Classificatory updates in verrucous and cuniculatum carcinomas: Insights from the 5th edition of WHO-IARC head and neck tumor classification.

The International Agency for Research on Cancer (IARC) and World Health Organization (WHO) collaboratively produce the 'WHO Blue Books' essential tools standardizing the diagnostic process for human cancers. Regular updates in this classification accommodate emerging molecular discoveries, advances in immunohistochemical techniques, and evolving clinical insights. The 5th edition of the WHO/IARC classification of head and neck tumors refines the 'Oral Cavity and Mobile Tongue' chapter, including sections for non-neoplastic lesions, epithelial tumors, and tumors of uncertain histogenesis. Notably, the epithelial tumors section is rearranged by tumor behavior, starting with benign squamous papillomas and progressing through potentially malignant oral disorders to oral squamous cell carcinoma (OSCC). The section on OSCC reflects recent information on epidemiology, pathogenesis, and histological prognostic factors. Noteworthy is the specific categorization of verrucous carcinoma (VC) and carcinoma cuniculatum (CC), both associated with the oral cavity and distinct in clinical and histologic characteristics. This classification adjustment emphasizes the oral cavity as their predominant site in the head and neck. Designating specific sections for VC and CC aims to provide comprehensive insights into these unique subtypes, elucidating their clinical features, distinct histological characteristics, prevalence, significance, and clinical relevance. By categorizing these subtypes into specific sections, the 5th edition of the WHO classification aims to provide a more nuanced and detailed account, enhancing our understanding of these specific variants within the broader spectrum of head and neck tumors.

Surgical management of a huge oral verrucous carcinoma: A case report and review of the literature.

Verrucous carcinoma is a well-recognized low-grade variant of squamous cell carcinoma. Cutaneous, oral, and anogenital forms exist. Exposure to persistent chronic irritation, inflammation, and repeated injury, as well as carcinogenic agents such as human papillomavirus infection, smoking, and alcohol use, are established risk factors. These neoplasms occur mostly in the oral cavity. The usual extraoral sites include the larynx, esophagus, genitals, and perineum. It is an extremely uncommon site of occurrence for the extraoral chin region. This unusual location makes the index case unique. Other uncommon sites reported include finger and foot. Case studies of verrucous carcinoma with huge tumor sizes are rare. Although it can be destructive locally, verrucous carcinoma typically does not spread to distant sites. Wide surgical excision with free margins is the most common treatment approach with a favorable prognosis. These tumors are likely to recur if they are incompletely excised, and recurred lesions tend to be more aggressive clinically as compared to their original counterparts. Herein, the authors describe a case of a huge oral verrucous carcinoma localized on the chin of a 43-year-old female patient. The clinical course, diagnostics, and proposed treatment have been discussed with the existing available literature.

Multiple verrucous squamous cell carcinomas developing on chronic hidradenitis suppurativa lesions-a rare case report from Romania.

Hidradenitis suppurativa (HS) is an uncommon, recurrent, inflammatory skin illness of the apocrine glands, with a questionable etiology. The disease is associated with a multitude of comorbidities, of which the appearance of malignancy is the most important. Squamous cell carcinoma is considered the most frequent malignancy that can appear in HS. A case report of a 72 years-old male is presented, who suffered over 40 years from persistent, extensive hidradenitis suppurativa in stage Hurley III, on the buttocks and perianal region, who recently presented two verrucous semi-consistent, skin-colored tumors on the right buttock. The biopsy and histopathological exam confirmed a verrucous type of squamous cell carcinoma. There are about 100 reported clinical cases of squamous cell carcinoma complicating hidradenitis suppurativa in the literature, but only a few describe a verrucous carcinoma as a clinical form. The particularity of the case is the rare appearance of multiple verrucous types of squamous cell carcinomas in a male patient, in Hurley Stage III, with a long HS disease duration, appearing on the perianal/gluteal region, being the first case report in our country. We suggest that a tumor screening should be done for all the patients with HS who have these risks.

Photodynamic therapy in the treatment of the right buccal mucosa verrucous carcinoma: a case report and literature review / 口腔疾病防治

Objective@#To explore the photodynamic treatment method and therapeutic effect of oral verrucous carcinoma and to provide a reference for the clinic.@*Methods@#This study follows the requirements of medical ethics. This paper summarized the photodynamic treatment of an oral verrucous carcinoma with a diameter of approximately 2.5 cm in the right buccal mucosa and retrospectively analyzed the characteristics and treatment of oral verrucous carcinoma and the photodynamic treatment of potential malignant lesions of the oral mucosa through a review of the literature.@*Results@#After four rounds of photodynamic therapy, the size of the right buccal lesion was significantly reduced. After 6 months of follow-up, the white verrucous hyperplasia of the right buccal mucosa had completely subsided, and there was no obvious scar formation. Three years after treatment, there was no recurrence of the lesion in the right buccal mucosa and no obvious scar formation in the treated area. The degree of mouth opening was 3 fingers, and there was no lymph node enlargement in the bilateral submandibular, submental or neck. The literature review shows that oral verrucous carcinoma is a rare subtype of squamous cell carcinoma with the characteristics and biological behaviors of slow growth, low malignancy, and rare metastasis. Surgery is the preferred treatment, but there are some limitations. Photodynamic therapy is a minimally invasive, repeatable treatment with mild adverse reactions. In recent years, photodynamic therapy has been gradually applied for the treatment of potential malignant disorders of the oral mucosa and early oral squamous cell carcinoma and has achieved positive results, but it has not been reported for the treatment of oral verrucous cancer@*Conclusion@#Photodynamic therapy is a new option for nonsurgical resection of oral verrucous carcinoma.

Protocol for Treatment of Oral Verrucous Carcinoma - A Systematic Review and Meta-Analysis.

Background: The objective of this study is to provide a structured protocol for the treatment of verrucous carcinoma (VC) based on size, bone invasion, recurrence and whether neck dissection is necessary or not. In addition, the study evaluates the probability of a wrong histopathological diagnosis. Data Sources: A search was conducted in the Cochrane Library, PubMed and Google from January 1962 to October 2022 by using MeSH terms and keywords. Studies reporting treatment modalities for VC and different histopathological diagnoses after excision of the lesion were selected except case reports and review articles. Study Eligibility Criteria: Thirteen articles were selected. Six hundred and thirty cases of VC were treated by surgery, surgery + neck dissection, radiotherapy, chemotherapy and combination therapy. Statistical analysis revealed surgical treatment as a preferred option. Despite being enlarged, the lymph node was negative for metastasis. So, in OVC cases neck dissection adds only unnecessary morbidity to patients. Participants and Interventions: Radiotherapy or chemotherapy can be used to downstage the disease. 23.3% of cases reported wrong histopathology diagnosis. Study Appraisal and Synthesis Methods: Patients treated for squamous cell carcinoma (SCC) will only experience unnecessary morbidity unless the correct diagnosis is made between VC and hybrid VC. Irrespective of size VC does not metastasise until there are no foci of SCC. Conclusions: Surgical excision of T1- and T2-sized lesions can be performed under local anaesthetic as a biopsy procedure. T3 or T4 lesion can be resected with a safe margin. If it comes as hybrid VC or VC with close margin (0.5 cm, <0.5 cm), neck dissection and further margin should be excised as a second procedure respectively.

Squamous cell carcinoma of the neovagina 47 years after gender-affirming surgery.

A 74-year-old transgender female presented with urinary difficulty and a painful lesion at her neo-vagina, 47 years after undergoing gender-affirming vaginoplasty. Initial biopsy reported Low-Grade Squamous Intraepithelial Lesion (LGSIL), while MRI revealed no inguinal or pelvic lymphadenopathy. Patient underwent partial neo-vaginectomy with wide local excision and formal urethroplasty. Pathology revealed verrucous carcinoma of the neovagina, a rare neoplasm in transgender female patients. This case highlights the importance of considering squamous cell carcinoma in the differential diagnosis of patients presenting lesions at neo-vagina and the need of screening methods for early detection of such neoplasms.

[Marjolin's ulcer associated with verrucous carcinoma in an immunocompromised patient]. / Úlcera de Marjolin asociada a carcinoma verrugoso en paciente inmunocomprometido.

Background: Marjolin's ulcer is the malignant degeneration of any chronic wound, with a latency period from tissue injury to variable malignant transformation that may occur up to 30 years later. Among the associated neoplasms, squamous cell carcinoma (SCC) is the predominant lineage in up to 71% of cases. The verrucous carcinoma variant has been estimated to have a low presentation, being described in the literature as 2% of all SCC and reported anecdotally in immunosuppressed patients, which justifies the objective of this publication. Clinical case: 65-year-old female patient with a history of being a carrier of human immunodeficiency virus (HIV) infection, who presented a verrucous carcinoma associated to a Marjolin ulcer secondary to herpes zoster and infection of soft tissues in the right leg, with a latency period of 10 years from the initial infectious process to histopathological confirmation. Conclusions: The finding of a verrucous carcinoma on a Marjolin ulcer has been little described in literature, with a lower incidence in the context of a patient with a history of being a carrier of HIV infection, finding 7 case reports, the oldest from 1998. For this reason, it is important to have diagnostic suspicion, to carry out an adequate study protocol and always making clinical-pathological correlation, in order to establish timely and individualized treatment.

Introducción: la úlcera de Marjolin es la degeneración maligna de cualquier herida crónica, con un periodo de latencia desde la lesión tisular a la transformación maligna variable que puede presentarse hasta 30 años después. De las neoplasias asociadas, el carcinoma espinocelular es la estirpe predominante hasta en 71% de los casos. La variante de carcinoma verrugoso se ha estimado con una presentación baja, pues ha sido descrito en la literatura como el 2% de todos los carcinomas espinocelulares y reportado de manera anecdótica en pacientes inmunosuprimidos, lo que justifica el objetivo de esta publicación. Caso clínico: mujer de 65 años con el antecedente de ser portadora de infección por virus de inmunodeficiencia humana (VIH), que presentó un carcinoma verrugoso asociado a una úlcera de Marjolin secundaria a herpes zóster e infección de tejidos blandos en pierna derecha, con un periodo de latencia de 10 años desde el proceso infeccioso inicial hasta la confirmación histopatológica. Conclusiones: el hallazgo de un carcinoma verrugoso asentado sobre una úlcera de Marjolin ha sido poco descrito en la literatura, con una menor incidencia en el contexto de un paciente con antecedente de ser portador de infección por VIH, ante lo cual encontramos 7 reportes de caso, el más antiguo de 1998. Por este motivo es importante contar con la sospecha diagnóstica, para poder hacer un protocolo de estudio adecuado y siempre haciendo correlación clínico-patológica, con la finalidad de instaurar un tratamiento oportuno e individualizado.

The stromal immunoexpression of CLIC4 may be related to the difference in the biological behavior between oral squamous cell carcinoma and oral verrucous carcinoma

Background: Oral squamous cell carcinoma (OSCC) has high morbidity and mortality rates while oral verrucous carcinoma (OVC), an uncommon variant of OSCC, exhibits a distinct biological behavior. CLIC4 protein plays a role in the cell cycle and apoptosis regulation and participates in the myofibroblasts transdifferentiation process, which are the main cells of the tumor stroma. This study analyzed the immunoexpression of CLIC4 and α-SMA in 20 OSCC cases and 15 OVC cases. Material and methods: A semiquantitative analysis of CLIC4 and α-SMA immunoexpression was performed in the parenchyma and stroma. Nuclear and cytoplasmic reactivity was analyzed separately for the CLIC4 immunostaining. The data were submitted to Pearson's chi-square and Spearman's correlation tests (p ≤ 0.05). Results: In the CLIC4 analysis, there was a significant difference in the immunoexpression of this protein between OSCC and OVC stroma (p < 0.001). It was observed a higher expression of α-SMA in the OSCC stroma. There was a positive and significant correlation between CLIC4 and α-SMA immunoexpression in the OVC stroma (r = 0,612; p = 0,015). Conclusions: The decrease or absence of nuclear CLIC4 immunoexpression in the neoplastic epithelial cells and the increase of its expression in the stroma may influence the difference in biological behavior between OSCC and OVC. (AU)

Treatment of Laryngeal Verrucous Carcinoma: 28-Year Retrospective Cohort Study and Literature Review.

Objective: Laryngeal verrucous carcinoma (LVC) comprises 1% to 4% of all laryngeal tumors. Although controversial, surgery has been the mainstay of treatment, due to concern about anaplastic transformation with radiotherapy. We aimed to study LVC patients to identify treatment patterns for primary and recurrent diseases. Study Design: Retrospective cohort study. Setting: Tertiary referral center. Methods: Patients with a pathological diagnosis of LVC treated over a 28-year period were included. Baseline demographics, and treatment outcome measures including 5-year laryngeal preservation rates (LPR), overall survival (OS), and recurrence-free survival (RFS) were included. A literature review of published studies within the same study period was also completed. Results: Thirty-two patients were included in the analysis (median age 61.5 years, 93.8% [30/32] male). Twenty-three patients had T1 disease, and 9 had T2 disease with no evidence of regional or metastatic disease. The most common presenting symptom was hoarseness (93.8%) and the majority within the glottis 81.3% (26/32). Twenty-nine patients underwent primary surgery only (28 local excisions, 1 vertical partial laryngectomy) meanwhile 3 underwent local excision with postoperative radiotherapy. LPR, OS, and RFS at 5 years were 95.8%, 90.1%, and 80.6%, respectively. Our literature review identified 23 previous studies, mostly single-institution retrospective case series. Our study was the largest Canadian study in the literature to date. Conclusion: All LVC patients were treated with primary surgery, consistent with the current literature with excellent 5-year OS and LPR. There was no consensus on the treatment of recurrent disease. Future prospective multicenter studies are warranted to further study this rare disease population.

Elective Neck Dissection for cT1-4 N0M0 Head and Neck Verrucous Carcinoma.

OBJECTIVE: To investigate the survival benefit of elective neck dissection (END) over neck observation in cT1-4 N0M0 head and neck verrucous carcinoma (HNVC). STUDY DESIGN: Retrospective cohort study. SETTING: The 2006 to 2017 National Cancer Database. METHODS: Patients with surgically resected cT1-4 N0M0 HNVC were selected. Linear, binary logistic, Kaplan-Meier, and Cox proportional hazards regression models were utilized. RESULTS: Of 1015 patients satisfying inclusion criteria, 223 (22.0%) underwent END. The majority of patients were male (55.4%) and white (91.0%) with disease of the oral cavity (67.6%) classified as low grade (90.0%) and cT1-2 (81.8%). The minority of ENDs (4.0%) detected occult nodal metastases. The rate of END increased from 2006 to 2017 for both cT1-2 (16.3% vs 22.0%, p = .126, R2 = 0.405) and cT3-4 (41.7% vs 70.0%, p = .424, R2 = 0.232) disease but these trends were not statistically significant. Independent predictors of undergoing END included treatment at an academic facility (adjusted odds ratio [aOR]: 1.75, 95% confidence interval [CI]: 1.19-2.55), cT3-4 disease (aOR: 3.31, 95% CI: 2.16-5.07), and tumor diameter (aOR: 1.09, 95% CI: 1.01-1.19) (p < 0.05). The 5-year overall survival (OS) of patients treated with and without END was 71.3% and 70.6%, respectively (p = .661). END did not significantly reduce the 5-year hazard of death (adjusted hazard ratio: 1.25, 95% CI: 0.91-1.71, p = .172). END did not significantly improve 5-year OS in univariate and multivariate analyses stratified by several patient, facility, tumor, and treatment characteristics. CONCLUSION: END does not confer an appreciable survival benefit in HNVC, even after stratifying univariate and multivariate analyses by several patient, facility, tumor, and treatment characteristics. LEVEL OF EVIDENCE: Level 4.

Management of huge verrucous carcinoma of lower lip: A case report at a tertiary hospital in northern Tanzania.

Key Clinical Message: Well-differentiated variant of squamous cell carcinoma. Slow growing, exophytic, cauliflower-like growth easily confused with a viral wart. Cutaneous, anogenital, and oral variant exist. Risk factors for oral variant include alcohol and smoking. Histopathologically exhibits lobules with a pushing margin and blunt borders. Abstract: Verrucous carcinoma (VC) is a low-grade variant of squamous cell carcinoma with specific clinicopathologic features and good prognosis when affecting skin. We report the case VC of lip in a-70-year-old lady. She underwent surgical excision with excellent outcomes. A brief review of the literature is provided.

A Rare Case of Verrucous Carcinoma and Trichoblastoma of the Neck: A Case Report and Literature Review.

Verrucous carcinoma (VC) is a variant of cutaneous squamous cell carcinoma. This phenomenon mainly affects the oropharynx, genitalia, and soles of the feet. VC is a well-defined, exophytic, cauliflower-like growth that is warty in nature. Trichoblastoma is a benign epithelial tumor composed of follicular germinative cells. It presents as a small, smooth, non-ulcerated, skin-colored nodule on the scalp, neck, thigh, and perianal regions. The dual presentation of verrucous carcinoma and trichoblastoma of the neck is rare. Though treatment can be achieved through surgical resection, early detection offers a good prognosis. We present the case of a 54-year-old homeless male who presented with an unusual neck mass that was initially misidentified as an abscess. Surgical debridement was performed, and histopathological analysis revealed the presence of a rare combination of VC and trichoblastoma. This report highlights the challenges of this rare presentation, which may be overlooked or misdiagnosed as an abscess.

Surgical Treatment of Penile Verrucous Squamous Cell Carcinoma in an HIV-Infected Patient: A Case Report.

Although uncommon, penile carcinoma can be a debilitating disease with various causes, and cancer is a significant contributor to morbidity and mortality in individuals infected with HIV. Verrucous carcinoma, a subtype of epidermoid carcinoma, is typically slow-growing and has a low propensity to metastasize. We present a case study of a 55-year-old HIV-positive patient with a massive squamous cell carcinoma of the penis that had been developing for over two years. To treat the condition, the patient underwent a total penectomy, perineal urethrostomy, and bilateral inguinal lymphadenectomy.

Crafting a prognostic nomogram for the overall survival rate of cutaneous verrucous carcinoma using the surveillance, epidemiology, and end results database.

Background: The aim of this study was to establish and verify a predictive nomogram for patients with cutaneous verrucous carcinoma (CVC) who will eventually survive and to determine the accuracy of the nomogram relative to the conventional American Joint Committee on Cancer (AJCC) staging system. Methods: Assessments were performed on 1125 patients with CVC between 2004 and 2015, and the results of those examinations were recorded in the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly divided at a ratio of 7:3 into the training (n = 787) and validation (n = 338) cohorts. Predictors were identified using stepwise regression analysis in the COX regression model for create a nomogram to predict overall survival of CVC patients at 3-, 5-, and 8-years post-diagnosis. We compared the performance of our model with that of the AJCC prognosis model using several evaluation metrics, including C-index, NRI, IDI, AUC, calibration plots, and DCAs. Results: Multivariate risk factors including sex, age at diagnosis, marital status, AJCC stage, radiation status, and surgery status were employed to determine the overall survival (OS) rate (P<0.05). The C-index nomogram performed better than the AJCC staging system variable for both the training (0.737 versus 0.582) and validation cohorts (0.735 versus 0.573), which AUC (> 0.7) revealed that the nomogram exhibited significant discriminative ability. The statistically significant NRI and IDI values at 3-, 5-, and 8-year predictions for overall survival (OS) in the validation cohort (55.72%, 63.71%, and 78.23%, respectively and 13.65%, 20.52%, and 23.73%, respectively) demonstrate that the established nomogram outperforms the AJCC staging system (P < 0.01) in predicting OS for patients with cutaneous verrucous carcinoma (CVC). The calibration plots indicate good performance of the nomogram, while decision curve analyses (DCAs) show that the predictive model could have a favorable clinical impact. Conclusion: This study constructed and validated a nomogram for predicting the prognosis of patients with CVC in the SEER database and assessed it using several variables. This nomogram model can assist clinical staff in making more-accurate predictions than the AJCC staging method about the 3-, 5-, and 8-year OS probabilities of patients with CVC.

Oral verrucous carcinoma: a diagnostic and therapeutic challenge.

BACKGROUND: Verrucous carcinoma is a low-grade variant of squamous cell carcinoma with specific morphologic, cytokinetic and clinical features. Despite low mitotic activity and slow growth, it can infiltrate adjacent tissues in advanced stages but does not metastasize. The most frequently affected site is the oral cavity. The following article provides latest updates in the etiology, clinical presentation, diagnostics and treatment options in oral verrucous carcinoma and discusses the existing dilemmas linked to this unique malignancy. CONCLUSIONS: Oral verrucous carcinoma must be differentiated from conventional squamous cell carcinoma due to its less aggressive behaviour with a more favourable prognosis. Close communication between clinician and pathologist is mandatory for making a correct diagnosis. Primary surgery with negative surgical margins seems to be the most successful treatment. However, management recommendations are not uniform since they are mostly based on case reports and small retrospective case series. Prospective and pooled multi-institutional studies are therefore needed.

A huge verrucous carcinoma of the lower lip reconstructed by double Abbe flap: A case report and literature review.

Lip verrucous carcinoma is a rare low-grade neoplasm, with an unsightly appearance and locally aggressive nature. Treatment of verrucous carcinoma is as yet challenging, no well-defined guidelines for effective and safe management of this disease are available. A case of a patient with a huge verrucous carcinoma of the lower lip successfully treated by surgical excision and double Abbe flap reconstruction technique is presented, and striking features of lip locations of this tumor as well as their management are discussed.

Early-stage glottic cancer of rare squamous cell carcinoma variants: a population-based study.

BACKGROUND: Squamous cell carcinoma (SCC) is the most common histological type of laryngeal cancer. Several variants of SCC have been reported. However, how these variants differ from conventional SCC and how they should be treated remain to be elucidated. OBJECTIVE: To compare the prognosis of early-stage glottic cancer among SCC variants. METHODS: We obtained data from 12471 cases using the Surveillance, Epidemiology, and End Results database. Disease-specific survival (DSS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. A Cox proportional hazard model was used to estimate hazard ratios (HRs) according to the variants. RESULTS: HRs for DSS and OS compared with well-differentiated SCC were 3.83 and 3.48 for adenosquamous, 1.42 and 1.42 for basaloid, 1.14 and 1.17 for papillary, 0.85 and 0.94 for spindle, and 0.81 and 1.00 for verrucous SCC. The difference in DSS among the treatment modalities was significant in conventional and papillary SCC (p < .001 and p = .032, respectively). CONCLUSIONS: The prognosis of SCC variants, except for adenosquamous SCC, is comparable to that of conventional SCC.

Squamous Cell Carcinoma of the Foot Occurring in a Wart.

Verrucous carcinoma is a rare form squamous cell carcinoma which appears similar to a wart. When it occurs in the feet, it can be easily misdiagnosed. It rarely metastasizes or recurs posttreatment. We report a case of a septuagenarian with recurrence of verrucous carcinoma diagnosed within 6 months at the site of previous treatment. Unique features in our patient's clinical presentation include his advanced age, being nondiabetic, and the rapid recurrence of carcinoma.Level of Evidence: Level IV: Case report.

Mohs micrographic surgery for verrucous carcinoma: a review of the literature.

Verrucous carcinoma is a rare, low grade variant of squamous cell carcinoma that rarely metastasizes but tends to display aggressive local behavior. Wide local excision is the most common treatment, but has high rates of local recurrence, ranging from 19 to 75% in the literature. The cases of verrucous carcinoma treated with Mohs micrographic surgery in the literature, as well as a previously unpublished case is summarized. PubMed was searched for terms related to verrucous carcinoma and Mohs micrographic surgery, and articles reporting cases of verrucous carcinoma treated with Mohs were reviewed and summarized. A previously unpublished case treated at our institution was also reported. Thirty-eight cases of verrucous carcinoma treated with Mohs surgery were analyzed. The average age of patients was 52.1, and 50% were male. The most common sites were the foot (47%) and the anogenital region (34%). Lesion duration ranged from 0.17 to 40 years with a mean of 4.8 years, and tumor diameter ranged from 1 to 10 cm with a mean of 4.6 cm. The local recurrence rate following Mohs was 16%, with nodal metastasis occurring in 3% and no cases of distant metastasis. As verrucous carcinoma demonstrates locally aggressive behavior and a high risk of local recurrence, Mohs micrographic surgery should be considered as first line treatment. Further research directly comparing wide local excision to Mohs surgery is needed.