Metaplastic carcinoma of the breast with melanocytic differentiation is an exceedingly rare tumor. We describe an additional metaplastic breast carcinoma with melanocytic differentiation that was initially diagnosed as malignant melanoma on core biopsy. The patient received neoadjuvant immunotherapy. The surgical specimen demonstrated closely associated epithelial and melanocytic components that had differing, but partially overlapping, immunohistochemical profiles. Molecular testing of the 2 components identified shared alterations in a few genes, supporting a clonal relationship. Following therapy, the melanocytic component showed an increase in tumor-infiltrating lymphocytes.
WHO Classification of Tumors Editorial Board. Breast Tumours. 5th ed. International Agency for Research on Cancer; 2019.
2.
PadmoreRFLaraJFAckermanDJ, et al.Primary combined malignant melanoma and ductal carcinoma of the breast. A report of two cases. Cancer. 1996;78:2515‐2525. doi:10.1002/(SICI)1097-0142(19961215)78:12<2515::AID-CNCR11>3.0.CO;2-Z
3.
RuffoloEFKoernerFCMalufHM. Metaplastic carcinoma of the breast with melanocytic differentiation. Mod Pathol. 1997;10(6):592‐596.
4.
NobukawaBFujiiHHiraiS, et al.Breast carcinoma diverging to aberrant melanocytic differentiation: a case report with histopathologic and loss of heterozygosity analyses. Am J Surg Pathol. 1999;23(10):1280‐1287. doi:10.1097/00000478-199910000-00015
5.
YenHFlorentineBKellyLK, et al.Fine-needle aspiration of a metaplastic breast carcinoma with extensive melanocytic differentiation: a case report. Diagn Cytopathol. 2000;23(1):46‐50. doi: 10.1002/1097-0339(200007)23:1<46::aid-dc11>3.0.co;2-f
6.
NoskeASchwabeMPahlS, et al.Report of a metaplastic carcinoma of the breast with multi-directional differentiation: an adenoid cystic carcinoma, a spindle cell carcinoma and melanoma. Virchows Arch. 2008;452(5):575‐579. doi:10.1007/s00428-008-0588-7
7.
BendicABozicMDurdovMG. Metaplastic breast carcinoma with melanocytic differentiation. Pathol Int. 2009;59(9):676‐680. doi:10.1111/j.1440-1827.2009.02426.x
8.
NzegwuMASuleEUzoigweJ, et al.Metaplastic breast carcinoma; melanocytic variant, a very rare tumour. J Surg Case Rep. 2015;2015:rju158. doi: 10.1093/jscr/rju158
9.
MayerCZilkerMBalint-LahatN, et al.Unusual variant of invasive ductal carcinoma suggesting metaplastic melanocytic differentiation. Hum Pathol Case Rep. 2021;23:200482.
10.
Da SilvaAGSoaresCMartinsL. Case report - metaplastic breast carcinoma with melanocytic differentiation. Eur J Surg Oncol.2022;48(2):e68. doi:10.1016/j.ejso.2021.12.062
11.
KoufopoulosNIBoutasIPouliakisA, et al.The “forgotten” subtypes of breast carcinoma: a systematic review of selected histological variants not included or not recognized as distinct entities in the current World Health Organization classification of breast tumors. Int J Mol Sci. 2024;25:8382. doi: 10.3390/ijms2515382
12.
JungHSLeffertsJATsongalisGJ. Utilization of the oncoscan microarray assay in cancer diagnostics. Appl Cancer Res. 2017;37:1. doi:10.1186/s41241-016-0007-3
13.
ShahPSHughesEGSukhadiaSS, et al.Validation and implementation of a somatic-only tumor exome for routine clinical application. J Mol Diagn. 2024;26:815‐824. doi:10.1016/j.jmoldx.2024.05.013
14.
HughesEGBergmanDTGreenDC, et al.Clinical implementation of expanded solid tumor fusion detection with whole-transcriptome sequencing at an academic medical center. JCO Precis Oncol. 2025;9:e2400830. doi: 10.1200/PO-24-00830
15.
Cimino-MathewsASubhawongAPElwoodH, et al.Neural crest transcription factor Sox10 is preferentially expressed in triple-negative and metaplastic breast carcinomas. Hum Pathol. 2013;44:959‐965. doi:10.1016/j.humpath.2012.09.005
16.
NewmanJBrahmbhattMStoffBK, et al.S-100 protein and SOX10-positive breast carcinoma mimicking metastatic melanoma. J Cutan Pathol. 2020;47:1187‐1191. doi:10.1111/cup.13822
17.
FliorentRBenedettoCTherouxZ. Metastatic triple-negative breast carcinoma mimicking melanoma: a potential diagnostic pitfall. J Cutan Pathol. 2024;51:654‐657. doi:10.1111/cup.14658
18.
SaunusJMDe LucaXMNorthwoodK, et al.Epigenome erosion and SOX10 drive neural crest phenotypic mimicry in triple-negative breast cancer. NPJ Breast Cancer. 2022;8:57. doi: 10.1038/s441523-022-00425-x
19.
KoršaLAbramovićMKovačevićL, et al.PRAME expression and its prognostic significance in invasive breast carcinoma. Pathol Res Pract. 2024;254:155096. doi:10.1016/j.prp.2024.155096
20.
ChangRCEhyaeeVWattarR, et al.Evaluation of PRAME expression in cases of breast carcinoma metastatic to skin. Am J Dermatopathol. 2026;48:107–113. doi:10.1097/DAD.0000000000003159
21.
Børresen-DaleAL. TP53 and breast cancer. Hum Mutat. 2003;21(3):292‐300. doi:10.1002/humu.10174
22.
Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490:61‐70. doi:10.1038/nature11412
23.
KhanSUUllahZShaukatH, et al.TP53 and its regulatory genes as prognosis of cutaneous melanoma. Cancer Inform. 2023;22:11769351231177267. doi:10.1177/11769351231177267
24.
DaviesHBignellGRCoxC, et al.Mutations of the BRAF gene in human cancer. Nature. 2002;417:949‐954. doi:10.1038/nature00766
25.
ColombinoMCaponeMLissiaA, et al.BRAF/NRAS mutation frequencies among primary tumors and metastases in patients with melanoma. J Clin Oncol. 2012;30:2522‐2529. doi:10.1200/JCO.2011.41.2452
26.
WolchokJDChiarion-SileniVRutkowskiP, et al.Final, 10-year outcomes with nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2025;392:11‐22. doi:10.1056/NEJMoa2407417
27.
NederlofIIsaevaOIde GraafM, et al.Neoadjuvant nivolumab or nivolumab plus ipilimumab in early-stage triple-negative breast cancer: a phase 2 adaptive trial. Nat Med. 2024;30:3223‐3235. doi:10.1038/s41591-024-03249-3
