Desmoplastic Melanoma Research Articles

TP53 mutation and tumoral PD-L1 expression are associated with depth of invasion in desmoplastic melanomas.

BackgroundDesmoplastic melanoma (DM) is a rare subtype of spindle cell malignant melanoma characterized by frequent local recurrences and hematogenous spread, but without molecular classification. The aim of the study was to investigate in a DM series the incidence of relevant gene alterations in cancer, the programmed death-ligand 1 (PD-L1) expression status and the association with clinicopathological features and melanoma progression.MethodsA total of 38 patients were included. Clinical follow-up and the histopathological features of all cases were retrospectively collected. PD-L1 expression by immunohistochemistry (IHC) and BRAF genomic alterations by real-time PCR were determined in 34 samples. Additionally, a molecular analysis by next-generation sequencing was performed in 25 DMs.ResultsTumors occurred predominantly in men (76%) and in the head and neck region (50%). Most tumors were pure DMs (66%), containing less than 10% of conventional melanoma. Overall, 48% of our cohort harbored TP53 mutations, most of them showing a molecular signature associated with ultraviolet (UV)-oncogenesis, and 29%, BRAF mutations. A positive correlation between TP53 with depth of invasion (P=0.005) and presence of elastosis (P=0.002) was found. High-expression of PD-L1 in tumor cells was observed in 38% of cases and correlated with depth of tumoral infiltration (P=0.003), TP53 (P=0.016), PD-1 (P<0.001) and tumor-infiltrating lymphocytes (TILS) (P<0.001). PD-L1 expression in immune cells correlated with PD-1 (P=0.006), tumoral PD-L1 expression (P=0.029) and TP53 mutation (P=0.002). Survival correlated with depth of invasion (P=0.003), stage of tumors (P=0.015), positive sentinel lymph node (P=0.004), lymph node metastasis (P=0.024) and distant metastasis (P<0.001).ConclusionsOur results suggest that progressed DMs with deep tumoral infiltration frequently harbor TP53 mutations, PD-L1 expression and present a high inflammatory response, probably related to adaptive immune resistance in this tumor-type.

Clinical and Demographic Profile of Cutaneous Melanoma: Pakistani Perspective

BACKGROUNDCutaneous melanomas (CMs) account for only a small proportion of skin cancers, however these are responsible for most skin cancer deaths. There has been a consistently increasing trend in their incidence across the globe.METHODSThis prospective case series study spanned over a period of three years. All patients with histologically confirmed CMs were included.RESULTSThere were 31 patients including 28 males and 3 females with the mean age of 58.25±11.33 years. The histological subtypes included 13 cases (41.93%) of nodular melanoma (NM), 11 patients (35.5%) of acral lentiginous melanoma (ALM), 3 cases (9.67%) of superficial spreading melanoma (SSM) and lentigo maligna melanoma (LMM) and one case (3.22%) of desmoplastic melanoma. Two patients (6.45%) presented with stage II, whereas 21 patients had (67.74%) stage III melanoma. There were 8 patients (25.80%) with stage IV. Time interval between onset of the lesion and first presentation to hospital ranged from 6 to 17 weeks with a mean of 12.45±3.2 weeks. The overall median survival for patients with stage III and IV was 8.75 months. The overall survival for stage II at one year was 100%.CONCLUSIONCMs more frequently affected males aged ≥58 years. Feet, face, trunk, hands and scalp were the affected anatomical body parts in decreasing order of frequency. NM and ALM were the more common histological subtypes. Majority of patients presented late and advanced stages of melanoma. Awareness about the sinister course of the disease will ensure early presentation with better treatment outcome.

Uncommon Subtypes of Malignant Melanomas: A Review Based on Clinical and Molecular Perspectives.

Malignant melanoma represents the most aggressive type of skin cancer. Modern therapies, including targeted agents and immune checkpoint inhibitors, have changed the dismal prognosis that characterized this disease. However, most evidence was obtained by studying patients with frequent subtypes of cutaneous melanoma (CM). Consequently, there is an emerging need to understand the molecular basis and treatment approaches for unusual melanoma subtypes. Even a standardized definition of infrequent or rare melanoma is not clearly established. For that reason, we reviewed this challenging topic considering clinical and molecular perspectives, including uncommon CMs—not associated with classical V600E/K BRAF mutations—malignant mucosal and uveal melanomas, and some unusual independent entities, such as amelanotic, desmoplastic, or spitzoid melanomas. Finally, we collected information regarding melanomas from non-traditional primary sites, which emerge from locations as unique as meninges, dermis, lymph nodes, the esophagus, and breasts. The aim of this review is to summarize and highlight the main scientific evidence regarding rare melanomas, with a particular focus on treatment perspectives.

Abstract 4342: Histological variants and sites of presentation of malignant melanoma in a resource poor setting: A histopathological review

Abstract Background: Melanoma is a malignant tumour that arises from melanocytic cells. The incidence is increasing worldwide in white population where fair skin people receive excessive sun exposure. Although relatively uncommon in Africa-Americans, recent trends shows increase incidence in Africa- Americans. Data on the incidence and biology of melanoma are few in Africa. This study review the variants and sites of melanoma in a resource poor setting in Nigeria with some immunohistochemical stains performed. Method: All cases of melanoma diagnosed in the Department of Pathology in a tertiary hospital in Nigeria over a three year period (2016-2018) were retrieved. Patient's information including site and age were also retrieved from their case notes. Immunohistochemistry using two antibodies S-100, HMB-45 was done. Results: A total 38 cases were seen during the study period with a male female ratio of 1:1.1. The age range was 5-80 years with a mean age of 48.8±18.1. The most common site for melanoma is the foot 19(50%), followed by the uvea 7(18.4%), skin and inguinal lymph node 4(10.5%), anorectal and conjunctiva had 2(5.3%). The commonest histological variant of melanoma was acral lentigenous melanoma 19(50%), Superficial spreading melanoma 4(10.5%), nodular melanoma 3(7.9%) and desmoplastic melanoma 1(2.6%). Immunohistochemistry was used on three cases to rule out differentials. Conclusion: Malignant melanoma in our setting is in contrast with African-Americans and Caucasians population base on site and histological type, hence future studies on molecular pathways of melanoma in Africa needs to be explored to show similarity or difference and the possibility of targeted immunotherapy. Citation Format: Kasimu Umar Adoke, Mohammed Faruk, Yawale Iliyasu, Saad Aliyu Ahmed. Histological variants and sites of presentation of malignant melanoma in a resource poor setting: A histopathological review [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4342.

Desmoplastic Melanomas Mimicking Neurofibromas.

Desmoplastic melanoma can be difficult to diagnose and on average have a significantly higher T stage at the time of diagnosis compared with conventional melanomas. Histologically, these tumors typically consist of spindle cells in a fibrous matrix. The spindle cells may display fibroblast and/or Schwann cell-like features. In this study, we describe the features of 12 cases of desmoplastic melanoma closely simulating neurofibroma. Although the spindle cells in these tumors may be indistinguishable from those of neurofibroma, features such as prominent fibroplasia (12/12), poor lateral circumscription (8/9), diffuse infiltration of subcutaneous tissue (7/9), and lymphoid aggregates (10/12) may be helpful clues to the diagnosis. No immunohistochemical markers were reliable in distinguishing neurofibroma-like desmoplastic melanomas from neurofibroma. Clinical follow-up was available in 8 cases, of which 4 were initially misdiagnosed as benign neoplasms and given no further re-excision. All 4 of these cases recurred; 2 of which showed transformation to a more aggressive phenotype.

Uncorrect diagnosis of tubercolar spondylodiscitis in aggressive and bone destructive metastasis of melanoma: A case report and literature review.

Differential diagnosis of destructive osteolytic spinal lesions can be a diagnostic challenge. In this study, we described a rare case of spinal metastases from primary desmoplastic melanoma which had incorrectly been diagnosed and treated as tuberculous spondylodiscitis. An 82-year-old male patient with ongoing low back pain and a history of lumbar localized Pott’s performed a lumbar spine MRI that showed osteolytic lesion with first hypothesis of spondylodiscitis L2-L3. The patient was hospitalized and cause of worsening of the lumbar pain underwent a following series of non-diagnostic CT-guided and open lumbar biopsy at L2-L3 with unsuccessful antibiotic-antitubercular therapy. A new MRI revealed a worsening of previous lesions, extension of the osteolytic lesion at the level of L1-L2 and L3-L4 with neurological impairment. The diagnosis of metastatic melanoma was obtained with surgical decompression and open posterior biopsy procedure. The case described is pathognomonic of the difficulty in detecting the correct diagnosis in front of similar clinical and radiological manifestations. The presence of a previous Pott’s disease in the same involved vertebral site was of crucial importance in deflecting the correct diagnostic classification of the pathology, which was possible to ascertain only following an extensive biopsy sampling in the last surgery performed.

Desmoplastic melanoma: an updated clinical review and the emerging role of genetic markers and immunotherapies.

Desmoplastic melanoma (DM) is a rare and histopathologically as well as prognostically distinct subset of melanoma that arises in chronically sun-damaged skin. DM is typically and relatively indolent in nature with most cases not progressing to metastatic disease. DM has been managed with both radiation and surgical approaches. Medical options for the treatment of metastatic DM have traditionally been limited. Recent advances in immunotherapies have shown promising responses in DM ushering in a new class of treatment options. Additionally, with the advent of whole exome sequencing, the genetic make-up of DM has been further characterized creating new possibilities for future targeted therapies.

Melanomas with activating RAF1 fusions: clinical, histopathologic, and molecular profiles

A subset of melanomas is characterized by fusions involving genes that encode kinases. Melanomas with RAF1 fusions have been rarely reported, mostly in clinical literature. To investigate this distinctive group of melanomas, we searched for melanomas with activating structural variants in RAF1, utilizing our case archive of clinical samples with comprehensive genomic profiling (CGP) by a hybrid capture-based DNA sequencing platform. Clinical data, pathology reports, and histopathology were reviewed for each case. RAF1 breakpoints, fusion partners, and co-occurring genetic alterations were characterized. From a cohort of 7119 melanomas, 40 cases (0.6%) featured fusions that created activating structural variants in RAF1. Cases with activating RAF1 fusions had median age of 62 years, were 58% male, and consisted of 9 primary tumors and 31 metastases. Thirty-nine cases were cutaneous primary, while one case was mucosal (anal) primary. Primary cutaneous melanomas showed variable architectures, including wedge-shaped and nodular growth patterns. Cytomorphology was predominantly epithelioid, with only one case, a desmoplastic melanoma, consisting predominantly of spindle cells. RAF1 5′ rearrangement partners were predominantly intrachromosomal (n = 18), and recurrent partners included MAP4 (n = 3), CTNNA1 (n = 2), LRCH3 (n = 2), GOLGA4 (n = 2), CTDSPL (n = 2), and PRKAR2A (n = 2), all 5′ of the region encoding the kinase domain. RAF1 breakpoints occurred in intron 7 (n = 32), intron 9 (n = 4), intron 5 (n = 2), and intron 6 (n = 2). Ninety-eight percent (n = 39) were wild type for BRAF, NRAS, and NF1 genomic alterations (triple wild type). Activating RAF1 fusions were present in 2.1% of triple wild-type melanomas overall (39/1882). In melanomas with activating RAF1 fusions, frequently mutated genes included TERTp (62%), CDKN2A (60%), TP53 (13%), ARID2 (10%), and PTEN (10%). Activating RAF1 fusions characterize a significant subset of triple wild-type melanoma (2.1%) with frequent accompanying mutations in TERTp and CDKN2A. CGP of melanomas may improve tumor classification and inform potential therapeutic options, such as consideration of specific kinase inhibitors.

Spectrum of Melanocytic Proliferation/Differentiation in a Large Series of Cutaneous Neurofibromas: An Under-Recognized Histopathologic Phenomenon and Potential Clue for Neurofibromatosis Type 1.

Neurofibromas (NFs) and melanocytic nevi share a common neuroectodermal origin and may occasionally show overlapping morphological features. The objective of this study was to assess the prevalence and spectrum of melanocytic proliferation/differentiation in NFs and also to test the hypothesis whether detection of this feature could be used as a potential clue for neurofibromatosis type 1 (NF-1). This was a retrospective study of 229 syndromic and 239 sporadic cutaneous NFs. Each case was assessed for an associated melanocytic component, both within the tumor and the overlying epidermis. Melan A immunohistochemistry was used in selected cases to further characterize this feature, particularly in diffuse NFs. An associated melanocytic component was detected in 77/229 syndromic and 12/239 sporadic cases (P < 0.00001). This was in the form of a junctional proliferation (lentiginous melanocytic hyperplasia or junctional nevus) or dermal differentiation (diffuse spindle cell or dermal nests of pigmented epithelioid melanocytes). Our study affirms that the spectrum of melanocytic proliferation/differentiation in NFs is broad and probably under-recognized. Awareness of this phenomenon is critical to avoid misdiagnosis of some diffuse NFs as primary melanocytic tumors, for example, desmoplastic melanomas. Given the strong link between dermal melanocytic differentiation and syndromic NFs, its detection could potentially serve as a useful clue for NF-1 in an appropriate clinical context.

Histopathologic Characteristics of Canine Desmoplastic Melanoma

An 11-year-old castrated male miniature Schnauzer, weighing 8 kg, presented with multiple masses on the humeri. Grossly, the masses were separated from the surrounding soft tissues. Desmoplastic melanoma is an uncommon tumor in dogs. Fine-needle aspiration cytology showed large spindle-shaped cells with a high nuclear-cytoplasmic ratio. Histopathology showed interlacing bundles of fibroblast-like cells, highly pleomorphic multinuclear cells, occasional atypical spindle cells separated by fibrocollagenous stroma, and lymphocyte aggregates admixed with abundant collagen. The tumors were diffusely positive for S100a, a strong marker for desmoplastic melanoma, and negative for desmin. Herein, we report the pathobiology of a rare, uncommon variant of melanoma in a dog.

The 2018 World Health Organization Classification of Cutaneous, Mucosal, and Uveal Melanoma: Detailed Analysis of 9 Distinct Subtypes Defined by Their Evolutionary Pathway.

There have been major advances in the understanding of melanoma since the last revision of the World Health Organization (WHO) classification in 2006. To discuss development of the 9 distinct types of melanoma and distinguishing them by their epidemiology, clinical and histologic morphology, and genomic characteristics. Each melanoma subtype is placed at the end of an evolutionary pathway that is rooted in its respective precursor, wherever appropriate and feasible, based on currently known data. Each precursor has a variable risk of progression culminating in its fully evolved, invasive melanoma. This review is based on the "Melanocytic Tumours" section of the 4th edition of the WHO Classification of Skin Tumours, published in 2018. Melanomas were divided into those etiologically related to sun exposure and those that are not, as determined by their mutational signatures, anatomic site, and epidemiology. Melanomas on the sun-exposed skin were further divided by the histopathologic degree of cumulative solar damage (CSD) of the surrounding skin, into low and high CSD, on the basis of degree of associated solar elastosis. Low-CSD melanomas include superficial spreading melanomas and high-CSD melanomas incorporate lentigo maligna and desmoplastic melanomas. The "nonsolar" category includes acral melanomas, some melanomas in congenital nevi, melanomas in blue nevi, Spitz melanomas, mucosal melanomas, and uveal melanomas. The general term melanocytoma is proposed to encompass "intermediate" tumors that have an increased (though still low) probability of disease progression to melanoma.

Radioterapia chorych na czerniaka

The role of radiotherapy (RT) in the treatment of melanoma is constantly evolving. Although melanoma is considered a radioresistant tumour with great potential for repairing sub-lethal damage, RT is an important component of treatment. Indications for sole or adjuvant radiotherapy of the primary lesion are limited and include desmoplastic melanoma, the presence of satellite lesions and/or in-transit metastases, the presence of melanoma cells in blood or lymphatic vessels, infiltration of nerve trunks, recurrence after previous surgery, and locally advanced melanomas of the head and neck region, especially inoperable. In the past, the most common indication for radiotherapy in melanoma was adjuvant treatment after lymphadenectomy in patients with risk factors for nodal recurrence (large metastasis diameter, multiple nodes involved, extracapsular extension). Adjuvant radiotherapy after lymphadenectomy has been shown to almost double the local control of the disease, but it does not affect patient survival and may also lead to significant toxicity. Nevertheless, currently the recommended approach is systemic adjuvant treatment (anti-PD-1 immunotherapy with pembrolizumab or nivolumab and, in the presence of BRAF mutation, BRAF/MEK inhibitors), and RT should be reserved for situations in which there are contraindications to other adjuvant treatment. Stereotactic techniques, including radiosurgery of brain metastases, are becoming more widely used. RT could be a definitive treatment for a limited number of metastases or in cases of limited progression on systemic treatment. The effectiveness of RT can be increased by combining with hyperthermia. An increasing number of reports suggest great benefit from the combination of RT with immunotherapy. At present, there is no convincing evidence supporting the combination of RT with molecularly targeted treatment, and according to emerging data on the toxicity of such a combination it should be used with caution.

SOX10 commonly stains scar in Mohs sections

Sox10 immunostaining is used for the diagnosis and margin evaluation of melanocytic lesions. Sox10 was initially thought not to stain fibrohistiocytic processes. Consequently, it was believed to reliably distinguish desmoplastic melanoma from scar. However, recent data from formalin sections suggest Sox10 is less specific than previously thought. In this report, we demonstrate that Sox10-stained Mohs sections commonly show strong, fractional staining of scar. When using Sox10 with frozen section immunohistochemistry, Mohs practitioners should recognize the potential of this marker to stain scar to avoid overdiagnosis of desmoplastic melanoma.

Desmoplastic melanoma

Desmoplastic melanoma is a rare variant of malignant melanoma that accounts for 1-5% of all forms of this neoplasm. It usually affects patients in the 6th and 7th decades of life. A 42-year-old female patient with progressive scalp lesion and diagnosis of desmoplastic melanoma is described, presenting good evolution with immunotherapy using Pembrolizumab, avoiding surgical treatment.

Remodeling the fibrotic tumor microenvironment of desmoplastic melanoma to facilitate vaccine immunotherapy.

Highly fibrotic and collagen-rich properties in desmoplastic melanoma (DM) result in an immune-suppressive fibrotic tumor microenvironment (TME) that resists clinical therapies. The different clinical and pathological properties, as compared to conventional melanoma, lead to delayed diagnosis and it is difficult to deliver drugs effectively due to fibrosis. Herein, we designed a chemo-immuno strategy focused on combining vaccination immunotherapy with multi-targeting sunitinib (SUN) nano-therapy to remodel TME and generate a robust immune response and a stronger synergistic anti-cancer effect. This strategy was evaluated side-by-side with non-desmoplastic melanoma and achieved significant improvement in therapeutic efficacy. The combination treatment was also synergistically assessed with the desmoplastic melanoma model. This strategy can remodel the fibrotic immunosuppressive TME and result in a robust cytotoxic T-cell response by reducing the collagen content, normalizing blood vessels, inhibiting tumor-associated fibroblasts and reducing high levels of suppressor immune cells. The modification of fibrotic immunosuppressive TME may serve as a good approach to further enhance immunotherapy for desmoplastic tumors.

Desmoplastic melanoma: The role of pure and mixed subtype in sentinel lymph node biopsy and survival.

BackgroundDesmoplastic melanoma (DM) is an uncommon type of melanoma. Two histological subtypes of DM can be distinguished: pure and mixed (PDM and MDM). We hypothesized that discrimination between these subtypes is associated with sentinel lymph node biopsy (SLNB) status and survival.MethodsClinicopathological data from PALGA, the Dutch Pathology Register were retrieved from patients diagnosed with DM in The Netherlands between 2000 and 2014. Clinical and pathological variables were extracted from pathology text files, including pure or mixed desmoplastic morphology. A Cox proportional hazard model was performed for overall and recurrence‐free survival (OS and RFS).ResultsA total of 239 patients with DM were included, representing 0.4% of all primary cutaneous melanoma in The Netherlands. A total of 114 PDM and 125 MDM patients were identified. MDM was significantly associated with positive SLNB status (P = .035). In multivariable analysis, age (HR 1.10, 95% CI 1.07‐1.14, P < .001) and ulceration (HR 1.98, 95% CI 1.05‐3.75, P = .036) were significant predictors for OS. For RFS, mixed subtype (HR 2.72 95% CI 1.07‐6.89, P = .035), male gender (HR 2.54, 95% CI 1.03‐6.27, P = .043), and Breslow thickness (HR 1.13 per mm, 95% CI 1.05‐1.21, P = .001) were significant predictors.ConclusionMDM is significantly associated with a positive SLNB status. Mixed subtype is significantly correlated with RFS, but not with OS. The distinction between pure and mixed desmoplastic subtype therefore seems to be of clinical importance.

The Importance of Using SOX10 for Exact Diagnosis of Desmoplastic Melanoma

Abstract Desmoplastic malignant melanoma is a rare variant of spindle cell melanoma commonly seen in older adults on sun-exposed areas. It accounts for 1–4 % of all cases of cutaneous melanoma. The common location of the desmoplastic melanoma is the head and neck region, whereasother sites are less common. A 45-year-old male presented with an proliferative growth on nose, after a trauma that was diagnosed as tumor. Histopathological examination with the help of wide panel of immunohistochemical methods and with emphasis on SOX10, was, after a broad diferential diagnosis concluded as a desmoplastic melanoma.

"Personalized Excision" of Malignant Melanoma-Need for a Paradigm Shift in the Beginning Era of Personalized Medicine.

The premises on which guidelines for the excision of primary cutaneous melanoma are based are illogical and fail to take into account peculiarities of the individual lesion. The horizontal margins of excision continue to be adjusted to the vertical thickness of the neoplasm, and recommended clinical margins do not reflect the histopathologic borders of melanoma. Micrographically controlled surgery has become accepted for acral melanomas and melanomas of the face and neck but not for melanomas on the trunk, arms, and legs, although the latter tend to be more sharply confined. Extending margins of excision for the purpose of removing inapparent metastases is fallacious because the latter are rare, their localization cannot be foretold, and satellite metastases are usually associated with distant metastases, so that patients do not profit from early removal of cutaneous lesions. The only meaningful objective of excision is complete removal of the primary melanoma. The success of excision must be controlled histopathologically. Because of limitations of the method, a histopathologic safety margin should be observed that must depend on the characteristics of the individual lesion. In sharply confined melanomas, a histopathologic margin of at least 1 mm is sufficient. In the case of poor demarcation, with solitary atypical melanocytes extending far beyond the bulk of the lesion, a broader histopathologic safety margin is advisable. Special caution should be exercised in the presence of regression and for desmoplastic melanomas, acral melanomas, and melanomas on the face and scalp. Instead of wide and deep excisions with standardized margins, "personalized excisions" are required for primary cutaneous melanoma. The concept of clinical safety margins is a relic of former times that has no place in modern medicine.

1355P - Tumour mutational burden and response to PD-1 inhibitors: An analysis of 89 cases of metastatic melanoma

BackgroundThe era of immunotherapy changed considerably prognosis of melanoma. Nonetheless, only around 40% can get benefit from this treatment, with no biomarkers identified for the therapeutic choice. On the basis of emerging clinical evidence, increased Tumor Mutational Burden (TMB) may be associated with higher sensitivity to immunotherapeutic agents. MethodsThe aim of this study was to analyze in advanced melanoma the relationship between the mutation load and: i) the histologic characteristics, ii) locations according to sun exposure and iii) response to PD-1 inhibitors, in advanced melanoma patients, in a retrospective multicentric analysis by sequencing using FoundationOne®. TMB was characterized as the number of somatic protein-coding base substitution or alterations mutations per megabase (Mb). DNA was extracted from paraffin embedded sections of primary tumor or metastasis. TMB was considered low between 1 and 5 muts/Mb, intermediate between 6 and 19, high if>20 muts/Mb. ResultsIn five centers in France, we included between October 2017 and March 2019 101 patients, aged from 16-year to 92-year-old, with metastatic melanomas. Results were available for 89 cases (12% DNA extraction failure). Acral (n=6, 20%), mucosal (n=5, 17%) and uveal melanoma (n=4, 13%) had a lower TMB compared to sun-exposed melanomas. No melanoma of non-sun-exposed areas had high burden (n=0); intermediate TMB was found in 21% (n=8) and low TMB in 63% of cases (n=19). Conversely, melanoma on chronic exposed areas (face and neck) had high TMB (5/7 cases; 71%). Complete and partial remission after 3 months of anti-PD-1 were more often observed in TMB high patients (n=4;20%) whereas in low and intermediate mutational patients, progression was found in respectively 62% (n=24) and 53% (n=16). ConclusionsTMB is affected by a variety of causes, including ultraviolet light in melanoma and smoking in lung cancer. Desmoplastic melanomas have been reported to have a high prevalence of somatic mutations whereas mucosal and acral have a 5-to 10-fold lower. Our study highlights the importance of TMB with higher response to PD-1 blockade. While it has to be confirmed, sun exposed areas or UV-signature may in be a valuable criterion in helping clinical decision-making. Editorial acknowledgementFoundation One Medicine and Roche Laboratories. Legal entity responsible for the studyFrench hospitals. FundingHas not received any funding. DisclosureC. Allayous: Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Amgen. All other authors have declared no conflicts of interest.

Endoscopic transpterygoid approach for resection of trigeminal neurotropic melanoma: Case report and technical note

BackgroundThe endoscopic transpterygoid approach to Meckel's cave is an established technique for resection of trigeminal schwannomas. Modern endoscopes provide excellent intraoperative visualization of anatomic structures and relevant pathology while the minimally-invasive nature of the procedure allows for rapid postoperative recovery. Neurotropic melanoma is a rare clinical entity that often involves the head and neck and can lead to cranial neuropathies when nerve invasion occurs. Pathological diagnosis of this lesion can be challenging due to its rarity and lack of classic melanoma markers such as Melan-A and HMB-45. Case descriptionIn this article, the authors describe the endoscopic transpterygoid approach to a neurotropic melanoma involving the maxillary and infraorbital nerves. To our knowledge, this is the first use of this surgical approach for resection of neurotropic melanoma. ConclusionsEndoscopic approaches to the trigeminal nerve allow for safe and effective resection of these lesions. However, a strong understanding of the microsurgical anatomy is necessary prior to such an undertaking.