmental archives and detected the expression of POU2F3 by immunohistochemical (IHC) staining. Selected cases with or without POU2F3 expression were subjected to gene expression analysis between two different groups using DESeq2 software. We identified 4 POU2F3-positive SCBC patients, 2 males and 2 females, with a mean age of 77 years. Three patients had hematuria, and 1 patient had dysuria. Radiologic findings showed a bladder mass. Pathologic diagnosis showed that 3 cases were pure SCBC and 1 was mixed urothelial cancer (UC). Histopathologically, four POU2F3-positive SCBC tumors were composed of small round cells with sparse cytoplasm, the nuclei were salt-and-pepper-like or finely granular. Tumor cells showed characteristic cytoplasmic staining with punctate positive signals for cytokeratin. Syn and CD56 were diffusely positive in all the 4 patients. CgA was positive in only one patient. POU2F3-positive SCBC showed higher expression levels of POU2F3, HMGA2 and PLCG2 genes by RNA-Seq. Our data showed the specific clinicopathologic features of 4 rare POU2F3-positive SCBC cases, and the distinct molecular feature was observed between POU2F3-positive and negative SCBC in the limited number of cases.

Case report: Preliminary response to tislelizumab plus S-1 in patients with metastatic gallbladder carcinoma: A report of five cases and a literature review.

Gallbladder cancer (GBC) and cholangiocarcinoma are common cancers of the biliary system and are associated with a poor prognosis. Surgery and chemotherapy provide limited benefit to patients with advanced biliary tract carcinoma. Novel immunotherapies and molecularly targeted therapies are more effective options; however, few patients benefit and drug resistance is a concern. Here, we report five cases of advanced GBC with either high programmed death-ligand 1 (PD-L1) expression or a high tumor mutation burden (TMB-H). The patients were treated with a combination therapy of tislelizumab and S-1. The tumors were effectively controlled in most patients. One patient developed immune-related pneumonia (irP) during treatment, which resolved after hormone therapy, and the patient underwent surgery. Tislelizumab and S-1 were administered again after surgery; however, recurrent irP required discontinuation, and the tumor progressed after drug withdrawal. These cases demonstrate that combined therapy of anti-programmed cell death protein-1 (PD-1) antibodies and S-1 is a safe and effective regimen with few side effects for GBC patients, especially for sensitive populations (patients with TMB-H, microsatellite instability, deficient mismatch repair, or high expression of PD-L1). To our knowledge, this is the first time that tislelizumab in combination with S-1 has been used to treat patients with advanced GBC.

ERG Expression is Helpful in Differentiating T-Lymphoblastic Lymphoma from Thymoma.

ETS-related gene (ERG) is the member of ETS-family of transcription factors and is commonly expressed in Ewing sarcoma. Recently, we found that ERG can also be expressed in lymphoblastic lymphoma. The aim of this article is to explore the expression patterns of ERG in T-lymphoblastic lymphoma, and to evaluate its diagnostic value for differentiating T-lymphoblastic lymphoma and nonneoplastic T-precursor cells in thymoma via immunohistochemistry. In this study, we explored the expression pattern of ERG in T-lymphoblastic lymphoma and thymoma specimens via immunohistochemistry. Sixteen T-lymphoblastic lymphoma and 18 thymoma specimens were evaluated for the expression of ERG. Our findings showed that ERG was expressed in 10 of the 16 (63%) T-lymphoblastic lymphoma specimens, and in only 1 of the 18 (6%) thymoma specimens. The positive and negative predictive value of ERG in T-lymphoblastic lymphoma was 91% and 74%, respectively. ERG is a helpful marker for the diagnosis of T-lymphoblastic lymphoma and is a promising new method to differentiate T-lymphoblastic lymphoma and the nonneoplastic T-precursor cells in thymoma.

Melan-A expression in non-melanocytic carcinoma: A potential diagnostic pitfall.

BACKGROUND: Melan-A/MART-1 is a melanocytic differentiation marker recognized as an antigen on melanoma cells. It is a useful diagnostic marker for pathologists in the diagnosis of melanocytic tumors. However, we recently found that Melan-A can be expressed in some non-melanocytic carcinomas that are rarely reported in the literature. METHODS: We analyzed the expression of Melan-A in 87 non-melanocytic carcinoma tissue samples by immunohistochemistry. Marker positivity was defined as ≥10% positive tumor cells. RESULTS: In 87 non-melanocytic carcinoma tissue samples, Melan-A was positive in six (6.89%) cases, of which four (66.7%) were male and two (33.3%) were female, with a mean age of 60 years (range 21-82 years). Five (83.3%) of the Melan-A-positive cases had distant metastases. Compared with Melan-A negative cases, Melan-A positive non-melanocytic carcinomas were significantly associated with poor prognosis (P=0.0023). CONCLUSIONS: Melan-A expression is relatively rare in non-melanocytic carcinoma cases. This report highlights a potential diagnostic pitfall in the diagnosis of melanoma, urges pathologists to exercise caution in cases of Melan-A positivity, and illustrates the need for an immunohistochemical marker panel to avoid misdiagnosis.

Remission from the 5-Fu-Based Chemotherapy to Gemcitabine-Based Chemotherapy-Based on the Pathological Classification of Periampullary Carcinoma: A Case Report and Literature Review.

Background: Periampullary carcinoma, which includes ampullary carcinoma, pancreatic head cancer, distal common bile duct cancer, and duodenal papillary cancer, is a relatively rare malignancy with uncertain therapeutic options. Although several studies have investigated the efficacy of multiple adjuvant chemotherapy regimens for periampullary carcinoma treatment, the optimal regimen remains to be determined. The inherent heterogeneity of the mucosal origin divides periampullary carcinoma into intestinal and pancreaticobiliary types. Therefore, the selection of chemotherapy regimens based on pathological type may have potential therapeutic significance. Case Presentation: A 72-year-old woman with moderately differentiated periampullary adenocarcinoma experienced disease progression after receiving FOLFOX regimen. Subsequently, the sample was subtyped first by H&E evaluation and then by the evaluation of an IHC panel composed of CK20, CDX2, MUC1, MUC2, and MUC5AC. The pathologists concluded that the patient's sample was of the pancreaticobiliary (PB) subtype. The subsequent change to gemcitabine plus S-1 adjuvant therapy achieved remission of liver metastases based on the pathological classification of the cancer. Conclusion: Based on the pathological classification, adjuvant chemotherapy with gemcitabine may be beneficial for patients with PB subtype periampullary carcinoma. 5-Fu-based adjuvant chemotherapy may be beneficial for patients with intestinal subtype periampullary carcinoma.

Defects of endoscopic biopsy in the diagnosis of periampullary carcinoma and recommendations for diagnosis and treatment: a retrospective study before and after surgery.

Background: Pancreaticoduodenectomy (PD) is the main curative treatment for periampullary carcinoma (PAC), but the high risk of complications in PD means an accurate preoperative diagnosis is essential, because benign lesions can be treated without PD. Despite as the preferred diagnosis method, preoperative endoscopic biopsy is characterized with high false-negative rate, which disturbs the making of surgical plans. We explored the degree of matching between preoperative and postoperative pathological diagnoses, analyzed the shortcomings of endoscopic biopsy, and provide recommendations for the diagnosis and treatment of periampullary tumors. Methods: We retrospectively analyzed 198 patients with periampullary tumors who underwent endoscopic biopsy and PD between June 2013 and February 2021. Data on disease characteristics, such as sex, age, total bilirubin (TBIL), direct bilirubin (DBIL), tumor markers, imaging features, preoperative and postoperative pathology were collected and reviewed. The measurement data with normal distribution were expressed by mean ± standard deviation, and the categorical data were expressed by the number of cases. Results: In our cohort, 196 patients (98.99%) were diagnosed with PAC based on postoperative pathology. Preoperative pathological biopsy was performed in 198 patients with dysplasia (n=76), inflammation (n=7), and PAC (n=115), among whom 111 were diagnosed with PAC at the first biopsy and 4/7 at the second biopsy. The false-negative rate for one preoperative biopsy was 85/196 (43.37%); 74/76 (97.37%) patients in the dysplasia subgroup and 7/7 (100%) patients in the inflammation subgroup showed malignant results after surgery. Conclusions: Preoperative endoscopic biopsy has a high false-negative rate. Multiple sites, greater depth, and more biopsies may increase accuracy. Patients preoperatively diagnosed with dysplasia have a high risk for cancer and are recommended to undergo PD directly.

Pore Size of 3D-Printed Polycaprolactone/Polyethylene Glycol/Hydroxyapatite Scaffolds Affects Bone Regeneration by Modulating Macrophage Polarization and the Foreign Body Response.

3D-printed porous bioactive ceramic scaffolds have been widely used in bone defect repair. However, material implantation is often accompanied by a foreign body response (FBR), which may affect host tissue regeneration. The physical properties of biomaterials, including shape, pore size, and porosity, control the relevant immune responses during tissue regeneration. To the best of our knowledge, the effect of the pore size of 3D-printed scaffolds on the immune response and bone-biomaterial integration has not been studied in vivo. Polycaprolactone/polyethylene glycol/hydroxyapatite (PCL/PEG/HA) bioactive scaffolds with different pore sizes, including 209.9 ± 77.1 µm (P200), 385.5 ± 28.6 µm (P400), and 582.1 ± 27.2 µm (P600), were prepared with a pneumatic extrusion 3D printer. Compared with other pore sizes, P600 significantly reduced the FBR and induced more M2 macrophage infiltration, vascular ingrowth, and new bone formation. Immunohistochemical staining revealed that the MyD88 protein might be involved in macrophage polarization-related signal transduction in response to the pore size. Based on these results, bone regeneration requires the active participation of the immune response, and the P600 PCL/PEG/HA scaffold is a preferable candidate for the repair of bone defects.

Expression of programmed death ligand-1 predicts poor outcome in nasopharyngeal carcinoma.

Programmed death ligand-1 (PD-L1) is a potentially important tumor immunotherapy target. However, whether PD-L1 expression is associated with survival in nasopharyngeal carcinoma (NPC) remains controversial. The aim of the present study was to investigate the association between PD-L1 expression and prognosis in NPC. The expression of PD-L1 was assessed in tumor specimens from 120 patients with NPC using immunohistochemistry. Staining was evaluated using the H-score method. The associations between PD-L1 expression and clinical characteristics and prognosis were analyzed. Overall, 78% of the patients had stage I-III and 22% had stage IV disease. The estimated 5-year overall survival (OS) and disease-free survival (DFS) rates for the entire cohort were 87.5 and 70.1%, respectively. PD-L1 expression was detected in 85 (71%) patients and was localized to the tumor cells. High tumor expression of PD-L1 (median H-score ≥5) was associated with significantly poorer OS (P=0.023) and DFS (P=0.002). Univariate analysis indicated that low PD-L1 expression was associated with better DFS compared with high PD-L1 expression (HR=0.163, 95% CI: 0.044-0.600, P=0.006 for DFS). Multivariate analysis revealed that T stage (HR=8.190, 95% CI: 1.355-18.152; P=0.023) and PD-L1 expression level (HR=0.124, 95% CI: 0.031-0.509; P=0.001) served as independent prognostic factors for DFS. In conclusion, tumor PD-L1 expression was found to be a significant prognostic factor in NPC, and high PD-L1 expression may be of prognostic value for recurrence and metastasis following conventional treatments.

BML-111 Protected LPS/D-GalN-Induced Acute Liver Injury in Rats.

Lipoxins (LXs) display unique pro-resolving and anti-inflammatory functions in a variety of inflammatory conditions. The present study was undertaken to investigate the effects of BML-111 (5(S),6(R),7-trihydroxyheptanoic acid methyl ester), the agonist of lipoxin A4 receptor, in a model of Lipopolysaccharides (LPS) and d-Galactosamine (d-GalN) induced acute liver injury, and to explore the mechanisms. Histopathological analyses were carried out to quantify liver injury degree. The activities of myeloperoxidase (MPO) were examined to evaluate the levels of neutrophil infiltration. The activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were detected to evaluate the functions of the liver. The amounts of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and interleukin-1ß (IL-1ß) were measured using enzyme-linked immunosorbent assay (ELISA), and the expression levels of transforming growth factor-ß1(TGF-ß1) and cyclooxygenase-2 (COX-2) were examined using Western blotting. The antioxidant capacity, the activities of inducible nitric oxide synthase (iNOS), the contents of malondialdehyde (MDA) and nitric oxide (NO) were analyzed with the kits via biochemical analysis. We established the model of acute liver injury with lipopolysaccharide and d-Galactosamine (LPS/d-GalN): (1) histopathological results and MPO activities, with the activities of AST and ALT in serum, consistently demonstrated LPS and d-GalN challenge could cause severe liver damage, but BML-111 could prevent pathological changes, inhibit neutrophil infiltration, and improve the hepatic function; (2) LPS/d-GalN increased TNF-α, IL-1ß, COX-2, and IL-10, while decreasing TGF-ß1. However, BML-111 could repress LPS/d-GalN -induced TNF-α, IL-1ß and COX-2, meanwhile increasing the expression levels of TGF-ß1 and IL-10; (3) LPS/d-GalN inhibited the activities of superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (T-AOC), and hydroxyl radical-scavenging ability, simultaneously increasing the levels of MDA and NO, so also the activity of iNOS. Otherwise, BML-111 could reverse all the phenomena. In a word, BML-111 played a protective role in acute liver injury induced by LPS and d-GalN in rats, through improving antioxidant capacity and regulating the balance of inflammatory cytokines.