Desmoplastic Neurotropic Melanoma Research Articles

Desmoplastic melanoma, neurotropism, and neurotrophin receptors--what we know and what we do not.

Desmoplastic melanoma (DM) is a relatively rare cytomorphologic variant of melanoma with a marked propensity for perineural invasion (PNI). Historically, DMs that display PNI have been grouped under the umbrella term of neurotropic melanoma (NM). However, definitions for NM and desmoplastic NM are not consistent in the literature, presenting a barrier to a comprehensive understanding of these lesions. In this review, we parse the literature on DM, NM, and desmoplastic NM, to clarify definitions and ascertain the incidence of PNI, with a view toward understanding its prognostic relevance. Neurotrophins, which represent a family of signaling peptides important to the development and maintenance of the peripheral nervous system, have been implicated in the pathogenesis of PNI in select lineage-unrelated malignancies. Given this, we also detail evidence linking neurotrophins and their receptors (TrkA, RET, p75NGFR, and NCAM) to the pathogenesis of PNI in melanoma.

Recurrent head and neck desmoplastic melanoma with perineural spread along the nervus mandibularis revealed by 18F-FDG PET/CT

This report describes a rare case of recurrent head and neck desmoplastic neurotropic melanoma with perineural spread along the nervus mandibularis. An 87-year-old male presented with a rapidly growing mass on the right side of the chin, 4 years after surgical excision of a desmoplastic non-melanotic melanoma of the tip of the chin, with lymphadenectomy of the right side submental and submandibular areas. A panoramic X-ray showed extensive widening of the mandibular canal compatible with perineural tumour growth. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) images revealed intense pathological uptake in the recurrent tumour mass located in the right lower buccal fold, and linear pathological uptake in the mandibular canal. Although magnetic resonance imaging is considered the standard of reference, recognition of perineural spread on 18F-FDG PET/CT is important, as it usually leads to a change in patient management from cure to palliation and may avert further diagnostic procedures.

Neuropathic pain in a patient with metastasis of a desmoplastic neurotropic melanoma to the trigeminal nerve: a case report

A 39-year-old female presented to our clinic with nonradiating, sharp, burning pain localized to the left ear and left neck. The patient has a history of desmoplastic neurotropic melanoma (DNM) in her left chin area and had undergone previous resections and chemoradiation. She was initially diagnosed with DNM sixteen years prior. Shortly after, she underwent resection of the melanoma. One year after the resection, the patient had a recurrence of her cancer. She had a second surgery with subsequent interferon chemoradiation. The patient remained in remission until three years later, when she was found on MRI to have a metastasis to her left temporal lobe and left trigeminal nerve. Along with a complete resection of the tumor, she underwent a course of cisplatin and radiation. Subsequent to this treatment, she started experiencing worsening pain in her left ear and left neck. On examination, the patient had decreased sensation in her left face along the jawline towards the left lip. She was initiated on gabapentin and the dosage was slowly titrated to 800mg BID and 1200mg QHS. Unable to tolerate the high dosage of gabapentin, she was started on methadone 5mg BID and gabapentin was titrated to 800mg TID. On this regime, the patient achieved adequate control of her neuropathic pain. DNM is a rare type of spindle cell melanoma that is locally aggressive with a high risk of local recurrence. Metastasis to the trigeminal nerve from a DNM is a rare presentation and has been reported in four cases in the literature. Aggressive chemoradiation usually ensures diagnosis and resection. As a result, chemoradiation induced neuropathic pain can also be an expected complication in these patients. However, this is the first report of successful treatment of the neuropathic pain due to local tumor invasion or a side effect of chemotherapy treatment.

Intracranial Trigeminal Nerve Metastasis of a Desmoplastic Neurotropic Melanoma: Case Report

Desmoplastic neurotropic mela-noma is a rare and highly malignant variant of melanoma. Solitary nervus trigeminus and Gasserian ganglion metastasis of a neurotropic melanoma has not been previously described in the literature. A 69-year-old man presented to our clinic with trigeminal neuralgia. 4 years previously he underwent tumor removal with an initial diagnosis of amelanotic malignant cutaneous melanoma; 1 year later, because of tumor recurrence, the patient underwent neck dissection, chemotherapy and radiation. Magnet resonance imaging (MRI) disclosed an enhancement of the Gasserian ganglion and tumor extension along the mandibular and maxillar nerves of the intracranial part of the trigeminal nerve suggestive of tumor. The intraoperative macroscopic appearance of the tumor was compatible with a neurinoma. Histopathological studies proved the tumor to be a desmoplastic neurotropic melanoma (DNM) that was related to the previously treated malignant melanoma. A metastatic tumor arising solely in a trigeminal nerve from a cutaneous malignant melanoma is quite rare; to our knowledge this may be the first report of such a case in the literature.

Desmoplastic neurotropic melanoma

Several studies have suggested that desmoplastic neurotropic melanoma (DNM) is associated with higher local recurrence rates than other types of melanoma. The authors investigated the local recurrence rates for patients with DNM after surgery alone or surgery followed by radiotherapy (RT). One hundred twenty-eight patients with DNM were treated at the Sydney Melanoma Unit and the Sydney Cancer Center from 1996 to 2007. All patients underwent local excision, 27 patients also received RT. For both groups, clinical and pathologic features, treatment details, and local recurrence data were analyzed. The median age at diagnosis was 65.5 years. The ratio of men to women was 2.7:1. The head and neck was the most common location (51%). The median Breslow thickness was 4 mm, and 99% of patients had Clark Level IV or V primary tumors. Patients who received adjuvant RT had thicker tumors (P = .003), deeper Clark level invasion (P < .001), and narrower excision margins (P < .001). There were 8 local recurrences, including 6 (6%) in the surgery only group and 2 (7%) in the adjuvant RT group. A positive margin (P < .001) and head and neck location (P = .03) were significant predictors of local recurrence. The local recurrence rate in this series was lower than the rates reported in historic control groups and in the authors' previous temporal cohort. The results indicated that clear surgical margins are of paramount importance in minimizing local recurrence; when margins are compromised, the addition of RT may reduce local recurrence rates compared with historic controls. A prospective randomized trial is needed to quantify the risk reduction with adjuvant RT.

Desmoplastic Neurotropic Melanoma in a Patient With Trigeminal Neuralgia

A 51-year-old man presented with a hard subcutaneous nodule adhering to the underlying bone structures of the left eyelid in 2004. Histopathology showed a desmoplastic neurotropic melanoma (DNM) with perineural invasion. Patient presented with a first recurrence in October 2005, which was treated by surgery. In August 2006 he presented with trigeminal neuralgia of the left face in the area innervated by the first and second branches of the trigeminal nerve. A PET scan clearly shows the tumoral hypermetabolism of the subcutaneous recurrence of the neurotropic melanoma with invasion of the second or maxillary branch that follows the nerve up to the trigeminal ganglion, which was detected despite the physiological high uptake in the temporal lobe. MRI confirms the invasion and a second PET and MRI 6 months later done to evaluate resectability showed progressive disease. DNM is a rare subtype of spindle cell melanoma. It corresponds to dermal proliferation of desmoplastic cells of neural differentiation. Unlike other melanomas, however, survival for DNM may be better compared with other forms of melanoma. This rare case report presents PET imaging involving cranial nerve invasion by this uncommon melanoma subtype.

Collision of desmoplastic‐neurotropic melanoma and squamous cell carcinoma on the lip

We report on a case of the collision of a desmoplastic-neurotropic melanoma and a squamous cell carcinoma on the lip. A 46-year-old male developed a multifocal infiltrative squamous cell carcinoma of the lower lip, which also showed sparse melanocyte atypia within the epidermis and an extensive spindle cell proliferation within the dermis, subcutaneous tissues and nerves. An immunohistochemical panel showed that the spindle cells were melanocytes, not derived from the squamous cell carcinoma. Double labeling with AE1/AE3 and S100 showed striking localized proximity of the spindle-cell melanocytic and keratinocyte components in some areas of this tumor. To our knowledge, this is the first report of the collision of a squamous cell carcinoma and desmoplastic-neurotropic melanoma.

Sclerosing ‘Mucinous’ Blue Nevus: A Clinical Simulator of Dermatofibroma

Abundant mucin deposition is an unusual finding for melanocytic lesions. This notion, however, should be toned down since mucin may be present in distinct melanocytic lesions. Indeed, following the first description of mucin depositions in neural differentiated naevi by Maize and Ackerman in 1987 1 this phenomenon was repeatedly observed.2,3,4,5 Especially in blue naevi mucin deposition is a peculiar observation. For blue naevi 5 variants are distinguished to avoid the misdiagnosis of melanoma with stromal mucin deposition6: (i) neural nevus, (ii) myxoid intradermal nevus, (iii) alveolar cellular blue nevus, (iiii) ancient melanocytic nevus, (v) sclerosing blue nevus. In 2003, Rongioletti and Innocenzi described the first two examples of sclerosing blue naevi with an abundant mucinous stroma. Herein, we describe the third case of this rare entity. It should be noted, that particularly this uncommon variant of a blue naevus is easily mistaken as desmoplastic-neurotropic melanoma in which the present stromal deposition of mucin is a more typical finding. A specimen from the right lower leg of a 53-year old man was referred to our dermatopathology department with the clinical diagnosis of a dermatofibroma. Clinically, the tumor appeared as a brown lesion with a regular and sharp border. The histopathological work up revealed a symmetrical, well circumscribed papule; the fibro-mucinous stroma contained spindle-shaped and dendritic melanocytes, which sometimes were arranged in whorls (Fig. 1A). Orderly arranged melanocytes in the periphery were characterized by pigmentation, as confirmed by melanin-staining. Melanophages were present as clearly seen in the reaction against CD68. Alcian blue staining confirmed the mucin deposition within the tumor and excluded an intradermal component (Fig. 1B). Immunohistochemical staining with Mart-1 (Fig. 1D) and S-100 confirmed both the nature and the distribution of the melanocytes. Notably no reaction was found against MIB-1 excluding a high proliferation rate (Fig. 1C). Thus all criteria for the diagnosis of a sclerosing mucinous blue naevus were fulfilled, and the differential diagnosis of a malignant melanoma was excluded. Moreover, the clinical diagnosis of a dermatofibroma was ruled out by lack of either epidermal changes or typical infiltrating pattern. Hemosiderin deposits which mimic melanin were excluded by special staining. Figure 1. (A) Fibro-mucinous stroma with spindle-shaped and dendritic melanocytes, which sometimes were arranged in whorls. Melanophages were present (20x Hematoxylin and Eosin). (B) Alcian blue staining confirmed the mucin deposition within the tumor (20x Mucin). ... The cause of mucin deposition in melanocytic lesions remains elusive. It was attributed to a partial involution of the respective lesions. Interestingly, the dermoscopy of the presented sclerotic blue nevus revealed a hypopigmented center; a notion which has been described before.7 In line with this hypothesis it is well established that cellularity of naevi decrease which age, whereupon melanocytes are replaced by fibrous matrix, mucin and sometimes fat.8 With the present case report we like to raise the awareness for this rare entity because of the momentous differential diagnosis. Further reports of such cases would help to learn more about its clinical, dermoscopic and histological features.

Melanoma of the nose.

Melanoma of the nose is rare and management guidelines are poorly defined. In the past, excision margins have often been much narrower than for melanoma elsewhere. The study was a retrospective clinicopathological study of 34 patients with cutaneous melanoma of the nose treated in a single unit. Desmoplastic neurotropic melanoma and lentigo maligna melanoma were the most common histological tumour types. Local recurrence occurred in eight patients, and in six cases appeared to be a result of inadequate excision margins. Regional lymph node metastases were associated with a very poor prognosis. Adequate surgical excision is the mainstay of successful treatment for melanoma of the nose. Excision margins for nasal melanoma should not be any less than for melanoma elsewhere. Careful planning is required, not only to gain local disease control and the best chance of cure, but also to achieve functionally and aesthetically acceptable results. Excision margins need not be compromised in view of the variety of local flaps that can be employed to close the primary defect.

Neurotropic melanoma invading the inferior alveolar nerve

Desmoplastic neurotropic melanoma (DNM) and neurotropic melanoma (NM), rare lesions of the head and neck, often present as a benign-appearing nodule which later progresses to cranial nerve involvement. To discuss treatment and outcome of 3 cases of DNM/NM of the lower lip. Three case reports with 12- to 54-month follow-up and literature review. The first case had an initial excision of melanoma of his lower lip and presented 16 years later with severe bilateral atrophy of his muscles of mastication with NM and underwent intensity modulated radiation therapy but no further resection. We also report two other cases of DNM of the lip, one of which received gamma knife radiosurgery for intracranial extension. Small retrospective case series. Locoregional recurrences from DNM are more common than distant metastasis warranting vigilant surveillance following resection of the initial lesion. Radiation therapy and gamma knife radiosurgery may be used for cases of unresectable recurrences.

Cutaneous Desmoplastic Melanoma

Desmoplastic melanoma (DM) is a fibrosing variant of spindle cell melanoma. It most often presents as an indurated lesion in chronically sun-damaged skin. Due to the lack of characteristic clinical features, early detection is uncommon. At the time of excision, the tumors usually extend into the reticular dermis or deeper. DM is prone to misdiagnosis. It may simulate histologically sclerosing melanocytic nevi as well as various benign and malignant nonmelanocytic lesions. There is significant morphologic variability among tumors classified as DM. Desmoplasia may be prominent throughout the entire tumor ("pure" DM) or represent a portion of an otherwise nondesmoplastic melanoma ("combined" DM). Some tumors show neuroma-like features with prominent nerve involvement, in which case the term "desmoplastic neurotropic melanoma" is used. Immunophenotypically, DMs are usually strongly and homogeneously positive for S-100 protein but are often negative or only focally positive for melanocyte differentiation antigens such as tyrosinase, gp100, Melan-A, and microphthalmia transcription factor. DM differs from conventional melanoma in its clinical course. It is associated with a higher tendency for local recurrence, but metastases to regional lymph nodes are less common. Evidence is also emerging that for patients with thick melanomas, the presence of a paucicellular fibrosing tumor histology (pure DM) is a favorable prognostic factor for survival.

Consultative (expert) second opinions in soft tissue pathology. Analysis of problem-prone diagnostic situations.

We reviewed 500 consecutive soft tissue lesions referred for expert consultation to determine types of lesions and/or situations in which major discrepancies occur. Of 266 cases (53.2%) accompanied by a diagnosis, essential agreement with the second opinion was noted in 68%, minor discrepancy in 7%, and major discrepancy in 25%. The 65 major discrepancies were distributed proportionally to the referring sources and could be divided into 4 groups: benign mesenchymal lesions diagnosed as sarcomas (45%), sarcomas diagnosed as benign tumors (23%), nonmesenchymal lesions diagnosed as sarcoma (20%), and major grading discrepancies (12%). Relatively few lesions accounted for a major proportion of major discrepancies. Problematic lesions were lipoma and fasciitis and their variants and desmoplastic-neurotropic melanoma. Needle biopsy specimens were somewhat more likely to be associated with a discrepant opinion. With the exception of nonmesenchymal lesions, the diagnosis for all major discrepant cases could be made on the basis of the H&E-stained slides, suggesting that failure to perform immunostains did not account for discrepancies. Lack of familiarity with rare or unusual lesions is probably more significant in explaining diagnostic discrepancies than is the increasing use of needle biopsy or the failure to perform immunohistochemical analysis.

Allelic loss at the neurofibromatosis type 1 (NF1) gene locus is frequent in desmoplastic neurotropic melanoma.

Mutations of the tumour-suppressor gene NF1 (neurofibromatosis 1) have been observed in neurofibromas and neurofibrosarcomas of patients with von Recklinghausen's disease and in sporadic nerve sheath tumours. In contrast, melanoma, another tumour type of neuroectodermal origin, rarely shows NF1 alterations. Desmoplastic neurotropic melanoma (DNM) is an uncommon melanoma subtype that shares morphological characteristics with nerve sheath tumours. Therefore, we analysed 15 DNM and 20 melanomas without morphological features of desmoplasia or neuroid differentiation (common melanomas) for loss of heterozygosity (LOH) at the NF1 locus and flanking regions. Allelic loss was detected in 10/15 (67%) DNM but only in 1/20 (5%) common melanomas. LOH was most frequently observed at marker IVS38, located in intron 38 of NF1. These data suggest a role for NF1 in the pathogenesis of DNM and support an earlier hypothesis that exon 37 might encode a functional domain. DNM may represent an interesting tumour model tor the further elucidation of the cellular functions and tumour-suppressive potential of neurofibromin.

De novo desmoplastic neurotropic melanoma of the lower lip: A neoplasm with ominous behavior

Desmoplastic neurotropic melanoma represents a rare histologic variant of malignant melanoma that is characterized by a proliferation of spindle cells in a densely collagenous stroma with pronounced neurotropism. A 60-year-old man appeared for evaluation of a mass in the lower lip. The labial mucosa was intact, and the lesion had been present for 2 months. The tumor was surgically removed, and after immunohistochemical and ultrastructural analysis it was diagnosed as desmoplastic neurotropic melanoma. The tumor recurred 6 months later, with involvement of the inferior alveolar nerve.

Desmoplastic and desmoplastic neurotropic melanoma

BACKGROUND It has been suggested that desmoplastic melanoma (DM) and desmoplastic neurotropic melanoma (DNM) are associated with worse prognoses and higher local recurrence rates than other forms of melanoma. In the current study, a large series of patients with DM and DNM treated at a tertiary referral center was reviewed. METHODS For 190 patients with DM and 90 patients with DNM accrued over a 10-year period, clinical features were recorded and all available histopathology was reviewed. The associations between clinical and pathologic variables, biologic behavior, and eventual outcome were analyzed. RESULTS The male-to-female ratio was 1.75:1 and the median patient age 61 years. The median tumor thickness was 2.5 mm, and 44% of cases were amelanotic. Five-year survival was 75%. Significant predictors of overall survival were a high mitotic rate (P = 0.003) and tumor thickness (P = 0.011). All the DNMs exceeded 1.5 mm in thickness and were graded as Clark's level IV or V. There was a significant increase in local recurrence when neurotropism was present (P < 0.001). The rate of local recurrence was not higher for DM than for other cutaneous melanomas. CONCLUSIONS There was no statistically significant difference in survival for patients with DM and those with DNM, and overall survival for both was similar to that for patients with other cutaneous melanomas. However, there was a lower rate of regional lymph node metastasis at initial presentation and as the first recurrence for both DM and DNM. The local recurrence rate was higher when the surgical clearance margin was <1 cm and when neurotropism was present. Cancer 1998;83:1128-1135. © 1998 American Cancer Society.

Desmoplastic and desmoplastic neurotropic melanoma

It has been suggested that desmoplastic melanoma (DM) and desmoplastic neurotropic melanoma (DNM) are associated with worse prognoses and higher local recurrence rates than other forms of melanoma. In the current study, a large series of patients with DM and DNM treated at a tertiary referral center was reviewed. For 190 patients with DM and 90 patients with DNM accrued over a 10-year period, clinical features were recorded and all available histopathology was reviewed. The associations between clinical and pathologic variables, biologic behavior, and eventual outcome were analyzed. The male-to-female ratio was 1.75:1 and the median patient age 61 years. The median tumor thickness was 2.5 mm, and 44% of cases were amelanotic. Five-year survival was 75%. Significant predictors of overall survival were a high mitotic rate (P=0.003) and tumor thickness (P=0.011). All the DNMs exceeded 1.5 mm in thickness and were graded as Clark's level IV or V. There was a significant increase in local recurrence when neurotropism was present (P < 0.001). The rate of local recurrence was not higher for DM than for other cutaneous melanomas. There was no statistically significant difference in survival for patients with DM and those with DNM, and overall survival for both was similar to that for patients with other cutaneous melanomas. However, there was a lower rate of regional lymph node metastasis at initial presentation and as the first recurrence for both DM and DNM. The local recurrence rate was higher when the surgical clearance margin was <1 cm and when neurotropism was present.

Desmoplastic neurotropic melanoma

Desmoplastic neurotropic melanoma (DNM) is a rare variant of a spindle cell melanoma. The majority of these tumors occur on the head and neck of elderly patients. The rather variable clinical appearance (e.g. frequent lack of pigmentation) makes initial diagnosis often difficult. Histologically, DNM may show a lentiginous melanocytic proliferation with atypia and pleomorphic spindle cells in the dermis. Immunostaining for S-100 is usually positive although staining for HMB-45 is frequently absent. As with other melanomas, surgery is the first line treatment for DNM. Unlike other melanomas, however, survival for DNM may be better compared with other forms of melanoma.

Desmoplastic neurotropic melanoma. A clinicopathologic analysis of 28 cases

Desmoplastic neurotropic melanoma (DNM) is a rare variant of malignant melanoma, the natural history and histogenesis of which still are being defined. The clinical and histologic features of 28 cases of DNM were studied. All published cases of DNM to date were reviewed. Paraffin sections from 26 cases were investigated with a panel of 10 tissue markers. The ultrastructural features of seven cases were evaluated. A comparison of this study's findings with that of other published cases revealed many similarities regarding clinical and pathologic findings and outcome. The patients were white (15 men:13 women; mean and median age, 59 years; range, 22-83 years). Most tumors were located on the head and neck (75%) and were nonpigmented (57%). An associated intraepidermal melanocytic proliferation was identified in 85% of the patients (lentigo maligna in 56%). Histologically, the dermal tumors were composed of tapered, nonpigmented spindle cells in peripheral nerve sheath patterns resembling neuromas, schwannomas, neurofibromas, and perineurial proliferations accompanied by variable neurotropism and desmoplasia; desmoplasia was the most notable feature in most tumors. The mean depth of tumor invasion was 4.1 mm (range, 0.32-9.0 mm). Tumors with continuity between the epidermal and dermal components had a significantly thinner depth of invasion and a more extensive intraepidermal melanocytic proliferation than those tumors with a grenz zone between the two components (2.3 mm vs. 4.6 mm, P = 0.015). Mitotic activity ranged from 0/HPF in 10 cases, 1-6/high power field (HPF) in 12 cases, and to greater than 6/HPF in 4 cases. An ulcer was present in 5/27 tumors, regression in 4/27, a microsatellite in 1, and brisk and had nonbrisk tumor infiltrating lymphocytic responses in 2 and 14, respectively. Vimentin was uniformly positive and keratins AE1.3 and Cam 5.2 and Leu-7 were uniformly negative. S100 protein, also uniformly positive, had patchy reactivity in most tumors that expressed EMA (43%). Smooth muscle actin (52%), neuron-specific enolase (42%), and FXIIIa (30%) had patchy positivity. HMB-45 was reactive only in the epidermal and superficial papillary dermal component in 21% of cases. Ultrastructurally, the common features were long, often intertwining cellular processes, intercellular junctions, and discontinuous basal lamina. Melanosomes were not identified. Follow-up data available on 26/28 patients (mean, 36 months; median, 24 months; range, 5-132 months) showed 20 (70%) alive without disease, 2 alive with disease and 3 dead from disease. Seven patients had recurrent local tumor (multiple in four); four had lymph node metastases, and three had visceral metastases. Patients with recurrent disease of any type had significantly thicker tumors (5.4 mm vs. 3.4 mm, P = 0.046) and were more likely to have an ulcerated tumor (P = 0.03). Actuarial 5-year survival for tumors with greater than a 4-mm thickness was 72%, which was greater than that for other types of melanoma with greater than a 4-mm thickness. Desmoplastic neurotropic melanomas are neuroectodermal tumors that usually arise from an intraepidermal melanocytic proliferation but rarely develop de novo in the dermis. Schwannian and perineurial differentiation may account for the desmoplasia and neurotropism encountered in these neoplasms. Desmoplastic neurotropic melanomas present at a more advanced stage locally and may be associated with a better survival than associated with conventional melanomas of similar depth of invasion.

Cellular Neurothekeoma A Distinctive Variant of Neurothekeoma Mimicking Nevomelanocytic Tumors

We describe the clinical, histopathologic, and immunohistochemical characteristics of five examples of a distinctive subtype of neurothekeoma we term "cellular neurothekeoma" (CNT). These lesions are nondescript papules or nodules primarily involving the head and neck areas of young adults. Histopathologically, CNT are fairly well-defined proliferations involving the reticular dermis; they consist of fascicles of polygonal and spindle cells with eosinophilic or pale-staining cytoplasm and neuroid characteristics. Low-grade cytologic atypia and mitotic activity are common. All immunohistochemical markers--including S-100 protein, myelin basic protein, epithelial membrane antigen, and histiocytic antigens--have failed to show positivity in our laboratory. Separation from myxomatous variants of neurothekeoma is based on greater cellularity, less myxomatous change, and less pronounced plexiform compartmentalization by fibrous septae, which resemble perineurium. The differential diagnosis usually includes spindle and epithelioid cell (Spitz) nevus, malignant melanoma (particularly desmoplastic-neurotropic melanoma), cellular blue nevus, and fibrohistiocytic proliferations. The recognition of CNT and its differentiation from melanoma are important so that overly aggressive therapy is avoided.