BRST5:Adenoid cystic carcinoma
Primary Author(s)*
Katherine Geiersbach, MD, Mayo Clinic, and Jun Liao, PhD, Columbia University Irving Medical Center
Cancer Category/Type
Breast Cancer / Epithelial Tumours of the Breast
Cancer Sub-Classification / Subtype
Rare and Salivary Gland-type Tumours / Adenoid cystic carcinoma
Definition / Description of Disease
Invasive carcinoma with a characteristic histologic pattern, comprised of epithelial and myoepithelial cells. Epithelial cells form glands with lumina containing mucoid material; associated stromal matrix is present, forming irregular spaces called pseudolumina. Subtypes include classic adenoid cystic carcinoma, solid-basaloid adenoid cystic carcinoma, and adenoid cystic carcinoma with high-grade transformation.
Synonyms / Terminology
Cylindroma (Historical)
Epidemiology / Prevalence
Rare; approximately 0.1% of all breast cancers
Clinical Features
| Signs and Symptoms | Palpable breast mass, mainly in elderly patients
Suspicious lesion on mammography |
| Laboratory Findings | Not applicable |
Sites of Involvement
Any quadrant of the breast; retroareolar most common
Morphologic Features
tubular, cribriform, and solid patterns
Immunophenotype
| Finding | Marker |
|---|---|
| Positive (universal) | Epithelial cells: low molecular weight cytokeratins CK7 and CK8; EMA; SOX10[1] |
| Positive (subset) | Epithelial cells: KIT (CD117)
Myoepithelial cells: heavy-chain myosin, calponin, S100, CD10, p63 |
| Negative (universal) | ER, PR, HER2, neuroendocrine markers (chromogranin, synaptophysin) |
| Negative (subset) |
Chromosomal Rearrangements (Gene Fusions)
Recurrent rearrangements of MYB (or, more rarely, the paralogous gene MYBL1) preserve the N-terminal DNA binding domain and transactivation domain in the chimeric gene product. The C-terminal regulatory domains of MYB or MYBL1 may be lost, but the intact gene is retained in the case of MYB amplification and in the case of some MYBL1 rearrangements.[3][4]
| Chromosomal Rearrangement | Genes in Fusion (5’ or 3’ Segments) | Pathogenic Derivative | Prevalence | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|---|---|---|
| t(6;9)(q23.3;p23) | MYB::NFIB | der(6) | 54% | Yes | No | Yes | Most common fusion breakpoints involve exon 14 of MYB fused to exon 9 or exon 8c of NFIB.[3][5][6] |
| t(8;9)(q13.1;p23) | MYBL1::NFIB | Reported breakpoints involve exon 14 of MYBL1 fused to exon 9 of NFIB[4] | |||||
| t(8;14)(q13.1;q24.1) | MYBL1::ACTN1 | Reported breakpoints involve exon 8 of MYBL1 fused to exon 10 of ACTN1[4] | |||||
| rea(6)(q23.3) | MYB | Loss of 3' portion of MYB reported in one case[4] |
Individual Region Genomic Gain/Loss/LOH
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| Chr # | Gain / Loss / Amp / LOH | Minimal Region Genomic Coordinates [Genome Build] | Minimal Region Cytoband | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|---|---|---|
| 1 | Gain | 1p36.12–p35.3[7] | |||||
| 6 | Gain/Amp | chr6:135,502,453-135,540,311 [GRCh37/hg19] | 6q23.3 | Yes | No | No | MYB amplification was a range of 3-10 copies by FISH associated with MYB overexpression[4] |
| 11 | Gain | 11p15.5[7] | |||||
| 12 | Gain | 12p13.31[7] | |||||
| 16 | Gain | 16p13.3[7] | |||||
| 17 | Gain | 17q21-q25.1[6] | |||||
| 19 | Gain | 19p13[7] | |||||
| 6 | Loss | 6q25.3-q26[7], 6q23.3-6q27[8] | |||||
| 9 | Loss | 9p11.1–q21.11[7] | |||||
| 12 | Loss | 12q12-q14.1[6] |
Characteristic Chromosomal Patterns
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| Chromosomal Pattern | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|
Gene Mutations (SNV/INDEL)
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| Gene; Genetic Alteration | Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other) | Prevalence (COSMIC / TCGA / Other) | Concomitant Mutations | Mutually Exclusive Mutations | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|---|---|---|---|
| NOTCH1, NOTCH2, and NOTCH3; inactivating sequence variants (missense, nonsense, frameshift truncating)[9] | Loss of function | 20-30% | Mostly solid basaloid subtype | |||||
| CREBBP; inactivating sequence variants (missense, nonsense, truncating)[9] | Loss of function | 15-20% | Mostly solid basaloid subtype | |||||
| CDK12; missense[9] | Loss of function | 30-40% | ||||||
| ARID1A[9] | ||||||||
| PIK3R1[9] |
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
Epigenomic Alterations
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Genes and Main Pathways Involved
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| Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
|---|---|---|
| MYB; gene fusion or amplification | Cell cycle (MYC and NOTCH signaling), DNA replication, DNA repair | Promotes cellular proliferation |
| MYBL1; gene fusion | ||
Genetic Diagnostic Testing Methods
FISH for MYB rearrangement; RT-PCR for MYB-NFIB fusion transcript; RNA-based sequencing (whole transcriptome or targeted)
Familial Forms
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Additional Information
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Links
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References
- ↑ 1.0 1.1 Yang, Chen; et al. (2019). "SOX10 Is a Sensitive Marker for Breast and Salivary Gland Adenoid Cystic Carcinoma: Immunohistochemical Characterization of Adenoid Cystic Carcinomas". Breast Cancer: Basic and Clinical Research. 13: 1178223419842185. doi:10.1177/1178223419842185. ISSN 1178-2234. PMC 6501487. PMID 31105427.
- ↑ Poling, Justin S.; et al. (2017-07). "MYB Labeling by Immunohistochemistry Is More Sensitive and Specific for Breast Adenoid Cystic Carcinoma than MYB Labeling by FISH". The American Journal of Surgical Pathology. 41 (7): 973–979. doi:10.1097/PAS.0000000000000878. ISSN 1532-0979. PMID 28498281. Check date values in:
|date=(help) - ↑ 3.0 3.1 Persson, Marta; et al. (2009-11-03). "Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck". Proceedings of the National Academy of Sciences of the United States of America. 106 (44): 18740–18744. doi:10.1073/pnas.0909114106. ISSN 1091-6490. PMC 2773970. PMID 19841262.
- ↑ 4.0 4.1 4.2 4.3 4.4 Kim, Jisun; et al. (2018-02). "MYBL1 rearrangements and MYB amplification in breast adenoid cystic carcinomas lacking the MYB-NFIB fusion gene". The Journal of Pathology. 244 (2): 143–150. doi:10.1002/path.5006. ISSN 1096-9896. PMC 5839480. PMID 29149504. Check date values in:
|date=(help) - ↑ D'Alfonso, Timothy M.; et al. (2014-11). "MYB-NFIB gene fusion in adenoid cystic carcinoma of the breast with special focus paid to the solid variant with basaloid features". Human Pathology. 45 (11): 2270–2280. doi:10.1016/j.humpath.2014.07.013. ISSN 1532-8392. PMID 25217885. Check date values in:
|date=(help) - ↑ 6.0 6.1 6.2 Martelotto, Luciano G.; et al. (2015-10). "Genomic landscape of adenoid cystic carcinoma of the breast". The Journal of Pathology. 237 (2): 179–189. doi:10.1002/path.4573. ISSN 1096-9896. PMC 4676955. PMID 26095796. Check date values in:
|date=(help) - ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 Wetterskog, Daniel; et al. (2012-01). "Adenoid cystic carcinomas constitute a genomically distinct subgroup of triple-negative and basal-like breast cancers". The Journal of Pathology. 226 (1): 84–96. doi:10.1002/path.2974. ISSN 1096-9896. PMID 22015727. Check date values in:
|date=(help) - ↑ Fusco, Nicola; et al. (2016-11). "Genetic events in the progression of adenoid cystic carcinoma of the breast to high-grade triple-negative breast cancer". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 29 (11): 1292–1305. doi:10.1038/modpathol.2016.134. ISSN 1530-0285. PMC 5083185. PMID 27491809. Check date values in:
|date=(help) - ↑ 9.0 9.1 9.2 9.3 9.4 Massé, Julie; et al. (2020-06). "Solid-type adenoid cystic carcinoma of the breast, a distinct molecular entity enriched in NOTCH and CREBBP mutations". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 33 (6): 1041–1055. doi:10.1038/s41379-019-0425-3. ISSN 1530-0285. PMID 31857685. Check date values in:
|date=(help)
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EXAMPLE Book
- Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p129-171.
Notes
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