Home > E. Pathology by systems > Skin > Spitz nevus

Spitz nevus

Wednesday 16 June 2004

Spindle and epithelioid cell nevus, spitz tumor, spitz’s nevus, spindle cell nevus, juvenile melanoma, benign juvenile melanoma, epitheliod junctional nevus; Spitz tumor

WKP

Definition: Spitz nevus is usually a pink papule on the extremities or face of young patients. It has little pigmentation, spindle and epithelioid cells, is usually compound, and may have eosinophilic globules known as Kamino bodies.

Synopsis

Benign, very common in children/young adults
Often misdiagnosed clinically as pyogenic granuloma
benign architectural features
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 m
Cytologic atypia and mitoses (typical, often superficial) can be seen

Filigree-like Rete Ridges, Lobulated Nests, Rosette-like Structures, and Exaggerated Maturation Characterize Spitz Tumors With NTRK1 Fusion
doi : 10.1097/PAS.0000000000001235

Images

Spitz nevus: Melanocytes with ample cytoplasm. Note the collagenous stroma which adds desmoplastic part of the name.

Variants

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

Digital cases

UI:337 - Spitz nevus

JRC:10786 : Spitz nevus

References

Clinical, Histopathologic, and Genomic Features of Spitz Tumors With ALK Fusions. Yeh I, de la Fouchardiere A, Pissaloux D, Mully TW, Garrido MC, Vemula SS, Busam KJ, LeBoit PE, McCalmont TH, Bastian BC. Am J Surg Pathol. 2015 Jan 19. PMID: 25602801

Variants

desmoplastic Spitz nevus

https://twitter.com/edusqo/status/817041798023483392

Differential diagnosis

malignant melanoma
dysplastic nevi with features of Spitz nevus
pigmented spindle cell nevus
desmoplastic Spitz nevus
plexiform spindle cell nevus - deep-penetrating nevus
cellular blue nevus
combined nevus
epithelioid cell histiocytoma
reticulohistiocytoma
cellular neurothekeoma

IHC

high expression of p16 (15111324)

Molecular biology

tyrosine kinase fusions

Spitz Tumors With ROS1 Fusion
Spitz Tumors With NTRK1 Fusion (#PMC7735398#)

HRAS mutations

HRAS-mutated Spitz tumor (20871217)
HRAS belongs to the family of ras genes, which contains the two additional members KRAS and NRAS.
HRAS maps to the distal end of chromosome 11p, and cancers with mutations in ras gene frequently amplify the mutated allele.
Sequencing of the two hot spots for mutations in HRAS, codons 12, 13, and 61, and found that about 70% of the Spitz nevi with 11p copy number increases showed oncogenic mutations (Bastian et al., 2000b).
In a study, one out of 21 Spitz nevi with a normal copy number of 11p that had a mutation of HRAS. These findings suggest that HRAS is at least one target of the selection forces that lead to increasing copy numbers.
HRAS mutations have been described in Spitz naevi, but thus far never in melanoma.
Thus far no HRAS mutations have been reported in spitzoid melanomas.
There is no evidence that cases with HRAS mutations were at risk to progress to melanoma.

NRAS mutations

NRAS mutations are found in about 25% of primary cutaneous melanomas (see Herlyn and Satyamoorthy, 1996 for a review).
Interestingly, HRAS itself is rarely mutated in melanoma (van Elsas et al., 1996; Jiveskog et al., 1998).

Molecular biology

ALK fusion

Activating kinase fusions have been described as early oncogenic events that are mutually exclusive with HRAS and BRAF mutations in Spitz tumors.
Spitz tumors with ALK rearrangement show distinct histopathologic features that should aid in improving classification of these diagnostically challenging tumors.
Spitz tumors with ALK fusions demonstrated unique histopathologic features.
Clefts and small vesicle-like spaces are arrayed between plump spindled melanocytes with fibrillar cytoplasm and enlarged nuclei.
These melanocytes are typically arrayed in elongated and fusiform nests with radial orientation.
The tumors often have extension into the dermis or subcutis with a wedge-shaped or bulbous lower border (45% and 17%, respectively).
An infiltrative growth pattern was often present at the periphery of the tumor and was highlighted by ALK immunohistochemistry.

Fusion of ALK to the melanophilin gene MLPH in pediatric Spitz nevi. 2019. doi : 10.1016/j.humpath.2019.03.002

Cytogenetics

add(6)(q12-13)

9566288

CNV - CGH (15163005)

copy number increases of chromosome 11p paralleled by mutations in the HRAS oncogene

The isolated copy number increases of chromosome 11p in Spitz nevi raised the question as to which gene on 11p drives the selection forces that led to the accumulation of extra copies of that chromosomal arm.

Gains	1q
Losses	Ch.9

LOH

Ch.9

Ch.10

Differential diagnosis

Mutation analysis to differentiate between Spitz naevus and spitzoid melanoma

A minor part of the Spitz naevi is unique among melanocytic tumours for having a single gain of 11p (26%) and/or HRAS mutations, the latter occurring in up to 29% of cases.

Demonstration of either a HRAS mutation or a single 11p gain therefore seems indicative of benign behaviour.

In difficult to diagnose spitzoid lesions, so-called Spitzoid tumours of uncertain malignant potential, assessment of one of these cytogenetic aberrations could be of help in making a more accurate diagnosis.

The observation that the 11p copy number increase indicating an isochromosome 11p was not seen in over 300 melanomas, and melanoma cell lines studied so far further argues against the possibility that these Spitz nevi are precursors to melanoma. (Bastian, 2003; 12789284)

See also

melanocytic tumors

References

HRAS-mutated Spitz tumors: A subtype of Spitz tumors with distinct features. van Engen-van Grunsven AC, van Dijk MC, Ruiter DJ, Klaasen A, Mooi WJ, Blokx WA. Am J Surg Pathol. 2010 Oct;34(10):1436-41. PMID: 20871217

Harvell JD, Kohler S, Zhu S, Hernandez-Boussard T, Pollack JR, van de Rijn M. High-resolution array-based comparative genomic hybridization for distinguishing paraffin-embedded Spitz nevi and melanomas. Diagn Mol Pathol. 2004 Mar;13(1):22-5. PMID: 15163005

Maldonado JL, Timmerman L, Fridlyand J, Bastian BC. Mechanisms of cell-cycle arrest in Spitz nevi with constitutive activation of the MAP-kinase pathway. Am J Pathol. 2004 May;164(5):1783-7. PMID: 15111324

Bogdan I, Burg G, Boni R. Spitz nevi display allelic deletions. Arch Dermatol. 2001 Nov;137(11):1417-20. PMID: 11708943