Low-grade Squamous Cell Carcinoma Research Articles

Giant condyloma, buschke-löwenstein tumor in the penis, presentation of a case and review of the literature

Background: Buschke-Löwenstein tumor is a presentation of condyloma acuminata; caused by human papillomavirus infection presenting as an exophytic, polypoid, cauliflower-like lesion; characterized by slow growth, local infiltration, contiguous tissue destruction; with a tendency to recurrence and produce fistulas or abscesses around the affected area. The most frequent location is the vulva, scrotum, penis, perineum and perianal region; Transmitted by sexual contact and more common in men, it is controversial whether it should be considered premalignant or a verrucous carcinoma; It does not present cellular atypia and a third can become malignant; recurrences are frequent. The risk factors are HPV, continuous irritation and poor hygiene of the genital area, phimosis, immunosuppression, smoking and drug addiction. Objective: review literature and case description. Case presentation: 45-year-old male with condylomatous lesion on the genitals of 4 months' duration, on the foreskin and ligament of the glans penis, and other minor lesions on the shaft of the penis; morbid obesity, uncontrolled type 2 diabetes mellitus. He is scheduled for circumcision and removal of the satellite lesions. Conclusion: Giant Buschke-Löwenstein condyloma is considered a low-grade squamous cell carcinoma, locally invasive, with aggressive behavior; Surgical treatment is the option.

Rare cutaneous verrucous carcinoma in the femoral region: a case report

BackgroundVerrucous carcinoma (VC) is a well-differentiated variant of squamous cell carcinoma (SCC) characterized by slow growth and low metastatic potential. Cutaneous verrucous carcinoma (CVC) or papillomatosis cutis carcinoides is the term used for VC in other locations than the oral, anogenital, and plantar regions. This rare tumor has a contradictory “benign” histology, but markedly aggressive clinical behavior. We present this case as background knowledge to corroborate clinical course, diagnosis, histopathology, and treatment options for this infrequent disease. Case DescriptionWe report a verrucous carcinoma on a 79-year-old man’s left thigh. Clinical examination showed a fungating mass with cauliflower-like appearance measuring 5x3x1 cm. Excisional biopsy revealed exo-endophytic proliferation of well-differentiated squamous epithelium invading the dermis with marked hyperkeratosis, parakeratosis, acanthosis, papillomatosis, pushing margins, and minimal cellular atypia (T2N0M0). It was successfully treated by wide local excision, inguinal lymph node dissection, and adjuvant radiotherapy. Follow-up after 1 year showed good wound healing without any loss of function or recurrence. ConclusionCutaneous verrucous carcinoma is a subtype of a low-grade SCC and is not an SCC with a verrucous presentation. Identification of the clinicopathological features is essential to distinguish CVC from its mimics and to make an early diagnosis. Although slow growth and confusing early-stage appearances can lead to delay in diagnosis or to misdiagnosis, this case has not raised many diagnosis problems regarding the cardinal manifestations of CVC. Regardless of any available therapeutic methods, surgical excision with safety margins is still a priority and CVC requires aggressive treatment.

T1 mapping and multimodel diffusion-weighted imaging in the assessment of cervical cancer: a preliminary study.

To evaluate the clinical feasibility of T1 mapping and multimodel diffusion-weighted imaging (DWI) for assessing the histological type, grade, and lymphovascular space invasion (LVSI) of cervical cancer. Eighty patients with cervical cancer and 43 patients with a normal cervix underwent T1 mapping and DWI with 11 b-values (0-2000 s/mm2). Monoexponential, biexponential, and kurtosis models were fitted to calculate the apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudo-diffusion (D*), perfusion fraction (f), mean diffusivity (MD), and mean kurtosis (MK). Native T1 and DWI-derived parameters (ADCmean, ADCmin, Dmean, Dmin, D*, f, MDmean, MDmin, MKmean, and MKmax) were compared based on histological type, grade, and LVSI status. Native T1 and DWI-derived parameters differed significantly between cervical cancer and normal cervix (all p < 0.05), except D* (p = 0.637). Native T1 and MKmean varied significantly between squamous cell carcinoma (SCC) and adenocarcinoma (both p < 0.05). ADCmin, Dmin, and MDmin were significantly lower while MKmax was significantly higher in the high-grade SCC group than in the low-grade SCC group (all p < 0.05). LVSI-positive SCC had a significantly higher MKmean than LVSI-negative SCC (p < 0.05). Both T1 mapping and multimodel DWI can effectively differentiate cervical cancer from a normal cervix and cervical adenocarcinoma from SCC. Furthermore, multimodel DWI may provide quantitative metrics for non-invasively predicting histological grade and LVSI status in SCC patients. Combined use of T1 mapping and multimodel DWI may provide more comprehensive information for non-invasive pre-operative evaluation of cervical cancer.

P16 expression in uterine cervical lesions and its role as diagnostic markers and clinical management

Background: Cervical cancer is one of the world's third most common gynecologic malignant tumors, especially in developing countries. This cancer is the most common cause of cancer-related death. High-risk human papillomavirus (HPV) is the main cause. p16 is a biological marker that can be used as a surrogate marker to increase diagnostic agreement for high-risk HPV infection. This study proved the differences in p16 expression in various age groups in low-grade cervical intraepithelial neoplasm (CIN), high-grade CIN, and squamous cell carcinoma (SCC). Methods: The research design was a cross-sectional analytic observational study, with a total sample of 40, taken from biopsy and surgery specimen patients diagnosed with CIN and SCC whose tissues were examined at the Anatomical Pathology Laboratory Faculty of Medicine Universitas Udayana/ Prof. dr. I G.N.G. Ngoerah General Hospital Denpasar. Histopathological diagnosis and determination of the type of cervical lesion were performed by Hematoxylin and Eosin (H&amp;E) staining. p16 expression was evaluated by immunohistochemistry. The results were analyzed using the chi-square test to prove differences in p16 expression in various age groups and the Kruskal-Wallis Test followed by the Mann-Whitney Test to prove differences in p16 expression in low-grade CIN, high-grade CIN and SCC, with a significance level of p &lt; 0.05. Results: The mean age of low-grade CIN was younger than high-grade CIN, which was 45.5±8.44 compared to 46.1±9.11. The mean age of low-grade and high-grade CIN is also younger than the mean age of SCC, which is 50.9±10.80. There was no significant difference in the expression of p16 in low grade CIN (p=0.34), high-grade CIN (p=0.45) and SCC (p=0.28) in various age groups. The expression of p16 was found significantly differ in all groups (p=0.011). Low-grade CIN significantly differed from high grade CIN (p=0.012) and SCC (p=0.008). However, we found same p16 expression in high-grade CIN and SCC (p = 0.866). Conclusion: p16 can be used as a screening method for diagnostic markers of high-risk HPV infection and a reference for planning therapy.

H-CNN combined with tissue Raman spectroscopy for cervical cancer detection

Cervical cancer is one of the most common cancers with a long latent period and slow onset process. Early and accurate identification of the stage of cervical cancer can significantly improve the cure rate and patient survival time. In this study, we collected 699 Raman spectral data of tissue sections from 233 different patients. We analyzed and compared the characteristics and differences of the mean Raman spectra of the seven tissues and pointed out the main differences in the biochemical composition of the seven tissues. In this study, 1D hierarchical convolutional neural network (H-CNN) is proposed by integrating the prior knowledge of hierarchical classification relations with the research of deep learning in Raman spectroscopy. H-CNN is based on CNN and is added with three network branches. Hierarchical classification is performed from coarse to fine for tissue samples of cervicitis, Low-grade Squamous Cell Carcinoma, High-grade Squamous Cell Carcinoma, Well Differentiated Squamous Cell Carcinoma, Moderately Differentiated Squamous Cell Carcinoma, Poorly Differentiated Squamous Cell Carcinoma and cervical adenocarcinoma. To evaluate the recognition performance of H-CNN, we compared it with traditional methods such as Bayesian classifier (NB), decision tree classifier (DT), support vector machine classifier (SVM) and CNN. The experimental results show that H-CNN can accurately identify different classes of tissue sections and has apparent advantages in several aspects such as recognition accuracy, stability and sensitivity compared with the other four traditional recognition methods. The classification Macro-Accuracy of H-CNN can reach 94.91%, Macro-Recall can reach 95.31%, Macro-F1 can reach 95.23%, and Macro-AUC can reach 97.35%. The hierarchical classification method proposed in this study can diagnose patients more accurately. This could lay the foundation for further research on Raman spectroscopy as a clinical diagnostic method for cervical cancer.

Evaluation of the Cytonucleomorphometric Parameters for Cases Diagnosed as Squamous Cell Abnormality on Conventional Cervico-Vaginal Pap Smears.

The natural history of cervical cancer is unique that it is preceded by a precancerous condition for a long time. Morphometry as a tool can be used in early and accurate diagnosis of these precancerous and cancerous lesions. The present study aims at assessing the utility of cellular and nuclear morphometry in differentiating squamous cell abnormality from benign conditions and also differentiating the categories of squamous cell abnormalities. Forty-eight diagnosed cases of squamous epithelial cell abnormality, that is, 10 cases each of atypical squamous cell of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), high-grade SIL (HSIL), and squamous cell carcinoma (SCC) and eight cases of ASC-H (ASC cannot exclude HSIL), were made the sample population and compared with a control population of 10 cases of negative for intraepithelial lesion or malignancy (NILM). Parameters like nuclear area (NA), nuclear perimeter (NP), nuclear diameter (ND), nuclear compactness (NC), cellular area (CA), cellular diameter (CD), cellular perimeter (CP), and nucleocytoplasmic (N/C) ratio were used. There was a significant difference in the six groups of squamous cell abnormality based on NA, NP, ND, CA, CP, and CD (P < 0.05) using one-way analysis of variance. Nuclear morphometry parameters like NA, NP, and ND were found to be the maximum for HSIL, followed by LSIL, ASC-H, ASC-US, SCC, and NILM groups in decreasing order. The mean CA, CP, and CD were found to be the maximum for NILM, followed by LSIL, ASC-US, HSIL, ASC-H, and SCC in decreasing order. On post hoc analysis, the lesions can be divided into three groups: NILM/normal; ASC-US and LSIL; and ASC-H, HSIL, and SCC, based on N/C ratio. In cervical lesions, holistic parameter of cytonucleomorphometry should be taken rather than taking nuclear morphometry only. N/C ratio is a highly statistically significant parameter that can differentiate between low-grade lesions and high-grade lesions.

Verrucous Carcinoma of the Toenail: A Case Report and Review of Literature

Verrucous carcinoma (VC) is a rare, highly keratinized, well-differentiated, low-grade squamous cell carcinoma. A 58-year-old male presented with a 5-year history of a recurrent growing hyperkeratotic mass with intermittent bloody discharge, ulceration and dystrophic nail change on the right fifth toe. Since multiple dermatologic treatments were yielding no response, punch biopsy was performed for a more accurate diagnosis and the result was consistent with verruca vulgaris. As the lesion was responding poorly despite further dermatologic treatments for verruca vulgaris, radical surgical resection was performed. Microscopic examination of the excised lesion revealed epidermis with hyperkeratosis, hypergranulosis, papillomatosis, and reticular dermis invasion, consistent with VC. Since the diagnosis changed to VC, and the resection margin was involved by the carcinoma, the patient underwent an amputation procedure at the proximal phalangeal base. This case report highlights the importance of diagnosing VC. In cases of lesions such as verruca vulgaris or onychomycosis that are not responsive to general treatment, physicians should consider VC as a differential diagnosis, to prevent delaying a proper diagnosis and progression of disease.

Evaluation of Matrix Metalloproteinases 2 and 9 in Oral Squamous Cell Carcinoma and Verrucous Carcinoma

Background: Squamous cell carcinoma (SCC) is the most common malignancy of the oral cavity with a highly aggressive nature. Verrucous carcinoma (VC) is a low-grade SCC with mild clinical and pathological characteristics. Extracellular matrix degradation (ECM) by several proteolytic enzymes, especially matrix metalloproteinases (MMPs), is an important factor in tumor growth, invasion, and metastasis. Objectives: The aim of this study was to evaluate the expression level of immunohistochemistry of MMPs 2 and 9 in SCC and VC of oral cavity. Patients and Methods: The present study was conducted on the data of 20 SCC and 18 VC samples obtained from the pathology department archives. Microscopic examination was performed after immunohistochemical staining of the samples for MMP-2 and MMP-9. Data analysis was performed in SPSS 20 software. Kruskal-Wallis test was used to compare variables between groups. Results: All SCC and VC samples were positive for MMP-2 and MMP-9. The mean expression level of MMP-9 was 24.41 ± 20.68 in VC and 48.27 ± 12.11 in SCC. The mean expression level of MMP-9 in SCC was higher than VC. In addition, the expression level of MMP-9 varied in different histopathological grades of SCC. Matrix metalloproteinase expression levels were different in SCC grades and was especially higher in grade III. The mean expression level of MMP-2 in VC was 35.28 ± 30.63 and in SCC was 23.50 ± 12.68. The mean expression level of MMP-2 in VC was higher than SCC. Conclusions: Our findings showed that the expression levels of MMPs 2 and 9 in SCC and VC are higher than healthy tissue.

Postpneumonectomy Empyema Following SARS-CoV-2 Infection in a Patient with Metastatic Lung Cancer

Abstract We present a case of a male patient who underwent right-sided pneumonectomy due to central low-grade squamous cell carcinoma of the right lung, chemo-, radio-, and immunotherapy. However, the disease progressed. In addition the patient got SARSCoV-2 pneumonia in the left lung, followed by postpneumonectomy empyema. Right-sided uniportal video-assisted thoracoscopy, debridement, and definitive drainage of the pleural cavity were performed.

Gene expression profiling of HPV-associated cervical carcinogenesis in formalin-fixed paraffin-embedded (FFPE) tissues using the NanoString nCounterTM platform.

Infection by high-risk human papillomavirus (HPV) causes genetic alterations in host cervical cells with consequent changes in gene expression affecting downstream molecular pathways, leading to the development of cervical cancer. In this exploratory study, we aimed to identify the perturbed cellular pathways during the various stages of cervical carcinogenesis. Total RNA was extracted from three formalin-fixed paraffin-embedded (FFPE) samples each of normal cervix, HPV-infected low-grade squamous intraepithelial lesion (LSIL), high-grade SIL (HSIL) and squamous cell carcinoma (SCC). Gene expression profiling was performed using the 770-gene panel from NanoString nCounter® PanCancer Pathways Panel to identify differentially expressed genes (DEGs) and significantly associated pathways in each stage of cervical cancer development. We identified 121 DEGs involved in cervical carcinogenesis. In the transformation from normal cells to LSIL, the MAPK, transcriptional misregulation and JAK-STAT pathways are implicated, while IL1B may promote inflammation and indirectly activates MMP9, resulting in collagen breakdown and cell migration. The cell cycle - apoptosis pathway with upregulation of E2F1 and MCM2, and DNA repair genes BRCA2-BRIP1 and FANCA are crucial during the progression from LSIL to HSIL. In the final stage of progression to SCC, the cell cycle and signaling pathways, as well as upregulation of c-MYC appear essential. In conclusion, archived FFPE-derived tissue samples are a valuable resource for gene expression profiling. The postulated dysregulated pathways and genes provide a guide of the molecular mechanisms that may be involved in the development of HPV-associated cervical cancer, for further investigation and validation studies.

Omega-3 polyunsaturated fatty acids: a modified approach for chemo-prevention of bladder cancer in a rat model and molecular studies of antineoplastic mechanisms

To test the chemo-preventative effects of omega-3 against bladder cancer (BC) induction in a rat model and its potential antineoplastic mechanisms. Ninety male Fisher rats were divided into three groups during a 22-week protocol: group 1 (control), group 2 (Placebo + N-butyl-N-4- hydroxybutyl nitrosamine (BBN) for induction of BC and group 3 received omega-3 (1200mg/kg/day) + BBN. At the end, blood samples and bladder tissues were collected and checked for the presence of malignancy, markers of angiogenesis (VEGF relative gene expression), inflammation (IL-6), proliferation (KI-67 expressions), oxidative stress (serum MDA and serum SOD) and epigenetic control (miRNA-145 level). At the end of the study, 60% and 86.6% rats survived in group 2 and 3 with significant weight loss among rats in group 2 when compared with other groups. In group 2, all rats developed visible bladder lesions of which five and 13 developed squamous cell carcinoma (SCC) and transitional cell carcinoma (TCC). In omega3-treated group, only one developed low grade SCC and one developed high grade non- invasive TCC. Bladders from omega-3-treated rats showed lower expression ofKI-67 (p < 0.05), VEGF (p < 0.001) and IL-6 (p < 0.001) and significant higher expression of mi-RNA (p < 0.001). Also, omega-3-treated group showed statistically significant lower MDA level (p < 0.001). Omega-3 inhibits bladder tumor growth in the BBN-induced BC rat model, due to anti-inflammatory, antioxidant, anti-proliferative, and anti-angiogenic properties together with epigenetic control.

Clinical and histopathological spectrum of genital lichen sclerosus in 133 cases: Focus on the diagnosis of pre-sclerotic disease.

Background Early inflammatory lesions of lichen sclerosus are histopathologically difficult to diagnose until the hallmark of the disease i.e., papillary sclerosis becomes visible in histological sections. Pre-sclerotic and late or resolved phases of the disease have not been extensively studied. Methods We retrospectively reviewed all cases diagnosed as genital lichen sclerosus over a ten-year period from 2006 to 2016, correlating the clinical findings with the histological features. Results A total of 133 cases of genital lichen sclerosus (90 males and 43 females) were identified. Both genders demonstrated a similar histological spectrum. Fifty eight (44%) cases were identified as having pre-sclerotic lichen sclerosus, 64 (48%) as having progressive disease and 11 (8%) cases were classified as fully resolved with atrophy. Asymptomatic vitiligoid lesions were identified in 19 (14%) cases of which 12 were male. Low-grade squamous cell carcinoma was seen within the areas affected by long-standing lichen sclerosus, in four patients (3%, 2 male). Limitations We studied only haematoxylin and eosin stained sections. The presence of basement membrane thickening could have been better illustrated with the periodic acid-Schiff stain. Conclusion The pathogenesis of lichen sclerosus probably involves an immune reaction to the basement membrane at the epidermal interface and around the adnexa. The initial band of inflammation shifts gradually downwards from the epidermal interface into the dermis destroying the vascular channels and appendages, resulting in excessive deposition of altered extracellular matrix. Basilar infiltration of lymphocytes along with a grossly vacuolated or thickened basement membrane is proposed as the characteristic diagnostic feature of the pre-sclerotic stage. Greater awareness of the clinicopathological spectrum of lichen sclerosus should enable early diagnosis and treatment, thereby preventing structural damage and possible malignant transformation in chronic cases.

A Rare Case of Verrucous Carcinoma of Foot

Verrucous carcinoma is a rare, locally invasive, well-differentiated, and low-grade squamous cell carcinoma, with low metastatic potential. To our knowledge such cases reported are only finger counting numbers. In this case report, we present a rare case of a patient with an ulcerative lesion in the plantar foot that clinically and radiographically faced with a dilemma whether it was an osteomyelitis or deep mycosis or viral warts with secondary infection. The initial surgical approach consisted of wide excision of the malignant neoplasm including some normal tissue too. Definite diagnosis is by histopathology only.

Carcinoma Cuniculatum with Bone Invasion Mimicking a Viral Wart

Carcinoma cuniculatum is a rare variant of low-grade and well-differentiated squamous cell carcinoma. It is a locally invasive tumor, although it has low metastatic potential. It was originally described in the plantar region but may exceptionally appear in other locations. It predominates in middle-aged men and presents clinically as an exophytic, solitary, painful tumor, with insidious growth. Histologically, this tumor simulates a variety of benign dermatoses and may require several biopsies for the correct diagnosis. It is often misdiagnosed as a viral wart, due to the clinical similarity and the indolent course. The treatment of choice is surgical excision due to the high risk of recurrence and locally aggressive behavior. Amputation can be performed in cases of deep tissue invasion. We present a case of carcinoma cuniculatum in which the late diagnosis favored the invasion of the underlying bone, resulting in amputation of the affected finger.

Optimal treatment for penile verrucous carcinoma: a systematic literature review

BackgroundVerrucous carcinoma, a rare low-grade well-differentiated squamous cell carcinoma, is known for its favorable biological behavior and lack of metastatic potential. However, aggressive resection is problematic in terms of compromised function and aesthetics. Hence, more conservative treatments are needed. Methods: To identify the up-to-date general biological behavior, diagnosis, and treatment trends, we searched PubMed using the keyword “penile verrucous carcinoma” without restrictions on publication date. Results: Current treatments for penile verrucous carcinoma include wide surgical excision, seldom preventive lymphadenectomy, and conservative chemotherapy without surgery or local excision with safe margins. Despite the advent of partial penectomy to minimally impact function and aesthetics, affected patients experience psychosexual problems. Local excision can be used to save the penile shaft and glans penis without preventive lymphadenectomy or adjuvant therapy and can achieve good clinical prognosis with rare recurrence. Conclusions: To preserve the functional and cosmetic aspects, we recommend local excision, especially for tumors measuring < 3 cm and classified as stage T1 according to the 2016 tumor node metastasis clinical and pathological classification for penile cancer.

Mutations in p53 Gene Exons in a Sample from the South of Spain in Oral Cancer.

BackgroundCancer is a genetic disease caused by mutations in DNA and epigenetic alterations that control gene expression. The majority of epidermoid carcinomas develop within the fields of epithelial genetic alterations. The mechanisms underlying tumorigenesis of epidermoid carcinoma are as yet unknown; therefore, precise identification of the risk factors is needed. Aim: The main aim of this study is to analyse and identify the emergence of the mutations described in the literature of the p53 gene with regard to the emergence of cancer in a sample of dysplastic and cancerous lesions in oral cavity mucosa in the population of the south of Spain, in order to determine the presence of said mutations and the percentage of them in our population. Material and MethodsA cross-sectional study was carried out, with a sample size of 22 patients with potentially malignant oral lesions ancillary to biopsy. All were patients, of both sexes, over 18 years of age from the Virgen del Rocío University Hospital with potentially malignant lesions in oral mucosa ancillary to biopsy (leukoplakias, erythroplasias or leukoerythopkias). An anatomopathological study was performed on all the samples and the lesions were divided into three types: low-grade dysplasia, high-grade dysplasia and squamous cell carcinoma. In respect of the genome study process, a complete search or scan for mutations in exons 5, 6, 8 and 9 of the p 53 gene was carried out, given that in the IARC database we observed that the 5 and 6 as well as the 8 and 9 exon sizes can be scanned completely in this way, since they have amplificon sizes of 476 and 445 base pairs respectively. ResultsIn the scan for the complete exons 5, 6, 8 and 9 only a single result of interest was found to be described. In patient NBI 57 a change was observed in the TAT triplet by ATT of EXON 6, the change being of the T nucleotide by the A and in both directions both in Forward and Reverse. The exact location in the NCBI is GR Ch 37 p13 on chromosome 17, EXON 6 of the P53 gene and the change is in the C.613 T>A nucleotide; NM_000546. ConclusionsOn reviewing this genetic variant in different scientific databases, such as ENSEMBL among others, in at least 6 different biocomputing tools it is described as a pathogen, therefore we can conclude that it is a pathogenic mutation for this case in particular. The rest of the mutations described in the literature on exons 5, 6, 8 and 9 of the p53 gene have not been found in our sample. Key words:Oral cancer, p53, Mutations, Exon.

Comparative transcriptomic profiling in HPV-associated cervical carcinogenesis: Implication of MHC class II and immunoglobulin heavy chain genes

AimWe aimed to determine the biological processes and pathways involved in cervical carcinogenesis associated with high-risk human papillomavirus (HPV) infection. Materials and methodsTotal RNA was extracted from three formalin-fixed paraffin-embedded (FFPE) samples each of normal cervix, HPV-infected low-grade squamous intraepithelial lesion (LSIL), high-grade SIL (HSIL) and squamous cell carcinoma (SCC). Transcriptomic profiling by microarrays was conducted followed by downstream Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. ResultsWe examined the difference in GOs enriched for each transition stage from normal cervix to LSIL, HSIL, and SCC, and found 307 genes to be differentially expressed. In the transition from normal cervix to LSIL, the extracellular matrix (ECM) genes were significantly downregulated. The MHC class II genes were significantly upregulated in the LSIL to HSIL transition. In the final transition from HSIL to SCC, the immunoglobulin heavy locus genes were significantly upregulated and the ECM pathway was implicated. ConclusionDeregulation of the immune-related genes including MHC II and immunoglobulin heavy chain genes were involved in the transitions from LSIL to HSIL and SCC, suggesting immune escape from host anti-tumour response. The extracellular matrix plays an important role during the early and late stages of cervical carcinogenesis.

Interdyscyplinary management of verrucous carcinoma in renal transplant recipient on long term immunosuppression. Clinical report.

BackgroundThe high risk of human papillomavirus (HPV) related anogenital lesions that lead to cancer in immunosuppressed renal transplant recipients (RTRs) has been previously reported [1,2]. One of them, Verrucous carcinoma, is un uncommon low–grade squamous cell carcinoma (SCC) affecting skin and mucosa, often associated with chronic immunosuppression in patients after organ transplantation. RTRs are at overall increased risk of developing skin cancers, predominantly the non-melanoma subtypes, including malignances observed in recipients after preempive kidney transplantation (PKT) [3,4,5]. The introduction of primary prevention, continuous monitoring in patients with known high-risk HPV, necessity of early diagnosis and treatment, prevention of malignancies in transplant recipients and long-term managing maintaining adequate immunosuppressive therapy, are necessary [6,7].

Indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase expression in HPV infection, SILs, and cervical cancer.

Human papillomavirus (HPV) infection is the central factor for cervical cancer, whereas epithelial immune mechanisms contribute to the progression of HPV infection and its associated lesions. The authors evaluated the expression of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) in cervicovaginal samples from women with normal cervical epithelium or with different degrees of squamous intraepithelial lesions (SILs) and cervical cancer. IDO expression was analyzed by immunocytochemistry in liquid-based cytology samples from 165 women, of whom 42 had cervical changes subclassified as low-grade SIL (n=6), high-grade SIL (n=30), or squamous cell carcinoma (SCC) (n=6), and 123 had negative Papanicolaou smears. IDO and TDO expression also were analyzed by immunohistochemistry, and HPV and other genital pathogens were evaluated by polymerase chain reaction analysis. Low IDO expression was observed in normal cervical epithelium irrespective of HPV status. Increased numbers of IDO-positive squamous cells and IDO-positive leukocytes were observed in women with SIL or SCC. TDO expression was detected in leukocytes infiltrating the stroma around intraepithelial or invasive cervical lesions. Higher IDO levels were detected in organotypic epithelial cultures established from keratinocytes transduced with the HPV16 E6/E7 oncoproteins. The upregulation of IDO expression in leukocytes and squamous cells in HPV-associated SIL and SCC suggests that immunosuppressive mechanisms involving tryptophan metabolism may have a role in cervical carcinogenesis. Although previous studies have suggested the role of IDO in HPV pathogenesis, this is the first evidence of TDO involvement in the process. Furthermore, the current data emphasize the role of leukocytes, especially neutrophil-like cells, as an IDO source.

Expressions of Immune Negative Regulator FoxP3+Treg and PD-L1 Protein in the Immune Microenvironment of Cervical Lesion.

Objective To explore the expression patterns of immune negative regulator FoxP3+Treg and PD-L1 protein in cervical carcinoma and its precancerous lesions. Methods The expression patterns of FoxP3+Treg and PD-L1 protein in 45 cases of cervical lesions tissues of the cervix and 20 cases of normal cervix tissues by using immunohistochemistry (IHC). Results Compared with the normal cervix,the expressions of FoxP3+Treg (H=43.211,P=0.000) and PD-L1 protein (t=213.00,P=0.001) were significantly increased in cervical lesions. Compared with the low-grade squamous cell carcinoma,the invasiveness of FoxP3+Treg was increased in high-grade squamous cell carcinoma (H=28.307,P=0.000),along with increased expression of PD-L1 protein (t=239.000,P=0.028). The FoxP3+Treg expression was positively correlated with PD-L1 protein expression in abnormally differentiated cells (rs=0.364,P=0.003). Conclusion Along with the progression of cervical cancer,the FoxP3+Treg amount increases in the local microenvironment,along with enhanced PD-L1 protein expression in abnormally differentiated cells.