Spitz Tumors and Melanoma in the Genomic Age: A Retrospective Look at Ackerman’s Conundrum
After 25 years, “Ackerman’s conundrum”, namely, the distinction of benign from malignant Spitz neoplasms, remains challenging. Genomic studies have shown that most Spitz tumors harbor tyrosine and serine/threonine kinase fusions, including <i>ALK</i>, <i>ROS1</i>, <i>NT...
| Main Author: | |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-12-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/15/24/5834 |
| _version_ | 1797381672200568832 |
|---|---|
| author | Carmelo Urso |
| author_facet | Carmelo Urso |
| author_sort | Carmelo Urso |
| collection | DOAJ |
| description | After 25 years, “Ackerman’s conundrum”, namely, the distinction of benign from malignant Spitz neoplasms, remains challenging. Genomic studies have shown that most Spitz tumors harbor tyrosine and serine/threonine kinase fusions, including <i>ALK</i>, <i>ROS1</i>, <i>NTRK1</i>, <i>NTRK2</i>, <i>NTRK3</i>, <i>BRAF</i> and <i>MAP3K8</i>, or some mutations, such as <i>HRAS</i> and <i>MAP3K8</i>. These chromosomal abnormalities act as drivers, initiating the oncogenetic process and conferring basic bio-morphological features. Most Spitz tumors show no additional genomic alterations or few ones; others harbor a variable number of mutations, capable of conferring characteristics related to clinical behavior, including <i>CDKN2A</i> deletion and <i>TERT</i>-p mutation. Since the accumulation of mutations is gradual and progressive, tumors appear to form a bio-morphologic spectrum, in which they show a progressive increase of clinical risk and histological atypia. In this context, a binary classification Spitz nevus-melanoma appears as no longer adequate, not corresponding to the real genomic substrate of lesions. A ternary classification Spitz nevus-Spitz melanocytoma-Spitz melanoma is more adherent to the real neoplastic pathway, but some cases with intermediate ambiguous features remain difficult to diagnose. A prognostic stratification of Spitz tumors, based on the morphologic and genomic characteristics, as a complement to the diagnosis, may contribute to better treatment plans for patients. |
| first_indexed | 2024-03-08T20:55:49Z |
| format | Article |
| id | doaj.art-7d9b41206a7f42a896e36e7c01731c60 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-08T20:55:49Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-7d9b41206a7f42a896e36e7c01731c602023-12-22T13:59:00ZengMDPI AGCancers2072-66942023-12-011524583410.3390/cancers15245834Spitz Tumors and Melanoma in the Genomic Age: A Retrospective Look at Ackerman’s ConundrumCarmelo Urso0Dermatopathology Study Center of Florence, I-50129 Florence, ItalyAfter 25 years, “Ackerman’s conundrum”, namely, the distinction of benign from malignant Spitz neoplasms, remains challenging. Genomic studies have shown that most Spitz tumors harbor tyrosine and serine/threonine kinase fusions, including <i>ALK</i>, <i>ROS1</i>, <i>NTRK1</i>, <i>NTRK2</i>, <i>NTRK3</i>, <i>BRAF</i> and <i>MAP3K8</i>, or some mutations, such as <i>HRAS</i> and <i>MAP3K8</i>. These chromosomal abnormalities act as drivers, initiating the oncogenetic process and conferring basic bio-morphological features. Most Spitz tumors show no additional genomic alterations or few ones; others harbor a variable number of mutations, capable of conferring characteristics related to clinical behavior, including <i>CDKN2A</i> deletion and <i>TERT</i>-p mutation. Since the accumulation of mutations is gradual and progressive, tumors appear to form a bio-morphologic spectrum, in which they show a progressive increase of clinical risk and histological atypia. In this context, a binary classification Spitz nevus-melanoma appears as no longer adequate, not corresponding to the real genomic substrate of lesions. A ternary classification Spitz nevus-Spitz melanocytoma-Spitz melanoma is more adherent to the real neoplastic pathway, but some cases with intermediate ambiguous features remain difficult to diagnose. A prognostic stratification of Spitz tumors, based on the morphologic and genomic characteristics, as a complement to the diagnosis, may contribute to better treatment plans for patients.https://www.mdpi.com/2072-6694/15/24/5834Spitz nevusatypical Spitz tumorSpitz melanomaSpitzoid neoplasmsmelanoma |
| spellingShingle | Carmelo Urso Spitz Tumors and Melanoma in the Genomic Age: A Retrospective Look at Ackerman’s Conundrum Cancers Spitz nevus atypical Spitz tumor Spitz melanoma Spitzoid neoplasms melanoma |
| title | Spitz Tumors and Melanoma in the Genomic Age: A Retrospective Look at Ackerman’s Conundrum |
| title_full | Spitz Tumors and Melanoma in the Genomic Age: A Retrospective Look at Ackerman’s Conundrum |
| title_fullStr | Spitz Tumors and Melanoma in the Genomic Age: A Retrospective Look at Ackerman’s Conundrum |
| title_full_unstemmed | Spitz Tumors and Melanoma in the Genomic Age: A Retrospective Look at Ackerman’s Conundrum |
| title_short | Spitz Tumors and Melanoma in the Genomic Age: A Retrospective Look at Ackerman’s Conundrum |
| title_sort | spitz tumors and melanoma in the genomic age a retrospective look at ackerman s conundrum |
| topic | Spitz nevus atypical Spitz tumor Spitz melanoma Spitzoid neoplasms melanoma |
| url | https://www.mdpi.com/2072-6694/15/24/5834 |
| work_keys_str_mv | AT carmelourso spitztumorsandmelanomainthegenomicagearetrospectivelookatackermansconundrum |