Spindle cell melanoma

Author: Daniel Yiu, Foundation Year Doctor, Department of Infectious Diseases, Oxford Foundation School, Frimley Health NHS Trust, Wexham Park Hospital, Slough, Berkshire, United Kingdom. DermNet NZ Editor-in-Chief: Adjunct A/Prof. Amanda Oakley, Dermatologist, Hamilton, New Zealand. Copy edited by Gus Mitchell. January 2019.

What is spindle cell melanoma?

Spindle cell melanoma is a rare histological variant of melanoma characterised by the presence of spindle-shaped melanocytes [1]. On microscopy, it is often mistaken for other skin and soft tissue cancers with spindle cell morphologies.

Desmoplastic melanoma is a variant of spindle cell melanoma where there are varying proportions of spindle cells and desmoplastic cells.

Further studies are needed to clarify clinical manifestations, risk factors, treatment management and prognosis of spindle cell melanoma.

Histologically proven spindle cell melanomas

Who gets spindle cell melanoma?

The actual incidence of spindle cell melanoma is unknown. Studies have suggested that between 1 and 14% of melanomas are of the spindle cell variant (including desmoplastic melanoma) [2,3].

Spindle cell melanomas more commonly occur in Caucasian males, affecting men and women at a ratio of 1.6:1 to 1.9:1 respectively. The average age at diagnosis is 50–80 years [1,4].

What causes spindle cell melanoma?

The exact cause of spindle cell melanoma is unknown. Spindle cell melanoma shares common mutations with conventional (epithelioid) melanoma.

  • Approximately 30% of spindle cell melanomas contain BRAF mutations, of which V600E is the most common.
  • NRAS and KIT mutations are rarely seen [4].

An association between spindle cell melanoma (including desmoplastic melanoma) and lentigo maligna has been observed in sun-exposed areas [5].

What are the clinical features of spindle cell melanoma?

Spindle cell melanoma frequently presents as a non-specific amelanotic (nonpigmented) nodule on the trunk, head, or neck [1,3].

It may also first present as widespread melanoma metastases.

What are the complications of spindle cell melanoma?

Metastasis is the major complication of spindle cell melanoma. Delays in diagnosis can occur due to its atypical presentation histologically [1–3].

Metastatic spindle cell melanoma

How is spindle cell melanoma diagnosed?

The non-specific features may lead to delays in the diagnosis of spindle cell melanoma, which is often not suspected clinically. The diagnosis is generally made on a biopsy of the lesion but can also be commonly mistaken for another tumour histologically [6].

A combination of histological clues and immunohistochemistry markers are required to diagnose spindle cell melanoma [3].

Features of spindle cell melanoma under microscopy include:

  • An abundance of spindle-shaped tumour cells (> 90% of a tumour)
  • Uniform, wavy and slender nuclei, with mild to moderate pleomorphism and with variable nuclear atypia
  • High mitotic index
  • Greater cellular cohesion on cytology than epitheloid types of melanoma [2,7]
  • Pagetoid spread of atypical melanocytes in spindle cell melanoma associated with lentigo maligna [8].

Special stains may be used to differentiate spindle cell melanoma from other spindle cell tumours.

  • S100, SOX10, p75m HMB-45, laminin T, laminin NT, melan-A, C-KIT are positive in spindle cell melanoma [2,3].
  • In spindle cell melanoma, a higher proportion of cells show Ki-67, cyclin D, and survivin after staining [9].
  • Cytokeratin stains are negative [10,11].

What is the differential diagnosis for spindle cell melanoma?

Spindle cell melanoma can be easily confused with other spindle cell tumours.

Desmoplastic melanoma

Desmoplastic melanoma was described as a variant of spindle cell melanoma in 1971 [6]. Recent studies suggest that desmoplastic melanoma and spindle cell melanoma represent two distinct types of melanoma, as differences in staining, genetic mutations, and clinical manifestations have been found [3].

  • When spindle cells represent > 90% of a tumour, a diagnosis of spindle cell melanoma is made.
  • When > 90% of a tumour is composed of desmoplastic cells, a diagnosis of desmoplastic melanoma is made.
  • Melanomas with both spindle cell and desmoplastic components at varying levels between 10% and 90% are referred to as mixed variants [2,3,12].
  • Collagen IV, CD68, MDM2 and Trichrome are positive in desmoplastic melanoma [3].
  • HMB-45, laminin T, laminin NT, Melan-A, and C-KIT are negative [2,3].

Reed naevus

Reed naevus (also called pigmented spindle cell nevus) is a melanocytic naevus with a largely spindle-cell appearance under microscopy. The architecture is symmetrical with good lateral demarcation, epidermal hyperplasia, and uniform nests of cells [9].

Cutaneous clear cell sarcoma

The differentiation of cutaneous clear cell sarcoma from spindle cell melanoma is largely histological, as both may stain positively for S100, HMB45 and Melan-A. Cutaneous clear cell sarcoma tends to show uniform patterns of spindle cell fascicles under microscopy, which are present throughout an entire tumour and encased by fibrous septa. The stroma tends to be hyalinised, sclerotic and reticulated [13].


Leiomyosarcoma pathology may be indistinguishable morphologically from melanoma.

  • Smooth muscle actin (SMA) stain is positive in leiomyosarcoma.
  • S100, P75, or HMB-45 are negative [10,14].

Atypical fibroxanthoma


  • Vimentin is positive in fibrosarcoma.
  • S100 and HMB-45 are negative [5,14].

Peripheral nerve sheath tumours

  • S100, CD34 and GAP43 are positive in peripheral nerve sheath tumours.
  • HMB 45 and Melan-A are negative [10,15].

Dermatofibrosarcoma protuberans

Spindle cell squamous cell carcinoma

  • Cytokeratin stains such as 34 beta E12 are positive in spindle cell squamous cell carcinoma.
  • S100 and HMB-45 is usually negative.
  • P75 is variable [10,11].

What is the treatment for spindle cell melanoma?

Treatment of spindle cell melanoma is similar to other forms of melanoma. Surgical excision is the first step in management [1].

What is the outcome for spindle cell melanoma?

Although the tendency for nodal involvement is low, the majority of spindle cell melanomas present with advanced disease [3]; worse prognosis is seen in Caucasian males of age > 66 years.

Advanced disease with nodal and distal metastasis is associated with worse outcomes in spindle cell melanoma, as are higher grades, which have been associated to poorer disease-specific survival (DSS) and overall survival (OS) [1].

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Related information



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  2. Piao Y, Guo M, Gong Y. Diagnostic challenges of metastatic spindle cell melanoma on fine-needle aspiration specimens. Cancer 2008; 114(2): 94–101. PubMed
  3. Weissinger SE, Keil P, Silvers DN, Klaus BM, Moller P, Horst BA, et al. A diagnostic algorithm to distinguish desmoplastic from spindle cell melanoma. Mod Pathol 2014; 27(4): 524–34. PubMed
  4. Kim J, Lazar AJ, Davies MA, Homsi J, Papadopoulos NE, Hwu WJ, et al. BRAF, NRAS and KIT sequencing analysis of spindle cell melanoma. J Cutan Pathol 2012; 39(9): 821–5. PubMed
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  13. Hantschke M, Mentzel T, Rutten A, Palmedo G, Calonje E, Lazar AJ, et al. Cutaneous clear cell sarcoma: a clinicopathologic, immunohistochemical, and molecular analysis of 12 cases emphasizing its distinction from dermal melanoma. Am J Surg Pathol 2010; 34(2): 216–22. PubMed
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Other websites

  • Spindle Cell Melanoma — NCI Thesaurus. National Institutes of Health. U.S. Department of Health and Human Services [cited November 17 2018]. 

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