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Resolving quandaries: basaloid adenoid cystic carcinoma or breast cylindroma? The role of massively parallel sequencing.

ABSTRACT: The aims of this study were to perform a whole-exome sequencing analysis of a breast cylindroma and to investigate the role of molecular analyses in the differentiation between breast cylindroma, a benign tumour that displays MYB expression, and CYLD gene mutations, and its main differential diagnosis, the breast solid-basaloid adenoid cystic carcinoma, a malignant tumour that is characterized by the presence of the MYB-NFIB fusion gene and MYB overexpression.A 66-year-old female underwent quadrantectomy after an irregular dense shadow was discovered in the right breast at the screening mammogram. Histologically, the tumour displayed features suggestive of a solid-basaloid variant of adenoid cystic carcinoma with a differential diagnosis of cylindroma. Fluorescence in situ hybridization, reverse transcription-polymerase chain reaction, immunohistochemistry and whole-exome sequencing revealed absence of the MYB-NFIB fusion gene, low levels of MYB protein expression and a clonal somatic CYLD splice site mutation associated with loss of heterozygosity of the wild-type allele.The results of the histological, immunohistochemical and molecular analyses were consistent with a diagnosis of breast cylindroma, providing a proof-of-principle that the integration of histopathological and molecular approaches can help to differentiate between a low-malignant potential and a benign breast tumour of triple-negative phenotype.

SUBMITTER: Fusco N

PROVIDER: S-EPMC4637261 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Resolving quandaries: basaloid adenoid cystic carcinoma or breast cylindroma? The role of massively parallel sequencing.

Fusco Nicola N Colombo Pierre-Emmanuel PE Martelotto Luciano G LG De Filippo Maria R MR Piscuoglio Salvatore S Ng Charlotte K Y CK Lim Raymond S RS Jacot William W Vincent-Salomon Anne A Reis-Filho Jorge S JS Weigelt Britta B

Histopathology 20150629 2

<h4>Aims</h4>The aims of this study were to perform a whole-exome sequencing analysis of a breast cylindroma and to investigate the role of molecular analyses in the differentiation between breast cylindroma, a benign tumour that displays MYB expression, and CYLD gene mutations, and its main differential diagnosis, the breast solid-basaloid adenoid cystic carcinoma, a malignant tumour that is characterized by the presence of the MYB-NFIB fusion gene and MYB overexpression.<h4>Methods and results ...[more]

PMID: 25951887

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Project description:Rare reports of anal carcinoma (AC) describe histologic resemblance to cutaneous cylindroma, but mutations in the tumor suppressor CYLD, the gene responsible for familial and sporadic cylindromas, have not been systematically investigated in AC. Here, we investigate CYLD-mutant AC, focusing on molecular correlates of distinct histopathology. Comprehensive genomic profiling (hybrid-capture-based DNA sequencing) was performed on 574 ACs, of which 75 unique cases (13%) harbored a CYLD mutation. Clinical data, pathology reports, and histopathology were reviewed for each CYLD-mutant case. The spectrum of CYLD mutations included truncating (n = 50; 67%), homozygous deletion (n = 10; 13%), missense (n = 16; 21%), and splice-site (n = 3; 4%) events. Compared with CYLD-wildtype AC (n = 499), CYLD-mutant ACs were significantly enriched for females (88% vs. 67%, p = 0.0001), slightly younger (median age 59 vs. 61 years, p = 0.047), and included near-universal detection of high-risk HPV sequences (97% vs. 88%, p = 0.014), predominantly HPV16 (96%). The CYLD-mutant cohort also showed significantly lower tumor mutational burden (TMB; median 2.6 vs. 5.2 mut/Mb, p < 0.00001) and less frequent alterations in PIK3CA (13% vs. 31%, p = 0.0015). On histopathologic examination, 73% of CYLD-mutant AC (55/75 cases) showed a striking cylindroma-like histomorphology, composed of aggregates of basaloid cells surrounded by thickened basement membranes and containing characteristic hyaline globules, while only 8% of CYLD-wildtype tumors (n = 34/409) contained cylindroma-like hyaline globules (p < 0.0001). CYLD-mutant carcinomas with cylindroma-like histomorphology (n = 55) showed significantly lower TMB compared with CYLD-mutant cases showing basaloid histology without the distinctive hyaline globules (n = 14) (median 1.7 vs. 4.4 mut/Mb, p = 0.0058). Only five CYLD-mutant cases (7%) showed nonbasaloid conventional squamous cell carcinoma histology (median TMB = 5.2 mut/Mb), and a single CYLD-mutant case showed transitional cell carcinoma-like histology. Within our cohort of ACs, CYLD mutations characterize a surprisingly large subset (13%), with distinct clinical and genomic features and, predominantly, a striking cylindroma-like histopathology, representing a genotype-phenotype correlation which may assist in classification of AC.

Project description:ObjectiveThe purpose of our study was to analyze the clinicopathologic features and surgical and oncological outcomes of adenoid cystic carcinoma (ACC) of the breast and to provide the basis for a clinical therapeutic schedule.MethodsA total of 14 patients with primary breast adenoid cystic carcinoma treated at Cancer Hospital of the Chinese Academy of Medical Sciences from January 2000 to December 2017 were included. Data on clinical presentation, treatment strategy, and outcome, as well as the pathological features of ACC, were reviewed and analyzed.ResultsFourteen patients were diagnosed with ACC of the breast, out of 23205 total patients treated for breast cancer (0.06%). All but three patients were postmenopausal, with a median age at diagnosis of 60.5 years (range, 39-73 years). The most common clinical presentation was a palpable mass (85.7%), and the imaging characteristics of all patients on color Doppler ultrasound and mammography were nonspecific. Six patients (42.9%) were suspected of having ACC by fine-needle aspiration cytology (FNAC) and were confirmed by postoperative histology and immunohistochemistry. All 14 patients underwent surgery, and no patient had a positive lymph node status. Median tumor size was 1.75 cm (range, 1-3 cm). Eight/14 (57.1%) patients were hormone receptor negative (HR-) and HER-2/neu (-) (HER2-). The remaining patients were hormone receptor positive (HR+). There was no significant difference in clinicopathological characteristics between the HR+ group and the HR- group (P>0.05). The mean follow-up period was 57 months. Local recurrence occurred in 14.3% of patients, 1.7% of patients had distant metastasis, all patients with local recurrence or distant metastasis were in the HR (-) group, and all patients were alive at the last follow-up.ConclusionACC of the breast cannot be simply summarized as triple-negative breast cancer because it also includes a small number of hormone receptor-positive breast cancers. Establishing a preoperative diagnosis is difficult on the basis of clinical imaging examination, FNAC may be useful tool in the diagnosis. the final diagnosis can only be assessed based on the results of the histopathological and immunohistochemical examination. Breast-conserving surgery may be an alternative treatment strategy, and axillary lymph node dissection or sentinel node biopsy may not be necessary in some cases.

Dataset Information

Resolving quandaries: basaloid adenoid cystic carcinoma or breast cylindroma? The role of massively parallel sequencing.

Publications

Resolving quandaries: basaloid adenoid cystic carcinoma or breast cylindroma? The role of massively parallel sequencing.

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