Squamous Cell Carcinoma Of Lower Lip Research Articles

Clinical outcomes of bilobed platysma myocutaneous flap technique with neck dissection in lower lip squamous cell carcinoma

BackgroundSquamous cell carcinoma (SCC) in the lower lip is among the most frequently encountered types of cancer. As the size of this cancer increases, the need for reconstruction becomes evident, posing a significant challenge. Depending on the staging results in these patients, neck dissection may be recommended. ObjectiveThis study aims to demonstrate the successful application or feasibility of our Bilobed Platysma Myocutaneous Flap technique in patients with lower lip SCC. MethodsThe Bilobed Platysma Myocutaneous Flap was applied to all patients. Following TNM staging, supraomohyoid and/or radical neck dissection were performed. Surveys were conducted with the patients, and scoring was implemented based on the results for evaluation. ResultsBetween 2014 and 2018, 23 patients underwent treatment with this flap, and all flaps survived. Among these patients, bilateral supraomohyoid neck dissection was performed on 14, while modified radical neck dissection on one side and supraomohyoid neck dissection on the other side were conducted on the remaining 9 patients. Throughout the 5-year follow-up period, no recurrence was observed in the patients. ConclusionThe combination of the Bilobed Platysma Myocutaneous Flap technique and neck dissection can be successfully employed in the reconstruction and treatment of lower lip cancers.

Assessment of the association of myofibroblasts and structural components of the extracellular matrix with histopathological parameters of actinic cheilitis and lower lip squamous cell carcinoma.

To evaluate the presence of myofibroblasts (MFs) in the development of lip carcinogenesis, through the correlation of clinical, histomorphometric and immunohistochemical parameters, in actinic cheilitis (ACs) and lower lip squamous cell carcinomas (LLSCCs). Samples of ACs, LLSCCs, and control group (CG) were prepared by tissue microarray (TMA) for immunohistochemical TGF-β, α-SMA, and Ki-67 and histochemical hematoxylin and eosin, picrosirius red, and verhoeff van gieson reactions. Clinical and microscopic data were associated using the Mann-Whitney, Kruskal-Wallis/Dunn, and Spearman correlation tests (SPSS, p < 0.05). ACs showed higher number of α-SMA+ MFs when compared to CG (p = 0.034), and these cells were associated with the vertical expansion of solar elastosis (SE) itself (p = 0.027). Areas of SE had lower deposits of collagen (p < 0.001), immunostaining for TGF-β (p < 0.001), and higher density of elastic fibers (p < 0.05) when compared to areas without SE. A positive correlation was observed between high-risk epithelial dysplasia (ED) and the proximity of SE to the dysplastic epithelium (p = 0.027). LLSCCs showed a higher number of α-SMA+ MFs about CG (p = 0.034), as well as a reduction in the deposition of total collagen (p = 0.009) in relation to ACs and CG. There was also a negative correlation between the amount of α-SMA+ cells and the accumulation of total collagen (p = 0.041). Collagen and elastic density loss was higher in larger tumors (p = 0.045) with nodal invasion (p = 0.047). Our findings show the possible role of MFs, collagen fibers, and elastosis areas in the lip carcinogenesis process.

Relationship between tumor thickness and GATA3 immunoexpression in lip and tongue squamous cell carcinomas.

Lower lip squamous cell carcinomas (LLSCCs) exhibit lower levels of aggressiveness, low relations with metastases and better prognosis when compared with intraoral squamous cell carcinomas. Differently from the oral tongue squamous cell carcinomas (OTSCCs) have a high tendency towards local invasion and lymph nodal dissemination. Our aim was to evaluate tumor thickness in cases of oral squamous cell carcinoma and correlate it with histological grade of malignancy and GATA3 immunoreactivity. Sixty specimens (30 LLSCCs and 30 OTSCCs) were scanned and digitized for the subsequent measurement of tumor thickness, histopathological examination, and quantitative analysis of GATA3 in the parenchyma and stroma of the tumors. Tumor thickness was lower in LLSCC compared to OTSCCs. Immunohistochemical analysis of GATA3 in parenchyma, stroma and both compartments showed higher immunoreactivity in LLSCCs compared to OTSCCs. We observed a negative correlation between tumor thickness and GATA3 expression in parenchyma, stroma, and both compartments. Our results revealed the presence of GATA3 in all cases both in the parenchyma and in the stroma. Higher expression was more related to LLSCCs, which are known to be less aggressive tumors than OTSCCs. A greater tumor thickness was found in OTSCCs, which was correlated with lower expression of GATA3, suggesting that this protein is involved in the inhibition of proliferative, migratory, and invasive capacity.

“Y” anastomosis, a solution in doubtful venous anastomosis: a case report and review of the literature

BackgroundLower lip squamous cell carcinoma is a significant subtype of head and neck cancer, constituting about 25–30% of cases. Traditional surgical methods, like primary closure, have limitations in managing large resections of lip tumors. Recent advancements in surgical techniques, particularly free flaps, have shown promising results in addressing these challenges. The Y-shaped anastomosis is an innovative approach aimed at enhancing the efficiency of microvascular free flap surgeries for improved lip cancer reconstruction outcomes.Case presentationA 77-year-old Persian male with lower lip squamous cell carcinoma underwent tumor resection with a 2 cm safety margin, bilateral neck dissection, and lip reconstruction using the right radial forearm free flap. The surgery incorporated a Y-shaped anastomosis to improve venous pedicle outcomes.ConclusionIn this case, it was decided not to open the first anastomosis but to add the second end to the side one to provide two vascular supports for the venous anastomosis. Y anastomosis makes the surgery easier and decreases complications resulting from vascular size mismatch.

Mucosal Roofing Flap Reconstruction to Minimize Horizontal Lip Length Loss and Preserve Mouth Opening in Lower Lip Squamous Cell Carcinoma

Lower lip reconstruction in cases with a full-thickness defect over one-third of the vermilion is challenging. Numerous conventional techniques have been applied with unsatisfactory surgical outcomes because of microstomia and oral commissure blunting due to shortened horizontal lip length. Herein, we present a case in which a full-thickness lower lip defect of more than one-third of the horizontal lip length was covered with a novel mucosal roofing flap reconstruction to minimize the loss of horizontal lip length and to preserve mouth opening. No recurrences or metastases were observed during 3 years and 6 months of follow-up, with horizontal lower lip length maintained and mouth opening of 2.5 finger breadths.

Role of the neck dissection in early-stage lower lip cancers.

In early-stage lip cancer, spread to cervical lymph nodes is extremely rare. Elective neck treatment options include suprahyoid or supraomohyoid neck dissection, sentinel lymph node biopsy, or close follow-up. Aim: In this study, our aim was to investigate the effect of elective surgery on survival in patients operated for early-stage lip cancer. Patients who underwent surgical treatment for lower lip squamous cell carcinoma between 2005 and 2020 were retrospectively analyzed. Age, gender, neck dissection status (yes/no), clinical and pathological T stage of the tumor, grade, and perineural invasion were recorded and 3-year and 5-year overall (OS) and disease-free survival (DFS) rates were estimated. Thirty patients were included: 20 patients had pT1 and 10 patients had pT2 tumors. Neck dissection was performed in 13 patients. The 5-year OS rate was 90.9% and 87.8% with and without dissection, respectively. Neck dissection did not appear to affect OS (P = 0.534) in these patients. The 5-year DFS rate was 96.4% in the overall group, while it was 91.7% and 100% in patients who did or did not undergo neck dissection, respectively (P = 0.756). Patients with or without neck dissection did not differ significantly in terms of OS and DFS. Watchful waiting with regular ultrasound imaging of the neck in patients with T1 and T2 lip tumors may be an appropriate therapeutic option.

Appropriate Surgical Margins for Excision of Squamous Cell Carcinoma of the Lower Lip.

Background Squamous cell carcinoma (SCC) is the most common malignancy on the lower lip. Surgical excision, the standard treatment for SCC, requires full-thickness excision. However, no consensus exists about the appropriate surgical margin. Therefore, we investigated the appropriate surgical margin and excision technique by analyzing 23 years of surgical experience with lower-lip SCC. Methods We reviewed 44 patients with lower-lip SCC who underwent surgery from November 1997 to October 2020. Frozen biopsy was performed with an appropriate margin on the left and right sides of the lesion, and the margin below the lesion was the skin above the sulcus boundary. If the frozen biopsy result was positive, an additional session was performed to secure a negative margin. Full-thickness excision was performed until the final negative margin. In each patient, the total number of sessions performed, final surgical margin, and recurrence were analyzed. Results Forty-one cases ended in the first session, 2 ended in the second session, and 1 ended in the third session. The final surgical margins (left and right; n = 88) were 5 mm (66%), 7 mm (9%), 8 mm (2.3%), 10 mm (20.4%), and 15 mm (2.3%). During an average follow-up of 67.4 months (range, 12-227 months), recurrence occurred in one patient. Conclusion The final surgical margin was 5 mm in 66% (58/88) of the cases, and 97.7% (86/88) were within 10 mm. Therefore, we set the first frozen biopsy margin to 5 mm, and we suggest that a 5-mm additional excision is appropriate when frozen biopsy results are positive.

Use of Cold Atmospheric Plasma in the Treatment of Squamous Cell Carcinoma: in vitro Effects and Clinical Application in Feline Tumors: A Pilot Study

Cold atmospheric plasma (CAP) has shown promising results against squamous cell carcinoma (SCC) in both in vivo and in vitro assays, mainly in humans and mice. Its applicability for treatment of feline tumors, however, remains unknown. This study aimed to evaluate the anticancer effects of CAP on a head and neck squamous cell carcinoma (HNSCC) cell lineage and against a clinical case of cutaneous SCC in a cat. Control and treatment groups employing the HNSCC cell line (SCC-25) were used, the latter exposed to CAP for 60 seconds, 90 seconds, or 120 seconds. The cells were subjected to the MTT assay nitric oxidation assay and thermographic in vitro analyses. The clinical application was performed in one cat with cutaneous SCC (3 sites). The lesions were treated and evaluated by thermographic, histopathological, and immunohistochemical examinations (caspase-3 and TNF-alpha). Treatment of the SCC-25 cells for 90 seconds and 120 seconds resulted in a significant nitrite concentration increase. Decreased cell viability was observed after 24 hours and 48 hours, regardless of exposure time. However, the cell viability reduction observed at 72 hours was significant only in the 120 seconds treatment. In vitro, the temperature decreased for all treatment times, while the plasma induced a slight increase in mean temperature (0.7°C) in the in vivo assay. Two of the 3 clinical tumors responded to the treatment: one with a complete response and the other, partial, while the third (lower lip SCC) remained stable. Both remaining tumors displayed apoptotic areas and increased expression of caspase-3 and TNF-alpha. Adverse effects were mild and limited to erythema and crusting. The CAP exhibited an in vitro anticancer effect on the HNSCC cell line, demonstrated by a dose-dependent cell viability reduction. In vivo, the therapy appears safe and effective against feline cutaneous SCC. The treatment did not result in a clinical response for 1 of 3 lesions (proliferative lower lip tumor), however, a biological effect was still demonstrated by the higher expression of apoptosis indicators.

INTRA-ORAL AND LOWER LIP SQUAMOUS CELL CARCINOMA: A COMPARATIVE ANALYSIS OF THE LYMPHOCYTIC HOST RESPONSE

Objectives To compare the effect of lymphocytic host response (LHR) in the prognosis of patients with tongue and/or floor of mouth squamous cell carcinoma (TFMSCC) and with lower lip squamous cell carcinoma (LLSCC). Study Design Records and slides from 179 patients were evaluated according to the histopathologic risk assessment (HRA) to LHR and submitted to bivariate (chi-square) and survival (Kaplan-Meier and log-rank) analyses. Results White male smokers at initial cTNM were the most affected, in both the TFMSCC and LLSCC. Tumors with strong LHR (61.9%) predominated and were classified as intermediate risk (56.9%) by AHR for TFMSCC and LLSCC. Associations between dense continuous band of LHR and smoking (P = .019), tumors located in the tongue or lower lip (P ≤ .0001), initial pTNM (P ≤ .0001), no recurrence (P = .021), moderately differentiated tumors (P = .001), and intermediate risk by AHR (P ≤ .0001) were observed. Patients with weak LHR had poor overall survival (OS) (P ≤ .0001) and disease-free survival (DFS) (P = .002). Conclusions For both lower lip cancer and intraoral cancer, the presence of a strong LHR demonstrates a favorable effect for OS and DFS and proved to be an important prognostic factor for these patients. To compare the effect of lymphocytic host response (LHR) in the prognosis of patients with tongue and/or floor of mouth squamous cell carcinoma (TFMSCC) and with lower lip squamous cell carcinoma (LLSCC). Records and slides from 179 patients were evaluated according to the histopathologic risk assessment (HRA) to LHR and submitted to bivariate (chi-square) and survival (Kaplan-Meier and log-rank) analyses. White male smokers at initial cTNM were the most affected, in both the TFMSCC and LLSCC. Tumors with strong LHR (61.9%) predominated and were classified as intermediate risk (56.9%) by AHR for TFMSCC and LLSCC. Associations between dense continuous band of LHR and smoking (P = .019), tumors located in the tongue or lower lip (P ≤ .0001), initial pTNM (P ≤ .0001), no recurrence (P = .021), moderately differentiated tumors (P = .001), and intermediate risk by AHR (P ≤ .0001) were observed. Patients with weak LHR had poor overall survival (OS) (P ≤ .0001) and disease-free survival (DFS) (P = .002). For both lower lip cancer and intraoral cancer, the presence of a strong LHR demonstrates a favorable effect for OS and DFS and proved to be an important prognostic factor for these patients.

A Bipedicled Lip Switch Flap From the Upper Lip for Delayed Re-Do Total Lower Lip Reconstruction: A Case Report

Several different techniques have been described for reconstructing vermilion lip defects. The key to successful reconstruction of the vermilion is to restore the original esthetic landmarks and appearance of the lip while preserving function. We present a case of a 49-year-old patient with a history of lower lip squamous cell carcinoma who presented to our institution status post resection and reconstruction with Bernard-von Burow cheek advancement flaps with Webster modification at an outside hospital. Her main complaint was the lack of lower lip vermillion and loss of lip height. This new defect was repaired using a bipedicled lip switch flap from the upper to lower lip. To our knowledge, this is the first time this technique has been reported in the literature to reconstruct a total vermilion lower lip defect. A bipedicled lip switch flap offers an alternative, reliable method for the repair of large vermilion lip defects that can produce satisfactory esthetic and functional outcomes.

Immunoexpression of PD-L1, CD4+ and CD8+ cell infiltrates and tumor-infiltrating lymphocytes (TILs) in the microenvironment of actinic cheilitis and lower lip squamous cell carcinoma.

Lower lip squamous cell carcinomas (LLSCC) could be associated with a previous history of potentially malignant oral diseases (PMOD), especially actinic cheilitis (AC), with high sun exposure being a well-described risk factor. Immune evasion mechanisms, such as the PD-1/PD-L1 (programmed cell death protein 1/programmed death-ligand 1) pathway has been gaining prominence since immunotherapy with immune checkpoint inhibitors showed a positive effect on the survival of patients with different types of neoplasms. Concomitant with the characterization of the tumor microenvironment, the expression of either or both PD-1 and PD-L1 molecules may estimate mutual relations of progression or regression of the carcinoma and prognostic values of the patient.Objective:Considering the importance of tumor microenvironment characterization, this study aims to determine the immunoexpression of PD-L1 and correlate with the frequency of CD4+ and CD8+ cells in AC and LLSCC lesions and with tumor-infiltrating lymphocytes (TILs) in LLSCC and its relationship with histopathological characteristics.Methodology:This sample includes 33 cases of AC and 17 cases of LLSCC. The cases were submitted to histopathological analysis and to CD4+, CD8+, and PD-L1+ cell determination by immunohistochemistry.Results:There was a significant difference among the frequencies of CD4+, CD8+, and PD-L1+ cells between AC and LSCC cases, higher in the last group. Moreover, histopathological and atypical changes in AC and LLSCC were correlated with the frequencies of PD-L1+, CD4+, and CD8+ cells. In AC, PD-L1+ cases had a low frequency of CD4+ cells, but on the other hand, PD-L1+ cases of LLSCC had a higher frequency of CD4+ and CD8+ cells.Conclusion:Therefore, the PD-L1 molecule may be a potential escape route for the immune response in oral lesions, but the mechanisms differ between AC and LLSCC. Future studies related to immune evasion and immunotherapy in oral lesions should consider the analysis of inflammatory infiltrate and TILs.

Case Report on Squamous Cell Carcinoma of the Lip

Introduction: Lip cancers are the most prevalent oral-maxillary malignancy. Lip cancer can be caused by a number of things, including smoking, exposure to ultraviolet (UV) rays, and drinking alcohol [1] In this article we report a case of lower lip squamous cell carcinoma in a 59 year old male patient who smoked heavily and had a history of direct sun exposure, and uv rays. His case report is important attributable to recurrent axillary metastases occurred after subsequent treatment.&#x0D; Clinical Findings: The patient chief complaint is burning sensation on consumption of hot &amp; spicy food since 3 months, apraxia, difficulty in mastication since 2 months approximately &amp; nerve parenthesis in lower lip.&#x0D; Diagnostic Evaluation: Hemoglobin (HB) -13.2gm,mch-27.9fl,mchc-33.3%, Total red blood cell (RBC) count-4.72million/cu.mm Rdw- 12.7%, Total white blood cell (WBC) count- 16500cu.mm, Monocytes -4%, Granulocytes- 85%, Lymphocytes -10%, Esonophils-2%, Basophilis-0%, Total platelet count-2.68 cu. mm.&#x0D; Histopathology report: A multiple, irregular, reddish, brownish tissue pieces aggregating 1×1cm. selection from given tissue piece shows histopathological features are suggestive of well differentiated squamous cell carcinoma. Therapeutic Intervention: post-chemo hydration, post-chemo drugs, BEP Chemotherapy (Bleomycin, Etoposide, Cisplatin).&#x0D; Summary and Conclusions: The patient who was a 59 years old male was admitted to the oral surgery ward. The patient was diagnosed as having squamous cell carcinoma of the lip and he had complained of having burning sensation on consumption of hot &amp; spicy food over the preceding 3 months, apraxia and difficulty in mastication, over a period of about 2 months, and nerve paresthesia within his lower lip. He underwent mandibulectomy with excision of the tumour. Following radical mandibulectomy and adjuvant chemotherapy and radiotherapy, the patient has remained well with no evidence of metastasis at his 4 months follow-up based upon clinical assessment and radiology imaging which does illustrate that radical surgery, plus chemo-radiation for locally advanced squamous cell carcinoma has been shown to be associated with a good short-term outcome and after further follow-up assessments, the long-term outcome of radical surgery and adjuvant chemotherapy would be known.

Immunohistochemical comparative analysis of IMP-3 and KI-67 in actinic cheilitis and lower lip squamous cell carcinoma.

Actinic cheilitis (AC) and lower lip squamous cell carcinoma (LLSCC) exhibit epithelial alterations mainly associated with chronic ultraviolet ray exposure. Currently, it is impossible to predict which AC cases will progress to LLSCC; thus, biomolecular markers have been studied. The aim of this study was to evaluate the immunoexpression of IMP-3 and KI-67 in AC and LLSCC. Forty AC and 40 LLSCC cases were submitted to peroxidase method and quantitatively analyzed, using the following scores: 0 (0% positive cells), + 1(≤ 30%), + 2 (> 30% to ≤ 60%), and + 3 (> 60%). Results were submitted to non-parametric Mann-Whitney (U) test. A p value < 0.05 was considered to indicate statistical significance. IMP-3 immunoexpression was observed in 26 AC cases, with predominance of the score 1 (35% of cases). This protein was also positive in 22 LLSCC cases, with predominance of the score 3 (37.5% of cases). Immunoexpression of KI-67 was observed in all studied cases, with predominance of the score 2 (70% of AC cases and 57.5% LLSCC cases). The association between IMP-3 and Ki-67 immunoexpression, AC dysplastic severity and LLSCC tumoral grade revealed no significant differences. The present results demonstrate that IMP-3 and Ki-67 immunoexpression are frequent in AC and in LLSCC. Moreover, these proteins could be involved in lower lip carcinogenesis process.

The relevance of miRNAs as promising biomarkers in lip cancer.

This study aimed to analyze the expression of miR-181b, miR-21, miR-31, and miR-345 in actinic cheilitis with and without epithelial dysplasia and lower lip squamous cell carcinomas, and to verify if the deregulated expression of these miRNAs would be indicative of malignant transformation. The sample was selected from formalin-fixed paraffin-embedded tissues of 19 actinic cheilitis without epithelial dysplasia, 32 actinic cheilitis with epithelial dysplasia, 42 lower lip squamous cell carcinomas, and 10 nonaltered oral mucosa of the lip. The microRNA (miR, miRNA) expression was quantified by real-time RT-PCR and the expression of the selected miRNAs among the groups of actinic cheilitis and lower lip cancer was compared by chi-square. A higher expression of miR-181b, miR-31, and miR-345 was found in actinic cheilitis without epithelial dysplasia in comparison to that in actinic cheilitis with epithelial dysplasia and with lower lip cancer. There were no differences in miR-21 expression between actinic cheilitis and lower lip cancer. Hierarchical clustering analysis showed a tendency for a downregulation of miR-181b, miR-21, miR-31, and miR-345 in most patients with lower lip cancers. The upregulation of miR-181b, miR-31, and miR-345 expression in actinic cheilitis without epithelial dysplasia and the decrease in the expression of these miRNAs in actinic cheilitis with epithelial dysplasia and in lower lip cancer are potential biomarkers of malignant progression. This miRNA signature can help to identify actinic cheilitis with potential to progress to lip cancer.

Reconstrucción de labio inferior con colgajo Karapandzic

Se presenta el caso de un paciente de 58 años de edad, que fue admitido en la unidad de cirugía oncológica, con diagnóstico de carcinoma de células escamosas en labio inferior. Presentaba defecto en labio inferior de espesor total, que involucra 2/3 de bermellón, de aproximadamente 7 x 4 cm, resultado de la resección quirúrgica oncológica de tumor que invadía dicha región. Se realiza reconstrucción de labio inferior con colgajo Karapandzic y avance de colgajo de mentón. Paciente egresa en condiciones satisfactorias.

STROMAL EXPRESSION OF TWIST AND PODOPLANIN IN ORAL TONGUE AND LOWER LIP SQUAMOUS CELL CARCINOMAS

Objective: To analyze podoplanin (PDPN) and Twist stromal immunoexpression profiles in a series of oral tongue squamous cell carcinoma (OTSCC) and lower lip squamous cell carcinoma (LLSCC) cases and evaluate their relationship with clinical-pathologic parameters. Study Design: PDPN and Twist immunoexpression were qualitatively evaluated by analyzing stromal fibroblast staining. The statistical associations and correlations with clinicopathologic characteristics were verified by the Mann-Whitney and Spearman tests. Results: In LLSCC, the male-to-female ratio was 3:1 with a mean age ± standard deviation (SD) of 66.8 ± 15.1 years, with the seventh decade being the most affected age group. In OTSCC, the male-to-female ratio was 3:1, with a mean age ± SD of 61.0 ± 12.7 years, with the sixth decade being the most affected age group. Regarding the clinical parameters in both lesions, there were no statistically significant results for PDPN; for Twist, stromal immunoexpression was statistically significant for cases in the earliest stages (I and II). In the Spearman test, a significant positive correlation was observed only in LLSCC cases (P

LOWER LIP SQUAMOUS CELL CARCINOMA IN A RENAL TRANSPLANT PATIENT: A CASE REPORT

Immunosuppressive therapy has as side effects the emergence of conditions and pathologies often with oral manifestations. We report a case of lower lip squamous cell carcinoma (SCC) in a renal transplant patient. A 60-year-old male patient, a farmer, attended the oral medicine service complaining of a mouth sore. In anamnesis, the patient reported being an alcoholic, receiving a renal transplant 15 years ago, and using immunosuppressive drugs. The intraoral examination revealed an ulcerated nodular lesion with hardened and raised edges, sessile and asymptomatic, rapidly growing and located on the lower lip. With the clinical diagnosis of SCC, an incisional biopsy was performed. Microscopic examination revealed malignant neoplasm epithelial cells exhibiting pleomorphism and cellular atypia invading the lamina propria of connective tissue, thus, the clinical diagnosis was confirmed. The patient was referred to oncology therapy where surgical excision was performed with safety margin. The patient is under follow-up with no signs of recurrence.

A case of lower lip squamous cell carcinoma in an HIV-infected patient

A case of lower lip squamous cell carcinoma in an HIV-infected patient

Modification in CLIC4 Expression is Associated with P53, TGF-β, TNF-α and Myofibroblasts in Lip Carcinogenesis.

Chloride intracellular channel-4 (CLIC4) is regulated by p53 and tumor necrosis factor-α (TNF-α), it is linked to the increase of transforming growth factor-β (TGF-β), and myofibroblastic differentiation in skin carcinogenesis. This study analyzed the immunoexpression of CLIC4, p53, TGF-β, TNF-α, and α-SMA in 50 actinic cheilitis (AC) and 50 lower lip squamous cell carcinoma (LLSCC). AC and LLSCC immunoexpression were categorized as score 1 (<5% positive cells), 2 (5-50%) or 3 (>50%). For CLIC4, nuclear and cytoplasmic immunostaining of epithelial cells was considered individually. For morphologic analysis, the World Health Organization criteria were used to epithelial dysplasia grade of ACs, and Bryne grading of malignancy system was applied for LLSCC. Higher nuclear CLIC4 (CLIC4n) and TGF-β were observed in ACs with low-risk of transformation, while cytoplasmic CLIC4 (CLIC4c), p53 and TNF-α were higher in the high-risk cases (p<0.05). In LLSCCs, CLIC4c was higher in cases with lymph node metastasis, advanced clinical stages, and histological high-grade malignancy. p53 expression was higher in high-grade LLSCCs, whereas TGF-β decreased as the clinical stage and morphological grade progressed (p<0.05). ACs showed an increased expression of CLIC4n and TGF-β, while CLIC4c and α-SMA were higher in LLSCCs (p<0.0001). Both lesions showed negative correlation between CLIC4n and CLIC4c, while in LLSCCs, negative correlation was also verified between CLIC4c and p53, as well as CLIC4c and TGF-β (p<0.05). Change of CLIC4 from the nucleus to cytoplasm and alterations in p53, TGF-β, TNF-α, and α-SMA expression are involved in lip carcinogenesis.

Detection of Occult Metastases in Patients with T1 and T2 Stage Lower Lip Squamous Cell Carcinomas after Positive Lymphoscintigraphy.

The aim of this study was to detect lower lip squamous cell carcinomas (SCC) that had metastasized to the lymph nodes and to evaluate if neck dissection was necessary for patients with T1 or T2-stage lip cancer after a sentinel lymph node biopsy (SLNB). The study was conducted as a prospective clinical study to detect occult neck metastases in patients with T1 or T2 stage SCC of the lower lip. Thirty-one patients were eligible and underwent echo-ultrasound, computer tomography, magnetic resonance and lymphoscintigraphy (LSG) as diagnostic procedures. LSG was performed on the same day as the surgical procedure, after intradermal injection of 37 Mbq Tc99m-Sn-colloid/mL at four peritumoral sites. In patients with positive LSG results, the sentinel lymph nodes were extracted surgically. The risk factors for cancer development were sun exposure and smoking. The highest accuracy for detecting lymph node enlargements was achieved with magnetic resonance imaging (MRI; 80.7%). LSG showed excellent sensitivity (100%) and negative predictive value (NPV; 100%). Overall, occult metastases were diagnosed with an SLNB in eight (25.8%) patients. According to the results, with great caution, we suggest that an SLNB is reasonable to initiate only for patients with positive sentinel nodes by positive LSG, to be used as a lower morbidity approach for selected patients with T1 and T2 stage cancers.