RESUMEN

OBJECTIVES: The aim of our study was to assess the proportion of high-grade histological lesions, according to HPV type, in patients referred for colposcopy involving a positive HPV-HR test and ASC-US cytology. METHODS: This is a retrospective descriptive study of asymptomatic patients aged 25 to 65 with a positive HPV-HR test and ASC-US cytology. Data were collected at the Nord-Franche-Comté Hospital from September 2019 to February 2022. The primary outcome was the proportion of high-grade histological lesions in patients with ASC-US cytology combined to HPV 16 or 18 (associated or not with other HPV type), compared with HPV no 16 no 18. RESULTS: Among the 298 patients included, 67% were HPV no 16 no 18, 22% HPV 16 associated or not with others and 11% HPV 18 associated or not with others. We found significantly fewer high-grade lesions in patients with ASC-US cytology and HPV no 16 no 18 than in patients with HPV 16 or 18 (8.5% versus 22.7%, p<0.01). In patients presenting an ASC-US cytology with HPV no 16, no 18: 53% of the biopsies found no histological lesion compared with 30% for the other HPVs (p<0.01). CONCLUSIONS: We've highlighted the reality of colposcopists: a high ratio of normal coloscopy associated with normal or low-grade biopsies, in patients with a positive HPV-HR test no 16, no 18 and ASC-US cytology.

RESUMEN

According to the "cancer stem cell" (CSCs) theory, tumors are a diverse and expanding group of malignant cells that originate from a small number of CSCs. Despite treatment, these cells can still become active and proliferate, which can result in distant metastasis and local recurrences. A new paradigm in cancer treatment involves targeting both CSCs and the cancer cells in a tumor. This review aims to examine the literature on methods published to overcome chemoresistance due to the presence of CSCs in head and neck cancers. The review was registered with PROSPERO (ID# CRD42024512809). After Pub Med, Scopus, and WoS database searches, 31 relevant articles on oral squamous cell carcinoma (OSCC) were selected. Compounds that increased chemosensitivity by targeting CSCs in head and neck squamous cell carcinoma (HNSCC) were divided into (1) natural products, (2) adjuvant molecules to traditional chemotherapy, and (3) CSCs targeting patient-specific fresh biopsies for functional precision medicine.

RESUMEN

Squamous cell carcinomas (SCCs) are the most prevalent malignant tumors affecting the cervix. The superficial spread of SCC along the inner surface of the uterus, replacing the endometrium with malignant cells, is a rare subtype of cervical cancer. We present the case of a 55-year-old woman who complained of per-vaginal white discharge and generalized weakness for one month. Clinical examination revealed a bulky and fibrosed cervical os. A cervical biopsy confirmed the diagnosis of poorly differentiated nonkeratinizing SCC. MRI showed an endocervical infiltrative, heterogeneously enhancing mass lesion involving the cervix, along with cervical stenosis and hydrometra. Irregular thickening with nodular enhancing deposits showing morphology similar to the cervical lesion and restricted diffusion were noted along the endometrial lining contiguous with the cervical lesion. The patient underwent a radical hysterectomy, and histopathological examination revealed poorly differentiated nonkeratinizing squamous cell cervical carcinoma with contiguous squamous cell extension into the uterine endometrium, confirming the diagnosis of superficially spreading cervical SCC. Establishing the continuity of the lesion on imaging and histopathological testing is critical to confirm the presence of a superficial spread of cervical cancer and rule out contemporaneous endometrial cancer.

RESUMEN

Background and Objectives: Although several studies have been achieved on the frequency of the HPV types among women with cervical cancer in Iran, HPV-positive samples were in some cases directed to specific-primer genotyping of HPV 16 and 18. Therefore, the other HPV types are underestimated. Several studies have also reported a greater prevalence of HPV 16 in cervical cancer in Iran than in the world. To clarify these subjects, the distribution of HPV types in women referred for colposcopy in Tehran was investigated. Materials and Methods: In this cross-sectional study, a total of 148 cervical samples from women with normal, atypical squamous cells of undetermined significance, cervical intraepithelial neoplasia I-III, and invasive cervical cancer histopathology were included. HPV was detected by PCR assay and all HPV-positive specimens were subjected to direct nucleotide sequencing. Results: Our results demonstrated that the total prevalence of HPV was 92.5%. The five most common HPV types were HPV 16 (49.3%), 18 (14.8%), 6 (7.4%), 31 (4.1%), and 11 (2.7%). About the histopathological stage, HPV 16 and 18 were dominant in all studied groups. In cervical cancer, HPV 16 and 18 were detected in 60% and 20% of cases, respectively. Conclusion: HPV 16 and 18 were the most common in cervical cancer in Iran.

RESUMEN

BACKGROUND: A cytologic diagnosis of atypical squamous cells, cannot exclude high-grade squamous lesion (ASC-H) poses a disproportionately high risk of cervical cancer development. The objective of this study was to analyze type-specific risks by mapping human papillomavirus (HPV) genotypes in ASC-H cytology. METHODS: In total, 1,048,581 Papanicolaou tests that had ASC-H cytology were retrieved. Concurrent HPV genotyping using proprietary multiplex real-time (MRT) and polymerase chain reaction (PCR) HPV tests and histologic follow-up findings were analyzed. RESULTS: Among 1678 patients who had ASC-H findings (0.16%), 1414 (84.3%) underwent concurrent HPV genotyping (MRT, 857; HPV PCR test, 557). The overall high-risk HPV (hrHPV)-positive rate was 84.4%. Of the 857 MRT cases, 63.9% were infected with a single hrHPV, and 24.4% had multiple genotypes. The most prevalent HPV types were HPV16/52/58/33/31. Lesions that were identified as cervical intraepithelial neoplasia 2 or worse (CIN2+) were detected in 498 of 906 cases (55.0%), including 81 cervical carcinomas (8.9%). The risk of CIN2+ for the composite group of HPV16/52/58/33/31-positive cases was 62.7%, representing 90.7% (264 of 291) of total CIN2+ lesions in ASC-H/hrHPV-positive cases by MRT. CIN2+ lesions were detected in 108 of 142 (76.1%) HPV16-positive and/or HPV18-positive women by the PCR the HPV test. Among 128 hrHPV-negative ASC-H cases by both methods, CIN2+ lesions were identified in 21 of 128 (16.4%), including five cervical carcinomas (3.9%). The sensitivity, specificity, positive predictive value, and negative predictive value for patients in the composite group with HPV16/52/58/33/31 were 88.0%, 40.8%, 62.7%, and 75.0%, respectively. CONCLUSIONS: Papanicolaou tests classified as ASC-H are associated with a high CIN2+ rate and warrant colposcopy, regardless of HPV status. The extent to which the risk-stratification provided by comprehensive HPV genotyping can inform the management of ASC-H cytology remains to be explored.

RESUMEN

Atypical fibroxanthoma (AFX) is a rare spindle cell proliferation arising from significant sun exposure. AFX often appears as a red papule, typically found in the head and neck region of elderly patients. Since there is no specificity in immunohistology, various stains differentiate AFX from other skin cancers. The stains include cluster of differentiation 68 (CD68), cluster of differentiation 163 (CD163), vimentin, cytokeratin epithelial (CKAE), and melanin. While local recurrence is common, AFX rarely metastasizes. Thus, the treatment options are complete surgical excision or micrographically oriented histographic surgery.

RESUMEN

Nasal mucosa tumors are an uncommon process and very dificult to work on with surgery. Radiotherapy associated or not with chemotherapy is the standard method to treat the disease. However, its access it is in the majority of the case not possible, making the surgery the best choice to try to achieve the patient's control. The anatomy of the region makes the complete surgical resection very difficult to achieve using the common and conventional blade scalpel surgery. The study features the advantages of using a CO2 laser to perform nasal mucosa carcinoma surgery in 6 dogs (N = 6). For the work we used an Aesculigth CO2 surgical laser model -Vetscalpel®, with the settings of 12Watts in a Superpulse mode, and a 0.25-0.4 mm focus to dissect the nasal mucosa, and a 1.5 mm focus for vaporization of the area. All the masses were histopathologically characterized as squamous cells carcinoma. The CO2 surgical laser allow us to work in a bloodless region promoting a more accurate dissection of the nasal mucosa sparing therefore the underlying and adjacent tissues and being less invasive. Also, it was possible to do the vaporization of the entire surgical area interviened. None of the patients presented relapse of clinical signs. Only 2 individuals were alive at the end of the study, presenting a survival rate of 420 and 514 days, which is in the same line of literature results of the treatment with radiotherapy combined with chemotherapy wich shows a median of 474-580 days. The study demonstrates successful outcomes with CO2 laser surgery in treating nasal mucosa SCC in dogs, with patients experiencing improved survival rates compared to traditional treatment methods. This highlights the efficacy and potential of CO2 laser surgery as a valuable tool in managing aggressive nasal tumors in veterinary oncology.

Asunto(s)

RESUMEN

Objective: Atypical squamous cells of undetermined significance cytology (ASC-US) is a challenging and equivocal diagnosis for pathologists in cervical Pap smears. The data on ASC-US cervical cytology in Bahrain are deficient. This study reviewed and identified the reporting rates, high-risk human papillomavirus (HPV) testing results, histopathologic follow-up findings, and the cytologic progression of patients diagnosed with ASC-US in Bahrain. Material and Methods: A retrospective chart review was conducted on the medical records of 23,888 women who had Pap smear test results between January 2019 and March 2022 at the main referral tertiary hospital in Bahrain to identify the ASC-US cases. High-risk HPV (hrHPV) genotype was identified, and the histopathological results of the cervical biopsy was recorded. In addition, cytologic follow-up Pap smear tests conducted within 1 year of ASC-US diagnosis were tracked to monitor the progression or regression of ASC-US. Results: In this study, 259 out of 23,888 women reported to have ASC-UC cytology results with a reporting rate of 1.1%. The mean age of the ASC-US cases was 43 ± 11.6. Thirty percent of the ASC-US cases tested positive for hrHPV, and they were predominantly infected with the other hrHPV genotype (75%). When the histopathological changes of the cervix were analyzed, 82.1% had normal histopathologic findings. However, low-grade cervical intraepithelial neoplasia-1 was reported in 2 cases (7.1%), and high-grade cervical lesions (cervical intraepithelial neoplasia-2 and higher) were reported in 3 cases (10.7%). Regarding the cytologic follow-up, most of the ASC-US cases were negative for intraepithelial lesion or malignancy (NILM) (73.8%) or had persistent ASC-US (17.9%). The remaining minority of cases progressed into either low-grade squamous intraepithelial lesions (6%) or high-grade squamous intraepithelial lesions (2.4%). There was a statistically significant and relatively strong association between the cytology follow-up findings and the hrHPV test results (χ2 [2] = 8.869, P < 0.012, Cramer's V = 0.417). Conclusion: This is the first and largest study to characterize the ASC-US cytology cases in Bahrain. The reporting rates of ASC-US fell within the worldwide reported range. Although most of the ASC-US cases regressed into NILM, ASC-US showed progression into more advanced cervical cytologic diagnoses or contributed to the malignant transformation of cervical tissue, especially in the presence of hrHPV infection which was positive in 30% of the ASC-US cases. This emphasizes the role of cotesting (combination of hrHPV genotyping and Pap smear test) and the importance of colposcopic evaluation of those women with cytologic follow-up tests at 1 year of diagnosis. Implementing these recommendations in the cervical cancer screening practice in Bahrain will help in having a better management plan for women diagnosed with ASC-US cervical cytology.

RESUMEN

Head and neck lesions often undergo fine-needle aspiration to determine the appropriate management and therapeutic decisions. However, there are numerous diagnostic challenges encountered with these specimens, particularly, if atypical squamous cells are identified. Here, we present a case of an enlarging right neck mass in a 38-year-old female and discuss the diagnostic difficulties and potential pitfalls. Additionally, we review the approach to diagnosis, including differential diagnostic considerations as well as available ancillary testing.

Asunto(s)

RESUMEN

BACKGROUND: Atypical squamous cells (ASC) in urine cytology are rarely found, and their clinical significance is not well studied. Previous studies were limited by a small number of cases and a lack of objective grading of ASC and/or their correlation with accompanying urothelial cell abnormality (UCA). METHODS: The institutional database was searched over 10 years for urine cytology reports containing ASC or from patients who had a concurrent diagnoses of high-grade (HG) urothelial carcinoma with squamous differentiation or squamous carcinoma. ASC were defined as keratinized squamous cells and were subcategorized as reactive, koilocytosis, low-grade (LG) atypia, and HG atypia. Correlations with age, sex, specimen type, accompanying UCA, number of ASC, and the risk of HG malignancy (ROHM) were assessed. RESULTS: ASC were present in 0.15% of all urine specimens (123 of 81,018). Slides and clinical follow-up were available on 91 patients (median age, 71 years). LG and HG squamous atypia had ROHMs of 70% and 92%, respectively. ASC not accompanied and accompanied by UCA had ROHMs of 37% and 94%, respectively. Most malignancies (34 of 67; 51%) showed rare ASC in urine. Reactive changes and koilocytosis had 0% ROHM. CONCLUSIONS: ASC in urine cytology is a significant finding and is associated with a high ROHM. In the absence of accompanying UCA, LG squamous atypia had a lower ROHM than HG atypia. In the presence of UCA, LG and HG squamous atypia had ROHMs of over 90%. These findings suggest that ASC and their grade of atypia should be noted in the cytology report, and clinicians should be made aware of their clinical significance.

Asunto(s)

RESUMEN

Fine-needle aspiration (FNA) is a commonly employed method for initial diagnosis and work-up of pulmonary nodules. Utilization of rapid on-site evaluation (ROSE) has the added benefit of allowing for triaging of material as appropriate for ancillary studies including microbiology testing. While many pulmonary lesions are easily categorized by cytologic evaluation, more difficult cases exist. In particular, pulmonary lesions demonstrating atypical squamoid cells can cause diagnostic challenge given the morphologic overlap between benign and malignant pulmonary lesions showing atypical squamoid cells. We herein review these common and uncommon squamoid lesions, which may enter within the differential when encountering atypical squamoid cells in pulmonary FNA specimens with emphasis on morphologic pitfalls and approaches to appropriate categorization.

Asunto(s)

RESUMEN

Immune checkpoint blockers (ICBs) targeting programmed cell death protein 1 (PD-1) have been proven to be an effective first-line therapy against programmed cell death 1 ligand 1 (PD-L1; also known as CD274 molecule)-expressing head and neck squamous cell carcinoma (HNSCC) in recent KEYNOTE-048 trial. However, associated changes in the tumor microenvironment (TME) and underlying mechanisms remain elusive. Oral tumors in C57/BL6 mice were induced by administering 7,12-dimethylbenzanthracene into the buccal mucosa. Single-cell suspension was isolated from tumor tissue; proliferating cells were injected subcutaneously into the left flank of mice to establish Ajou oral cancer (AOC) cell lines. Subsequently, a syngeneic PD-L1-expressing HNSCC model was developed by injecting AOC cells into the buccal or tongue area. The model recapitulated human HNSCC molecular features and showed reliable in vivo tumorigenicity with significant PD-L1 expression. ICB monotherapy induced global changes in the TME, including vascular normalization. Furthermore, the antitumor effect of ICB monotherapy was superior to those of other therapeutic agents, including cisplatin and inhibitors of vascular endothelial growth factor receptor 2 (VEGFR2). The ICB-induced antitumorigenicity and TME normalization were alleviated by blocking the type I interferon pathway. In summary, ICB monotherapy is sufficient to induce TME normalization in the syngeneic model; the type I interferon pathway is indispensable in realizing the effects of ICBs. Furthermore, these results explain the underlying mechanism of the efficacy of ICB monotherapy against PD-L1-expressing HNSCC in the KEYNOTE-048 trial.

Asunto(s)

RESUMEN

Background: Mounting evidence has linked cancer metabolic reprogramming with altered redox homeostasis. The pentose phosphate pathway (PPP) is one of the key metabolism-related pathways that has been enhanced to promote cancer growth. The glucose 6-phosphate dehydrogenase (G6PD) of this pathway generates reduced nicotinamide adenine dinucleotide phosphate (NADPH), which is essential for controlling cellular redox homeostasis. Objective: This research aimed to investigate the growth-promoting effects of G6PD in non-small cell lung cancer (NSCLC). Methods: Clinical characteristics and G6PD expression levels in lung tissues of 64 patients diagnosed with lung cancer at the King Chulalongkorn Memorial Hospital (Bangkok, Thailand) during 2009-2014 were analyzed. G6PD activity in NSCLC cell lines, including NCI-H1975 and NCI-H292, was experimentally inhibited using DHEA and siG6PD to study cancer cell proliferation and migration. Results: The positive expression of G6PD in NSCLC tissues was detected by immunohistochemical staining and was found to be associated with squamous cells. G6PD expression levels and activity also coincided with the proliferation rate of NSCLC cell lines. Suppression of G6PD-induced apoptosis in NSCLC cell lines by increasing Bax/Bcl-2 ratio expression. The addition of D-(-)-ribose, which is an end-product of the PPP, increased the survival of G6PD-deficient NSCLC cell lines. Conclusion: Collectively, these findings demonstrated that G6PD might play an important role in the carcinogenesis of NSCLC. Inhibition of G6PD might provide a therapeutic strategy for the treatment of NSCLC.

Asunto(s)

RESUMEN

BACKGROUND: Head and neck squamous cell carcinoma (HNSC) is the seventh most common cancer worldwide. Although there are several options for the treatment of HNSC, there is still a lack of better biomarkers to accurately predict the response to treatment and thus be more able to correctly treat the therapeutic modality. METHODS: First, we typed cases from the TCGA-HNSC cohort into subtypes by a Bayesian non-negative matrix factorization (BayesNMF)-based consensus clustering approach. Subsequently, genomic and proteomic data from HNSC cell lines were integrated to identify biomarkers of response to targeted therapies and immunotherapies. Finally, associations between HNSC subtypes and CD8 T-cell-associated effector molecules, common immune checkpoint genes, were compared to assess the potential of HNSC subtypes as clinically predictive immune checkpoint blockade therapy. RESULTS: The 500 HNSC cases from TCGA were put through a consensus clustering approach to identify six HNSC expression subtypes. In addition, subtypes with unique proteomics and dependency profiles were defined based on HNSC cell line histology and proteomics data. Subtype 4 (S4) exhibits hyperproliferative and hyperimmune properties, and S4-associated cell lines show specific vulnerability to ADAT2, EIF5AL1, and PAK2. PD-L1 and CASP1 inhibitors have therapeutic potential in S4, and we have also demonstrated that S4 is more responsive to immune checkpoint blockade therapy. CONCLUSION: Overall, our HNSC typing approach identified robust tumor-expressing subtypes, and data from multiple screens also revealed subtype-specific biology and vulnerabilities. These HNSC expression subtypes and their biomarkers will help develop more effective therapeutic strategies.

RESUMEN

Background Correctly identifying cutaneous squamous cell carcinoma (cSCC) mimickers can be both clinically and histopathologically challenging. We present a series of patients with biopsy-proven cSCCs for whom multiple surgeries were avoided by assessing the clinical situation, recognizing an alternative diagnosis that pathologically mimics cSCC, and prescribing appropriate therapy for the underlying condition. Methodology Seven female patients presented for treatment of biopsy-proven cSCC affecting the lower leg. After further investigation, we observed that these women shared similar characteristics, including age ranging from the 5th to the 9th decade, often experiencing stress, exhibiting associated pruritus with diverse causes, having few or no previous skin cancers, and generally showing minimal photodamage. Results In all cases, surgery was deferred and patients demonstrated complete clinical response to therapies directed toward an alternative diagnosis. Repeat biopsies of treated lesions revealed no evidence of cSCC. Conclusions Not all histologically diagnosed cases of cSCC should be treated with surgery, and each patient should be worked up thoroughly to evaluate for an alternative diagnosis. Possible clinical and histologic cSCC mimickers include allergic contact dermatitis (ACD), stasis dermatitis, hypertrophic lichen planus (LP), and drug eruption, among others. In the described population, pruritic papules on the lower leg should prompt further investigation to prevent the morbidity associated with unnecessary surgery.

RESUMEN

Inguinal hernias are the most common type of hernias, and most are repaired surgically with mesh placement to prevent future reoccurrence. Mesh infection and hernia recurrence are some of the rare complications of mesh placement, and chronic mesh infections increase the risk of squamous cell carcinoma at the site. Squamous cell carcinoma (SCC) in the setting of a mesh infection presents in a similar manner to a Marjolin ulcer and is treated with the removal of the tumor and degraded infected mesh. However, in this case, the patient presented atypically with an absence of mesh involvement. This report aims to explore the etiology of SCC due to mesh infections as well as describe the perplexing case of inguinal SCC in the absence of mesh involvement.

RESUMEN

OBJECTIVE: This study aimed to investigate the preventive effect of a vaginal gel on p16/Ki-67-positive abnormal cytological cervical findings (ASC-US, LSIL) and hr-HPV in women. METHODS: The study included 134 women with p16/Ki-67-positive ASC-US or LSIL. Participants were selected from a randomized controlled trial that focused on women with histological diagnoses of p16-positive CIN1 lesions or CIN2. In the treatment group (TG), 57 patients applied the vaginal gel daily for three months, while 77 patients in the "watchful wait" control group (CG) received no treatment. The study's endpoints were cytological development, p16/Ki-67 and hr-HPV clearances. RESULTS: At three months, cytopathological results improved in 74% (42/57) of patients in the TG, compared with 18% (14/77) in the CG. Progression occurred in 7% (4/57) of TG patients compared with 18% (14/77) of CG patients. The p16/Ki-67 status changed statistically significantly in favor of the TG (p < 0.001), with 83% (47/57) becoming negative, compared with 18% (14/77) in the CG. The prevalence of hr-HPV decreased significantly in the TG by 51%, and by 9% in the CG (p < 0.001). CONCLUSIONS: Topical application of the gel resulted in statistically significant clearance of hr-HPV and p16/Ki-67 concomitant with amelioration of cytological findings, thus providing effective prevention and protection against oncogenic development. TRIAL REGISTRATION: ISRCTN11009040, on 10 December 2019.

RESUMEN

Introduction: Atrophy of the reproductive tract mucosa caused by the decrease of estrogen may increase the detection rate of ASC-US in cervical cytology of post-menopausal women. In addition, other pathogenic infections and inflammation can change the cellular morphology and increase the detection rate of ASC-US. However, further studies are needed to elucidate whether the high detection rate of ASC-US in post-menopausal women leads to the high referral rate of colposcopy. Methods: This retrospective study was conducted to document ASC-US in cervical cytology reports at the Department of Cytology at Gynecology and Obstetrics, Tianjin Medical University General Hospital between January 2006 and February 2021. We then analyzed 2,462 reports of women with ASC-US at the Cervical Lesions Department. A total of 499 patients with ASC-US and 151 cytology with NILM participants underwent vaginal microecology tests. Results: The average reporting rate of ASC-US in cytology was 5.7%. The detection rate of ASC-US in women aged > 50 years (7.0%) was significantly higher than that in women aged ≤50 years (5.0%) (P<0.05). The CIN2+ detection rate was significantly lower in the post- (12.6%) than in pre-menopausal (20.5%) patients with ASC-US (P <0.05). The prevalence of abnormal reporting rate of vaginal microecology was significantly lower in the pre-menopausal group (56.2%) than that in the post-menopausal group (82.9%) (P<0.05). The prevalence of bacterial vaginosis (BV) (19.60%) was relatively high in the pre-menopausal group, but the abundance of bacteria-inhibiting flora (40.79%) was mainly an abnormality in the post-menopausal group. The vaginal microecological abnormality rate of the women with HR-HPV (-) of ASC-US was 66.22%, which was significantly higher than that of the HR-HPV (-) and the NILM group (52.32%; P<0.05). Discussion: The detection rate of ASC-US in women aged > 50 years was higher than that ≤50 years, but the detection rate of CIN2+ was lower in the post-menopausal women with ASC-US. However, vaginal microecological abnormalities may increase the false-positive diagnosis rate of ASC-US. The vaginal microecological abnormalities of the menopausal women with ASC-US are mainly attributed to infectious diseases such as BV, and it mainly occurs in the post-menopausal women was bacteria-inhibiting flora. Therefore, to avoid the high referral rate for colposcopy, more attention should be paid to the detection of vaginal microecology.

Asunto(s)

RESUMEN

Cutaneous metastasis of primary visceral neoplasm is an unusual phenomenon. However, cutaneous metastasis as an initial presentation of clinically silent visceral neoplasm is exceedingly rare. We are reporting a unique case of an elderly male patient who presented with a solitary scalp metastasis as an initial manifestation of underlying lung cancer. Further diagnostic evaluation revealed neoplastic primary lung disease. This case report emphasizes the importance of physicians being aware of these unusual clinical presentations of visceral malignancies. It is also critical to order appropriate diagnostic tests promptly to establish an accurate diagnosis and begin the proper treatment for a better prognosis. Skin lesions can be a diagnostic manifestation of lung cancer and predict a poor prognosis. We conclude that in patients with a history of smoking or lung cancer who present with cutaneous lesions, the possibility of skin metastasis of primary lung cancer should always be considered in the differential diagnosis.

RESUMEN

OBJECTIVES: CD103+CD8+T cells is a subtype of T cells with excellent tumor killing ability and it could response to immune checkpoint blockade therapy in several types of cancer, but the phenotype, role and molecular mechanism CD103+CD8+T cells in the OSCC still unclear. MATERIALS AND METHODS: The distribution and phenotype of CD103+CD8+T cells were investigated by performing multiplexed immunohistochemistry on human OSCC tissue microarray and flow cytometric analysis of fresh OSCC tumor-infiltrating lymphocytes (TILs). By in vivo use of anti-CD103 monoclonal antibody (mAb) in the 4MOSC1 tumor-bearing mouse model, CD103+CD8+T cell infiltration and cytotoxicity was clarified. RESULTS: The majority of CD8+T cells in both human and animal OSCC intra-tumoral region were CD103+CD8+T cells with high expression levels of cytotoxic molecules, which can be impaired by CD103 blockade. In addition, combined use of anti-CD103 mAb with anti-CTLA-4 mAb displayed impaired immune checkpoint blockade therapy efficiency. CONCLUSION: CD103+CD8+T cells are the major intra-tumoral subset of CD8+T cells in both animal and human OSCC, and that CD103+CD8+T cells demonstrate remarkable tumor-infiltrating and tumor-killing properties, thereby CD103+CD8+T cells may critical for anti-CTLA-4 immunotherapy in OSCC.

Asunto(s)