Cutaneous Squamous Cell Carcinoma Of The Head And Neck Research Articles

Correlation of Ultraviolet Radiation Levels With the Incidence of Cutaneous Squamous Cell and Merkel Cell Carcinomas in Non-sunbelt Locales in the United States: 2010-2017.

Non-melanoma skin cancer (NMSC) is the most common human malignancy worldwide, with increasing incidence in the United States (US). Recent environmental data have shown that ultraviolet radiation (UVR) levels have increased in the US, particularly in the higher latitudes, but the potential impact of this on NMSC incidence is not well known, despite estimates that 90% of NMSC is due to sun exposure. Our exploratory study synthesizes environmental data with demographic and clinical data to determine whether UV indices (UVIs) and non-sunbelt (non-SB) locale (latitudes >40 degrees, which comprises most of the US) might contribute to incidence rates of two types of NMSC: cutaneous squamous cell and Merkel cell carcinomas. UVIs from 2010 to 2017 were obtained from the National Oceanic and Atmospheric Administration database and meshed with corresponding locales in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database (version 8.4.0.1). Four SB and five NSB locales contained sufficient data for analysis. Linear mixed modeling was performed with the outcome variable of the age-adjusted incidence of NMSC cancer (comprised of cutaneous squamous cell carcinoma of the head and neck (CSCCHN) and Merkel cell carcinoma (MCC)), the two most common types of NMSC contained within SEER). Non-SB locale and percent of days with UVI >3 were independent variables. Percent of days with UVI >3 increased during this period, as did the overall NMSC (combined CSCCHN and MCC) skin cancer incidence, though MCC incidence alone did not increase during our study period.Environmental factors that significantly contributed to the age-adjusted overall NMSC (combined CSCCHN and MCC) cancer incidence (per 100,000 individuals) included NSB locale (b=1.227, p=0.0019) and percent of days with UVIs >3 (b=0.028, p<0.0001), as well as clinical factors of percent white race and percent male, by linear mixed modeling. Our results are limited by the completeness of the NOAA and SEER databases, and do not include basal cell carcinoma. Nevertheless, our data demonstrate that environmental factors, such as latitude in NSB locale and UVI indices, can affect the age-adjusted overall NMSC (defined as CSCCHN and MCC in this study) incidence even in this relatively short period of time. Prospective studies over longer time periods are needed to identify the extent to which these findings are clinically significant so that increased educational efforts to promote sun-safe behaviors can be maximally effective.

Long-term outcomes of a phase II trial of neoadjuvant immunotherapy for advanced, resectable cutaneous squamous cell carcinoma of the head and neck (CSCC-HN).

9519 Background: In a pilot phase II trial, we investigated the use of neoadjuvant immunotherapy to induce a pathologic response in patients with stage III/IV (M0) cutaneous squamous cell carcinoma of the head and neck (CSCC-HN). Here, we report the long-term outcomes according to pathologic response. Methods: Patients with newly diagnosed or recurrent stage III/IV (M0) (AJCC 8th Ed) CSCC-HN were treated with 2 doses of cemiplimab 350 mg intravenously every 3 weeks prior to surgery. The primary endpoint was overall response rate (ORR) per RECIST v1.1. Secondary endpoints included safety, pathologic response, disease-free and overall survival. Results: Of 20 patients enrolled, 7 (35%) had recurrent disease and 12 (60%) were stage IV on presentation. Neoadjuvant immunotherapy was generally well-tolerated and there were no surgical delays. Adverse events (AEs) were observed in 7 (35%) patients; 1 (5%) grade 3 diarrhea, 6 (30%) ≤ grade 2 AEs. ORR by RECIST was 30%. However, 85% (17/20) achieved a pathologic response (≤50% viable tumor), with pathologic complete response (pCR) in 11 (55%), major pathologic response (MPR, ≤10% viable tumor) in 4 (20%) and pathologic partial response (pPR, &gt;10% and ≤50% viable tumor) in 2 (10%). Patients with a pCR did not receive planned radiotherapy after surgery. Patients who did not have a pathologic response (&gt; 50% viable tumor) either progressed and died (1, 5%) or developed recurrence (2, 10%) despite surgery and adjuvant radiation or chemoradiation. At a median follow up of 34.5 months (range: 7.7-42.7), none of the patients who achieved a pathologic response have recurred. Conclusions: Consistent with other cancer types, pathologic response to neoadjuvant immunotherapy is durable in patients with advanced, resectable CSCC-HN. Adjuvant radiation therapy may be spared in patients who achieve a pCR and warrants further investigation. Clinical trial information: NCT03565783.

Selected Articles from This Issue

Current treatments for diffuse lower-grade gliomas are noncurative, and patients with long-term disease control often experience disease- or treatment-related symptoms. Vorasidenib, a first-in-class, brain-penetrant dual inhibitor of mutant IDH1/2 (mIDH1/2), reduced tumor growth and levels of the oncometabolite D-2-hydroxyglutarate in an orthotopic mIDH glioma mouse model. In a phase I, first-in-human study, Mellinghoff and colleagues reported a favorable safety profile and preliminary clinical activity for vorasidenib at doses &lt;100 mg once daily in recurrent or progressive mIDH1/2 glioma. Introducing mIDH-targeted therap. during what is now the “watch-and-wait” period could potentially delay the need for more toxic treatments.Biomarkers are needed to identify patients with metastatic melanoma who will benefit from targeted therapy. Brase and colleagues analyzed biomarkers in pretreatment melanoma samples from the dabrafenib plus trametinib arm of the randomized, phase III COMBI-v trial using a large-scale digital pathology approach. High T-cell/low B-cell signatures were associated with improved overall survival compared to high T-cell/high B-cell signatures. Patients with high B-cell signatures had high tumor B-cell infiltration, decreased MAPK activity, and evidence of immunosuppression. These results suggest that B cells may serve as a prognostic marker for patients with melanoma to determine the utility of dabrafenib plus trametinib, although further validation of this work is needed.The standard of care for patients with locoregionally advanced, resectable cutaneous squamous cell carcinoma of the head and neck (CSCC-HN), is surgery followed by radiotherapy. However, this regimen is problematic for cosmetic and functional reasons, and due to recurrence. Ferrarotto and colleagues conducted a clinical trial of neoadjuvant PD-1 inhibition in patients with stage III-IVA CSCC-HN. This treatment strategy was, generally, well tolerated. Of 20 patients enrolled, the RECIST response rate was (30%), while the pathologic response rate (pCR and MPR) was 70%. Patients with pCR and MCR showed enhanced inflammation of the tumor microenvironment. These results are encouraging for the treatment of this disease, but further clinical trials are warranted.Androgen receptor (AR) inhibitors are a core treatment modality in metastatic prostate cancer, but cross-resistance between agents hinders sequential use. To explore genomic contributors to cross-resistance, Annala and colleagues analyzed 458 plasma cell-free DNA samples from 202 clinical trial patients receiving sequential AR inhibitors. Targeted and exome sequencing revealed frequent shifts in the somatic populations present in circulating tumor DNA after treatment. Acquired genomic alterations converged upon the AR gene. Recurrent acquisition of aggressive AR genotypes after multiple lines of AR inhibition treatment suggests that the AR remains a driver of resistance and a key therapeutic target.

Surgically Treated Advanced Cutaneous Squamous Cell Carcinoma of the Head and Neck: Outcome Predictors and the Role of Adjuvant Radiation Therapy.

Advanced cutaneous squamous cell carcinoma of the head and neck (CSCCHN) is associated with poor outcome despite multimodality therapy. Comprehensive risk stratification may pinpoint the most suitable adjuvant treatment. This study aimed to evaluate the outcomes of surgically treated locoregional CSCCHN and to identify prognostic indicators of treatment outcomes. We retrospectively analyzed disease variables, pathologic characteristics, and management in association with treatment outcomes of all consecutive advanced CSCCHN patients who underwent surgical resection at Tel Aviv Sourasky Medical Center. From 2008 to 2018, 74 patients met the inclusion criteria. Only perineural invasion (PNI) was significantly associated with worse overall survival (OS) (P = .001). Location within the facial "mask areas" was significantly associated with pathologically negative cervical disease (P = .001). Forty-seven patients underwent adjuvant radiation therapy (RT) which significantly improved OS and disease-free survival versus surgery alone (P = .025 and P = 0.035, respectively). PNI was associated with worse OS in surgically treated advanced CSCCHN. Adjuvant RT conferred better outcomes despite high risk features.

The role of parotidectomy for advanced cutaneous squamous cell carcinoma of the head and neck.

Regionally metastatic cutaneous squamous cell carcinoma of the head and neck (CSCCHN) is usually managed surgically; however, the role of parotidectomy remains controversial. Herein we elucidate the controversy and present our experience. We retrospectively analyzed disease variables, extent of parotidectomy, and pathologic characteristics in association to outcome measures of all advanced CSCCHN patients who underwent definitive surgical resection from 2008 to 2018. Sixty-seven patients were enrolled, of whom 47 (70%) underwent parotidectomy; 27 superficial and 20 that included deep lobe resection. Parotidectomy had improved 5-year overall survival (OS) and disease-free survival (DFS) when neck was clinically involved (67.6% vs. 22.2%, P = 0.003 and 75.8% vs. 33.3% P = 0.002, respectively). Elective parotidectomy did not confer survival benefit for patients with no clinical involvement of the parotid gland (41.7% vs. 35%, P = 0.977). Recurrent disease was predictive for parotid metastases (P = 0.034). Thirty-nine patients received adjuvant radiotherapy, which significantly improved OS and DFS versus surgery alone (70.7% vs. 38.1%, P = 0.004 and 77.8% vs. 57.9%, P = 0.014, respectively). Parotidectomy was associated with improved survival of cervically spread CSCCHN.

Solid organ transplantation worsens the prognosis of patients with cutaneous squamous cell carcinoma of the head and neck region-Comparison between solid organ transplant recipients and immunocompetent patients.

Cutaneous squamous cell carcinoma of the head and neck (CSCC-HN) appears to behave more aggressively in immunosuppressed patients. We aimed to investigate this hypothesis by comparing solid organ transplant recipients (SOTR) with CSCC-HN to immunocompetent patients. A retrospective comparative study was conducted for SOTR and immunocompetent patients who were treated for CSCC-HN. A total of 177 SOTR and 157 immunocompetent patients with CSCC-HN were included. Lymph node metastases were more common in the SOTR group (9% vs 3%), and distant metastases occurred only in SOTR (3% of patients). SOTR had a higher rate of recurrences (19% vs 10%), which were mostly regional (7%) and distant (3%). The 2-year disease-specific survival of SOTR was lower (93% vs 100%). SOTR with CSCC-HN has significantly worse outcomes compared to immunocompetent patients. Solid-organ transplantation should be regarded as a negative prognostic factor in patients with CSCC-HN.

LBA74 - Phase II study of neoadjuvant cemiplimab prior to surgery in patients with stage III/IV (M0) cutaneous squamous cell carcinoma of the head and neck (CSCC-HN)

BackgroundCutaneous squamous cell carcinoma (CSCC) harbors a high tumor mutation burden (TMB) due to ultraviolet light-mediated DNA damage, and are highly immune-responsive. Cemiplimab, a monoclonal antibody directed against programmed death 1 (PD-1), is approved by the FDA and EMA as treatment for advanced CSCC patients who are not candidates for curative surgery. Here we explore the efficacy of neoadjuvant cemiplimab in CSCC- head and neck (HN) patients for whom surgery and radiation was planned. MethodsPatients with stage III/IV (M0) (AJCC 8th Ed) CSCC-HN were treated with 2 doses of cemiplimab 350mg intravenously every 3 weeks prior to surgery. The primary endpoint was overall response rate (ORR) per RECIST v1.1. Secondary endpoints included pathologic response rate, safety and tolerability, and analysis of candidate biomarkers from pre- and post-treatment blood and tumor specimens. ResultsTwenty patients (18M, 2F) enrolled with median age 69 years (range: 42-88) and stage III (n=8) or IV (n=12) disease. Seven (35%) patients experienced grade 1 or 2 adverse events (AEs); 6 (30%) grade 1 rash/pruritis, 1 (5%) grade 2 myalgia, and 1 (5%) grade 2 fatigue. There were no grade ≥ 3 AEs and no surgical delays. ORR by RECIST was 30% (6 partial response, 12 stable disease, 2 progressive disease). Pathologic complete response (pCR) was observed in 11 (55%) patients and major pathology response (MPR, ≤ 10% viable tumor) in an additional 3 (15%) patients. TMB and PD-L1 expression analyses in pre-treatment samples are in process. Eleven (55%) patients did not receive planned radiotherapy after surgery based on the pathologic responses. No recurrences have been observed with a median follow up of 3.8 months (range: 1.5-11.2). ConclusionsNeoadjuvant cemiplimab was well-tolerated and induced a pCR or MPR in 70% of stage III/IV (M0) CSCC patients. A multicenter phase II study is planned to confirm these results and to describe the ability of neoadjuvant cemiplimab to allow less extensive treatment. Clinical trial identificationNCT03565783. Legal entity responsible for the studyThe University of Texas MD Anderson Cancer Center. FundingRegeneron. DisclosureN. Gross: Advisory / Consultancy, Research grant / Funding (self): Regeneron; Advisory / Consultancy: PDS Biotechnology; Advisory / Consultancy: Intuitive Surgical. B.S. Glisson: Research grant / Funding (institution): Pfizer; Research grant / Funding (self): ISA Pharmaceuticals. All other authors have declared no conflicts of interest.

Phase 2 Trial of Adjuvant Concurrent Cetuximab and Radiation for High-Risk Cutaneous Squamous Cell Carcinoma of the Head and Neck

Aggressive cutaneous squamous cell carcinoma of the head and neck (CSCCHN) is most often treated with surgical resection followed by adjuvant radiation therapy (RT) with or without concurrent chemotherapy and locoregional control (LRC) remains problematic with 2 yr LRC of 60% to 80%. The addition of cytotoxic chemotherapy has not demonstrated benefit over adjuvant RT in randomized trials. NCT01979211 is a multi-institutional single arm phase 2 trial of concurrent adjuvant RT and cetuximab after primary surgical resection for CSCCHN. Eligibility criteria include high-risk (>N1, + PNI, bone or cartilage invasion) or locally recurrent CSCCHN after gross total resection. Primary endpoint is 2 yr LRC. Secondary endpoints include DFS, OS, acute and late toxicities (CTCAE v4.03), and patient reported quality of life with FACT-HN and Dermatology Life Quality Index (DLQI). Correlative studies include whole exome sequencing of primary tumor and nodal metastases. Twenty-three of planned 40 patients are accrued to date with a median 12 months of follow-up. Eighteen patients have completed all therapy per protocol with minimum 3-month follow-up. Of the patients, 91% were male, mean age 69 (range 50-80), all Zubrod 0-1. Of these, 18 patients, acute toxicities are as follows: 91% had grade 1 toxicities, mostly acneiform rash and mucositis, grade 2 reported in 61% patients including skin (39%), mucositis/oral pain (39%), fatigue (11%), allergic reaction (5%). Three patients had grade 3 skin toxicity, 1 patient had grade 3 mucositis. No grade 4 or 5 toxicities to date. Two patients developed locoregional failures, no one has developed distant metastases. 2 patients have died, 1 related to confirmed LRR. To date, mean baseline DLQI score is 5.5 (+/- 0.5) and at 3 mo post-RT is 3.9 (+/- 0.4), indicating a “small” improvement in skin QOL from postresection, preadjuvant therapy baseline. Mean baseline FACT- HN score is 120 (+/- 18) and 118 (+/- 25) at 3 mo post-RT. Postoperative concurrent cetuximab and RT for high risk CSCCHN appears well tolerated with favorable LRC thus far in comparison to institutional historic controls and quality of life scores comparable to other trials using concurrent cetuximab and RT for mucosal HNSCC.

Insight into the epidemiology of cutaneous squamous cell carcinoma with perineural spread.

Perineural spread (PNS) of cutaneous squamous cell carcinoma of the head and neck (SCCHN) can be associated with poor outcomes. Disease understanding and awareness is limited leading to delayed diagnosis and treatment. The purpose of this study was to identify epidemiological features of patients with PNS of cutaneous SCCHN. Tumor characteristics and demographics of patients with PNS of cutaneous SCCHN managed through a single institution were collected between 1998 and 2013. One hundred twenty patients were included in this study. The majority had a history of skin cancer (85.8%). The median time from primary tumor treatment to PNS symptom onset was 16 months (range, 1-86 months). A total of 34.2% had no perineural invasion (PNI) detected in the primary, and 22.5% had no known primary tumor. Only 5.8% of the patients had nodal involvement at presentation. Patients can present with PNS from cutaneous SCCHN with no known primary tumor or with primary tumors without PNI. The majority of patients presented without regional nodal involvement. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1416-1420, 2016.

Outcomes after surgery and postoperative radiotherapy for perineural spread of head and neck cutaneous squamous cell carcinoma.

Queensland, Australia, has the highest rates of cutaneous squamous cell carcinoma (SCC). Perineural invasion (PNI) is associated with reduced local control and survival. A retrospective review of a prospective database of patients with clinical PNI from cutaneous SCC of the head and neck (SCCHN) treated with surgery and postoperative radiotherapy (PORT) between 2000 and 2011 and a minimum of 24 months follow-up. Patients were excluded if immunosuppressed, had non-SCC histology, or were treated palliatively. Fifty patients (mean age, 60 years) with median follow-up of 50 months were included in this study. A total of 54.8% of known primary tumors had incidental PNI. Ten percent had nodal disease at presentation. MRI neurogram was positive in 95.8%. Recurrence-free survival (RFS) at 5-years was 62%. Five-year disease-specific survival (DSS) and overall survival (OS) were 75% and 64%, respectively. There were no perioperative deaths. This report demonstrates that long-term survival is achievable in patients with clinical PNI from cutaneous SCCHN after surgery and PORT. © 2015 Wiley Periodicals, Inc. Head Neck 38: 824-831, 2016.

Outcomes of nodal metastatic cutaneous squamous cell carcinoma of the head and neck treated in a regional center.

Given its metastatic potential and high incidence, cutaneous squamous cell carcinoma of the head and neck (SCCHN) has significant morbidity and mortality. We conducted a retrospective review of prospectively collected data for 113 consecutive patients with nodal metastatic cutaneous SCCHN treated surgically with curative intent in a regional center. Survival curves were generated by the Kaplan-Meier method. Five-year overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were 80%, 83%, and 75%, respectively. Twenty-six patients (23%) relapsed, with 92% of relapses occurring within 2 years of surgery. Immunosuppression (p = .008) and N classification (p = .043) predicted decreased DFS on univariate analysis. On multivariate analysis, only immunosuppression independently predicted DFS (p = .034). This study validates the current N classification system, supports the adverse effect of immunosuppression, and suggests that intense follow-up for 2 years postsurgery is warranted. Survival at this regional center is comparable to that achieved at metropolitan tertiary cancer centers.

Histopathological features of clinical perineural invasion of cutaneous squamous cell carcinoma of the head and neck and the potential implications for treatment

Nonmelanoma skin cancer (NMSC) with perineural invasion (PNI) is most commonly seen in cutaneous squamous cell carcinoma of the head and neck (SCCHN). The cranial nerves are a conduit for skin cancer to reach the brainstem. The histopathological features of 51 tissue specimens from 49 patients with cutaneous SCCHN and clinical PNI were assessed with consecutive transverse and longitudinal sections. No skip lesions were identified. Tumor spread was contiguous in all specimens. No tumor spread into the perineural space from surrounding or adjacent tumor was seen. Proximal large cranial nerves showed epineural involvement in 3.9% in areas with large tumor bulk, extensive PNI, and intraneural invasion. Perineural tumor spread in cutaneous SCCHN was contiguous and no skip lesions were evident in nerve specimens assessed in this series. Spread beyond cranial nerve perineurium was uncommon, reflecting its multilayer barrier function at this level. These findings may have treatment implications.

Sentinel Lymph Node Biopsy in Cutaneous Squamous Cell Carcinoma of the Head and Neck

Objectives: 1) Recognize the potential indications for sentinel lymph node biopsy (SLNB) in the treatment of aggressive cutaneous squamous cell carcinoma of the head and neck (CSCCHN). 2) Understand how to incorporate SLNB into the multidisciplinary management of high-risk CSCCHN. Methods: A retrospective review was performed on patients with CSCCHN at a tertiary care head and neck surgical oncology center who underwent SLNB between August 2011 and January 2013. This is a pilot, feasibility study with the main outcome measures of regional failure and surgical complications. Results: Five patients (4 males, 1 female) with a median age of 69 (range 55-80) were identified with an average follow up of 34 weeks (range 2-63). No patients were immunocompromised. 4 had poorly differentiated lesions, 2 of which were recurrent. Traditional wide local excision was performed in 4 patients, while Mohs surgery was performed on 1 patient. An average of 1.6 sentinel lymph nodes were identified on preoperative imaging (range 1-3), with an average of 4.6 SLN excised (range 2-8). One patient demonstrated a positive sentinel node (20%), facilitating additional treatment with radiation to the primary and regional lymphatics, as he refused completion lymphadenectomy. There were no postoperative complications, including facial nerve weakness. All patients are alive without evidence of disease at the last reported encounter. Conclusions: SLNB is feasible in patients with high-risk CSCCHN, allowing prompt treatment of the regional lymphatics. Further multi-center, multidisciplinary, prospective studies are required to clarify the indications and impact of SLNB in CSCCHN.

Effects of epidermal growth factor receptor and insulin‐like growth factor 1 receptor inhibition on proliferation and intracellular signaling in cutaneous SCCHN: Potential for dual inhibition as a therapeutic modality

Combined inhibition of epidermal growth factor receptor (EGFR) and insulin-like growth factor-1 receptor (IGF-1R) has been proposed as a therapy for cutaneous squamous cell carcinoma of the head and neck (SCCHN). Receptor expression and downstream signaling were assessed in cutaneous squamous cell carcinoma (SCC) cell lines and patient samples. EGFR and IGF-1R signaling was inhibited in cutaneous SCC cell lines using erlotinib and/or picropodophyllin. EGFR and IGF-1R were overexpressed in cutaneous SCCHN specimens relative to normal skin. Dual inhibition of both receptors prevented cell growth and decreased activation of Akt and p42/44 mitogen-activated protein kinase (MAPK) more effectively than either inhibitor alone. Dual inhibition of EGFR and IGF-1R is effective at blocking cell growth, and is correlated with inhibition of Akt and p42/44 MAPK, suggesting that this may be a promising treatment for cutaneous SCCHN.

Epidemiology of Clinical Perineural Invasion in Cutaneous Squamous Cell Carcinoma of the Head and Neck

Perineural invasion (PNI) in cutaneous squamous cell carcinoma of the head and neck (CSCCHN) is associated with decreased survival. Large-nerve PNI presents with clinical signs and symptoms and/or magnetic resonance imaging evidence of cranial nerve involvement. We sought to determine which variables predict a worse outcome and to analyze patterns of failure. Case series with planned data collection. Tertiary care center. Patients with large-nerve PNI from CSCCHN between 1996 and 2006 were identified from a prospectively collected database. Clinical and demographic variables were recorded. Local control rates and survival analysis were performed using Kaplan-Meier curves. Thirty-six patients were identified (28 men and 8 women). The mean age was 61 years. Twenty-nine were treated with curative intent, and 7 received palliation. The mean follow-up was 35 months. Involvement of V3, disease zone, and the type of therapy were significantly associated with overall survival (P < .05). The 5-year disease-free survival for patients by therapy was 50% for subcranial surgeries, 53.6% for skull base surgery, and 0% for radiation and palliative therapies (P < .001). None of the patients treated with a skull base resection had a central recurrence, while all patients who received palliation had a central failure. Disease extent, type of therapy, and involvement of V3 are all significant predictors of survival in PNI from CSCCHN. We confirmed that the natural history of the disease is central progression and that this can be halted, if detected early enough, by a properly planned skull base resection.

Surgical resection for clinical perineural invasion from cutaneous squamous cell carcinoma of the head and neck

Perineural invasion (PNI) in cutaneous squamous cell carcinoma of the head and neck (SCCHN) is associated with decreased survival. Patients with large nerve or clinical PNI present with clinical signs and symptoms or MRI evidence of cranial nerve involvement. These patients often succumb to disease that spreads into the brainstem. In our experience, when the disease extends up to the Gasserian or Geniculate ganglion, surgical resection with negative margins provides the best chance for cure. Herein we review our experience to validate our clinical observations. We identified patients with large nerve PNI from cutaneous SCCHN between January 1996 and 2006 from a prospectively collected database. Patients who underwent surgical resection as their primary mode of therapy were included. Clinical and demographic variables were recorded. Survival analysis was performed with Kaplan-Meier curves, and the log-rank test was used for significance testing between groups. Twenty-one patients were identified. The mean age was 60 (range, 38-86) years, with 15 men and 6 women. Nineteen patients had a formal skull base resection, whereas 2 patients had a subcranial resection. We had 3 complications in our series: extradural hemorrhage (n = 1), cerebrospinal fluid leak (n = 1), and wound infection (n = 1). None of the patients who underwent a formal skull base resection to include the lateral cavernous sinus (ie, Gasserian ganglion) suffered ocular palsies or permanent morbidity when the orbit was preserved (n = 11). We had no surgical deaths. The average length of stay was 9 days (SD 6.3 days). The 5-year disease specific survival rate for the entire group was 64.3%. V3 involvement resulted in lower, although not significant, 5-year disease-free survival rates- 0% for those patients with involvement (n = 4) versus 66.8% for no involvement of V3 (n = 17). Appropriately planned surgical resection of PNI in cutaneous SCCHN up to the ganglion as dictated by the disease extent may improve survival without significant added morbidity.

Reduced αB-crystallin staining in perineural invasion of head and neck cutaneous squamous cell carcinoma

Objective Perineural invasion (PNI) in cutaneous squamous cell carcinoma of the head and neck (CSCCHN) carries poor prognosis. Tumor markers associated with neurotropism in CSCCHN have not been identified. Our objective was to study the expression of αB-crystallin in CSCCHN with neurotropism. Study Design Cross-sectional review of pathologic specimens. Setting Tertiary care center. Subjects and Methods Tissue from patients with CSCCHN with clinical PNI who underwent surgery between 1998 and 2005 was immunostained for αB-crystallin. In addition, non-PNI CSCCHN and normal nerve sections were also stained. Staining intensity was calculated by the histologic, or H, score (product of the intensity and proportion of tumor cells stained). The H-score ranged from 0.0 to 3.0, with 0 indicating negative staining in all cells and 3.0 indicating strong staining in 100 percent of cells. Results Tissue was available in 15 clinical PNI CSCCHN patients. The analysis was also carried out in 14 non-PNI patients matched by stage and four normal greater auricular nerve (GAN) sections. The mean H-score was 0.56 for CSCCHN with PNI, 1.06 for non-PNI CSCCHN, and 3.0 for normal nerves. The difference in H-score between PNI and non-PNI CSCCHN was statistically significant ( P = 0.04). Conclusion CSCCHN with clinical PNI has decreased staining for αB-crystallin. This finding further demonstrates the differences between clinical PNI and non-PNI CSCCHN tumors. Additional studies are required to identify cell surface markers expressed by CSCCHN that confer neurotropism capabilities.

Predicting the pattern of regional metastases from cutaneous squamous cell carcinoma of the head and neck based on location of the primary

We aimed to analyze the distribution of regional nodal metastases according to primary tumor location in patients with cutaneous squamous cell carcinoma of the head and neck (SCCHN). Analysis of 295 neck dissections performed for patients with clinically evident regional metastases from cutaneous SCCHN between 1987 and 2009. Level I involvement in the absence of level II or III only occurred in patients with facial primaries. In patients with clear nodes in level II-III, the risk of level IV-V involvement was 0.0% for external ear primaries, 2.7% for face and anterior scalp, and 15.8% for posterior scalp and neck. In patients undergoing parotidectomy for metastatic cutaneous SCCHN with a clinically negative neck, the results of this study support selective neck dissection including level I-III for facial primaries, level II-III for anterior scalp and external ear primaries, and levels II-V for posterior scalp and neck primaries.

Neural cell adhesion molecule expression: No correlation with perineural invasion in cutaneous squamous cell carcinoma of the head and neck

Perineural invasion (PNI) in cutaneous squamous cell carcinoma of the head and neck (CSCCHN) is associated with decreased survival, particularly in patients with clinical signs of cranial nerve involvement. There is evidence to indicate that neural cell adhesion molecule (N-CAM) confers capability of PNI. We analyzed our own patient population to determine if N-CAM predicted clinical PNI in CSCCHN. Tissue from patients with CSCCHN and clinical PNI, who underwent surgery between 1998 and 2005, was immunostained for N-CAM. In addition, non-PNI CSCCHN and normal nerve sections were also stained. A section of neuroendocrine tumor was included in each slide as a positive control. In addition, most of the sections also had an "inbuilt control" in the CD56 positive natural killer T cells that formed part of the inflammatory reaction to the tumors. Tissue was available from 14 patients with CSCCHN and clinical PNI. The analysis was carried out in 14 patients without PNI and 4 normal nerves. N-CAM was not expressed in any of our PNI CSCCHN specimens or non-PNI controls. It was strongly expressed in the neuroendocrine tumors and positive in-built controls, as well as in normal nerve tissue. N-CAM expression did not predict neurotropism in our patient population. Additional studies are required to identify the cell surface markers expressed by CSCCHN which confer neurotropism capabilities.