Search

Resumen: El melanoma desmoplásico (MD) representa entre el 0,4-4% de todos los melanomas. Se presenta como un tumor constituido predominantemente por melanocitos fusiformes amelanóticos inmersos en un estroma colágeno abundante. Se clasifica en MD puro o mixto, basándose en la proporción de melanoma desmoplásico frente a la del melanoma no desmoplásico presente en el tumor infiltrante. En el MD puro el componente desmoplásico representa más del 90% del melanoma infiltrante mientras que, en el MD combinado o mixto, el componente desmoplásico representa menos del 90%.El MD es más frecuente en varones (ratio 1,7-2:1); la edad media al diagnóstico oscila entre 66-69 años y suele localizarse en áreas de fotoexposición crónica, a menudo asociado a un lentigo maligno. Su reconocimiento clínico es difícil ya que se presenta como una pápula o placa no pigmentada, indurada y de bordes mal definidos, que recuerda a una cicatriz.El MD es un tumor con una alta tendencia a la recurrencia local y en el caso del MD puro, una baja tendencia a la diseminación ganglionar. Sin embargo, en las series más contemporáneas, su pronóstico global parece ser similar al de melanomas no desmoplásicos (MND) del mismo grosor. Su abordaje clínico posee algunos matices diferenciales, en comparación al resto de melanomas, que se revisan en el presente trabajo. Abstract: Desmoplastic melanoma (DM) accounts for 0.4% to 4% of all melanomas. These skin tumors are mainly formed by amelanotic spindled melanocytes immersed in an abundant collagen stroma and are classified as pure when the desmoplastic component accounts for at least 90% of the invasive tumor and as mixed or combined otherwise. DMs are more common in men (male to female ratio, 1.7 to 2:1), and the mean age at diagnosis is 66 to 69 years. The tumors tend to occur in chronically sun-exposed areas, often in association with lentigo maligna, and are difficult to recognize because they can resemble a scar, presenting as a firm, unpigmented papule or plaque with poorly defined borders. DMs also have a strong tendency to recur locally, and pure variants rarely spread to the lymph nodes. Nonetheless, recently published series suggest that patients with DM have a similar prognosis to those with nondesmoplastic melanoma of the same thickness. The clinical management of DM varies in certain aspects from that of other melanomas and is reviewed in this article.

Yaqi Fan,1 Mingyuan Xu,2 Yulin Liang,2 Nanhui Wu,2 Feiyan Wang,3 Qian Du,2 Yun Bai,1 Yeqiang Liu1 1Department of Pathology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, 200050, People’s Republic of China; 2Shanghai Skin Disease Hospital, Shanghai, 200443, People’s Republic of China; 3Shanghai Skin Disease Clinical College of Anhui Medical University, Shanghai Skin Disease Hospital, Shanghai, 200443, People’s Republic of ChinaCorrespondence: Yeqiang Liu; Yun BaiDepartment of Pathology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, 1278 Bao’de Road, Shanghai, 200443, People’s Republic of ChinaTel/Fax +86 21 61833180Email lyqdoctor@163.com; baiyun@chgc.sh.cnPurpose: To investigate the clinicopathological characteristics and immunophenotype of desmoplastic melanoma (DM) in the Chinese population.Patients and Methods: We report three cases of DM diagnosed by the Pathology Department of Shanghai Dermatology Hospital. We describe the clinical and pathological characteristics of the three cases and examine molecular markers used in the diagnosis of DM. Finally, we summarize the current literature in the DM field.Results: Clinically, lesions in the three DM patients were characterized by non-pigmented nodules or papules. Microscopically, we observed an abundance of fibrous interstitium mixed with spindle cells exhibiting various degrees of atypia. Occasionally, these structures exhibited changes in lentigo maligna at the epidermal junction, accompanied by the presence of lymphoid follicular structures and neurophilic behavior. Diagnosis of DM was confirmed by immunohistochemical staining, which revealed high expression levels of S-100 and SOX-10. Melanocyte markers were focally positive or negative. Unlike DMs from other populations, our three patients were negative for WT-1 and P53. All three cases received surgical resection, which is the preferred treatment for DM, and none of the patients experienced recurrence.Conclusion: DM in these Chinese patients was similar to that observed in other DM populations in terms of immunophenotype and clinical and histological features. A notable absence in p53 staining was observed in the three cases reported here, suggesting that p53 negativity should not exclude the diagnosis of DM in the Chinese population.Keywords: desmoplastic melanoma, uneven pigmented nodules, histology, Chinese population, immunophenotypes

The local recurrence rates of malignant skin tumors after micrographic controlled surgery using complete circumferential peripheral and deep margin assessment (CCPDMA) are reported to be low. However, in daily practice, tumor entities with a significantly higher recurrence rate are found.The aim of the investigation was to identify these high-risk tumors to develop approaches for risk stratification.We included different malignant tumors that were surgically treated and examined with CCPDMA using paraffin sections and HE staining. Re-excisions were performed until the tumor was completely removed.Ninety-nine thousand three hundred seventy-two tumors were included in the study; the follow-up period was 4 years (median). Eight tumor entities were identified as high-risk entities, showing a significantly higher local recurrence rate of over 20%: desmoplastic squamous cell carcinoma, desmoplastic melanoma, Merkel cell carcinoma, microcystic adnexal carcinoma, pleomorphic sarcoma, liposarcoma as well as angiosarcoma, and extramammary Paget's disease.Complete circumferential peripheral and deep margin assessment allows complete control of the resection margins and enables skin-sparing resections with low recurrence rates for basal cell carcinomas, nondesmoplastic squamous cell carcinomas, lentiginous melanomas, and dermatofibrosarcoma protuberans. However, other tumors show significantly higher recurrence rates and therefore need to be classified as high-risk tumors.

Background Subungual melanoma (SUM) is a rare form of melanoma confined to the nailbed and is rarely of the desmoplastic subtype. The often subtle nature of SUM, initially starting as a small dark spot or line in the nailbed, means deeper invasion can occur before a patient seeks clinical evaluation for a large, ulcerated lesion. We report the only known case of perineural spread of SUM of the lower extremity and describe its extensive path of perineural spread from the toe. Case Description A 72-year-old man with a distant history of SUM status post second ray amputation, presented for evaluation of ipsilateral foot drop. Imaging revealed nodular involvement of tibial, peroneal, and sciatic nerves. Biopsies revealed desmoplastic melanoma and he was treated with nivolumab. Conclusions We report the only known case of perineural spread of SUM of the lower extremity and describe the pathoanatomy of perineural spread. A high index of suspicion for recurrent disease should be maintained even many years after completion of treatment.

Desmoplastic melanoma commonly occurs on the head and neck in a pure form, but occasionally, it occurs in a mixed tumor with another type, usually superficial spreading melanoma (SSM), and rarely as a metastasis from a primary SSM. We report here a primary SSM on the leg of a 32-year-old male which metastasised to lymph nodes, and 10 years later recurred at the primary site initially with mixed features but evolving to resemble a uniformly desmoplastic, deeply invasive melanoma. This unusual case has implications for clinical management and is additionally notable for its reversal in behavior, from metastatic to local infiltrative type, correlating with the change in morphology.

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.

Perineural invasion, or neurotropism, is defined by the presence of cancer cells either within the neuronal sheath or found along the nerves. In melanoma, it is most commonly associated with invasive desmoplastic melanoma, a melanoma that is most commonly associated with malignant melanoma in situ, lentigo maligna type. Initially, perineural invasion was included in the reported Breslow thickness; however, recent data suggest that it should not be included. In this report, we describe a case of malignant melanoma in situ, lentigo maligna type, with associated neurotropism in the absence of invasive component.

The development of flat pigmented lesions on chronically sun-damaged (CSD) skin of the face may represent the clinical manifestation of a wide variety of hyperplastic/neoplastic melanocytic proliferations. We report the exceptional case of an acquired pigmented patch occurring on CSD skin, histopathologically characterized by diffuse hyperplasia of dendritic/spindled melanocytes in the superficial dermis within a widened band of actinic elastosis. This lesion was associated with a small focus of early invasive lentigo maligna melanoma (LMM). We show the melanocytic nature of the population of dermal pigmented cells by means of single and double immunohistochemical staining for melanocytic and histiocytic markers. The biologic significance of the focus of LMM within the hyperpigmented lesion (whether random collision phenomenon or causally related occurrence), as well as the pathogenesis of the whole dermal lesion are difficult to elucidate. Our case emphasizes the need for a better understanding of the pathophysiology of so-called dermal melanocytes.

Cutaneous spindle cell squamous cell carcinoma (SpSCC) is a rare and often aggressive subtype of squamous cell carcinoma (SCC), which usually appears in sun-exposed areas, in areas that have received prior ionizing radiation, or in immunosuppressed individuals. SpSCCs are histologically characterized by keratinocytes infiltrating the dermis as single cells with elongated nuclei rather than as cohesive nests or islands and, in contrast to conventional SCC, are lacking features of keratinization. Immunohistochemical studies are useful to distinguish SpSCC from other spindle cell neoplasms, such as spindle cell/desmoplastic melanoma, cutaneous leiomyosarcoma, and atypical fibroxanthoma. We present a rare case of a patient with SpSCC in the gluteal region with regional lymph node metastasis. The patient was treated with wide excision of the tumor, inguinal lymph node dissection, and adjuvant radiotherapy. Cutaneous SpSCC is clinically similar to conventional SCC but can demonstrate more aggressive behavior. This case is rare since it was localized in the gluteal region of an otherwise healthy man.

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.

Desmoplastic melanoma (DM) accounts for 0.4% to 4% of all melanomas. These skin tumors are mainly formed by amelanotic spindled melanocytes immersed in an abundant collagen stroma and are classified as pure when the desmoplastic component accounts for at least 90% of the invasive tumor and as mixed or combined otherwise. DMs are more common in men (male to female ratio, 1.7 to 2:1), and the mean age at diagnosis is 66 to 69 years. The tumors tend to occur in chronically sun-exposed areas, often in association with lentigo maligna, and are difficult to recognize because they can resemble a scar, presenting as a firm, unpigmented papule or plaque with poorly defined borders. DMs also have a strong tendency to recur locally, and pure variants rarely spread to the lymph nodes. Nonetheless, recently published series suggest that patients with DM have a similar prognosis to those with nondesmoplastic melanoma of the same thickness. The clinical management of DM varies in certain aspects from that of other melanomas and is reviewed in this article.

Malignant melanoma is one of the most aggressive skin tumors with an increasing incidence and high mortality. The aim of this article is to draw attention to the difficulties of differential diagnosis of malignant melanoma and the importance of early surgical treatment. The authors describe a case of locally advanced desmoplastic malignant melanoma located in the periorbital area of 73-year-old patient, causing massive ulceration, expansion to skull base and orbit, and psychological deterioration of the patient.

Background Desmoplastic melanoma (DM) is a rare variant of cutaneous melanoma with a high rate of local recurrence. Recent studies have indicated a potential benefit in local control with the addition of adjuvant radiotherapy (RT). Objective This study sought to evaluate the outcomes of adjuvant RT for patients with DM. Materials and methods The National Cancer Database was queried (2004-2015) for patients with newly diagnosed, nonmetastatic DM. Patients were divided into 2 groups based on the adjuvant therapy they received: RT or observation. Statistics included multivariable logistic regression to determine factors predictive of receiving adjuvant RT, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling to determine variables associated with OS. Results There was no difference in median OS between patients treated with RT when compared with patients observed (111.4 months vs 133.9 months, p = .1312). On multivariable analysis, older age, T stage ≥2, N stage ≥1, and no receipt of immunotherapy were associated with worse OS. Conclusion In this large study evaluating efficacy of adjuvant RT in DM, no overall survival benefit was observed among patients receiving adjuvant RT.

The indisputable contribution of dermatoscopy in early diagnosis of melanoma is widely recognized. In the last quinquennium, new data concerning specific melanoma subtypes have come to light. The dermatoscopic morphology of superficial spreading melanoma (SSM) has been extensively investigated in the literature. Atypical network, irregular dots, irregular globules, irregular streaks and irregular blotch correspond to histopathologic alterations at the level of the junction, blue-white veil and atypical vessels suggest intradermal growth, whereas regression structures, negative network and white shiny streaks might reflect junctional or dermal alterations. The list of melanoma specific criteria has been recently updated to include features that typify early melanoma, such as irregular hyperpigmented areas and prominent skin markings and features seen in melanoma on sun damaged skin such as angulated lines. Nodular melanoma lacks most of the aforementioned criteria and is typified by the coexistence of blue and black color, atypical vessels and pink color. Lentigo maligna dermatoscopic criteria mainly develop at the outline of the follicular openings. However, at an early stage these features might be very subtle and the diagnosis should be based on the exclusion of benign tumors (inverse approach). Acral lentiginous melanoma is typified by a parallel ridge pattern, but also SSM criteria should be taken into consideration. The diagnosis of subungual melanoma is based on the assessment of the color and characteristics of the pigmented nail band. For the diagnosis of mucosal melanoma, the assessment of colors is more informative than the assessment of structures and the detection of blue, white or gray should raise the suspicion of melanoma. White shiny streaks and regression structures are the most common features of desmoplastic melanoma. The diagnosis of nevoid melanoma might be highly challenging and require information on the lesion's history. Melanoma on small- and medium-sized congenital nevi is typified by an eccentric location of the suspicious area, negative network and gray angulated lines. Recent advances in knowledge on the dermatoscopic characteristics of peculiar subtypes of the tumor significantly enrich the diagnostic armamentarium of clinicians. The challenge of the forthcoming years is to better characterize biologically aggressive melanomas and to optimize the screening strategies so as to identify them.

An 83-year-old man presented with a tumor of the neck, clinically consistent with an epidermal inclusion cyst. Excisional biopsy revealed a deeply infiltrating spindled cell tumor. Immunohistochemical markers for S100, SOX-10, Melan-A, HMB-45, and NK1/C3 were negative. Based on the presence of an area of lentigo maligna and the histologic pattern of the spindle cell component, a diagnosis of desmoplastic melanoma was made despite the absence of immunophenotypic evidence for melanocytic differentiation. To the best of our knowledge, the complete lack of both S100 and SOX-10 makes this tumor an unprecedented case. To avoid ruling out the diagnosis of desmoplastic melanoma prematurely, physicians should be made aware of this possible immunohistochemical profile.

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.

There are multiple, genetically distinct pathways that give rise to melanoma. Melanomas on sun-damaged skin (MSDS), including lentigo maligna and desmoplastic melanoma, have distinct genetic profiles and are uniquely linked to chronic ultraviolet exposure. In this article, we discuss the etiologies of lentigo maligna and desmoplastic melanoma, emerging diagnostic adjuncts that might be helpful for accurately identifying these lesions, and the clinical relevance of their frequent co-occurrence. We present unique and overlapping features of these entities and discuss challenges in MSDS management, including margin assessment, excision, and the potential role of nonsurgical therapy. Last, we address the role of immunotherapy in invasive disease. Understanding MSDS as distinct from melanoma arising on intermittently sun-exposed or sun-protected skin will ultimately help optimize patient outcomes.

BACKGROUND Pure desmoplastic melanoma (pDM) is an uncommon subtype of malignant melanoma with comparative high rates of local recurrence and low rates of sentinel lymph node positivity. The melanoma-specific survival (MSS) of pDM compared to other melanoma subtypes is unclear, with conflicting reports and lack of multivariable analyses. OBJECTIVES We aimed to describe clinicopathological characteristics of a cohort of patients with pDM and to compare the MSS of pDM with superficial spreading melanoma (SSM). METHODS A prospective cohort study was performed of all primary invasive cutaneous pDM with known tumour location and thickness reviewed at a tertiary referral centre over 21 years. RESULTS A total of 119 primary cutaneous invasive pDMs from 3570 total invasive cutaneous melanomas were included. Compared to 2272 SSMs, and due largely to their greater average thickness, patients with pDM had worse MSS (unadjusted hazard ratio, HR, 2.56, 95% confidence interval, CI, 1.56-4.22). After adjustment for clinicopathologic factors (including thickness, ulceration, mitotic rate, age and sex), there was evidence that patients with pDM had an improved MSS (adjusted HR, 0.49; 95% CI, 0.28-0.87). Median thickness of head and neck pDM was greater than non-head and neck pDM (P

Desmoplastic melanoma (DM) is a rare morphological subtype of melanoma that remains uncharacterized. The aim of the present study was to investigate the incidence of DM, its general demographics, clinicopathological features and disease-specific prognostic factors. DM cases were sampled from the Surveillance, Epidemiology and End Results (SEER) program from between 1973 and 2017. A total of 3,657 cases (median age, 68 years) were identified. The results indicated that DM primarily occurred in Caucasian subjects, with a male-to-female ratio of 2:1. Statistically significant overall survival (OS) and disease-specific survival (DSS) rate differences were identified according to sex, age, treatment, T stage, N stage and SEER historic tumor stage (P68 years, male sex, American Joint Committee on Cancer (AJCC) stage II and III, and SEER historic tumor stage of the regional tumor were all factors associated with poorer OS and DSS rates. The findings also revealed that surgical treatment was associated with favorable DSS and OS rates. In conclusion, DM occurred primarily in Caucasian subjects of 60–80 years of age, with predominance in males. Furthermore, age, sex, AJCC stage, SEER historic tumor stage and surgical treatment were identified as independent prognostic factors of DM in terms of DSS and OS.

Desmoplastic melanoma, a distinct and uncommon variant, is characterized as an invasive lesion with proliferation of fusiform melanocytes in the dermis and subcutaneous tissue, associated with varying patterns of desmoplasia. Neurotropism and neural differentiation may occur. The clinical presentation is variable and nonspecific, easily confused with other fibrous neoplasms. The disease is locally aggressive and shows lower metastasis rates than other types of melanoma. Histopathology may be insufficient, requiring positive immunohistochemistry for S-100 protein and other antigens of melanocytic differentiation. Because desmoplastic melanoma represents a true clinical, dermoscopic, and histopathological diagnostic challenge, a case of invasive desmoplastic melanoma is reported, affecting a photoexposed area in an elderly woman after histological revisions and an initial diagnosis of fibroma.

Cutaneous melanoma is a public health issue and the head and neck region is of particular interest, despite accounting for only 9.0% of the total body surface, it harbours 20% of melanoma cases. Data from the literature show that scalp melanomas (SM) carry high mortality rates, with a 10-year survival rate of 60% which lead them to be named as the “invisible killer”. Moreover, SMs are more common in the elderly than in young population, and they occur six times more frequently in men than in women. This is probably related to the higher incidence of androgenetic alopecia and a higher cumulative and intermittent ultraviolet damage on the scalp. Histologically, SM is a heterogenous group, including lentiginous melanoma (LM), desmoplastic melanoma, superficial spreading and nodular melanoma. Thin melanomas tend to display an atypical network or pseudo-network and regression in dermoscopy. Blue-white veil, irregular pigmented blotches and an unspecific pattern are most commonly detected in thick lesions. On reflectance confocal microscopy (RCM), the most frequent pattern is irregular meshwork, but also ringed and disarranged pattern have been described. Differential diagnosis includes benign solar lentigo, actinic keratoses, lichen planus like keratosis, melanocytic nevi and blue nevi. All suspicious lesions should be biopsied; therefore, an excisional biopsy with 2 mm margins is usually the best option. The management of SM is the same as for melanoma on other body sites. However, sentinel node biopsy tends to be more challenging, as well as achieving adequate excision margins of the primary tumor. In this review, we summarize clinical, pathologic, dermoscopic and RCM features of SM, and focus on its epidemiology, risk factors and best management options.

Desmoplastic melanoma (DMM) is a rare variant of melanoma that presents major diagnostic challenges. It can mimic both benign or other malignant tumors and may be easily confused by clinicians and pathologists. We report a patient who presented with a pink-colored papule on the left lateral neck. Histopathology revealed a nodular spindle cell tumor in the dermis resembling a neurofibroma at low power. However, higher-power evaluation and the use of immunohistochemical staining confirmed the diagnosis of DMM.We present this case to highlight the ongoing challenges of diagnosing DMM both clinically and histologically and to review the salient features of this often benign-appearing tumor. Advancing age, male gender, and head and neck location are associated with an increased risk of DMM-specific death. It is important that new or changing lesions in the correct cohort and location are biopsied promptly.

Our collective understanding of melanoma genomics has rapidly expanded in the past decade, bringing great promise to patients affected with the most severe and aggressive cases of melanoma. In this review, we present the practical clinical impact of genetics and genomics on modern melanoma diagnosis and treatment. Characterization of somatic driver mutations, which can be used to distinguish different subtypes of melanoma such as nonacral cutaneous melanoma (NACM), desmoplastic melanoma (DM), acral melanoma (AM), mucosal melanoma (MM) and uveal melanoma (UM), has led to the development of many targeted therapies against these tumours. Although targeted therapies exist for certain mutations, such as BRAF and KIT, other genotypes respond to newer-generation immune therapies such as immune checkpoint inhibitors. Epigenetics also plays a critical role in melanoma pathogenesis and drug resistance, holding promise for new treatment avenues. In this review, special attention is placed on clinical trials and translational research, especially novel genomic tests aimed to benefit patients on an individualized level in the current emerging era of personalized therapy.

BACKGROUND Perineuriomatous nevi are rare and diagnostically problematic. We report a series of eight perineuriomatous nevi to highlight the diagnostic features. METHODS Cases were retrospectively reviewed and characterized. RESULTS Median age was 42.5 years (range 25-64), with equal sex distribution. Lesions occurred on the arm (n = 4), trunk (n = 2), and head/neck (n = 2). Median size was 7.5 mm (range 5-12 mm). Clinical differential diagnoses included atypical nevus (3), blue nevus (1), neurofibroma (1), and dermatofibroma (1). Lesions were circumscribed, dome-shaped (5/8), and biphasic (8/8) with nested epithelioid cells and wavy spindled cells arranged in whorled fascicles in a myxocollagenous stroma. When present, junctional growth was lentiginous (4/8). No cases displayed pleomorphism or mitotic figures. The perineuriomatous component stained positively for epithelial membrane antigen (8/8 focal to diffuse) and CD34 (4/5 focal to diffuse). SOX10 and S100 protein stained all nevoid cells and in some cases a subset of intermingled spindled cells in perineuriomatous areas, where other melanocytic markers were negative. p16 protein expression was uniformly retained (3/3), and p53 negative (0/2). Nevoid cells in most lesions were positive for BRAFV600E (5/7). Ki67 was mildly elevated (~5%) in 3/3 cases. CONCLUSIONS Recognizing the histopathologic and immunophenotypic features in these unusual nevi helps avoid overdiagnosis.

The vast majority of patients newly diagnosed with melanoma present with clinically localized disease, and sentinel lymph node biopsy (SLNB) is a standard of care in the management of these patients, particularly in intermediate thickness cases, in order to provide important prognostic data. However, SLNB also has an important role in the management of patients with other subtypes of melanoma such as thick melanomas, certain thin melanomas, and specific histologic variants of melanoma such as desmoplastic melanoma. Furthermore, there have been technical advances in the SLNB technique, such as the development of newer radiotracers and use of SPECT/CT, and there is some data to suggest performing a SLNB may be therapeutic. Finally, the management of patients with a positive sentinel lymph node (SLN) has undergone dramatic changes over the past several years based on the results of recent important clinical trials. Treatment options for patients with SLN metastases now include surveillance, completion lymph node dissection, and adjuvant therapy with checkpoint inhibitors and targeted therapy. SLNB continues to play a crucial role in the management of patients with melanoma, allowing for risk stratification, potential regional disease control, and further treatment options for patients with a positive SLN.

Malignant peripheral nerve sheath tumors are rare soft tissue sarcomas that are often associated with neurofibromatosis type-1. These tumors share common immunohistochemistry findings which can make diagnosis difficult. We present the case of a woman who presented with a diagnosis of metastatic melanoma of the index finger of her left hand but was eventually diagnosed with primary epithelioid malignant peripheral nerve sheath tumor. We will be highlighting the diagnostic challenge of differentiating between these two very different malignancies.

The synchronous incidence of 2 different subtypes of melanoma is very rare. Desmoplastic melanoma (DM) can be a diagnostic challenge because of its frequent appearance as a dermal banal spindle cell proliferation. We present a case of a 30-year-old man who developed an irregular, purple, tender plaque measuring 2.5 cm on the right pretibial region. Wide excision of the right leg lesion showed superficial spreading melanoma with epithelioid cells and no spindle cell component. Sentinel lymph node (SLN) biopsy showed an atypical melanocytic proliferation involving one inguinal lymph node with subcapsular and intraparenchymal components. There were spindled tumor cells in lymph node capsule with hyperchromatic nuclei, which were nested within desmoplastic stroma, and were S100- and SOX10-positive and MART1- and HMB-45 negative; in addition to epithelioid tumor cells, which were S100-, SOX10-, and MART1-positive. Multiple discontinuous foci, subcapsular atypical melanocytes, and extracapsular extension helped in excluding capsular nevus. These findings were consistent with DM. Herein, we present an unusual case of primary cutaneous superficial spreading melanoma of the right leg with a predominantly epithelioid morphology that developed metastases to the SLN. The metastasis exhibited divergent differentiation, including both epithelioid morphology identical to the primary, but with additional features of DM that were nonoverlapping with the primary lesion.

Background Cutaneous 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. Methods This prospective case series study spanned over a period of three years. All patients with histologically confirmed CMs were included. Results There 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%. Conclusion CMs 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.

Background Desmoplastic melanoma (DM) is an uncommon malignancy associated with a high local recurrence rate. The aim of this systematic review was to determine the positivity rate of sentinel lymph node biopsy (SLNB) in patients with DM. The secondary outcome was to establish if SLNB is warranted for both pure DM (PDM) and mixed DM (MDM). Methods A full systematic literature review of SLNB in DM was performed by two authors in January 2016. Ovid MEDLINE, Ovid EMBASE and the Cochrane Central Register of Controlled Trials were searched. Results Sixteen studies involving 1519 patients having SLNB in DM were included, of which 99 patients had positive SLNB (6.5%). Two articles reported a significantly reduced disease-free survival (DFS) with positive SLNB and three published a reduced melanoma-specific survival (MSS). Six studies compared SLNB in MDM and PDM. Of the 275 patients, 38 (13.8%) had a positive SLNB in MDM compared to 17 of 313 patients (5.4%) with positive SLNB in PDM. Conclusions Rates of positive SLNB in DM are reduced compared to other variants of melanoma; however, nodal status may still predict DFS and MSS. MDM is associated with a higher rate of micro-metastases to regional lymph nodes than PDM, and DFS and MSS may be lesser in MDM than in PDM. We would recommend the consideration of SLNB in MDM. However, with such low rates of positive SLNB in PDM, and in the absence of high-risk features to stratify patients, we would not recommend SLNB in PDM.

Facial swelling has several etiologies. In patients with head and neck malignancies, this can include primary disease progression or iatrogenic causes. A 66-year-old man presented with increased facial swelling and erythema for 18 months. He had a history of baseline postoperative facial lymphedema following head and neck surgery and radiotherapy for desmoplastic melanoma approximately 20 years ago. However, his facial edema acutely worsened 18 months prior to presentation. A medication review revealed that he was regularly taking melatonin for the past two years. Approximately two weeks after cessation of melatonin therapy, the patient's facial appearance returned to baseline. In conclusion, it is important for clinicians to perform a thorough medication review for patients with facial swelling and erythema.

Background Desmoplastic 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. Methods Clinicopathological 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). Results A 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, MDM 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.

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.

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.

Importance: The clinical and dermoscopic features of the vast majority of uncommon variants of cutaneous melanoma have been rarely reported, leading to difficulty in making accurate diagnoses. Objective: To define the main clinical and dermoscopic features of the most frequently reported but uncommon histologic variants of cutaneous melanoma. Evidence Review: A 2-step systematic review of the literature was performed (from inception to November 2018) using PubMed, Embase, and Cochrane Central Register of Controlled Trials databases. The first step identified those uncommon variants of melanoma for which at least 1 case reporting dermoscopy was described in the literature. The keywords searched were melanoma, uncommon, rare, dermoscopy, and dermatoscopy. In the second step, each previously identified uncommon variant was searched for in the same databases by combining the following terms with melanoma, dermoscopy, and dermatoscopy: Amelanotic, hypopigmented, animal, melanocytoma, balloon, desmoplastic, follicular, nested, nevoid, dermal, spitz, spindle, and verrucous. The institution's database was also searched from January 2012 to September 2019 for histopathologically confirmed cases of the same melanoma variants. Each reviewer also assessed the quality of reporting in the included articles based on previously described guidelines. Findings: In total, 62 articles met the inclusion criteria, reporting 433 melanoma cases. An additional 56 cases of uncommon melanoma variants were retrieved from the institution's database for a total of 489 cases: 283 cases of amelanotic superficial spreading melanoma, 18 cases of animal-type and pigmented epithelioid melanocytoma, 7 cases of balloon cell melanoma, 71 cases of desmoplastic melanoma, 3 cases of follicular melanoma, 10 cases of nested melanoma, 33 cases of nevoid melanoma, 2 cases of primary dermal melanoma, 57 cases of spitzoid melanoma, and 5 cases of verrucous melanoma. These variants of melanoma occurred more frequently in women than men (147 cases vs 132 cases). Clinically, these tumors were mainly palpable (162 of 217 [74.7%]) or amelanotic (283 of 489 [57.9%]) lesions that could resemble other benign or malignant skin conditions; dermoscopy typically revealed a homogeneous pinkish background, white structures, and polymorphic vessels. The mean age of all included was 58 years (range, 1-89 years). Conclusions and Relevance: Uncommon melanoma variants may resemble both inflammatory disorders and other cutaneous neoplasms, representing a diagnostic pitfall even for the most experienced dermatologist. The purpose of this systematic review was to provide an extensive and detailed overview of specific clinical and dermoscopic features of each uncommon melanoma variant, highlighting the main criteria for differentiating these variants from other benign or malignant skin lesions..

This review presents the main challenges encountered when diagnosing unusual variants of malignant melanoma with the aim of raising awareness to allow application of the most appropriate treatment strategies. Although these melanomas are often rare, their misdiagnosis potentially jeopardizes patients' health and survival, and has medicolegal implications. The clinical and histologic presentations of melanoma vary greatly, and assessment of uncommon melanomas can be difficult for practitioners because of their scarcity and resemblance to other dermatologic entities. The most problematic melanoma types are desmoplastic melanoma, polypoid melanoma, primary dermal melanoma, verrucous malignant melanoma, pigmented epithelioid melanocytoma, mucosal melanoma, follicular melanoma and melanoma with non-melanocytic differentiation. The two most difficult-to-diagnose subtypes of melanoma are the nevoid and the amelanotic melanomas. Some specific attributes of these variants can be more easily recognized with digital dermatoscopy, facilitating early detection and possibly avoiding invasive procedures. Key cases with the most notable clinical, dermatoscopic, and histopathologic features are presented, highlighting the practical issues of making an accurate diagnosis and choosing the best therapy.

BACKGROUND: Desmoplastic melanoma (DM) is a sub-variant of spindle cell melanoma, accounting for less than 4 percent of all cutaneous melanomas. It occurs later in life and is associated with chronic sun exposure. DM prognosis is considered more favorable than other variants, with lower rates of metastasis and higher survival. Recently DM has been further sub-classified into pure and mixed, calling into question surgical management and patient outcomes as well as viability of current nationwide databases without this distinction. METHODS: We identified all patients with a histopathologic diagnosis of desmoplastic melanoma from the Cleveland Clinic electronic melanoma database (n=58) from 1997–2013. Clinical and histopathologic data were collected. Comparison in clinical variables was performed between patients who had pure (n=15) and mixed (n=43) variants of DM. RESULTS: There were no differences in age, gender, location of lesion, Breslow depth, ulceration, or regression. Patients with mixed desmoplastic melanoma were more likely to have lymphovascular invasion (p=0.03) compared to pure desmoplastic melanoma. There was no difference in performance of sentinel lymph node biopsy (p=0.25) or sentinel lymph node positivity (p=0.31) between the two groups. Recurrence was present in 13.3% of pure and 30.2% of mixed patients. Overall Kaplan Meier 3 year survival was 75% for pure and 80% for mixed desmoplastic melanoma (p=0.53). CONCLUSION: Pure and mixed desmoplastic melanomas appear to have similar clinical characteristics and outcomes. This indicates that analysis of national datasets without this sub classification remains viable.

The clinical and pathological diagnosis of desmoplastic melanoma is difficult, because almost 50% of desmoplastic melanoma cases involve non-pigmented lesions and the tumor cells can resemble fibroblasts or Schwannian cells based on their frequent amelanotic features. Moreover, desmoplastic melanoma typically has low positive rates for melanoma markers, with the exception of the S-100 protein. We report the case of an 81-year-old Japanese man with an 8-mm desmoplastic melanoma. He initially noticed a painless and non-pigmented skin lesion that did not grow noticeably for 6 months. It was unlikely that he had von Recklinghausen disease, and the mass was initially considered a dermatofibroma. Excisional biopsy revealed an intradermal mass, with the superficial portion mimicking neurofibroma and the deeper portion exhibiting nodular growth of sarcomatoid spindle cells. The tumor region lacked intradermal proliferation of atypical melanocytic cells, intracytoplasmic melanin, and expression of melanoma markers (except S-100 protein and Sox10). Although a malignant peripheral nerve sheath tumor derived from neurofibroma was possible, the slow growth with diffuse and strong immunoreactivity to the S-100 protein and Sox10 favored a diagnosis of desmoplastic melanoma. Pathologists should recognize that desmoplastic melanoma may not involve in situ lesions or the immunohistochemical expression of standard melanoma markers. Keywords: Desmoplastic melanoma, Malignant peripheral nerve sheath tumor, Neurofibroma, Neurotrophic melanoma

The current classification of melanocytic tumors includes clinical, pathological, and molecular data. A subset of lesions remains difficult to classify according to these complex multilayer schemes. We report two cases of deeply infiltrating melanomas with a sclerosing background. The first case occurred on the back of a middle-aged man appearing clinically as a dermatofibroma. The architectural and cytological aspects resembled those of a desmoplastic melanoma but the strong expression of both melanA and HMB45, two stainings usually reported as negative in this entity, raised the question of an alternate diagnosis. The second case was a large, slowly growing, perivulvar tumor in a middle-aged woman. The morphology was complex with a central junctional spitzoid pattern associating an epidermal hyperplasia with large nests of large spindled melanocytes. The dermal component was made of deeply invasive strands and nests of nevoid unpigmented melanocytes surrounded by fibrosis; a perineural invasion was present at the periphery of the lesion. In both cases, aCGH found, among many other anomalies, a chromosomal breakpoint at the BRAF locus. RNA sequencing identified in both an AKAP9-BRAF gene fusion. A complementary resection was performed and no relapses have been observed in the respectively 15 and 6 months of follow-up. Both of these melanomas remained unclassified. We further review the variety of melanocytic tumors associated with such BRAF fusions.

Rationale: Tumor-associated fibroblasts (TAFs) play a critical role in the suppressive immune tumor microenvironment (TME), compromising the efficacy of immunotherapy. To overcome this therapeutic hurdle, we developed a nanoemulsion (NE) formulation to deliver fraxinellone (Frax), an anti-fibrotic medicine, to TAFs, as an approach to reverse immunosuppressive TME of desmoplastic melanoma. Methods: Frax NE was prepared by an ultrasonic emulsification method. The tumor inhibition effect was evaluated by immunofluorescence staining, masson trichrome staining and western blot analysis. Immune cell populations in tumor and LNs were detected by flow cytometry. Results: This Frax NE, with a particle size of around 145 nm, can efficiently accumulate in the tumor site after systemic administration and was taken up by TAFs and tumor cells. A significant decrease in TAFs and stroma deposition was observed after intravenous administration of Frax NE, and Frax NE treatment also remolded the tumor immune microenvironment, as was reflected by an increase of natural-killer cells, cytotoxic T cells (CTLs) as well as a decrease of regulatory B cells, and myeloid-derived suppressor cells in the TME. In addition, after treatment by Frax NEs, T helper 1 (Th1) cytokines of interferon gamma (IFN-γ), which effectively elicit anti-tumor immunity, were enhanced. Transforming growth factor-β (TGF-β), chemokine (C-C motif) ligand 2 (CCL2) and interleukin 6 (IL6), which inhibit the development of anti-tumor immunity, were reduced. Although Frax NE demonstrated an inhibitory effect on tumor growth, this mono-therapy could only achieve partial antitumor efficacy, and the tumor growth effect was not maintained long-term after dosing stopped. Therefore, a tumor-specific peptide vaccine was combined with Frax NEs. The combination led to enhanced tumor-specific T-cell infiltration, activated death receptors on the tumor cell surface, and induced increased apoptotic tumor cell death. Conclusion: Collectively, Frax NE combined with tumor-specific peptide vaccine might be an effective and safe strategy to remodel fibrotic TME, thereby enhancing immune response activation, resulting in a prolonged efficiency for advanced desmoplastic melanoma.

Desmoplastic melanoma (DM) represents an infrequently occurring and distinct histologic pattern of melanomas, often lacking mutations in genes typically altered in conventional melanomas including BRAF , NRAS , and KIT . We aimed at better characterizing the genetic profile of this subgroup of melanomas to match patients with available therapies. Pathology reports were reviewed for 1,240 consecutive melanoma cases sequenced by comprehensive genomic profiling (CGP) using a hybrid-capture based next generation sequencing during the course of clinical care. The mutational profile of the 12 DM identified was compared with the remaining 1,228 melanomas examined. We report a median tumor mutational burden (TMB) of 77 mutations per megabase (mut/Mb) in DM, which was significantly greater than a median of 35 mut/Mb in non-DM. A UV DNA damage signature was detected in 10/12 (83%) DM. For a subset of patients with available clinical course, we report that 100% (5/5) had clinical benefit from treatment with PD-1 inhibitors as monotherapy. TMB and UV signature show significant promise as an approach to identify patients who are likely to benefit from PD-1 targeted immunotherapy.

Palisaded encapsulated neuromas (PENs) are benign cutaneous nerve sheath proliferations that typically occur as flesh-colored papules solitarily on the head and neck in adults, with a slight predilection for females. Histopathologically, they are partially or completely encapsulated intradermal nodules with Schwann cells and axons in fascicles separated by clefts. Although these features are often characteristic, the hypercellular variant of PEN can pose a diagnostic challenge in distinguishing between other cellular neural and melanocytic lesions. We herein report a case of hypercellular PEN, which showed striking similarity to desmoplastic melanoma.

Desmoplastic melanoma (DM) is a rare form of malignant melanoma. DMs may present with a non-specific appearance which can make diagnosis difficult. Surgical excision with wide margins is the preferred treatment. DMs tend to be locally aggressive and adjuvant radiotherapy may improve local control of disease.

Objective To describe the epidemiological characteristics and survival of desmoplastic melanoma of the head and neck (DMHN) and discuss the factors influencing survival variation among DMHN, DM of other sites (DMnHN), and conventional melanoma of the head and neck (CMHN). Study Design Retrospective cohort study. Setting Surveillance, Epidemiology, and End Results (SEER) database (years 1992-2013). Subjects and Methods Incidence and survival data for 1095 patients with DMHN, 1139 patients with DMnHN, and 40,257 patients with CMHN were obtained. Kaplan-Meier and Cox proportional hazards regression models were used to calculate survival outcomes. Results Patients with DMHN were diagnosed at greater Breslow thickness ( P.001), stage ( P.001), and Clark's level ( P.001) compared to DMnHN and CMHN. Kaplan-Meier survival analysis demonstrated disease-specific survival (DSS) at 5 and 10 years for DMHN to be 80.5% and 74.7%, respectively, compared with 89.1% and 86%, respectively, for DMnHN and 88.1% and 83%, respectively, for CMHN (log-rank test; P.001). On multivariate Cox regression analysis, age at diagnosis ( P.001), Breslow depth4.00 mm ( P = .006), lymph node status ( P.001), and presence of ulceration ( P.001) were found to be independent predictors of DSS for DMHN. Conclusion The increasing incidence and poor survivability of DMHN compared to DMnHN and CMHN are parsimoniously explained by the later stage of disease and depth of invasion at diagnosis, highlighting the importance of improved diagnosis and awareness of DMHN.

Desmoplastic melanoma (DM) and cutaneous malignant peripheral nerve sheath tumors (MPNST) reveal histological and immunohistochemical similarities, including S100 positivity and negative staining for conventional melanocytic markers. We present 3 cases of cutaneous S100-positive spindle cell tumors in elderly patients, in which first findings led to initial misdiagnoses as cutaneous MPNST and benign peripheral sheath nerve tumor (neurofibroma). The identification of adjacent atypical melanocytic hyperplasia in the overlying skin along with tumor cell proliferation, also in the superficial dermis, the neurotropic component and the absence of any relationship between the tumor and a major nerve, pre-existing neural benign tumor or the existence of stigmata suggestive of neurofibromatosis raised consideration of a DM. Careful attention should be paid to the presence of a firm dermal nodule and atypical scar lesions especially in sun-exposed areas (mainly head and neck region) in elderly patients associated with S100-positive spindle cell proliferation, solar elastosis and adjacent atypical melanocytic proliferation. In such cases, the possibility of a DM should be excluded with caution, especially if the tumor reveals a paucicellular morphology resembling various non-melanocytic neoplasms including malignant or benign peripheral sheath nerve tumors.