Challenging pitfalls in frozen section pathology: a case of mandible ghost cell odontogenic carcinoma and the literature review.

BACKGROUND: Ghost cell odontogenic carcinoma (GCOC) is a rare malignancy characterized by the presence of ghost cells, preferably in the maxilla. Only slightly more than 50 case reports of GCOC have been documented to date. Due to the rarity of this tumor and its nonspecific clinical criteria, there is a heightened risk of misdiagnosis in clinical examination, imaging findings, and pathology interpretation. CASE PRESENTATION: A 50-year-old male patient presented to the hospital due to experiencing pain in his lower front teeth while eating for the past 2 months. Upon examination, a red, hard, painless mass was found in his left lower jaw, measuring approximately 4.0 cm × 3.5 cm. Based on the malignant histological morphology of the tumor and the abundant red-stained keratinized material, the preoperative frozen section pathology misdiagnosed it as squamous cell carcinoma (SCC). The surgical resection specimen pathology via paraffin section revealed that the tumor was characterized by round-like epithelial islands within the fibrous interstitium, accompanied by a large number of ghost cells and some dysplastic dentin with infiltrative growth. The malignant components displayed marked heterogeneity and mitotic activity. Additionally, a calcified cystic tumor component of odontogenic origin was observed. Hemorrhage, necrosis, and calcifications were present, with a foreign body reaction around ghost cells. Immunoreactivity for ß-catenin showed strong nuclear positivity in tumor cells, while immunostaining was completely negative for p53. The Ki67 proliferation index was approximately 30-40%. The tumor cells exhibited diffuse CK5/6, p63, and p40 immunoreactivity, with varying immunopositivity for EMA. Furthermore, no BRAFV600E mutation was identified by ARMS-PCR. The final pathology confirmed that the tumor was a mandible GCOC. CONCLUSION: We have reported and summarized for the first time the specific manifestations of GCOC in frozen section pathology and possible pitfalls in misdiagnosis. We also reviewed and summarized the etiology, pathological features, molecular characteristics, differential diagnosis, imaging features, and current main treatment options for GCOC. Due to its rarity, the diagnosis and treatment of this disease still face certain challenges. A correct understanding of the pathological morphology of GCOC, distinguishing the ghost cells and the secondary stromal reaction around them, is crucial for reducing misdiagnosis rates.

Mitral valve leaflet blood cyst treated with minimally invasive approach: a case report and review of literature.

INTRODUCTION: Cardiac blood cyst is a very rare benign tumor of the heart in adults. Though it is very common in the first half year of life, it regresses with time and its occurrence is very rare in children older than six months and in adults. Until now less than 100 valvular blood cyst cases have been reported in adults. CASE PRESENTATION: We present a case of a 66-year-old male who presented to us with exertional chest tightness, shortness of breath, and right leg weakness for two weeks. He was diagnosed with a cardiac mass two months ago in another hospital. The physical examination was unremarkable. Abdominal ultrasound showed a cyst in the liver and left kidney. Echocardiography showed a mass-occupying lesion of a cystic nature in the mitral valve with moderate mitral regurgitation. Based on echocardiography findings and computed tomography report, the preliminary diagnosis of mitral valve cystic tumor was made. The patient underwent minimally invasive resection of the cyst. The posterior mitral cusp was repaired and a mitral annuloplasty ring was placed. The postoperative recovery was uneventful. The histopathology report confirmed the diagnosis of a cardiac blood cyst. The patient was followed up for six months without any complications. This case is presented to enrich the medical literature on the cardiac blood cyst. CONCLUSION: Although a cardiac blood cyst is a rare entity in adults, it still should be considered in the differential diagnosis of cardiac tumors. Because the natural history and hemodynamic effects are very diverse, large symptomatic cardiac blood cysts, especially in the left heart should be resected to avoid complications.

CircDENND2D Inhibits PD-L1-Mediated Non-Small Cell Lung Cancer Metastasis and Immune Escape by Regulating miR-130b-3p/STK11 Axis.

Local recurrence and distant metastasis of non-small cell lung cancer (NSCLC) caused by immune escape is one of the root causes of treatment difficulties. We aim to investigate the mechanism of immune escape in NSCLC. NSCLC tissues were collected. Cell proliferation was detected by CCK-8 assay. Cell migration and invasion ability was measured by Transwell assay. The expressions of E-cadherin, N-cadherin and PD-L1 were detected by Western blot. NSCLC cells were co-cultured with CD8+ T cells to simulate tumor microenvironment in vitro. The proportion of CD8+ T cells and apoptosis were detected by flow cytometry. Dual-luciferase reporter gene assay confirmed the targeting relationship of circDENND2D and STK11. The expressions of circDENND2D and STK1 were down-regulated, while miR-130b-3p expression was up-regulated in NSCLC tissues. Overexpression of circDENND2D or STK11 inhibited NSCLC cells proliferation, migration and invasion, and attenuated the immune escape of NSCLC cells. CircDENND2D targeted miR-130b-3p to competitively promote STK11 expression. STK11 knockdown or miR-130b-3p overexpression attenuated the function of circDENND2D overexpression on NSCLC cells. CircDENND2D inhibited metastasis and immune escape of NSCLC by regulating miR-130b-3p/STK11 axis.

Rheumatism as a cause of cardiac hemangioma: a rare case report and review of literature with special focus on etiology.

BACKGROUND: Cardiac hemangioma is a very rare benign tumor of the heart which accounts for 1-2% of all primary cardiac tumors. Multiple cardiac hemangiomas are even rarer with only three cases published in the literature. Pathologically it can be divided into cavernous hemangioma, capillary hemangioma, arteriovenous hemangioma, mixed-type hemangioma, and so on. At present, the etiology of cardiac hemangioma is not completely clear. In this study, we present multiple cardiac hemangiomas located in the right atrium and discuss the new unreported possible cause (rheumatism) of cardiac hemangioma. This is the fourth case of multiple cardiac hemangiomas in the medical literature and the first time to present rheumatism as the cause of cardiac hemangioma. CASE PRESENTATION: A 53-year-old man presented to the clinic with intermittent chest tightness and shortness of breath for 2 years. On echocardiography, multiple soft tissue masses in the right atrium were found. The patient had rheumatic heart disease with severe mitral stenosis and moderate tricuspid regurgitation. Two masses with a diameter of about 20 mm and 15 mm were seen in the right atrium. One mass was located on the inferior margin of the fossa ovalis and the other was adjacent to the inferior vena cava. Both masses were successfully removed surgically. The mitral valve replacement and tricuspid valve plasty were performed at the same time. The postoperative histopathology results confirmed the diagnosis of cavernous hemangioma. CONCLUSION: The occurrence of multiple hemangiomas in the heart is possible, especially in the presence of rheumatism. Rheumatism is one of the possible etiologies of cardiac hemangioma. Cardiologists and cardiac surgeons should be aware of its occurrence and should consider cardiac hemangioma as a differential diagnosis especially in rheumatic heart disease patients when they present with soft tissue cardiac masses for accurate management.

Adenosine 2A receptor contributes to the facilitation of post-infectious irritable bowel syndrome by γδ T cells via the PKA/CREB/NF-κB signaling pathway.

BACKGROUND: Immunological dysfunction-induced low-grade inflammation is regarded as one of the predominant pathogenetic mechanisms in post-infectious irritable bowel syndrome (PI-IBS). γδ T cells play a crucial role in innate and adaptive immunity. Adenosine receptors expressed on the surface of γδ T cells participate in intestinal inflammation and immunity regulation. AIM: To investigate the role of γδ T cell regulated by adenosine 2A receptor (A2AR) in PI-IBS. METHODS: The PI-IBS mouse model has been established with Trichinella spiralis (T. spiralis) infection. The intestinal A2AR and A2AR in γδ T cells were detected by immunohistochemistry, and the inflammatory cytokines were measured by western blot. The role of A2AR on the isolated γδ T cells, including proliferation, apoptosis, and cytokine production, were evaluated in vitro. Their A2AR expression was measured by western blot and reverse transcription polymerase chain reaction (RT-PCR). The animals were administered with A2AR agonist, or A2AR antagonist. Besides, γδ T cells were also injected back into the animals, and the parameters described above were examined, as well as the clinical features. Furthermore, the A2AR-associated signaling pathway molecules were assessed by western blot and RT-PCR. RESULTS: PI-IBS mice exhibited elevated ATP content and A2AR expression (P < 0.05), and suppression of A2AR enhanced PI-IBS clinical characteristics, indicated by the abdominal withdrawal reflex and colon transportation test. PI-IBS was associated with an increase in intestinal T cells, and cytokine levels of interleukin-1 (IL-1), IL-6, IL-17A, and interferon-α (IFN-α). Also, γδ T cells expressed A2AR in vitro and generated IL-1, IL-6, IL-17A, and IFN-α, which can be controlled by A2AR agonist and antagonist. Mechanistic studies demonstrated that the A2AR antagonist improved the function of γδ T cells through the PKA/CREB/NF-κB signaling pathway. CONCLUSION: Our results revealed that A2AR contributes to the facilitation of PI-IBS by regulating the function of γδ T cells via the PKA/CREB/NF-κB signaling pathway.

Glycyrrhetinic acid proliposomes mediated by mannosylated ligand: Preparation, physicochemical characterization, environmental stability and bioactivity evaluation.

Glycyrrhetinic acid is a bioactive compound extracted from licorice that exhibits inhibition effect on various cancers. However, its hydrophobicity results in low bioavailability that limits application. We aim to overcome this barrier, the present research was performed to prepare glycyrrhetinic acid proliposomes mediated mannosylated ligand (mannose-diester lauric diacid-cholesterol, MDC) and to evaluate its physicochemical characterizations, environmental stability and bioactivity. In preliminary optimization studies of glycyrrhetinic acid proliposomes mediated MDC (MDC-GA-PL), four optimum operating parameters, cryoprotectant of glucose and mannitol, the mixed cryoprotectant ratio (glucose/mannitol) of 1:1, a cryoprotectant/egg phosphatidylcholine mass ratio of 10/1, and -60 â„ƒ pre-freezing temperature, were obtained after investigation. Under the optimum lyophilization conditions, MDC-GA-PL was freeze-dried and reconstituted proliposomes were characterized. These proliposomes showed that MDC-GA-PL were well-dispersible spherical particles with an average particle size of 120.80 nm, a polydispersity index about 0.095, a zeta potential of -33.15 mV, encapsulation efficiency of 85.9% and drug loading of 6.38%. In vitro drug release study showed that glycyrrhetinic acid release of MDC-GA-PL conforms to the Higuchi release model. In addition, these proliposomes were stable during six months at 4 â„ƒ. Moreover, acute toxicity assay revealed no substantial safety concern for MDC-GA-PL. Finally, in vitro bioactivity of proliposomes was evaluated. Cytotoxicity effect and apoptosis efficiency of MDC-GA-PL by HepG2 cells was significantly higher than that of glycyrrhetinic acid proliposomes without MDC, demonstrating that MDC has a desirable effect on liver target. Overall, we have reason to believe that MDC-GA-PL would be a promising target delivery to improve therapeutic against hepatic diseases.

Upregulated adenosine 2A receptor accelerates post-infectious irritable bowel syndrome by promoting CD4+ T cells' T helper 17 polarization.

BACKGROUND: Post-infectious irritable bowel syndrome (PI-IBS) is generally regarded as a functional disease. Several recent studies have reported the involvement of low-grade inflammation and immunological dysfunction in PI-IBS. T helper 17 (Th17) polarization occurs in IBS. Adenosine and its receptors participate in intestinal inflammation and immune regulation. AIM: To investigate the role of Th17 polarization of CD4+ T cells regulated by adenosine 2A receptor (A2AR) in PI-IBS. METHODS: A PI-IBS model was established by infecting mice with Trichinella spiralis. The intestinal A2AR and CD4+ T lymphocytes were detected by immunohistochemistry, and the inflammatory cytokines were detected by enzyme-linked immunoassay. CD4+ T lymphocytes present in the animal's spleen were separated and cultured with or without A2AR agonist and antagonist. Western blotting and real-time quantitative polymerase chain reaction were performed to determine the effect of A2AR on the cells and intestinal tissue. Cytokine production was determined. The protein and mRNA levels of A2AR associated signaling pathway molecules were also evaluated. Furthermore, A2AR agonist and antagonist were injected into the mouse model and the clinical features were observed. RESULTS: The PI-IBS mouse model showed increased expression of ATP and A2AR (P < 0.05), and inhibition of A2AR improved the clinical features in PI-IBS, including the abdominal withdrawal reflex and colon transportation test (P < 0.05). The number of intestinal CD4+ T cells and interleukin-17 (IL-17) protein levels increased during PI-IBS, which was reversed by administration of the A2AR antagonist (P < 0.05). CD4+ T cells expressed A2AR and produced IL-17 in vitro, which was regulated by the A2AR agonist and antagonist. The A2AR antagonist increased the production of IL-17 by CD4+ T cells via the Janus kinase-signal transducer and activator of transcription-receptor-related orphan receptor γ signaling pathway. CONCLUSION: The results of the present study suggested that the upregulation of A2AR increases PI-IBS by promoting the Th17 polarization of CD4+ T cells.

Cardiac Lymphoma Diagnosed by Multi-Modality Imaging: A Case Report.

A 79-year-old female patient who presented with a cardiac mass detected by conventional echocardiography was ultimately diagnosed with a malignant tumor by myocardial contrast echocardiography. A positron emission tomography/computed tomography examination showed tumors in the right atrium consistent with the findings of the contrast-enhanced ultrasound. Finally, the patient was confirmed by pathology to have cardiac lymphoma. Because no lesions were found elsewhere in the body, primary cardiac lymphoma was diagnosed by combining multi-modal imaging examination and pathological examination. Although conventional echocardiography may identify a cardiac mass, it is difficult to identify whether they are malignant or not. Myocardial contrast echocardiography helps to identify the location, shape, and size of the mass, its relationship with the surrounding tissue, and evaluate its blood supply. Thus, this imaging modality is of great value for identifying the likely etiology of a cardiac mass. Multi-modal imaging is complementary to echocardiography for determining the location of cardiac masses, invasion of surround structures, extra cardiac spread, and determination of whether a mass is likely benign or malignant. Multi-modality imaging provides an important basis for clinical treatment and decision-making.

Identification of differentially expressed proteins associated with recurrence in ovarian endometriotic cysts.

The objective of this study was to identify proteins that are differentially expressed in the cystic wall tissues of ovarian endometriotic cysts, simple ovarian cysts, and in normal ovarian tissues. Specimens of ovarian endometriotic cyst wall tissue, simple ovarian cyst wall tissue, and normal ovarian tissue (six specimens per group) were collected from patients who received gynecologic surgery, respectively. Differentially expressed proteins related to the ovarian endometriotic cysts were screened by use of isobaric tags for relative and absolute quantitation (iTRAQ) combined with functional annotation and bioinformatics analyses. All differentially expressed proteins related to cysts were validated using immunohistochemistry methods in recurrent and non-recurrent ovarian endometriotic cyst. A total of 359 proteins were identified as up-regulated in ovarian endometriotic cyst groups when compared with both the normal ovary and simple ovarian cyst groups. The levels of 27 proteins were >two-fold higher in the ovarian endometriotic cyst group than that in the other two groups. Of note, the five most significantly upregulated proteins were Charcot-Leyden Crystal Galectin (CLC), Defensin, alpha 1 (DEFA1), S100 calcium-binding protein A9 (S100A9), S100 calcium-binding protein A8 (S100A8), and Ferritin Light Chain (FTL). Immunohistochemistry results showed that the changes of S100A9 and S100A8 were consistent with the results shown by iTRAQ. However, no similarity of CLC, DEFA1, and FTL proteins was found between iTRAQ and immunohistochemistry. The ratio of patients with abnormally high S100A9 and S100A8 expression in the recurrent ovarian endometriotic cyst group was significantly higher than that in the non-recurrent group (P < 0.05). Our data identify differentially expressed proteins S100A9 and S100A8, and suggest they may serve as novel molecular markers to predict postoperative recurrence of an ovarian endometriotic cysts.Abbreviations: iTRAQ: isobaric tags for relative and absolute quantitation; HPRD: Human Protein Reference Database; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; EM: Endometriosis; COX-2: cyclooxyenase-2; NF-kB: nuclear factor kappa-B; PR-B: progesterone receptor type B.

Heat shock protein 70 protects mouse against post-infection irritable bowel syndrome via up-regulating intestinal γδ T cell's Th17 response.

BACKGROUND: This study investigated the role of HSP70 in modulating intestinal γδ T cells' Th17 response in Trichinella spiralis-induced PI-IBS mice model. METHODS: The intestinal HSP70's expression and mRNA level were measured by Western blot and RT-PCR. The intestinal γδ T cell's morphological changes were analyzed using immunofluorescence staining and confocal laser scanning microscope. The pro-inflammatory cytokines' level was detected by ELISA. The isolated and purified γδ T cells were pre-incubated with HSP70 and their functions including proliferation, apoptosis, activation and production of IL-17 were also detected. RESULTS: Heat treatment augmented intestinal HSP70 expression and alleviated the clinical presentations in PI-IBS mice. Meanwhile, intestinal γδ T cells and local IL-17 level were increased by pre-induction of HSP70. HSP70 promoted the proliferation of PI-IBS mice's intestinal γδ T cells, inhibited the apoptosis and stimulated these cells to secret IL-17 rather than IFN-γ. CONCLUSION: Our results suggest that HSP70 plays a protective role via up-regulating intestinal γδ T cell's Th17 response in PI-IBS mice.

[Testicular cellular fibroma: a clinicopathological observation].

OBJECTIVE: To investigate the clinicopathological characteristics, differential diagnosis and prognosis of testicular cellular fibroma. METHODS: We comprehensively analyzed the clinical presentation, histomorphology and immunohistochemistry of a case of testicular cellular fibroma, reviewed the relevant literature, and discussed its pathological features and differential diagnosis. RESULTS: A 30-year-old man presented with complaint of discomfort and painless enlargement in the right testis. The tumor was found to be a testicular fibroma characterized by a solid, thickly or thinly encapsulated, circumscribed and gray-white mass. Microscopically, fusiform cells were arranged into a storiform and herringbone pattern or fascicles. The tumor exhibited a great deal of cellularity and no nuclear polymorphisms, with a mitotic rate of 0-1/10 HP. Immunohistochemistry showed that the tumor cells were positive for Vimentin, patchily positive for S-100 and SMA, but negative for Desmin, alpha-inhibin, CD34 and CD99. The positive rate of Ki-67 was less than 1%. CONCLUSION: Testicular cellular fibroma is a rare testicular sex cord stromal tumor, pathologically resembling its ovarian counterpart. It can be distinguished from other testicular spindle cell tumors by morphology and immunohistochemical staining. For the treatment of testicular cellular fibroma, surgical resection often has a good prognosis.

Low incidence of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly in Tianjin, northern China.

The purpose of this study was to examine the incidence of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma of the elderly in a representative northern Chinese population. Overall, 212 cases of primary diffuse large B-cell lymphoma were analyzed for EBV-positive status by detection of EBV-encoded RNA using in situ hybridization. Immunophenotypic identity was verified by a streptavidin-biotin peroxidase detection system using the markers CD20, CD3, CD10, BCL6 and MUM1. The prevalence of EBV-positive diffuse large B-cell lymphoma in elderly northern Chinese patients was 3.8% (eight of 212). All eight cases were negative for CD10 and BCL6 immunostaining. The incidence is less frequent than that of southern China and other East-Asian countries. Patients tend to be older, present with a non-germinal center B-cell-like immunophenotype and have a poor outcome.

Synthesis and biological evaluation of amide derivatives of diflunisal as potential anti-tumor agents.

To discover the new medicinal activity, the structure of diflunisal has been modified. Forty amide derivatives of diflunisal were synthesized starting from diflunisal in three steps. Their inhibition growth rate of human lung cancer cell (A549) and human endometrial adenocarcinoma cell (Ishikawa) in vitro was evaluated. The preliminary assay results showed that compounds 6j, 7o and 8c exhibited good anti-tumor activities and excellent selectivity for the Ishikawa cell, may be potential anti-tumor agents.

[Inhibitory effect of viral macrophage inflammatory protein-II on metastasis of breast cancer cell line MCF-7 through antagonising CXCR4].

BACKGROUND & OBJECTIVE: CXCR4-stromal cell-derived factor-1 (CXCR4-SDF-1alpha) system has been proved to be involved in targeting metastasis of breast cancer. Some antagonists of CXCR4 have inhibitory effects on metastasis of breast cancer. This study was to investigate effect of viral macrophage inflammatory protein-II (vMIP-II), an antagonist of CXCR4, on metastasis of breast cancer cell line MCF-7. METHODS: Proliferation of MCF-7 cells stimulated by vMIP-II of different concentrations (10, 50, 100, 500, and 1 000 ng /ml) was detected by MTT assay, clone formation rate was assessed by agar clone assay. Adhesion and chemotaxis assays were also used to evaluate the effect of vMIP-II on MCF-7 cells in different steps of metastasis. RESULTS: MCF-7 cells treated with vMIP-II of a series of concentrations for 72 h showed no proliferation change (P >0.05). vMIP-II (50-1 000 ng /ml) suppressed colony formation of MCF-7 cells in a concentration-dependent manner. After MCF-7 cells treated with 300 ng/ml of vMIP-II for different time (0, 0.5, 2, and 6 h), inhibition peak of cell adherence to fibronectin (FN) and Matrigel was observed. The number of migration was low in MCF-7 cells in the presence of vMIP-II of 500 ng/ml (24+/-10) was lower than that of control MCF-7 cells (60+/-9) (P< 0.05). CONCLUSIONS: The clone formation rate of MCF-7 cells may negatively correlates with the concentration of vMIP-II. vMIP-II may inhibit MCF-7 cells adhesion to FN and Matrigel, and suppress chemotactic activity of MCF-7 cells toward extracts of human lung protein.