An Evaluation of High-Risk HPV in Squamous Cell Carcinomas of the Lip in a South African Cohort.

BACKGROUND: To determine the prevalence of HR-HPV in a series of lip SCC from South African patients, using currently accepted HPV-testing methodologies and to define the clinical and histomorphologic features of HPV-associated lip SCC. METHODS: Fifty SCC of lip and 50 control cases were tested for HR-HPV using p16 and HR-HPV DNA PCR. p16-equivocal/positive and HPV DNA PCR-positive SCC were further evaluated for the expression of HPV-16 and HPV-18 mRNA transcripts using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) to confirm transcriptionally active HPV. RESULTS: p16 was positive in 22% (n = 11) and equivocal in 4% (n = 2) of the SCC. One p16-positive case showed positivity for both HPV-16 DNA and HPV-16 E6/E7 mRNA transcripts (HPV prevalence rate of 2%). The HPV-positive case was non-keratinizing and occurred in an 80-year-old female. The two p16-equivocal cases were HR-HPV DNA positive and mRNA PCR negative. p16 was found to have a positive predictive value of 9%. CONCLUSION: Findings from our cohort of lip SCC suggest that HR-HPV may have an insignificant role in the pathogenesis of SCC at this site. Due to its low ppv, p16 is insufficient to establish HR-HPV infection in SCC of the lip. The combination of p16 and DNA PCR appears to correlate with the presence of transcriptionally active virus. HPV E6/E7 mRNA detection is the gold standard for identifying HR-HPV. mRNA testing is not widely available in sub-Saharan Africa due to technical and financial constraints; however, the test appears to be of great value in p16-equivocal lip SCC.

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.

BACKGROUND: 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). METHODS: Samples of ACs, LLSCCs, and control group (CG) were prepared by tissue microarray (TMA) for immunohistochemical TGF-ß, 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). RESULTS: 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-ß (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). CONCLUSIONS: Our findings show the possible role of MFs, collagen fibers, and elastosis areas in the lip carcinogenesis process.

Reconstruction of Squamous Cell Carcinoma on Oral Commissure With Hatchet-Shaped Flap.

The mouth is a unique and prominent element of the lower face. Given the complex anatomy, aesthetic appearance, and function of the oral commissure, its reconstruction due to various causes presents a significant challenge for surgeons. Squamous cell carcinoma (SCC) of the lip is the most common type of oral cancer, accounting for approximately 25% to 30% of all oral cancers. Wide excision is the treatment of choice, and the prognosis is generally favorable. We encountered a case of SCC of the right oral commissure in a 69-year-old man. We designed a hatchet-shaped flap to minimize anatomical disruption and, as a result, achieved satisfactory outcomes in terms of both functionality and aesthetics.

Functional and esthetic reconstruction of composite lower lip defects with a motor-innervated chimeric facial artery buccinator myomucosal-submental island flap.

OBJECTIVE: This study aimed to assess the functional and esthetic outcomes of a chimeric innervated buccinator myomucosal-submental island flap (BMM-SIF) for large composite lower lip reconstruction. METHODS: This retrospective study included five patients who underwent lower lip tumor resection and BMM-SIF reconstruction at the Hospital of Stomatology, Sun Yat-sen University, between August 2021 and February 2023. Lip function was evaluated using water leakage, cheek puffing tests, and superficial electromyography. Lip appearance was observed using photographs and evaluated through subjective interviews. Donor-site conditions, including facial symmetry and mouth opening, were monitored. RESULTS: All the BMM-SIFs survived. Drooling was the main complication observed shortly after surgery. The water leakage test showed complete oral competence for liquid holding in the 7th month; however, moderate air leakage was present in two patients. Electromyography revealed myoelectric signals from the innervated buccinator at the recipient site. Facial expression and food intake were typically managed. The shape and projection of the vermilion were harmonious and satisfactory for each patient. Neither microstomia nor mouth opening limitation was observed, with an average inter-incisor distance of 37.25±4.4 mm. CONCLUSION: Chimeric motor-innervated BMM-SIF effectively reconstructed large full-thickness lower-lip defects with satisfactory functional and esthetic outcomes.

Case of eccrine chondroid syringoma of the upper lip.

Chondroid syringoma (CS) is a benign, slow-growing mixed tumour that arises from the sweat glands and usually presents in the head and neck area. Histopathological examination is important for proper diagnosis, as CS is often confused with epidermal cysts due to its rare presentation. This article presents a man in his 40s with a right upper lip mass that emerged 6 months prior to presentation. An intraoral surgical excision was performed and the histopathological analysis revealed solid epithelial cells that formed multiple, non-branching ducts lined by cuboidal epithelium. Cystic spaces were filled by heterogeneous eosinophilic material embedded in chondromyxoid stroma. Histopathology identified the lesion as an eccrine-variant CS. The patient recovered well.

Squamous cell carcinoma of lip: Clinical feature analysis and suggestion of reconstruction algorithm.

Reconstruction of lips after squamous cell carcinoma (SCC) removal should restore functional and aesthetic roles; however, it remains a challenge. In this study we describe the clinical features of lip SCC and suggest a reconstruction algorithm. We retrospectively analyzed 34 patients with lip SCC who underwent reconstruction after Mohs micrographic surgery between January 2006 and March 2022. The mean age of the patients was 70.2 years. Seven tumors were on the upper lip and 27 tumors were on the lower lip. Twenty-five defects were located on the mucosal lip, eight defects involved both the mucosal and cutaneous lips, and one defect was confined to the cutaneous lip. Eighteen defects were smaller than 50% of the total lip size, and 16 were larger than 50%. Primary closure was mostly performed for defects smaller than 50% of the lip size (9/18 cases), and local flap, according to the location and size of the defects, was performed for larger defects. Thirteen patients experienced postoperative complications but improved within 1 year after surgery, except for one patient. We suggest a reconstruction algorithm with a 50% cut-off value. Defects smaller than 50% of the lip size could be reconstructed by primary closure. Even larger defects could be reconstructed by creation of a local flap from the remaining adjacent tissue with minimal postoperative complications.

Unresectable infantile myofibroma discovered in utero.

The authors present a case of a proliferative nodule located beneath an infant's lower lip that was initially discovered on prenatal ultrasound and fetal magnetic resonance imaging (MRI). Biopsy revealed a smooth muscle actin-positive spindled cell proliferation with hemangiopericytoma-like vessels consistent with infantile myofibromatosis (IM). Since the location prevented surgical management, the clinicians opted to observe the lesion. Ultimately, the lesion fully regressed on its own confirming conservative management is an option for isolated IM.

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.

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?

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.

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.