Clinical and pathological correlation of P53 expression in oral cancers.

In our study, we aimed to evaluate the overexpression of P53 in 155 oral squamous cell carcinomas and to correlate with various clinicopathological features like depth of invasion, lymph nodal involvement, and margin status, which affect the local recurrence and prognosis. This cross-sectional study included 155 oral squamous cell carcinoma patients who underwent surgical resection of primary and nodal disease. The histopathological and clinical features were noted. Immunohistochemical expression was reported, and other clinicopathological features were correlated. Statistical analysis was performed using SPSS software. In the present study, out of 155 patients, 127(81.9%) are males, and the majority are more than 50 years (55%). The most common site of oral carcinoma is the tongue, followed by buccal mucosa. An aberrant or mutational type of P53 was seen in 90 cases (58%), while the wild type was observed in 65 patients (42%). Expression of P53 is not similar in different sites of the oral cavity but is more frequently seen in the Gingiva, followed by retromolar trigone, lip, buccal mucosa, and tongue. There is a significant association between P53 expression and degree of tumor differentiation, T staging, and depth of invasion, involved margin, node positivity, and extranodal extension.

Possible role of ALDH1 and CD44 in lip carcinogenesis.

BACKGROUND: Lip squamous cell carcinoma (LSCC) accounts for 12% of all head and neck cancers. It is caused by chronic exposure to ultraviolet light solar radiation and related to previous actinic cheilitis (AC). This study aimed to investigate the immunostaining of the putative cancer stem cells (CSC) markers ALDH1 and CD44 in AC (n=30) and LSCC (n=20). ALDH1 positivity was found to be statistically higher in LSCC than in AC lesions (p=0.0045), whilst CD44 expression was statistically higher in AC than in LSCC lesions (p=0.0155). ALDH1+ cells in AC lesions were associated with specific clinical features: a younger age (<60 years old), the female gender, white skin, not smoking or consuming alcohol, and a fast evolution, and not associated with the chronic exposure to UV radiation (p<0.0001). CD44 positivity was associated with patients who were male, feoderm, smoked, consumed alcohol, underwent occupational exposure to UV-radiation, and demonstrated lesions with log-time evolution (p<0.0001). ALDH1 + cells were associated with mild dysplasia using a system from the World Health Organization (WHO), and with a low risk of malignant transformation, according to the binary system (p<0.0001). CD44+ cells were also associated with moderated dysplasia, according to the WHO system. In LSCC, ALDH1 + cells were positively associated with patients who were older (≥ 60 years old), smokers, and with those who consumed alcohol (p<0.0001). CD44 + cells in LSCC were associated with older (≥ 60 years old) patients as well, but also with female patients, white skin, non-smokers, and individuals who did not consume alcohol (p<0.0001), all of whom showed distinct patterns in pre- and malignant lesions of both markers. Additionally, in LSCC, both ALDH1 and CD44 staining were associated with smaller tumor sizes (T1/T2; p<0.0001). In summary, although both ALDH1 and CD44 were associated with the presence of dysplasia in AC lesions, the present findings suggest that ALDH1 and CD44 may be activated by different etiopathogenic pathways, predominantly in distinct steps of oral carcinogenesis. CD44 would thus be more significantly related to the potentially malignant lesion, while ALDH1 would be closely linked to malignancy.

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

Background: 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. Methods: 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. Results: 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). Discussion: 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.

Clinicopathological Analysis of Actinic Cheilitis: A Systematic Review with Meta-analyses.

BACKGROUND: This systematic review aimed to conduct a complete investigation of the demographic aspects, clinicopathological features, degrees of epithelial dysplasia, and malignant transformation rate of actinic cheilitis. METHODS: The study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the International Prospective Register of Systematic Reviews (CRD42020201254). A search without year and language restrictions was performed using PubMed/MEDLINE, Embase, Virtual Health Library, Scopus, Web of Science, and gray literature. Studies that provided information on patients with actinic cheilitis were included, excluding those with general information on other diseases or other types of cheilitis. Risk of bias was explored using the Joanna Briggs Institute tool. Narrative and quantitative data syntheses were performed using meta-analyses and subgroup analyses. Association tests were also performed. RESULTS: Thirteen studies (728 patients) were included. The most prevalent clinical signs were dryness (99%), blurred demarcation between the lip vermilion and skin (82%), scaling (69%), and atrophy (69%). Regarding epithelial dysplasia, a prevalence of mild dysplasia (34.2%), followed by moderate (27.5%), and severe (14.9%). The malignant transformation rate was 14%. Crusts, ulcerations, and erythematous areas were associated with lip carcinoma (p < 0.001), and scaling was associated with actinic cheilitis (p < 0.001). CONCLUSIONS: This study revealed several features of actinic cheilitis, providing an overview of the disease. It is suggested that new studies help develop policy guides for the standardization of clinical criteria, enabling more rigorous and homogeneous analysis of actinic cheilitis.

Reconstruction of Macrocheilia on the Lower Lip Through Bilateral Limited Excision and a Stepwise Single-Stage Approach (BLESS).

BACKGROUND: The surgical management of macrocheilia secondary to port-wine stains is complicated. OBJECTIVE: This study aimed to propose an innovative method for treating macrocheilia on the lower lip. METHODS: Patients who underwent the reconstruction of macrocheilia on the lower lip through the innovative approach were examined. Their preoperative and postoperative standard photographs were taken to evaluate the changes in lip length and thickness. The scores on Vancouver scar scale (VSS) and visual analog scale (VAS) were evaluated. RESULTS: Thirty-two patients who underwent the reconstruction of macrocheilia were examined. A follow-up of 12.2 months (6-36 months) was conducted. The lower lip contour and the mentolabial groove were reconstructed to normal appearance. The lip length was shortened from 5.38 ± 0.49 cm pretreatment to 4.59 ± 0.30 cm posttreatment (p = .016). The exposed vermilion was shortened from 2.05 ± 0.48 cm to 1.26 ± 0.12 cm posttreatment (p < .01). The mean VSS and VAS scores were 2.2 ± 1.5 and 8.4 ± 1.3, respectively. CONCLUSION: The bilateral limited excision and stepwise single-stage approach were safe and effective for reconstructing prominent macrocheilia on the lower lip. The technique was also easy to command for the beginners.

Lip Squamous Cell Carcinoma With Spontaneous Eruption and Drainage.

A 69-year-old woman with a newly diagnosed squamous cell carcinoma of the lower lip mucosa presented 3 days after initiating neoadjuvant immune checkpoint blockade immunotherapy with redness and swelling of the tumor site. What is your diagnosis?

Lower lip basal cell and squamous cell carcinomas: a reappraisal of the similarities and differences in clinical presentation and management.

Basal cell carcinoma and squamous cell carcinoma are the two most common types of carcinomas, affecting a total of 5.4 million people each year in the United States. Sun-exposed areas, especially the face and nose, are most affected given the strong association between these carcinomas and ultraviolet radiation. Less research has been done surrounding carcinomas of the lip, despite the significant aesthetic and functional importance of this area. Although lip carcinomas tend to follow a classic, unique distribution pattern that favors basal cell carcinoma on the upper lip and squamous cell carcinoma on the lower lip, more cases of lower lip basal cell carcinoma are being reported, warranting further educational awareness to differentiate carcinomas of the lower lip. In this article, we provide an updated overview of the risk factors, presentations, differential diagnoses, metastatic risks, evaluation, management guidelines, and outcomes of lower lip carcinoma. Of note, recent advances in imaging modalities are beginning to show promise as a non-invasive, affordable, and rapid way to detect and stage tumors. We conclude that increased clinical awareness and investigation of lower lip carcinoma is needed to improve early intervention, as a delayed diagnosis can rapidly alter the management and outcomes of lip carcinomas.

Laminin Immunostaining in Biopsies as a Useful Biomarker of Early Invasion in Actinic Cheilitis and Differential Diagnosis Between Actinic Cheilitis and Lip Cancer: New Insights.

BACKGROUND: Squamous cell carcinoma of the lip (LSCC) and oral cavity can be life-threatening if not diagnosed early. Precancerous lesions like actinic cheilitis (AC), can transform into LSCC. Laminin is a fundamental component for basement membrane (BM) and its integrity may prevent neoplastic invasion. Therefore, laminin immunostaining of BM may be useful in identifying early invasion in actinic cheilitis and thus in the differential diagnosis between AC and invasive LSCC or high-grade epithelial dysplasia (ED). MATERIALS AND METHODS: Biopsies from 46 patients with oral lesions were histologically analyzed and immunohistochemically stained for laminin-1. RESULTS: AC was diagnosed in 34 patients and LSCC in 12 patients, including 3 patients with AC and concomitant high-grade ED/in situ carcinoma. Laminin-1 immunostaining revealed intense and linear expression of the BM in AC with low-grade ED. Loss of laminin expression was observed in LSCC. Intracellular laminin expression in parabasal cells was noted in AC with high-grade ED/in situ carcinoma. CONCLUSION: Laminin immunostaining could be useful in identifying AC cases suspected of early invasion. It could also contribute to the histopathological differential diagnosis between AC with low- and high-grade ED and between AC and invasive LSCC. The findings of this study provide new insights into the mechanism involved in the progression process of AC into LSCC, encouraging preclinical studies that may document the stochastic role of laminin in this process.

An unusual case of pediatric embryonal rhabdomyosarcoma with subsequent diagnosis of neurofibromatosis type 1.

A 10-month-old girl presented with a 4-month history of a rapidly growing lesion on the lower lip. Initial assessment and Doppler ultrasound supported a diagnosis of pyogenic granuloma. However, emergent biopsy revealed an embryonal rhabdomyosarcoma, a highly malignant tumor commonly associated with cancer-susceptible syndromes including neurofibromatosis type 1 (NF1). Despite having no apparent clinical features of NF1 at initial presentation, she was later found to have multiple café-au-lait spots and a subsequent diagnosis of NF1 was made.

Laser Therapy for the Treatment of Actinic Cheilitis: A Systematic Review.

Actinic cheilitis (AC) is a chronic inflammation of the lip considered an oral, potentially malignant disorder associated with an increased risk of lip squamous cell carcinoma (SCC) development. Controversies surrounding current therapeutic modalities of AC are under debate, and the implications of laser treatment have not been specifically investigated through a systematic review design. The present study aims to evaluate the degree of evidence of laser for the treatment of AC in terms of efficacy and safety. We searched for primary-level studies published before January 2022 through MEDLINE/PubMed, Embase, Web of Science, Scopus and CENTRAL, with no limitation in publication language or date. We evaluated the methodological quality and risk of bias of the studies included using the updated Cochrane Collaboration's tool for assessing risk of bias (RoB-2). Twenty studies (512 patients) met our eligibility criteria. Laser therapy showed a complete clearance of AC in 92.5% patients, with a maximum recurrence rate of 21.43%, and a very low frequency of malignant transformation to SCC (detected in only 3/20 studies analyzed). In addition, cosmetic outcomes and patient satisfaction were described as excellent. In conclusion, our findings indicate that laser therapy is a high efficacy approach to AC.

An ulcerating plaque of the lower lip.

A middle-aged man presented to a cancer centre with a painful, ulcerating plaque of the lower lip, which had been diagnosed as squamous cell carcinoma. Computed tomography revealed increased focal metabolic activity in the lip, and histology revealed spirochaetes.

Epithelial-mesenchymal transition modulates lower lip carcinogenesis and promotes cancer progression.

OBJECTIVE: To investigate and compare the immunoexpression of E-cadherin, α-SMA, TGF-ß and Snail proteins between cases of actinic cheilitis (AC) and squamous cell carcinoma of the lower lip (LLSCC). STUDY DESIGN: E-cadherin, α-SMA, TGF-ß and Snail antibody immunostaining was analyzed semiquantitatively in 54 AC cases and in 49 LLSCCs. The cases were classified as low and high expression for analysis of the association with clinicopathological variables and overall survival (OS) and disease-free survival (DFS) rates. RESULTS: High expression of E-cadherin (cytoplasmic) (p = 0.001) and α-SMA (p < 0.001) was identified in LLSCCs, as well as low expression of TGF-ß in LLSCCs (p < 0.001) and high expression of Snail in AC cases (p = 0.006). Survival analysis revealed that high expression of α-SMA at the tumor invasion front, a network immunostaining pattern of this protein, and high expression of TGF-ß in tumor buds were significantly associated with poor OS (p < 0.05). There was a higher risk of death among LLSCC cases with high expression of α-SMA (HR = 5.90, p = 0.03). High expression of TGF-ß in tumor buds was significantly associated with poor DFS (p = 0.007) and with a higher risk of negative outcomes for DFS (HR = 4.44, p = 0.014). CONCLUSIONS: The present results suggest the potential involvement of dysregulation of proteins associated with epithelial-mesenchymal transition in the modulation of lip carcinogenesis and greater aggressiveness of LLSCC.

The Use of Vastus Lateralis Muscle Flap for Functional Lip Reconstruction.

BACKGROUND: Total or near-total lip defects poses a serious challenge to a reconstructive surgeon with static procedures not providing desired functional and aesthetic outcomes. The dynamic lip reconstructive methods using functional muscles have become a current issue in recent years showing admirable results. This study present 3 cases of successful total and near-total lip reconstruction are presented using vastus lateralis muscle. METHODS: This is a retrospective analysis of a consecutive series of 3 patients (2 men and 1 woman) aged 44 to 56 years (mean) who had resection of extensive squamous cell carcinoma 2 had both upper and lower lip involved and 1 had lower lip involvement only. After resection patients had near total full thickness lower lip defect and 40% upper lip defect. The innervated vastus lateralis muscle free flap was transferred to the lip and end-to-end vascular anastomosis on the facial artery and end-to-side to internal jaguar vein was performed. The marginal mandibular branch of the facial nerve was used for nerve coaptation. The inner and outer surfaces of the flaps were grafted with a thick-split-thickness skin graft. Drooling rating scale and patient and observer scar assessment scale as well as electromyography were performed to evaluate oral competency and aesthetic outcome. RESULTS: All patients underwent single stage near-total lower lip and 2 had part of upper lip reconstruction successfully and survived the surgical operation. One patient lost the skin graft and was managed consecutively and muscle granulated and healed. Two patients underwent radiation therapy and 1 died before starting radiation due to other unnatural causes. The 2 patients achieved perfect oral sphincter competence without drooling and at 9months postoperative demonstrated successful reinnervation of the vastus lateralis muscle. CONCLUSIONS: This study demonstrates that lip reconstruction using an innervated vastus lateralis muscle free flap is a reliable method, providing a functional lip.

Relevance of perimarginal nodes for head and neck cancer.

OBJECTIVE: To estimate the prevalence of metastasis in the perimarginal nodes (PMNs) (also known as perifacial, preglandular and retroglandual nodes) in head and neck cancer. METHODS: We recruited 136 patients affected by cancers of the oral cavity, lip, oropharynx, skin and by cáncer of unknown primary (CUP), who were candidates for level IB dissection. PMNs were identified and sent separately for histological analysis. Correlation between metastasis to the PMNs and characteristics of the primary tumour were reported. RESULTS: The incidence of metastasis was 17% from oral cancer, 50% from lip cancer and 12.5% from skin cancer. No metastases were reported for oropharynx cancer or CUP. The only factor that correlated with the incidence of metastases was origin of the tumour from the upper part of oral cavity. CONCLUSION: PMNs represent a frequent site of metastasis in oral and lip cancers. In cancer of the oropharynx, their involvement has not been not reported, while their role in skin cancers remains to be clarified.

Recurrent squamous cell carcinoma of the lower lip: salvage surgery outcome.

Squamous cell carcinoma (SCC) of the lip is one of the most commonly occurring oral cancers, mainly involving the lower lip. Despite a good prognosis in cases of early detection, survival rates drop dramatically in the presence of recurrence. While there are many studies in the literature regarding the management of primary tumours, the rate of recurrence in lower lip SCC is low and therefore there are few data and articles about them. We retrospectively reviewed patients affected by recurrent SCC of the lower lip treated surgically from 2011 to 2019 in a single centre. Data and results were compared with those in the literature. A total of 16 patients (mean [range] age: 78.1 [62-93] years) were eligible for inclusion. The disease-free survival rate at 2 and 5 years was 29.6% and the overall survival rate at 2 and 5 years was 14.4%. A significantly higher rate of failure and a worse prognosis was observed in patients with neck involvement. The prognosis of recurrent lower lip SCC is unfavourable with extremely low survival rates. This issue is probably linked to the oncological pathology but also to the advanced age of most patients, the presence of several comorbidities and, consequently, the high risk of perioperative mortality. For this reason, the analysis of data sets reported in the literature may help the surgeon in the management of recurrences and selection of patients.