Squamous Cell Carcinoma Transformation Research Articles

INNV-22. CEREBELLOPONTINE EPIDERMOID CYST TO SQUAMOUS CELL CARCINOMA: MALIGNANT TRANSFORMATION, LEPTOMENINGEAL CARCINOMATOSIS, AND MANAGEMENT

Abstract BACKGROUND Intracranial epidermoid cysts (EDC) are rare, slow-growing, congenital tumors, that generally follow a benign course. EDCs have a rare potential for transformation to squamous cell carcinoma (SCC). We present a case of a malignant EDC transformation to SCC with leptomeningeal (LM) dissemination. METHODS Case report and review of literature. CASE PRESENTATION A 44-year-old female presented for evaluation of left-sided tinnitus and sensorineural hearing loss, which revealed a left cerebellopontine angle (CPA) tumor. She underwent a subtotal resection at age 47. One year later, she had rapid symptomatic recurrence of the cyst, as well as LM deposits of the right internal acoustic canal bundle, the left trigeminal nerve, and along the lumbar and sacral spine. She underwent repeat resection of the CPA lesion, with pathology now consistent with SCC, with CDKN2A loss. She received focal radiation therapy at the posterior fossa and the lumbar spine. SCC-directed chemotherapy with pembrolizumab and carboplatin followed by 5 cycles of pembrolizumab monotherapy was given as adjuvant therapy, prior to her developing symptomatic LM disease. CONCLUSION Malignant transformation of intracranial EDC is a rare occurrence in these typically benign tumours. Prognosis is especially poor when there is associated LM involvement, with median survival noted to be 10 months. Awareness of this phenomenon amongst clinicians is needed to ensure appropriate surveillance and aggressive treatment if it remains within patient wishes, though there is no consensus on recommendations for treatment. The patient presented has maintained disease stability with LM dissemination for over 10 months and ongoing, with a regimen of chemoradiotherapy informed by therapeutic approach to systemic SCC. To our knowledge, this is the first reported case of EDC to SCC transformation and LM dissemination stabilized with chemoradiotherapy using an immune-checkpoint inhibitor.

Epidemiology and Risk Factors of Actinic Keratosis. What is New for The Management for Sun-Damaged Skin.

Actinic keratosis (AK) is considered a chronic skin disease mostly caused by long-term exposure to UV radiation and other risk factors such as immunosuppression, leading to an individual susceptibility for skin cancer manifestation. The treatment of AK is laborious and costly, and the incidence of skin cancer is forecasted to double until the year 2030 in an aging society.Risk factors in AK for malignant transformation in cutaneous squamous cell carcinoma (cSCC) are not fully understood, but studies suggest that histological features, such as atypia in the basal epidermal third and basal proliferation (PRO score) in AK play a pivotal role for development of malignancy. As the clinical appearance of AK does not correlate with the risk for malignancy, guidelines suggest treating every single AK lesion upon diagnosis. Skin imaging techniques, such as line-field confocal optical coherence tomography (LC-OCT) can help to provide an individual holistic follow-up for AK lesions by non-invasive visualization of atypia and basal proliferation. A follow-up for patients with AK may be critical for treatment success in terms of strengthening therapy adherence. When AK presents therapy refractory, cSCC manifests in nearly 30% of the cases after several years. Patients with AK suffering from field cancerization and immunosuppression are susceptible for a severe course of disease including metastasis and high mortality rates. Those vulnerable subgroups benefit from close skin cancer screening, early adequate treatment and chemoprevention, such as niacinamide or acitretin. Skin cancer prevention is substantial. Primary prevention should include chemical and physical UV-light protection and avoidance of indoor tanning. Secondary prevention is essential in high-risk populations, such as fair skin type elderly men and STORs. Tertiary prevention should comprise adequate treatment strategies to prevent therapy resistance, reoccurrence and cSCC, especially when field cancerization and immunosuppression are present.

Squamous cell carcinoma malignant transformation in mature cystic teratoma of the ovary: a case report and review of the literature

BackgroundMature cystic teratoma of the ovary is classified among the benign ovarian germ cell neoplasms, and its malignant transformation occurs very rarely (in about 2%). As a result of nonspecific signs and symptoms, preoperative diagnosis of theses malignancies is a challenge to clinicians, resulting in delayed diagnosis (in advanced stages) and poor outcomes.Case presentationWe report the case of a 43-year-old Iranian woman with progressive distension of the abdomen and hypogastric pain, who was diagnosed with squamous cell carcinoma transformation in a mature cystic teratoma of the ovary confirmed by histopathology examination. Total abdominal hysterectomy, bilateral salpingooophorectomy, and comprehensive staging surgery were performed for the patient, and she was scheduled for chemotherapy after the surgery. She responded well to the treatment and is currently continuing her chemotherapy process.ConclusionThere are a great number of reports in the literature regarding mature cystic teratoma of the ovary transformation into malignancy, so these neoplasms must be considered as a possible differential diagnosis and should be evaluated in older individuals with abdominal pain and palpable mass, or those with considerable tumor diameter and raised serum tumor markers.

Spatial transcriptomics reveals that metabolic characteristics define the tumor immunosuppression microenvironment via iCAF transformation in oral squamous cell carcinoma

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism, and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.

FOXD1 promotes proliferation, migration, and epithelial-mesenchymal transformation in esophageal squamous cell carcinoma by targeting SNAI1

The transcription factor Forkhead box D1 (FOXD1) is a crucial member of the FOX family and is widely expressed in human embryonic cells, where it plays a regulatory role in organogenesis. However, the precise functions and molecular mechanisms of FOXD1 in esophageal squamous cell carcinoma (ESCC) are not fully clarified. This study aimed to analyze the expression of FOXD1 in ESCC, investigate its relationship with clinicopathological features and prognosis, and elucidate its role in ESCC tumorigenesis and progression. We found a significant up-regulation of FOXD1 mRNA and protein expression in ESCC (p < 0.01), which exhibited a negative correlation with prognosis. Notably, the expression level of FOXD1, along with tumor TNM stage and lymph node metastasis, emerged as independent prognostic factors for ESCC patients (p < 0.01). In addition, we observed that FOXD1 promoted ESCC cell proliferation, migration, and invasion in vitro. Furthermore, we identified a positive correlation between FOXD1 and SNAI1 in ESCC. Through direct binding to the SNAI1 promoter, FOXD1 enhanced its transcriptional activity, thereby regulating the epithelial-mesenchymal transition (EMT) process and activating TGF-β signaling. These findings suggested that FOXD1 may function as a tumor activator and represent a potential novel therapeutic target for ESCC.

Immuno-oncologic signature of malignant transformation in oral squamous cell carcinoma

The purpose of this study is to identify the immuno-oncologic (IO) signature at the surgical tumor margin (TM) of oral squamous cell carcinoma (OSCC) that is involved in the process of malignant transformation. Under institutional review board approval, TM of 73 OSCC were investigated using immunohistochemistry for the immune biomarker, programmed death ligand-1 (PD-L1). NanoString 770 IO-focused gene set was analyzed in 5 pairs of TM and invasive tumor (T). PD-L1 regulation in response to interferon-gamma (IFN-γ) was investigated in an oral potentially malignant cell line (OPMC). Programmed death ligand-1 expression in the epithelial margin directly correlated with its expression in the underlying immune cells (P=.0082). Differential gene expression showed downregulation of PD-L1 and IFN-γ 6 gene signature in the TM relative to T pair.CD8 and macrophages were higher in TM. CNTFR, LYZ, C7, RORC, and FGF13 downregulation in T relative to TM. TDO2, ADAM12, MMP1, LAMC2, MB21D1, TYMP, OASL, COL5A1, exhausted_CD8, Tregs,and NK_CD56dim were upregulated in T relative to TM. Finally, IFN-γ induced upregulation of PD-L1 in the OPMC. Our work suggests a role for IFN-γ in PD-L1 upregulation in OPMC and presents novel IO transcriptional signatures for frankly invasive OSCC relative to TM.

Exosomal PIK3CB promotes PD-L1 expression and malignant transformation in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC), which accounts for 90% of esophageal carcinomas, seriously endangers human health. Worse still, the 5-year overall survival of ESCC is approximately 20%. Elucidation of the potential mechanism and exploration of promising drugs for ESCC are urgently needed. In this study, a high level of exosomal PIK3CB protein was found in the plasma of ESCC patients, which might indicate a poor prognosis. Moreover, a significant Pearson's correlation was observed at the protein level between exosomal PIK3CB and exosomal PD-L1. Further study revealed that cancer cell-intrinsic and exosome-derived PIK3CB promoted the transcriptional activity of the PD-L1 promoter in ESCC cells. Moreover, treatment with exosomes with lower levels of exosomal PIK3CB decreased the protein level of the mesenchymal marker β-catenin while increasing that of the epithelial marker claudin-1, indicating the potential regulation of epithelial-mesenchymal transition. Consequently, the migratory ability and cancer stemness of ESCC cells and the growth of tumors formed by ESCC cells were decreased with the downregulation of exosomal PIK3CB. Therefore, exosomal PIK3CB plays an oncogenic role by promoting PD-L1 expression and malignant transformation in ESCC. This study may provide new insight into the inherent biological aggressiveness and the poor response to currently available therapies of ESCC. Exosomal PIK3CB may be a promising target for the diagnosis and therapy of ESCC in the future.

Skin Cancer Associated With Chronic Leg Ulcers in the Population of Olmsted County, Minnesota

Malignant skin tumors in the setting of chronic leg ulcers (CLUs) are often underdiagnosed which may contribute to treatment delay and poor outcomes. The aims of our study were to determine the incidence and clinical characteristics of skin cancers in leg ulcers in the Olmsted County population from 1995 to 2020. We used the Rochester Epidemiology Project (a collaboration between health care providers) infrastructure to describe this epidemiology, allowing “population-based” research. Electronic medical records of adult patients with International Classification of Diseases diagnosis codes for leg ulcers and skin cancers on the legs were queried. Thirty-seven individuals with skin cancers in nonhealing ulcers were identified. The cumulative incidence of skin cancer over the 25-year period was 37:7864 (0.47%). The overall incidence rate was 470 per 100,000 patients. Eleven (29.7%) men and 26 (70.3%) women were identified with mean age of 77 years. History of venous insufficiency was present in 30 (81.1%) patients and diabetes in 13 (35.1%) patients. Clinical characteristics of CLU with skin cancer included abnormal granulation tissue in 36 (94.7%) and irregular borders in 35 (94.6%) cases. Skin cancers among CLUs included 17 (41.5%) basal cell carcinomas, 17 (41.5%) squamous cell carcinomas, 2 (4.9%) melanomas, 2 (4.9%) porocarcinomas, 1 (2.4%) basosquamous cell carcinoma, and 1 (2.4%) eccrine adenocarcinoma. The apparent association between chronic wounds and subsequent biopsy-proven skin cancer of the same site was primarily observed in elderly patients; malignant transformation of wounds favored basal cell carcinoma and squamous cell carcinoma. This retrospective cohort study further characterizes the association between skin cancers and chronic leg wounds.

Malignant Transformation of an Intracranial Epidermoid Cyst 25 Years After Initial Surgery: A Case Report and Systematic Review

We report a unique case of a suspected recurrent intracranial epidermoid cyst (EDC) that was found on pathology to have undergone malignant transformation to squamous cell carcinoma (SCC) approximately 25years after initial resection. Additionally, we performed a systematic review including 94 studies reporting intracranial EDC to SCC transformation. Ninety-four studies were included in our systematic review. PubMed, Scopus, Cochrane Central, and EMBASE were searched in April 2020 for studies regarding histologically confirmed SCC arising within an EDC. Kaplan-Meier estimations were used to estimate time to event including survival, and log rank tests were used to test for significance. All analyses were conducted using STATA 14.1 (StataCorp, College Station, Texas, USA); tests were two-sided, and statistical significance was defined using the alpha threshold of 0.05. The overall median time to transformation was 60months (95% confidence interval {CI}, 12-96). Transformation time was significantly shorter in the no surgery group (10months, 95% CI undefined) versus the other 2 groups (60months, 95% CI, 12-72 in surgery only and 70months, 95% CI, 9-180 in surgery+adjuvant therapy group, both P < 0.01). Overall survival was significantly longer in the surgery+adjuvant therapy group (13months, 95% CI, 9-24) versus the other 2 groups (3months, 95% CI, 1-7 in surgery only and 6months, 95% CI, 1-12 in the no surgery group, both P<0.01). We report a rare case of delayed malignant transformation of an intracranial EDC to SCC, occurring nearly 25years after initial resection. Transformation time in the no-surgery group was statistically significantly shorter as compared to the surgery only and surgery+adjuvant therapy groups. Overall survival was statistically significantly higher in the surgery+adjuvant therapy group as compared to the surgery only and no surgery groups.

ACTN1 interacts with ITGA5 to promote cell proliferation, invasion and epithelial-mesenchymal transformation in head and neck squamous cell carcinoma.

The aim of this study was to detect the expression levels of α-Actinin 1 (ACTN1) and ITGA5 in HNSCC and to explore how ACTN1/ITGA5 regulated the proliferative and invasive abilities, as well as the EMT of Head and neck squamous cell carcinoma (HNSCC) cells. The viability, proliferative, invasive and migrative abilities of HNSCC cells after transfection were, in turn, detected by CCK8 assay, colony formation assay, EdU staining, transwell, as well as wound healing. E-cadherin in transfected cells was assessed utilizing immunofluorescence. RT-qPCR confirmed the transfection effect of ACTN1 and ITGA5 in HNSCC cells and the interaction between ACTN1 and ITGA5 in HNSCC cells was determined by co-immunoprecipitation (Co-IP). With Western blot application, the contents of ACTN1, ITGA5, proliferation-, invasion- and migration-related proteins were estimated. A xenograft model based on nude mice was conducted and Ki-67 content in tumor tissues was evaluated employing immunohistochemistry (IHC) staining. ACTN1 interacted with ITGA5. The contents of ACTN1 and ITGA5 were found to be abundant in HNSCC tissues and cells and associated with poor prognosis. ACTN1 depletion imparted suppressive impacts on cell proliferative, invasive and migrative abilities as well as EMT of HNSCC cells, which were reversed by ITGA5 overexpression. In addition, ACTN1 deficiency repressed the growth and metastasis of tumor tissues in tumor xenografts of nude mice. ACTN1 positively interacts with ITGA5 to promote proliferation, invasion and EMT of HNSCC cells. Also, ACTN1 promotes tumor growth and metastasis.

TDO2+ myofibroblasts mediate immune suppression in malignant transformation of squamous cell carcinoma.

Characterization of the dynamic change in the immunological landscape during malignant transformation from precancerous lesions to cancerous lesions in squamous cell carcinoma (SCC) is critical for the application of immunotherapy. Here, we performed single-cell RNA-Seq (scRNA-Seq) of 131,702 cells from 13 cancerous tissues of oral squamous cell carcinoma (OSCC), 3 samples of precancerous oral leukoplakia, and 8 adjacent normal samples. We found that tumor-infiltrating CD4+ and CD8+ T cells were functionally inhibited by immunosuppressive ligands expressed on various types of myeloid cells or neutrophils in the process of oral carcinogenesis. Notably, we identified a subset of myofibroblasts that exclusively expressed tryptophan 2,3-dioxygenase (TDO2). These TDO2+ myofibroblasts were located distally from tumor nests, and both CD4+ and CD8+ T cells were enriched around them. Functional experiments revealed that TDO2+ myofibroblasts were more likely to possess the ability for chemotaxis toward T cells but induced the transformation of CD4+ T cells into Tregs and caused CD8+ T cell dysfunction. We further showed that use of the TDO2 inhibitor LM10 attenuated the inhibitory states of T cells, restored the T cell antitumor response, and prevented the progression of OSCC malignant transformation in murine models. Our study reveals a multistep transcriptomic landscape of OSCC and demonstrates that TDO2+ myofibroblasts are potential targets for immunotherapy.

Squamous-Cell Carcinoma in Mature Cystic Teratoma of the Ovary - A Case Report

Mature cystic teratoma is the most common benign germ cell tumor of the ovary. More than 80% of MCTs develop during the reproductive year. About 1% of the dermoid cysts undergo malignant transformation, most commonly squamous cell carcinoma in post-menopausal age group. We report a rare case of Squamous cell carcinoma transformation in mature cystic teratoma which was diagnosed and confirmed by histopathology and immunohistochemistry.

Floor of Mouth Squamous Cell Carcinoma Presenting as an Abscess.

Oral squamous cell carcinoma (OSCC) is the most common malignancy encountered in oral cavity. Etiology is often multifactorial but strongly associated with chronic tobacco smoking, excessive alcohol consumption and tobacco chewing. Factors such as poor oral hygiene, ill-fitting dentures causing chronic mucosal irritation can also contribute to the cancer development. In recent years, studies shown association of HPV infections, especially subtypes 16 and 18 in malignant transformation of head and neck squamous cell carcinoma, as it present may change prognosis, outcomes and management strategies from HPV-negative OSCC. OSCC have variable presentation, and most of the patients tend to seek treatment at later stage of disease. The lesion may present as leukoplakia or erythroplakia and may be ulcerated with indurated base and rolled out edges. We describe an uncommon presentation of floor of mouth squamous cell carcinoma which presented as localized abscess.

Stage Ia squamous cell carcinoma as the malignant transformation of giant and unusual mature teratoma of the ovary in an elderly patient

BackgroundMature cystic teratomas of the ovary (MCTO) are a type of germ cell tumor that may contain well-differentiated tissues developed from three germ cell layers and constitute about 20% of ovarian germ cell tumors. They are rare ovarian tumors with an annual incidence variable from 1.2 to 14.2 cases per 100,000 that occur mainly in women of reproductive age. They are frequently benign with a slow growth rate, even if they can undergo a malignant transformation in about 1–2% of cases.Case presentationHere, we present the case of an elderly woman referred to gynecological first aid for acute abdominal pain and showing a giant and unusual MCTO at rapid growth with malignant transformation in squamous cell carcinoma (FIGO stage Ia). The patient underwent pelvic mass removal trough emergency longitudinal midline laparotomic incision with intraoperative frozen pathologic examination. A complete surgical staging during the first surgery was performed. After about 9 years of follow-up, she died of non-oncological reasons without recurrence.ConclusionsPresent case highlights that CMTO with malignant transformation should always be suspected in elderly women in presence of pelvic mass at rapid growth, even if in absence of other clinical and ultrasonographic signs of malignancy. An intraoperative frozen pathologic examination may drive the best treatment.

Co-Culture of MSCs with miR-496 Prompts Epithelial-Mesenchymal Transformation of Oral Squamous Cell Carcinoma (OSCC)

This study discusses the molecular mechanism of co-culture of MSCs with miR-496 in the EMT of OSCC. miR-496 expression in OSCC tissues and cells was detected by qRT-PCR. The MSCs+si-NC, MSCs+pc-DNA-NC, MSCs+si-miR-496, MSCs+pc-DNA-miR-496 was transfected into SCC-PKUs to analyze cell apoptosis, proliferation and clone formation as well as the expression of proteins related with EMT. miR-496 in OSCC tissues was elevated and positively related with the clinical stage of OSCC patients. The cell activity and invasive ability of SCC-PKU was increased after co-culture of MSCs and pc-DNA-miR-496 along with increased expression of EMT-related proteins. However, all above changes were reversed after treatment with MSCs and si-miR-496. In conclusion, co-culture of MSCs and miR-495 prompts the occurrence and development of OSCC through regulating EMT processes, indicating that they might be novel targets for the treatment of OSCC.

Sinonasal Papilloma and Its Associated Malignancy: Study from a Tertiary Referral Hospital in Indonesia

Background&#x0D; Sinonasal papilloma is a benign tumor arising from Schneiderian epithelia in sinonasal mucosa. It has the propensity towards malignant transformation. This preliminary study aims to report clinicopathological aspects of sinonasal papilloma and its malignant transformation rate.&#x0D; Methods&#x0D; A descriptive, cross-sectional study was conducted in Anatomical Pathology Department, FKUI/RSCM over a period of 2014-2019) A total of 127 histologic specimens with diagnosis of sinonasal papilloma obtained from 80 cases.&#x0D; Results&#x0D; The prevalence of sinonasal papilloma among all sinonasal neoplasms is 17.6%. Inverted papilloma was the most common histologic type 91.3%, exophytic papilloma 6.3% and oncocytic papilloma 2.5%, among male (70%), age rate 50 years old. Malignant transformation of squamous cell carcinoma 12.5%, and recurrence 21.3%, nasal congestion was the most complaint 50%. Cases were usually in T3 of Krouse stage 37.5% and managed with functional sinus endoscopic surgery 51.3%. Histological parameters were grade II 54.4%, surface keratinization 17.5%, bony trabeculae 41.3%, nasal polyps 20% and dense lymphocytic infiltrates 53.8%, foam cell infiltrates 2.5%. Mild to moderate dysplasia 8.8% and severe dysplasia 18.8%.&#x0D; Conclusion&#x0D; Sinonasal papilloma was rare sinonasal benign tumor. Inverted papilloma type was local aggressive, recurrence, dysplastic and malignant transformation, among male, age 50 years old, main complaint of nasal congestion, in Krouse stage T3, and managed by Functional Sinus Endoscopy Surgery (FSES

Whole-exome sequencing of transforming oral lichen planus reveals mutations in DNA damage repair and apoptosis pathway genes.

Oral lichen planus confers a 1% risk of transformation to oral squamous cell carcinoma. While prior exome sequencing studies have identified multiple genetic mutations in oral squamous cell carcinoma, mutational analyses of lichen planus-derived OSCC are lacking. We sought to clarify genomic events associated with oral lichen planus transformation. Using rigorous diagnostic criteria, we retrospectively identified patients with non-transforming oral lichen planus (i.e., known to be non-transforming with 5years of clinical follow-up; n=17), transforming oral lichen planus (tissue marginal to oral squamous cell carcinoma, n=9), or oral squamous cell carcinoma arising in lichen planus (n=17). Gene mutational profiles derived from whole-exome sequencing on fixed mucosal specimens were compared among the groups. The four most frequently mutated genes in transforming oral lichen planus and oral squamous cell carcinoma (TP53, CELSR1, CASP8, and KMT2D) identified 12/17 (71%) of oral squamous cell carcinomas and 5/9 (56%) of transforming oral lichen planus but were absent in non-transforming oral lichen planus. We identified other known oral squamous cell carcinoma mutations (TRRAP, OBSCN, and LRP2) but also previously unreported mutations (TENM3 and ASH1L) in lichen planus-associated oral squamous cell carcinomas. These findings suggest alterations in DNA damage response and apoptosis pathways underlie lichen planus-related oral squamous cell carcinoma transformation and are supported by mutational signatures indicative of DNA damage. This study characterized patterns of mutational events present in oral lichen planus associated with squamous cell carcinoma and in squamous cell carcinoma associated with oral lichen planus but not in non-transforming oral lichen planus.

Malignant Transformation of Intracranial Epidermoid Cyst to Squamous Cell Carcinoma, Case Report and Literature Review

Intracranial Epidermoid cysts (ECs) are rare, benign tumor of central nervous system that appears from maintain ectodermal implants. Malignant transformation of an EC to squamous-cell carcinoma (SCC) is rarely reported. Intracranial squamous cell carcinoma has known as a poor prognosis condition that optimal modalities remain uncertain. We present the case of 43-years old male complained 3 months severe headache and right eye hemianopia. Primary evaluation depicted right homogenous brain mass which was successfully totally removed. Pathological assessment found epidermoid cyst without any sign of malignancy. Six months later, patient was referred with episodes of intermittent headache and right eye blindness. After initial imaging, new tumor was growth in same site of frontal epidermoid cyst. Second surgery was performed and pathological report discloses to be a malignant SCC. SCC transformation was confirmed by two expert neuro- pathologists. The exact underlying mechanism causing malignant transformation is not definitely known and it seems SCC may have been transformed due to chronic inflammatory respond to epidermoid cyst. Literature reviews demonstrate that, although, optimal total resection in addition adjuvant radiotherapy is the recommended management of choice, patient’s general survival of this condition is generally poor and long-term follow-up is important.

MicroRNA-665 facilitates cell proliferation and represses apoptosis through modulating Wnt5a/\u03b2-Catenin and Caspase-3 signaling pathways by targeting TRIM8 in LUSC

BackgroundMicroRNAs (miRNAs) are involved in the oncogenesis, development and transformation of lung squamous cell carcinoma (LUSC). miR-665 is clinically significant and acts as a pivotal function in some cancers. Nevertheless, the effects and the potential mechanisms of miR-665 in human LUSC are still unknown.MethodsTo analyse the clinical significant of miR-665 in human LUSC, quantitative real-time PCR (qRT-PCR) was use to measure miR-665 expression in LUSC specimen tissues and cell lines. Tripartite motif 8 (TRIM8) was verified a target of miR-665 by performing bioinformatic prediction and luciferase reporter assay. The expression levels of TRIM8 were examined through qRT-PCR and Western blotting in LUSC specimen tissues. CCK8 assay was fulfilled for analyzing the function in LUSC cell proliferation. Flow cytometry was used to detect cell and apoptosis. TRIM8 silencing and overexpression further verified the biological effects as those caused by miR-665.ResultsHere we reported that miR-665 expression was upregulated in LUSC specimen tissues and cell lines. High miR-665 levels were related to differentiation, tumor size and TNM stage. miR-665 mimics facilitated LUSC cell growth and cell cycle G1-S transition and repressed apoptosis. miR-665 inhibitor suppressed cell proliferation and G1-S transition and promoted apoptosis. miR-665 expression was negatively correlated with TRIM8 mRNA expression in LUSC. Luciferase reporter assay confirmed that TRIM8 was a direct target gene of miR-665. miR-665 mimics downregulated the TRIM8 levels, and miR-665 inhibitor upregulated the TRIM8 levels in LUSC cells. Particularly, silencing TRIM8 led to the similar effects of miR-665 mimics in LUSC cells. Overexpression of TRIM8 inhibited LUSC cell proliferation in vitro and in vivo. Furthermore, miR-665 promoted LUSC cell proliferation through facilitating the Wnt5a/β-catenin signaling pathway and restrained apoptosis via inhibiting Caspase-3 signaling pathway, whereas TRIM8 suppressed cell growth by repressing the Wnt5a/β-catenin signaling pathway and induced apoptosis through activating Caspase-3 signaling pathway.ConclusionsThe current study demonstrates that miR-665 facilitates LUSC cell proliferation and cell cycle transition by regulation of the Wnt5a/β-Catenin signaling pathway and represses cell apoptosis via modulation of Caspase-3 signaling pathway by directly targeting TRIM8. These findings suggest that miR-665 might be a potential new target for LUSC therapy.

Squamous cell carcinoma arising in recurrent pilonidal sinus in an older woman

Malignant transformation is a rare complication of pilonidal sinus. We report the case of a 90-year-old female who had a recurrent pilonidal sinus with fistulous abscess formation. We excised the whole pilonidal sinus because the infection could not be controlled by oral antibiotics. Squamous cell carcinoma (SCC) was found in the sinus tract with a negative surgical margin. A whole abdominal computed tomography scan was performed, which showed no distant metastasis and no enlargement of the bilateral inguinal lymph nodes. This case study illustrates that SCC transformation may present in the recurrent and long-standing pilonidal sinus. We suggested that all pilonidal sinus lesions should be sent for pathologic examination to early detect malignant transformation.