Histopathologic and Cytogenetic Features of Pulmonary Adenoid Cystic Carcinoma

Roden, Anja C.; Greipp, Patricia T.; Knutson, Darlene L.; Kloft‐Nelson, Sara M.; Jenkins, Sarah M.; Marks, Randolph S.; Aubry, Marie Christine; García, Joaquín J.

doi:10.1097/jto.0000000000000656

Cited by 41 publications

(41 citation statements)

References 18 publications

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“…Since then, studies have established that this genetic alteration is specific to AdCC, irrespective of anatomical location [8] . In AdCCs, the presence of the fusion transcript ranges from 28 to 86%, while c-Myb protein expression has been noted in 55 to 97% of cases on IHC [5,6,8,12,13,[21][22][23] . A recent study has documented the presence of fusion transcript in 41% of pulmonary AdCCs; however, c-Myb IHC was not performed in this study [6] .…”

Section: Discussionmentioning

confidence: 99%

“…In AdCCs, the presence of the fusion transcript ranges from 28 to 86%, while c-Myb protein expression has been noted in 55 to 97% of cases on IHC [5,6,8,12,13,[21][22][23] . A recent study has documented the presence of fusion transcript in 41% of pulmonary AdCCs; however, c-Myb IHC was not performed in this study [6] . It has been noted that c-Myb overexpression also occurs in cases without fusion, implying that expression of c-Myb may be mediated by other pathways as well [8] .Therefore, overexpression of c-Myb may be utilised for the diagnosis of AdCC aided by sequential FISH only in the immunopositive cases [24] .…”

Section: Discussionmentioning

confidence: 99%

“…The presence of fusion is identified in 30-100% of AdCCs in the head and neck as well as the breast [2,5] . However, there are only occasional reports of c-Myb overexpression in bronchopulmonary AdCCs [6] , based on the analysis of histologic specimens and not on cytology material. We therefore undertook this study to evaluate the immunohistochemical expression of c-Myb in AdCC of the lower respiratory tract (LRT), from cytological and histological material, and to correlate the results obtained with clinicopathological variables.…”

Section: Introductionmentioning

confidence: 99%

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c-Myb Overexpression in Cytology Smears of Tracheobronchial and Pulmonary Adenoid Cystic Carcinomas

Vallonthaiel

Jain²,

Singh³

et al. 2016

Acta Cytologica

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Aims: Adenoid cystic carcinoma (AdCC) is a malignant epithelial neoplasm that occurs rarely in the lower respiratory tract (LRT). AdCC at various sites is associated with the novel fusion transcript MYB-NFIB, along with the overexpression of the Myb protein. The expression of the Myb protein in AdCC of the LRT has not been evaluated much. Study Design: Cases of AdCC of the LRT diagnosed on cytology or histology were retrieved from our institutional archives. c-Myb expression was analyzed on immunocytochemistry/immunohistochemistry (ICC/IHC) and was correlated with clinicopathological parameters. Results: Twenty-three samples of AdCC originating from the LRT were included in the study. Four cases were diagnosed on cytology, 3 of which had corresponding histology specimens. The remaining 19 cases had either biopsy or resection. Most of the patients presented with endobronchial mass. The mean age was 49.4 years and a male predominance was seen. ICC and IHC for c-Myb showed positivity in 75 and 59% of the cases, respectively. Western blot was used to validate IHC results. Conclusion: AdCC of the LRT is rare and hence poses diagnostic difficulty. Cytology smears can be utilized for c-Myb ICC. The presence of c-Myb immunopositivity in most cases may possibly make Myb a diagnostic biomarker and a therapeutic target for personalized treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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c-Myb Overexpression in Cytology Smears of Tracheobronchial and Pulmonary Adenoid Cystic Carcinomas

Vallonthaiel

Jain²,

Singh³

et al. 2016

Acta Cytologica

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“…A large majority of ACC tumors, which occur mainly in salivary glands but also in breast and other tissues (7–9), contain a recurrent t(6;9) translocation, which fuses the MYB proto-oncogene on chromosome 6q to the NFIB gene on chromosome 9p, potentially resulting in the expression of novel MYB - NFIB fusion oncogenes (1, 7, 8, 10, 11). The MYB gene encodes the c-Myb (MYB) transcription factor, which has a highly conserved, N-terminal DNA binding domain, a central domain required for transcriptional activation and conserved C-terminal domains controlling specificity and negative regulation (12, 13).…”

Section: Introductionmentioning

confidence: 99%

Recurrent Fusions in MYB and MYBL1 Define a Common, Transcription Factor–Driven Oncogenic Pathway in Salivary Gland Adenoid Cystic Carcinoma

et al. 2016

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Adenoid Cystic Carcinoma (ACC), the second most common malignancy of salivary glands, is a rare tumor with bleak prognosis for which therapeutic targets are unavailable. We used RNA-sequencing (RNA-seq) to analyze low-quality RNA from archival, formaldehyde-fixed, paraffin-embedded samples. In addition to detecting the most common ACC translocation, t(6;9) fusing the MYB proto-oncogene to NFIB, we also detected previously unknown t(8;9) and t(8;14) translocations fusing the MYBL1 gene to the NFIB and RAD51B genes, respectively. RNA-seq provided information about gene fusions, alternative RNA splicing and gene expression signatures. Interestingly, tumors with MYB and MYBL1 translocations displayed similar gene expression profiles, and the combined MYB and MYBL1 expression correlated with outcome, suggesting that the related Myb proteins are interchangeable oncogenic drivers in ACC. Our results provide important details about the biology of ACC and illustrate how archival tissue samples can be used for detailed molecular analyses of rare tumors.

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“…In recent years, in addition to this molecular feature characteristic of MASC, other diagnostic molecular signatures have been described for salivary gland tumors, even the ones developing in the LRT, and some with a high prevalence and discrete specificity (8, 34, 35, 42). With respect to MEC, specific translocations involving the CRTC1 gene and MAML2 or CRTC3 and MAML2 have been described, with frequencies up to 80 and 6% respectively (8, 43, 44).…”

Section: Discussionmentioning

confidence: 99%

Cytology of Primary Salivary Gland-Type Tumors of the Lower Respiratory Tract: Report of 15 Cases and Review of the Literature

et al. 2017

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Primary pulmonary salivary gland-type tumors are rare neoplasms arising from the seromucinous submucosal glands of the lower respiratory tract (LRT), the most common of which are mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma. They are morphologically indistinguishable from their salivary gland counterpart and recognizing them is a challenge, especially on cytological specimens. We analyzed 15 cases of histologically proven primary salivary gland tumors of the LRT to identify cytomorphological features and define potential diagnostic clues that might assist cytopathologists in the preoperative diagnosis of these neoplasias. Three out of the four cases of adenoid cystic carcinomas showed the characteristic tridimensional cell clusters and hyaline globules, whereas the last one did not show malignant cells; only two cases of MEC presented the three characteristic cell types (i.e., squamous, intermediate, and mucin secreting) on cytology. Since these neoplasms are rare and do not have a completely specific set of cytological features, it is important for practicing cytopathologists to be aware of the possibility of encountering them, in specimens from patients with LRT masses, in order to render the correct diagnosis.

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Histopathologic and Cytogenetic Features of Pulmonary Adenoid Cystic Carcinoma

Abstract: A MYB rearrangement was identified in 41% of PACC and was 100% specific. FISH studies for MYB may be of diagnostic utility in PACC, particularly on small biopsy specimens. MYB rearrangement in PACC does not seem to be associated with clinical features or prognosis.

Cited by 41 publications

References 18 publications

c-Myb Overexpression in Cytology Smears of Tracheobronchial and Pulmonary Adenoid Cystic Carcinomas

c-Myb Overexpression in Cytology Smears of Tracheobronchial and Pulmonary Adenoid Cystic Carcinomas

Recurrent Fusions in MYB and MYBL1 Define a Common, Transcription Factor–Driven Oncogenic Pathway in Salivary Gland Adenoid Cystic Carcinoma

Cytology of Primary Salivary Gland-Type Tumors of the Lower Respiratory Tract: Report of 15 Cases and Review of the Literature

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