YAP1-MAML2 Fusion as a Diagnostic Biomarker for Metaplastic Thymoma

BackgroundMetaplastic thymoma is a very rare tumor with only a few case reports documented in literature. Hence, its molecular features have not been well explored.Material and MethodsSeventeen specimens of metaplastic thymoma were sequenced and retrospectively analyzed by fluorescence in situ hybridization (FISH) and immunohistochemistry in the study. In addition, seven cases of micronodular thymoma with lymphoid stroma and nine cases of type A thymoma were also investigated.ResultsAmong these metaplastic thymomas, fifteen cases showed classical histological features, and two cases displayed characteristic micronodular-like growth patterns. DNA and RNA based next-generation sequencing identified and confirmed highly recurrent Yes Associated Protein 1 (YAP1) - Mastermind Like Transcriptional Coactivator 2 (MAML2) translocation (13/17, 76.5%) in metaplastic thymoma but not in micronodular thymoma with lymphoid stroma (0/7, 0%) and type A thymoma (0/9, 0%). In addition, six nonsense mutations were also detected in the metaplastic thymoma. FISH in microdissection specimens indicated that both epithelioid and spindle cell components harbored YAP1-MAML2 gene rearrangements.ConclusionsOur study explored the genetic alterations in epithelioid and spindle cell components in metaplastic thymoma. Furthermore, YAP1-MAML2 gene rearrangements emerged as a potential diagnostic biomarker helpful for distinguishing metaplastic thymoma from type A and micronodular thymoma with lymphoid stroma.

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Mixed Type A Thymoma and Micronodular Thymoma With Lymphoid Stroma

International Journal of Surgical Pathology ◽

10.1177/1066896917742723 ◽

2017 ◽

Vol 26 (4) ◽

pp. 336-337

Author(s):

Renqing Wang ◽

Ling Nie

Keyword(s):

Mixed Type ◽

Type A ◽

Lymphoid Stroma ◽

Type A Thymoma

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A Rare Case of Mixed Type A Thymoma and Micronodular Thymoma with Lymphoid Stroma

Journal of Pathology and Translational Medicine ◽

10.4132/jptm.2014.10.27 ◽

2015 ◽

Vol 49 (1) ◽

pp. 75-77 ◽

Cited By ~ 2

Author(s):

Yoon Jin Cha ◽

Joungho Han ◽

Jimin Kim ◽

Kyung Soo Lee ◽

Young Mog Shim

Keyword(s):

Rare Case ◽

Mixed Type ◽

Type A ◽

Lymphoid Stroma ◽

Type A Thymoma

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Encapsulated Follicular Thyroid Carcinoma Exhibiting Glandular and Spindle Cell Components

Pathology - Research and Practice ◽

10.1016/s0344-0338(96)80134-8 ◽

1996 ◽

Vol 192 (1) ◽

pp. 67-71 ◽

Cited By ~ 7

Author(s):

Y. Mizukami ◽

A. Nonomura ◽

T. Michigishi ◽

M. Noguchi ◽

T. Ishizaki

Keyword(s):

Thyroid Carcinoma ◽

Spindle Cell ◽

Follicular Thyroid Carcinoma ◽

Cell Components

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Malignant Transformation of Metaplastic Thymoma into High-Grade Sarcomatoid Carcinoma: A Case Report

International Journal of Surgical Pathology ◽

10.1177/10668969211070484 ◽

2021 ◽

pp. 106689692110704

Author(s):

Zheng Hua Piao ◽

Jin Ping Chen ◽

Hai Ren Chen ◽

Xin Cheng Zhou

Keyword(s):

Mediastinal Mass ◽

Spindle Cell ◽

Postoperative Radiotherapy ◽

Sarcomatoid Carcinoma ◽

Anterior Mediastinal Mass ◽

High Grade ◽

Ki 67 ◽

Cellular Atypia ◽

Spindle Cells ◽

Cell Components

The correlation of histogenesis between metaplastic thymoma and thymic sarcomatoid carcinoma is unclear. We report a case of metaplastic thymoma transformed into high-grade sarcomatoid carcinoma. A 64 × 54 × 32 mm anterior mediastinal mass in a 61-year-old woman microscopically consisted mainly of classic metaplastic thymoma, with the center dominated by high-grade sarcomatoid carcinoma. In some areas, both epithelial and spindle cell components of the metaplastic thymoma showed increased cellular atypia, mitotic activity, and focal necrosis and gradually transformed into the polygonal/pleomorphic and spindle cell components of sarcomatoid carcinoma. Immunohistochemically, the characteristics of the polygonal/pleomorphic sarcomatoid cells were similar to those of the epithelial component of metaplastic thymoma, while the spindle sarcomatoid cells were more similar to the spindle cells component of metaplastic thymoma. The Ki-67 index was less than 5% in the metaplastic thymoma areas but up to 70% in the sarcomatoid carcinoma area. Radical operation and postoperative radiotherapy were performed. Multifocal relapses at the pleura occurred 13 months after surgery.

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POU2F3 beyond thymic carcinomas: expression across the spectrum of thymomas hints to medullary differentiation in type A thymoma

Virchows Archiv ◽

10.1007/s00428-021-03229-9 ◽

2022 ◽

Author(s):

Yosuke Yamada ◽

Akihiko Sugimoto ◽

Masahito Hoki ◽

Akihiko Yoshizawa ◽

Masatsugu Hamaji ◽

...

Keyword(s):

Type A ◽

Type A Thymoma ◽

Thymic Carcinomas

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Lung metastases in an atypical type A thymoma variant

Journal of Thoracic Disease ◽

10.21037/jtd.2017.07.109 ◽

2017 ◽

Vol 9 (9) ◽

pp. E805-E807

Author(s):

Masaki Hashimoto ◽

Yoshitane Tsukamoto ◽

Shohei Matsuo ◽

Toru Nakamichi ◽

Nobuyuki Kondo ◽

...

Keyword(s):

Lung Metastases ◽

Type A ◽

Type A Thymoma

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Breast Cancer: A Molecularly Heterogenous Disease Needing Subtype-Specific Treatments

Medical Sciences ◽

10.3390/medsci8010018 ◽

2020 ◽

Vol 8 (1) ◽

pp. 18 ◽

Cited By ~ 2

Author(s):

Ugo Testa ◽

Germana Castelli ◽

Elvira Pelosi

Keyword(s):

Breast Cancer ◽

Genomic Instability ◽

Hormone Receptors ◽

Early Stage ◽

Brca Mutation ◽

Clonal Evolution ◽

Metastatic Breast ◽

Genetic Alterations ◽

Telomere Maintenance ◽

Molecular Features

Breast cancer is the most commonly occurring cancer in women. There were over two-million new cases in world in 2018. It is the second leading cause of death from cancer in western countries. At the molecular level, breast cancer is a heterogeneous disease, which is characterized by high genomic instability evidenced by somatic gene mutations, copy number alterations, and chromosome structural rearrangements. The genomic instability is caused by defects in DNA damage repair, transcription, DNA replication, telomere maintenance and mitotic chromosome segregation. According to molecular features, breast cancers are subdivided in subtypes, according to activation of hormone receptors (estrogen receptor and progesterone receptor), of human epidermal growth factors receptor 2 (HER2), and or BRCA mutations. In-depth analyses of the molecular features of primary and metastatic breast cancer have shown the great heterogeneity of genetic alterations and their clonal evolution during disease development. These studies have contributed to identify a repertoire of numerous disease-causing genes that are altered through different mutational processes. While early-stage breast cancer is a curable disease in about 70% of patients, advanced breast cancer is largely incurable. However, molecular studies have contributed to develop new therapeutic approaches targeting HER2, CDK4/6, PI3K, or involving poly(ADP-ribose) polymerase inhibitors for BRCA mutation carriers and immunotherapy.

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Involvement of bcl-2 gene in Japanese follicular lymphoma

Blood ◽

10.1182/blood.v73.3.787.787 ◽

1989 ◽

Vol 73 (3) ◽

pp. 787-791 ◽

Cited By ~ 40

Author(s):

R Amakawa ◽

S Fukuhara ◽

H Ohno ◽

S Doi ◽

S Oguma ◽

...

Keyword(s):

United States ◽

Follicular Lymphoma ◽

The United States ◽

Chain Gene ◽

Gene Rearrangements ◽

Chromosome 18 ◽

Breakpoint Cluster Region ◽

Cluster Region ◽

Molecular Features ◽

Significant Difference

Abstract A t(14;18) (q32;q21) chromosome translocation is closely associated with the follicular lymphoma, which is prevalent in the United States, and the t(14;18) causes the juxtaposition of a bcl-2 gene on chromosome 18 with an immunoglobulin heavy-chain gene locus on chromosome 14. Genomic DNAs from 30 Japanese patients with follicular lymphoma were examined for the molecular features by Southern blot hybridization. Using probe b for the major breakpoint cluster region of a bcl-2 gene, the rearrangements were detected in eight patients. Six of the eight patients had breakpoints located within the major breakpoint region, while two had breakpoints outside this cluster region but within the region of the 7.5-kb SstI fragment containing the probe b sequence. In two patients, pFL-2 probe detected the bcl-2 gene rearrangements that occurred near or within the minor breakpoint cluster region. These ten patients had a rearranged JH-containing fragment that migrated with the rearranged bcl-2 fragment. In the other 20 patients, these two chromosome 18-specific DNA probes did not detect the bcl-2 rearrangements. Compared with studies performed in the United States, the statistical analysis indicates a significant difference in frequency of the bcl-2 gene rearrangements near or within the major breakpoint cluster region (P = 0.0027) and the minor breakpoint cluster region (P = 0.029). However, the distribution difference of these events was not significant.

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