Invasive Squamous Cell Research Articles

Invasive Orbital Squamous Cell Carcinoma in a Patient with Multiple Myeloma

Background Orbital squamous cell carcinoma (SCC) is a rare entity. It is often a result of local invasion of SCC originating from the skin, nasopharynx, nasal cavity, paranasal sinuses, conjunctiva, lacrimal glands, or sac or less commonly occurs through hematogenous metastasis. Herein, we report a patient with orbital SCC with a history of multiple myeloma (MM). Case presentation. A 45-year-old woman with a history of MM in the past two years presented to our clinic complaining of gradual right eye proptosis for six months. The relative afferent pupillary defect was detected in the right eye on her examination. Ocular movements of the right eye were limited in all directions. Orbital magnetic resonance imaging demonstrated an infiltrative mass in the right orbit extended from the anterior to the orbital apex and the optic canal. The patient underwent debulking, and a histopathology examination revealed SCC results. No other secondary site was found to be the origin of the tumor. Result The patient underwent chemotherapy and subsequent radiotherapy. To our knowledge, this is the first report of concomitant MM and primary orbital SCC.

Gluteal Fold V-Y Advancement Flap for Genital Reconstruction following Radical Vulvectomy with Bilateral Inguinofemoral Lymphadenectomy in Vulvar Cancer: A Case Report

Background: Vulvar cancer is a rare malignancy representing about 4% of all genital cancers in women. Historically, the gold standard for treatment of squamous cell carcinoma of the vulva was en bloc radical vulvectomy with bilateral inguinofemoral lymphadenectomy. For the reconstruction the options are primary closure, skin grafts, or local and distant flaps. In this case we used the gluteal fold fasciocutaneous V-Y advancement flap that is sensate and thin with a reliable blood supply, can be advanced easily, and can be performed in a single-stage procedure. Care Report: We present a clinical case of an 82- year old female patient who had an exophytic vulvar lesion, which grew progressively with the histopathologic diagnosis of invasive vulvar squamous cell carcinoma. It was decided to perform radical vulvectomy with right unilateral lymphadenectomy and reconstruction with Gluteal Fold V-Y Advancement Flap. During the post-surgical period it recurred with wound dehiscence and finally skin necrosis developed in the area of the left thigh. Surgical debridement, escharectomy, harvesting and application of skin graft, and closure of the femoral hernia with omentum patch were performed with no associated complications. Follow-up was carried out during the next 3 months after surgery. She presented adequate evolution of the flap and left thigh area. Conclusions: The Gluteal Fold V-Y Advancement Flap is an excellent option for the reconstruction of the vulvovaginoperineal area after a radical vulvectomy. It provides us with a good prognosis and quality of life for the patient. Article Details Issue

VEGF-D Serum Level as a Potential Predictor of Lymph Node Metastasis and Prognosis in Vulvar Squamous Cell Carcinoma Patients.

BackgroundRadical surgical resection of the primary tumor with mono/bilateral inguinofemoral lymph node dissection is the standard treatment for invasive vulvar squamous cell carcinoma (VSCC) and is frequently related to severe morbidity. Tailoring surgical treatment is of paramount importance, and a comprehensive preoperative evaluation is mandatory. Vascular endothelial growth factor D (VEGF-D) is considered a regulator of lymphangiogenesis involved in tumor spread via lymphatic vessels. The aim of this study was to evaluate the potential of VEGF-D in the prediction of inguinofemoral lymph node metastasis.MethodsWe analyzed the preoperative levels of serum VEGF-D (sVEGF-D) from two independent cohorts of patients with VSCC by enzyme-linked immunosorbent assay and its protein expression on tumor tissue by immunohistochemistry. Logistic regression was performed to identify the independent risk factors for lymph node metastasis, and Cox proportional hazard model was used for survival analysis.ResultsHigh levels of sVEGF-D, but not tissue VEGF-D, significantly correlated with positive groin nodes and a more advanced International Federation of Gynecologists and Obstetricians (FIGO) stage. In multivariable analysis, a high sVEGF-D level was an independent predictor of lymph node metastasis and worse prognosis. A prediction model based on sVEGF-D, tumor grade assessed on biopsy, tumor diameter, and lymph node clinical evaluation was able to predict lymph node metastasis, reaching C-index values of 0.79 and 0.73 in the training and validation cohorts, respectively.ConclusionsThe preoperative sVEGF-D level might be a reliable biomarker for the prediction of lymph node metastasis and prognosis in patients with VSCC, supporting better clinical/surgical decision. Multicenter prospective studies are required to confirm our findings.

Digital Image Analysis-Based Evaluation of Claudin-1 and Claudin-7 Delocalization in Cutaneous Squamous Cell Carcinoma and in Its Precancerous State.

Accumulating evidence has revealed that delocalization of the transmembrane proteins, Claudin-1 and Claudin-7, to the cytoplasm and/or nucleus occurs in various tumors. However, their subcellular distribution in terms of the membrane, cytoplasm, and nucleus and relationship with signaling pathways have not been elucidated during carcinogenesis. We first determined the expression of these proteins in the membrane, cytoplasm, and nucleus using ImageJ software and automatically collected the immunohistochemical quantification of dysplasia (actinic keratosis (AK)), carcinoma in situ (CIS; Bowen's disease (BD)), and invasive cutaneous squamous cell carcinoma (SCC) for digital image analysis (DIA). The activity of p-ERK, p-AKT, and p-mTOR and their correlation with subcellular Claudin-1 and Claudin-7 were also performed. Finally, we validated Claudin-1 and Claudin-7 delocalization at the cytoplasm and nucleus in cultured human normal keratinocytes and cutaneous SCC cells. Claudin-1 and Claudin-7 were delocalized as revealed by membranous, cytoplasmic, and nuclear staining in sun-exposed skin, AK, BD, and SCC. In BD, both membranous and cytoplasmic Claudin-1 (nuclear Claudin-1 decrease but no significant difference) were higher than AK, while Claudin-7 almost had the opposite situation. In SCC, cytoplasmic and nuclear Claudin-1 (membranous Claudin-1 no significant difference) was lower than in AK and sun-exposed skin, while Claudin-7 had higher membranous and cytoplasmic but lower nuclear expression. Moreover, p-AKT and p-mTOR (but not p-ERK) were downregulated in the SCC. Subcellular Claudin-1 and Claudin-7 were not only correlated with each other, but also correlated with p-ERK in BD and p-AKT and p-mTOR in SCC. Together, these results imply the delocalization of Claudin-1 and Claudin-7 and their correlation with MAPK/ERK and PI3K-AKT-mTOR signaling pathways in tumorigenesis and infiltration in cutaneous SCC.

Test of cure and beyond: superiority of thermal ablation over LLETZ in the treatment of high-grade CIN

PurposeAmong the treatment modalities for high-grade cervical intraepithelial neoplasia (CIN), large-loop excision of the transformation zone (LLETZ) is the commonest offered in the UK, whereas thermal ablation (TA) has not been common in several decades, despite several notable advantages. TA and LLETZ are both routinely undertaken in our colposcopy unit, and extensive follow-up data have been used to interrogate outcomes between the two modalities and determine whether one modality may be preferred over the other.MethodsUp to 8 years of follow-up data (cytology and histology) were collected for patients who have undergone LLETZ or TA and failed post-treatment test of cure (ToC). These data were analysed and used to plot Kaplan–Meier survival curves, in order to compare outcomes: negative cytology, dyskaryosis, low- and high-grade CIN and invasive squamous cell carcinoma.Resultsi) Very few women treated with TA developed recurrent high-grade CIN in the follow-up period; (ii) LLETZ-treated women had a significantly higher rate of recurrence than those treated by TA; (iii) women who failed both virology and cytology components of post-treatment ToC had higher recurrence than those who failed only one, and the rate of recurrence was highest in those treated by LLETZ (> 65%).ConclusionTA is an effective treatment of high-grade CIN, with a high chance of achieving double-negative ToC and low recurrence relative to LLETZ. We recommend the wider adoption of TA, so that young women of reproductive age have a choice of treatment with no reported adverse effects on pregnancy outcomes.

Pathologic Determination of Multifocality in pT1a1 Squamous Cell Carcinoma of the Cervix: A Retrospective Analysis.

When more than one focus of stromal invasion is present in a superficially invasive cervical squamous cell carcinoma (SCC), determination of the tumoral lateral extent/horizontal extension, and hence tumor-nodes-metastases (TNM) staging, can be problematic. In recent years, a diagnostic approach to distinguish multifocal pT1a1 from pT1b cases has gained increased attention. These criteria call for classifying SCC as multifocal when invasive foci are separated by blocks of uninvolved cervical tissues, and/or are located on separated cervical lips in a tumor that is discontinuous, and/or are situated far apart (≥2 mm) from each other. In this study, we assess our experience with multifocal stage pT1a1 cervical SCC that was retrospectively classified as such using these criteria. Slides from the loop electrosurgical excision or conization specimens, comprising 212 pT1a1, 173 pT1a2, and 206 pT1b cases, were reviewed. Twenty-four (11%) of the 212 pT1a1 cases were classified as multifocal after review. The 24 multifocal pT1a1 cases were compared with the 188 unifocal pT1a1 cases regarding a variety of clinicopathologic parameters. Notably, these 2 groups showed no significant differences regarding all parameters that were evaluated, including patient age, recurrence rate, primary tumoral features in the primary excision specimen (rate of positive margins, median depth of stromal invasion, frequency of lymphovascular invasion), and frequency of residual disease in additional excisions. In summary, we demonstrate comparably favorable patient outcomes in both unifocal and multifocal cases of pT1a1 SCC of the cervix, and, accordingly, we conclusively affirm the validity of the aforementioned criteria for establishing multifocality.

Bladder squamous cell carcinoma in a pregnant woman: case report and review of the literature

BackgroundBladder tumors in pregnancy are extremely rare. No more than 50 cases have been published to date, including all histologic variants, and only three cases of bladder squamous cell carcinoma have been described.Case presentationWe present a clinical case of a 31-year-old woman with bladder squamous cell carcinoma in the second trimester of pregnancy. After a C-section at 30 weeks, we performed radical cystectomy with extended bilateral lymphadenectomy, hysterectomy and right oophorectomy. The Studer neobladder technique was performed for urinary tract reconstruction. Definitive pathology showed invasive bladder squamous cell carcinoma, Grade 2, with microscopic infiltration of the perivesical fat, negative margins, and 3/28 lymph nodes with carcinoma (pT3aN2M0). The patient underwent 18 months of surveillance after radical cystectomy, without recurrence by PET-CT.ConclusionsBladder cancer in pregnant women is extremely rare but must be considered in those with recurrent gross hematuria and/or recurrent urinary tract infection. To our knowledge, this case involves the longest recurrence-free survival of a pregnant woman with squamous cell bladder cancer published thus far.

A RARE OCCURRENCE OF ESOPHAGEAL SPINOCELLULAR CARCINOMA IN A YOUNG ADULT

Esophageal squamous cell carcinoma is a relatively uncommon neoplasm that affects advanced age groups. Here we report a case of an invasive esophageal squamous cell carcinoma that affected a 17-year-old male patient with some evidence showing that the early stages of neoplastic development were throughout childhood. No risks factors were identified and the patient had an excellent long-term outcome.

Prognostic value of S1PR1 and its correlation with immune infiltrates in breast and lung cancers

BackgroundSphingosine-1-phosphate receptor (S1PR1) is involved in vascular development, a key process in tumorigenesis. This study aimed to evaluate its roles in tumor development and prognosis.MethodsS1PR1 expression levels were analyzed using TIMER and Oncomine database, and the prognostic significance of S1PR1 was assessed using PrognoScan and Kaplan-Meier plotter databases. The relationship between S1PR1 and tumor-infiltrated immune cells was analyzed using TIMER.ResultsS1PR1 expression was remarkably lower in breast and lung cancer tissues than in the corresponding normal tissues. Lower expression was related to poor overall survival and disease-free survival in breast invasive carcinoma (BRCA), lung adenocarcinoma (LUAD), and lung squamous cell carcinoma (LUSC). A functional network analysis confirmed the function of S1PR1 in regulating vasculogenesis. In addition, S1PR1 levels were significantly negative with regard to the tumor purity of BRCA (r = − 0.508, P = 1.76e-66), LUAD (r = − 0.353, P = 6.05e-16), and LUSC (r = − 0.402, P = − 5.20e-20). Furthermore, S1PR1 levels were significantly positive with regard to infiltrating CD8+ (r = 0.38, P = 5.91e-35) and CD4+ T cells (r = 0.335, P = 1.03e-26), macrophages (r = 0.219, P = 3.67e-12), neutrophils (r = 0.168, P = 2.03e-7), and dendritic cells (DCs) (r = 0.208, P = 9.14e-11) in BRCA; S1PR1 levels were significantly positive with regard to CD8+ T cells (r = 0.308, P = 3.61e-12), macrophages (r = 0.376, P = 1.01e-17), neutrophils (r = 0.246, P = 4.15e-8), and DCs (r = 0.207, P = 4.16e-6) in LUAD; and positive with regard to B cells (r = 0.356, P = 1.57e-15), CD8+ (r = 0.459, P = 3.83e-26) and CD4+ T cells (r = 0.338, P = 3.98e-14), macrophages (r = 0.566, P = 2.61e-45), neutrophils (r = 0.453, P = 1.79e-25), and DCs (r = 0.56, P = 2.12e-40) in LUSC.ConclusionsS1PR1 levels are positively correlated with multiple immune markers in breast and lung cancer. These observed correlations between S1PR1 and the prognosis and immune cell infiltration provide a foundation for further research on its immunomodulatory role in cancer.

Ocular surface squamous neoplasia: Population demographics, pathogenesis and risk factors

Background: Ocular surface squamous neoplasia (OSSN) is a unifying term used to describe conjunctival intra-epithelial neoplasia, squamous cell carcinoma in situ and invasive squamous cell carcinoma.Aim: The aim of this article was to describe the demographics, clinical features, pathogenesis and risk factors of OSSN.Method: A literature search was conducted using the search criteria ‘ocular surface squamous neoplasia’, ‘diagnosis’, ‘epidemiology’, ‘pathogenesis’ and ‘risk factors’.Results: Ocular surface squamous neoplasia is the most common ocular tumour, with incidence rates ranging from 0.01 to 3.4 per 100 000 persons/year. There are two main patterns of disease presentation: older white males in temperate climates where human immunodeficiency virus (HIV) and human papilloma virus (HPV) are not associated; and a younger patient population in tropical climates where HIV and HPV are more prevalent. The pathogenesis primarily revolves around ultraviolet B exposure and HPV infection that cause genetic mutations and uncontrolled cellular proliferation, whilst HIV infection and vitamin A impair tumour surveillance mechanisms. Ocular surface squamous neoplasia is first suspected clinically before formal confirmation of the diagnosis. Morphologically, it can be divided into three groups: placoid, nodular and diffuse. Placoid lesions can further be sub-divided into gelatinous, leukoplakic and papilliform lesions. Nodular lesions have the poorest prognosis, with the highest risk of metastasis and recurrence.Conclusion: Ocular surface squamous neoplasia is a common ocular tumour associated with ultraviolet radiation, HPV and HIV infection. The pathogenesis revolves around acquired genetic mutations, unregulated cellular proliferation and impaired tumour surveillance mechanisms.

Anticancer effects induced by artichoke extract in oral squamous carcinoma cell lines

BackgroundOral squamous cell carcinoma is occupying the eighth position of all malignant neoplasia worldwide. Nowadays, natural compounds found in vegetables and fruits are important resources of many anticancer drugs especially those with high levels of phytochemicals representing an efficient strategy for cancer prevention and treatment. Artichoke (Cynara cardunculus L.) is a kind of antioxidant-rich vegetables demonstrated a potential anticancer activity on various types of cancer cells related to its content of phenolic compounds. Anticarcinogenic effects of polyphenolic extracts were reported to cause a reduction in cell viability, inhibition of cell growth, and initiation of apoptotic mechanisms. The present study aimed to investigate the cell cycle arrest, cytotoxic, and apoptotic effects of artichoke extract against the invasive oral squamous cell carcinoma.ResultsA pure extract from the edible part and leaves of fresh artichoke was added to oral squamous carcinoma cell lines and to control group to evaluate the expression of caspase-9, Bcl-2, and Bax genes. Artichoke extract demonstrated the highest cytotoxic effect against cancer cell lines which increased in a time-dependent manner. No apparent effects were observed in the normal control group. Expression of Bax and caspase-9 genes revealed a highly significant increase in cancer cell lines (p = 0.0001) when compared to the control group. In addition to a highly significant decrease (p = 0.005) in Bcl-2 of cancer cells. It was demonstrated that artichoke extract induced cell growth arrest at G2/M phase which revealed a significant increase (p < 0.05) in comparison to the untreated control group.ConclusionArtichoke exerts potent cell cycle arrest, cytotoxic, and apoptotic effects on oral squamous carcinoma cell lines.Graphical abstract

Abstract B56: YAP1 inhibits host cell immunity and increases human papillomavirus (HPV) infection to drive cervical tumorigenesis

Abstract Although human papillomavirus (HPV) is believed to be the major causative agent for cervical cancer, accumulating evidence indicates that HPV alone is insufficient to induce cervical cancer. The molecular mechanisms underlying cervical cancer development remain unclear. In the present study, we provide evidence showing that the Hippo/YAP pathway plays a critical role in cervical carcinogenesis. We found that genetic alteration of the Hippo/YAP pathway frequently occurred in human cervical cancer patients and was associated with poor prognosis of these patients. Keratin 14 promoter-driven expression of constitutively active YAP1 (YAP S127A) in mouse cervical epithelial cells induced invasive cervical squamous cell carcinoma (CVSCC), suggesting that hyperactivation of YAP1 is sufficient to induce cervical cancer. Importantly, hyperactivation of YAP1 in cervical epithelial cells not only increased the putative HPV receptor molecules and cellular susceptibility to HPV infection, but also disrupted the host cell innate immune system, resulting in failure of HPV viral recognition, suppression of type I IFN production, inhibition of the IFNRs/JAKs/STATs pathway, and blockage of production of antiviral interferon-stimulated genes. Cervical epithelial-specific YAP1 and HPV double knockin mouse models showed that YAP1 synergizes with HPV to promote the initiation and progression of CVSCC. The present study demonstrates that the Hippo/YAP pathway plays a central role in the development of CVSCC and the synergism between hyperactivated YAP1 and high-risk HPV may be the key driver of cervical cancer development. The Hippo/YAP signaling pathway may represent a promising target for developing novel strategies to prevent and treat cervical cancer. Citation Format: Xiangmin Lv, Chunbo He, Cong Huang, Hongbo Wang, Li Chen, Peichao Chen, John S. DavisS, Bo R. Rueda, Cheng Wang. YAP1 inhibits host cell immunity and increases human papillomavirus (HPV) infection to drive cervical tumorigenesis [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr B56.

Recurrent and Invasive Primary Squamous Cell Carcinoma of the Chest Wall: A Case Report

Squamous cell carcinoma is a type of skin cancer with abnormal proliferation of keratinocytes. Its incidence reaches approximately 20% of cases of non-melanoma skin cancer, which has increased in recent decades due to growth in life expectancy, increased sun exposure, the use of tanning beds and improved detection of this type of tumors. We present a patient who was diagnosed with a squamous cell skin carcinoma in the chest wall, treated initially with surgical resection. A few years recurred in the same place, so the patient received radiotherapy with poor response. Ultimately a new surgical approach was performed with a wide margin resection by a multidisciplinary surgical team. Multidisciplinary management in this type of procedure is important so that the long-term result is optimal for the patient.

Regional intra-arterial polychemotherapy to increase the effectiveness of conservative treatment of locally invasive oral squamous cell carcinoma

The objective is using a clinical example to demonstrate the possibilities of intra-arterial polychemotherapy (PCT) in the combined treatment of oral squamous cell carcinoma.Clinical case. A 43-year-old oral squamous cell carcinoma patient with metastases to cervical lymph nodes, left side (T3N2bM0, stage IV) underwent 2 courses of regional neoadjuvant intra-arterial PCT (docetaxel at a dose of 105 mg, cisplatin at a dose of 105 mg), accessed through a. lingualis. A total dose of 6,800 mg of 5-fluorouracil was administered as a 96-hour infusion. PCT induced oral mucositis of grade 2, no hematological side effects were observed. Clinical examination revealed that tumor volume decreased by 60 %. Ultrasound detected no changes in lymph nodes. Second step included resection of oral cavity bottom tissues, atypical tongue resection, marginal resection of the lower jaw on the left, radical neck dissection on the left. Histological study of the surgical material of primary tumor region as well as metastases of the cervical lymph nodes on the tumor side revealed pathomorphism of 4 grade. In the postoperative period, oral cavity and neck were irradiated from 2 sides. No signs of the disease were detected within 9 months after the combined treatment.Conclusion. The clinical case demonstrates the high efficiency of regional intra-arterial PCT in patients with locally invasive oral squamous cell carcinoma. It seems relevant to further study its possibilities in the combined treatment of locally invasive forms of oral squamous cell carcinoma.

1651 Colon, Urothelial and Sebaceous Malignancy All in One: A Rare Presentation of Muir-Torre Syndrome

INTRODUCTION: Muir-Torre syndrome (MTS) is a rare autosomal-dominant condition and phenotypic variant of Lynch syndrome caused by mutations in DNA mismatch repair genes MSH2, MSH6, and MLH1. Clinical diagnostic criteria include the presence of at least one sebaceous gland neoplasm and one visceral malignancy, often colonic or genitourinary. Compared to Lynch syndrome, the prevalence of MTS is likely underreported. We present a unique case of a patient with incidental findings of multiple visceral malignancies associated with skin cancer. CASE DESCRIPTION/METHODS: A 57-year-old Caucasian man presented for surveillance colonoscopy. His family history was significant for father with colon cancer at age 50, lung, and renal cancer. The patient was diagnosed with sebaceous adenocarcinoma, invasive squamous cell, and basal cell carcinomas requiring excisional surgery at age 46. Screening colonoscopy at that time was normal, with repeat after 7 years noting diminutive sigmoid tubular adenomas that were resected. Current colonoscopy revealed 14 colon polyps, multiple with high grade dysplasia, and an invasive sigmoid adenocarcinoma. Staging CT A/P was negative for metastatic disease. CEA was normal. The patient opted for left hemicolectomy instead of total proctocolectomy. Tumor pathology revealed moderately differentiated adenocarcinoma with negative margins (pT4N0M0). Colon cancer genetic testing showed lack of expression of MSH2/MSH6 and germline MSH2 mutation, confirming the diagnosis of MTS. A month later he developed hematuria and acute kidney injury that culminated in a new diagnosis of invasive high-grade urothelial carcinoma. Neoadjuvant chemotherapy was started with plan for cystectomy. DISCUSSION: MTS is a rare condition that warrants early recognition, regular follow-up and observation for new malignancies. Our case highlights the importance of awareness and the need for early, universal screening in high-risk individuals. MTS patients should undergo screening colonoscopy at ages 20–25 with surveillance every year thereafter to offer mortality benefit. If colon cancer is diagnosed, total rather than partial colectomy is preferred due to a high metachronous cancer rate of 25%. Patients and relatives should be counseled on increased risk of future malignancies. Reconstruction of family history may allow for the identification and selection of patients in whom to proceed with clinical, molecular, and immunohistochemical analysis. Clinicians must therefore be cognizant of this disease and its enduring effects.

Synoptic reporting in Mohs micrographic surgery.

There is currently no standardised reporting format for Mohs surgery with its operation reports mostly written in a narrative form making them prone to unintentional errors and omission of necessary data. Synoptic histology reporting is used to describe excised skin cancers such as melanomas and, more recently, squamous cell and basal cell carcinomas. Since Mohs surgery is utilised as the gold standard treatment for locally invasive squamous and basal cell carcinomas, we propose the use of our model of synoptic reporting to ensure the completeness and consistency of Mohs surgery operation reports.

Association of lymph node involvement with the prognosis of pathological T1 invasive non-small cell lung cancer

BackgroundLymph node involvement could help to predict the prognosis of pathological T1 (pT1, diameters of ≤3 cm) non-small cell lung cancer (NSCLC). This study assessed the clinicopathological factors and associated lymph node involvement in invasive lung adenocarcinoma (IAC) and squamous cell lung cancer (SCC) and the overall and disease-free survival associated with these factors.MethodsThree hundred and twenty-five patients with pathological T1 NSCLC (253 IAC and 72 SCC) were retrospectively analyzed from a pool of 1094 primary lung cancer patients. The data were assessed using multiple logistic regression, Kaplan-Meier curves and multivariable analyses.ResultsAmong patients with a ≤30-mm tumor lesion (N = 325), N1 and N2 lymph node involvement was found in 28 (8.6%) and 34 (10.4%) patients, respectively. Lymph node metastasis occurred in 13.0% (33/253) of pT1 IAC patients and 40.3% (29/72) of SCC patients. Carcinoembryonic antigen (CEA) levels, SCC by histology, and tumor lesions larger than 1.0 cm were associated with lymph node involvement (P < 0.0001, <0.0001, and 0.048, respectively). In IAC patients, negative lymph nodes were associated with better overall survival compared with lymph node-positive ones (P = 0.021). No significant difference was observed in SCC patients regardless of lymph node status (P = 0.40). Multivariable Cox analysis revealed that lymph node involvement was an independent prognostic predictor of overall IAC patient survival (P = 0.041), but not of SCC patient survival (P = 0.470). Chemotherapy was administered to 72.2% (52/72) of SCC patients, a significantly higher rate when compared with that of IAC patients (42.3%, 107/253).ConclusionsLymph node metastasis was inversely associated with the overall survival of IAP patients, but not with the survival of SCC patients. Patients with pT1 SCC exhibited a significantly higher rate of lymph node involvement when compared with IAC patients. Thus, a systematic lymph node dissection should be performed in pT1 IAC patients, especially in patients with IAC larger than 1.0 cm, for additional treatment selections to improve survival.

Stepwise Multicenter Introduction of Intensity Modulated Radiation Therapy for Anal Cancer in the United Kingdom: From Consensus Guidance to Large-Scale Prospective Audit, Prior to Future Clinical Trials

Purpose/Objective(s) The ACT 2 trial determined the standard UK radiotherapy technique in chemoradiotherapy for anal cancer. Intensity-modulated radiotherapy (IMRT) is increasingly used due to reduced acute toxicity, however the implementation in a multicenter setting is challenging. We planned a stepwise implementation of IMRT prior to the PLATO study; an anal cancer trial due to open in 2016, investigating optimization of radiotherapy dose. We developed a consensus guidance document, adapting the ACT 2 doses and volumes for IMRT, and this was presented and published in 2014 [1]. We then performed an audit of clinical practice prior to the opening of the PLATO trial. Materials/Methods The Royal College of Radiologists carried out a prospective national audit, over a 6-month period between February and July 2015. All UK cancer centers were asked to submit details of consecutive anal cancer patients receiving radiotherapy over that period. Results Two hundred and forty-two cases were received from 41 centers. Median age was 62 (range = 29 to 90), with a female to male ratio of 2.8. 99% had invasive squamous cell, basaloid, or cacogenic carcinoma. T1/2 and T3/4 constituted 53.5% and 46.7% of tumors respectively. 49.6% had positive lymph nodes. 64.5% and 28.1% underwent Mitomycin / 5FU and Mitomycin / Capecitabine respectively. Initial analysis reveals 187 (77.3%) received treatment using inverse planning of which 148 patients received full dose radiotherapy using the doses and delivery proposed in the guidance. For toxicity comparisons the grade 3 + 4 toxicity in 3 groups were compared; those treated as per consensus guidance, those treated using the ACT 2 protocol within the audit and the published toxicity from the ACT 2 trial. Toxicity was as follows: Non-hematological - 40%, 49%, and 62%; hematological - 17%, 13%, and 26%; skin - 26%, 43%, 48%; and pain - 12%, 17%, 26%. Diarrhea was reported in 12%, 2%, and 9%. Further analysis demonstrated this was different in capecitabine-based and 5FU-based chemotherapy regimens; 16% versus 6%. The median treatment time was 38, 39, and 38 days; the number of interruptions in radiotherapy treatment was 5%, 11%, and 15%; the number of patients completing chemotherapy was 84%, 89%, and 77%; treatment-related deaths were 0%, 4%, and <1%. Conclusion This large-scale UK audit demonstrates the reduced toxicity of IMRT, implemented using consensus guidance, in comparison to the previous ACT 2 protocol. This stepwise implementation of novel radiotherapy techniques, prior to their use in a large trial, is likely to have beneficial implications for investigators due to reduced requirements for training, education, and possibly quality assurance. [1] Muirhead R, Adams RA, Gilbert DC, Glynne-Jones R, Harrison M, Sebag-Montefiore D, Hawkins MA. Anal cancer: developing an intensity-modulated radiotherapy solution for ACT2 fractionation. Clin Oncol 2014;26:720-721

Immunohistochemical expression of ARID1A in penile squamous cell carcinomas

INTRODUCTION AND OBJECTIVES: ARID1A, a member of the chromatin remodeling genes family, has been suggested as a novel tumor suppressor gene in gynecologic malignancies. However, its role in penile cancer has yet to be determined. This study assesses the immunohistochemical expression of ARID1A in invasive penile squamous cell carcinomas (SCC). METHODS: 112 cases of formalin-fixed paraffin-embedded penile SCC from Paraguay were used to build 4 tissue microarrays (TMA). Each tumor was sampled 3 12 times. Histologic subtyping and grading was done using recently published criteria (Hum Pathol 2012; 43:771). ARID1A expression was evaluated by immunohistochemistry using a polyclonal rabbit anti-ARID1A (BAF250A) antibody (HPA005456, Sigma-Aldrich, St Louis, MO). An H score is calculated in each spot as the sum of expression intensity (0-3) X extent (0-100). Median H score per case was used for statistical analysis. RESULTS: Distribution of subtypes was as follows: usual SCC, 48 cases; warty-basaloid carcinoma, 25 cases; warty carcinoma, 16 cases; basaloid carcinoma, 11 cases; papillary carcinoma, 9 cases; and 1 case each of sarcomatoid, verrucous, and usual-verrucous (hybrid) carcinomas. Distribution of histologic grades vas as follows: grade 1, 5 cases; grade 2, 30 cases; grade 3, 77 cases. Human papillomavirus (HPV) DNA was detected by PCR in 20 of 52 (38%) analyzed samples. ARID1A expression was observed in all cases, ranging from 3% to 100% of tumor cells (median, 95%). In 96 cases (86%) ARID1A expression was observed in 90% or more of tumor cells. ARID1A expression was not associated with histologic subtype (P 0.79) or HPV status (P 0.18). However, the Kruskal-Wallis test yielded a P 0.054 for the association between ARID1A and histologic grade. The Cuzick test showed that this trend was significant (P 0.026). CONCLUSIONS: ARID1A is expressed in penile SCC, in most cases at high levels. A significant trend was found between histologic grade and ARID1a expression, with higher ARID1A expression at higher histologic grades. The implications of our findings for penile cancer oncogenesis and prognosis merits further investigation.

Radiation incidents and accidents in diagnostic and interventional radiology. What to do next in interventional radiology

The International Commission on Radiological Protection (ICRP) defines interventional Radiology (IR) procedures as the techniques that encompass guided diagnostic and therapeutic interventions either by percutaneous or other access under local anaesthesia and/or sedation. Fluoroscopic imaging is applied to best localise the lesion or the treatment site as well as to continuously monitor and record the procedure. Whereas diagnostic radiology is generally safe for patients and staff, these techniques involve high risk of skin injuries of patients and occupational overexposure of staff involved. IR skin injuries are termed as fluoroscopy-induced radiation dermatitis. They usually appear within 7–14 days of exposure and may be acute or chronic. A certain threshold is required, reached either at once or in cumulative radiation doses. It causes inflammation of the skin, presenting as erythema, pain, and pruritus that may later transform into ulceration, atrophy, telangiectasia, sclerosis, discoloration, and malignancy, such as invasive basal cell or squamous cell carcinoma. A number of cases are reported in the literature in order to emphasize the importance of recognizing fluoroscopy as a cause of radiation dermatitis among other skin injuries. Interventionalists are often unaware of the high radiation doses to which a patient’s skin may be subjected, even with the use of modern, state of the art equipment. This paper will consider the knowledge, techniques and possible regulatory requirements necessary to prevent radiological incidents and accidents and provide recommendations in the case such events occur.