Mesenchymal plasticity of devil facial tumour cells during in vivo vaccine and immunotherapy trials.

Immune evasion is critical to the growth and survival of cancer cells. This is especially pertinent to transmissible cancers, which evade immune detection across genetically diverse hosts. The Tasmanian devil (Sarcophilus harrisii) is threatened by the emergence of Devil Facial Tumour Disease (DFTD), comprising two transmissible cancers (DFT1 and DFT2). The development of effective prophylactic vaccines and therapies against DFTD has been restricted by an incomplete understanding of how allogeneic DFT1 and DFT2 cells maintain immune evasion upon activation of tumour-specific immune responses. In this study, we used RNA sequencing to examine tumours from three experimental DFT1 cases. Two devils received a vaccine prior to inoculation with live DFT1 cells, providing an opportunity to explore changes to DFT1 cancers under immune pressure. Analysis of DFT1 in the non-immunised devil revealed a 'myelinating Schwann cell' phenotype, reflecting both natural DFT1 cancers and the DFT1 cell line used for the experimental challenge. Comparatively, immunised devils exhibited a 'dedifferentiated mesenchymal' DFT1 phenotype. A third 'immune-enriched' phenotype, characterised by increased PDL1 and CTLA-4 expression, was detected in a DFT1 tumour that arose after immunotherapy. In response to immune pressure, mesenchymal plasticity and upregulation of immune checkpoint molecules are used by human cancers to evade immune responses. Similar mechanisms are associated with immune evasion by DFTD cancers, providing novel insights that will inform modification of DFTD vaccines. As DFT1 and DFT2 are clonal cancers transmitted across genetically distinct hosts, the Tasmanian devil provides a 'natural' disease model for more broadly exploring these immune evasion mechanisms in cancer.

Clinical efficacy of Mohs surgery combined with topical photodynamic therapy for facial basal cell carcinoma.

PURPOSE: The purpose of this study is to investigate the clinical efficacy of Mohs surgery in combination with topical photodynamic therapy (PDT) for facial basal cell carcinoma. PATIENTS AND METHODS: Eighty-six patients with facial basal cell carcinoma treated in our department from April 2011 to December 2013 were included. Mohs surgery was used to remove the lesions followed by direct suturing, skin flap grafting, or medium thickness free-skin grafting to repair the incisions. Topical PDT was performed three times, at an interval of 2 weeks, immediately after the sutures were removed. The patients were followed up for 2 years after the operation to evaluate tumor recurrence. RESULTS: Recurrence was not observed within 1 year after Mohs surgery combining PDT; however, one case of recurrence was found at the 2-year follow-up. CONCLUSION: The efficacy of Mohs surgery combining topical PDT is a definite treatment for facial basal cell carcinomas, as it reduced the tumor recurrence rate and maintained the relative integrity of the local tissues and appearance. This method could be a new effective treatment method for the facial basal cell carcinoma.

[Facial skin cancers: Comparison of opinions in French multidisciplinary team meetings]. / Cancers cutanés de la face : avis comparés de réunions de concertation pluridisciplinaire françaises.

BACKGROUND: The aim of our study was to evaluate the diversity, or homogeneity, of recommendations made in multidisciplinary team meetings (MTM) concerning the management of facial skin cancers in France, and to analyze the determinants thereof. PATIENTS AND METHODS: We contacted a panel of dermatology and ENT multidisciplinary teams (MDT) and collected their recommendations made at meetings regarding 3 clinical cases: squamous cell carcinoma in a renal transplant patient with an incomplete excision margin (case 1), locally advanced basal cell carcinoma (case 2), and lentigo maligna (case 3). The responses were analyzed globally and then based on 2 subgroups defined by the presence or absence of a dermatologist in the MTM. The effect of the makeup of the MTM (based on the presence of a dermatologist, a plastic surgeon, an oncologist and an ENT specialist) was evaluated for the main therapeutic proposals. RESULTS: The opinions of the 45 MDMs that responded to the survey were mixed for the three cases as regards important elements such as the indication of surgical revision for case 1, the proposal of an alternative treatment to surgery for case 2, and monitoring arrangements for case 3. Certain proposals were associated with the presence of a dermatologist in the MTM, such as discussion of adaptation of immunosuppressive treatment and details of the surgical margins to be applied for case 1, as well as simple monitoring and details of monitoring arrangements in case 3. CONCLUSION: It is important to maintain dermatologists in MTMs on account of their expertise in all therapeutic areas concerning skin cancers.

Cutaneous squamous cell carcinomas on special locations: perioral, periocular and genital area.

If tumours arise in special locations such as around the eyes, mouth or in the genital area, patients and physicians are challenged by the need for complete removal of the tumour with safety margins and high demands on function and aesthetic aspects. Treatment should be performed by specialized physicians including ophthalmologists, head and neck surgeons, surgical, medical and radiation oncologists. The first-line treatment for most cutaneous malignancies is surgical excision; however, in several situations, such as well-differentiated cutaneous squamous cell carcinomas (cSCC) in the periocular or anal region, radiotherapy is a very reasonable and sometimes treatment of first choice, especially in patients with advanced age. In periocular SCC, radiotherapy with superficial x-ray combined with eye shielding, while in anal SCC, radiotherapy combined with chemotherapy is recommended. However, after failure of local treatment options including surgery and radiotherapy, systemic medications are indicated in order to achieve tumour control or cure. Systemic therapies include immunotherapy, targeted therapy or chemotherapy. Preventive strategies are based on UV protection in facial, and vaccination in HPV associated anogenital SCCs.

Maintaining Quality of Life: Electrochemotherapy for Palliative Periorbital Malignancy.

Electrochemotherapy has been used successfully for treatment of recurrent head and neck skin cancers and skin metastasis. It combines both electroporation and chemotherapy. The authors report 4 patients, who all had metastatic periorbital malignancy. These patients were palliative with widespread metastatic malignancy. All patients had either already had multiple procedures or declined surgical resection and preferred less involved measures. The authors report technique and outcomes. Patient 1: 83-year-old man with recurrent malignant melanoma (MM) nodules (BRAF negative) in the left medial orbit and medial canthal area after rhinectomy and previous resections. Patient 2: 72-year-old man with metastatic MM who developed painful and unsightly metastatic nodules on the right and left forehead and the left medial canthus. Patient 3: 93-year-old man with background of widespread multiple myeloma, considered palliative. He developed a left forehead SCC, apparent as a fungating ulcer, which caused significant pain due to perineural invasion. Patient 4: 91-year-old woman with recurrent metastatic sebaceous cell carcinoma of the left lower eyelid obstructing her vision. All patients experienced an improvement in their pain and quality of life. None of the patients developed any significant periorbital inflammation or adverse complications. Electrochemotherapy may be a useful palliative treatment for periorbital tumors. It improves pain and reduces tumor volume. It can be considered for tumors where palliative radiotherapy may be contraindicated.Electrochemotherapy is a useful palliative treatment for metastases to the periorbital area, improving pain and size of the tumors.

Management of a Large Congenital Hemangioma Obstructing Visual Axis: A Case Report and Review of Literature.

Congenital hemangiomas comprise a subset of vascular tumors with clinicopathologic features that are distinct from the more common infantile hemangioma. The authors present a patient with a large congenital hemangioma involving the forehead and brow which obstructed the visual axis and created significant risk for deprivational amblyopia. Management of the congenital hemangioma involved customized headgear to clear the visual axis and early vascular embolization of feeder vessels with the subsequent successful surgical resection at 23 days of life.A large amblyogenic congenital hemangioma required a multidisciplinary approach involving early vascular embolization of feeder vessels and subsequent surgical resection at 23 days of life.

The Management and Prognosis of Facial and Scalp Angiosarcoma: A Retrospective Analysis of 15 Patients.

BACKGROUND: Angiosarcomas are extremely aggressive malignant tumors that arise from vascular endothelial cells. The risk factors, etiology, prognostic factors, and optimal management strategies for angiosarcomas are as yet unknown. METHODS: We retrospectively analyzed data from 15 patients who were treated in Asan Medical Center, Seoul, Republic of Korea, in the past 12 years, to assess the effect of different treatment modalities and reconstructive methods on the locoregional recurrence, metastasis, and overall survival. RESULTS: A total of 15 patients were identified (median age at diagnosis, 72 years; range, 61-82 years). Median tumor size was 6 cm. Median follow-up was 287 days. The median overall survival was 14.96 months; a total of 13 (87%) patients had died by the end of the study.The median locoregional recurrence, metastasis, and overall survival were 7.3, 6.5, and 16.7 months, respectively. On univariate analysis, the use of adjuvant therapy after surgery (vs surgery without adjuvant therapy) was associated with delayed median time to detection of recurrence (7.9 months vs 3.1 months, respectively; P = 0.825), delayed median time to metastasis (8.7 months vs 3.1 months, respectively; P = 0.191), and better median overall survival (7.3 months vs 3.1 months, respectively; P = 0.078).The use of flap versus skin graft as a reconstructive method was associated with delayed median recurrence (8.75 vs 7.32 months, respectively; P = 0.274) and earlier median metastasis (3.75 vs 6.53 months, respectively; P = 0.365), but the same median overall survival of 16.7 months (P value: 0.945) and tumor smaller or bigger than 5 cm show earlier median time to detection of recurrence (4.17-7.32 months; P = 0.41), earlier median time to metastasis (3.75-6.53 months; P = 0.651), but better median overall survival of 18.21 versus 16.7 months, respectively (P = 0.111). CONCLUSIONS: Multimodal treatment that combines surgery with adjuvant therapy is the best management strategy that influences survival positively in patients with angiosarcoma. The study shows that the reconstructive method does not affect the prognosis in these patients. So it is better to choose the simplest suitable resection and reconstructive method with the least complications and to avoid unnecessary procedures.

Advances in Immunotherapy and Periocular Malignancy.

Immunotherapy has significantly advanced the field of oncology in recent decades. Understanding normal immunosurveillance, as well as the ways in which tumor cells have evolved to evade it, has provided the knowledge for development of drugs that allow one's own immune system to target and destroy malignant cells (immunotherapy). Cutaneous malignancies are particularly sensitive to this class of drugs. In a very sensitive anatomic region such as the periocular tissue, where surgical excision may come with significant morbidity, this technology has had a strong impact in the successful treatment of historically challenging tumors.

Devil Facial Tumours: Towards a Vaccine.

The Tasmanian devil is the only mammalian species to harbour two independent lineages of contagious cancer. Devil facial tumour 1 (DFT1) emerged in the 1990s and has caused significant population declines. Devil facial tumour 2 (DFT2) was identified in 2014, and evidence indicates that this new tumour has emerged independently of DFT1. While DFT1 is widespread across Tasmania, DFT2 is currently found only on the Channel Peninsula in south east Tasmania. Allograft transmission of cancer cells should be prevented by major histocompatibility complex (MHC) molecules. DFT1 avoids immune detection by downregulating MHC class I expression, which can be reversed by treatment with interferon-gamma (IFNγ), while DFT2 currently circulates in hosts with a similar MHC class I genotype to the tumour. Wild Tasmanian devil numbers have not recovered from the emergence of DFT1, and it is feared that widespread transmission of DFT2 will be devastating to the remaining wild population. A preventative solution for the management of the disease is needed. Here, we review the current research on immune responses to devil facial tumours and vaccine strategies against DFT1 and outline our plans moving forward to develop a specific, effective vaccine to support the wild Tasmanian devil population against the threat of these two transmissible tumours.

Head and neck pleomorphic myxoid liposarcoma in a child with Li-Fraumeni syndrome.

INTRODUCTION: Pleomorphic myxoid liposarcoma is a rare and aggressive cancer seen in the pediatric population that has been previously associated with hereditable cancer disorders like Li Fraumeni syndrome. We present a case report and review of the relevant literature. CASE PRESENTATION: Pleomorphic myxoid liposarcoma presenting as a second primary tumor in a child with a strong family history for cancer led to diagnosis of Li-Fraumeni syndrome, which is associated with TP53 tumor suppressor gene inactivation. MANAGEMENT AND OUTCOME: The tumor was fully excised, but postoperative radiation was deferred to limit future radiation-induced tumorgenesis. DISCUSSION: Pleomorphic myxoid liposarcoma is rare but aggressive, and should prompt caregivers to test for potential hereditable cancer disorders. Li-Fraumeni syndrome is associated with early onset neoplasia and development of recurrent primary tumors. Its presence affects treatment decisions and methods of surveillance. Chemoradiation should be used judiciously in this population.

An Unusual Presentation of Merkel Cell Carcinoma in a HIV Patient: A Case Report and Literature Review.

Merkel cell carcinoma (MCC) is a rare, rapidly growing, aggressive neuroendocrine skin cancer that generally arises on sun-exposed areas of body such as head, neck, upper limbs, and shoulders of people with light complexity. Typically, MCC presents as shiny, flesh-colored or bluish-red, intracutaneous nodule, possibly with ulceration or crusting. In most of the cases, there is an association with Merkel cell polyomavirus. Even though these are very aggressive tumors, early detection and treatment has always given favorable outcome. There seems to be no consensus in definite prognostic markers, and advanced stages have the worst outcome even with treatment. There has been a recent trend in using PD-I/PD-L1 target therapy rather than chemotherapy in these cancers and have shown to improve survival by many months. In this article, we report a very unusual presentation of MCC first found on left frontoparietal skull as an 8-cm diameter fixed, subcutaneous mass without any typical features of MCC and was found to have metastatic spread to lung and liver. The patient was treated with palliative radiotherapy to brain and chemotherapy with cisplatin/etoposide with addition of immunotherapy later.

Face and Scalp Basal Cell Carcinoma Treatment: A Review of the Literature.

Basal cell carcinoma (BCC) is the most frequent skin cancer and is characterized by slow growth, even if it can be locally invasive and rarely metastasizes. Many different phenotypic presentations and histopathologic subtypes have been described, and the current guidelines subdivide BCCs into low-risk (nodular and superficial) and high-risk subtypes (micronodular, infiltrating, and morphoeic BCC and those with squamous differentiation). Dermoscopy allows the identification of the features associated with these different subtypes. Compared with the low-risk forms of BCC, more aggressive ones tend to undergo more frequently incomplete surgical excision and perineural invasion, so the identification of these lesions before surgery is extremely important. The gold standard of treatment is surgery, particularly for the H region of the face and infiltrative lesions, but other options are available and selected according to many variables, including body area, age, comorbidities, and clinical, dermoscopic, and histopathological features of the lesion. Moreover, the possible complications of surgical approaches, namely healing defects, failure of skin grafts, and wound infection, should be considered. In this review we discuss the management of BCC localized on the face and scalp, according to the currently available treatment options.

Patient-reported outcome measures for facial skin cancer: a systematic review and evaluation of the quality of their measurement properties.

BACKGROUND: Skin cancer is the commonest malignancy worldwide, often occurring on the face. Both the condition and treatment can lead to scarring and facial disfigurement, affecting a patient's health-related quality of life (HRQoL), which can be measured using patient-reported outcome measures (PROMs). OBJECTIVES: This systematic review identifies PROMs for facial skin cancer and appraises their methodological quality and psychometric properties using up-to-date methods. METHODS: MEDLINE, Embase, PsycINFO, Cochrane and CINAHL were searched systematically in accordance with PRISMA guidelines, identifying all PROMs designed for or validated in facial skin cancer. Methodological quality and evidence of psychometric properties were assessed using the COnsensus-based Standards for the Selection of Health Measurement INstruments (COSMIN) checklist and criteria proposed by Terwee and colleagues. A best-evidence synthesis and assessment of instrument focus on post-resection reconstruction was also performed. RESULTS: We included 24 studies on 11 PROMs. Methodological quality and psychometric evidence was variable, with the Patient Outcome of Surgery - Head/Neck (POS-H/N), Skin Cancer Index (SCI), Skin Cancer Quality of Life Impact Tool (SCQOLIT) and Essers and colleagues demonstrating the greatest level of validation. None scored well in their relevance to post-skin cancer reconstruction of the face. CONCLUSIONS: This systematic review critically appraises PROMs for facial skin cancer using internationally accepted criteria. The identified PROMs demonstrate a variation in the quality of validation performed, with a need to improve this across all PROMs in the field. Only through improving the quality of available PROMs and their focus on the post-treatment aesthetic and functional outcome will we be able to truly appreciate the concerns of our patients and improve the management of facial skin cancer.

"Chemical" surgery in treating basal cell carcinoma in elderly.

The incidence of basal cell carcinoma (BCC) has been increasing in the last decades due to population aging and precise diagnosis. The difficulty that physicians face frequently is related to the treatment decision for BCC; when treating BCC, correct and personalized choices must be taken into consideration by selecting from a large variety of therapeutic options such as: surgical excision ("the golden standard therapy"), electrodessication, cryosurgery, radiation therapy, laser, photodynamic therapy, curettage, topical treatment (imiquimod, 5-fluorouracil, vismodegib), or combining different treatments. The present authors present series of cases of patients diagnosed with BCC, highlighting that "chemical surgery" using 70% trichloroacetic acid could be a valuable option in the treatment of nonaggressive BCC of the face.