Currently, the incidence of esophageal cancer continues to rise around the world. Because of its good early prognosis, it is of great significance to establish an effective model for predicting the survival of EC patients. The purpose of this study was to predict survival after diagnosis in Esophageal Cancer (EC) patients by constructing a valid clinical nomogram. In this study, 5037 EC patient samples diagnosed from 2010 to 2015 were screened by accessing the SEER database, and 8 independent prognostic factors were screened by various methods, and Cox multivariate regression was included to construct a prognostic model and nomogram for esophageal cancer. to estimate esophageal cancer recurrence and overall survival. Calibration of the nomogram predicted probabilities of 1-year, 3-year and 5-year survival probability, which were closely related to actual survival. In conclusion, this study validated that the column-line graphical model can be considered an individualized quantitative tool for predicting the prognosis of patients with EC in order to assist clinicians in making therapeutic decisions.

Cutaneous squamous cell carcinoma is a significant cause of morbidity for immunosuppressed patients such as organ transplant recipients; however, histological parameters which predict the likelihood of tumor progression are typically based on general population studies in which immunosuppressed patients represent only a small fraction of cases.

To determine the histological parameters which have independent prognostic value for cutaneous squamous cell carcinoma arising in renal transplant recipients.

Case-control study incorporating a retrospective blinded histological review of 70 archived specimens of cutaneous squamous cell carcinoma diagnosed in renal transplant recipients, comprising 10 cases where the tumor had progressed and 60 controls.

Progression was significantly associated with head and neck location, size, depth, poor histological grade, perineural invasion (including small caliber perineural invasion), lymphovascular invasion, and a desmoplastic growth pattern.

The retrospective nature and the low number of cases compared to controls.

In immunosuppressed patients both small caliber perineural invasion and a desmoplastic growth pattern may also have prognostic significance in addition to other histological parameters already recognized in formal staging schemes.

Eccrine porocarcinoma (EPC) constitutes a rare malignant adnexal tumor, which accounts for about 0.005-0.01% of all cutaneous malignancies. It may develop de novo or arise from an eccrine poroma, after a latency period of years or even decades. Accumulating data suggest that specific oncogenic drivers and signaling pathways may be implicated in its tumorigenesis, while recent data have demonstrated a high overall mutation rate attributed to UV exposure. Diagnosis may be challenging and should rely on the combination of clinical, dermoscopical, histopathological and immunohistochemical findings. The literature is controversial regarding tumor behavior and prognosis and, therefore, there is no consensus on its surgical management, utility of lymph-node biopsy and further adjuvant or systemic treatment. However, recent advances in tumorigenesis of EPC may aid in the development of novel treatment strategies, which could improve survival of advanced or metastatic disease, such as immunotherapy. This review presents an update of the epidemiology, pathogenesis and clinical presentation of EPC and summarizes current data on diagnostic evaluation and management of this rare cutaneous malignancy.

Basal cell carcinoma (BCC) is a slow-growing malignant tumor characterized by local invasiveness but an exceptionally rare metastatic potential. It ideally affects sun-exposed skin of older patients with more propensity for the facial region.

To evaluate the different clinicopathological characteristics of the facial BCC and the efficacy and safety of diode laser for the treatment of these lesions.

We retrospectively reviewed facial BCC lesions of < 1.5 cm in diameter and subjected them to diode laser ablation during the period from September 2016 to August 2021 at Al-Ramadi Teaching Hospital, Ramadi City, Iraq. Data matching the age, gender, duration, site, and clinical and histological types were registered for every subject. The functional and aesthetic outcomes and complications following diode laser ablation for each patient were also recorded.

Of 67 patients with facial BCC, there was 65.67% from the age group ≥ 60 years and 58.21% males. The mean duration of the lesions was 5.15 ± 1.836 mo. The most involved location was the nose (29.85%). About half of the cases belong to the noduloulcerative type. Solid histological type comprises 40.3% of the cases, while the least was keratotic (13.4%). Moreover, 65.2% of the solid cases were from the age group ≤ 60 years and 38.6% of the adenoid type from the age group > 60 years (P value = 0.007). Excellent aesthetic and functional outcomes were reported in all cases after 6 mo of follow-up. Few complications were reported after diode laser ablation.

Facial BCC was mostly seen in the elderly and men. The mean duration was 5.15 mo. The nose was the commonest involved site. Noduloulcerative lesions were seen in approximately half of the lesions. The age of the patients determined the histological type of the lesion (solid type was mostly seen in the age group ≤ 60 years, while, adenoid in the age group > 60 years). Diode laser ablation showed excellent functional and aesthetic outcomes following a 6-mo follow-up.

Studies on the relationship between stathmin 1 (STMN1) and cutaneous squamous cell carcinoma (cSCC) are limited. We aimed to evaluate the relationship between clinicopathological factors and STMN1 and p53 expressions in cSCC and compare them with those in the precursor lesions of cSCC and normal tissue. A total of 195 patients, followed between January 2014 and December 2021, with diagnoses of primary cSCC (n = 129), in situ cSCC (n = 20), or actinic keratosis (n = 46), as well as 29 histopathologically normal tissue samples, were included in the study. Immunohistochemical staining for STMN1 and p53 was performed. In the cSCC group, STMN1 scores were higher in poorly differentiated ( P = 0.001) and ulcerated ( P < 0.001) tumors. A linear relationship between STMN1 score and tumor area, tumor thickness, and mitosis was found ( P = 0.001, P = 0.003, and P < 0.001, respectively). There was no statistically significant correlation between STMN1 and p53 scores. Our results support the previous view that STMN1 may be associated with some adverse clinicopathological and high-risk features of cSCC. To the best of our knowledge, this is the first and largest study to investigate STMN1 expression in cSCC, precancerous lesions of cSCC, and normal tissues.

Basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma are the three main types of nonmelanoma skin cancers and their rates of occurrence and mortality have been steadily rising over the past few decades. For radiologists, it is still difficult to treat patients with advanced nonmelanoma skin cancer. Nonmelanoma skin cancer patients would benefit greatly from an improved diagnostic imaging-based risk stratification and staging method that takes into account patient characteristics. The risk is especially elevated among those who previously received systemic treatment or phototherapy. Systemic treatments, including biologic therapies and methotrexate (MTX), are effective in managing immune-mediated diseases; however, they may increase susceptibility to NMSC due to immunosuppression or other factors. Risk stratification and staging tools are crucial in treatment planning and prognostic evaluation. PET/CT appears more sensitive and superior to CT and MRI for nodal and distant metastasis as well as in surveillance after surgery. The patient treatment response improved with advent and utilization of immunotherapy and different immune-specific criteria are established to standardized evaluation criteria of clinical trials but none of them have been utilized routinely with immunotherapy. The advent of immunotherapy has also arisen new critical issues for radiologists, such as atypical response pattern, pseudo-progression, as well as immune-related adverse events that require early identification to optimize and improve patient prognosis and management. It is important for radiologists to have knowledge of the radiologic features site of the tumor, clinical stage, histological subtype, and any high-risk features to assess immunotherapy treatment response and immune-related adverse events.

To examine the clinicopathological features, mortality and morbidity in high-risk cutaneous squamous cell carcinoma (cSCC) patients in Western Australia (WA).

A retrospective cohort study was conducted through hospital record review on cSCC patients discussed at multidisciplinary meetings at the two largest WA hospitals between March 2015 and December 2016.

129/ 141 patients were evaluable with median follow-up of 43.9 (range 3.0-53.2) months. Patients were predominantly older males (84%) with significant comorbidities [Charlson Comorbidity Index (CCI) ≥5 (76%)] and history of previous non-melanoma skin cancer (57%) with advanced disease (57% stage IV without distant metastasis, AJCC 7^th edition). Pathological high-risk features were common including nodal extracapsular extension (47%) and cranial nerve involvement (16%). Clinical morbidity was significant with a median of 2 (range 0-13) excisions and 2 (range 0-21) cSCC-related hospitalisations for any cSCC event following the index case discussion. Recurrences of the primary index lesion occurred in 60% of patients and 20% had ≥2 recurrences. Median overall survival for patients with non-metastatic disease was 39.8 (range 25.9-53.7) months and 16.1 (range 0.2-32.0) months for metastatic disease. CCI ≥5, advanced nodal stage and ≥2 recurrences were significantly associated with mortality on multivariable analyses (p<0.05). Nodal extracapsular extension and any recurrences were identified as significant risk factors for disease-specific mortality on multivariable analyses (p<0.05).

High-risk cSCC patients have significant health needs represented by high baseline comorbidities, multiplicity of cSCC events and the number of health-care associated interventions. There is an unmet need for robust cancer data collection. This article is protected by copyright. All rights reserved.

Deep convolutional neural networks (DCNNs) can classify skin diseases at a level equivalent to a dermatologist, but their performance in specific areas requires further research.

To evaluate the performance of a trained DCNN-based algorithm in classifying benign and malignant lip diseases.

A training set of 1629 images (743 malignant, 886 benign) was used with Inception-Resnet-V2. Performance was evaluated using another set of 344 images and 281 images from other hospitals. Classifications by 44 participants (six board-certified dermatologists, 12 dermatology residents, nine medical doctors not specialized in dermatology and 17 medical students) were used for comparison.

The outcomes based on the area under curve, sensitivity and specificity were 0·827 [95% confidence interval (CI) 0·782-0·873], 0·755 (95% CI 0·673-0·827) and 0·803 (95% CI 0·752-0·855), respectively, for the set of 344 images; and 0·774 (95% CI 0·699-0·849), 0·702 (95% CI 0·579-0·808) and 0·759 (95% CI 0·701-0·813), respectively, for the set of 281 images. The DCNN was equivalent to the dermatologists and superior to the nondermatologists in classifying malignancy. After referencing the DCNN result, the mean ± SD Youden index increased significantly for nondermatologists, from 0·201 ± 0·156 to 0·322 ± 0·141 (P < 0·001).

DCNNs can classify lip diseases at a level similar to dermatologists. This will help unskilled physicians discriminate between benign and malignant lip diseases. What's already known about this topic? Deep convolutional neural networks (DCNNs) can classify malignant and benign skin diseases at a level equivalent to dermatologists. The lips are a unique feature in terms of histology and morphology. Previous studies of DCNNs have not investigated tumours on specific locations. What does this study add? This study shows that DCNNs can distinguish rare malignant and benign lip disorders at the same rate as dermatologists. DCNNs can help nondermatologists to distinguish malignant lip diseases. What are the clinical implications of this work? DCNNs can distinguish malignant and benign skin diseases even at specific locations such as the lips, as well as board-certified dermatologists. Malignant lip diseases are rare and difficult for less trained doctors to differentiate them from benign lesions. This study shows that in dermatology, DCNN can help improve decision-making processes for rare skin diseases in specific areas of the body.

Cutaneous squamous cell carcinoma (cSCC) has metastatic potential, but the prognostic value of current staging systems in nonselected patients is uncertain.

To assess the effect of risk factors for metastasis and to evaluate validity and usefulness of 4 staging systems for cSCC using population-based data.

This was a nationwide, population-based, nested case-control study. The Cancer Registry of Norway, which receives compulsory data on all cancers in the Norwegian population of approximately 5.2 million inhabitants. All patients diagnosed as having a primary invasive cSCC in the period 2000 to 2004 (n = 6721) were identified. Of these, 112 patients were diagnosed with metastasis within 5 years. As control patients, 112 patients with cSCC without metastases, matched for sex and age at diagnosis, were identified by random. Clinical data and biopsy specimens of primary cSCC were collected for all 224 patients. The biopsies were reexamined histologically by an experienced pathologist using well-established criteria for cSCC, yielding 103 patients with metastasis (cases) and 81 cSCC without metastasis (controls).

The ability of 4 cSCC staging systems (ie, the American Joint Committee on Cancer, 7th edition [AJCC 7] staging system, the staging system used by Breuninger et al, the Brigham and Women's Hospital [BWH] staging system, and the AJCC, 8th edition [AJCC 8] staging systems) to identify patients who developed metastasis with 5 years of follow-up. External validation was performed by logistic regression, discrimination (sensitivity, specificity, proportion correctly classified, concordance index), and calibration (R2, Hosmer-Lemeshow test, plots) statistics.

Of 6721 patients; 3674 (54.7%) were men and 3047 (45.3%) were women, with a mean age at diagnosis of 78 years. Of the 103 patients with cSCC diagnosed with metastasis within 5 years, 60 [58.3%] were men, and mean [SD] age 72.7 [13.5] years. Of the 81 patients with cSCC without metastasis, 51 [63.0%] were men, and mean [SD] age 74.6 [11.7] 15 years. The staging systems distinguished poorly to moderately between patients who developed metastasis and those who did not. The ability to cluster patients with similar outcomes within the same staging category was low, particularly when using the AJCC 7 system. Using the AJCC 7 system, the risk of metastasis for T2 patients was 3-fold, compared with T1 patients (OR, 2.96; 95% CI, 1.43-6.15). In the system used by Breuninger et al, high-risk categories for diameter and tumor thickness and the BWH system's T2b category collected relatively homogeneous groups. In the systems used by Breuninger et al and Brigham-Women's Hospital, risk of metastasis was significantly elevated with increasing stage or risk category. Using the system by Breuninger et al, the risk of metastasis was less than 3-fold for tumors in the high-risk category of the combined variable (OR, 2.72; 95% CI, 1.29-5.74). The BWH system gave ORs for metastasis at 4.6 (95% CI, 2.23-9.49) and 21.31 (95% CI, 6.07-74.88) for the T2a and T2b categories, respectively.

Using population-based data, 4 current staging systems for cSCC were unsatisfactory in identifying nonselected cSCC patients at high risk for metastasis. The system used by Breuninger gave the best results.

The role of telomere biology and telomerase activation in skin cancers has been investigated in melanoma and basal cell carcinoma but limited evidence is available for cutaneous squamous cell carcinoma (cSCC). We will review the current knowledge on the role of telomere and telomerase pathway in cSCC pathogenesis. At the somatic level, both long and short telomere lengths have been described in cSCC. This telomere dichotomy is probably related to two different mechanisms of tumour initiation which determines two tumour subtypes. Telomere shortening is observed during the invasive progression from in situ forms of cSCC, such as Bowen's disease (BD) and actinic keratosis (AK), to invasive cSCC. At the germline level, controversial results have been reported on the association between constitutive telomere length and risk of cSCC. Approximately 75⁻85% of cSCC tumours are characterized by a high level of telomerase activity. Telomerase activation has been also reported in AKs and BD and in sun-damaged skin, thus supporting the hypothesis that UV modulates telomerase activity in the skin. Activating TERT promoter mutations have been identified in 32⁻70% of cSCCs, with the majority showing the UV-signature. No significant correlation was observed between TERT promoter mutations and cSCC clinico-pathological features. However, TERT promoter mutations have been recently suggested to be independent predictors of an adverse outcome. The attention on telomere biology and telomerase activity in cSCC is increasing for the potential implications in the development of effective tools for prognostic assessment and of therapeutic strategies in patients with cutaneous cSCC.

Head and neck cancers comprise 4% of the cancer burden in the United States each year. Many types of head and neck cancers present as an asymptomatic, nontender neck mass or nonspecific symptoms, such as hoarseness, sore throat, and pain. Head and neck cancers are frequently diagnosed incidentally by the primary care physician or dentist. This review summarizes the epidemiology, clinical manifestations, diagnosis, and treatment of several common head and neck cancers in order to provide an increased awareness for the internist to facilitate early detection of these diseases.

Vismodegib is the first selective Hedgehog inhibitor approved for the treatment of locally advanced and metastatic basal cell carcinoma (BCC). In this article, we describe our experience with the use of this drug to treat advanced and/or multiple BCCs at a cancer center over 5 years.

We analyzed the following variables: patient age and sex; tumor location, size, type, and characteristics; time since onset; primary or recurrent status; duration of treatment; response to treatment (complete, partial, stabilization, or absence of response); adverse effects; and recurrences.

We treated 22 patients, of whom 20 had locally advanced BCCs and 2 had metastatic BCCs with lymph node involvement. The treatment was administered over a mean of 11.8 months. Nine patients (41%) achieved complete response and 10 (45%) partial response. The disease was stabilized in 3 (14%). Two patients relapsed after a median of 21 months. The main adverse effects were dysgeusia, alopecia, and muscle cramps, all of which were mild. None of the patients developed squamous cell carcinoma in an area treated with vismodegib, although metatypical changes were observed after treatment.

With a response rate of 96%, vismodegib is a safe and effective treatment for locally advanced BCC. Adverse effects are generally mild but they need to be taken into account owing to their high frequency.

Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma. Incidence of MCC continues to rise, and risk factors include advanced age, pale skin, chronic sun exposure, and immune suppression. Diagnosing MCC utilizes a combination of morphology and immunohistochemistry. Merkel cell polyomavirus (MCPyV) is present in approximately 70-80% of MCCs and represents a key pathogenic driver in those MCCs. In contrast, MCPyV-negative MCCs arise through progressive accumulation of ultraviolet-light induced somatic mutations. Staging of MCC proceeds according to the American Joint Commission on Cancer (AJCC) 8th Edition, which utilizes features of the primary tumor together with regional lymph node(s) (clinically and/or pathologically detected) and/or distant metastases. Many potentially useful biomarkers have been studied to refine risk stratification in MCC. In recent years, the host immune infiltrate has been leveraged as immune checkpoint blockade has emerged as an efficacious mode of treatment for patients with advanced MCC.

Non-melanoma skin cancer represents one-third of all malignancies and its incidence is expected to rise until the year 2040. Cutaneous squamous cell carcinoma (cSCC) represents 20 % of all non-melanoma skin cancer and is a deadly threat owing to its ability to metastasize to any organ in the body. Therefore, a better understanding of cSCC is essential to strengthen preventative measures and curable treatment options. Currently, research demonstrates that cSCC is diagnosed at a rate of 15-35 per 100,000 people and is expected to increase 2-4 % per year. With respect to metastatic cSCC, this disease is more common in men; people over the age of 75 years; and inhabitants of the south and mid-west USA. In 2010, the American Joint Committee on Cancer updated the Cancer Staging Manual's primary tumor designation to now include high-risk factors; however, factors such as immunosuppression and tumor recurrence were not included. Other staging systems such as Brigham and Women's Hospital have allowed for increased stratification of cSCC. High-risk cSCC is defined as a cSCC that is staged as N0, extends beyond basement membrane, and has high-risk features associated with sub-clinical metastasis. High-risk features are depth of invasion (>2 mm), poor histological differentiation, high-risk anatomic location (face, ear, pre/post auricular, genitalia, hands, and feet), perineural involvement, recurrence, multiple cSCC tumors, and immunosuppression. Epidermal growth factor receptor and nuclear active IκB kinase (IKK) expression are also predictive of metastatic capabilities. Clinically, the initial lesions of a cSCC tumor can present as a painless plaque-like or verrucous tumor that can ultimately progress to being large, necrotic, and infected. Tumors can also present with paresthesias or lymphadenopathy depending on the location involved. With respect to prognosis, metastatic cSCC is lethal, with several large studies demonstrating a mortality rate of >70 %. Therefore, treatment of metastatic cSCC is difficult and depends on the location involved and extent of metastasis. Treatment options include surgery, radiation therapy, chemotherapy, and any combination of the above. Surgery alone can be used for metastatic cSCC treatment, but is not as effective as surgery in conjunction with radiation therapy. Radiation therapy has some success as a monotherapy in low-risk or cosmetically sensitive areas such as the external ear, eyelid or nose. According to the 2013 National Comprehensive Cancer Network Guidelines, cisplatin as a single agent or combined with 5-fluorouracil hold the strongest support for the treatment of metastatic cSCC; however, the supporting evidence is inconsistent and a curative chemotherapeutic approach is still lacking. Epidermal growth factor receptor inhibitors are a newer class of agents being used in metastatic cSCC and hold some promise as a therapy for this disease. Other areas of interest in finding curative treatments for metastatic cSCC include p53, hypermethylation of specific genes, chromatin remodeling genes, and the RAS/RTK/PI3K pathway. This review addresses the epidemiology, staging, risk factors, clinical presentation, management, and new trends in the treatment of high-risk and metastatic cSCC.

Squamous cell carcinoma of the scalp is a common clinical problem in an aging population. Despite its high incidence, little has been documented regarding treatment or outcomes.

We retrospectively analysed 235 cases treated with curative intent at Peter MaCallum Cancer Centre between 1998 and 2010. The cohort was analysed for its characteristics, management, survival and prognostic factors.

The patients were primarily male (88%) with a median age of 79 years (range 53-98 years). There was a high proportion of immunosuppressed patients (29%) and stage T2 (48%) tumours. Management included surgery (45%), radiotherapy (28%) and surgery and adjuvant radiotherapy (26%). Median follow up from treatment was 4.5 years. Estimated 5-year overall survival (OS), disease-specific survival and progression-free survival (PFS) were 59, 94 and 51%, respectively. The 5-year cumulative incidence of local and regional relapse was 11 and 7%, respectively. There were four patients who developed distant metastases and died of their disease. Statistically significant prognostic factors identified for poor outcomes for OS and PFS were T2 stage (hazard ratio [1.7 and 2.1) and immunosuppression (HR 3.3 and 3.4).

We conclude the presence of immunosuppression and T2 stage is prognostic for survival. Further research to establish treatment principles is warranted.

Merkel cell carcinoma (MCC) is an aggressive cancer with frequent metastasis and death with few effective therapies. Because programmed death ligand-1 (PD-L1) is frequently expressed in MCC, immune checkpoint blockade has been leveraged as treatment for metastatic disease. There is therefore a critical need to understand the relationships between MCPyV status, immune profiles, and patient outcomes.

IHC for CD3, CD8, PD-1, PD-L1, and MCPyV T-antigen (to determine MCPyV status) was performed on 62 primary MCCs with annotated clinical outcomes. Automated image analysis quantified immune cell density (positive cells/mm²) at discrete geographic locations (tumor periphery, center, and hotspot). T-cell receptor sequencing (TCRseq) was performed in a subset of MCCs.

No histopathologic variable associated with overall survival (OS) or disease-specific survival (DSS), whereas higher CD3⁺ (P = 0.004) and CD8⁺ (P = 0.037) T-cell density at the tumor periphery associated with improved OS. Higher CD8⁺ T-cell density at the tumor periphery associated with improved DSS (P = 0.049). Stratifying MCCs according to MCPyV status, higher CD3⁺ (P = 0.026) and CD8⁺ (P = 0.015) T-cell density at the tumor periphery associated with improved OS for MCPyV⁺ but not MCPyV^- MCC. TCRseq revealed clonal overlap among MCPyV⁺ samples, suggesting an antigen-specific response against a unifying antigen.

These findings establish the tumor-associated immune infiltrate at the tumor periphery as a robust prognostic indicator in MCC and provide a mechanistic rationale to further examine whether the immune infiltrate at the tumor periphery is relevant as a biomarker for response in ongoing and future checkpoint inhibitor trials in MCC. Clin Cancer Res; 22(22); 5553-63. ©2016 AACR.

Merkel cell polyomavirus (MCPyV) is the main aetiological agent of Merkel cell carcinoma (MCC). Serum antibodies against the major MCPyV capsid protein (VP1) are detected in the general population, whereas antibodies against MCPyV oncoproteins (T antigens) have been reported specifically in patients with MCC.

The primary aim was to assess whether detection of serum antibodies against MCPyV proteins at baseline was associated with disease outcome in patients with MCC. The secondary aim was to establish whether evolution of these antibodies during follow-up was associated with the course of the disease.

Serum T-antigen and VP1 antibodies were assessed by enzyme-linked immunosorbent assay using recombinant proteins in a cohort of 143 patients with MCC, including 84 patients with serum samples available at baseline.

Low titres of VP1 antibodies at baseline (< 10 000) were significantly and independently associated with increased risk of recurrence [hazard ratio (HR) 2·71, 95% confidence interval (CI) 1·13-6·53, P = 0·026] and death (HR 3·74, 95% CI 1·53-9·18, P = 0·004), whereas T-antigen antibodies were not found to be associated with outcome. VP1 antibodies did not differ between patients in remission and those with recurrence or progression during follow-up. However, T-antigen antibodies were more frequently detected in patients with recurrence or progression at 12 months (P = 0·020) and 24 months (P = 0·016) after diagnosis.

VP1 antibodies constitute a prognostic marker at baseline, whereas T-antigen antibodies constitute a marker of disease recurrence or progression if detected > 12 months after diagnosis.

Label-free DNA imaging is highly desirable in biology and medicine to perform live imaging without affecting cell function and to obtain instant histological tissue examination during surgical procedures. Here we show a label-free DNA imaging method with stimulated Raman scattering (SRS) microscopy for visualization of the cell nuclei in live animals and intact fresh human tissues with subcellular resolution. Relying on the distinct Raman spectral features of the carbon-hydrogen bonds in DNA, the distribution of DNA is retrieved from the strong background of proteins and lipids by linear decomposition of SRS images at three optimally selected Raman shifts. Based on changes on DNA condensation in the nucleus, we were able to capture chromosome dynamics during cell division both in vitro and in vivo. We tracked mouse skin cell proliferation, induced by drug treatment, through in vivo counting of the mitotic rate. Furthermore, we demonstrated a label-free histology method for human skin cancer diagnosis that provides comparable results to other conventional tissue staining methods such as H&E. Our approach exhibits higher sensitivity than SRS imaging of DNA in the fingerprint spectral region. Compared with spontaneous Raman imaging of DNA, our approach is three orders of magnitude faster, allowing both chromatin dynamic studies and label-free optical histology in real time.

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.

Aggressive cutaneous squamous cell carcinoma (cSCC) is often a disfiguring and lethal disease. Very little is currently known about the mutations that drive aggressive cSCC.

Whole-exome sequencing was performed on 39 cases of aggressive cSCC to identify driver genes and novel therapeutic targets. Significantly, mutated genes were identified with MutSig or complementary methods developed to specifically identify candidate tumor suppressors based upon their inactivating mutation bias.

Despite the very high-mutational background caused by UV exposure, 23 candidate drivers were identified, including the well-known cancer-associated genes TP53, CDKN2A, NOTCH1, AJUBA, HRAS, CASP8, FAT1, and KMT2C (MLL3). Three novel candidate tumor suppressors with putative links to cancer or differentiation, NOTCH2, PARD3, and RASA1, were also identified as possible drivers in cSCC. KMT2C mutations were associated with poor outcome and increased bone invasion.

The mutational spectrum of cSCC is similar to that of head and neck squamous cell carcinoma and dominated by tumor-suppressor genes. These results improve the foundation for understanding this disease and should aid in identifying and treating aggressive cSCC.

Recent guidelines from the American Joint Committee on Cancer (AJCC) and National Comprehensive Cancer Network (NCCN) have been proposed for the assessment of "high-risk" cutaneous squamous cell carcinomas (cSCCs). Though different in perspective, both guidelines share the common goals of trying to identify "high-risk" cSCCs and improving patient outcomes. Thus, in theory, both definitions should identify a similar proportion of "high-risk" tumors. We sought to evaluate the AJCC and NCCN definitions of "high-risk" cSCCs and to assess their concordance. Methods. A retrospective review of head and neck cSCCs seen by an academic dermatology department from July 2010 to November 2011 was performed. Results. By AJCC criteria, most tumors (n = 211,82.1%) were of Stage 1; 46 tumors (13.9%) were of Stage 2. Almost all were of Stage 2 due to size alone (≥2 cm); one tumor was "upstaged" due to "high-risk features." Using the NCCN taxonomy, 231 (87%) of tumors were "high-risk." Discussion. This analysis demonstrates discordance between AJCC and NCCN definitions of "high-risk" cSCC. Few cSCCs are of Stage 2 by AJCC criteria, while most are "high-risk" by the NCCN guidelines. While the current guidelines represent significant progress, further studies are needed to generate a unified definition of "high-risk" cSCC to optimize management.

Cutaneous squamous cell carcinoma (cSCC) constitutes the most common cancer capable of metastasis. While the latest version of the American Joint Committee on Cancer guidelines represents a significant step forward in accurate staging of cSCC, several proven independent risk factors remain excluded. We review the current literature on the incidence and proven independent risk factors of metastasis for cSCC and proposes their full inclusion in the staging system for primary lesions.

Skin has the highest incidence and variety of tumors of all organs. Its structure is of great complexity, and every component has the potential to originate a skin neoplasm (SN). Because of its exposed nature, skin is vulnerable to carcinogenic stimuli such as UV radiation. Various entities can cause SN. Nonmelanotic skin cancers (NMSC) are the most common of all cancers, with over one million cases diagnosed annually in the US. Basal cell carcinoma (BCC) accounts for approximately 80% of all NMSC, most of the remaining 20% being squamous cell carcinoma (SCC). The skin of the head and neck is the most common site for tumors, accounting for more than 80% of all NMSC. BCC, SCC, and malignant melanomas (MM) represent 85-90% of all SN. Merkel cell tumors (MCC), lymphoepithelioma-like carcinomas of the skin (LELCS), dermato-fibro-sarcomas, leiomyosarkomas, and Kaposi-sarcomas are less frequent in the facial skin region and the external ear. Based on data from the German Federal Cancer Registry (2003/2004), 140,000 people in Germany were affected by SN (100,000 BCC, 22,000 SCC, 22,000 MM). This number increases considerably if malignant precursors, such as actinic keratosis, are included. Each year, the frequency of SN diagnosis rises by 3-7%. Among all known malignant tumors, MM exhibits the highest rate of increase in incidence. In the past, SN was primarily diagnosed in people aged 50 years or older. However, recently, the risk for developing SN has shifted, and younger people are also affected. Early diagnosis is significantly correlated with prognosis. Resection of SN creates defects that must be closed with local or microvascular flaps to avoid functional disturbing scar formation and deflection of the nose, eyelids, or lips. All therapeutic strategies for SN, the current standard for adjuvant and systemic treatment, and the management of the increasing number of patients under permanent blood thinner medication are described with regard to the treatment of SN.

If detected early, squamous cell carcinoma can be cured. This type of cancer accounts for 90% of head and neck malignancies and can be highly metastatic. Radiation and chemotherapy are recommended for advanced lesions such as described in this case.

Immune suppressed organ transplant recipients suffer increased morbidity and mortality from primary cutaneous SCC. We studied tumor microenvironment in transplant-associated SCC (TSCC), immune-competent SCC and normal skin by IHC, IF and RT-PCR on surgical discard. We determined T cell polarization in TSCC and SCC by intracellular cytokine staining of T cell crawl outs from human skin explants. We studied the effects of IL-22, an inducer of keratinocyte proliferation, on SCC proliferation in vitro. SCC and TSCC are both associated with significantly higher numbers of CD3(+) and CD8(+) T cells compared to normal skin. TSCC showed a higher proportion of Foxp3(+) T regs to CD8(+) T cells compared to SCC and a lower percentage of IFN-γ producing CD4(+) T cells. TSCC, however, had a higher percentage of IL-22 producing CD8(+) T cells compared to SCC. TSCC showed more diffuse Ki67 and IL-22 receptor (IL-22R) expression by IHC. IL-22 induced SCC proliferation in vitro despite serum starvation. Diminished cytotoxic T cell function in TSCC due to decreased CD8/T-reg ratio may permit tumor progression. Increased IL-22 and IL-22R expression could accelerate tumor growth in transplant patients. IL-22 may be an attractive candidate for targeted therapy of SCC without endangering allograft survival.

Chronic leg ulcers are one of the most common medical conditions and are a substantial source of morbidity.

To investigate the prevalence of skin cancer mimicking leg ulcers.

This observational study included all patients with a clinical diagnosis of chronic leg ulcers (CLU) admitted to the Wound Care Unit, Division of Dermatology, University of Bologna, between March 2008 and February 2011. Patients' general health was assessed, and skin biopsy and vascular Doppler of the lower limbs were performed.

Two hundred fifty-seven patients ages 45 to 98 with CLU were included. Skin biopsies were performed in all patients. Pathologic results showed that 10 patients had ulcerative lesions of neoplastic origin. Surgical excision was performed in all patients with neoplasms. After at least 1 year of follow-up, no recurrences were observed.

Our findings highlight the important role of systematic biopsies in diagnosing ulcerated tumors of the lower legs and indicate a high prevalence of large ulcerated basal cell carcinomas.

Recently the "Union for International Cancer Control" (UICC) and the "American Joint Committee on Cancer" (AJCC) changed their TNM (tumor, node, metastasis) classification of cutaneous carcinomas.

We compared these classifications, tested their practicability with 615 prospectively collected, unselected, primary cutaneous squamous cell carcinomas, and introduced additional classification criteria.

Neither classification contains information about prognosis. Non-metastasizing types of cutaneous carcinoma should be excluded. The vermilion border of the lower lip and the eyelids should be included. Both systems have been improved, but in part they are irreproducible. The AJCC has introduced six "high-risk features" to differentiate between T1 and T2. However, this does not seem reasonable. Only rare cases are classified as T4. Both systems have different N classifications. A clinical cT classification based on tumor size 2 cm seems reasonable but not sufficient. It should be complemented by a postoperative p (pathologic) T classification based on tumor thickness: "no risk"≤ 2 mm thickness (0% risk of metastasis), "low risk" > 2 mm to 6 mm thickness (4% risk of metastasis), and "high risk" > 6 mm thickness (16% risk of metastasis). Immune suppression, poor differentiation/desmoplasia, and the ear as tumor site are additional risk factors for metastasis, currently not evaluable.

The classifications are unsuitable for a realistic estimate of the risk of metastasis which is possible using a combination of tumor size and thickness. The N staging system should consider histopathologic findings.

The 7th edition of the AJCC Cancer Staging Manual represents a dramatic shift in the way that cutaneous squamous cell carcinoma (cSCC) is staged, in that it is first attempt to incorporate evidence-based medicine into the staging guidelines for cSCC. In our opinion, the changes made to the seventh edition represent a significant improvement over previous editions and will ultimately lead to improved patient stratification, more accurate prognostic data, and a better framework to guide clinical decision making. However, there are a number of issues within the latest guidelines that require clarification or are impractical for clinical practice. The purpose of this paper is to highlight the key changes to the 6th edition staging manual as they pertain to cSCC, to point out impractical component of the 7th edition and/or aspects that require further clarification, and to make recommendations that address any current shortcomings to improve subsequent editions. Specific focus will be given to the inclusion of separate guidelines for cSCC and Merkel cell carcinoma (MCC), the incorporation of high-risk factors as modifiers of T stage, the addition of new guidelines for advanced T stage, and the changes in stratification of lymph node status. This paper is modified from a more comprehensive treatment of the staging of nonmelanoma skin cancer by Warner and Cockerell entitled "The new 7th edition American joint committee on cancer staging of cutaneous nonmelanoma skin cancer: a critical review," in the American Journal of Clinical Dermatology (paper accepted, pending publication).