Kinase Fusions in Spitz Melanocytic Tumors: The Past, the Present, and the Future
, Francesca Ambrogio 2, Anna Colagrande 3, Andrea Marzullo 3, Rita Alaggio 4, Irma Trilli 5, Giuseppe Ingravallo 3 and Gerardo Cazzato 3,*Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsA good and helpful review, well written.
A table summarizing the key features (clinical, histologic and molecular) would be helpful).
Is it possible to show some histologic pictures ?
Minor Points: p6, line 255. delete ... I will review this part tommorow.
Author Response
Reviewer n’1: A good and helpful review, well written.
Answer n’1: Dear Reviewer n’1, thank you very much for your wonderful words.
Reviewer n’1: A table summarizing the key features (clinical, histologic and molecular) would be helpful).
Answer n’2: Thank you for this tip. We added a table following your suggestions. Thanks a lot.
Reviewer n’1: Is it possible to show some histologic pictures ?
Answer n’3: Yes, we added some histopathological pictures such as examples of ALK and ROS1 rearranged-tumours.
Reviewer n’1: Minor Points: p6, line 255. delete ... I will review this part tommorow.
Answer n’4: Done. Thank you very much.
Reviewer 2 Report
Comments and Suggestions for Authors1. This very comprehensive review of gene fusions in Spitz tumors could benefit by some photomicrographs of histopathologically distinctive fusions (e.g. ALK, NRTK3, MAP3K8).
2. The section on MAP3K8 should mention that mutations in this gene also occur in some spitzoid tumors, analogous to BRAF. Also, TERT rearrangement was present in the case analyzed in ref. 75.
Comments on the Quality of English LanguageWell written, some capitalization unnecessary.
Author Response
Reviewer n’2: 1. This very comprehensive review of gene fusions in Spitz tumors could benefit by some photomicrographs of histopathologically distinctive fusions (e.g. ALK, NRTK3, MAP3K8).
Answer n’1: Thank you very much. We added some histopathological pictures such as examples of ALK and ROS1 rearranged-tumours.
Reviewer n’2: 2. The section on MAP3K8 should mention that mutations in this gene also occur in some spitzoid tumors, analogous to BRAF. Also, TERT rearrangement was present in the case analyzed in ref. 75.
Answer n’2: Thank you very much.
Reviewer 3 Report
Comments and Suggestions for AuthorsThis paper reviews kinase fusions in Spitz family tumors. My comments and questions are below.
-While this paper focuses on kinase fusions, it would be good to mention that some Spitz nevi have HRAS mutations instead of kinase fusions in the introduction.
-In the ALK discussion for this reference "recent paper [11] reported the case of a 3- 114 year-old female with an exophytic papule on vermilion border of lower lip that had the 115 morphological and immunophenotypical features of ALK-rearranged Spitz tumours but 116 was distinguished by its diffuse neurotropism", you do not explicitly state that this was a confirmed ALK gene fusion tumor. Was it confirmed with IHC or FISH?
-ALK staining is typically diffuse cytoplasmic, but in some cases other patterns such as membranous immunohistochemical staining pattern has been described
Bahrani E, Kunder CA, Teng JM, Brown RA, Rieger KE, Novoa RA, Cloutier JM. Spitz nevus with EHBP1-ALK fusion and distinctive membranous localization of ALK. J Cutan Pathol. 2022 Jun;49(6):584-588.
-"3.6. Serine-threonine kinases rearranged Spitz tumours I will review this part tomorrow…" It seems part of the paper is not finished.
-There has been one report of a death from a BRAF fusion Spitz tumor. This should be included in the BRAF fusion section:
Lee S, Barnhill RL, Dummer R, Dalton J, Wu J, Pappo A, Bahrami A. TERT Promoter Mutations Are Predictive of Aggressive Clinical Behavior in Patients with Spitzoid Melanocytic Neoplasms. Sci Rep. 2015 Jun 10;5:11200.
-It would be great to have some photomicrographs to illustrate at least some of the histopathologic features discussed in this paper.
Author Response
Reviewer n’3: -While this paper focuses on kinase fusions, it would be good to mention that some Spitz nevi have HRAS mutations instead of kinase fusions in the introduction.
Answer n’1: Thank you very much dear Reviewer n’3. We added this information to the main text.
Reviewer n’3: -In the ALK discussion for this reference "recent paper [11] reported the case of a 3- 114 year-old female with an exophytic papule on vermilion border of lower lip that had the 115 morphological and immunophenotypical features of ALK-rearranged Spitz tumours but 116 was distinguished by its diffuse neurotropism", you do not explicitly state that this was a confirmed ALK gene fusion tumor. Was it confirmed with IHC or FISH?
Answer n’2: Thank you very much for this question dear Reviewer n’3. We added the informations about IHC and FISH.
Reviewer ‘3: -"3.6. Serine-threonine kinases rearranged Spitz tumours I will review this part tomorrow…" It seems part of the paper is not finished.
Answer n’3: Sorry for this mistake.
Reviewer n’3: -There has been one report of a death from a BRAF fusion Spitz tumor. This should be included in the BRAF fusion section:
Lee S, Barnhill RL, Dummer R, Dalton J, Wu J, Pappo A, Bahrami A. TERT Promoter Mutations Are Predictive of Aggressive Clinical Behavior in Patients with Spitzoid Melanocytic Neoplasms. Sci Rep. 2015 Jun 10;5:11200.
Answer n’4: Thank you dear Reviewer n’3. We added this important information.
Reviewer n’3: -It would be great to have some photomicrographs to illustrate at least some of the histopathologic features discussed in this paper.
Answer n’5: Yes, we added some histopathological pictures such as examples of ALK and ROS1 rearranged-tumours.
