Home > Skin melanocytic tumor > Atypical Spitz tumor (Spitz melanocytoma)

Skin melanocytic tumor

Spitz neoplasms

Atypical Spitz tumor (Spitz melanocytoma)


Resident / Fellow Advisory Board: Caroline I.M. Underwood, M.D.
Hailey Fisher, B.S.
Sepideh Nikki Asadbeigi, M.D.

Last author update: 4 January 2024
Last staff update: 4 January 2024

Copyright: 2002-2024, PathologyOutlines.com, Inc.

PubMed Search: Atypical Spitz tumor

See Also: Spitz nevus

Hailey Fisher, B.S.
Sepideh Nikki Asadbeigi, M.D.
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Clinical features | Diagnosis | Prognostic factors | Case reports | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Videos | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2
Cite this page: Fisher H, Asadbeigi SN. Atypical Spitz tumor (Spitz melanocytoma). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/skintumormelanocyticatypicalspitz.html. Accessed December 25th, 2024.
Definition / general
  • Atypical Spitz tumor (AST) is a classification of Spitz tumors that shares genetic and morphological characteristics between Spitz nevi and Spitz melanoma; it has variable potential for malignant progression
Essential features
  • Nevus that consists of epithelioid and spindled melanocytes and contains sufficient morphological and genetic atypia to distinguish from Spitz nevus but is insufficient for a diagnosis of melanoma
  • Has a higher risk of sentinel lymph node involvement but typically has an indolent behavior (Arch Pathol Lab Med 2015;139:1263)
  • Potential for malignancy is difficult to discern
  • Often contains HRAS mutation or tyrosine kinase fusions involving ROS1, NTRK1, NTRK3, ALK, BRAF, RET, MET and MAP3K8
Terminology
  • Spindle and epithelioid cell nevus with atypia and metastasis
  • Spitzoid tumor of uncertain malignant potential
  • Benign juvenile melanoma (historical)
  • Atypical Spitzoid melanocytic tumor
ICD coding
  • ICD-O: 8770/1 - Spitz melanocytoma (atypical Spitz tumor)
  • ICD-11
    • 2F20.Y - other specific types of melanocytic nevus
    • XH9WF4 - Spitz nevus, atypical
    • 2F72.1 - Spitzoid tumor of uncertain malignant potential
Epidemiology
Sites
Pathophysiology
  • Cell proliferation mediated by mutations in genes associated with Spitz tumor, such as kinase fusion or inactivation of CDKN2A
Clinical features
Diagnosis
  • Biopsy
  • Modified ABCD (asymmetry, border irregularity, color variegation, diameter > 6 mm) and dermoscopy are used for detection of Spitzoid lesions but biopsy is necessary to evaluate the degree of atypia (Lancet Child Adolesc Health 2019;3:646)
  • Any asymmetrical, raised or nodular lesion should be biopsied for evaluation of atypia (Br J Dermatol 2017;177:645)
Prognostic factors
Case reports
Treatment
Microscopic (histologic) description
  • Can be junctional, compound or dermal but compound form is more common
  • Greater degree of atypia compared to benign Spitz nevus (cytological atypia or architectural overlap with dysplastic nevus) and involves 1+ features atypical for Spitz nevus; not enough atypia to be equivocal to melanoma
  • Overlap features with benign Spitz nevus
    • Spitzoid cytomorphology
    • Junctional component with vertically oriented nests and retraction artifact
    • Intranuclear pseudoinclusion
    • Eosinophilic nucleoli
    • Epidermal hyperplasia
    • Vertical junctional nests
  • Overlap features with melanoma
    • Large size (> 10 mm)
    • Asymmetry
    • Poor circumcision
    • Ulceration
    • Deep dermal component
    • Absence of maturation
    • Increased dermal mitosis in deep or peripheral component
  • Primarily epithelioid, spindle or mixed melanocytes that may present with (Front Oncol 2022:12:889223)
    • Large tumor consisting of cellular fascicles of melanocytes
    • Expansile growth with compression of stroma
    • Most commonly asymmetrical
    • Lymphocytic infiltrate
    • Fewer Kamino bodies
    • Pagetoid spread (often peripheral)
    • Junctional nests with vertical orientation of cells (Arch Pathol Lab Med 2015;139:1263)
    • Average Breslow depth: 2.4 mm (Cancer 2009;115:631)
  • ASTs with ALK fusion (Am J Surg Pathol 2017;41:491)
    • Wedge shaped with large diameter
    • Plexiform growth of intersecting fusiform melanocytes
  • ASTs with NTRK1 fusion (Am J Surg Pathol 2017;41:491)
    • Smaller nests
    • Presence of Kamino bodies and rosette formation
  • ASTs with MAP3K8 fusion
Microscopic (histologic) images

Contributed by Sepideh Nikki Asadbeigi, M.D. and AFIP
ALK fusion

ALK fusion

infiltrative border

Infiltrative border

Atypical cytomorphology

Atypical cytomorphology

Bulbous infiltrating base

Bulbous infiltrating base


epidermal hyperplasia

Epidermal hyperplasia

Lack of maturation in the deep portion

Lack of maturation in deep portion

Large epithelioid cells with amphophilic <br>cytoplasm

Large epithelioid
cells with
amphophilic
cytoplasm

Positive stains
Negative stains
Molecular / cytogenetics description
Videos

Common histological features associated with Spitz nevus

Sample pathology report
  • Skin, left cheek, shave biopsy:
    • Atypical Spitz tumor (see comment)
    • Comment: The sections show nests of melanocytes involving the epidermis and upper dermis. The melanocytes are nested and show some pagetoid scatter. The melanocytes show pink-lavender cytoplasm with large nuclei. The nucleoli are conspicuous and eosinophilic. Mitotic figures are present in superficial dermis (2/10 high power fields). The nests show some maturation. Immunohistochemistry shows diffuse positivity with SOX10. HMB45 shows loss of staining with maturation. p16 shows preserved nuclear staining in majority of the melanocytes and PRAME is negative within the nevomelanocytes. BRAF V600E immunohistochemistry is negative. The overall histology is consistent with atypical Spitz tumor. The margins are involved and a complete excision is recommended.
Differential diagnosis
  • Benign Spitz nevus:
  • Spitzoid melanoma:
    • Older patients
    • Distinction can be very challenging with only light microscopy; all of the following features can be present in both AST and Spitz melanoma but are more common in melanoma (Arch Pathol Lab Med 2015;139:1263, Am J Dermatopathol 2012;34:478)
      • High grade cytologic atypia
      • Poor nesting and prominent pagetosis in junctional component
      • Deep, numerous, atypical and marginal mitosis
      • Intravascular invasion
      • High cellular density
      • Lack of maturation
      • Consumption of epidermis
      • Infiltrative pattern
      • Immunohistochemistry
        • Complete or extensive p16 loss
        • Strong and diffuse PRAME positivity
        • High Ki67 index
        • Deep HMB45 expression
      • Molecular findings
        • Presence of TERT, BRAF and CDKN2A alterations are supportive of Spitz melanoma diagnosis (Pediatr Dermatol 2022;39:409)
        • FISH: aberration in 9p21,6p25,11q13 and 8q24
        • Chromosomal microarray (comparative genomic hybridization): multiple (> 3) and complex chromosomal abnormalities
        • Lack of tyrosine kinase mutation
        • Lack of HRAS mutation
    • Cellular neurothekeoma:
      • Positive S100 and MelanA staining in ASTs and negative in cellular neurothekeoma
    • Epithelioid fibrous histiocytoma:
      • Negative melanocytic marker
      • Lack of junctional component
    • Dysplastic Clark nevus:
      • Commonly in older population with sun damaged skin
      • Lack of distinct spindle and epithelioid morphology seen in Spitz neoplasms
Board review style question #1
BRQ image


A 17 year old patient with an ulcerated pink papule on the face underwent a shave biopsy, which showed a tumor with cells staining strongly positive for MelanA and HMB45. The tissue was sent for molecular study. The presence of which alteration is more indicative of a malignant process?

  1. ALK
  2. GNAQ
  3. HRAS
  4. TERT
Board review style answer #1
D. TERT. The sections show a melanocytic proliferation with Spitzoid cytomorphology. Atypical features such as frequent mitosis and pushing borders are present, which can be seen in both ASTs and Spitz melanomas. The presence of TERT is supportive of a Spitz melanoma diagnosis. Answers A and C are incorrect because ALK fusion and HRAS deletion are common in Spitz lesions and can be observed in benign, atypical and malignant lesions. Answer B is incorrect because GNAQ mutation is common in blue nevi.

Comment Here

Reference: Atypical Spitz tumor (Spitz melanocytoma)
Board review style question #2
Which immunohistochemical pattern is more indicative of an atypical Spitz tumor rather than a benign Spitz nevus?

  1. HMB45 positivity in junctional melanocytic nests
  2. Negative BRAF V600E in melanocytic nuclei
  3. p16 positivity in 40% of melanocytes
  4. Weak PRAME positivity in 5% of melanocytes
Board review style answer #2
C. p16 positivity in 40% of melanocytes. Complete or extensive loss of p16 is more supportive of an atypical or malignant Spitz neoplasm. CDKN2A homozygous deletion can lead to p16 loss, which is indicative of a higher grade or malignant lesion. Answer B is incorrect because BRAF V600E immunohistochemistry is generally negative in Spitzoid lesions and its positivity should raise suspicion of melanoma. Answer A is incorrect because HMB45 shows a loss of staining with descent and the positivity of the stain only in the junctional component is supportive of benignity. Answer D is incorrect because weak and focal PRAME positivity (1+) is not strongly supportive of an atypical lesion and can be observed in benign Spitz nevi.

Comment Here

Reference: Atypical Spitz tumor (Spitz melanocytoma)
Back to top
Home > Skin melanocytic tumor > Atypical Spitz tumor (Spitz melanocytoma)
Image 01 Image 02