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.

[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.

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.

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.

"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.

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.

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.

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.

CO2 laser and photodynamic therapy: Study of efficacy in periocular BCC.

Basal cell carcinoma (BCC), the most common type of skin cancer in the world, usually arises in sun-exposed areas of the skin. The therapeutic approach to periocular BCC has changed in the last few years. Currently the treatment, considering the delicate localization of the disease, must not only ensure complete recovery from the neoplastic disease, but must also satisfy functional and aesthetic criteria. In this study we tried to evaluate the efficacy of CO2 laser and photodynamic therapy in periocular BCC.

Treatment of cutaneous angiosarcoma of the scalp and face in Chinese patients: local experience at a regional hospital in Hong Kong.

INTRODUCTION: Angiosarcoma is a rare aggressive sarcoma that occurs mostly in the skin of the head and neck in the elderly population. The optimal management is dubious and most studies are from Caucasian populations. We aimed to examine the treatment and outcome of this disease in Chinese patients. METHODS: Data of patients with histopathologically verified cutaneous angiosarcoma of the head and neck during December 1997 to September 2016 were retrieved from our hospital cancer registry. The demographic data, clinicopathological information, modality of treatment, and outcomes were reviewed. RESULTS: During the study period, 17 Chinese patients were treated. Their median age was 81 years. The tumours were present in the scalp only (n=11), face only (n=4), or both scalp and face (n=2). Only two patients had distant metastases. The modalities of treatment were surgery (n=6), surgery and adjuvant radiotherapy (n=1), palliative radiotherapy (n=5), or palliative chemotherapy (n=3). The remaining two patients refused any treatment initially. Of the seven patients treated surgically, there were four local and two regional recurrences. The median time to relapse was 7.5 months. Overall, 16 patients had died; causes of death were disease-related in 12 whereas four other patients died of inter-current illnesses. One patient was still living with the disease. The median overall survival was 11.1 months and the longest overall survival was 42 months. CONCLUSION: The outcome of angiosarcoma in our series is poor. A high index of suspicion is mandatory for prompt diagnosis. Adjuvant radiotherapy is recommended following surgery. The benefit and role of systemic treatment in various combinations with surgery or radiotherapy require further study.

Periorbital melasma: Hierarchical cluster analysis of clinical features in Asian patients.

BACKGROUND: Studies have shown melasma lesions to be distributed across the face in centrofacial, malar, and mandibular patterns. Meanwhile, however, melasma lesions of the periorbital area have yet to be thoroughly described. METHODS: We analyzed normal and ultraviolet light-exposed photographs of patients with melasma. The periorbital melasma lesions were measured according to anatomical reference points and a hierarchical cluster analysis was performed. RESULTS: The periorbital melasma lesions showed clinical features of fine and homogenous melasma pigmentation, involving both the upper and lower eyelids that extended to other anatomical sites with a darker and coarser appearance. The hierarchical cluster analysis indicated that patients with periorbital melasma can be categorized into two clusters according to the surface anatomy of the face. Significant differences between cluster 1 and cluster 2 were found in lateral distance and inferolateral distance, but not in medial distance and superior distance. Comparing the two clusters, patients in cluster 2 were found to be significantly older and more commonly accompanied by melasma lesions of the temple and medial cheek. CONCLUSION: Our hierarchical cluster analysis of periorbital melasma lesions demonstrated that Asian patients with periorbital melasma can be categorized into two clusters according to the surface anatomy of the face.

B Cell Lymphoma Underlying Paraffinoma of Glabella.

Soft tissue reactions to paraffin include inflammation, fibrosis, disfigurement, and granulomatous inflammation with foreign body giant cell reaction. The authors report the case of a 77-year-old woman with cutaneous marginal zone B cell lymphoma located on glabella, arising in association with underlying paraffinoma. While it is unclear whether the implant directly contributed to the development of lymphoma, this association has not been previously documented, prompting this report.

The role of radiotherapy and intrathecal CNS prophylaxis in extralymphatic craniofacial aggressive B-cell lymphomas.

To define the role of radiotherapy and intrathecal prophylaxis in extralymphatic craniofacial involvement (ECFI) of aggressive B-cell lymphoma, we analyzed 11 consecutive German High-Grade Non-Hodgkin Lymphoma Study Group trials. ECFI occurred in 290/4155 (7.0%) patients (orbita, 31; paranasal sinuses, 93; main nasal cavity, 38; tongue, 27; remaining oral cavity, 99; salivary glands, 54). In a multivariable analysis adjusted for International Prognostic Index rituximab improved event-free and overall survival both in patients with and without ECFI. Three-year event-free (79% vs 79%; P = .842) and overall survival (86% vs 88%; P = .351) rates were similar in 145 patients receiving and 57 not receiving radiotherapy. Without rituximab, the 2-year cumulative rate of central nervous system (CNS) disease was increased in 205 ECFI patients compared with 2586 non-ECFI patients (4.2% vs 2.8%; P = .038), whereas this was not observed with rituximab (1.6% in 83 ECFI vs 3.4% in 1252 non-ECFI patients; P = .682). In 88 ECFI patients who received intrathecal prophylaxis with methotrexate, the 2-year rate of CNS disease was 4.2% compared with 2.3% in 191 patients who did not (P = .981). In conclusion, rituximab eliminates the increased risk for CNS disease in patients with ECFI. This retrospective analysis does not support intrathecal prophylaxis or radiotherapy to ECFI patients in complete remission/unconfirmed complete remission. These findings should be confirmed in a prospective study.

Cryosurgery during Imiquimod (Immunocryosurgery) for Periocular Basal Cell Carcinomas: An Efficacious Minimally Invasive Treatment Alternative.

BACKGROUND/AIM: Periocular basal cell carcinomas (pBCC) remain a treatment challenge. Our aim was to retrospectively evaluate the feasibility and efficacy of immunocryosurgery for the treatment of pBCC. METHODS: Immunocryosurgery is given in 5-week cycles of daily imiquimod, with cryosurgery on day 14. Patients treated between 1/1/2008 and 31/12/2014 were included in this study. RESULTS: Immunocryosurgery was offered to 19 patients. Of these, 16 (i.e., 6 males and 10 females, average age 74.9 years, median tumor diameter 15 mm, range 5-60 mm), with 1 tumor each, were treated. Six tumors (37.5%) were relapses after surgery and 2 were of metatypical histology. All BCC were high risk for recurrence after treatment; 10 tumors had 2 risk factors for relapse, 5 had 3, and 1 had 4. The follow-up period ranged between 3 and 60 months (average 25.6 months). Of the 16 tumors treated, 14 (all with a diameter <40 mm) cleared with immunocryosurgery (total efficacy 87.5%); 7 out of 16 tumors (44%; all with a diameter ≤20 mm) cleared with 1 conventional 5-week immunocryosurgery treatment cycle. Seven additional tumors (including 2 with a diameter >20 mm) required intensified treatment schemes (of up to 10 weeks) for clearance. The 2 tumors that did not clear responded partially and were also the 2 largest ones (diameter 40 and 60 mm). Of the 14 cleared tumors, 2 relapsed during follow-up; 1 cleared with immunocryosurgery. At the last examination during follow-up, 13 out of 16 (81%) patients were in sustained clinical remission. CONCLUSIONS: For most pBCC, immunocryosurgery is a feasible and efficacious alternative to surgical excision.

Sequential Curettage, 5-Fluorouracil, and Photodynamic Therapy for Field Cancerization of the Scalp and Face in Solid Organ Transplant Recipients.

BACKGROUND: Field cancerization with actinic keratoses and squamous cell carcinoma in situ (AK/SCCIS) represents a common therapeutic challenge in solid organ transplant recipients (SOTRs). These patients often show inadequate responses to methods traditionally used as monotherapy (e.g., topical chemotherapy). OBJECTIVE: To describe the clinical outcomes and feasibility of a sequential approach to treatment of field cancerization in SOTRs. METHODS: Four SOTRs with field cancerization of the scalp and/or face were treated using a sequential approach. Light curettage of hypertrophic lesions was followed by application of 5-fluorouracil 5% cream twice daily for 5 days and photodynamic therapy (PDT) with 1-hour incubation on day 6. Pain level during and after PDT was recorded. Photographs were obtained immediately before and after treatment and at follow-up appointments. RESULTS: All 4 patients tolerated this approach well and demonstrated excellent responses to treatment with complete or near-complete clinical resolution of AK/SCCIS lesions. Patients remained free of AK/SCCIS based on clinical examination 1 to 6 months after treatment. CONCLUSION: For SOTRs with field cancerization, sequential therapy represents a viable therapeutic regimen with good tolerability and durable clinical response. This approach warrants further investigation to determine which therapeutic combinations have optimal tolerability and efficacy.

Infantile hemangiomas, complications and treatments.

Infantile hemangiomas (IHs) are the most common vascular tumors of infancy. While the majority regress without the need for intervention, approximately 10%, often site dependent, can cause serious complications and require treatment. IH complications can be categorized as life threatening, obstructive, ulcerative or disfiguring. Life threatening complications include airway and hepatic IHs. Functional complications obstructing vital structures or impairing function include periocular, nasal, labial, parotid, auricular, and breast IHs. Local complications arise from ulceration or those in cosmetically sensitive areas. Therapeutic options for complicated IHs include pharmacologic (topical or systemic), surgical, or laser interventions. Topical agents are best employed for small, superficial, and localized IHs; while systemic therapy is reserved for larger IHs and those with more aggressive growth characteristics with propranolol as first-line therapy.

Infantile hemangiomas and structural anomalies: PHACE and LUMBAR syndrome.

In a subset of patients, infantile hemangiomas may be associated with structural anomalies. Structural anomalies may affect the upper body (PHACE Syndrome) or the lower body (LUMBAR Syndrome). Since their initial descriptions, improved understanding of these two syndromes has lead to recognition of a broader phenotypic spectrum than initially recognized. This paper aims to provide an updated review of the presentation, associated anomalies, and management of PHACE and LUMBAR syndromes, two well-characterized syndromes associated with IH.

Management of Giant Facial Neurofibroma With Intratumoral Hematoma in Neurofibromatosis Type 1 Patient.

Type-1 neurofibromatosis, a common autosomal dominant disease, is also known as von Recklinghausen disease. Surgical procedures to treat this condition are challenging because of the brittleness of the surrounding blood vessels and soft tissues that bring the risk of causing fatal bleeding. With improvements in neurovascular embolization procedures, some literatures have been published about the application of preoperative embolization for neurofibromatosis. This case report describes a 60-year-old female with Type-1 neurofibromatosis, who presented giant facial neurofibromas with intratumoral hemorrhage on both cheeks. This patient demonstrates that these huge and challenging lesions can be successfully treated with preoperative embolization and surgical treatment. We also discuss the timing of surgical treatment with such lesions.

Multiple Familial Trichoepithelioma Successfully Treated With CO2 Laser and Imiquimod.

A 33-year-old woman presented with more than 100 flesh-colored papules and nodules centrally located on the face (Figure 1). Since their first appearance at the age of 7, the lesions had increased in number and spread laterally from the nasolabial folds. She underwent surgical removal at age 10 with recurrence afterward. Her mother, maternal grandmother, and maternal great aunt have similar lesions on the face. Histopathologic examination confirmed the diagnosis of trichoepitheliomas and multiple familial trichoepithelioma (MFT).