Squamous cell carcinoma initially occurring on the tongue dorsum: a case series report with molecular analysis.

BACKGROUND: Squamous cell carcinoma (SCC) of the dorsum of the tongue is extremely rare, and it clinically resembles various benign lesions. Somatic mutations in TP53 and some driver genes were implicated in the development of SCC; however, the somatic genetic characteristics of dorsal tongue SCC remain unknown. With a detailed analysis of gene mutations in dorsal tongue SCC, we aimed to better understand its biology. METHODS: Four cases of SCC initially occurring on the tongue dorsum were evaluated for clinical and histological findings and immunohistochemical expression of p53 and p16. Gene mutations were analyzed using next-generation sequencing with a custom panel of driver genes. RESULTS: We retrospectively investigated 557 cases of tongue SCC, and only four cases of SCC initially occurred on the tongue dorsum. The four patients (cases 1-4) were one woman and three men with a mean age of 53.75 years (range: 15-74 years). Histological analysis revealed well-differentiated SCC. Through molecular analysis, we identified pathogenic somatic mutations, namely, TP53 p.C176F (c.527G > T) in case 3 and TP53 p.R282W (c.844 C > T) in case 4. No pathogenic variants were identified in the PI3K/AKT or RAS/RAF pathways. The p53 immunohistochemical examination revealed a wild-type expression pattern in cases 1-3 and strong expression in case 4. The results of p16 immunostaining were negative in all cases. CONCLUSIONS: We described four previously unreported genetic characteristics of dorsal tongue SCC. Somatic TP53 mutations may contribute to the development of a subset of dorsal tongue SCC; however, more cases with genetic analysis need to be accumulated.

Recurrent cementoblastoma with multifocal growth and cellular atypia: a case report.

BACKGROUND: Cementoblastoma is a rare odontogenic tumor characterized by the formation of osteocementum-like tissue on a tooth root directly by neoplastic cementoblasts. Although it is categorized as benign, it has a high potential for growth with a certain degree of recurrence risk. However, there are only a few studies describing the features of recurrent cementoblastoma. The diagnosis of recurrent cementoblastoma is challenging not only due to its cytological atypia but also because of its large size and multicentric growth pattern. These characteristics suggest a potential for malignancy. CASE PRESENTATION: A 29-year-old woman was transferred to our university dental hospital complaining of swelling of the right mandible. She had a history of enucleation of cementoblastoma associated with the third molar of the right mandible. Five years after the initial treatment, imaging demonstrated well-circumscribed multicentric radiopaque lesions in the same area. Histologically, the lesion consisted of osteocementum-like tissue rimmed with polygonal or plump tumor cells. Several cells were large epithelioid cells with bizarre nucleoli, which may be reminiscent of malignant tumors. Otherwise, there were no apparent malignant findings, including proliferative activity or atypical mitotic figure. Besides, tumor cells were positive for c-FOS, a marker of osteoblastoma and cementoblastoma. Eventually, the patient was diagnosed with recurrent cementoblastoma. CONCLUSIONS: Pathological analyses of this case suggested that the recurrent event in the cementoblastoma altered its growth pattern and tumor cell shape. Moreover, in the case of enucleation surgery, long-term follow-up is important because there is some recurrent risk of cementoblastoma, although it is not high.

Comprehensive phenotypic and genomic characterization of venous malformations.

Venous malformations (VMs) are the most common vascular malformations. TEK and PIK3CA are the causal genes of VMs, and may be involved in the PI3K/AKT pathway. However, the downstream mechanisms underlying the TEK or PIK3CA mutations in VMs are not completely understood. This study aimed to identify a possible association between genetic mutations and clinicopathological features. A retrospective clinical, pathological, and genetic study of 114 patients with VMs was performed. TEK, PIK3CA, and combined TEK/PIK3CA mutations were identified in 49 (43%), 13 (11.4%), and 2 (1.75%) patients, respectively. TEK-mutant VMs more commonly occurred in younger patients than TEK and PIK3CA mutation-negative VMs (other-mutant VMs), and showed more frequent skin involvement and no lymphocytic aggregates. No significant differences were observed in sex, location of occurrence, malformed vessel size, vessel density, or thickness of the vascular smooth muscle among the VM genotypes. Immunohistochemical analysis revealed that the expression levels of phosphorylated AKT (p-AKT) were higher in the TEK-mutant VMs than those in PIK3CA-mutant and other-mutant VMs. The expression levels of p-mTOR and its downstream effectors were higher in all the VM genotypes than those in normal vessels. Spatial transcriptomics revealed that the genes involved in "blood vessel development", "positive regulation of cell migration", and "extracellular matrix organization" were up-regulated in a TEK-mutant VM. Significant genotype-phenotype correlations in clinical and pathological features were observed among the VM genotypes, indicating gene-specific effects. Detailed analysis of gene-specific effects in VMs may offer insights into the underlying molecular pathways and implications for targeted therapies.

Rab32 and Rab38 maintain bone homeostasis by regulating intracellular traffic in osteoclasts.

Osteoclasts play a crucial role in bone homeostasis by forming resorption pits on bone surfaces, resulting in bone resorption. The osteoclast expression of Rab38 protein is highly induced during differentiation from macrophages. Here we generated mice with double knockout (DKO) of Rab38 and its paralogue, Rab32, to investigate the roles of these proteins in osteoclasts. Bone marrow-derived macrophages from Rab32/38 DKO mice differentiated normally into osteoclasts in vitro. However, DKO osteoclasts showed reduced bone resorption activity. These osteoclasts also demonstrated defective secretion of tartrate-resistant acid phosphatase and cathepsin K into culture medium. Furthermore, the plasma membrane localization of a3, an osteoclast-specific a subunit of V-ATPase, was abrogated in DKO mice, substantiating the reduced resorption activity. In vivo, Rab32- and Rab38-positive cells were attached to the bone surface. Eight-week-old DKO mice showed significantly thickened trabecular bones in micro-CT and histomorphometry analysis, as well as reduced serum levels of cross-linked C-telopeptide of type I collagen, indicating diminished bone resorption in vivo. In DKO male mice over 10 weeks of age, hyperostosis appeared at the talofibular syndesmosis, the distal junction of the tibia and fibula. Furthermore, middle-aged mice (10 to 12 months of age) exhibited kyphosis, which is not usually observed in wild-type male mice until around 24 months of age. These results indicate that Rab32 and Rab38 contribute to osteoclast function by supporting intracellular traffic, thereby maintaining normal bone homeostasis.Key words: Rab32, Rab38, osteoclast, lysosome-related organelle, secretory lysosome.

Clear Cell Squamous Cell Carcinoma of the Maxillary Gingiva Associated with PIK3CA and HRAS Mutations: Report of a Case and Literature Review.

BACKGROUND: Squamous cell carcinoma (SCC) is the most common oral malignancy, and somatic mutations in some driver genes have been implicated in SCC development. Clear cell SCC (CCSCC) is a rare histological variant of SCC, and various clear cell neoplasms must be considered in the differential diagnosis of CCSCC in the oral cavity. Based on a limited number of CCSCC cases reported in the oral cavity, CCSCC is considered an aggressive variant of SCC with a poor prognosis; however, its genetic characteristics remain unknown. METHODS: A maxillary gingival tumor in an 89-year-old female was described and investigated using immunohistochemical staining, special staining, fluorescence in situ hybridization, and next-generation sequencing (NGS) with a custom panel of driver genes, including those associated with SCC and clear cell neoplasm development. RESULTS: Histopathological examination revealed a proliferation of atypical epithelial cells with abundant clear cytoplasm and enlarged and centrally placed round nuclei. The tumor was exophytic with deep, penetrating proliferation. The atypical clear cells were continuous with the conventional SCC cells. Immunohistochemical analysis showed that the clear cells were positive for CK AE1/AE3 and CK5/6 and nuclear-positive for p63. In contrast, the clear cells were negative for αSMA, S100, HMB45, Melan-A, CD10, and p16. p53 immunoreactivity exhibited a wild-type expression pattern. Additionally, the clear cells were positive for periodic acid-Schiff (PAS) and negative for diastase-PAS, mucicarmine, and Alcian blue. Based on these results, the diagnosis of CCSCC was confirmed. Molecular analysis of the clear cells identified PIK3CA p.E542K (c.1624G>A) and HRAS p.G12A (c.35 G>C) somatic mutations classified as oncogenic. No pathogenic variants were identified in TP53, EWSR1, AKT1, PTEN, BRAF, KRAS, NRAS, RASA1, or MAML2. CONCLUSIONS: We report a case of CCSCC of the oral cavity with PIK3CA and HRAS mutations. The identification of PIK3CA and/or HRAS mutations is rare in SCC; however, both mutations are important potential targets for antitumor therapy. A detailed analysis of gene mutations in CCSCC may lead to a better understanding of its biological behavior and an improved prognosis, as well as a differential diagnosis from other clear cell neoplasms.

Dentinogenic ghost cell tumor treated with a combination of marsupialization and radical resection: a case report and review of the literature.

BACKGROUND: Dentinogenic ghost cell tumor is a rare benign tumor that accounts for less than 3% of all cases and consists of the stellate reticulum, which is made up of enamel epithelioid and basaloid cells. Although DGCT is a benign tumor, the local infiltration of the odontogenic epithelium or recurrences have been reported, and its detailed pathology and treatments remain unclear. CASE PRESENTATION: This report describes the case of a 60-year-old Japanese male diagnosed with a maxillary dentinogenic ghost cell tumor. Images showed well-circumscribed, multilocular cystic lesions with a calcified substance in the interior. Marsupialization was performed along with biopsy to prevent the expansion of the lesion, and a partial maxillectomy was performed 2 years after the initial examination. Histopathological findings showed ameloblastomatous proliferation containing clusters of ghost cells and dentinoid materials, resulting in the diagnosis of dentinogenic ghost cell tumor. This article also reviews recently reported cases of dentinogenic ghost cell tumor. CONCLUSION: It is important to perform marsupialization, proper resection, and postoperative follow-up because of possible recurrence.

Multiple orthokeratinized odontogenic cysts: clinical, pathological, and genetic characteristics.

BACKGROUND: Orthokeratinized odontogenic cyst (OOC) is a rare developmental odontogenic cyst of the jaw. It was originally believed to be a variant of odontogenic keratocyst (OKC) but is now considered to be a distinct entity. OOC usually presents as a single lesion and recurs infrequently. On the other hand, OKC often presents with multiple lesions and displays locally aggressive behavior and a high recurrence rate associated with the protein patched homolog 1 (PTCH1) gene mutation. Multiple OOC cases are extremely rare and seem to be aggressive, but their pathogenesis is not fully understood. This study aimed to determine the clinical, pathological, and genetic characteristics of multiple OCC. METHODS: Three cases of multiple OOC were evaluated for clinical and histological findings, and immunohistochemical expression of Ki-67 and Bcl-2. Furthermore, PTCH1 mutations were analyzed by next-generation sequencing using a custom panel to cover the entire exon of PTCH1. RESULTS: The three cases of multiple OOC included two men and one woman with a mean age of 25.3 years old (range, 18-38 years old). Each case had two or three OOCs (total of seven OOCs), all of which were simultaneously detected. Of the seven OOCs that manifested as multiple jaw cysts, seven (100%) occurred in the posterior regions, four (57.1%) occurred in the mandible, and four (57.1%) were associated with an impacted tooth. Histological examination revealed cysts lined by orthokeratinized stratified squamous epithelium. Immunohistochemistry showed a low Ki-67 labeling index and no Bcl-2 expression in the seven OOCs. No pathogenic PTCH1 mutations were detected in any of the seven OOCs. None of the patients had any other symptoms or signs of recurrence at the last follow-up (6-60 months). CONCLUSION: Multiple OOCs appeared to occur more often in younger patients than solitary OOC. Both multiple and solitary OOCs may be related diseases within the entity of odontogenic cysts. Multiple OOCs are clinicopathologically and genetically distinct from OKC.

The lactate sensor GPR81 regulates glycolysis and tumor growth of breast cancer.

Metabolic reprogramming is a malignant phenotype of cancer. Cancer cells utilize glycolysis to fuel rapid proliferation even in the presence of oxygen, and elevated glycolysis is coupled to lactate fermentation in the cancer microenvironment. Although lactate has been recognized as a metabolic waste product, it has become evident that lactate functions as not only an energy source but a signaling molecule through the lactate receptor G-protein-coupled receptor 81 (GPR81) under physiological conditions. However, the pathological role of GPR81 in cancer remains unclear. Here, we show that GPR81 regulates the malignant phenotype of breast cancer cell by reprogramming energy metabolism. We found that GPR81 is highly expressed in breast cancer cell lines but not in normal breast epithelial cells. Knockdown of GPR81 decreased breast cancer cell proliferation, and tumor growth. Mechanistically, glycolysis and lactate-dependent ATP production were impaired in GPR81-silenced breast cancer cells. RNA sequencing accompanied by Gene Ontology enrichment analysis further demonstrated a significant decrease in genes associated with cell motility and silencing of GPR81 suppressed cell migration and invasion. Notably, histological examination showed strong expression of GPR81 in clinical samples of human breast cancer. Collectively, our findings suggest that GPR81 is critical for malignancy of breast cancer and may be a potential novel therapeutic target for breast carcinoma.

Tumor-infiltrating ICOS+ Effector Regulatory T-Cells in Oral Squamous Cell Carcinoma as a Promising Biomarker for Prognosis and 'Hot' Tumor.

BACKGROUND: Tumor immunity in the tumor microenvironment is activated in patients with feasible clinical responses to immune checkpoint inhibitors. The immunological profile of tumor-infiltrating lymphocytes (TILs) obtained from patients with oral squamous cell carcinoma (OSCC) was examined in relation to their prognosis. MATERIALS AND METHODS: Surface antigens, including immune checkpoint molecules, on TILs from 31 patients with primary OSCC were analyzed by flow cytometry. The activation status of TILs was examined through a heatmap analysis and unsupervised clustering classified patients into groups with activated or inactivated TILs. A supervised machine-learning algorithm for single-cell analyses in relation to prognosis was run using the Cluster Identification, Characterization, and Regression (CITRUS) program. RESULTS: None of surface antigens were related to prognosis. The CITRUS program revealed a relationship between CD45RA-CD4+ CD25high inducible T-cell co-stimulator (ICOS)+ TILs and recurrence, and also identified a similar fraction significantly specific to the group with activated TILs. The disease-free survival rate for patients with ≥95% ICOS+ TILs was significantly lower than that for those with <95% ICOS+ TILs. Furthermore, a review of clinicopathological factors related to prognosis identified the percentage of ICOS+ TILs to be an independent prognostic factor for patients with OSCC. CONCLUSION: CD25highICOS+ regulatory T-cells in TILs have potential as a biomarker for predicting recurrence after surgical treatment and clinical responses to immune checkpoint inhibitors in patients with OSCC.

PIK3CA mutation correlates with mTOR pathway expression but not clinical and pathological features in Fibfibroipose vascular anomaly (FAVA).

BACKGROUND: Fibro-adipose vascular anomaly (FAVA) is a rare and new entity of vascular anomaly. Activating mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene were identified at a frequency of 62.5% in FAVA cases. The PIK3CA mutations excessively activate mammalian target of rapamycin (mTOR) pathway, which promotes angiogenesis and lymphangiogenesis, implying that PIK3CA mutations may act as drivers of FAVAs. This study investigated the correlations between PIK3CA mutational status, clinicopathological features and immunohistochemical expression of the mTOR pathway in a series of FAVA. METHODS: We retrospectively evaluated the clinical and pathological findings of four FAVA cases. We performed next-generation sequencing (NGS) with a custom panel of genes associated with the mTOR pathway and genes responsible for other vascular anomalies; followed by direct sequencing and immunohistochemical analysis of the mTOR pathway. RESULTS: Two PIK3CA-mutation cases and two PIK3CA-wild-type (wt) cases exhibited similar typical clinical features of FAVA. Histological analysis revealed venous malformation, lymphatic malformation, nerves containing enlarged abnormal vessels and fibrofatty tissue were observed regardless of PIK3CA mutational status. In contrast to clinical and histological findings, the immunohistochemical expression of activated AKT and mTOR that are upstream of the mTOR pathway was detected in abnormal vessels of PIK3CA-mutation cases but not in those of PIK3CA-wt cases. However, activated eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) and ribosomal protein S6 kinase 1 (S6K1), both of which are downstream effectors of the mTOR pathway, were expressed in abnormal vessels of both PIK3CA-mutation and PIK3CA-wt cases. Furthermore, targeting NGS did not find any common genetic mutations involved in the mTOR pathway among PIK3CA-wt cases. CONCLUSIONS: There was no significant association between the presence of PIK3CA mutations and the clinicopathological features of FAVA, suggesting that the PIK3CA gene is not necessarily involved in the onset of FAVA. FAVAs lacking PIK3CA mutations may be caused by other gene mutations that activate 4EBP1 and S6K1.

Clear Cell Carcinoma in the Oral Cavity with Three Novel Types of EWSR1-ATF1 Translocation: A Case Report.

Clear cell carcinoma (CCC) is a rare epithelial malignant tumor of the salivary glands. It is characterized by tumor cells with clear cytoplasm, hyalinized stroma, and most importantly the fusion genes EWSR1-ATF1, EWSR1-CREM, and EWSR1-PLAG1. Break-apart FISH has been performed for multiple CCC cases, but direct sequencing analysis has been performed in relatively few. Herein, we report an interesting case of CCC harboring three EWSR1-ATF1 translocations: EWSR1 exon 8-ATF1 exon 4, EWSR1 exon 7-ATF1 exon 4, and EWSR1 exon 7-ATF1 exon 5. This case indicates the possibility of independent EWSR1-ATF1 gene translocations, and could provide insight into CCC tumorgenesis.

Salivary duct carcinoma of the submandibular gland presenting a diagnostic challenge: A case report.

BACKGROUND: Salivary duct carcinoma (SDC) is a rare, extremely aggressive malignancy that arises in the submandibular gland. It can metastasize locally early and therefore is an important differential diagnosis of metastatic disease in cervical lymph nodes or specific lymphadenitis such as tuberculous cervical lymphadenitis. CASE SUMMARY: We report a case of SDC in the submandibular gland that presented diagnostic difficulty. The lesion was coincidentally discovered through examination of the radiolucent area of the maxilla. Imaging failed to confirm the possibility of specific inflammation, leading us to execute an open biopsy to verify the diagnosis. The surgical specimen showed that the submandibular gland was primarily replaced with a calcified body. Following histological analysis and confirmation, we performed surgical resection, radiotherapy, and various chemotherapies. CONCLUSION: Radiographic imaging characteristics of lymph node metastases of salivary gland cancer, especially of SDC, may resemble other cervical lymphadenitis; calcification at the submandibular gland is the landmark of SDC occurring at the subman-dibular gland.

Primary Alveolar Soft Part Sarcoma of Cheek: Report of a Case and Review of the Literature.

Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma characterized by an alveolar or organoid arrangement of polygonal tumour cells separated by fibrovascular septa. A specific fusion gene [ASPS critical region 1 (ASPSCR1)-TFE3] was detected in ASPS. Despite being a slow-growing tumour without pain and dysfunction, ASPS is characterized by early metastasis, which leads to poor prognosis. Herein, we report a rare case of primary ASPS of the cheek harbouring ASPSCR1 (exon 7)-TFE3 (exon 5) fusion gene in a 21 year-old woman. This tumour was a well-circumscribed, smooth, round mass that was clinically suspected as a benign tumour. However, histologically, it was observed that the polygonal tumour cells were arranged in solid and alveolar growth patterns. Post-operative examination of the whole body excluded the possibility of metastasis at other sites. Thus, careful immunohistochemical and genetic analyses, as well as whole-body examination, demonstrated that the tumour was a primary ASPS of the cheek.

Clear Cell Carcinoma of Palatal Minor Salivary Gland Harboring a Novel EWSR1-ATF1 Fusion Gene: Report of a Case and Review of the Literature.

Clear cell carcinoma (CCC) is a rare low-grade malignant salivary gland carcinoma. EWSR1-ATF1 fusion has been characterized as a consistent finding in CCC, with breakpoints described between EWSR1 exon 11 and ATF1 exon 3. So far, over 100 cases of CCC harboring EWSR1 rearrangement arising from salivary gland of the oral cavity have been reported. Although EWSR1 involvement in these cases was confirmed by EWSR1 break-apart FISH indicating the translocation, sequence analysis for EWSR1-ATF1 fusion type has been reported only in three cases of CCC so far. Herein, we report a CCC case with novel EWSR1-ATF1 fusion (EWSR1 exon 15 and ATF1 exon 5) arising in minor salivary gland and review the role of the chimeric variants in some malignancies with EWSR1-ATF1 rearrangement. Current tumor was composed of the small nests of clear tumor cells and hyalized fibrous stroma. Immunohistochemically, the tumor was positive for AE1/AE3, CK5/6 and p63, negative for S100, Melan-A, SMA and CD10. After 8 months of follow-up, there are no evidence of recurrence.

Fibro-adipose vascular anomaly (FAVA): three case reports with an emphasis on the mammalian target of rapamycin (mTOR) pathway.

BACKGROUND: Fibro-adipose vascular anomaly (FAVA) is a new entity of vascular anomalies with somatic and mosaic gain-of-function mutations of the phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). PIK3CA mutation excessively activates mammalian target of rapamycin (mTOR) pathway, which promotes angiogenesis and lymphangiogenesis. Histologically, FAVA is composed of intramuscular fibrous and adipose tissues with venous malformation (VM). Although sirolimus known as a mTOR inhibitor has good response to FAVA, expression pattern of the mTOR pathway was still unclear. Herein, we immunohistochemically investigated three novel FAVA patients with an emphasis on the mTOR pathway (p-S6K1, p-4EBP1 and p-AKT). CASE PRESENTATION: Case 1: A 10-year-old female had complained of pain in the left thigh since she was 6-year-old. Under the clinical diagnosis of VM, she underwent surgical resection for the lesion. Case 2: A 29-year-old female patient had complained of discomfort and mild pain in the left shoulder since she was 18-year-old. After childbirth, she had severe ongoing pain and contracture of the shoulder. Under clinical diagnosis of VM, surgical resection was performed. Case 3: A 53-year-old female had complained of pain and knee restriction after surgical treatment of a knee tumor at the age of 31. Under the clinical diagnosis of atypical lipomatous tumor or high grade liposarcoma, surgical resection was performed. Histologically, all three patients presented with characteristic features of fibrous and adipose tissues with abnormal vessels within the skeletal muscle, leading to diagnosis of FAVA. Although VM has been reported as an important finding in FAVA, immunohistological findings demonstrated that abnormal vessels comprised complex of VM and lymphatic malformation (LM) in all cases. Furthermore, besides vascular malformation, abnormal fibrous and adipose tissues of FAVA expressed mTOR pathway components. CONCLUSIONS: We presented three new cases of FAVA. Histological and immunohistochemical analyses revealed that VM and LM complex was an important finding in FAVA, and that the mTOR pathway components were expressed in abnormal fibrous tissue, adipose tissue and vascular malformation. These findings suggested that FAVA might be a mesenchymal malformation caused by PI3K/AKT/mTOR pathway.

Analysis of mTOR pathway expression in lymphatic malformation and related diseases.

The mammalian target of rapamycin (mTOR) inhibitor sirolimus is an effective treatment for difficult-to-treat lymphatic anomalies. However, little is known about the expression of mTOR pathway components in lymphatic anomalies. Here we investigated the expression pattern of mTOR pathway components and their phosphorylated forms (mTOR, p-mTOR, 4EBP1, p-4EBP1, S6K1 and p-S6K1) in normal lymphatic vessels and lymphatic anomalies using immunohistochemistry. We studied 18 patients of lymphatic anomalies, including lymphatic malformation (LM, n = 14), Kaposiform lymphangiomatosis (KLA, n = 2) and Kaposiform hemangioendothelioma (KHE, n = 2). Normal lymphatic vessels expressed 4EBP1, S6K1 and p-S6K1, but not p-4EBP1, mTOR or p-mTOR. The mTOR was detected in all lymphatic anomalies, whereas its activation form p-mTOR was detected in half cases of KLA and KHE but not in LM. All lymphatic anomalies expressed S6K1 and its activated form p-S6K1. The expression of 4EBP1 was also found in all lymphatic anomalies, but its activation was detected in approximately half of them. The activation of mTOR was seen in tumor (KLA and KHE) but not in malformation (LM), whereas the activation of S6K1 and 4EBP1 was seen in all and half of lymphatic anomalies, respectively.

Galectin-1 expression is associated with tumour immunity and prognosis in gingival squamous cell carcinoma.

AIMS: Galectin-1 (Gal-1) is a ß-galactoside-binding protein that overexpresses in cancer and plays pivotal roles in tumour progression. Gal-1 regulates angiogenesis and invasiveness, and suppresses tumour immunity by inducing T cell apoptosis. Several studies have examined the relationship between Gal-1 and tumour immunosuppression in vivo, but they have not examined the clinicopathological relationship between Gal-1 expression and apoptotic T cell number in human tissue. In this study, we investigated the association between Gal-1 expression and apoptotic T cells of gingival squamous cell carcinoma (GSCC), as well as other clinicopathological factors. METHODS: Immunohistochemical investigation of 80 GSCC specimens using anti-Gal-1, anti-CD3, anti-CD4, anti-CD8, anti-CD34, antipodoplanin and anticleaved caspase-3 (CC-3) antibodies was performed. Relative expression levels of CD3 and CC-3, as well as CD8 and CC-3 were assessed simultaneously by double immunostaining. Gal-1 expression and T cell apoptosis were evaluated in 6 high-power fields (3 in the tumour and 3 in the stroma). RESULTS: Gal-1 expression in GSCC was significantly correlated with T cell infiltration (p=0.036), and apoptosis of CD3+ and CD8+ T cells (p<0.001). Moreover, Gal-1 expression was significantly correlated with lymph node metastasis (p=0.021), histological differentiation (p<0.001) and overall survival rate (p=0.021). CONCLUSIONS: These findings suggest that Gal-1 plays an important role in immune escape of GSCC cells, and Gal-1 expression level may be a useful clinicopathological prognostic marker for GSCC.

Atypical glomus tumor arising in the liver: a case report.

BACKGROUND: Glomus tumors typically occur in the subcutaneous tissue of distal extremities, but rarely in visceral organs. Most glomus tumors are benign, while others have been reported to have malignant potential. Herein, a unique case of a liver glomus tumor with atypical histological features is reported. CASE PRESENTATION: A 39-year-old man felt fullness in the epigastrium, and an enhanced computed tomography (CT) scan of the abdomen and pelvis revealed a 21-cm solid and cystic mass in the left liver lobe. The patient underwent a left hepatic lobectomy, and the tumor was pathologically identified as a glomus tumor with atypical histological features in the liver. This case is unique for three reasons. First, cases of glomus tumors in the liver are extremely rare. Second, this is the first report of a hepatic glomus tumor with histologically atypical features. Third, immunohistochemical staining showed focal positivity for synaptophysin. A literature review revealed that glomus tumors in visceral organs positive for synaptophysin show histological atypical features in most cases. CONCLUSIONS: This is the first case of a glomus tumor with atypical histological features arising in the liver. This unique case and literature review yielded interesting findings and enabled us to postulate that synaptophysin positivity may be indicative of atypical histological features in glomus tumors arising in visceral organs.

The structure of a new cardenolide diglycoside and the biological activities of eleven cardenolide diglycosides from Nerium oleander.

A new cardenolide diglycoside (1) was isolated from Nerium oleander together with ten known cardenolide diglycosides 2-11. The structure of compound 1 was established on the basis of their spectroscopic data. The in vitro anti-inflammatory activity of compounds 1-11 was examined on the basis of inhibitory activity against the induction of the intercellular adhesion molecule-1 (ICAM-1). Compounds 2-5 were active at an IC(50) value of less than 0.8 µM. The cytotoxicity of compounds 1-11 was evaluated against three human cell lines normal human fibroblast cells (WI-38), malignant tumor cells induced from WI-38 (VA-13), and human liver tumor cells (HepG2). Compound 3 was active toward VA-13 cells, and compounds 2-5 were active toward HepG2 cells at IC(50) values of less than 1.3 µM. The multidrug resistance (MDR)-reversal activity of compounds 1-11 was evaluated on the basis of the amount of calcein in MDR human ovarian cancer 2780AD cells in the presence of each compound. Compounds 1 and 8 showed moderate effects on calcein accumulation.