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The 7th Edition AJCC Staging System for Cutaneous Squamous Cell Carcinoma Accurately Predicts Risk of Recurrence for Heart and Lung Transplant Recipients
Abstract
Cutaneous squamous cell carcinoma (cSCC) is the most common malignancy after solid organ transplantation, with an increased risk of recurrence and metastasis over the general population. The newly updated 7th edition American Joint Committee on Cancer (AJCC) staging system for cSCC is based on consensus expert opinion and requires validation in large cohort studies and in specific patient subpopulations.
Our objective was to evaluate the risk of cSCC recurrence in a high-risk population of heart and lung transplant recipients, based on the 7th edition AJCC staging system.
We performed a 10-year retrospective cohort study of all primary cSCC diagnosed in heart and lung transplant recipients at a tertiary care academic dermatology center.
The cumulative incidence of local recurrence was 4% for cSCC in situ and 19% for stage I cSCC at 5 years, and 54% for stage II cSCC at 3 years. Stage II tumors had a 10-fold greater risk of recurrence than stage I, and a 43-fold greater risk of recurrence than in situ tumors.
This study is limited to a specific patient subgroup at a tertiary care center, and may not be generalizable to all populations.
Heart and lung transplant recipients are at high risk for local recurrence of cSCC. These data substantiate the prognostic accuracy of the newly updated 7th edition AJCC staging system for stage 0, I, and II cSCC in this population and demonstrate the aggressive behavior of this cancer in immunosuppressed patients.
... -LR [51] -NM [2,24,25] -DSD [2,14,19,31] [ 2 cm is not significant: ...
... -LR [2,21,37,51] -NM [21,52] -DSD [14,21] Ear is a high-risk location for: ...
... -LR [2,51] -DSD [14] Lower and upper extremities are not a high-risk location for: ...
Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer, and the number of deaths due to cSCC is estimated to be greater than the number attributed to melanoma. While the majority of cSCC tumors are resectable with clear margins by standard excision practices, some lesions exhibit high-risk factors for which there is evidence of their association with recurrence, metastasis, and disease-specific death. The most commonly used staging systems and guidelines in the USA for cSCC are based on these clinical and pathologic high-risk factors; however, these are limited in their ability to predict adverse events, thus posing a challenge for implementing risk-directed patient management. Since the development of local recurrence and/or metastasis has a profound impact on the survival of patients with cSCC, accurate identification of patients at high risk for poor outcomes is critical, potentially allowing for early and appropriate adjuvant therapy. This review summarizes the current cSCC literature with a focus on how differing clinical assessments within each of the five selected risk factors (perineural invasion, differentiation, depth of invasion, size, and location) can influence the evaluation of patient outcomes, along with summarizing the utility of staging and guidelines, and highlighting the potential for molecular tools to improve upon cSCC risk assessment.
... Aunque en té rminos absolutos el CEC tiene un pronó stico favorable, su elevada frecuencia y el incremento en la esperanza de vida de la població n lo convierten en una entidad clínicamente relevante 4,11 . Para considerar los factores pronó sticos en el CEC, nos centraremos en primer lugar en los factores pronó stico clínicos y, a continuació n, en los factores histopatoló gicos má s importantes, algunos de los cuales se emplean para clasificar a los pacientes en los distintos sistemas de estadificació n [12][13][14] . Bá sicamente son estos los factores pronó sticos que nos permiten etiquetar a un tumor como de bajo o alto riesgo y cuyo conocimiento nos permite abordar el manejo de la enfermedad de forma adecuada. ...
... El tamañ o horizontal del tumor primario es un factor pronó stico bien conocido en el CEC [13][14][15][16][17][18][19][20][21][22][23][24] . Diversos estudios han podido relacionar su influencia sobre el riesgo de recidiva local 12,22,25 , de metá stasis 14,15,[17][18][19]21,23 o de ambas 13,16,24 . El punto de corte se establece en 20 mm de diá metro y se ha asociado a un riesgo 3 veces mayor de recidiva local y 6 veces má s alto de metá stasis 24 . ...
... El punto de corte se establece en 20 mm de diá metro y se ha asociado a un riesgo 3 veces mayor de recidiva local y 6 veces má s alto de metá stasis 24 . De hecho, este es un pará metro que se emplea en el sistema de estadificació n del American Joint Committee on Cancer (AJCC) 12 y en uno alternativo desarrollado má s recientemente 13,20 . Localizació n del tumor primario en un á rea de alto riesgo La localizació n del tumor tambié n se ha relacionado con el pronó stico de la enfermedad. ...
... The ''cases'' were defined as lesions where there was evidence of progression within 24 months of diagnosis (prior studies of cSCC in immunosuppressed patients have reported a median time to progression of 6 months). 18 Lesions for which metastases were present at the time of initial diagnosis were regarded as cases. The ''controls'' were defined as lesions where there was no evidence of further progression with a follow-up time of at least 24 months. ...
... [23][24][25][26] While earlier schemes focused predominantly on size and features of advanced spread (such as bony invasion), more recent schemes have included histological parameters such as depth of invasion, poor differentiation, and perineural invasion. 15 While these schemes show broad correlation with outcome in organ transplant recipients, 8,18 a background of immunosuppression is in itself a ''high-risk'' feature, 16 and some have suggested that it should be included as such in formal staging schemes. [27][28][29] The objective of this study was to investigate the correlation of histological parameters with tumor progression in an immunosuppressed population, as it seemed plausible that some criteria which were not independently predictive at a population level may have more significance in this high-risk group. ...
Background
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.
Objectives
To determine the histological parameters which have independent prognostic value for cutaneous squamous cell carcinoma arising in renal transplant recipients.
Methods
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.
Results
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.
Limitations
The retrospective nature and the low number of cases compared to controls.
Conclusion
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.
... The malignancy extension was categorised as either lymphatic or venous invasion. 25,26 We used the tumour staging protocol of the American Joint Committee on Cancer (AJCC) TNM staging system 7th edition for nonmelanoma skin cancer (NMSC). The staging is based on tumour diameter, lymph node metastatic invasion, and distant metastasis grading. ...
... The staging is based on tumour diameter, lymph node metastatic invasion, and distant metastasis grading. [25][26][27][28] The surgical intervention was decided according to tumour characters, staging, and ulcer depth. The ulcer was excised with a safety margin not less than 3 cm. ...
The study spotlights a severe uncommon post‐burn complication, Marjolin's ulcer, in upper Egypt plastic and wound care centres. This problem is mainly related to inadequate medical care and awareness. No community or race is immune. The underlying malignant transformation mechanism remains unclear. The study aims, according to our experience, to review the prognostic factors through the management protocol of Marjolin's ulcers. This prospective study was conducted in the Aswan University Plastic & Burn surgery department in South Egypt between 2013 and 2020 and investigated 226 patients with chronic post‐burn ulceration. Nineteen cases were proved to have Marjolin's ulcer, and the other cases that had been excluded from being malignant went for reconstruction with split‐thickness skin graft with/without flap after adequate ulcer debridement. The surgical, oncologic, radiologic indications, and prognostic factors were reviewed according to our management outcome—the assessment with follow‐up period extended over 5 years. Histopathology of ulcers ranged among mild, moderate, and poorly differentiated squamous cell carcinoma. One scalp ulcer case showed basosquamous pathology. Most cases presented at age above 50, but no age was immune. The mean latent period was 29 years on average. The lesions' sites varied in their anatomic location where they involved the upper extremity, the scalp, and the lower extremity that had a predilection. Although surgical excision is the primary management line for tumour ablation, other factors may change the management course. During the follow‐up period, neoplasm recurrence in the form of lymph node enlargement and/or locoregional metastasis was detected in eight cases. Within 1 year after the intervention, six recurrent cases died, and two were saved. In addition to the case study, this paper reviewed the literature and provided our team a good experience in light of the NCCN protocol for non‐melanotic cutaneous carcinoma, although we suffered limited medical resources. It is concluded that early accurate diagnosis, low‐grade malignancy, and well‐planned individualised surgery with adjuvant radiotherapy were the best prognostic factors. The close follow‐up for an early sign of disease recurrence is paramount.
... Patients with certain hematologic malignancies, organ transplants, HIV, pharmacologic immunosuppression, and certain genodermatoses are at higher risk of developing SCC [28][29][30][31]. Moioli et al. recently noted a non-significant, but higher percentage of residual SCCis or SCC in serially sectioned excision specimens of biopsy-proven SCCis from immunosuppressed patients [32]. ...
... The rate of complete tumor clearance after biopsy was significantly lower in immunosuppressed patients than in immunocompetent patients. Metchnikoff et al. reported a 5-year recurrence rate of 4% for SCCis in organ transplant patients treated primarily with non-excisional treatments [29]. In a single retrospective study, recurrence of SCCis after surgical excision was 9% in immunocompromised patients, compared to 3% in immunocompetent patients [33]. ...
The treatment of cutaneous squamous cell carcinoma in situ by Mohs micrographic surgery is currently deemed as appropriate by the Mohs Appropriate Use Criteria. However, squamous cell carcinoma in situ is a very superficial, indolent, low-risk tumor amenable to destructive and non-surgical treatments. It is uncommon for squamous cell carcinoma in situ to have progressed to invasive malignancy subsequent to definitive management. The suggestion that squamous cell carcinoma in situ on certain anatomic locations has a poorer prognosis is widely assumed but lacks an evidence base. We recommend that most primary squamous cell carcinoma in situ in non-immunosuppressed patients be scored inappropriate or uncertain for Mohs micrographic surgery by the Mohs Appropriate Use Criteria. Multiple other efficacious treatment options exist for managing squamous cell carcinoma in situ, including curettage and cryotherapy, curettage and electrodessication, and topical therapies.
... T stage (T1, T2) was classified according to the American Joint Committee on Cancer (AJCC) guidelines 2010. 23 GR was calculated by dividing the largest tumour diameter (mm) by the tumour age (time from when the tumour was noticed to when it was diagnosed/ removed, in months). Tumour diameter was determined by histological studies using H&E-stained slides to avoid possible interobserver measurement bias. ...
... In addition, rapidly growing tumours (> 4 mm/month) were associated with the early appearance of events of poor outcome in this study, in contrast to slowly growing Clinical and Experimental Dermatology tumours (< 4 mm/month). In our cohort, faster GR was also associated with higher tumour stage in the AJCC 23 staging system; however, GR was independent of other tumour features, such as the grade of differentiation and of the growth pattern of invasion. ...
Background
Cutaneous squamous cell carcinoma (cSCC) represents the most common form of skin cancer after basal cell carcinoma, and can be both locally invasive and metastatic to distant sites. Growth rate (GR) has been poorly evaluated in cSCC, despite clinical evidence suggesting that GR is an important risk factor in cSCC.
Aim
To analyse the influence of GR in cSCC prognosis.
Methods
We retrospectively evaluated GR in a series of 90 cSCCs and tried to correlate GR with prognosis in cSCC.
Results
We demonstrated that tumours with a GR of > 4 mm/month exhibit a higher risk of nodal progression and a shorter progression time to lymph node metastasis in cSCC than those with GR of < 4 mm/month. As expected, GR correlated with tumour proliferation, as determined by Ki‐67 expression.
Conclusions
We consider a GR of 4 mm/month as the cutoff point that distinguishes between rapid‐ and slow‐progressing tumours and, more importantly, to identify a subset of high‐risk cSCCs.
... Some pathologic characteristics, such as the tumor depth in millimeters, are not recorded consistently and may impact some instances of AJCC staging. Furthermore, certain AJCC stages of CVC fall short of exact prognostic classification when outcome metrics differ (15)(16)(17). ...
Background
The aim of this study was to establish and verify a predictive nomogram for patients with cutaneous verrucous carcinoma (CVC) who will eventually survive and to determine the accuracy of the nomogram relative to the conventional American Joint Committee on Cancer (AJCC) staging system.
Methods
Assessments were performed on 1125 patients with CVC between 2004 and 2015, and the results of those examinations were recorded in the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly divided at a ratio of 7:3 into the training (n = 787) and validation (n = 338) cohorts. Predictors were identified using stepwise regression analysis in the COX regression model for create a nomogram to predict overall survival of CVC patients at 3-, 5-, and 8-years post-diagnosis. We compared the performance of our model with that of the AJCC prognosis model using several evaluation metrics, including C-index, NRI, IDI, AUC, calibration plots, and DCAs.
Results
Multivariate risk factors including sex, age at diagnosis, marital status, AJCC stage, radiation status, and surgery status were employed to determine the overall survival (OS) rate (P<0.05). The C-index nomogram performed better than the AJCC staging system variable for both the training (0.737 versus 0.582) and validation cohorts (0.735 versus 0.573), which AUC (> 0.7) revealed that the nomogram exhibited significant discriminative ability. The statistically significant NRI and IDI values at 3-, 5-, and 8-year predictions for overall survival (OS) in the validation cohort (55.72%, 63.71%, and 78.23%, respectively and 13.65%, 20.52%, and 23.73%, respectively) demonstrate that the established nomogram outperforms the AJCC staging system (P < 0.01) in predicting OS for patients with cutaneous verrucous carcinoma (CVC). The calibration plots indicate good performance of the nomogram, while decision curve analyses (DCAs) show that the predictive model could have a favorable clinical impact.
Conclusion
This study constructed and validated a nomogram for predicting the prognosis of patients with CVC in the SEER database and assessed it using several variables. This nomogram model can assist clinical staff in making more-accurate predictions than the AJCC staging method about the 3-, 5-, and 8-year OS probabilities of patients with CVC.
... In the literature, there are also cross-sectional studies reporting that these changes are more frequent, earlier and more severe in patients undergoing heart transplant than in patients with other solid organ transplants. 1,2 It is suggested that the dose of immunosuppressive treatment used in heart transplant is higher than the dose used in other solid organ transplants. In this review, similar to the literature, general knowledge about solid organ transplantation and experiences of kidney transplant patients have been utilized. ...
In solid organ transplant patients; many skin diseases are more common and more resistant to treatment, because of the multiple medications and immunosuppressive therapies. In order to increase survival, it is important to evaluate and follow these patients with a multidisciplinary team including the dermatologist. In this review, the following are reviewed along with the current literature; skin and mucosa findings due to immunosuppressive therapies used in solid organ transplant patients, inflammatory, infectious and neoplastic skin diseases which are increased compared to the normal population, and the important points in diagnosis and treatment of these diseases.
... However, approximately 5% of patients with NMSC harbor highrisk clinicopathologic features for loco-regional recurrence, distant metastasis, and death [7,8]. The American Joint Committee of Cancer (AJCC) describes several factors associated with high-risk of tumor recurrence and metastasis such as the site of disease (ears and lips), poor histological differentiation, perineural invasion (PNI), and host factors such as immunosuppression [9]. ...
Opinion statement:
The mainstay treatment of localized non-melanoma skin cancer (NMSC) is surgical excision or Mohs surgery. However, approximately 5% of patients with NMSC harbor high-risk clinicopathologic features for loco-regional recurrence, and distant metastasis. Prognostic factors such as close or positive margins, tumor size ≥ 2 cm, poor tumor differentiation, perineural invasion, depth of invasion, and immunosuppression have all been associated with increased loco-regional recurrence and impaired survival rates. In these patients more aggressive treatments are needed and radiotherapy (RT) is often discussed as adjuvant therapy after surgical resection. Due to the retrospective setting and the heterogeneity of the available studies, indications for adjuvant RT in patients with localized resected NMSC harboring high-risk features remain debated. Studies highlighting the limitations of our current understanding of the independent prognosis of each risk factor are needed to better define the role of adjuvant RT on outcome of localized NMSC and standardize its indications in the clinical setting.
... The tumor thickness was chosen as the major criterion for risk stratification analogous to the data of Brantsch et al. and tumors with a tumor thickness of less than 5 mm were not included in this analysis [5]. However, all tumors included showed a diameter of more than 20 mm, which corresponds to a tumor stage of at least T2 according to the current AJCC classification [24]. ...
Squamous cell carcinomas are among the most common skin tumors and show a risk of metastasis depending on various factors such as tumor thickness, localization, histological subtype and immune status of the patient. Sentinel lymph node biopsy (SLNB) SLNB represents a possibility for assessing the locoregional lymph node status. In this study, the role of the SLNB in lymph node status and survival was analyzed. Retrospectively, 720 patients with high-risk squamous cell carcinoma (tumor thickness > 5 mm) were examined. 150 patients agreed to SLNB, 570 patients did not undergo histologic confirmation of lymph node status and were included directly in follow-up. In 101 patients, a sentinel lymph node was successfully marked and extirpated, followed by regular follow-up examinations.
A total of 11.11% of the patients showed lymph node metastasis in the course of their treatment, with no difference in the proportion of patients in the SLNB group (11.9%) and the observation group (11.4%) (p = 0.873). The proportion of distant metastasis also did not differ between the groups (p = 0.898). In 3.96% of the patients in the SLNB group, a metastasis was found in the sentinel lymph node. Tumor-specific death was observed in 7.14% of the patients in the SLNB group and 4.74% in the observation group (p = 0.269). Although SLNB is a principally suitable method for determining lymph node status, the available data do not provide any benefit regarding further metastasis or tumor-specific survival.
... El pobre grado diferenciación se ha relacionado con un mal pronóstico del CEC en múltiples estudios 11,16,17,[19][20][21][22][25][26][27][69][70][71][72][73][74][75][76][77][78][79] . Según las series, entre el 8 76 y el 25% 16 de los CEC son pobremente diferenciados. ...
Resumen
El carcinoma epidermoide cutáneo (CEC) es el segundo tumor más frecuente en humanos y tiene una incidencia creciente e infraestimada. En la literatura nos encontramos con términos como CEC de alto riesgo, CEC localmente avanzado, CEC metastásico, CEC avanzado y CEC agresivo, que pueden dar lugar a confusión y que en algunas ocasiones no se encuentran del todo bien definidos. En esta revisión pretendemos aclarar estos conceptos con la idea de lograr homogeneidad en su descripción, algo que parece necesario a la luz de los nuevos fármacos aprobados y en desarrollo para este tumor.
... 16 To improve appropriate case selection for MMS, Appropriate Use Criteria (AUC) have been established for Mohs surgery 12,13 but have not been widely embraced by insurers. These AUC criteria and other clinical guidelines such as those established for skin cancer by The National Comprehensive Cancer Network, 17,18 American Joint Commission on Cancer 19 and American Society of Dermatologic Surgery 20,21 should serve to inform treatment decisions for skin cancer. ...
Importance:
Outlier physician practices in health care can represent a significant burden to patients and the health system.
Objective:
To study outlier physician practices in Mohs micrographic surgery (MMS) and the associated factors.
Design, setting, and participants:
This retrospective analysis of publicly available Medicare Part B claims data from January 2012 to December 2014 includes all physicians who received Medicare payments for MMS from any practice performing MMS on the head and neck, genitalia, hands, and feet region of Medicare Part B patients.
Main outcomes and measures:
Characteristics of outlier physicians, defined as those whose mean number of stages for MMS was 2 standard deviations greater than the mean number for all physicians billing MMS. Logistic regression was used to study the physician characteristics associated with outlier status.
Results:
Our analysis included 2305 individual billing physicians performing MMS. The mean number of stages per MMS case for all physicians practicing from January 2012 to December 2014 was 1.74, the median was 1.69, and the range was 1.09 to 4.11. Overall, 137 physicians who perform Mohs surgery were greater than 2 standard deviations above the mean (2 standard deviations above the mean = 2.41 stages per case) in at least 1 of the 3 examined years, and 49 physicians (35.8%) were persistent high outliers in all 3 years. Persistent high outlier status was associated with performing Mohs surgery in a solo practice (odds ratio, 2.35; 95% CI, 1.25-4.35). Volume of cases per year, practice experience, and geographic location were not associated with persistent high outlier status.
Conclusions and relevance:
Marked variation exists in the number of stages per case for MMS for head and neck, genitalia, hands, and feet skin cancers, which may represent an additional financial burden and unnecessary surgery on individual patients. Providing feedback to physicians may reduce unwarranted variation on this metric of quality.
... Time to events of poor clinical evolution during follow up (in months) (a) LR; (b) NP; (c) distant progression, which was considered when the tumor developed metastases in solid organs during the follow-up period; (d) death from CSCC and (e) any of the aforementioned events. 23 Tissue microarray and immunohistochemistry Tissue samples, formalin-fixed paraffinembedded, were used to prepare tissue microarrays using a tissue arrayer device (Beecher Instruments, Sun Prairie, WI, USA). Three 1-mm-diameter cylinders from each tumor were included to ensure reproducibility and homogeneous staining of the slides. ...
... We next investigated whether the hypomethylation-induced overexpression of DSS1 was correlated to the main clinicopathological characteristics of melanoma [16] and SCC [17]. As shown in Fig. 3, DSS1 expression was significantly higher in the presence of metastasis (P b .001 ...
Previous studies have found a link between high expression levels of the Deleted in Split hand/Split foot 1 (DSS1) gene and cancer progression. The aim of this study was to examine whether overexpression of DSS1 is a feature of melanoma and squamous cell carcinoma (SCC) and if any epigenetic modifications are involved. Evaluation of DSS1 expression profile indicated that the gene is overexpressed in 112/130 cutaneous melanomas (86.1%), 41/64 uveal melanomas (64.1%), 67/82 mucosal melanomas (81.7%), and 61/75 SCC samples (81.3%), relative to normal skin. An inverse correlation between DSS1 expression and methylation status of the promoter was found. In vitro studies showed that treatment of DSS1-methylated melanoma and SCC cells with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine significantly increased DSS1 expression at mRNA and protein levels. Interestingly, a significant association between high DSS1 expression levels and some clinicopathological variables, such as metastasis, ulceration, and reduced overall/disease-free survival was observed. In summary, these data suggest that the extent of promoter methylation plays a role in modulating DSS1 gene expression and highlight that promoter hypomethylation is a frequent event in melanoma and SCC closely linked to poor prognosis.
... 21 Tumours were staged according to the 7th edition of the American Joint Committee on Cancer Staging Guidelines (AJCC) for CSCC. 23 ...
Introduction:
Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans, after basal cell carcinoma, and its incidence is dramatically rising. CSCC is rarely problematic, but given its high frequency, the absolute number of complicated cases is also high. It is necessary to identify molecular markers to recognize those CSCC with poor prognosis. There is controversy concerning the role of EGFR (epidermal growth factor receptor) as a marker of prognosis in CSCC. In addition, EGFR-targeted therapies have emerged in recent years and a better understanding of the role of EGFR in CSCC may help some patients in predicting prognosis and guide curative management.
Patients and methods:
We evaluated clinical and histopathological features, including events of bad clinical evolution, in a series of 94 CSCC. We also analysed EGFR expression by immunohistochemistry, FISH and QPCR.
Results:
We detected EGFR in 85 (90.4%) cases, with overexpression in 33 (35.1%) cases, and aberrant EGFR expression in the cytoplasm in 50 (53.1%) cases. EGFR overexpression in the primary tumours was associated with lymph node progression, TNM stage progression and proliferation (Ki-67 staining) in CSCC. EGFR overexpression and poor grade of differentiation were the strongest independent variables defining lymph node metastasis and progression in CSCC in a logistic regression model.
Conclusion:
We demonstrate that EGFR overexpression has prognostic implications associated with lymph node metastasis and progression in CSCC. This article is protected by copyright. All rights reserved.
... Although some reviews report the risk of local recurrence, regional metastases, distant metastases, and diseasespecific death as 5%, 5%, 1%, and 1%, respectively, the rate of metastases may exceed 20% in patients with selected high-risk features, with overall survival between 46% and 70% at 5 years (15,16). The incidence of recurrence was predicted by stage based on the revised seventh edition AJCC staging system in a study of 224 primary cSCCs from 41 heart and lung transplant recipients (17,18). The overall 5-year incidence of recurrence in this cohort was 16%, which is consistent with prior studies of cSCC in solid organ transplant recipients. ...
Advancements in solid organ transplantation successfully extend the lives of thousands of patients annually. The tenet of organ stewardship aims to prevent the futile expenditure of scarce donor organs in patient populations with high mortality risk, to the detriment of potential recipients with greater predicted life expectancy. The development of skin cancer posttransplantation portends tremendous morbidity, adversely affecting quality of life for many transplant recipients. This special article, provided by of members of the International Transplant Skin Cancer Collaborative (ITSCC), will provide the transplant professional with a consensus opinion and recommendations as to an appropriate wait period pretransplantation for transplant candidates with a history of either cutaneous squamous cell carcinoma, malignant melanoma, or Merkel cell carcinoma.
... These staging systems are not optimal since they have been developed for all head and neck SCCs, which encompass tumours with very different aggressiveness. They also lack extensive validation, as they have been only validated in series of organ transplant recipients with cSCC [43]. In addition, they are short of an accurate prognostic discrimination in certain stages where outcome measures vary significantly. ...
Nonmelanoma skin cancers (NMSC) are the most common malignancies in solid organ transplant recipients. The most common types of skin cancer in these patients are squamous cell carcinoma (SCC), followed by basal cell carcinoma. In immunosuppressed patients, specifically patients after solid organ transplantation, these carcinomas tend to be more aggressive and have a much higher incidence of metastasizing compared to general population. We present a case of a patient who developed numerous SCCs after successful heart transplantation. SCCs which occurred in our patient were mostly treated surgically. However, the lesion on the scalp relapsed after it had been treated surgically three times and therefore superficial x-ray radiation therapy was administered due to its localization and extensive size. In the next year, five more new SCCs occurred throughout the patient's body and all of them were removed surgically. Soon afterwards, the patient died from adenocarcinoma of the colon which rapidly progressed and metastasized.
In this study, we sought to identify the potential impacts of disease characteristics on the prognosis of cutaneous squamous cell carcinoma (cSCC). We searched the PubMed, EmBase, and Cochrane Library databases from their inception until February 2020 to identify studies that investigated the prognosis of cSCC. The pooled effect estimates were applied using odds ratios (OR) and 95% confidence intervals (CI) and were calculated using the random-effects model. Forty-three studies including a total of 21,530 patients and reporting 28,627 cases of cSCC were selected for the final meta-analysis. Poor differentiation (OR, 3.54; 95% CI, 2.30-5.46; P < 0.001), perineural invasion (OR, 3.27; 95% CI, 1.60-6.67; P = 0.001), Breslow greater than 2 mm (OR, 5.47; 95% CI, 2.63-11.37; P < 0.001), diameter greater than 20 mm (OR, 4.62; 95% CI, 2.95-7.23; P < 0.001), and location on temple (OR, 3.20; 95% CI, 1.12-9.15; P = 0.030) were associated with an increased risk of recurrence, whereas immunosuppression status and location on cheek, ear, or lip were not associated with the risk of recurrence. Poor differentiation (OR, 6.82; 95% CI, 4.66-9.99; P < 0.001); perineural invasion (OR, 7.15; 95% CI, 4.73-10.83; P < 0.001); Breslow greater than 2 mm (OR, 6.11; 95% CI, 4.05-9.21; P < 0.001); diameter greater than 20 mm (OR, 5.01; 95% CI, 2.56-9.80; P < 0.001); and location on ear (OR, 2.38; 95% CI, 1.39-4.09; P = 0.002), lip (OR, 2.15; 95% CI, 1.26-3.68; P = 0.005), and temple (OR, 2.77; 95% CI, 1.20-6.40; P = 0.017) were associated with an increased risk of metastasis, whereas immunosuppression status and location on cheek did not affect the risk of metastasis. Finally, poor differentiation (OR, 5.97; 95% CI, 1.82-19.62; P = 0.003), perineural invasion (OR, 6.64; 95% CI, 3.63-12.12; P < 0.001), and Breslow greater than 2 mm (OR, 3.42; 95% CI, 1.76-6.66; P < 0.001) were associated with an increased risk of disease-specific death, whereas diameter; immunosuppression status; and location on ear, lip, and temple did not affect the risk of disease-specific death. We found that differentiation, perineural invasion, depth, diameter, and location could affect the prognosis of cSCC. The potential role of other patient characteristics on the prognosis of cSCC should be identified in further large-scale prospective studies.
Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in humans and its incidence is both underestimated and on the rise. cSCC is referred to in the literature as high-risk cSCC, locally advanced cSCC, metastatic cSCC, advanced cSCC, and aggressive cSCC. These terms can give rise to confusion and are not always well defined. In this review, we aim to clarify the concepts underlying these terms with a view to standardizing the description of this tumor, something we believe is necessary in light of the new drugs that have been approved or are in development for cSCC.
One in twenty solid organ transplant recipients (SOTRs) will develop a highly morbid or fatal cutaneous carcinoma after transplantation. The majority of these cases develop on the head and neck and may require intervention on the part of dermatology, dermatologic surgery, otolaryngology, transplant medicine, radiation oncology, and medical oncology. In this review, we discuss the problem of cutaneous squamous cell carcinoma (cSCC) in SOTRs as well as the prognostic factors and management strategies to care for this population.
Kutane Plattenepithelkarzinome sind die zweithäufigsten malignen Tumoren der Haut. Meist sind sie primär chirurgisch therapierbar. Es wurden verschiedene Risikofaktoren sowohl für lokale Rezidivierung als auch Metastasierung und tumorspezifischen Tod beschrieben. Zur Risikostratifizierung stehen verschiedene Klassifikationssysteme zur Verfügung. Die Tumordicke ist der stärkste Risikofaktor sowohl für die Entwicklung von Lokalrezidiven, aber auch für Metastasierung und tumorspezifischen Tod. Außerdem spielen der Immunstatus von Patienten, die Lokalisation sowie histologische Faktoren wie Wachstumsmuster und Differenzierung eine wichtige Rolle für die Einschätzung des individuellen Risikos. Entsprechend diesen Parametern sollten Patienten in ein risikoadaptiertes Nachsorgeschema eingeschlossen werden. Das Risiko für ein Lokalrezidiv sowie Metastasierung ist in den ersten Jahren nach Exzision am höchsten, weshalb die Nachsorge hier engmaschiger durchgeführt werden sollte.
Background:
Immunosuppressed patients have worse outcomes from cutaneous squamous cell carcinomas (cSCCs), although unclear whether it is due to the development of more high-stage tumors or worse outcomes for a given stage.
Objective:
Analyze the impact of immunosuppression on the development of cSCCs and tumor stage-dependent outcomes.
Materials and methods:
Single-institution 1:2 case-control study of primary invasive cSCCs from 2005 to 2015 in 106 mixed-cause immunosuppressed patients and 212 control subjects matched to age, gender, and race.
Results:
Four hundred twelve cSCCs from 106 immunosuppressed patients and 291 tumors from 212 matched immunocompetent patients were included. Both cohorts had similar T-stage distribution, with <5% high-stage tumors, that is, AJCC-7 T2, AJCC-8 T3, and BWH T2b/T3. Immunosuppression significantly increased the likelihood of poor outcomes (POs) (aggregate of local recurrence (LR), nodal and distant metastasis, and squamous cell carcinoma-related deaths) for low-stage tumors, that is, AJCC-7 T1 (odds ratio [OR], 4.29), AJCC-8 T1 (OR, 3.45), AJCC-8 T2 (OR, 3.75), BWH T1 (OR, 3.53), and BWH T2a (OR, 3.41) tumors. There was no significant difference in the treatment: most tumors were treated with Mohs (71% vs 75%) or excision (21% vs 20%) in both cohorts.
Conclusion:
Immunosuppressed patients have an increased risk of POs, specifically LRs, from low-stage cSCCs. Definitive treatment of cSCCs is recommended.
Background:
Staging systems for cutaneous squamous cell carcinoma (CSCC) include Brigham and Women's Hospital (BWH) and American Joint Committee on Cancer staging system, eighth edition (AJCC-8).
Objective:
To evaluate and compare AJCC-8 and BWH staging systems for CSCC in immunosuppressed patients.
Materials and methods:
A retrospective cohort study of immunosuppressed patients diagnosed with primary CSCC from 2012 to 2016. The main end point was any poor outcome (PO), which included local recurrence, nodal metastasis, and disease-specific death.
Results:
Fifty-eight immunosuppressed patients had 263 CSCCs. Fifty percent of tumors were AJCC-8 T1, 44.7% T2, and 4.8% T3. Fifty percent of tumors were BWH T1, 48.5% T2a, 1.3% T2b, and 0.4% T3. Risk of PO for AJCC-8 was 1.7%, 8.8%, and 36.4% for T1, T2, and T3, respectively (p < .01). Risk of PO for BWH was 1.8%, 9.9%, 33.3%, and 100.0% for T1, T2a, T2b, and T3, respectively (p < .01). Thirty-six percent of AJCC-8 T3/T4 tumors had POs compared with 5.1% in low T1/T2 stages (p = .002). Fifty percent of BWH T2b/T3 tumors had POs compared with 5.3% in low T1/T2a stages (p = .01).
Conclusion:
AJCC-8 and BWH staging systems stratify CSCC with similar distinctiveness, homogeneity, and monotonicity for immunosuppressed patients.
Cutaneous squamous cell carcinoma is the second most common form of nonmelanoma skin cancer after basal cell carcinoma and accounts for the majority of nonmelanoma skin cancer-related deaths. In 2017, the American Joint Committee on Cancer revised the staging guidelines of cutaneous squamous cell carcinoma to reflect recent evidence concerning high-risk clinicopathologic features. This update reviews the literature on prognostic features and staging, including the eighth edition of the American Joint Committee on Cancer Staging Manual. A wide range of histopathologic variants of cutaneous squamous cell carcinoma exists, several of which are associated with aggressive behavior. A review of cutaneous squamous cell carcinoma variants, emphasizing diagnostic pitfalls, immuhistochemical findings and prognostic significance, is included. Of note, the eighth edition of the American Joint Committee on Cancer Staging Manual refers to squamous cell carcinoma of the head and neck only.
The immune system plays a critical role in skin cancer development, progression and destruction. Skin cancers in individuals with compromised immune systems represent a growing challenge in terms of their frequency and diversity as well as their atypical and often aggressive nature. Mortality and morbidity associated with skin tumours in this clinical context are often considerable, their pathogenesis is multifactorial and an evidence base to guide management is lacking in many key areas.
Purpose:
Immunosuppressed solid organ transplant recipients (SOTRs) have an increased risk of developing cutaneous squamous cell carcinomas (cSCCs) with metastatic potential. This study sought to determine the rate of regional lymph node involvement in a large cohort of solid organ transplant patients with cutaneous head and neck squamous cell carcinoma.
Materials and methods:
A retrospective chart review was performed on solid organ transplant patients with head and neck cutaneous squamous cell carcinoma treated at a tertiary academic medical center from 2005 to 2015.
Results:
130 solid organ transplant patients underwent resection of 383 head and neck cutaneous squamous cell carcinomas. The average age of the patient was 63. Seven patients (5%) developed regional lymph node metastases (3 parotid, 4 cervical lymph nodes). The mean time from primary tumor resection to diagnosis of regional lymphatic disease was 6.7months. Six of these patients underwent definitive surgical resection followed by adjuvant radiation; one patient underwent definitive chemoradiation. 6 of the 7 patients died of disease progression with a mean survival of 15months. The average follow up time was 3years (minimum 6months).
Conclusions:
Solid organ transplant recipients with cutaneous squamous cell carcinoma of the head and neck develop regional lymph node metastasis at a rate of 5%. Regional lymph node metastasis in this population has a poor prognosis and requires aggressive management and surveillance.
On account of a variety of risk factors, solid organ transplant recipients are prone to develop malignant tumours. One major risk is of course the immunosuppression implemented to keep rejection episodes at bay. This chapter focuses on the risk factors for tumour development, the main groups of tumour encountered in heart transplant patients (post-transplant lymphoproliferative disorders, non-melanoma skin neoplasms, solid organ tumours) and current therapeutic strategies. A selection of illustrative cases of post-transplant lympho-proliferative disorders that occurred in recipients of different solid organ transplant procedures is included.
Background:
The American Joint Committee on Cancer 7th edition (AJCC-7) and Brigham and Women's Hospital (BWH) staging criteria for cutaneous squamous cell carcinoma (cSCC) have not been validated in immunosuppressed patients.
Objective:
To compare the AJCC-7 and BWH staging systems for cSCCs in immunosuppressed patients.
Methods and materials:
A single-institution retrospective cohort study of cSCCs in immunosuppressed patients. Risks of local recurrence (LR), nodal metastasis (NM), in-transit metastasis, and any poor outcome (PO) were compared among AJCC-7 and BWH tumor T stages.
Results:
One hundred six patients had 412 primary invasive cSCCs. Eighty-five percent were AJCC-7 T1, and 15% T2. Risks of NM and PO for AJCC-7 T1 versus T2 were 0.9% versus 5% and 12.8% versus 23.3%, respectively, p < .05. Eighty-one percent of tumors were BWH T1, 18% T2a, 1% T2b, and 0.2% T3. Risk of LR for BWH T1 versus T2a was 11.4% versus 20.3%, p < .01. Risk of NM increased from 0.3% for T1 to 4.1%, 25%, and 100% for T2a, T2b, and T3, p < .05. Ninety percent of PO occurred in low-stage BWH T1/T2a.
Conclusion:
Low T-stage cSCCs account for most POs. Brigham and Women's Hospital staging criteria better risk stratifies cSCCs in immunosuppressed patients for risk of NM and LR.
Cutaneous squamous cell carcinoma (SCC) is a malignancy that arises from epidermal keratinocytes. Although the majority of cutaneous SCC cases are easily treated without further complication, some behave more aggressively and carry a poor prognosis. These "high-risk" cutaneous SCCs commonly originate in the head and neck and have an increased tendency toward recurrence, local invasion, and distant metastasis. Factors for high-risk cutaneous SCC include large size (>2 cm), a deeply invasive lesion (>2 mm), incomplete excision, high-grade/desmoplastic lesions, perineural invasion (PNI), lymphovascular invasion, immunosuppression, and high-risk anatomic locations. Both the National Comprehensive Cancer Network(®) (NCCN(®) ) and the American Joint Committee on Cancer (AJCC) identify several of these high-risk features of cutaneous SCC. The purpose of this article was to review the high-risk features included in these guidelines, as well as their notable discrepancies and omissions. We also provide a brief overview of current prophylactic measures, surgical options, and adjuvant therapies for high-risk cutaneous SCC. © 2016 Wiley Periodicals, Inc. Head Neck, 2016.
When compared to the general population, organ transplant recipients (OTRs) have a 65- to 250-fold increased risk of developing cutaneous squamous cell carcinoma (SCC). In addition to increased risk of SCC development, OTRs experience a higher tumor burden, more aggressive SCCs, and increased risk of metastasis and skin cancer-related mortality, making staging, prognosis, and treatment determinations in OTR patients especially important, yet lacking full clarity in the literature. High-risk cutaneous SCCs are those tumors associated with a high risk of subclinical metastasis and subsequent adverse events including local recurrence, nodal metastases, and disease-specific death. There is concern that the current staging systems for cutaneous SCCs may not accurately define a “high-risk” SCC, and the lack of prospective data makes it even more difficult to define “high-risk” features in the immunosuppressed OTR population. With no universally accepted standard definition of high-risk features, the different high-risk factors proposed by several consensus guidelines require individual exploration. OTRs also represent a desirable target for chemoprevention of SCCs, and while only oral retinoids have shown benefit specifically in OTR patients, data pertaining to other proposed agents also warrant review.
Squamous cell carcinoma (SCC) is the 2nd most common cancer diagnosed worldwide. While overall cure rates are excellent, 2–5 % of tumors recur, metastasize, and cause death. Generally accepted risk factors for recurrence and metastasis include size > 2 cm, depth beyond Clark’s Level IV or V, poorly differentiated or undifferentiated histology, location on the lip, location on the ear, perineural invasion (PNI), recurrent tumors, and tumors occurring in an immunosuppressed host. These risk factors have served as the foundation for the development of the American Joint Committee on Cancer (AJCC) and International Union Against Cancer (UICC) staging systems, as well as National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for cutaneous SCC.
In 2010, the AJCC divided cutaneous SCC staging from other nonmelanoma skin cancer staging and proposed a separate staging system based on review of available literature and expert consensus opinion. Several studies have demonstrated this new stratification system may be suboptimal and have published alternative systems which offer improved prognostic discrimination. This chapter will review the available data on high-risk cutaneous SCC, summarize the current staging and prognostic stratification systems, identify areas of ambiguity in SCC staging and outcomes, and discuss areas of research that may improve future prognostic stratification systems.
Importance
To date, the magnitude of association and the quality of evidence for cutaneous squamous cell carcinoma (cSCC) and risk factors for outcomes have not been reviewed and analyzed systematically.Objective
To systematically analyze all published data on risk factors for recurrence, metastasis, and disease-specific death (DSD) of cSCC.Data Sources
Comprehensive search of Ovid MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus, from each database’s inception to May 14, 2015.Study Selection
Inclusion criteria were studies of at least 10 patients, comparative data for at least 1 cSCC risk factor, and an outcome of interest. Exclusion criteria were noncutaneous squamous cell carcinoma (SCC), anogenital SCC, inability to extract cSCC data from other malignancy data, SCC in situ, Marjolin ulcer, and genetic disorders predisposing to cSCC.Data Extraction and Synthesis
Two reviewers independently abstracted the data. Meta-analysis was performed using the random-effects model. Risk of bias was assessed by the Newcastle-Ottawa Scale.Main Outcomes and Measures
A priori outcomes were recurrence, metastasis, and DSD.Results
Thirty-six studies (17 248 patients with 23 421 cSCCs) were included. Significant risk factors for recurrence were the following: Breslow thickness exceeding 2 mm (risk ratio [RR], 9.64; 95% CI, 1.30-71.52), invasion beyond subcutaneous fat (RR, 7.61; 95% CI, 4.17-13.88), Breslow thickness exceeding 6 mm (RR, 7.13; 95% CI, 3.04-16.72), perineural invasion (RR, 4.30; 95% CI, 2.80-6.60), diameter exceeding 20 mm (RR, 3.22; 95% CI, 1.91-5.45), location on the temple (RR, 3.20; 95% CI, 1.12-9.15), and poor differentiation (RR, 2.66; 95% CI, 1.72-4.14). Significant risk factors for metastasis were: invasion beyond subcutaneous fat (RR, 11.21; 95% CI, 3.59-34.97), Breslow thickness exceeding 2 mm (RR, 10.76; 95% CI, 2.55-45.31), Breslow thickness exceeding 6 mm (RR, 6.93; 95% CI, 4.02-11.94), diameter exceeding 20 mm (RR, 6.15; 95% CI, 3.56-10.65), poor differentiation (RR, 4.98; 95% CI, 3.30-7.49), perineural invasion (RR, 2.95; 95% CI, 2.31-3.75), immunosuppression (RR, 1.59; 95% CI, 1.07-2.37), and location on the temple (RR, 2.82; 95% CI, 1.72-4.63), ear (RR, 2.33; 95% CI, 1.67-3.23), or lip (RR, 2.28; 95% CI, 1.54-3.37). Significant risk factors for DSD were: diameter exceeding 20 mm (RR, 19.10; 95% CI, 5.80-62.95), poor differentiation (RR, 5.65; 95% CI, 1.76-18.20), location on the ear (RR, 4.67; 95% CI, 1.28-17.12) or lip (RR, 4.55; 95% CI, 1.41-14.69), invasion beyond subcutaneous fat (RR, 4.49; 95% CI, 2.05-9.82), and perineural invasion (RR, 4.06; 95% CI, 3.10-5.32). Evidence quality was considered low to moderate.Conclusions and Relevance
Tumor depth is associated with the highest RR of local recurrence and metastasis of cSCC, and tumor diameter exceeding 20 mm is associated with the highest RR of DSD. Unified, consistent collection and reporting of risk factors in a prospective, multicentered effort are needed to further understand the increasing incidence of cSCC.
The lifelong immunosuppression required for maintenance of allograft function in organ transplant recipients (OTR) increases the risk of cutaneous malignancies in this population. Prolonged survival posttransplantation further permits the development of late dermatologic complications of iatrogenic immunosuppression, particularly skin cancer. Cutaneous squamous cell carcinoma (CSCC) is the most common posttransplant malignancy, and in OTR can present as multiple, aggressive, and rapidly metastasizing lesions that are challenging to manage. Due to the high morbidity and potential mortality of CSCC in OTR, close dermatologic surveillance and aggressive treatment are essential. This review will address the challenge of managing posttransplant CSCC in the OTR population with a summary of the current therapeutic strategies in this patient cohort. The management of metastatic CSCC remains challenging, despite promising results from chemotherapeutic agents and novel targeted molecular inhibitors combined with radiation therapy. Ultimately, therapeutic considerations for CSCC in OTR should be determined in a multidisciplinary setting including the dermatologist, the transplant team, and appropriate specialists.
La Société française d’otorhinolaryngologie (SFORL) a organisé un groupe de travail chargé de la rédaction de recommandations pour la prise en charge des patients immunodéprimés atteints de tumeurs de la tête et du cou de point de départ cutané. Ces recommandations abordent la prise en charge diagnostique et thérapeutique ainsi que les mesures de prévention des tumeurs de la tête et du cou à point de départ cutané survenant chez les immunodéprimés, en particulier les transplantés et les patients infectés par le VIH.
Objectives
The French ENT Society (SFORL) created a workgroup to draw up guidelines for the management of immunodeficient patients with head and neck cancer of cutaneous origin. The present guidelines cover diagnostic and therapeutic management and prevention of head and neck cancer of cutaneous origin in immunodeficient patients, and in particular in transplant patients and those with HIV infection.
Materials and methods
The present guidelines were based on a critical multidisciplinary reading of the literature. Immunosuppression and its varieties are defined. The usual risk factors for skin cancer and those specific to immunodeficiency are presented. The prevention, assessment and management of cutaneous carcinoma, melanoma, Kaposi's sarcoma and lymphoma are dealt with. The level of evidence of the source studies was assessed so as to grade the various guidelines. When need be, expert opinions are put forward.
Results
Immunodeficient patients are at higher risk of head and neck skin tumors. The level of risk depends on the type of deficiency; there is an especially high risk of squamous cell carcinoma in transplant patients and of Kaposi's sarcoma in HIV-positive subjects. Various viruses are associated with skin cancers. Skin tumors are often evolutive in case of immunodeficiency, requiring rapid treatment. Management is generally the same as in immunocompetent subjects and should be discussed in a multidisciplinary team meeting. Immunosuppression may need to be modulated. In organ transplant patients, the only class of immunosuppressants with proven antitumoral efficacy are mTOR inhibitors, particularly in cutaneous squamous cell carcinoma. The rhythm of clinical surveillance should be adapted according to the risk of recurrence. Preventive measures should be undertaken.
Conclusion
Skin cancers in immunodeficiency are highly evolutive, requiring the earliest possible treatment. Immunosuppression may need modulating. As the risk of recurrence may be elevated, careful surveillance should be implemented. Preventive measures should also be undertaken.
IMPORTANCE The appropriate clinical setting for the application of sentinel lymph node biopsy (SLNB) in the management of cutaneous squamous cell carcinoma (cSCC) is not well characterized. Numerous case reports and case series examine SLNB findings in patients who were considered to have high-risk cSCC, but no randomized clinical trials have been performed. OBJECTIVE To analyze which stages in the American Joint Committee on Cancer (AJCC) criteria and a recently proposed alternative staging system are most closely associated with positive SLNB findings in nonanogenital cSCC. DESIGN, SETTING, AND PARTICIPANTS Medical literature review and case data extraction from private and institutional practices to identify patients with nonanogenital cSCC who underwent SLNB. Patients were eligible if sufficient tumor characteristics were available to classify tumors according to AJCC staging criteria and a proposed alternative staging system. One hundred thirty patients had sufficient data for AJCC staging, whereas 117 had sufficient data for the alternative system. EXPOSURE Nonanogenital cSCC and SLNB. MAIN OUTCOMES AND MEASURES Positive SLNB findings by cSCC stage, quantified as the number and percentage of positive nodes. RESULTS A positive SLN was identified in 12.3% of all patients. All cSCCs with positive SLNs were greater than 2 cm in diameter. The AJCC criteria identifed positive SLNB findings in 0 of 9 T1 lesions (0%), 13 of 116 T2 lesions (11.2%), and 3 of 5 T4 lesions (60.0%). No T3 lesions were identified. The alternative staging system identified positive SNLB findings in 0 of 9 T1 lesions (0%), 6 of 85 T2a lesions (7.1%), 5 of 17 T2b lesions (29.4%), and 3 of 6 T3 lesions (50.0%). Rates of positive SLNB findings in patients with T2b lesions were statistically higher than those with T2a lesions (P = .02, Fisher exact test) in the alternative staging system. CONCLUSIONS AND RELEVANCE Our findings suggest that most cSCCs associated with positive SLNB findings occur in T2 lesions (in both staging systems) that are greater than 2 cm in diameter. The alternative staging system appears to more precisely delineate high-risk lesions in the T2b category that may warrant consideration of SLNB. Future prospective studies are necessary to validate the relationship between tumor stage and positive SLNB findings and to identify the optimal staging system.
No established standard of care exists for aggressive cutaneous squamous cell carcinoma (CSCC).
We sought to establish an aggressive CSCC management protocol by reviewing high-risk CSCC (HCSCC) and very high-risk CSCC (VCSCC) cases at our institution.
This was a retrospective review of all CSCC cases treated at our institution.
A total of 27 patients were identified of 1591 cases treated between 2000 and 2011. Four patients with HCSCC received surgery alone and 1 received surgery and radiation. All remain disease free (median follow-up 5 years). Among patients with VCSCC, 4 received surgery alone: 1 (25%) showing a complete response and 3 (75%) showing disease progression. Eleven received surgery and radiation: 4 (36.4%) with complete response (median follow-up 3 years) and 7 (63.6%) with disease progression (median time to recurrence 6 months). Six received surgery and cetuximab: 3 (50%) had a complete response (median follow-up 3 years), 2 (33%) had disease progression, and 1 (14%) could not be assessed because of inability to tolerate infusions. One patient received surgery, cetuximab, and radiation, and remains disease-free after 4 years.
Lack of randomization, blinding, a true control arm, or standardization of treatment protocols are limitations.
Patients with very HCSCC may have improved outcomes with surgery and adjuvant cetuximab.
Creating a staging system for cancer is not easy. The goal is to stratify patients based on the likelihood of developing an adverse event, most commonly metastasis or death. Groupings should be distinctive (the likelihood of developing the adverse event differs between groups), monotonous (the likelihood increases with increasing stage), and homogeneous (the likelihood is similar within each group).1 It has also been suggested that staging systems should be clinically relevant (no one grouping is too rarely or too frequently utilized) and parsimonious (all other things being equal, simpler is better).2 Finally, as suggested by Jambusaria-Pahlajani et al3 in this issue of the journal, in cancers like cutaneous squamous cell carcinoma (CSCC), in which the likelihood of metastasis and death is low, it is helpful if a staging system can “concentrate” those patients who are most likely to develop adverse events. This will allow testing and use of adjuvant interventions in those individuals for whom it is most appropriate.
The development of malignancies in recipients of a cardiothoracic transplant (CTT)—that is, heart, lung, or heart and lung recipients—is of concern. Cutaneous and lymphoproliferative malignancies comprise the two major groups of malignancies encountered. A small subgroup of patients will develop potentially life-threatening aggressive cutaneous malignancies (ACM); these are poorly defined and documented in the literature. The authors report the results for 619 CTT recipients from a single institution.
Skin cancer incidence has been shown to be increased in the context of transplant-associated immunosuppression. There is, however, limited information specifically about the incidence of skin cancer after cardiac transplantation in the United States. A 10-year retrospective cohort study of 6271 heart transplants at 32 US transplant centers revealed increased postprocedure incidence of nonmelanoma and melanoma skin cancers, especially cutaneous squamous cell carcinoma, for which the incidence increased from 4- to 30-fold compared to the age and gender equivalent general population. Incidence of skin cancer in this study was consistent with prior single-center data regarding cardiac transplant patients. Comparison of all-cause mortality statistics for patients with basal cell carcinoma, squamous cell carcinoma and melanoma, respectively, demonstrated increased mortality associated with melanoma. Skin cancer screening and prophylaxis may be of some utility in reducing morbidity and mortality in cardiac transplant patients.
To determine long-term tumor recurrence rates after treatment of primary nonmelanoma skin cancer (NMSC). Data are currently insufficient to permit evidence-based choices among treatments for NMSC.
Prospective study of an inception cohort observed for a median of 6.6 years after treatment.
Dermatology clinic at a Veterans Affairs hospital. Care was provided by dermatology resident or attending physicians.
Consecutive sample of all 495 patients with 616 primary NMSCs diagnosed in 1999 and 2000 and treated with electrodessication and curettage (ED&C), excision, or Mohs surgery. Follow-up was available for 608 tumors (99%).
Tumor recurrence, determined by medical record review, with validation by clinical examination.
The mean age at diagnosis was 71 years; 97% were men. Overall, 127 tumors were treated with ED&C (20.9%); 309 with excision (50.8%); and 172 with Mohs surgery (28.3%). Over the course of the study, 21 tumors recurred (3.5% [95% confidence interval (CI), 2.2%-5.2%]): 2 after ED&C (1.6% [95% CI, 0.2%-5.6%]), 13 after excision (4.2% [95% CI, 2.2%-7.1%]), and 6 after Mohs surgery (3.5% [95% CI, 1.3%-7.4%]).
Recurrence of primary NMSC after treatment occurred in less than 5% of tumors. The recurrence rate after ED&C was lower than expected, and the recurrence rate after Mohs surgery was higher than expected. These findings may be related to the risk for recurrence in the treatment groups.
Basal and squamous cell skin cancers, collectively known as nonmelanoma skin cancers (NMSC), are the most common skin cancers. More than 1 million cases of NMSC are estimated to be diagnosed each year in the United States, and the incidence is rising rapidly. Although rarely metastatic, basal and squamous cell cancers can produce substantial local destruction, along with disfigurement. They are associated with substantial annual costs for treatment, despite their general good prognosis. The most significant environmental carcinogen for NMSC is sunlight. Most of these tumors develop on sun-exposed skin sites, commonly on the head and neck area. Important updates for 2010 include revision of the guidelines detailing dissection and treatment of squamous cell carcinoma on the head and neck.
Cutaneous squamous cell carcinoma is an increasing public health concern, representing the second most common cancer in the United States. High-risk cutaneous squamous cell carcinoma represents a subgroup of this disease, where patients are at higher risk of metastasis and death. To date, there are no accepted criteria for defining or managing these patients. This review discusses the current state of knowledge of high-risk cutaneous squamous cell carcinoma and outlines reasonable management strategies based on available data.
The development of malignancies in recipients of a cardiothoracic transplant (CTT)--that is, heart, lung, or heart and lung recipients-is of concern. Cutaneous and lymphoproliferative malignancies comprise the two major groups of malignancies encountered. A small subgroup of patients will develop potentially life-threatening aggressive cutaneous malignancies (ACM); these are poorly defined and documented in the literature. The authors report the results for 619 CTT recipients from a single institution.
Between 1984 and 1995, 619 recipients received a CTT. With a minimum follow-up of 2 years, 66 patients (10.7%) were diagnosed with a major malignancy, and 27 of these 66 patients developed ACM. ACM were defined as having one or more of the following characteristics: local invasion and/or regional metastases at diagnosis, poor differentiation, and locoregional and/or systemic relapse following therapy. All malignant melanomas were considered ACM. Data on malignancy occurrence were documented in the clinical notes of the heart and lung transplant unit. A retrospective analysis was undertaken from these notes.
Tumor histology was predominantly poorly differentiated squamous cell carcinoma (55%) (SCC) and malignant melanoma (30%) (MM). No patient developed Kaposi sarcoma (KS). The median time from transplant to diagnosis of ACM was 52 months (range, 8-127 months). Thirteen of 27 patients have died; 10 of them died of metastatic disease. The mean time to death was 20 months (range, 8-54 months). Of 14 patients alive, 5 have disease. All but one of the 19 patients diagnosed with nonmelanoma ACM received radiotherapy, either as part of initial treatment or on relapse. Eight patients have subsequently suffered an infield relapse.
The development of ACM in CTT recipients resulted in substantial morbidity and mortality. Poor results were obtained with standard surgery and radiotherapy. Treatment modalities for and the underlying pathobiology of ACM in organ transplant recipients require detailed research if improved outcomes are to be achieved.
To identify nonmelanoma skin cancer patients with squamous cell carcinoma (SCC) who are at greatest risk of disease-specific mortality.
Prospectively enrolled patients with a minimum of one pathologically confirmed skin SCC lesion, definitive treatment of the SCC lesion(s) resulting in no evidence of disease, and at least 2 months of follow-up after definitive treatment were eligible for the present longitudinal analysis. They received comprehensive clinical, pathologic evaluations and follow-up for patterns of failure and mortality.
We enrolled 210 patients (187 men and 23 women) with a total of 277 skin SCC lesions and a median enrollment age of 68 years (range, 34 to 95 years). Median follow-up of surviving patients was 22 months. Three-year overall and disease-specific survival (DSS) rates were 70% and 85%, respectively. In univariate analyses, the clinical-pathologic factors associated with adverse DSS were local recurrence at presentation (P = .05), invasion beyond subcutaneous tissues (P = .009), perineural invasion (P = .002), lesion size (P = .0003), and depth of invasion (P = .05). Statistical models identified a homogeneous high-risk group of patients with lesions > or = 4 cm, perineural invasion, and deep invasion beyond subcutaneous structures. Three-year DSS was 100% for patients with no risk factors versus 70% for patients with at least one risk factor.
Lesion size > or = 4 cm and histologic evidence of perineural invasion and deep invasion beyond subcutaneous structures were the clinical-pathologic factors most significantly associated with disease-specific mortality in skin SCC.
Immunosuppressed organ allograft recipients have a 3- to 4-fold increased risk of developing tumours, but the risk of developing certain cancers is increased several hundredfold. With the exception of skin and lip cancers,most of the common malignancies seen in the general population are not increased in incidence. Instead, there is a higher frequency of some relatively rare tumours, including post-transplant lymphomas and lymphoproliferative disorders (PTLD), Kaposi’s sarcoma (KS), renal carcinomas, in situ carcinomas of the uterine cervix, hepatobiliary carcinomas, anogenital carcinomas and various sarcomas (excluding KS). Skin and lip cancers present some unusual features: a remarkable frequency of KS, reversal of the ratio of basal to squamous cell carcinomas seen in the general population, the young age of the patients, and the high incidence of multiple tumours (in 43%of the patients). Anogenital cancers occur at a much younger age than in the general population. Salient features of PTLD are the high frequency of Epstein-Barr virus-related lesions, frequent involvement of extranodal sites, a marked predilection for the brain and frequent allograft involvement.
As the immunosuppressed state per se and various potentially oncogenic viruses play a major role in causing these cancers, preventative measures include reducing immunosuppression to the lowest level compatible with good allograft function and prophylactic measures against certain virus infections. Reduction of exposure to sunlight may also decrease the incidence of skin cancer. In addition to conventional treatments (resection, radiation therapy, chemotherapy) patients may receive antiviral drugs, interferon-α and various other manipulations of the immune system. A significant percentage of cases of PTLD and KS respond to reduction or cessation of immunosuppressive therapy.
Introduction:
There is an increased incidence of cancer in patients after organ transplantation. We reviewed a large series of cardiothoracic transplant recipients to determine the incidence and natural history of head and neck malignancy.
Methods:
A total of 1069 heart (n = 855), heart/lung (n = 111), and lung (n = 103) transplants were performed at Stanford University from January 1968 to February 1998. Demographic data, risk factors, and disease course were evaluated in patients who developed cancer. The mean length of follow-up was 8.9+/-5.2 years.
Results:
One hundred twenty patients (11.2%) developed 547 non-lymphomatous malignancies. The mean number of malignancies per cancer patient was 4.6. The average time from transplantation to development of cancer was 63.1 months. A total of 50.5% of malignancies presented in the head and neck; 96.4% of these were cutaneous in origin and 3.6% were noncutaneous. Of cutaneous malignancies, 79.3% were squamous cell carcinoma and 15.9% were basal cell carcinoma Cutaneous malignancies most commonly presented on the scalp, cheek, lip, and neck. Noncutaneous malignancies involved the oral cavity (5), thyroid (4), and parotid (1). Thirteen percent of cutaneous head and neck cancers behaved aggressively, requiring extensive management including radical surgery, radiation, and/or chemotherapy. A total of 34.2% of cancer patients developed metastases and 54.9% of cancer patients died as a direct result of cancer. A total of 68% of cancer patients were smokers and 23.8% had significant alcohol use.
Conclusion:
Transplant recipients have an increased incidence of cancer presenting in the head and neck. Malignancies in transplant patients behave more aggressively than in the general population. Recognition of this aggressive biological behavior and heightened cancer surveillance should result in improved outcomes.
Lung transplant recipients (LTR) have an increased risk of cutaneous squamous cell carcinoma (SCC) due to immunosuppressive therapy. Voriconazole, which is associated with phototoxic side effects in some patients, may be an additional risk factor for SCC in this population.
To test whether voriconazole is a risk factor for developing SCC in LTR, we evaluated cumulative exposure to voriconazole in 327 adults who underwent lung transplantation at one center between 1991 and 2010. Voriconazole exposure was assessed as a time-varying covariate. We used survival analysis methods to assess the risk of developing SCC over time.
Exposure to voriconazole was associated with a 2.6-fold increased risk for SCC. This phenomenon was dose-dependent: the risk for SCC increased by 5.6% with each 60-day exposure at a standard dose of 200 mg twice daily. At 5 years after transplant, voriconazole conferred an absolute risk increase for SCC of 28%.
These results suggest that caution should be taken when using voriconazole in LTR because this drug increases the already high risk for SCC in this population.
The incidence of cutaneous squamous cell carcinoma (cSCC) is increasing. Although most patients achieve complete remission with surgical treatment, those with advanced disease have a poor prognosis. The American Joint Committee on Cancer (AJCC) is responsible for the staging criteria for all cancers. For the past 20 years, the AJCC cancer staging manual has grouped all nonmelanoma skin cancers, including cSCC, together for the purposes of staging. However, based on new evidence, the AJCC has determined that cSCC should have a separate staging system in the 7th edition AJCC staging manual.
We sought to present the rationale for and characteristics of the new AJCC staging system specific to cSCC tumor characteristics (T).
The Nonmelanoma Skin Cancer Task Force of AJCC reviewed relevant data and reached expert consensus in creating the 7th edition AJCC staging system for cSCC. Emphasis was placed on prospectively accumulated data and multivariate analyses. Concordance with head and neck cancer staging system was also achieved.
A new AJCC cSCC T classification is presented. The T classification is determined by tumor diameter, invasion into cranial bone, and high-risk features, including anatomic location, tumor thickness and level, differentiation, and perineural invasion.
The data available for analysis are still suboptimal, with limited prospective outcomes trials and few multivariate analyses.
The new AJCC staging system for cSCC incorporates tumor-specific (T) staging features and will encourage coordinated, consistent collection of data that will be the basis of improved prognostic systems in the future.
The increased incidence of skin cancers in solid organ transplant recipients (OTR) has been well established. However, our understanding of the potential aggressive behavior of these cancers has been largely based on the findings of multiple different studies analyzing isolated indicators of aggressive behavior. The purpose of this study was to determine the aggressiveness of nonmelanotic skin cancers in a large transplant population compared with an immunocompetent control population with similar cancers.
Immunosuppressed transplanted patients and an immunocompetent control group matched in size with squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) were evaluated for the factors of aggressiveness. A retrospective chart review was performed. Data obtained included transplant type, number of cancers, local recurrence rate, lymph node involvement, lymphatic invasion, perineural invasion, deep spread, subsequent treatment with radiation or chemotherapy, and death from disease.
Three hundred seven patients had SCC (OTR: 153, control: 154), and 246 patients had BCC (OTR: 123, control: 123). SCC in OTR was significantly more likely to have an increased number of primary tumors, deep tissue spread, perineural and lymphatic invasion, recurrence, and need for radiation or chemotherapy. BCC in OTR was not associated with more aggressive disease when compared with controls with BCC.
SCC in OTR behaves significantly more aggressively than in immunocompetent patients. BCC in the OTR population does not seem to act more aggressively.
Head and neck cutaneous squamous cell carcinoma (HNCSCC) although rarely fatal has significant adverse public health effects due to high medical costs, compromised quality of life, functional impairment and other serious consequences. The present longitudinal cohort study of HNCSCC was designed to determine whether certain clinical-pathologic features of HNCSCC are associated with reduced overall and recurrence-free survival, as suggested by previous data.
The cohort sample consisted of 315 consecutive patients presenting with primary HNCSCC of the head and neck. Life-table analysis and Kaplan-Meier survival analysis were performed. Multivariate Cox's proportional hazards regression models were used to assess the effects of covariates on the length of the interval.
There were 145 male and 170 female Caucasian patients. At the time of analysis, 222 patients were alive. The mean follow-up time of a patient after enrolment has been 46.7 months (range, 12-124 months). Broder's differentiation grade, perineural involvement, the presence of inflammation and T-stage were independent adjusted predictors for overall survival. pT and N-stage, inflammation and perineural involvement were significant predictors for recurrence-free survival while adjuvant irradiation was associated with a 92% reduced risk for recurrence. Life-table analysis showed that 87% and 69% study patients were free from recurrence at years 3 and 5, respectively.
Certain clinico-pathological predictors can be used to discriminate subsets of high-risk patients that could benefit from long-term follow-up. After excision in negative margins, patients with HNCSCC should be referred to specialised multidisciplinary oncology clinics for counselling on adjuvant radiotherapy and follow-up.
To examine the incidence, tumor burden, and risk factors for nonmelanoma and other skin cancer types in this heart transplant cohort.
Retrospective review of patient medical records.
Tertiary care center. Patients All heart transplant recipients at Mayo Clinic from 1988 to 2006.
Cumulative incidence of skin cancer and tumor burden, with Cox proportional hazards regression models used to evaluate risk factors for posttransplant primary and secondary nonmelanoma skin cancer.
In total, 312 heart transplant patients had 1395 new skin cancers in 2097 person-years (mean, 0.43 per year per patient) with a range of 0 to 306 for squamous cell carcinoma (SCC) and 0 to 17 for basal cell carcinoma (BCC). The cumulative incidence rates of any skin cancer were 20.4%, 37.5%, and 46.4% at 5, 10, and 15 years after heart transplant, respectively. Cumulative incidence of SCC after the first BCC was 98.1% within 7 years. Multivariate analysis showed that posttransplant nonskin cancer, increased age, and heart failure etiologic factors other than idiopathic disease were associated with increased risk of SCC. Posttransplant herpes simplex viral infection, increased age, and use of mycophenolate mofetil for immunosuppression were associated with increased risk of BCC.
With prolonged survival, many heart transplant patients have numerous skin cancers. Vigilant sun protection practices, skin cancer education, and regular skin examination are appropriate interventions in these high-risk patients.
We reviewed all studies since 1940 on the prognosis of squamous cell carcinoma (SCC) of the skin and lip. The following variables are correlated with local recurrence and metastatic rates: (1) treatment modality, (2) prior treatment, (3) location, (4) size, (5) depth, (6) histologic differentiation, (7) histologic evidence of perineural involvement, (8) precipitating factors other than ultraviolet light, and (9) host immunosuppression. Local recurrences occur less frequently when SCC is treated by Mohs micrographic surgery. This local recurrence rate differential in favor of Mohs micrographic surgery holds true for primary SCC of the skin and lip (3.1% vs 10.9%), for ear SCC (5.3% vs 18.7%), for locally recurrent (previously treated) SCC (10% vs 23.3%), for SCC with perineural involvement (0% vs 47%), for SCC of size greater than 2 cm (25.2% vs 41.7%), and for SCC that is poorly differentiated (32.6% vs 53.6%).
On review of 520 patients with 967 squamous cell carcinomas of the skin of the face treated at The University of Texas M.D. Anderson Hospital and Tumor Institute at Houston during a 10 year period, 14 percent of the patients were noted to have perineural extension of tumor. Study of the patients with perineural tumor demonstrated an increased incidence of spindle cell and adenosquamous cell types, an increased incidence of cervical lymphadenopathy and distant metastasis, and significantly reduced survival curves compared with those of patients with squamous cell skin carcinoma without perineural invasion. Tabulation confirmed that the maxillary and mandibular branches of the trigeminal nerve and the facial nerve were most commonly involved. For patients with squamous cell skin carcinomas with perineural invasion, aggressive therapy is recommended, specifically, resection of involved tissues and nerves and appropriate regional lymphadenectomy followed by postoperative radiotherapy. This plan affords the best opportunity for tumor control. The indications for exploration of the middle fossa of the intracranial portion of the trigeminal nerve deserve further study.
The Rhode Island Follow-Back Study was initiated to elucidate the magnitude and characteristics of nonmelanoma skin cancer mortality. All deaths reported among Rhode Island residents during 1979 through 1987 and attributed to nonmelanoma skin cancer were investigated and medical records sought. Most were misclassified, primarily due to squamous cell carcinoma of mucosal surfaces in the head and neck. In Rhode Island and nationally, this source of misclassification is increasingly frequent. Appropriate adjustment of national statistics for misclassification reveals a consistent decline in nonmelanoma skin cancer mortality rates from 1969 through 1988, although the actual numbers of deaths are increasing due to growth and aging of the population. Examination of the records of those Rhode Island residents who did die from nonmelanoma skin cancer demonstrated that most had squamous cell carcinoma, and many of those arose from the ear. These analyses suggest that particular emphasis should be placed on the ear in public health campaigns geared toward the prevention and early detection of nonmelanoma skin cancer.
Over the past 2 years, we have examined all patients with a functioning renal allograft attending a regional nephrology unit. A total of 291 patients were examined. 172 (59%) were found to have cutaneous warts, and 64 (21.9%) had non-melanoma skin cancer (NMSC). The proportion of patients with both warts and NMSC increased with time from transplantation: 40% of patients who had been transplanted for more than 9 years had NMSC. Fifteen patients had extensive dysplastic change in all sun-exposed areas, particularly the dorsal aspect of the hands. This subgroup of patients develop large numbers of tumours, particularly squamous cell carcinomas (SCC), and require close surveillance and frequent surgery. One patient has died as a result of rapidly evolving metastases from an SCC on the dorsum of the hand. Excision and grafting of the backs of the hands in four patients, and long term etretinate therapy in 6 patients have led to a marked reduction in the frequency of surgery to remove tumours. The very high rate of NMSC, frequently multiple, found in this study of UK residents is a source of concern and indicates the need for close dermatological monitoring of allograft recipients, with intensive surveillance of patients with extensive dysplasia, who may develop tumours requiring surgery every few weeks.
Cutaneous malignancy is a major cause of morbidity in organ transplant recipients.
Our purpose was to report on skin cancer in Australian heart transplant recipients with analysis of HLA factors.
We reviewed histologically proven skin cancers in the first 455 patients undergoing organ transplantation in Sydney, Australia.
The cumulative incidence of skin cancer was 31% at 5 years and 43% at 10 years with a squamous cell carcinoma/basal cell carcinoma ratio of 3:1. Caucasian origin, increasing age at transplantation, and duration of follow-up were significantly associated with skin cancer. Skin cancer accounted for 27% of 41 deaths occurring after the fourth year. Recipient HLA-DR homozygosity was associated with skin cancer overall, whereas HLA-DR7 was a protective factor in skin cancer overall, squamous cell carcinoma, and Bowen's disease. HLA-A1 and HLA-A11 were significant protective factors in Bowen's disease.
Skin cancer is a major cause of morbidity and long-term mortality in heart transplant patients.
Immunosuppressed organ allograft recipients have a 3- to 4-fold increased risk of developing tumours, but the risk of developing certain cancers is increased several hundredfold. With the exception of skin and lip cancers, most of the common malignancies seen in the general population are not increased in incidence. Instead, there is a higher frequency of some relatively rare tumours, including post-transplant lymphomas and lymphoproliferative disorders (PTLD), Kaposi's sarcoma (KS), renal carcinomas, in situ carcinomas of the uterine cervix, hepatobiliary carcinomas, anogenital carcinomas and various sarcomas (excluding KS). Skin and lip cancers present some unusual features: a remarkable frequency of KS, reversal of the ratio of basal to squamous cell carcinomas seen in the general population, the young age of the patients, and the high incidence of multiple tumours (in 43% of the patients). Anogenital cancers occur at a much younger age than in the general population. Salient features of PTLD are the high frequency of Epstein-Barr virus-related lesions, frequent involvement of extranodal sites, a marked predilection for the brain and frequent allograft involvement. As the immunosuppressed state per se and various potentially oncogenic viruses play a major role in causing these cancers, preventative measures include reducing immunosuppression to the lowest level compatible with good allograft function and prophylactic measures against certain virus infections. Reduction of exposure to sunlight may also decrease the incidence of skin cancer. In addition to conventional treatments (resection, radiation therapy, chemotherapy) patients may receive antiviral drugs, interferon-alpha and various other manipulations of the immune system. A significant percentage of cases of PTLD and KS respond to reduction or cessation of immunosuppressive therapy.
Squamous cell carcinoma (SCC) of the skin exhibits a significant propensity to metastasize. A number of variables have been reported to influence the tendency of SCC to metastasize. Because of the increasing incidence of skin cancer, it is becoming increasingly important to identify those neoplasms which are biologically more aggressive. We report 25 cases of metastatic SCC and compare them to 175 cases of nonmetastasizing SCC treated during the same period.
To characterize tumors with the greatest tendency to metastasize.
A tumor registry from the Dermatologic Surgery Unit at the Medical University of South Carolina was accessed to obtain records on 200 patients diagnosed with invasive SCC managed by Mohs surgery from 1988 to 1998. A retrospective analysis was conducted. The characteristics of patients with metastatic SCC and those with nonmetastatic SCC were compared using the chi-squared test and Fisher's exact test.
Of 200 tumors, 25 (12.5%) metastasized. Size, Clark's level, degree of differentiation, the presence of small tumor nests, infiltrative tumor strands, single-cell infiltration, perineural invasion, acantholysis, and recurrence all correlated strongly with metastasis. Location, ulceration, inflammation, and Breslow depth did not correlate with the development of metastasis.
Patients with tumors that exhibit certain clinical and histologic features are more likely to metastasize and need close follow-up to detect recurrence and metastasis early, allowing for appropriate life-saving intervention. Sentinel lymph node biopsy should be considered in patients with high-risk SCC.
To estimate (1) the magnitude of and the components and factors associated with nonmelanoma skin cancer (NMSC) mortality and (2) the proportion of deaths misclassified as NMSC.
Population-based follow-back study.
All Rhode Island residents whose deaths between 1988 and 2000 were attributed to NMSC.
Distribution of diagnoses, verification of the causes of death, and characterization of associated factors.
The proportion of misclassified deaths was significantly higher for nongenital NMSC (57%) than for genital NMSC (18%; P<.001). Most of the deaths misclassified as nongenital NMSC were caused by squamous cell carcinoma of mucosal surfaces. The age-adjusted NMSC mortality rate was 0.91 (per 100 000 persons per year), of which almost half (0.45) were due to genital carcinoma. Nonmelanoma skin cancer mortality increased sharply with age. The mortality rate from nongenital NMSC in men was more than twice that in women, but for genital NMSC this ratio was reversed. Skin cancers originating on the ear were responsible for more than a quarter of all deaths caused by nongenital NMSC. No cases of NMSC mortality occurred in organ transplant recipients. Many individuals had comorbid psychiatric conditions or evidence of unreasonable delay in seeking medical care for their lesions.
Misclassifying the cause of death as nongenital NMSC accounts for a large source of error on death certificates in Rhode Island. Overall, nongenital squamous cell carcinoma and basal cell carcinoma death rates have declined, and mortality due to genital carcinoma was about half of total NMSC deaths. The dermatology community should emphasize prevention of mortality from genital skin cancer, while continuing to stress the importance of reducing excessive exposure to UV light and prompt treatment of NMSC.
The purpose of this study was to analyze a large series of skin cancers in solid organ transplant recipients to determine their biologic behavior.
A retrospective review of all US transplant recipients with skin cancer reported to the Israel Penn International Transplant Tumor Registry was performed.
Transplant recipients from the United States with skin malignancies were identified (n = 2018) and assigned to 1 of 3 groups: squamous cell cancer (SCC), basal cell cancer (BCC), or combined malignancies (BCC/SCC). Squamous cell to basal cell cancer ratio was found to be 1.9 to 1. The ratio of extrarenal to renal allograft recipients was identical for all 3 groups (3:1). The median interval from transplant to skin cancer diagnosis was greater than 4 years in each group and longest in those with isolated SCC lesions. In the SCC group, there was a 9% incidence of nodal or secondary site involvement affecting the cervix, perineum, or lung. The highest recurrence rate was demonstrated in the combined malignancy group. Cancer-specific deaths were significantly higher in the SCC (8%) and BCC/SCC (6.8%) groups compared to the BCC (3.6%) group.
This large experience indicates that SCC is more common than BCC in transplant recipients. SCC alone or in combination with BCC appears aggressive and is associated with significant mortality.
Patients with cutaneous squamous cell carcinoma (SCC) may develop metastatic SCC to nodes in the head and neck. Recent data support best outcome with the addition of adjuvant radiotherapy. This study aims to present further supportive evidence.
Retrospective chart review.
Patients were identified with metastatic cutaneous SCC to nodes of the head and neck treated with surgery or surgery and adjuvant radiotherapy. Relapse and outcome were analyzed using Cox regression analysis. Disease-free survival and overall survival rates were calculated using Kaplan-Meier survival curves.
Between 1980 to 2000, 167 patients were treated with curative intent at Westmead Hospital, Sydney. Median age was 67 years (range, 34-95) in 143 men and 24 women with a minimum follow-up of 24 months. Patients underwent surgery (21/167; 13%), or surgery and adjuvant radiotherapy (146/167; 87%). The majority (98/167; 59%) of metastatic nodes were located in the parotid and/or cervical nodes. The remaining 69 (41%) had metastatic cervical nodes (levels I-V). Forty-seven patients (28%) had recurrences, with the majority (35/47; 74%) as locoregional failures. On multivariate analysis, spread to multiple nodes and single-modality treatment significantly predicted worse survival. Patients undergoing combined treatment had a lower rate of locoregional recurrence (20% vs. 43%) and a significantly better 5-year disease-free survival rate (73% vs. 54%; P = .004) compared to surgery alone.
In patients with metastatic cutaneous head and neck SCC, surgery and adjuvant radiotherapy provide the best chance of achieving locoregional control and should be considered best practice.
Unlike its more common non-invasive form, invasive squamous cell carcinoma (SCC) of the skin can be biologically aggressive and is prone to recur. The objectives of this study were to identify relevant clinicopathologic prognostic factors associated with the outcomes of patients with invasive SCC in order to define a high-risk group.
We retrospectively reviewed the records of patients with invasive cutaneous SCC of the trunk or extremities who received surgical treatment at a tertiary care cancer center over the past 10 years. We examined the patterns of presentation, all known clinical and histological risk factors for recurrence, and their association with survival.
136 patients were identified, of whom 102 (74%) were male. Patterns of presentation included primary (n = 91), locally recurrent (n = 16), regional nodal (n = 24), and distant (n = 5) disease. Univariate analysis identified poorly differentiated carcinomas (hazard ratio [HR] = 2.92, P = .016), scar carcinomas (HR = 3.12, P = .008), tumor size > 2 cm (HR = 3.79, P = .006), and regional nodal disease (HR = 5.77, P < .0001) as significant risk factors for recurrence or death. On multivariate analysis, however, only regional nodal disease at presentation (HR = 7.64, P < .0001) was found to be significant.
Patients with invasive SCCs metastatic to regional nodes constitute a group at high risk for recurrence and death. Such patients should be considered for adjuvant therapy trials.
Squamous cell carcinoma (SCC) is the second most common type of skin cancer in the United States. Cutaneous SCC has the potential to metastasize and cause morbidity and mortality.
Our purpose was to review and summarize the literature on metastatic cutaneous SCC, including risk factors for metastasis, data from clinical studies, and current management.
Multiple studies confirm that even well-differentiated and small tumors (<2 cm) may metastasize. Over the past two decades, additional literature on the risk factors for metastatic cutaneous SCC, including immunosuppression, has been published. In addition, new staging systems have been proposed that may influence management of these tumors. Chemotherapy regimens are numerous, but remain limited in ability to improve overall survival.
Although we know more about the risk factors, survival for patients with metastatic cutaneous SCC depends on extent of nodal involvement. Therefore, emphasis should remain on prevention and aggressive treatment of cutaneous SCC and vigilant observation for signs and symptoms of metastasis.
Cutaneous squamous-cell carcinomas (SCC) are among the most common cancers capable of metastasis. Current Tumour Node Metastasis (TNM) staging includes horizontal tumour size, involvement of extradermal structures, and degree of differentiation. The aim of this study was to prospectively analyse the key factors predicting metastasis and local recurrence in cutaneous SCC.
We assessed prospectively investigated potential risk factors for metastasis or local recurrence of SCC, previously suggested by retrospective studies and small case series, in 615 white patients. Between Jan 1, 1990, and Dec 31, 2001, all patients underwent surgery for cutaneous SCC with complete histological examination of the three-dimensional excision margins (3D-histology) in one centre. Univariate and multivariate analysis included tumour thickness, horizontal size, body site, histological differentiation, desmoplastic growth, history of multiple SCC, and immunosuppression. Primary endpoints were time to metastasis and time to local recurrence, defined as the time from date of diagnosis of the primary tumour to the date of diagnosis of metastasis or local recurrence, respectively.
653 patients were enrolled in the study. 38 patients were lost to follow-up leaving 615 assessable patients (median age 73 years [range 27-98]). During a median follow-up period of 43 months (range 1-165), 26 (4%) of 615 patients developed metastases and 20 patients developed local recurrence (3%). Tumours 2.0 mm or less in thickness did not metastasise. Metastases occurred in 12 (4%) of 318 tumours between 2.1 mm and 6.0 mm in thickness, and in 14 (16%) of 90 tumours with a thickness greater than 6.0 mm. On multivariate analysis, key prognostic factors for metastasis were increased tumour thickness (hazard ratio 4.79 [95% CI 2.22-10.36]; p<0.0001), immunosuppression (4.32 [1.62-11.52]; p=0.0035), localisation at the ear (3.61 [1.51-8.67]; p=0.0040), and increased horizontal size (2.22 [1.18-4.15]; p=0.0128). The risk of local recurrence depended on increased tumour thickness (6.03 [2.71-13.43]; p<0.0001) and desmoplasia (16.11 [6.57-39.49]; p<0.0001).
Only SCC greater than 2.0 mm in thickness are associated with a significant risk of metastasis. Tumours greater than 6.0 mm are associated with a high risk of metastasis and local recurrence. Desmoplastic growth is an independent risk factor for local recurrence. Studies should assess the role of follow-up visits and sentinel-lymph-node biopsy in high-risk patients.
Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip: implications for treatment modality selection
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Chapter 29 Cutaneous squamous cell carcinoma and other cutaneous carcinomas. AJCC cancer staging manual
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Head and neck cancer in cardiothoracic transplant recipients
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