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Abstract Objective Cutaneous Squamous Cell Carcinoma (cSCC), a tumor with a significantly increasing incidence, is mostly diagnosed in the head region, where tumors have a worse prognosis and a higher risk of metastases. The presence of metastases reduces specific five-year survival from 99% to 50%. As the risk of occult metastases does not exceed 10%, elective dissection of the tributary parotid and neck lymph nodes is not recommended. Methods We retrospectively analyzed a group of 12 patients with cSCC of the head after elective dissections of regional (parotid and cervical) nodes by means of superficial parotidectomy and selective neck dissection. Results We diagnosed occult metastases neither in the cervical nor parotid nodes in any patient. None were diagnosed as a regional recurrence during the follow-up period. Conclucion Our negative opinion on elective parotidectomy and neck dissection in cSCC of the head is in agreement with the majority of published studies. These elective procedures are not indicated even for tumors showing the presence of known (clinical and histological) risk factors for lymphogenic spread, as their positive predictive value is too low. Elective parotidectomy is individually considered as safe deep surgical margin. If elective parotidectomy is planned it should include only the superficial lobe. Completion parotidectomy and elective neck dissection are done in rare cases of histologically confirmed parotid metastasis in the parotid specimen. Preoperatively diagnosed parotid metastases without neck involvement are sent for total parotidectomy and elective selective neck dissection. Cases of clinically evident neck metastasis with no parotid involvement, are referred for comprehensive neck dissection and elective superficial parotidectomy. The treatment of concurrent parotid and cervical metastases includes total conservative parotidectomy and comprehensive neck dissection. Level of evidence How common is the problem? Step 4 (Case-series) Is this diagnostic or monitoring test accurate? (Diagnosis) Step 4 (poor or non-independent reference standard) What will happen if we do not add a therapy? (Prognosis) Step 4 (Case-series) Does this intervention help? (Treatment Benefits) Step 4 (Case-series) What are the COMMON harms? (Treatment Harms) Step 4 (Case-series) What are the RARE harms? (Treatment Harms) Step 4 (Case-series) Is this (early detection) test worthwhile? (Screening) Step 4 (Case-series)
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ABSTRACT Introduction: Previous research demonstrated benefits of late conversion to mTOR inhibitors against cutaneous squamous cell carcinomas (cSCC) in kidney transplant recipients (KTR), despite of poor tolerability. This study investigated whether stepwise conversion to sirolimus monotherapy without an attack dose modified the course of disease with improved tolerability. Methods: This prospective exploratory study included non-sensitized KTR with more than 12-months post-transplant, on continuous use of calcineurin inhibitors (CNI)-based therapy, and with poor-prognosis cSCC lesions. Incidence densities of high-risk cSCC over 3-years after conversion to sirolimus-monotherapy were compared to a non-randomized group with high-risk cSCC but unsuitable/not willing for conversion. Results: Forty-four patients were included (83% male, mean age 60 ± 9.7years, 62% with skin type II, mean time after transplantation 9 ± 5.7years). There were 25 patients converted to SRL and 19 individuals kept on CNI. There was a tendency of decreasing density of incidence of all cSCC in the SRL group and increasing in the CNI group (1.49 to 1.00 lesions/patient-year and 1.74 to 2.08 lesions/patient-year, p = 0.141). The density incidence of moderately differentiated decreased significantly in the SRL group while increasing significantly in the CNI group (0.31 to 0.11 lesions/patient-year and 0.25 to 0.62 lesions/patient-year, p = 0.001). In the SRL group, there were no sirolimus discontinuations, no acute rejection episodes, and no de novo DSA formation. Renal function remained stable. Conclusions: This study suggests that sirolimus monotherapy may be useful as adjuvant therapy of high-risk cSCC in kidney transplant recipients. The conversion strategy used was well tolerated and safe regarding key mid-term transplant outcomes.
RESUMO Introdução: Pesquisas anteriores demonstraram benefícios da conversão tardia para inibidores de mTOR contra carcinomas espinocelulares cutâneos (CECs) em receptores de transplante renal (RTR), apesar da baixa tolerabilidade. Este estudo investigou se a conversão gradual para monoterapia com sirolimo sem dose de ataque modificou o curso da doença com melhor tolerabilidade. Métodos: Esse estudo prospectivo exploratório incluiu RTR não sensibilizados com mais de 12 meses pós-transplante, uso contínuo de terapia imunossupressora baseado em inibidor de calcineurina (CNI) associado a micofenolato de sódio ou azatioprina, com lesões de CECs de mau prognóstico. Comparou-se densidades de incidência de CECs de alto risco durante 3 anos após conversão para monoterapia com sirolimo à um grupo não randomizado com CECs classificados conforme os mesmos critérios de gravidade do grupo sirolimo, mas inadequado/não disposto à conversão. Resultados: Foram incluídos 44 pacientes (83% homens, idade média 60 ± 9,7 anos, 62% com fototipo de pele II, tempo médio pós-transplante 9 ± 5,7 anos). 25 pacientes foram convertidos para SRL e 19 indivíduos mantidos em CNI. Foi observado tendência de diminuição da densidade de incidência de todos CECs no grupo SRL e de aumento no grupo CNI (1,49 a 1,00 lesões/paciente-ano; 1,74 a 2,08 lesões/paciente-ano; p = 0,141). A densidade de incidência de lesões moderadamente diferenciadas diminuiu significativamente no grupo SRL enquanto aumentou significativamente no grupo CNI (0,31 a 0,11 lesões/paciente-ano; 0,25 a 0,62 lesões/paciente-ano; p = 0,001). No grupo SRL não houve descontinuação do sirolimo, nenhum episódio de rejeição aguda e nenhuma formação de DSA de novo. Função renal permaneceu estável. Conclusões: Esse estudo sugere que a monoterapia com sirolimo pode ser útil como terapia adjuvante de CECs de alto risco em RTR. A estratégia de conversão usada foi bem tolerada e segura em relação aos principais desfechos do transplante a médio prazo.
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OBJECTIVE To study the effect and mechanism of dihydrochromone-spliced polycyclic pyrrole-spiroepoxidole compound 3m on cutaneous squamous cell carcinoma. METHODS Using human cutaneous squamous cell carcinoma A431 and Colo-16 cells as research subjects， CCK-8 assay was used to detect the effects of different concentrations of 3m （5， 10， 20， 40， 80 μmol/L） on the proliferation of A431 and Colo-16 cells after 24， 48 and 72 hours； the median inhibitory concentration （IC50） was calculated at 48 h of treatment. A431 and Colo-16 cells were divided into control group， 3m low-concentration and high- concentration groups （15， 30 μmol/L）. After treated with relevant drugs or culture medium for 48 h， the morphological changes of cells in each group were observed by inverted microscope. Clone formation rate， migration rate and number of cell invasions， cell cycle distribution and apoptosis rate were detected. The phosphorylation， or expression of Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3） signaling pathway related proteins [JAK2， STAT3， B-cell lymphocyte-2 （Bcl-2）， Bcl-2- associated X protein （Bax）]， and their mRNA expression in cells were detected. RESULTS 3m could significantly inhibit the proliferation of A431 and Colo-16 cells after treated for 24， 48， 72 h （P＜0.01）， and IC50 of them were 20.36， 23.72 μmol/L， respectively. After 48 hours of treatment， compared with control group， A431 and Colo-16 cells arranged sparsely and loosely connected in 3m low-concentration and high-concentration groups. The clone formation rate， migration rate， number of cell invasions， mRNA expressions of JAK2， STAT3 and Bcl-2， the phosphorylation of JAK2 and STAT3， protein expression of Bcl-2 were significantly decreased/weakened （P＜0.01）. Proportion of cell cycle in G2 phase， apoptosis rate， protein and mRNA expression of Bax were increased significantly （P＜0.01）； and all the above effects were in dose-dependent manner. CONCLUSIONS 3m can inhibit the proliferation， clone formation， migration and invasion abilities of cutaneous squamous cell carcinoma A431 and Colo-16 cells in a dose-dependent manner， the mechanism of which may be associated with inhibiting the activity of JAK2/STAT3 signaling pathway， and inducing cell apoptosis.
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OBJECTIVE：To stud y the effects of sinapine thiocyanate （ST） on the proliferation ，epithelial mesenchymal transformation（EMT）and metastasis of human cutaneous squamous cell carcinoma SCL- 1 cells，and to investigate its possible mechanism. METHODS ：Human cutaneous squamous cell carcinoma SCL- 1 cells were divided into blank control group （0.1％ DMSO） and ST different concentration groups （5，10，20 μmol/L）. CCK- 8 assay，5-ethynyl-2′-deoxyuridine（EDU）test， scratch test and Transwell chamber invasion test were adopted to test the proliferation ，migration and invasion ability. The expression of N-cadherin and E-cadherin were detected by Western blot and immunofluorescence assay . Other SCL- 1 cells were collected and divided into blank control group （0.1％ DMSO），ST group （20 μmol/L），ST+NSC228155 group [ 20 μmol/L ST+100 μmol/L NSC228155（EGFR agonist ）] and ST+SC 79 group [ 20 μmol/L ST+20 μmol/L SC79（PI3K/Akt agonist ）]. The proliferation ，migration and invasion ability of SCL- 1 cells in each group were detected by CCK- 8 assay，scratch test and Transwell chamber invasion assay. The expression of epidermal growth factor receptor （EGFR），phosphatidylinositol 3 kinase（PI3K），phosphorylated phosphatidylinositol 3 kinase（p-PI3k），protein kinase B （Akt）and phosphorylated protein Akt （p-Akt）protein of cells in blank control group and ST different concentration groups（5，10，20 μmol/L）were determined by Western blot assay so as to validate the relationship between ST effect and EGFR/ PI3K/Akt signaling pathway. SCL- 1 cells and human normal skin fibroblasts cell WS 1 were divided into blank control group （0.1％ DMSO），ST group （20 μmol//L），ZD1839 group（positive control ，20 μmol//L，EGFR inhibitor ）and LY 294002 group（positive control，20 μmol//L，PI3K/Akt inhibitor ）. CCK- 8 assay was used to detect the cell proliferation in order to evaluate the cells cytotoxicity of ST. RESULTS ：Compared with blank control group ，the proliferation ，migration and invasion ability of SCL- 1 cells were significantly decreased in 5，10，20 μmol/L ST groups（P＜0.05）. Western blot and immunofluorescence assay showed that the expression of N-cadherin in SCL- 1 cells were decreased significantly in 5，10，20 μmol/L ST groups（P＜0.05），while the protein expression of E-cadherin was increased significantly （P＜0.05）；the protein expressions of EGFR ，p-PI3K and p-Akt were significantly decreased （P＜0.05）. Compared with ST group ，the proliferation ，migration and invasion ability of SCL- 1 cells were increased significantly in ST + NSC 228155 group and ST + SC 79 group （P＜0.05）. Compared with blank control group ，the proliferation ability of WS 1 cells had no significant change in ST group ，while the proliferation ability of SCL- 1 cells was decreased significantly （P＜0.05）；the proliferation ability of the two kinds of cells were decreased significantly in ZD 1839 group and LY 294002 group（P＜0.05）. Compared with ST group ，the proliferation ability of WS 1 cells was decreased significantly in ZD1839 group and LY 294002 group（P＜0.05），but there was no significant difference in the proliferation ability of SCL- 1 cells （P＞0.05）. CONCLUSIONS ：ST may inhibit the proliferation ，EMT and metastasis of SCL- 1 cells through inhibiting the activation of EGFR/PI 3K/Akt signaling pathway ，and its side effects are few.
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The objective of this study was to investigate whether the conjugation of gold nanoparticles (GNPs) to 5-aminolevulinic acid (5-ALA) could enhance the anti-tumor efficiency of photodynamic therapy (PDT) in epidermoid carcinoma cells. The mRNA and protein expression levels were determined by quantitative real-time PCR and western blot, respectively. Cell viability, apoptosis, invasion, and migration were determined by MTT assay, flow cytometry, transwell invasion assay, and migration assay, respectively. Singlet oxygen generation was detected by the singlet oxygen sensor green reagent assay. Our results showed that PDT with 5-ALA and GNPs-conjugated 5-ALA (5-ALA-GNPs) significantly suppressed cell viability, increased cell apoptosis and singlet oxygen generation in both HaCat and A431 cells, and PDT with 5-ALA and 5-ALA-GNPs had more profound effects in A431 cells than that in HaCat cells. More importantly, 5-ALA-GNPs treatment potentiated the effects of PDT on cell viability, cell apoptosis, and singlet oxygen generation in A431 cells compared to 5-ALA treatment. Further in vitro assays showed that PDT with 5-ALA-GNPs significantly decreased expression of STAT3 and Bcl-2 and increased expression of Bax in A431 cells compared with PDT with 5-ALA. In addition, 5-ALA-GNPs treatment enhanced the inhibitory effects of PDT on cell invasion and migration and Wnt/β-catenin signaling activities in A431 cells compared to 5-ALA treatment. In conclusion, our results suggested that GNPs conjugated to 5-ALA significantly enhanced the anti-tumor efficacy of PDT in A431 cells, which may represent a better strategy to improve the outcomes of patients with cutaneous squamous cell carcinoma.
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Humans , Skin Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Metal Nanoparticles/administration & dosage , Levulinic Acids/pharmacology , Photochemotherapy , RNA, Neoplasm , Cell Survival/drug effects , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effectsABSTRACT
Objective Studies are rarely reported on the effect of short peptides of the pigment epithelium derived factor (PEDF) on the proliferation of human cutaneous squamous (SCL-1) cells. The purpose of this study is to investigate segmented cloning and expression of the PEDF protein and observe its effect on the proliferation of human SCL-1 cells. Methods The target genes of PEDF1, PEDF2 and PEDF3 were amplified by PCR and the recovered fragments subjected to double digestion of NheⅠ and Hind Ⅲ and inserted into the pET28a(+) plasmid. The product was transformed into human E coli BL21 and induced to express, followed by isolation and purification of the fusion protein. CCK-8 assay was used to detect the proliferation of the SCL-1 cells with PEDF1, PEDF2 and PEDF3 at 100, 400, 800 and 1000 nmol/L at 24, 48 and 72 hours. Results The prokaryotic expression vectors of PEDF1, PEDF2 and PEDF3 were successfully constructed, and their fusion proteins prepared, with the molecular weight of 18 000, 17 000 and 13 000, respectively. The proliferation of the SCL-1 cells was significantly decreased in the 800 and 1000 nmol/L PEDF3 groups compared with that in the 0 nmol/L PEDF3 group at 24 hours (0.16 ± 0.03 and 0.78 ± 0.07 vs 1.00 ± 0.00, P < 0.05), inhibited in a concentration-dependent manner in the 400, 800 and 1000 nmol/L PEDF3 groups at 48 hours (P < 0.05), markedly lower in the 800 and 1000 nmol/L PEDF3 groups at 72 hours (0.53 ± 0.05 and 0.51 ± 0.05) than in the in the 400 and 0 nmol/L PEDF3 groups (0.60 ± 0.05 and 1.00 ± 0.00) (P < 0.05). Conclusion The PEDF fusion proteins were successfully segmentally cloned and expressed and PEDF3 inhibited the proliferation of SCL-1 cells, which has paved the ground for further screening of active functional short peptides of PEDF.
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BACKGROUND: Programmed cell death ligand 1 (PD-L1) plays a major role in the immune responses of a variety of cancers. Recently, several studies revealed that PD-L1 is differently expressed in some cases of non-melanoma skin cancer. The expression of PD-L1 in cutaneous squamous cell carcinoma has not yet been described in Korea. OBJECTIVE: To investigate the expression of PD-L1 in cutaneous squamous cell carcinoma and its association with variable clinicopathological factors. METHODS: We performed immunohistochemical staining of 52 cutaneous cell carcinoma cases, including 28 high-risk cases and 24 low-risk cases. Cases were selected from patients who had visited the department of dermatology of our hospital from 2001 to 2017. The expression patterns were assessed using the H-score. Cases demonstrating at least 1+ of PD-L1 in more than 1% of tumor cells were considered positive. RESULTS: PD-L1 expression of tumor cells was 19.2% (10/52) for all cases, 0.0% (0/24) for the low-risk group, and 35.7% (10/28) for the high-risk group. PD-L1 positive cutaneous squamous cell carcinoma cases showed a significantly higher proportion of large tumors and tumors with deep invasion and a higher lymphatic metastasis rate when compared to PD-L1 negative cutaneous squamous cell carcinoma cases. CONCLUSION: Our study shows that cutaneous squamous cell carcinoma exhibits PD-L1 expression in 19.2% of cases. PD-L1 positive tumors are associated with high-risk cases of cutaneous squamous cell carcinoma, which may help guide the choice of therapeutic strategy.
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Humans , Carcinoma, Squamous Cell , Cell Death , Dermatology , Epithelial Cells , Korea , Lymphatic Metastasis , Neoplasm Metastasis , Skin NeoplasmsABSTRACT
Objective:To investigate the effect of inhibiting of BAG-1 gene expression on proliferation and apoptosis of cutaneous squamous cell carcinoma.Methods:siRNA of BAG-1 was transfected in cutaneous squamous cell carcinoma A431 by Lipo-fectamineTM2000,cells were transfected for 48 h,the BAG-1 mRNA expression was detected by RT-PCR,BAG-1 protein expression was detected by Western blot;CCK8 and flow cytometry were used to detect the cell proliferation and apoptosis;Western blot was used to detect the expression of Bax,β-catenin and Survivin protein;IL-6 and VEGF content were detected by ELISA kit.Results:Compared with control group and negative control group,transfection of BAG-1 with siRNA could significantly inhibit the expression of BAG-1 at the transcriptional and translational levels;compared with the control group,the cells proliferation in BAG-1-siRNA group significantly decreased,apoptosis rate was significantly increased,Bax protein expression was up-regulated,expression of β-catenin,Survivin protein were down regulated,the contents of IL-6 and VEGF were decreased significantly(P<0.05).Conclusion:Silencing of BAG-1 expression can reduce the proliferation of cutaneous squamous cell carcinoma,promote apoptosis,up regulate Bax expression and down regulate the expression of Wnt/β-catenin signaling pathway,and reduce the secretion of IL-6 and VEGF factors.
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[Objective]To observe the biological characteristics of CD133 positive cells derived from cutaneous squa-mous cell carcinoma(cSCC),and to investigate the mechanism of self-renewal of cancer stem cells(CSC)and the malig-nant behavior in cSCC.[Methods]The flow cytometry was applied to purify CD133+cells and CD133-from cutaneous squa-mous cell carcinoma cell line Colo-16.The effects of CD133 on the cell proliferative,self renew and migratory activity of two group cells were detected by MTT assay,Sphere formation assay and Transwell assay.Western blot and quantitative flu-orescent PCR were performed to investigate the expression of cancer stem cell associated gene CD44,OCT4 and SOX2 in two groups of cells.Examined the expression level of CD133 in actinic keratosis,squamous cell carcinoma in situ and cSCC by immunohistochemistry.[Result]The CD133+Colo-16 cells exhibited significantly stronger proliferation,self-renewal and metastasis ability(P<0.05)and present higher level protein and mRNA expression on CD44,SOX2 and OCT4(P<0.05). In addition,the expression level of CD133 was dynamic rise during the continuous evolution of actinic keratosis,squamous cell carcinoma in situ and cSCC.[Conclusions]The expression level of CD133 may be related to the tumorigenesis of cSCC and the malignant behavior including proliferative,self renew and migratory activity,and CD133+cSCC cells show the properties of cancer stem cells.The occurrence and development of cSCC may be related to the CSC,which express CD133.
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OBJECTIVE: To investigate the effect of ABT-263,an anti-apoptotic protein inhibitor,on human cutaneous squamous cell carcinoma A431 cells,and to explore its molecular mechanisms. METHODS: i) Total protein was extracted from human immortalized epidermal cells( Ha Ca T cells) and A431 cells in logarithmic growth phase. The protein expression of B-cell lymphoma-2( BCL-2) and BCL2-like 1( BCL-XL) was detected by Western blotting. ii) The A431 cells were treated with ABT-263( inhibitor group) and dimethyl sulfoxide( control group) at a concentration of 50 μmol/L for 4 and 9 hours. The morphological changes of the cells were examined by transmission electron microscopy. iii) The A431 cells were treated with 0,10,25,40,and 50 μmol/L of ABT-263 for 24 hours,and the cell viability was determined by CCK-8 assay. iv) The A431 cells were treated with different doses of ABT-263,and the expression of cleaved Caspase-3, cleaved poly( ADP-ribose) polymerase-1( PARP-1), phosphorylated protein kinase B [p AKT(ser473)],phosphorylated glycogen synthase kinase-3β(p GSK3β) and phosphorylated histone H2 AX(γH2 AX) was detected by Western blot. RESULTS: The relative expression of BCL-2 and BCL-XL in A431 cells were higher than those in Ha Ca T cells( P < 0. 01). Transmission electron microscopy results showed that A431 cells in inhibitor group gradually changed from normal morphology to apoptotic morphology,showing loss of microvilli,increased nuclear chromatin density and aggregation around the nuclear membrane,and nuclear fragmentation. The cell viability of A431 cells in 10,25,40 and 50 μmol/L groups were lower than those in control group( P < 0. 05). The relative expression of cleaved Caspase-3 and cleaved PARP-1 in A431 cells in 10,30 and 50 μmol/L groups were higher than those in control group( P < 0. 05).The relative expression of p AKT( ser473) and p GSK3β in A431 cells in 10,25,40 and 50 μmol/L groups were lower than those of the control group( P < 0. 05) and γH2 AX protein expression was higher than that of the control group( P <0. 05). A431 cell viability and p GSK3β protein expression decreased with the increase of inhibitor dosage( P < 0. 01).The relative expression of cleaved Caspase-3 and γH2 AX protein increased with the increase of inhibitor dosage( P <0. 01),showing dose-effect relationship. CONCLUSION: ABT-263 can induce apoptosis of A431 cells through mitochondria pathway and induce the inactivation of AKT/GSK3β pathway,which can promote the apoptosis of A431 cells with a doseeffect relationship.
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El Pilomatrixoma es un tumor anexial benigno. Presenta una variante histopatológica infrecuente denominada pilomatrixoma proliferante reportada en 1997 por Kaddu et al. Corresponde a una lesión compuesta predominantemente por una proliferación lobular de células basaloides, con atipia nuclear variable y figuras mitóticas, áreas focales que contienen material cornificado eosinófilo, junto con células sombra. Se propuso al pilomatrixoma proliferante como un subconjunto histopatológico distintivo del pilomatrixoma y se consideró como una variante proliferativa con un perfil histopatológico benigno. La dermatoscopía en este tumor, sobre todo en pacientes de edad avanzada, puede llegar a constituir una trampa dermatoscópica, que es difícil de diferenciar de otras lesiones, como el melanoma o el carcinoma de células basales. Existen múltiples reportes de casos en la literatura donde se informa de pilomatrixomas clásicos o proliferantes simulando otras neoplasias. Presentamos el caso de una paciente de 88 años con pilomatrixoma proliferante facial que simuló clínicamente un carcinoma de células escamosas y llevó a confusión diagnóstica inicial, se destacan las características histopatológicas y clínicas de los pilomatrixomas proliferantes.
Pilomatrixoma is a benign adnexal tumor. It has an infrequent histopathological variant called proliferating pilomatrixoma reported in 1997 by Kaddu et al. It corresponds to a lesion composed predominantly by a lobular proliferation of basaloid cells, with variable nuclear atypia and mitotic figures, focal areas containing eosinophilic cornified material, together with shadow cells. The proliferating pilomatrixoma was proposed as a distinctive histopathological subset of the pilomatrixoma and was considered as a proliferative variant with a benign histopathological profile. Dermatoscopy in this tumor, especially in elderly patients, can result in a dermatoscopic trap, which makes it difficult to differentiate from other lesions, such as melanoma or basal cell carcinoma. There are multiple reports of cases in the literature where classic or proliferating pilomatrixomas were reported simulating other neoplasms. We present the case of an 88-year-old patient with a proliferating facial pilomatrixoma that clinically simulated a squamous cell carcinoma and led to an initial diagnostic confusion, highlighting the histopathological and clinical characteristics of the proliferating pilomatrixoma.
Subject(s)
Humans , Male , Aged, 80 and over , Skin Neoplasms/diagnosis , Carcinoma, Squamous Cell/diagnosis , Pilomatrixoma/diagnosis , Hair Diseases/diagnosis , Skin Neoplasms/pathology , Nose , Pilomatrixoma/pathology , Neoplasms, Squamous Cell/pathology , Dermoscopy , Diagnosis, Differential , Hair Diseases/pathologyABSTRACT
BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is a malignant proliferation of keratinocytes of the epidermis. It may have the potential to metastasize distally in contrast to the cutaneous basal cell carcinoma. OBJECTIVE: We investigated the recent trend of cSCC development from a clinical, histopathological, and prognostic perspective. METHODS: One hundred and sixty cases of cSCC in patients who had visited the Samsung Changwon Hospital over the past 10 years (between 2006 and 2016) were retrospectively studied. We analyzed their age, sex, location, etiologic factor, histopathologic finding, and treatment. RESULTS: The average age of cSCC was 77 years old and the sex ratio was 1:2.27. The most commonly involved location was the head and neck (73.13%). The etiologic factors were unknown (61.88%), actinic keratosis (23.13%), Bowen's disease (10.63%), burn scar (2.5%), chronic eczema (0.63%) and chronic inflammatory disease (0.63%). The average tumor diameter and thickness were 18.1 mm and 3.58 mm, respectively. The degrees of differentiation were well-differentiated (68.75%), moderately differentiated (28.75%) and poorly differentiated (2.5%). The occurrence rate of cSCC metastasis was 6.25% (10 cases/160 cases). The most common primary locations of cSCC metastasis were the lower extremities (5 cases/10 cases) and head and neck (2 cases/10 cases). All 10 cases were metastasis to adjacent lymph nodes. Five cases showed metastasis to distant lymph nodes, the lungs, liver or bone. The average tumor diameter and thickness of cSCC metastasis were 45.3 mm and 9.46 mm, respectively. Histopathologically, the degrees of differentiation were well-differentiated, moderately differentiated and poorly differentiated type (4 cases, 5 cases, and 1 case, respectively). CONCLUSION: The location of the lower extremities (p=0.000) and a size larger than 20 mm (p=0.000) were related to cSCC metastasis. cSCC metastasis was found at an average of 7.5 months after diagnosis. High-risk cSCC patients should be followed closely, particularly during the first 2 years after diagnosis.
Subject(s)
Humans , Bowen's Disease , Burns , Carcinoma, Basal Cell , Carcinoma, Squamous Cell , Cicatrix , Diagnosis , Eczema , Epidermis , Epithelial Cells , Head , Keratinocytes , Keratosis, Actinic , Liver , Lower Extremity , Lung , Lymph Nodes , Neck , Neoplasm Metastasis , Retrospective Studies , Sex RatioABSTRACT
Background: Squamous and basal cell carcinomas together constitute the majority of non-melanoma skin cancers. These malignancies are infrequent in Indians as compared to the white skinned population. Literature on squamous cell carcinoma in dark skin is limited. Aim: To analyze the risk factors and to characterize the histopathological subtypes of cutaneous squamous cell carcinoma in Indian patients in an area, non-endemic for arsenicosis. Methods: A retrospective analysis of data from January 2003 to August 2013 was performed to evaluate the predisposing factors and histopathological types of cutaneous squamous cell carcinoma at the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh. Demographic and disease characteristics such as age, gender and predisposing factors, particularly premalignant dermatoses were recorded and histopathology slides were reviewed. Results: Of the 13,426 skin biopsy specimens received during the 10-year period, there were 82 (0.6%) cases of squamous cell carcinoma and 170 (1.7%) of basal cell carcinoma. The mean age at diagnosis of cutaneous squamous cell carcinoma was 53.7 years and the male to female ratio was 2:1. The most common site of involvement was the lower limbs in 34 (41.5%) patients. Marjolin’s ulcer was present in 36 (43.9%) cases. No predisposing factor was identifi ed in 35 (42.7%) patients. Histopathologically, the tumors were classifi ed most commonly as squamous cell carcinoma not otherwise specifi ed in 33 (40.2%) cases. Limitations: This was a retrospective study and details of occupation and interval between the precursor lesions and development of tumor were not recorded. Immunohistochemistry for human papilloma virus and p53 tumor suppressor protein were not performed as these tests were not available. Conclusion: Cutaneous squamous cell carcinoma is uncommon in Indian patients and a high index of suspicion is necessary when a rapidly enlarging nodule, verrucous fungating plaque or an ulcer with everted margins develops in long standing scars and other predisposing dermatologic conditions. Histopathological examination is mandatory to confi rm the diagnosis and identify the subtype and this has prognostic implications.
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Cutaneous squamous cell carcinoma (SCC) is the second most common skin malignant neoplasm. Cutaneous SCC shows a broad spectrum, ranging from easily managed superficial tumors to highly infiltrative, metastasizing ones that can cause death. We have experienced two patients with SCC with intracranial extension. One case was an 88-year-old man with a tumor on the forehead treated with Mohs micrographic surgery who presented with local recurrence at the perilesional region of the primary site after 3 years. Wide excision was performed, and histologic findings showed a SCC that extended to the dura mater. The other case was a 69-year-old woman who presented with an erythematous 2x4 cm-sized plaque on the right temple, and a biopsy examination revealed SCC. The patient refused surgery and 7 months later, presented with a 5x10 cm-sized oozing plaque with multiple ulcers. Radiologic evaluation demonstrated intracranial invasion and right retropharyngeal metastatic lymph nodes. She was treated with radiotherapy for 4 months.
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Biopsy , Carcinoma, Squamous Cell , Dura Mater , Forehead , Lymph Nodes , Mohs Surgery , Neoplasm Metastasis , Radiotherapy , Recurrence , Skin , UlcerABSTRACT
Objective To investigate the carcinogeic role of miR-365 in cuntanerous squamous cell carcinoma (cSCC).Methods Normal HaCaT cells were divided into control and irradiation groups,the later was exposed by UVB irradiation (50 J/m2).MicroRNA expression profiles of the two groups were analyzed by microRNA array.The expression variations of miR-365 in HaCaT,A431,Tca8113 and HSC-1 cells were validated by qRT-PCR analysis.The colony-forming and invasion capacities were dectected by colony forming assay and Transwell migration assay in vitro,respectively.HaCaTpre-miR365-2 highly expressing miR-365 was constructed by retroviral vector infection.Tumorigenicity evaluation was carried out by subcutaneously inject of the cells at the right back flank of nude mice.Results There were 30 microRNAs differentially expressed in HaCaT cells after UVB irradiation and miR-365 was one of the most sensitive miRNAs(as high 6.7 times as control).Expression of miR-365 in all the cSCC cell lines A431,Tca8113 and HSC-1 were significantly higher than that in HaCaT cell,in which the maximum was A431 (15.67 ±1.12 times,P ＜ 0.01),and the minimum was TcaS113 (4.72 ± 0.85 times,P ＜ 0.05).Knockdown of miR-365 in cSCC cell lines significantly inhibited the colony forming ability (t =13.68,P ＜ 0.05) and cell migration (t =19.98,P ＜ 0.05) in vitro.HaCaT cells overexpressing miR-365 by transient transfection significantly increased the ability of colony formation (t =7.11,P ＜ 0.05) and cell migration (t =22.03,P ＜0.05) in vitro.In addition,HaCaTpre-miR-365-2 cell line stably expressing miR-365 could successfully establish tumors in nude mice.Conclusions MiR-365 is an oncogene for cutaneous squamous cell carcinoma.
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BACKGROUND: Ionotropic glutamate receptors of the N-methyl-D-aspartate receptor (NMDAR) type are expressed on keratinocytes and play a role in the proliferation, differentiation, and cornification of keratinocytes. However, the expression profile of NMDAR and its role in cutaneous malignancy is unclear. OBJECTIVE: We analyzed the expression of NMDAR-1 in cutaneous squamous cell carcinoma (SCC) and investigated the relationship between NMDAR-1 expression and clinicopathological parameters. METHODS: Thirty-two patients with biopsy-proven cutaneous SCC were enrolled in this study. Each patient was analyzed for tumor diameter, location, local recurrence, and metastasis by conducting a chart review. The SCC specimens were histologically divided into differentiated and undifferentiated groups based on Broders' system. NMDAR-1 expression was examined by performing immunohistochemistry, and the relative staining intensity in the SCCs was graded into 5 levels. According to the staining intensity of NMDAR-1, the specimens were categorized into two groups: the higher group and the lower group. RESULTS: Fifteen (88%) of 17 tumors in the higher group were differentiated SCC, whereas 14 (93%) of 15 tumors in the lower group were undifferentiated SCC. In addition, NMDAR-1 expression was inversely correlated with metastasis (p=0.049). Local recurrence was associated with a lower staining intensity, but the results were not statistically significant. CONCLUSION: Our results demonstrate that NMDAR-1 expression in cutaneous SCC is significantly correlated with its differentiation and metastasis. Therefore, it may be a prognostic indicator for cutaneous SCC.
Subject(s)
Humans , Carcinoma, Squamous Cell , Immunohistochemistry , Keratinocytes , N-Methylaspartate , Neoplasm Metastasis , Receptors, Ionotropic Glutamate , RecurrenceABSTRACT
Introducción: Un subgrupo de pacientes con carcinoma epidermoide cutáneo (CEC) tiene alto riesgo de presentar metástasis ganglionares regionales. El mapeo linfático y biopsia del ganglio centinela (MLBGC) ha sido exitosamente utilizado para evaluar la presencia de metástasis ganglionares subclínicas en diversos tumores. bjetivo: Evaluar la utilidad de la técnica del MLBGC en los pacientes con CEC de alto riesgo para detectar la presencia de metástasis ganglionares regionales subclínicas. Material y métodos: De enero 2002 a marzo 2004, un total de 20 pacientes con CEC de alto riesgo con ganglios linfáticos regionales clínicamente no palpables fue evaluado con linfografía preoperatoria y MLBGC. Resultados: En 1 de cada 5 pacientes (20 %), el ganglio centinela reveló la presencia de micrometástasis. Ningún paciente con GC negativo manifestó progresión tumoral ganglionar regional durante un seguimiento medio de 23.5 meses (rango de 7 a 44 meses). Conclusiones: El MLBGC fue técnicamente posible con baja morbilidad. El MLBGC puede tener un importante papel en el tratamiento de los pacientes con CEC de alto riesgo con ganglios linfáticos regionales no palpables. Esta técnica puede ayudar a identificar los pacientes con metástasis en los ganglios linfáticos regionales que pueden beneficiarse de una disección ganglionar radical. Además provee importante información para utilizar terapias adyuvantes a la cirugía.
BACKGROUND: Some sub-groups of cutaneous squamous cell carcinoma (CSCC) display a higher risk for regional metastasis. Sentinel lymph node staging has been used successfully to evaluate nodal metastasis in selective tumors. OBJECTIVE: Assess the feasibility of sentinel node to detect occult regional lymph node metastasis in high-risk CSCC. MATERIAL AND METHODS: Between January 2002 and March 2004, a total of 20 patients received pre-operative lymphoscintigraphy and sentinel lymphadenectomy for high-risk CSCC with clinically non-palpable regional lymph nodes. RESULTS: In one of each 5 patients (20%), sentinel lymph node showed histological evidence of microinvolvement. No patients with negative sentinel node showed tumor dissemination during follow-up, with a mean of 23.5 months (range 7-44). CONCLUSIONS: Sentinel lymph node biopsy is technically feasible with low morbidity. Sentinel lymphadenectomy may play an important role in the management of high-risk CSCC with clinically non-palpable regional lymph nodes. This technique can help identify patients with regional lymph node metastases who may benefit from complete lymphadenectomy. This improved staging may allow clinicians to better stratify patients who might benefit from adjuvant therapy.
Subject(s)
Humans , Male , Female , Middle Aged , Aged, 80 and over , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/secondary , Skin Neoplasms/pathology , Sentinel Lymph Node Biopsy , Feasibility Studies , Lymphatic Metastasis , Risk FactorsABSTRACT
Objective To evaluate the expressions and roles of survivin (SVV), bcl-2 and proliferating cell nuclear antigen(PCNA) in cutaneous squamous cell carcinoma (SCC). Methods The expressions of SVV, bcl-2 and PCNA were investigated by SP immunohistochemistry technique in 82 cases of SCC and 18 normal skin samples. Results There were 79.3% of SCC patients with the expression of SVV (P