Genetic and epigenetic alterations in the differential diagnosis of malignant melanoma and spitzoid lesion

Takata, Minoru; Lin, Jingrong; Takayanagi, Shunsaku; Suzuki, Takefumi; Ansai, Shin‐ichi; Kimura, Tetsunori; Cerroni, Lorenzo; Saida, Toshiaki

doi:10.1111/j.1365-2133.2007.07924.x

Cited by 75 publications

(75 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A limited number of studies have examined BRAF mutations in AST, and only one study reported finding a BRAF mutation in AST [25][26][27]. Mutations in NRAS (neuroblastoma RAS viral [v-ras] oncogene homolog) have also been reported in melanoma [25,26,28], but not in conventional Spitz nevi [25,26,28]. The inconsistencies between published studies may be related to a lack of consensus among dermatopathologists on histologic criteria used in the diagnosis of spitzoid melanocytic lesions [13].…”

Section: Braf/nrasmentioning

confidence: 88%

“…However, when the spectrum of spitzoid lesions is expanded to include unusual or atypical variants, such as spitzoid dysplastic nevi or Reed's nevi, the incidence of BRAF mutations is increased [27][28][29]. A limited number of studies have examined BRAF mutations in AST, and only one study reported finding a BRAF mutation in AST [25][26][27]. Mutations in NRAS (neuroblastoma RAS viral [v-ras] oncogene homolog) have also been reported in melanoma [25,26,28], but not in conventional Spitz nevi [25,26,28].…”

Section: Braf/nrasmentioning

confidence: 99%

“…BRAF (v-raf murine sarcoma viral oncogene homolog B1) mutations may be found in approximately 50% of conventional melanomas and 80% of ordinary nevi [25,26], and a small subset of spitzoid melanomas [27]. The vast majority of conventional Spitz nevi do not contain BRAF mutations [26].…”

Section: Braf/nrasmentioning

confidence: 99%

See 2 more Smart Citations

Difficulties in the diagnosis of spitzoid melanocytic lesions

Olsen

Patel

et al. 2010

Expert Review of Dermatology

View full text Add to dashboard Cite

Section: Braf/nrasmentioning

confidence: 88%

Section: Braf/nrasmentioning

confidence: 99%

See 1 more Smart Citation

Difficulties in the diagnosis of spitzoid melanocytic lesions

Olsen

Patel

et al. 2010

Expert Review of Dermatology

View full text Add to dashboard Cite

“…Indeed, investigation of key molecular aberrations in AST, such as mutations of the HRAS gene, have suggested that these lesions may merely represent a group of Spitz nevi and Spitzoid melanomas that are unclassifiable by light microscopy and not in fact genetically distinct entities [2]. This is a position that has been championed by Ackerman and colleagues for some time and is analogous to the viewpoint that 'classical' atypical nevi are a mixture of benign nevi and early melanomas, rather than precursors of melanomas per se [5][6][7][8].…”

Section: Expert Commentarymentioning

confidence: 98%

Lack of significance of sentinel lymph node biopsy for the prognosis and management of the atypical Spitz tumor of uncertain biologic potential

Alexandroff¹,

Forno²,

Johnston³

2009

Expert Review of Dermatology

View full text Add to dashboard Cite

“…[15][16][17][18][19] This is in contrast to all spitzoid melanomas and conventional melanomas that have been analyzed to date, in which HRAS mutations are rare. 17,19,20 In addition, BRAF and NRAS mutations are uncommon in Spitz nevi, whereas they are common in melanomas. 21 Thus the presence of an HRAS mutation in a melanocytic neoplasm with Spitzoid morphology appears to favor the diagnosis of Spitz nevus, rather than a Spitzoid melanoma.…”

mentioning

confidence: 99%

Identification of HRAS mutations and absence of GNAQ or GNA11 mutations in deep penetrating nevi

Bender

McGinniss²,

Esmay

et al. 2013

Modern Pathology

View full text Add to dashboard Cite

HRAS is mutated in B15% of Spitz nevi, and GNAQ or GNA11 is mutated in blue nevi (46-83% and B7% respectively). Epithelioid blue nevi and deep penetrating nevi show features of both blue nevi (intradermal location, pigmentation) and Spitz nevi (epithelioid morphology). Epithelioid blue nevi and deep penetrating nevi can also show overlapping features with melanoma, posing a diagnostic challenge. Although epithelioid blue nevi are considered blue nevic variants, no GNAQ or GNA11 mutations have been reported. Classification of deep penetrating nevi as blue nevic variants has also been proposed, however, no GNAQ or GNA11 mutations have been reported and none have been tested for HRAS mutations. To better characterize these tumors, we performed mutational analysis for GNAQ, GNA11, and HRAS, with blue nevi and Spitz nevi as controls. Within deep penetrating nevi, none demonstrated GNAQ or GNA11 mutations (0/38). However, 6% revealed HRAS mutation (2/32). Twenty percent of epithelioid blue nevi contained a GNAQ mutation (2/10), while none displayed GNA11 or HRAS mutation. Eighty-seven percent of blue nevi contained a GNAQ mutation (26/30), 4% a GNA11 mutation (1/28), and none an HRAS mutation. Within Spitz nevi, none demonstrated GNAQ or GNA11 mutations (0/30). Seventeen percent contained an HRAS mutation (5/30). All GNAQ and GNA11 mutations were p.Q209L (c.626A4T) point mutations, except 2 GNAQ mutations, which contained novel c.625_626CA4TT double mutations. Four HRAS mutations were in exon 2, and three in exon 3. This is the first study to identify HRAS mutations in deep penetrating nevi. The presence of HRAS mutations and absence of GNAQ or GNA11 mutations in deep penetrating nevi suggests classification of these unusual nevi within the Spitz nevus category of melanocytic tumors, rather than the blue nevus category. Modern Pathology (2013) 26, 1320-1328; doi:10.1038/modpathol.2013.77; published online 19 April 2013 Keywords: blue nevus; deep penetrating nevus; epithelioid blue nevus; GNA11; GNAQ; HRAS; spitz nevus Melanocytic nevi with epithelioid cytomorphology include epithelioid and spindle cell (Spitz) nevi, epithelioid blue nevi, and deep penetrating nevi. Deep penetrating nevus, a term first coined by Seab et al, 1 are unusual melanocytic neoplasms difficult to classify. Deep penetrating nevi are uncommon but are of importance due to their histological and clinical overlap with melanoma. They most commonly present on the extremities, followed by the head and neck and upper trunk. 2 The age range at presentation is wide; however, as with Spitz nevi, deep penetrating nevi most commonly present in younger patients (adolescence and young adults). They typically present as predominantly dermal to focally compound melanocytic proliferations with extension into the reticular dermis particularly along adnexal structures and neurovascular bundles, often extending into the subcutis. They tend to have a relatively symmetric wedge-shaped nodular growth pattern, although superficial variants can occur. 2 A plexiform disp...

show abstract

Genetic and epigenetic alterations in the differential diagnosis of malignant melanoma and spitzoid lesion

Abstract: Genetic and epigenetic analyses may be useful as an additional diagnostic tool to distinguish between melanoma and Spitz naevus, and may help to define subgroups in atypical Spitz tumours.

Cited by 75 publications

References 39 publications

Difficulties in the diagnosis of spitzoid melanocytic lesions

Difficulties in the diagnosis of spitzoid melanocytic lesions

Lack of significance of sentinel lymph node biopsy for the prognosis and management of the atypical Spitz tumor of uncertain biologic potential

Identification of HRAS mutations and absence of GNAQ or GNA11 mutations in deep penetrating nevi

Contact Info

Product

Resources

About