Impact of Cutaneous Squamous Cell Carcinoma Histologic Features on Percent Interrater Agreement Regarding Tumor Differentiation.

BACKGROUND: Poor differentiation predicts adverse outcomes in cutaneous squamous cell carcinoma (CSCC), but there is no standardized, reliable grading system. OBJECTIVE: To explore which histologic features have the greatest impact on CSCC differentiation interrater agreement. MATERIALS AND METHODS: In a prior study, 40 raters graded differentiation for 45 squamous cell carcinomas, and percent interrater agreements were calculated. Cases graded as well/moderately differentiated with 100% agreement (10), those graded as poorly differentiated with ≥80% agreement (5), and those that received a variety of grades with ≤60% agreement (7) were pulled for the current study. Three raters graded individual histologic features for each case, and percent interrater agreements were calculated using both the well/moderately/poorly differentiated grading system and a dichotomized system. RESULTS: The percent interrater agreements were 34.8% for mitoses, 53% for pleomorphism, 59.1% for keratinization, 66.7% for cellular cohesion/intercellular bridges, and 78.8% for tumor edges. Percent agreements improved with dichotomous grading; the largest improvement was seen within the group of cases that had been graded as well/moderately differentiated with 100% agreement in the prior study. CONCLUSION: Future squamous cell carcinoma differentiation grading systems would benefit from eliminating mitotic rate, clearly defining how to grade other features, and dichotomous grading.

Risk factors and timing of subsequent cutaneous squamous cell carcinoma in patients with cutaneous squamous cell carcinoma: A retrospective cohort study.

BACKGROUND: Information about the frequency and timing of subsequent cutaneous squamous cell carcinoma (cSCC), along with associated risk factors, is limited. However, this information is crucial to guide follow-up care for these patients. OBJECTIVE: To evaluate the risk and timing of subsequent cSCC in patients who presented with an initial diagnosis of cSCC. METHODS: Retrospective review of an institutional review board-approved, single-institution registry of invasive cSCC. All patients had at least 2 primary cSCCs diagnosed on 2 separate dates 2 months apart. RESULTS: A total of 299 primary cSCCs were included. At 6 months from initial cSCC diagnosis, 18.06% (n = 54) of patients developed subsequent cSCC; at 1 year, 31.77% (n = 94); at 3 years, 67.56% (n = 202); and at 5 years, 87.96% (n = 263) developed subsequent cSCC. Risk factors associated with subsequent cSCC include age at initial diagnosis (hazard ratio [HR], 1.02; 95% confidence interval, 1.004-1.027; P = .008), T2 stage (HR, 1.66; 95% CI, 1.07-2.57; P = .025), and poor tumor grade. Tumor grades well, moderate, and unknown have HRs of 0.21 (P < .001), 0.16 (P .001), and 0.25 (P = .001), respectively. CONCLUSIONS: Of patients who develop subsequent cSCC, 18.06% do so within 6 months, and 31.77% do so within 1 year of initial cSCC diagnosis. Patients with advanced age, poor histologic differentiation, and American Joint Committee on Cancer T2 stage are at highest risk. Close clinical follow-up after the initial diagnosis is recommended.

Outcomes in intermediate-risk squamous cell carcinomas treated with Mohs micrographic surgery compared with wide local excision.

BACKGROUND: Brigham and Women's Hospital stage T2a squamous cell carcinomas, demonstrating a single high-risk feature, have a low risk of metastasis and death but an increased risk of local recurrence. Little evidence exists for the best treatment modality and associated outcomes in T2a squamous cell carcinoma. OBJECTIVE: We aimed to compare outcomes for T2a squamous cell carcinoma treated by Mohs micrographic surgery compared with wide local excision with permanent sections. METHODS: Retrospective review of an institutional review board-approved single-institution registry of T2a squamous cell carcinoma. RESULTS: Three hundred sixty-six primary T2a tumors were identified, including 240 squamous cell carcinomas (65.6%) treated with Mohs micrographic surgery and 126 (34.4%) treated with wide local excision. A total of 32.5% of patients were immunosuppressed and mean oncologic follow-up was 2.8 years. Local recurrence was significantly more likely after wide local excision (4.0%) than after Mohs micrographic surgery (1.2%) (P = .03). Multiple logistic regression demonstrated immunocompromised state (odds ratio [OR] 5.1; 95% confidence interval [CI] 1.1-23.3; P = .03) and wide local excision (OR 4.8; 95% CI 1.1-21.6; P = .04) associated with local recurrence; and wide local excision (OR 7.8; 95% CI 2.4-25.4; P < .001), high-risk head and neck location (OR 8.3; 95% CI 1.8-38.7; P = .004), and poor histologic differentiation (OR 4.7; 95% CI 1.4-15.4; P = .03) associated with poor outcomes (overall recurrence or disease-specific death). CONCLUSION: Mohs micrographic surgery provides improved outcomes in Brigham and Women's Hospital T2a squamous cell carcinoma.

Recent and Emerging Therapies for Cutaneous Squamous Cell Carcinomas of the Head and Neck.

OPINION STATEMENT: Cutaneous squamous cell carcinoma (cSCC) of the head and neck is typically managed with Mohs Micrographic Surgery (MMS) for cosmetic reasons. MMS also improves oncologic outcomes for high-risk tumors. Patients with certain high-risk subsets of the disease also benefit from adjuvant radiation therapy. The PD-1 inhibitor, cemiplimab, was recently approved for treatment of locally advanced and metastatic cSCC unamenable to curative surgery or radiation therapy after the drug demonstrated encouraging, durable response rates. Cemiplimab and other systemic immunotherapies are now being evaluated in clinical trials in the neoadjuvant and adjuvant settings as well. Localized immunotherapies are also being studied, including oncolytic viruses such as talimogene laherparepvec, a modified herpes simplex virus previously approved for the treatment of advanced cutaneous melanoma. Most importantly, multidisciplinary care is crucial in optimizing outcomes for patients with high-risk cSCC of the head and neck.

Antistreptococcal treatment of psoriasis: a systematic review.

Streptococcal infections may contribute to psoriasis development, and antistreptococcal treatments are considered potential therapies, but their effectiveness remains uncertain due to limited systematic evidence. Our objective was to analyze antistreptococcal therapies' effectiveness in improving psoriasis. We conducted a systematic review following PRISMA guidelines, evaluating antistreptococcal treatment efficacy in psoriasis patients from PubMed, Scopus, and Embase databases until August 14, 2022. Eligible studies included psoriasis patients undergoing antistreptococcal therapy, regardless of demographics or psoriasis type. 50 studies (1778 patients) were analyzed, with penicillins/aminopenicillins as the most studied antibiotics (21 studies), showing mixed outcomes, some reporting significant improvement in guttate psoriasis, while others showed no significant difference. Rifampin demonstrated positive results in most of ten studies, and macrolides showed varying effectiveness in two studies. Tonsillectomy in 14 studies (409 patients) mainly focusing on guttate and chronic plaque psoriasis showed positive outcomes, indicating improved symptoms and quality of life. Limitations include heterogeneous studies, sampling bias, and quality of evidence. This systematic review reveals limited and varied evidence for systemic antibiotic therapy efficacy in psoriasis treatment, while tonsillectomy emerges as a potentially beneficial antistreptococcal option, urging further well-designed, controlled studies with larger sample sizes and standardized protocols for better comparisons.

Use of the Retroauricular Pull-Through Sandwich Flap for Repair of an Extensive Conchal Bowl Defect With Complete Cartilage Loss.

Reconstruction of an extensive conchal bowl defect with notable cartilage loss is challenging due to the unique shape of the concha, the need for adequate structural support, and the lack of adjacent tissue reservoirs. Repair of a full-thickness conchal bowl defect has included 3-stage approaches, such as the anterior pedicled retroauricular flap. For an extensive conchal defect with substantial cartilage loss but intact posterior auricular skin, we recommend consideration of the retroauricular pull-through sandwich flap, which combines a cartilage graft and retroauricular interpolation flap pulled through a posterior auricular incision to resurface the anterior ear.

Disease Progression in Cutaneous Squamous Cell Carcinoma Patients With Satellitosis and In-transit Metastasis.

BACKGROUND/AIM: Satellitosis/in-transit metastasis (S-ITM) has prognostic value in melanoma and Merkel cell carcinoma, but is not incorporated into cutaneous squamous cell carcinoma (cSCC) staging. PATIENTS AND METHODS: From our IRB-approved registry, patients with high-risk cSCC, including patients with S-ITM, were identified. Univariate (UVA) and multivariate (MVA) analyses were performed to compare disease progression (DP) and overall survival (OS). Cumulative incidence of DP and OS analyses were performed using Fine-Gray and Kaplan-Meier methods, respectively. RESULTS: A total of 18 S-ITM subjects were compared to 247 high risk subjects including T3N0 (n=143), N1-N3 without extranodal extension (ENE) (n=56), N1-N3 with ENE (n=26) and M1 disease (n=22). Median follow up was 16.5 months. Three-year rates of DP were 22% for T3N0, 42% for S-ITM, 48% for T4 bone invasion, 50% for N1-N3 without extranodal extension (ENE), 53% for N1-N3 with ENE, and 66% for M1. Patients with S-ITM did not experience significantly worse DP compared to those with T3N0 (HR=1.96, 95%CI=0.8-4.9; p=0.14). CONCLUSION: Cutaneous SCC patients with S-ITM experienced outcomes similar to locally advanced non-metastatic cSCC patients. Larger studies are needed to guide incorporation into staging systems.

Selectively sparing the submandibular gland when level Ib lymph nodes are included in the radiation target volume: An initial safety analysis of a novel planning objective.

BACKGROUND: Submandibular gland (SMG) metastases are extremely rare in head and neck cancer, even in the presence of level Ib lymph node (LN) involvement. In recent years, we have contoured the SMG and specifically attempted to limit its dose exposure even in patients in whom the level Ib LN station is targeted. This study reports our preliminary feasibility and safety experience with selective submandibular gland sparing. METHODS: Patients with squamous cell cancer (SCC) of the oral cavity or oropharynx with T1-2, N0-3, M0 disease in whom at least a single level Ib lymph node region was included in the target volume were identified. All patients were treated from 2009 to 2014 with definitive or postoperative IMRT with or without chemotherapy. Patients with recurrent disease, previous radiation or treated palliatively were excluded. RESULTS: A total of 174 patients met criteria for inclusion. Among the 185 level Ib LN stations that were deliberately targeted in the clinical treatment volume, 32 submandibular glands were contoured, excluded from the target volume and avoided during treatment planning. Mean dose to the spared SMG were reduced by 12% (66.6 Gy vs. 58.9 Gy, p < .001). None of these patients experienced any level 1b LN failures. CONCLUSION: Selective sparing of the submandibular gland when targeting the level 1b nodes in oral cavity and oropharynx cancer is feasible, reduces the mean dose to submandibular glands and does not result in increased level 1b nodal failure rates. Additional studies with larger cohorts are needed to validate this preliminary observation.

Malignant Transformation of Molecularly Classified Adult Low-Grade Glioma.

PURPOSE: Malignant transformation (MT) of adult grade 2 glioma (low-grade glioma [LGG]) is associated with adverse survival. We sought to describe the incidence, outcomes, and risk factors for MT of molecularly classified LGG. METHODS AND MATERIALS: We reviewed a single-institutional database of adults who received a diagnosis of LGG with data allowing for molecular classification from 1980 to 2018 to evaluate time to MT and its associated risk factors. MT was defined as pathologic confirmation of grade 3-4 glioma and/or imaging characteristics consistent with MT by multidisciplinary consensus. RESULTS: Among the included 486 adults with molecularly classified LGG, median age was 39 years (range, 18-78), median tumor size was 3.9 cm (range, 0.3-13.0), and 262 (54%) were male. Molecular classification was IDHmut1p/19qcodel in 169 (35%), IDHmut1p/19qintact in 125 (26%), and IDHwt in 192 (40%) patients. Adjuvant management was observation in 246 (51%) patients, temozolomide alone in 82 (16%), radiation therapy alone in 63 (13%), and radiation therapy concurrent with temozolomide in 81 (17%). Temozolomide monotherapy was more likely to be given to IDHmut1p/19qcodel patients (P < .001). Median follow-up was 5.3 years. MT occurred in 84 (17%) patients, with a 5-year freedom from MT of 86% (95% confidence interval [CI], 82%-90%). Median overall survival after MT was 2.4 years (95% CI, 1.5-3.3) and was associated with molecular classification (P = .03) and grade at MT (P < .001). Factors associated with MT were male sex (hazard ratio [HR], 2.1; 95% CI, 1.2-3.6; P = .009), tumor size ≥5 cm (HR, 3.5; 95% CI, 2.0-6.2; P < .001), IDHmut1p/19qintact (HR, 2.7; 95% CI, 1.3-5.6; P = .009) or IDHwt classification (HR, 5.5; 95% CI, 2.5-11.8; P < .001), and adjuvant temozolomide monotherapy (HR, 3.8; 95% CI, 1.4-10.3; P = .008). CONCLUSIONS: MT of LGG has a poor prognosis associated with unfavorable molecular groups. Analysis of our large cohort identified adjuvant temozolomide monotherapy as the only modifiable risk factor for MT and provides the first clinical evidence of temozolomide-associated MT among molecularly classified adult LGG. This novel finding supplements our understanding of temozolomide-induced hypermutation and informs precision management of LGG.

Risk Factors for Progression Among Low-Grade Gliomas After Gross Total Resection and Initial Observation in the Molecular Era.

PURPOSE: To identify risk factors for progression-free survival (PFS) in the molecular era among patients with low-grade glioma (LGG) who undergo gross total resection (GTR) followed by initial observation. METHODS AND MATERIALS: We reviewed patients with World Health Organization grade 2 LGG treated at a single institution. We included only those who underwent magnetic resonance imaging (MRI)-confirmed GTR followed by initial observation. Molecular classification was obtained at either the time of diagnosis or pathology review. Cox proportional hazards regression, the Kaplan-Meier method, and the log-rank test were used. P values <.05 were considered statistically significant. RESULTS: We included 144 patients who underwent MRI-confirmed GTR between 1994 and 2014 followed by initial observation. Median age was 29 years (interquartile range [IQR], 18-41), median tumor size was 2.7 cm (IQR, 1.8-4.0), and median follow-up was 81 months (IQR, 36-132). Molecular classification was 13% IDH-mutant 1p19q-codeleted; 21% IDH-mutant 1p19q-intact; 39% IDH1-R132H-wildtype; and 28% undetermined. For the entire cohort, 5- and 10-year PFS and overall survival were 71% and 53%, and 98% and 90%, respectively. On multivariate analysis, factors associated with worse PFS included increasing age at diagnosis (hazard ratio [HR], 1.05; 95% CI, 1.00-1.09; P = .03), increasing preoperative tumor size (HR, 1.07; 95% CI, 1.04-1.10; P < .0001), and IDH-mutant 1p19q-intact classification (HR, 3.18; 95% CI, 1.15-8.74, P = .025). Median PFS for patients with IDH-mutant 1p19q-codeleted, IDH-mutant 1p19q-intact, and IDH1-R132H-wildtype tumors were 113 months, 56 months, and not reached, respectively. Molecular classification was significantly associated with PFS (P < .0001) but not overall survival (P = .20). CONCLUSIONS: Among patients with LGG who undergo MRI-confirmed GTR and initial observation in the molecular era, increasing age, increasing tumor size, and IDH-mutant 1p19q-intact classification are associated with worse PFS. Because tumor progression is associated with adverse health-related quality of life, these factors may aid clinicians and patients in the shared decision-making process regarding goals of surgery and timing of postoperative therapy. Further study is required to elucidate why IDH-mutant 1p19q-intact LGGs are at higher risk for early progression.

Suboptimal Outcomes in Cutaneous Squamous Cell Cancer of the Head and Neck with Nodal Metastases.

BACKGROUND/AIM: There are limited data regarding survival, failure patterns, and factors associated with disease recurrence in patients with cutaneous squamous cell cancer of the head and neck (cSCC-HN) with nodal metastases. PATIENTS AND METHODS: A retrospective analysis of patients with cSCC-HN metastatic to cervical and/or parotid lymph nodes treated with surgery and post-operative radiation therapy was performed. RESULTS: This study included 76 patients (57 immunocompetent and 18 immunosuppressed) with a median follow-up of 18 months. Overall survival, disease-free survival (DFS), and disease recurrence (DR) at 2 years was 60%, 49%, and 40%, respectively. Immunosuppressed patients had significantly lower 2-year DFS (28% vs. 55%; p=0.003) and higher DR (61% vs. 34%; p=0.04) compared to immunocompetent patients. Analysis of immunocompetent patients demonstrated extracapsular extension (ECE) as the only factor associated with DR (p<0.0001). CONCLUSION: Patients with nodal metastases from cSCC-HN have suboptimal outcomes. ECE and immunosuppression were significantly associated with DR.