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Pathology of Desmoplastic

Melanoma and Neurotropic


Dr Sampurna Roy MD               

Pathology Quiz Case 71: Case history and images

Diagnosis: Desmoplastic Melanoma




Desmoplastic melanoma (DM) is a variant of melanoma characterized by the presence of amelanotic fusiform melanocytes dispersed in a prominent collagenous stroma.

Desmoplastic neurotropic melanoma (DNM) is a neurotropic variant of desmoplastic melanoma.

DM and DNM occurred most often in lentiginous-type melanomas. Lentigo maligna melanoma is associated with DM and DNM

Clinical presentation:

The clinical presentation of DM and DNM differs from that of other melanomas. These lesions usually occur in older patients (median age of 61 years, compared with a median age of 46 years for other melanomas.)

Clinically, the lesions are usually found on the head and neck region and present as bulky firm fibrous masses of tumour or indurated plaques.

These are usually amelanotic lesions.

Most desmoplastic melanomas are variants of lentigo maligna melanoma.

Microscopic features:

Poorly demarcated, infiltrating intradermal tumours often with sparse cellularity.

The tumour consists of elongated spindle-shaped (fibroblast like) cells surrounded by mature collagen bundles. 

A few scattered cells display hyperchromatic, atypical nuclei.  Occasional mutinucleate cells may be present.

The tumour displays haphazard, fascicular or storiform growth pattern.

The stromal component varies in different tumours. 

In spindle cell melanoma there is less desmoplasia. 

In desmoplastic melanoma there are scattered collection of lymphocytes and plasma cells.

It is often difficult to find melanin in usual Hematoxylin and Eosin sections.

Small foci of neural transformation and neurotropism may be present. 

The presence of neurotropism correlates with a tendency to local recurrence.

Mitotic figures are usually present.

Desmoplastic melanoma is often associated with a lentigo maligna epidermal component overlying or towards one edge of the lesion.

The tumour infiltrates deep and it may be difficult to estimate the full extent of the tumour.


The tumour cells are positive for S100 protein and neuron specific enolase in about 95% of cases.

HMB45 is usually negative in desmoplastic melanoma.

In spindle cell melanoma about 50% of cases show some HMB45  positivity (these cases have aggressive behaviour)

Melan A is negative in desmoplastic melanoma. It has been reported  that some cases of metastatic desmoplastic melanoma are CD34 positive.

Actin is also expressed in some cases.

Occasionally, the spindle cells of desmoplastic melanoma can be negative for S100 protein , making distinction from other spindle cell lesions difficult.

Differential Diagnosis:

Desmoplastic melanoma should be distinguished  from other spindle cell lesions such as sclerosing melanocytic nevi,
nodular fasciitis,  atypical fibroxanthoma,  dermatofibrosarcoma protruberance and spindle cell squamous carcinoma and scar tissue.

Unlike immature scar tissue, in desmoplastic melanoma there is neurotropism, epidermal proliferation of melanocytes, and S100 protein and/ or HMB45 positivity. (Histologic differentiation of desmoplastic melanoma from cicatrices. Am J Dermatopathol. 1998;20(2):128-34)

The sclerotic/desmoplastic and hypopigmented blue naevi are uniformly positive for Melan-A, while desmoplastic melanoma is negative in the spindle cell compartment.

The nuclei in desmoplastic melanoma have a haphazard pattern and in scar tissue the nuclei have a  parallel arrangement.

Spitzoid melanoma (cells are more plump) should also be excluded from spindle cell melanoma (cells are longer and thinner, less aggressive clinical behaviour).

Neurotropic Melanoma:

Neurotropic melanoma is a rare variant of cutaneous melanoma.

The tumour has high incidence of local recurrence and low rate of distant metastases

The neurotropic melanoma is characterized by spindle shaped cells showing neuroma-like pattern.

These tumour cells infiltrate around nerve bundles in the deep dermis and subcutaneous tissue. Hence the lesion is called neurotropic melanoma.

Often a combined desmoplastic and neurotropic patterns are present. 

Differential diagnosis : Neural and melanocytic lesions (desmoplastic melanocytic nevus , neurofibroma and malignant schwannoma).

Diagnostic clues:

- Search for lentiginous and junctional components in a spindle cell lesion of actinically damaged skin.

- Asymmetrical lesion.

- A greater degree of atypia in the deep dermal and subcutaneous components.

- Single files of atypical spindle cells among sclerotic collagen bundles.

- The lymphoid reaction at the advancing edge of the lesion.

- Neurotropic growth. Invasion of deep vascular channels


Further reading:

Biology of desmoplastic melanoma: a case-control comparison with other melanomas.

Cutaneous desmoplastic melanoma.

Desmoplastic melanoma: a pathologically and clinically distinct form of cutaneous melanoma.

Neurotropic melanoma invading the inferior alveolar nerve.

Distinction of desmoplastic melanoma from non-desmoplastic melanoma by gene expression profiling.

Melanoma claims: from overreaction to oversight (College of American Pathologists).

Expression of Melan-A and Ki-67 in desmoplastic melanoma and desmoplastic nevi.

Cutaneous desmoplastic melanoma: reappraisal of morphologic heterogeneity and prognostic factors.

Desmoplastic melanoma: a diagnostic trap for the unwary.  

Primary mucosal desmoplastic melanoma of the head and neck.

Desmoplastic neurotropic melanoma of the head and neck: the role of radiation therapy

Desmoplastic melanoma of the head and neck: histopathologic and immunohistochemical study of 28 cases.

Desmoplastic and neurotropic melanoma.

Desmoplastic malignant melanoma of the lip: a report of 6 cases and review of the literature.

S100-positive spindle cells in scars: a diagnostic pitfall in the re-excision of desmoplastic melanoma.

Desmoplastic and spindle cell melanomas express protein markers of the neural crest but not of later committed stages of Schwann cell differentiation.

Immunoprofile of MITF, tyrosinase, melan-A, and MAGE-1 in HMB45-negative melanomas.





Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)








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