Cancer in the Wilderness.

How a chance discovery in the Tasmanian rainforest changed the course of my scientific career.

Genome sequencing and analysis of the Tasmanian devil and its transmissible cancer.

The Tasmanian devil (Sarcophilus harrisii), the largest marsupial carnivore, is endangered due to a transmissible facial cancer spread by direct transfer of living cancer cells through biting. Here we describe the sequencing, assembly, and annotation of the Tasmanian devil genome and whole-genome sequences for two geographically distant subclones of the cancer. Genomic analysis suggests that the cancer first arose from a female Tasmanian devil and that the clone has subsequently genetically diverged during its spread across Tasmania. The devil cancer genome contains more than 17,000 somatic base substitution mutations and bears the imprint of a distinct mutational process. Genotyping of somatic mutations in 104 geographically and temporally distributed Tasmanian devil tumors reveals the pattern of evolution and spread of this parasitic clonal lineage, with evidence of a selective sweep in one geographical area and persistence of parallel lineages in other populations.

Intergenomic signatures of coevolution between Tasmanian devils and an infectious cancer.

Coevolution is common and frequently governs host-pathogen interaction outcomes. Phenotypes underlying these interactions often manifest as the combined products of the genomes of interacting species, yet traditional quantitative trait mapping approaches ignore these intergenomic interactions. Devil facial tumor disease (DFTD), an infectious cancer afflicting Tasmanian devils (Sarcophilus harrisii), has decimated devil populations due to universal host susceptibility and a fatality rate approaching 100%. Here, we used a recently developed joint genome-wide association study (i.e., co-GWAS) approach, 15 y of mark-recapture data, and 960 genomes to identify intergenomic signatures of coevolution between devils and DFTD. Using a traditional GWA approach, we found that both devil and DFTD genomes explained a substantial proportion of variance in how quickly susceptible devils became infected, although genomic architectures differed across devils and DFTD; the devil genome had fewer loci of large effect whereas the DFTD genome had a more polygenic architecture. Using a co-GWA approach, devil-DFTD intergenomic interactions explained ~3× more variation in how quickly susceptible devils became infected than either genome alone, and the top genotype-by-genotype interactions were significantly enriched for cancer genes and signatures of selection. A devil regulatory mutation was associated with differential expression of a candidate cancer gene and showed putative allele matching effects with two DFTD coding sequence variants. Our results highlight the need to account for intergenomic interactions when investigating host-pathogen (co)evolution and emphasize the importance of such interactions when considering devil management strategies.

Generation of Devil Facial Tumour Cells Co-Expressing MHC With CD80, CD86 or 41BBL to Enhance Tumour Immunogenicity.

The major histocompatibility complex (MHC) molecules play an integral role in the adaptive immune response to transmissible cancers through tumour antigen presentation and recognition of allogeneic MHC molecules. The transmissible devil facial tumours 1 and 2 (DFT1 and DFT2) modulate MHC-I antigen presentation to evade host immune responses and facilitate transmission of tumours cells to new Tasmanian devil (Sarcophilus harrisii) hosts. To enhance T-cell-driven tumour immunogenicity for vaccination and immunotherapy, DFT1 and DFT2 cells were co-transfected with (i) NLRC5 for MHC-I expression or CIITA for MHC-I and MHC-II expression, and (ii) a co-stimulatory molecule, either CD80, CD86 or 41BBL. The co-transfected DFT cells presented enhanced expression of MHC-I and/or MHC-II. As few devil-specific monoclonal antibodies exist, we used recombinant CTLA4 and 41BB fused to a fluorescent protein to confirm expression of cell surface CD80, CD86 and 41BBL. The capacity for these cells to induce T-cell responses including PD1 and IFNG expression was evaluated in in vitro co-culture assays with captive devil peripheral blood mononuclear cells (PBMCs). Although PBMC viability had increased, there was no evidence of enhanced T-cell activation. This system can be used to identify additional factors required to promote activation of naïve devil T-cells in vitro.

A Review of Topical Sirolimus for the Treatment of Facial Angiofibromas in Tuberous Sclerosis Complex.

OBJECTIVE: This article assesses the efficacy, safety, pharmacology, and clinical applications of topical sirolimus 0.2% gel for the treatment of tuberous sclerosis complex (TSC)-associated facial angiofibromas. DATA SOURCES: A review of the literature was conducted using the Medline (PubMed) and EMBASE databases using the keywords topical sirolimus, rapamycin, Hyftor, and tuberous sclerosis. STUDY SELECTION AND DATA EXTRACTION: Articles written in English and relevant to the topic were included. DATA SYNTHESIS: In the phase 2 trial, the mean improvement factor, a composite measure of improved tumor size and redness, was achieved in all patient groups (P < 0.001) with significant responses among the adult and pediatric subgroups at week 12. There were no serious adverse events recorded. In the phase 3 trial, 60% of participants responded to treatment in the sirolimus group compared with 0% in the placebo group with different response rates between the adult and pediatric subgroups at week 12. Sirolimus gel had no serious adverse events, and dry skin was the most common adverse reaction. Patients who had completed the 12-week trials were then enrolled in a long-term trial; angiofibromas had response rates of 78.2% to 0.2% sirolimus gel. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING DRUGS: Topical sirolimus 0.2% is a first-in-class, newly Food and Drug Administration (FDA)-approved, mammalian target of rapamycin (mTOR) inhibitor that is a promising and safe, noninvasive alternative to surgical procedures for TSC-associated angiofibromas. CONCLUSIONS: Topical sirolimus 0.2% gel is a moderately effective treatment for TSC-associated facial angiofibromas with an adequate safety profile.

Dermoscopy of Lentiginous Melanomas and Equivocal Benign Pigmented Macules of the Scalp: A Case-Control Multicentric Study.

INTRODUCTION: Although the dermoscopic features of facial lentiginous melanomas (LM), including lentigo maligna and lentigo maligna melanoma, have been extensively studied, the literature about those located on the scalp is scarce. This study aims to describe the dermoscopic features of scalp LM and assess the diagnostic accuracy of dermoscopy to discriminate them from equivocal benign pigmented macules. METHODS: Consecutive cases of scalp LM and histopathology-proven benign but clinically equivocal pigmented macules (actinic keratoses, solar lentigos, seborrhoeic keratoses, and lichen planus-like keratoses) from four referral centres were included. Dermoscopic features were analysed by two blinded experts. The diagnostic performance of a predictive model was assessed. RESULTS: 56 LM and 44 controls were included. Multiple features previously described for facial and extrafacial LM were frequently identified in both groups. Expert's sensitivity to diagnose scalp LM was 76.8% (63.6-87.0) and 78.6% (65.6-88.4), with specificity of 54.5% (38.9-69.6) and 56.8% (41.0-71.7), and fair agreement (kappa coefficient 0.248). The strongest independent predictors of malignancy were (OR, 95% CI) chaos of colour (15.43, 1.48-160.3), pigmented reticular lines (14.96, 1.68-132.9), increased density of vascular network (3.45, 1.09-10.92), and perifollicular grey circles (2.89, 0.96-8.67). The predictive model achieved 85.7% (73.8-93.6) sensitivity, 61.4% (45.5-75.6) specificity, and 81.5 (73.0-90.0) area under curve to discriminate benign and malignant lesions. A diagnostic flowchart was proposed, which should improve the diagnostic performance of dermoscopy. CONCLUSION: Both facial and extrafacial dermoscopic patterns can be identified in scalp LM, with considerable overlap with benign pigmented macules, leading to low specificity and interobserver agreement on dermoscopy.

Patient Satisfaction Following Primary Closure or Second Intention Healing After Conventional Nasal Skin Cancer Excision: A Cross-sectional Cohort Study.

BACKGROUND: Nasal reconstruction after conventional surgical excision (CSE) of nonmelanoma skin cancer (NMSC) can be challenging. After excision and before the pathologic report, a simple reconstruction is favored. Yet, little is known about patient satisfaction after primary closure and second intention healing. OBJECTIVE: Patient satisfaction after nasal defect reconstruction with primary closure or second intention healing, using the FACE-Q Skin Cancer. METHODS: All patients who underwent CSE of nasal NMSC with immediate primary closure or second intention healing between March 2018 and March 2020 at Máxima Medisch Centrum Veldhoven were identified and asked to complete the FACE-Q Skin Cancer. RESULTS: Of 183 patients, 140 patients completed the questionnaire. Fifty-five defects were closed by primary closure (38.5%) and 88 by second intention healing (61.5%). Thirty-one complications were reported (16.7%), of which 87.1% ( n = 27) after second intention healing ( p = .004). Both groups experienced high facial and scar satisfaction, low appearance-related distress, and no to minimal adverse effects. Second intention healing had 2.7 higher odds of achieving the maximum scar satisfaction score ( p = .02). CONCLUSION: This study shows high satisfaction on facial and scar appraisal, low appearance-related distress, and no to minimal adverse effects for second intention healing and primary closure after CSE of nasal NMSC.

Dermoscopic-Guided Shave Removal of Acquired Facial Melanocytic Nevi in Dark-Skinned Individuals.

BACKGROUND: Acquired melanocytic nevi are common benign skin lesions that require removal under certain circumstances. Shave removal is a straightforward treatment modality with a risk of recurrence. OBJECTIVE: To evaluate the outcome of dermoscopy-guided shave removal of acquired melanocytic nevi in the face of dark-skinned individuals who are more liable to postsurgical complications. METHODS: The study was conducted on 64 patients with acquired facial melanocytic nevi. Serial shave removal using a razor blade guided by dermoscopic examination was done until nevus-free tissue was seen, followed by electrocauterization of the base. Cosmetic outcome, patients' satisfaction, and recurrence rate were evaluated during follow-up. RESULTS: Excellent cosmetic outcome was achieved in 54.69% of patients, while 39.06% had an acceptable outcome, and 6.25% of patients had poor cosmetic outcome. Meanwhile, the recurrence rate was noticed in 5 cases only (7.8%). CONCLUSION: Dermoscopic-guided shave removal provides an easy procedure of treating common melanocytic nevi with an acceptable cosmetic result and a lower rate of recurrence even in patients with darker skin phenotypes.

A Systematic Review of Laser Treatment for Angiofibromas in Tuberous Sclerosis.

BACKGROUND: While mammalian target of rapamycin inhibitors have revolutionized the management of angiofibroma in tuberous sclerosis complex (TS), physical modalities such as laser are still indicated for recalcitrant lesions. OBJECTIVE: The authors performed a systematic review of the efficacy and safety of laser treatment for TS-related facial angiofibroma. METHODS: The electronic databases such as MEDLINE, Embase, PubMed, Cochrane Central Register of Controlled Trials, and Web of Science were searched from inception to October 10, 2023, for eligible records. RESULTS: Forty-seven articles met the inclusion criteria, representing a total of 217 patients with TS-related facial angiofibroma who received laser treatment. Several lasers have been trialed in patients including carbon dioxide ( n = 95, 43.7%), pulsed dye ( n = 21, 9.7%), argon ( n = 16, 7.4%), neodymium-doped: yttrium aluminum garnet ( n = 12, 5.5%), copper vapor ( n = 9, 4.1%), potassium titanyl phosphate ( n = 7, 3.2%), erbium: yttrium aluminum garnet ( n = 2, 0.9%), lasers and various combination therapies ( n = 55, 25.3%). CONCLUSION: Potassium titanyl phosphate, pulsed dye, and neodymium-dopsed:yttrium aluminum garnet lasers are better suited to manage the vascular components of angiofibroma while ablative lasers such as erbium: yttrium aluminum garnet and carbon dioxide lasers may present better options for lesions with a prominent fibrous component. While several lasers have been trialed with broadly favorable results, the low level of evidence precludes definitive conclusions, and no single laser appears superior.

Two Cases of Cutaneous Sarcomatoid Squamous Cell Carcinoma Resembling Cutaneous Giant Cell Tumor of Soft Tissue.

ABSTRACT: Cutaneous sarcomatoid squamous cell carcinoma is well-described with histology resembling pleomorphic undifferentiated sarcoma featuring collagenous or myxoid stroma with or without elements of keratinizing squamous carcinoma. This report presents 2 cases of dedifferentiated squamous cell carcinoma (SCC) composed of sheets of malignant mononuclear cells with malignant osteoclast-like multinucleated giant cells, extravasated blood, and hemosiderin resembling cutaneous giant cell tumor (cGCT). In the first case, an exophytic facial mass of a 96-year-old woman removed by shave showing extensive cGCT-like tumor but with microscopic elements of SCC in situ and positivity for cytokeratin 5/6 in the malignant spindle cells and SCC. The second case involved a 32-year-old man with a pedunculated penile mass removed by shave biopsy, displaying malignant cytology resembling cGCT, focal staining for cytokeratin AE1/AE3 and p63, and CD68 highlighting the osteoclast-like giant cells. Molecular analysis revealed CDKN2A, TP53, and TERT. Upon reexcision, case 2 showed focally invasive keratinizing SCC associated with differentiated penile intraepithelial neoplasia and lichen sclerosus. Skin specimens with an exophytic mass histologically resembling cGCT but with malignant cytology should be meticulously evaluated for elements of SCC. Molecular analysis, detecting mutations like H3F3 or HMGA2-NCOR2 fusion, can aid in distinguishing cutaneous sarcomatoid squamous cell carcinoma from GCT bone or GCT soft tissue.

The Application of "Table Tennis Racquet" Random Skin Flap in the Treatment of Facial Skin Carcinoma.

BACKGROUND: The repair of facial skin and soft tissue defects remains a clinical challenge. The author introduced a novel "table tennis racquet" random skin flap for wound repair after facial skin cancer excision and discussed its survival mechanisms. METHODS: A lateral mandibular neck skin flap shaped like a table tennis racquet with no well-known blood vessels at the narrow pedicle was designed in 31 cases to repair tissue defects. Among them, there were 8 cases of skin carcinoma in the frontotemporal area and 23 cases of skin carcinoma in the cheek. The flap area was 8.0 × 7.0 cm at maximum and 3.0 × 2.5 cm at minimum, with a pedicle width of 1.0-2.0 cm and a pedicle length of 2.0-6.0 cm. RESULTS: All 31 "table tennis racquet" random skin flaps survived, although there were 3 cases with delayed healing of distal flap bruising. All of them had an ideal local shape after repair with a concealed donor area and inconspicuous scars. CONCLUSIONS: This flap has a "table tennis racquet" shape with a pedicle without well-known blood vessels and has a length-to-width ratio that exceeds that of conventional random flaps, making it unconventional. Because of its long and narrow pedicle, it not only has a large rotation and coverage area but also can be designed away from the defect area, avoiding the defect of no donor tissue being localized near the defect. Overall, this approach is an ideal option for repairing tissue defects after enlarged excision of facial skin carcinoma.

Reconstruction of Multiple Lip and Facial Defects With Bipaddle and Sensate Radial Forearm Free Flap.

ABSTRACT: Free flaps and their modifications are used to reconstruct multiple large defects in the lip and face. In this study, we present our results on the reconstruction of these defects using bipaddle and sensate free radial forearm-palmaris longus flaps and subsequent revision surgeries. Patient medical records of 11 patients with a mean age of 63.9 ± 12.8 years were retrospectively reviewed. Functional oral competence, lip cosmetics, lip sensation, and donor forearm scars were evaluated using the drooling rating scale, visual analog scale, Semmes Weinstein Monofilament test, and patient and observer scar assessment scale, respectively. The mean dimensions of distal and proximal skin paddles of bipaddle free radial forearm-palmaris longus flaps were 12.7 ± 9.9 and 20.5 ± 3.8 cm2. Mean lengths of the bridge and proximal pedicles were 4.7 ± 1.6 and 5.5 ± 0.7 cm. All the flaps survived. No drooling was observed in the 2 patients without lower lip defects. The mean drooling scores of the 9 patients with lower lip defects were statistically different (Analysis of Variance, pANOVA < 0.00001) at 3, 6, 9, and 12 months postoperatively. The differences between 3 and 12 months were the most significant (pANOVA < 0.00001, pTUKEY < 0.000001). The lip sensation and drooling scores showed a strong positive correlation (r = 0.8504). All patients were able to speak fluently, drink fluid without leakage, and blow a balloon easily. All patients and observers were satisfied with the lip cosmetics, with no significant difference between satisfaction scores (P = 0.087615).There was a statistically significant difference (P < 0.00001) between mean sensation scores of surrounding healthy lip (2.94 ± 0.27) and free flaps (4.15 ± 0.4). All the donor scars healed uneventfully.

Use of Free Internal Mammary Artery Perforator Flap Harvested With Minimally Invasive Approach for Facial Reconstruction: Report of Two Cases.

The internal mammary artery perforator (IMAP) flap has been widely used for chest wall and neck reconstruction. The color of its skin paddle closely resembles that of facial skin, making it attractive for facial reconstruction. However, there has been insufficient investigations reporting the use of free IMAP flap. Furthermore, even in such studies, somewhat invasive procedures, including rib cartilage resection, were employed to ensure sufficient pedicle length, potentially increasing donor morbidity. Our report presents two cases of successful facial defect reconstruction using a free IMAP flap harvested with minimal donor site damage, showing its feasibility. In the first case, a 48-year-old male underwent wide excision for a malignant melanoma on his right cheek, resulting in a 4 × 4.5 cm full-thickness defect. A free IMAP flap with a 2.5 cm pedicle, was harvested without rib cartilage resection, preserving IMA main trunk, and transferred with anastomosed to the angular vessels within the defect. The second patient presented with a 4.5 × 3.5 cm basal cell carcinoma on the left cheek, necessitating wide excision and leaving a 6 × 5 cm defect. A free IMAP flap was harvested with the same approach and successfully reconstructed the defect with connected to the superficial temporal vessels using vascular bridge. Both patients were discharged complication-free, with no recurrence during 24 and 15 months of follow-up, respectively. They were highly satisfied with the final skin color and texture outcomes. Harvesting a free IMAP flap while minimizing donor morbidity may offer an attractive option for facial reconstruction.

Long-Term Comparison of Esthetic Outcomes Between Hatchet and Transposition Flaps in Facial-Defect Reconstruction.

BACKGROUND: Transposition flaps are commonly used for facial-defect repair after wide excision of skin cancers. However, such repair often causes excessive tension at the donor site that can result in distortion of the adjacent area. The hatchet flap, a rotation-advancement flap, can prevent distortion by redistributing the donor site tension evenly to the recipient site. This study aims to compare the esthetic outcomes of the hatchet flap and transposition flap in facial-defect reconstruction. METHODS: We retrospectively included 50 patients who underwent facial reconstruction with the hatchet flap or transposition flap after excision of skin cancer. They were followed up for more than 6 months. At the last follow-up visit, the esthetic outcome was evaluated by subjective and objective assessments using the patients and observer scar assessment scale and Manchester scar scale. RESULTS: Thirty patients and 20 patients underwent reconstruction using the hatchet flap and the transposition flap, respectively. The total score from the patient and observer scar assessment scale was significantly lower in the hatchet flap group compared with the transposition flap group (p = 0.009). The Manchester scar scale showed a total score of 7.67 ± 2.2 for the hatchet flap and 9.95 ± 1.99 for the transposition flap: in the color (p < 0.001), distortion (p < 0.001), and texture (p < 0.02) categories, the hatchet flap yielded significantly better outcomes than the transposition flap. CONCLUSIONS: The hatchet flap had good esthetic outcome for facial reconstruction and could be a valuable option for reconstructing facial defects. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266.

Grid-Based Structural and Dimensional Skin Cancer Classification with Self-Featured Optimized Explainable Deep Convolutional Neural Networks.

Skin cancer is a severe and potentially lethal disease, and early detection is critical for successful treatment. Traditional procedures for diagnosing skin cancer are expensive, time-intensive, and necessitate the expertise of a medical practitioner. In recent years, many researchers have developed artificial intelligence (AI) tools, including shallow and deep machine learning-based approaches, to diagnose skin cancer. However, AI-based skin cancer diagnosis faces challenges in complexity, low reproducibility, and explainability. To address these problems, we propose a novel Grid-Based Structural and Dimensional Explainable Deep Convolutional Neural Network for accurate and interpretable skin cancer classification. This model employs adaptive thresholding for extracting the region of interest (ROI), using its dynamic capabilities to enhance the accuracy of identifying cancerous regions. The VGG-16 architecture extracts the hierarchical characteristics of skin lesion images, leveraging its recognized capabilities for deep feature extraction. Our proposed model leverages a grid structure to capture spatial relationships within lesions, while the dimensional features extract relevant information from various image channels. An Adaptive Intelligent Coney Optimization (AICO) algorithm is employed for self-feature selected optimization and fine-tuning the hyperparameters, which dynamically adapts the model architecture to optimize feature extraction and classification. The model was trained and tested using the ISIC dataset of 10,015 dermascope images and the MNIST dataset of 2357 images of malignant and benign oncological diseases. The experimental results demonstrated that the model achieved accuracy and CSI values of 0.96 and 0.97 for TP 80 using the ISIC dataset, which is 17.70% and 16.49% more than lightweight CNN, 20.83% and 19.59% more than DenseNet, 18.75% and 17.53% more than CNN, 6.25% and 6.18% more than Efficient Net-B0, 5.21% and 5.15% over ECNN, 2.08% and 2.06% over COA-CAN, and 5.21% and 5.15% more than ARO-ECNN. Additionally, the AICO self-feature selected ECNN model exhibited minimal FPR and FNR of 0.03 and 0.02, respectively. The model attained a loss of 0.09 for ISIC and 0.18 for the MNIST dataset, indicating that the model proposed in this research outperforms existing techniques. The proposed model improves accuracy, interpretability, and robustness for skin cancer classification, ultimately aiding clinicians in early diagnosis and treatment.

A case of melanoma in situ of the central forehead repair by V-Y advancement flap and Burow graft.

Large defects on the face after Mohs surgery have posed significant reconstructive challenges. A 90-year-old man presented with melanoma in situ of the central forehead, which resulted in a 4.5cmx4.3cm defect after multiple stages of Mohs surgery. Although different approaches for forehead repair with nasal root involvement are possible, we demonstrate that the V-Y advancement flap and subsequent Burrow graft for nasal root repair represents a viable closure technique for large circular defects of the central forehead.

Fast and safe clinical response to sonidegib in a 98-year old woman affected by locally advanced basal cell carcinoma.

A 98-year-old woman presented with histologically confirmed locally advanced basal cell carcinoma of the face. A multidisciplinary approach excluded surgery because of the site near sensitive organs, extension, age, and comorbidities. Patient and caregivers declined radiotherapy considering the necessity of multiple hospital appointments. The patient was then placed on therapy with sonidegib, an oral inhibitor of the Hedgehog signaling pathway. There was a very rapid clinical response after only 28 days of treatment. The basal cell carcinoma improved progressively, with no adverse events reported. This case illustrates the efficacy and safety of this treatment in an advanced age patient. This treatment had a remarkably positive impact on quality of life, including that of the caregivers.

The Free Flap Reconstruction of Facial Defects after Squamous Cell Carcinoma Excision.

Background and Objectives: Cutaneous squamous cell carcinoma is the second most common skin cancer. There are many methods for the reconstruction of facial subunit defects after skin cancer excision. The face is vital to a person's life and should be reconstructed considering functional and aesthetic aspects. Despite a variety of flap types and techniques, it is still challenging to meet the various demands. The aim of this study was to compare free flaps for facial reconstruction after resection of cutaneous squamous cell carcinoma. Materials and Methods: This study included 14 patients from January 2021 to June 2023. Patients who underwent facial SCC resection and subsequent reconstruction using free flaps were analyzed retrospectively. Age, sex, and localization were recorded. Follow-ups ranged from 5 to 21 months, with an average of 13 months. Results: All free flaps survived well except one case of partial flap necrosis. In most patients, good to excellent functional and aesthetic results were obtained. The donor site healed uneventfully in all patients. Conclusions: Free flap reconstruction is an excellent choice in wide skin oncologic defects. In terms of texture, it also could be a good surgical method. The use of a fraxel laser can progressively facilitate improved color matching with the surrounding skin.

Congenital orofacial teratoma in a 22-week foetus.

No abstract available.

The differentiation state of the Schwann cell progenitor drives phenotypic variation between two contagious cancers.

Contagious cancers are a rare pathogenic phenomenon in which cancer cells gain the ability to spread between genetically distinct hosts. Nine examples have been identified across marine bivalves, dogs and Tasmanian devils, but the Tasmanian devil is the only mammalian species known to have given rise to two distinct lineages of contagious cancer, termed Devil Facial Tumour 1 (DFT1) and 2 (DFT2). Remarkably, DFT1 and DFT2 arose independently from the same cell type, a Schwann cell, and while their ultra-structural features are highly similar they exhibit variation in their mutational signatures and infection dynamics. As such, DFT1 and DFT2 provide a unique framework for investigating how a common progenitor cell can give rise to distinct contagious cancers. Using a proteomics approach, we show that DFT1 and DFT2 are derived from Schwann cells in different differentiation states, with DFT2 carrying a molecular signature of a less well differentiated Schwann cell. Under inflammatory signals DFT1 and DFT2 have different gene expression profiles, most notably involving Schwann cell markers of differentiation, reflecting the influence of their distinct origins. Further, DFT2 cells express immune cell markers typically expressed during nerve repair, consistent with an ability to manipulate their extracellular environment, facilitating the cell's ability to transmit between individuals. The emergence of two contagious cancers in the Tasmanian devil suggests that the inherent plasticity of Schwann cells confers a vulnerability to the formation of contagious cancers.