Skin melanocytic tumor
Spitz neoplasms
Spitz nevus
Author: Katharina Wiedemeyer, M.D.
Editorial Board Members: Kiran Motaparthi, M.D., Robert E. LeBlanc, M.D.
Last author update: 15 November 2021
Last staff update: 13 October 2023
Copyright: 2002-2024, PathologyOutlines.com, Inc.
PubMed Search: Spitz nevus [title] review[ptyp]
See also: Atypical Spitz nevus
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Wiedemeyer K. Spitz nevus. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/skintumormelanocyticspitz.html. Accessed December 24th, 2024.
Definition / general
- Spitz nevi are benign neoplasms composed of large epithelioid or spindled melanocytes (Adv Anat Pathol 2010;17:73)
Essential features
- Benign melanocytic tumors
- Composed of large spindled and epithelioid melanocytes
- Primarily affect children and young adults
- Treatment options: observation or complete excision
Terminology
- First described by Sophie Spitz in 1948 (Am J Pathol 1948;24:591)
- Synonyms for Spitz nevus:
- Spindle cell nevus
- Spindle and epithelioid cell nevus
ICD coding
- ICD-O: 8770/0 - epithelioid and spindle cell nevus
Epidemiology
- Exact data about prevalence and incidence are lacking
- Approximately 1 - 2% of all excised nevi are Spitz nevi
- Predilection for children and young adults but may occur at any age
- Females are affected more commonly than males
- Congenital Spitz nevi are very rare
- References: Cancer 1977;40:217, Am J Surg Pathol 2002;26:654
Sites
- Anatomical distribution of Spitz nevi is wide
- Lower extremities, the face (especially in children) and the trunk (preferably in adults) are most commonly affected
- Reference: Adv Anat Pathol 2010;17:73
Pathophysiology
- Generally arises de novo and lacks oncogenic mutations common to conventional and blue nevi
- Congenital variants have been described
Etiology
- Etiology of Spitz nevi is unknown
- Spitzoid melanocytic neoplasms have significant morphologic and molecular differences from conventional melanocytic lesions
Clinical features
- Prototypic or conventional Spitz nevi are solitary, well circumscribed, symmetrical, pink or pigmented, dome shaped papules several millimeters in size, typically < 6 mm
- May appear verrucous and may ulcerate
- Can resemble hemangioma or pyogenic granuloma
- Rarely occur in multiples, either disseminated or in clusters (agminated Spitz nevi)
- Show a risk of recurrence after incomplete excision
- Behavior is entirely benign
- Reference: Am J Dermatopathol 2009;31:107
Diagnosis
- The diagnosis of conventional Spitz nevi is straightforward clinically and histopathologically
- Spitz nevi need to be distinguished from atypical Spitz tumors and spitzoid melanomas including Spitz melanomas
Laboratory
- Not applicable; no laboratory values exist to diagnose or monitor Spitz nevi
Prognostic factors
- Conventional Spitz nevi are benign, the prognosis is good
- Recurrences should be treated with re-excision
Case reports
- Infant with a congenital Spitz nevus clinically mimicking melanoma (J Am Acad Dermatol 2002;47:441)
- 4 year old boy with acral pigmented Spitz nevus that clinically mimicked acral lentiginous malignant melanoma (Ann Dermatol 2011;23:246)
- 4 year old Caucasian boy with agminated Spitz nevus arising in normal skin with redundant HRAS mutation (Eur J Dermatol 2017;27:73)
- 8 year old girl with a pseudogranulomatous Spitz nevus mimicking a granulomatous dermatitis (J Cutan Pathol 2013;40:330)
- 9 year old boy with angiomatoid Spitz nevus (Pathology 2016;48:739)
Treatment
- Complete excision with evaluation of margins
Clinical images
Gross description
- Well circumscribed, dome shaped pink or pigmented papule, size is several millimeters (usually < 1 cm)
Microscopic (histologic) description
- Conventional Spitz nevi are well circumscribed, symmetrical and show an overall wedge shaped silhouette
- Consist of large junctional and dermal melanocytic nests formed by spindled or epitheliod cells
- Melanocytes are large, spindled or epitheliod, contain abundant pale or ground glass cytoplasm and finely dispersed pigment (if present)
- Mild nuclear pleomorphism may occur, mitoses are rare or absent
- Melanocytic nests may show maturation with depth and break up into single melanocytes at the dermal base of the lesion
- Junctional nests often show separation artifacts (clefting) to the surrounding epidermis and are oriented perpendicularly to the epidermis
- Mild pagetoid scatter of single melanocytes may be a feature but is usually confined to the lower half of the epidermis and found only in the center of the lesion
- Transepidermal elimination of melanocytic nests may occur
- A typical finding of classic Spitz nevi are PAS+, eosinophilic, hyaline globules, so called Kamino bodies, located at the dermoepidermal junction
- Perivascular lymphocytic infiltrates are variably present
- Histopathological variants of Spitz nevi:
- Pigmented spindle cell nevus (Reed nevus)
- Angiomatous Spitz nevus
- Desmoplastic Spitz nevus
- Plexiform Spitz nevus
- Polypoid Spitz nevus
- Agminated Spitz nevus
- Pseudogranulomatous Spitz nevus
- Myxoid Spitz nevus
- Combined Spitz nevus
- Reference: J Am Acad Dermatol 2014;71:1077
Microscopic (histologic) images
Contributed by Katharina Wiedemeyer, M.D., Ph.D.
Symmetrical, sharply demarcated tumor
Nested spindled and epitheliod melanocytes
Epidermal hyperplasia and large junctional nests
Kamino bodies and clefting of junctional nests
Epithelioid cell morphology
No cell atypia within dermis
Spindle cell morphology
Cytology description
- Cytology is not performed on Spitz nevi; for cell morphology please see Microscopic (histologic) description
Positive stains
- S100
- MART1 / MelanA
- SOX10
- HMB45 in junctional melanocytes and cells of papillary dermis
- Ki67 proliferation index < 5%
- p16
- ALK, ROS, NTRK (in Spitz nevi with fusions involving ALK, ROS or NTRK)
- Reference: Mod Pathol 2003;16:505
Negative stains
Electron microscopy description
- No elecron miscroscopic studies of Spitz nevi exist
Molecular / cytogenetics description
- Biologically distinct entity, unlike common aquired melanocytic nevi and melanoma no BRAF or NRAS mutations
- Genomic rearrangements of ALK (ALK fusions), ROS1 and NTRK1 kinases can occur
- HRAS mutation occurs, especially in desmoplastic Spitz nevi
- References: Pathology 2016;48:113, Am J Surg Pathol 2014;38:925, Nat Commun 2014;5:3116
Sample pathology report
- Skin, left arm (clinical nevus), excision:
- Spitz nevus, conventional (see comment)
- Comment: The gross specimen is a 0.5 cm, pink-brown, dome shaped papule of the right arm. Microscopically, the tumor is symmetrical and well demarcated with a wedge shaped growth pattern. There is epidermal hyperplasia with hypergranulosis and hyperkeratosis. The tumor consists of large melanocytic nests composed entirely of spindle and epithelioid cells containing abundant cytoplasm with varying amounts of melanin granules. Single Kamino bodies are found at the dermal-epidermal junction, with occasional upward scatter of single melanocytes confined to the center of the lesion. No atypia is noted. Dermal melanocytes show maturation with depth and are dispersed singly within the collagen bundles at the base of the tumor. No dermal mitoses are found. Immunohistochemical staining demonstrates strong positivity for S100 protein; HMB45 staining is partially positive within junctional and upper dermal nests. The margins are clear.
Differential diagnosis
- Atypical Spitz tumor:
- Age usually > 10 years or postpubertal
- Atypical Spitz tumors are usually larger (> 5 - 10 mm) than Spitz nevi and show some worrisome histological features, such as asymmetry, pagetoid scatter in the periphery of the tumor, moderate nuclear pleomorphism and hyperchromatic nuclei
- Mitotic rate can be increased but no mitoses are found in the deep dermis
- There is no reliable immunohistochemical marker to distinguish atypical Spitz tumor from Spitz nevus or Spitz melanoma
- Malignant Spitz tumor / Spitz melanoma:
- Age usually postpubertal
- Histopathological criteria of malignancy are size > 10 mm, an asymmetric outline with poor circumscription, infiltrative growth, consumption of the epidermis, ulceration, nuclear pleomorphism, increased mitotic activity within dermis including atypical mitoses, lack of maturation of cells with depth and lymphovascular invasion
- References: Surg Pathol Clin 2017;10:281, Pathology 2016;48:113
Additional references
Board review style question #1
- Spitz nevi
- Are benign melanocytic neoplasms affecting children and young adults
- Behave biologically similar to melanoma
- Frequently show BRAF mutations
- Require wide excision and sentinel lymph node biopsy
- Usually affect sun exposed skin of elderly adults
Board review style answer #1
A. Are benign melanocytic neoplasms affecting children and young adults
Comment Here
Reference: Spitz nevus
Comment Here
Reference: Spitz nevus
Board review style question #2
- Histopathologically, Spitz nevi
- Are always unpigmented
- Can show Kamino bodies at the epidermodermal junction
- Exhibit marked cytological atypia
- Often show atrophy of the epidermis
- Show mitoses in the dermis
Board review style answer #2
