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Graphical abstract, Highlights • Skin cancer is a fatal public health concern rising continuously all over the world. • Several environmental and genetic risk factors are associated with cutaneous carcinogenesis. • Use of nanocarriers for targeted delivery of anticancer agents is the most advanced approach. • Polymeric structures are suitable for tumor selective delivery of drugs, genes and imaging agents. • Polymeric micro/nanostructures have successfully used for combination anticancer therapies., Background Skin cancer has been the leading type of cancer worldwide. Melanoma and non-melanoma skin cancers are now the most common types of skin cancer that have been reached to epidemic proportion. Based on the rapid prevalence of skin cancers, and lack of efficient drug delivery systems, it is essential to surge the possible ways to prevent or cure the disease. Aim of review Although surgical modalities and therapies have been made great progress in recent years, however, there is still an urgent need to alleviate its increased burden. Hence, understanding the precise pathophysiological signaling mechanisms and all other factors of such skin insults will be beneficial for the development of more efficient therapies. Key scientific concepts of review In this review, we explained new understandings about onset and development of skin cancer and described its management via polymeric micro/nano carriers-based therapies, highlighting the current key bottlenecks and future prospective in this field. In therapeutic drug/gene delivery approaches, polymeric carriers-based system is the most promising strategy. This review discusses that how polymers have successfully been exploited for development of micro/nanosized systems for efficient delivery of anticancer genes and drugs overcoming all the barriers and limitations associated with available conventional therapies. In addition to drug/gene delivery, intelligent polymeric nanocarriers platforms have also been established for combination anticancer therapies including photodynamic and photothermal, and for theranostic applications. This portfolio of latest approaches could promote the blooming growth of research and their clinical availability.

Objective Thyrotoxicosis from local invasion of the thyroid gland by an extrathyroidal malignancy is rare. We describe a patient with thyrotoxicosis secondary to invasion of the thyroid gland by an oropharyngeal squamous cell carcinoma (OPSCC). To our best knowledge, this has not been reported. Methods A 62-year-old Indian man with histologically proven, p16-negative, cT3N3bM0 (stage IVb) posterior OPSCC was admitted for elective gastrostomy. Biochemical thyroid profile was normal before admission, and there was no thyroid invasion radiologically. The patient developed persistent fever and tachycardia associated with an elevated white cell count and C-reactive protein. This was treated as sepsis, and antibiotic therapy was initiated for 17 days without response. An extensive septic workup did not reveal any infection. A subsequent neck computed tomography revealed rapid progression of the OPSCC, with the invasion of bilateral thyroid lobes. Thyroid function tests revealed primary hyperthyroidism. Antibodies indicative of Graves’ disease were negative. A tracheostomy was performed due to impending airway compromise. Results The patient showed minimal clinical improvement with medical management, and thyroid function continued to worsen. He died due to cardiorespiratory collapse due to tumor progression, new-onset atrial fibrillation, and poor underlying cardiac function. Conclusion We report a rare observation of thyrotoxicosis secondary to thyroid gland invasion by OPSCC. This highlights the need for a high index of suspicion of malignancy-induced hyperthyroidism and evaluation of thyroid function early in febrile/tachycardic patients with locoregionally advanced head and neck SCCs. Urgent oncological treatment may be necessary to control thyrotoxicosis.

Video Video 1 This is a case of a patient with esophageal squamous cell carcinoma who underwent endoscopic submucosal dissection and subsequent esophagectomy. The endoscopic findings using imaged endoscopy, magnification, and Lugol’s are demonstrated. There is a demonstration of endoscopic and pathological correlation in addition to the emphasis on a patient-centered multidisciplinary approach to esophageal neoplasia and the diagnostic utility of endoscopic submucosal dissection.

Σκοπός της διατριβής ήταν η μελέτη της βιβλιογραφίας για το ακανθοκυτταρικό επιθηλίωμα άκρας χειρός. Πραγματοποιήθηκε έρευνα στο pubmed 200 άρθρων με κριτήρια: ακανθοκυτταρικό επιθηλίωμα, πρωτοπαθείς όγκοι άκρας χειρός. Από αυτά έγινε μελέτη 15 άρθρων από το 2015 μέχρι και το 2022. Έγινε μελέτη της βιβλιογραφίας και των κατευθυντήριων οδηγιών του 2022 για την διάγνωση, την αντιμετώπιση και παρακολούθηση τω ασθενών βάσει Ν.C.C.N, και B.A.D. Στην εργασία παρουσιάστηκαν περιληπτικά τα χαρακτηριστικά των πρωτοπαθών όγκων άκρας χειρός και αναλυτικά τα χαρακτηριστικά του ακανθοκυτταρικού επιθηλιώματος. Πραγματοποιήθηκε ανασκόπηση των νέων παραγόντων κινδύνου εμφάνισης του ακανθοκυτταρικού επιθηλιώματος, της διερεύνησης, διάγνωσης και θεραπείας της συγκεκριμένης νόσου., The aim of the present thesis was the study of literature considering the hand squamous cell carcinoma. A pubmed research was done with the key words: scc, hand squamous cell carcinoma and upper extremity tumors. 200 articles were found and 15 of them, from the period of 2015 to 2022 were reviewed. N.C.C.N. and B.A.D. quidelines of 2002 were also reviewed considering the diagnosis, treatment and follow – up of patients with hand SCC. In the thesis, a literature review was done about the new data found about the risk factors of squamous cell carcinoma at hand, the diagnosis methods, the treatment and follow up of the patients.

A major mitochondrial enzyme for protecting cells from acetaldehyde toxicity is aldehyde dehydrogenase 2 (ALDH2). The correlation between ALDH2 dysfunction and tumorigenesis/growth/metastasis has been widely reported. Either low or high ALDH2 expression contributes to tumor progression and varies among different tumor types. Furthermore, the ALDH2∗2 polymorphism (rs671) is the most common single nucleotide polymorphism (SNP) in Asia. Epidemiological studies associate ALDH2∗2 with tumorigenesis and progression. This study summarizes the essential functions and potential ALDH2 mechanisms in the occurrence, progression, and treatment of tumors in various types of cancer. Our study indicates that ALDH2 is a potential therapeutic target for cancer therapy., Graphical abstract ALDH2 dysfunction contributes to the occurrence and development of cancer. A better understanding of the relationship between ALDH2 and cancer can provide a new strategies of treating cancer patients by targeting ALDH2.Image 1

Clinical trials investigating immune checkpoint inhibitors (ICIs) largely excluded solid organ transplant recipients (SOTRs), as immunostimulation by these drugs may subvert host tolerance to the transplanted tissue, potentially leading to allograft rejection.1 Consequently, data concerning the safety and efficacy of ICIs in these patients remain limited. ICI trials also routinely excluded patients with preexisting autoimmune disease given the concern for possible disease exacerbations, resulting in similarly limited data in this population.2 We report a unique case of a SOTR with ulcerative colitis (UC) and metastatic cutaneous squamous cell carcinoma (SCC) who was successfully treated with anti-programmed cell death protein 1 ICI therapy, initially with nivolumab, then with cemiplimab, which is approved by the US Food and Drug Administration for advanced cutaneous SCC.3

Background and aim Although, the anticancer potential of Aqueous Azadirachta indica leaf extract (AAILE) has been robustly established against cutaneous squamous cell carcinoma (SCC) in mice, however, its ability in modulating tumor associated extra cellular matrix (ECM) is largely unknown. Therefore, the present study was conceived to explore changes in ECM during murine skin cancer and its chemoprevention by AAILE. Experimental procedure Skin tumors were induced using a two-stage model of carcinogenesis employing topical application of 7,12-Dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoyl phorbol-13-acetate (TPA) as carcinogen and promoter respectively. AAILE was administered orally to the animals. Male Laca mice were divided into four groups: control, AAILE, DMBA/TPA and AAILE + DMBA/TPA. Results The tumors obtained in DMBA/TPA and AAILE + DMBA/TPA groups were histologically identified as SCC. Tumor induction in these groups was accompanied by raised serum carcinoembryonic antigen (CEA) levels when compared to control counterparts. Assessment of hydroxyproline levels and histochemical staining with sirius red and trichrome stain revealed an increase in collagen in tumors of DMBA/TPA group. An increase in glycosaminoglycans (GAGs) levels was also observed in DMBA/TPA group as made evident by biochemical studies and histochemical staining using mucicarmine and alcian blue-periodic acid schiff’s stain. Administration of AAILE to DMBA/TPA treated animals caused a decrease in collagen and GAG levels along with a decrease in serum CEA levels. Conclusion Skin tumors exhibited altered presence of ECM components which is indicative of a modified ECM. AAILE administration antagonised tumor associated ECM alterations which may be contributing to its chemopreventive activity as reported previously., Graphical abstract Image 1, Highlights • DMBA/TPA induced cutaneous squamous cell carcinoma (SCC) in mice. • SCC formation accompanied by enhanced serum carcinoembryonic antigen (CEA) levels. • Dysregulated extra cellular matrix (ECM) components in tumors of DMBA/TPA group. • Altered histological presence and levels of collagen and glycosaminoglycans in tumors. • Chemoprevention by A.indica reduced CEA levels and antagonised ECM alterations.

Trop-2 is a transmembrane signal transducer that can induce cancer growth. Using antibody targeting and N-terminal Edman degradation, we show here that Trop-2 undergoes cleavage in the first thyroglobulin domain loop of its extracellular region, between residues R87 and T88. Molecular modeling indicated that this cleavage induces a profound rearrangement of the Trop-2 structure, which suggested a deep impact on its biological function. No Trop-2 cleavage was detected in normal human tissues, whereas most tumors showed Trop-2 cleavage, including skin, ovary, colon, and breast cancers. Coimmunoprecipitation and mass spectrometry analysis revealed that ADAM10 physically interacts with Trop-2. Immunofluorescence/confocal time-lapse microscopy revealed that the two molecules broadly colocalize at the cell membrane. We show that ADAM10 inhibitors, siRNAs and shRNAs abolish the processing of Trop-2, which indicates that ADAM10 is an effector protease. Proteolysis of Trop-2 at R87-T88 triggered cancer cell growth both in vitro and in vivo. A corresponding role was shown for metastatic spreading of colon cancer, as the R87A-T88A Trop-2 mutant abolished xenotransplant metastatic dissemination. Activatory proteolysis of Trop-2 was recapitulated in primary human breast cancers. Together with the prognostic impact of Trop-2 and ADAM10 on cancers of the skin, ovary, colon, lung, and pancreas, these data indicate a driving role of this activatory cleavage of Trop-2 on malignant progression of tumors.

Verrucous candidiasis (VC) of the oral mucosa can present with pseudocarcinomatous hyperplasia, often confused with squamous cell carcinoma (SCC). Here, we describe a case of florid VC secondary to fluconazole-resistant Candida albicans and report an initial significant response to oral posaconazole and surgical excisions. However, after 12 months of close follow-up, the patient's VC progressed to frank SCC, demonstrating the malignant potential of refractory VC cases.

Highlights • Pulmonary lymphoepithelioma-like carcinoma (LELC) is extremely rare in Japan. • None of the studies regarding LELC in Japan described an association with PD-L1. • This is the first case of LELC in Japan with both expression of EBER-ISH and PD-L1. • An investigation of PD-L1 would be useful considering the PD-1/PD-L1 blockade. • Thus, PD-L1 expression should be examined in patients with pulmonary LELC., Introduction and importance Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non-small cell lung cancer (NSCLC) that is classified as a subtype of unclassified carcinoma by the WHO. LELC is usually associated with Epstein-Barr virus (EBV) infection. LELC has often been observed in Southeast Asia; however, it is extremely rare in Japan. Case presentation A 60-year-old Japanese woman presented with an abnormal shadow in the left lung on chest radiography. Chest computed tomography showed a nodule located between the lingular and basal anteromedial segments. A blood test suggested an existing EBV infection, and LELC was suspected preoperatively in the transbronchial lung biopsy. She underwent a lingular and basal bi-segmentectomy. The EBV-encoded small ribonucleic acid in-situ hybridization (EBER-ISH) was positive, and she was diagnosed with LELC. Moreover, programmed death-ligand 1 (PD-L1) expression was moderately positive. No recurrence was observed for 30 months. Clinical discussion Although LELC has been reported as a low-grade malignancy with a good prognosis, the frequency of PD-L1 expression in LELC seems to be higher than that in other NSCLCs. Moreover, it has been reported that LELC patients with high PD-L1 expression are likely to have early recurrence/metastasis and poor prognosis. Conclusion An investigation of PD-L1 expression for LELC would be useful considering the benefit of PD-1/PD-L1 blockade in patients with pulmonary LELC with high PD-L1 expression. The present case is the first report of LELC with positive expression of EBER-ISH and PD-L1 in Japan.

Introduction Dermatoses contribute to a large burden of global disease, but the relationship between socioeconomic status and the effect of dermatologic conditions in Europe is not well understood. Methods We selected Global Burden of Disease Study data sets to analyze disability-adjusted life-years (DALYs) and the annual rate of change of dermatoses between 1990 and 2017 in 43 European countries. The principal country-level economic factor used was gross domestic product per capita from the World Bank. Statistical analysis was performed with Spearman ρ correlation. Results Wealthier European countries had higher DALYs for melanoma, basal cell carcinoma, psoriasis, atopic dermatitis, acne, seborrheic dermatitis, alopecia, asthma, contact dermatitis, and viral skin disease. Poorer countries had higher DALYs of squamous cell carcinoma, urticaria, decubitus ulcers, pruritus, scabies, tuberculosis, and syphilis. Thirteen European countries were in the top 10th percentile globally for annual increase in skin and subcutaneous disease burden. Conclusion The majority of European countries have experienced an increase in skin and subcutaneous diseases in recent decades relative to the rest of the world, but the burden of individual dermatoses in Europe varies by country and socioeconomic status. DALYs can potentially serve as a purposeful measure for directing resources to improve the burden of skin disease in Europe.

Muir-Torre syndrome is an autosomal-dominant disorder caused by germline mutations in 1 of the 4 key DNA mismatch repair (MMR) genes, MSH2, MSH6, PMS2, and MLH1. Patients with Muir-Torre syndrome present with skin lesions, which play an important role in early detection of the disease and are considered cutaneous markers. The diagnostic criteria for Muir-Torre syndrome are at least 1 skin neoplasm with sebaceous differentiation, at least 1 visceral malignancy, and germline mutation of the MMR genes.1,2 Sebaceous adenoma is rare and is considered the most significant cutaneous marker for Muir-Torre syndrome.3 Abbas and Mahalingam4 suggested that when a young patient presents with a sebaceous neoplasm outside the head and neck area, immunohistochemical analysis of the MMR genes should be conducted for Muir-Torre syndrome screening. If loss of any MMR proteins is identified, microsatellite instability study or germline analysis is warranted for further diagnosis. In addition, presence of multiple keratoacanthomas should also prompt immunostaining studies for screening.3 In Muir-Torre syndrome, the keratoacanthoma usually presents with sebaceous differentiation.3 For a specific patient, loss of MMR proteins in the skin lesions and in the visceral tumors should be in concordance because of the presence of germline mutation. However, here we examined a visceral tumor and all 16 skin lesions from a patient with Muir-Torre syndrome and found genetic heterogeneity among several samples. All 13 sebaceous adenomas and the visceral tumor showed the same expression pattern of the MMR genes in line with the germline mutation, whereas other skin lesions such as keratoacanthoma and squamous cell carcinoma (SCC) showed aberrant expression patterns. To our knowledge, this is the first study reporting the phenomenon of genetic heterogeneity in a Muir-Torre syndrome patient.

Background Because primary squamous cell carcinoma (SCC) of the breast is a rare disease, the standard therapy has not been established. We examined the clinical outcomes of postoperative adjuvant radiotherapy for breast SCC. Material and methods We conducted a multicenter retrospective cohort study. Patients diagnosed with primary breast SCC who received adjuvant radiotherapy as part of their primary definitive treatment were included. Overall survival (OS), breast cancer-specific survival (BCSS), and recurrence-free interval (RFi) were evaluated. Results Between January 2002 and December 2017, 25 breast SCC patients received adjuvant radiotherapy as a primary treatment were included. Median follow-up time was 43.5 months. Three (12%), fifteen (60%) and seven (28%) patients had clinical stage I, II and III disease, respectively. Fourteen patients underwent breast-conserving surgery and subsequent adjuvant radiotherapy. Eleven patients underwent mastectomy and post-mastectomy radiotherapy. Ten patients received regional lymph node irradiation. Nine (36%) patients had disease recurrence. The first site of recurrence was locoregional in five, but distant metastasis arose in one. Concurrent local and distant metastasis were seen in two. Six cases of local recurrence occurred within the irradiated site. Seven patients died, and six of the deaths were due to breast cancer. Five-year OS, BCSS, and Rfi were 69%, 70%, and 63%, respectively. In multivariate analysis, age and lymphatic invasion were associated with increased risk of recurrence. Conclusion Breast SCC has a high incidence of locoregional recurrence and poor prognosis. Age and lymphatic invasion are significant risk factors for recurrence., Highlights • Clinical outcome of adjuvant radiotherapy for SCC of the breast was evaluated. • Breast SCC had poor prognosis and a high incidence of locoregional recurrence. • In-field recurrence following radiotherapy occurred frequently. • Age and lymphatic invasion were significantly associated with increased risk of recurrence.

Microcystic adnexal carcinoma is a rare malignant neoplasm first characterized in 1982.1 Since the first report, at least 300 cases have been described in the literature, and it has been shown to have features of both eccrine ductal and pilosebaceous differentiation.2 Although it has been suggested that photodamage and iatrogenic irradiation are contributing factors to the development of microcystic adnexal carcinoma, it is uncertain whether systemic immunosuppression confers an increased risk, as with other nonmelanoma skin cancers. Here we present a case of microcystic adnexal carcinoma in a liver transplant recipient. To our knowledge, this represents only the fourth case of microcystic adnexal carcinoma reported in transplant recipients and the first reported in a patient with liver transplantation.3, 4, 5

Highlights • Estrogen receptor or progesterone receptor positivity are unusual in cervical adenocarcinomas. • Estrogen receptor positivity in pregnancy could be associated with a faster growth rate. • Both patients presented remain free of recurrence after definitive treatment., The incidence of adenocarcinoma of the cervix in pregnancy is exceptionally rare, and thus there is no consensus on its management. Here, we report two cases of adenocarcinoma of the cervix diagnosed in the context of pregnancy. In our first case, a patient referred to colposcopy for atypical glandular cells of undetermined significance was subsequently diagnosed with well differentiated endocervical adenocarcinoma on cone biopsy. Just prior to the cone biopsy, she was incidentally found to have a first trimester pregnancy loss. The patient subsequently underwent a radical hysterectomy and bilateral sentinel lymph node dissection. Final pathology revealed a stage 1B1 (FIGO 2009) well differentiated adenocarcinoma of the cervix. Interestingly, the tumour was positive for estrogen receptor, which is unusual for cervical adenocarcinoma. In our second case, a patient presented with a pedunculated, exophytic cervical neoplasm at 31 weeks GA with self-limiting antepartum hemorrhage. The primary lesion measured 52 mm in diameter on MRI and was amputated at the base during the patient’s elective repeat cesarean section. Final pathology revealed a stage IB2 (FIGO 2009) mucinous adenocarcinoma of the cervix. The patient subsequently underwent a radical hysterectomy and bilateral pelvic lymph node dissection 17 weeks after initial presentation. The depth of invasion was 2.2 mm, restricted to the inner third of the cervical wall, and there was no lymphovascular space invasion in the surgical specimen. Surgical margins, parametria, and lymph nodes were all negative for adenocarcinoma. This tumour was also found to be estrogen receptor/progesterone receptor (ER/PR) positive, again unusual for cervical adenocarcinoma. P16 was strongly positive and HPV DNA studies were also positive for human papilloma virus 18. The patient received adjuvant external beam radiotherapy to the pelvis and currently remains in remission.

Highlights • Cervical squamous cell carcinoma does metastasize to the breast. • Vagina exam is essential in a patient who presents with a breast mass. • Immunohistochemistry is key in differentiating a primary lesion from a metastasis.

Cemiplimab (Libtayo, Regeneron Pharmaceuticals, Tarrytown, NY) is a monoclonal antibody that targets the programmed cell death receptor 1. In 2018, the Food and Drug Administration approved cemiplimab for the treatment of patients with metastatic cutaneous squamous cell carcinoma (SCC) or locally advanced cutaneous SCC that is not a candidate for surgery or radiation.1 Immune checkpoint inhibitors have been implicated in the development of bullous disorders.2,3 We report the first case, to our knowledge, of a patient who developed severe steroid-resistant bullous pemphigoid shortly after initiating therapy with cemiplimab, requiring discontinuation of the programmed cell death receptor 1 inhibitor and treatment with rituximab.

Epithelial sheath neuroma (ESN) is an uncommon cutaneous tumor that was first described in 2000 by Requena et al.1 This term was coined because of the presence, on microscopic examination, of squamous epithelium surrounding dermal nerve fibers in a sheath. In the literature, 10 cases are reported date, all occurring in patients older than 40 years, predominantly in women. Clinically, it is described as a firm, erythematous papule or nodule located on the upper back. This report describes 3 additional cases of ESN that were identified and successfully treated and reviews previously published cases to further characterize this uncommon lesion.

Highlights • Case of esophageal cancer associated with an aberrant V2. • Used preoperative 3D-CT for performing safe VATS-E. • Preoperative contrast-enhanced 3D-CT clearly depicted the aberrant V2., Background Subcarinal lymphadenectomy is an essential procedure in curative esophagectomy for esophageal cancer. The right superior pulmonary vein (RSPV) and its branches are usually located in front of the right main or intermediate bronchus. However, an anomalous posterior branch (aberrant V2) of RSPV passes behind the right intermediate bronchus, where the aberrant V2 may be embedded in the subcarinal nodal packet. This can lead to unanticipated bleeding when dissecting the subcarinal lymph node. We present a case study on the use of preoperative three-dimensional contrast-enhanced computed tomography (3D-CT) for performing a safe video-assisted thoracoscopic surgery-esophagectomy in lower thoracic esophageal cancer. Case presentation A 77-year-old man had esophageal cancer associated with an aberrant V2 passing behind the right intermediate bronchus. Esophagogastroduodenoscopy revealed a type 1 tumor in the lower thoracic esophagus. Contrast-enhanced and 3D-CT scans showed a space-occupying lesion with contrast enhancement and an aberrant V2 passing behind the right intermediate bronchus, respectively. The patient was then diagnosed with lower thoracic esophageal cancer (cT2cN1cM0 cStage II). As per the patient’s request, he underwent a surgery-first approach followed by adjuvant chemotherapy. The patient underwent video-assisted thoracoscopic surgery-esophagectomy (VATS-E) with three-field lymphadenectomy, and a large aberrant V2 involving the subcarinal nodal packet was recognized behind the right intermediate bronchus. After the thoracoscopic subtotal esophagectomy with three-field lymph node dissection, laparoscopy-assisted reconstruction of the esophagus was performed with elevation of the gastric conduit to the neck. Recurrent laryngeal nerve palsy was not observed. He started to receive rehabilitation for swallowing on day 3 and resumed oral intake on day 10 after surgery. The final pathological diagnosis was squamous cell carcinoma of the esophagus (pT3N1M0 pStageIII). Conclusions Preoperative contrast-enhanced 3D-CT clearly depicted the aberrant V2, which enabled us to perform a safe VATS-E with three-field lymphadenectomy. Thorough understanding of the anatomical configuration of the pulmonary vessels and bronchus is important for avoiding unexpected bleeding during subcarinal lymphadenectomy. 3D-CT imaging study is useful for recognizing the anomalous RSPV before surgery.

Highlights • Liver metastasis of anal squamous cell carcinoma with a presented pseudocyst is very rare. • Some hepatic diseases such as infections, simple biliary cysts, and neoplasms demonstrate a cystic change of the liver. • Metastasis should be suspected when CT findings in patients with a history of gastrointestinal cancer show cystic changes involving the liver., Introduction Liver metastasis of an anal squamous cell carcinoma (SCC) with a pseudocyst is uncommon. There are many diseases which form hepatic cystic lesions and sometimes it is difficult to arrive at an accurate diagnosis. Presentation of case A 69-year-old woman visited our hospital with complaints of bloody stool and difficult defecation. A palpable mass in the anal canal was found on digital examination. The laboratory tests revealed anemia and raised levels of SCC antigen. On endoscopy a type 2 tumor was identified in the anal canal and biopsy revealed SCC. The patient was diagnosed with advanced anal SCC (cT2N1aM0, cStage IIIA) as a result of the examination and underwent chemoradiotherapy (CRT); unfortunately the tumor persisted after CRT. A salvage abdominoperineal resection with D2 and left lateral lymph node dissection was conducted. Histopathologically, the tumor was diagnosed as poorly differentiated SCC. She was readmitted for fever 3 weeks after surgery, and the abdominal CT showed multiple low density areas with enhancement at the edge of the liver, suggesting abscess or metastasis. The metastatic SCC was revealed by cytology of liver drainage and liver biopsy. Discussion Anal cancers are sometimes encountered however; a pseudo cystic presentation of a liver metastasis is very rare which makes it difficult to distinguish from other diseases. Conclusion We present a case of SCC in the anal canal with liver metastasis presenting as a hepatic pseudocyst.

Background: Human papillomavirus (HPV)16 can be separated into genetic sub-lineages (A1–4, B1–4, C1–4, D1–4) which may have differential cervical cancer risk. Methods: A next-generation sequencing assay was used to whole-genome sequence 7116 HPV16-positive cervical samples from well-characterised international epidemiological studies, including 2076 controls, 1878 squamous cell carcinoma (SCC) and 186 adenocarcinoma/adenosquamous cell carcinoma (ADC), and to assign HPV16 sub-lineage. Logistic regression was used to estimate region-stratified country-adjusted odds ratios (OR) and 95%CI. Results: A1 was the most globally widespread sub-lineage, with others showing stronger regional specificity (A3 and A4 for East Asia, B1–4 and C1–4 for Africa, D2 for the Americas, B4, C4 and D4 for North Africa). Increased cancer risks versus A1 were seen for A3, A4 and D (sub)lineages in regions where they were common: A3 in East Asia (OR=2.2, 95%CI:1.0–4.7); A4 in East Asia (6.6, 3.1–14.1) and North America (3.8, 1.7–8.3); and D in North (6.2, 4.1–9.3) and South/Central America (2.2, 0.8–5.7), where D lineages were also more frequent in ADC than SCC (3.2, 1.5–6.5; 12.1, 5.7–25.6, respectively). Conclusions: HPV16 genetic variation can strongly influence cervical cancer risk. However, burden of cervical cancer attributable to different sub-lineages worldwide is largely driven by historical HPV16 sub-lineage dispersal. Keywords: HPV16, Cervical cancer, HPV carcinogenesis, HPV epidemiology, HPV genomics, Whole virus genome sequencing

The clinical manifestations of human papilloma virus (HPV) infection are vast, ranging from common warts to squamous cell carcinomas (SCCs). Immunodeficient populations are particularly susceptible to HPV infection in part because of deficiencies of cell-mediated immunity and diminished production of neutralizing antibodies.1 In particular, recipients of allogenic stem cell transplantation (allo-SCT) exhibit an increased risk for cutaneous SCC (cSCC) development, with a 20-year posttransplant incidence of 3.4%.2 Patients that have chronic graft versus host disease (cGVHD) are even more dramatically affected, with a risk of cSCC 5 times higher than that of the general population.3

Introduction Introduction of multimodality treatment as the standard of care for management of esophageal and gastroesophageal junction (GEJ) cancer over the last years has led to significant improvement in survival for patients with localized disease. Nevertheless, treatment with curative intent is not considered in the case of metastatic disease. We report a case of a locally advanced GEJ adenocarcinoma with solitary resectable synchronous metastases at the jejunum and a good response to neoadjuvant therapy followed by esophagectomy with curative intention. Case presentation This is the case of a patient with poorly differentiated adenocarcinoma of the GEJ with synchronous metastases at the jejunum. The patient underwent extensive work-up including PET-CT. The metastases at the jejunum were completely resected during an initial staging laparoscopy and there was no evidence of further metastatic disease. The patient received chemotherapy and re-staging showed remarkable tumor response. Esophagectomy with curative intent was performed. Histopathology showed complete pathologic response after chemotherapy. Although our patient had a stage IV disease at presentation, he remained metastasis-free for a significant period of time, with no evidence of any distant recurrence during a follow-up of 16 months after esophagectomy. Discussion and conclusions Synchronous metastasis to the small bowel from an esophageal carcinoma is a rare entity. Routine PET-CT in addition to conventional CT may assist in more precise staging of a patient with resectable disease. Stage IV esophageal cancer with limited and resectable metastatic disease and good tumor response to oncological therapy may be considered for treatment with potentially curative intent., Highlights • Synchronous metastasis to the small bowel from an esophageal carcinoma is a rare entity. • PET-CT in addition to conventional CT may assist in more precise staging of esophageal cancer. • Esophageal cancer with resectable metastases may be considered for treatment with curative intent.

Background Previous analysis showed that the incidence rates of skin cancer in Singapore increased from 1968 to 2006, especially among older Chinese, and particularly for basal cell carcinoma (BCC). Objective We updated the skin cancer incidence rates and time trends among the Chinese, Malays, and Indians in Singapore. Methods We analyzed the skin cancer incidence from the nationwide Singapore Cancer Registry from 1968 to 2016. Results Among 12,692 cases diagnosed from 1968 to 2016, there were 8367 (65.9%) cases of BCC, 3598 (28.3%) of squamous cell carcinoma (SCC), and 727 (5.8%) of melanoma. The mean ages at skin cancer diagnosis were 72.7 years for SCC, 66.9 years for BCC, and 59.8 years for melanoma. Sun-exposed areas accounted for 81.3% of BCCs, 61.6% of SCCs, and 26.7% of melanomas. The age-standardized incidence rate of cutaneous BCC was highest in the Chinese and increased by 2.5 fold over the study period, followed by a lower rate and slower increase in the Malays, and the lowest rate among the Indians. The SCC and melanoma incidences remained low in all 3 ethnicities during this study period. The Chinese had the highest relative risk for developing any skin cancer (P

A 45-year-old man (Case 1) from a rural area in the state of Rio de Janeiro, Brazil presented with a 2-year history of dry cough and an extensive ulcerated genital lesion. Chest radiography showed a bilateral perihilar infiltrate. A 56-year-old man (Case 2) from the countryside of Rio de Janeiro presented with a 14-month history of an ulcerated tongue, dysphagia, and weight loss. In both cases, clinical samples were collected for histologic examination using hematoxylin-eosin and Grocott methenamine silver stains.

As the major cell surface receptors for the extracellular matrix, integrins regulate adhesion and migration and have been shown to drive tumor growth and progression. Previous studies showed that mice lacking integrin α3β1 in the epidermis fail to form skin tumors during two-step chemical tumorigenesis, indicating a protumorigenic role for α3β1. Furthermore, genetic ablation of α3β1 in established skin tumors caused their rapid regression, indicating an essential role in the maintenance of tumor growth. In this study, analysis of immortalized keratinocyte lines and their conditioned media support a role for α3β1 in regulating the expression of several extracellular proteases of the keratinocyte secretome, namely BMP-1, matrix metalloprotease (MMP)-9, and MMP-3. Moreover, immunofluorescence revealed reduced levels of each protease in α3β1-deficient tumors, and RNA in situ hybridization showed that their expression was correspondingly reduced in α3β1-deficient tumor cells in vivo. Bioinformatic analysis confirmed that the expression of BMP1, MMP9, and MMP3 genes correlate with the expression of ITGA3 (gene encoding the integrin α3 subunit) in human squamous cell carcinoma and that high ITGA3 and MMP3 associate with poor survival outcome in these patients. Overall, our findings identify α3β1 as a regulator of several proteases within the secretome of epidermal tumors and as a potential therapeutic target.

Made available in DSpace on 2021-06-25T10:54:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-04-01 Department of Infectious Diseases Dermatology Diagnostic Imaging and Radiotherapy São Paulo State University (UNESP) Botucatu Medical School Department of Infectious Diseases Dermatology Diagnostic Imaging and Radiotherapy São Paulo State University (UNESP) Botucatu Medical School