Clinicopathologic features and genomic analysis of pulmonary blastomatoid carcinosarcoma

Abstract Background: This study was designed to investigate the clinicopathologic features of pulmonary blastomatoid carcinosarcoma and explore the genomic profiles of epithelial and mesenchymal components in this tumor. Methods: Three cases of pulmonary blastomatoid carcinosarcoma were enrolled in this study. Clinic-pathologic information and prognostic data were retrospectively reviewed. Diagnostic immunohistochemistry was performed. The epithelial and mesenchymal components were microdissected to investigate the genomic profiles by performing capture-based targeted next generation sequencing. Results: The epithelial component in patient one was consistent of low-grade and high-grade fetal lung adenocarcinoma and displayed aberrant nuclear expression of β-catenin and missense mutation of CTNNB1 in its low-grade epithelial. The epithelial component in another two patients were consistent of high-grade fetal lung adenocarcinoma/enteric adenocarcinoma and harbored no mutation of CTNNB1. The mesenchymal components in all three tumors were primitive round/spindle cells in morphology without definite differentiation and showed cytoplasmic dot positive of β-catenin and no corresponding mutation. Within a tumor, both components exhibited relatively comparable molecular profile. In patient one, 4 mutations: RB1, FAT3, PTCH1 and LRP1B were shared by both epithelial and mesenchymal components. Epithelial had additional mutations in BCOR, CTNNB1, CTCF, FAT1 and DICER1. In patient two, 12 mutations were shared. The epithelial had BRCA2 mutations and the mesenchymal had mutations in CREBBP, ALK, DNMT3A, ASXL2, MYCN andRICTOR. Patient three had 6 shared mutations. The epithelial had an additional mutation in KAT6A and the mesenchymal had an additional mutation in APC. Collectively, we observed heterogeneity between epithelial and mesenchymal components of the same tumor. Conclusions: Parallel detection of genetic abnormalities in epithelial and mesenchymal components of blastomatoid carcinosarcoma could provide evidence for tumor differentiation, molecular targeting and further distinguish them from conventional pulmonary blastoma and carcinosarcoma.

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Clinicopathologic features and genomic analysis of pulmonary blastomatoid carcinosarcoma

10.21203/rs.2.18869/v2 ◽

2020 ◽

Author(s):

Jikai Zhao ◽

Chan Xiang ◽

Ruiying Zhao ◽

Ping Guo ◽

Jingjing Zheng ◽

...

Keyword(s):

Epithelial Cells ◽

Lung Adenocarcinoma ◽

Genomic Analysis ◽

Fetal Lung ◽

Molecular Profile ◽

Low Grade ◽

High Grade ◽

Clinicopathologic Features ◽

Epithelial Component ◽

Additional Mutation

Abstract Background:This study was designed to investigate the clinicopathologic features of pulmonary blastomatoid carcinosarcoma and explore the genomic profiles of epithelial and mesenchymal components in this tumor. Methods: Three cases of pulmonary blastomatoid carcinosarcoma were enrolled in this study. Clinicopathologic informationand prognostic data were retrospectively reviewed. Diagnostic immunohistochemistry was performed. The epithelial and mesenchymal components were microdissected to investigate the genomic profiles by performing capture-based targeted next generation sequencing. Results:The epithelial components in patient one consisted of low-grade and high-grade fetal lung adenocarcinoma. Low-grade epithelial cells showed nuclear expression of β-catenin and missense mutation of CTNNB1. The epithelial components in another two patients consisted of high-grade fetal lung adenocarcinoma/enteric adenocarcinoma. The epithelial cells showed membrane staining of β-cateninand harbored no mutation of CTNNB1. The mesenchymal components in all three tumors were composed of primitive round/spindle cells without definite differentiation and showed cytoplasmic dot positive of β-catenin and no corresponding mutation. Within a tumor, both components exhibited relatively comparable molecular profile. In patient one, 4 mutations: RB1, FAT3, PTCH1and LRP1Bwere shared by both epithelial and mesenchymal components. Epithelial component had additional mutations in BCOR, CTNNB1, CTCF, FAT1and DICER1. In patient two, 12 mutations were shared. The epithelial component had BRCA2mutation and the mesenchymal had mutations in CREBBP, ALK, DNMT3A, ASXL2, MYCN andRICTOR. Patient three had 6 shared mutations. The epithelial component had an additional mutation in KAT6Aand the mesenchymal had an additional mutation in APC. Collectively, we observed heterogeneity between epithelial and mesenchymal components of the same tumor. Conclusions:Blastomatoid carcinosarcoma showed characteristic morphology and immunophenotype.Parallel detection of genetic abnormalities in epithelial and mesenchymal components could provide further evidence for tumor differentiation, molecular targeting and differential diagnosis.

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PATH-41. POLYMORPHOUS LOW-GRADE NEUROEPITHELIAL TUMOR OF THE YOUNG WITH FGFR3-TACC3 FUSION MIMICKING HIGH-GRADE GLIOMA: CASE REPORT AND SERIES OF HIGH-GRADE CORRELATES

Neuro-Oncology ◽

10.1093/neuonc/noab196.493 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi124-vi124

Author(s):

Danielle Golub ◽

Peter C Pan ◽

Benjamin Liechty ◽

Cheyanne Slocum ◽

Tejus Bale ◽

...

Keyword(s):

Progression Free Survival ◽

High Grade Glioma ◽

Proliferation Index ◽

Molecular Profile ◽

Low Grade ◽

High Grade ◽

Molecular Features ◽

Tert Promoter ◽

Tert Promoter Mutations ◽

Promoter Mutations

Abstract BACKGROUND Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently-described entity that can occasionally histologically and molecularly mimic high-grade glioma. The histologic and molecular features that predict aggressive behavior in FGFR3-TACC3 altered tumors are unclear. CASES We present a rare case of an indolent neuroepithelial neoplasm in a 59-year-old female with imaging initially suggestive of high-grade glioma and analyze common molecular features between this case and a series of high-grade gliomas. After total resection, pathology of the case patient revealed predominantly low-grade cytomorphology, abundant microcalcifications, unusual neovascularization, and a low proliferation index. The lesion was diffusely CD34 immunoreactive and harbored both an FGFR3-TACC3 fusion and a TERT promoter mutation. Based on the overall histologic and molecular profile, a diagnosis of PLNTY was favored. The patient was thereafter observed without adjuvant therapy with no evidence of progression at 15-month follow-up. In contrast, a series of eight adult patients with glioblastomas harboring FGFR3-TACC3 fusions and correspondingly aggressive clinical courses are also presented. Common molecular findings included IDH-wildtype status, absence of 1p19q codeletion, and CDKN2A loss. TERT promoter mutations and lack of MGMT promoter methylation were also frequently observed. These patients demonstrated a median 15-month overall survival and a 6-month progression-free survival. CONCLUSIONS PLNTY is a rare low-grade entity that can display characteristics of high-grade glioma, particularly in adults. The potential for a unique entity mimicking PLNTY which may act as a precursor lesion for a more malignant phenotype should be considered in cases with FGFR3-TACC3 fusions and other high-grade features.

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Low-grade serous ovarian carcinoma: an evolution toward targeted therapy

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2019-000832 ◽

2019 ◽

Vol 30 (10) ◽

pp. 1619-1626 ◽

Cited By ~ 3

Author(s):

Ioannis A Voutsadakis

Keyword(s):

Clinical Trials ◽

Targeted Therapy ◽

Ovarian Carcinoma ◽

Molecular Profile ◽

Low Grade ◽

High Grade ◽

Novel Therapies ◽

Precursor Lesions ◽

Molecular Defects ◽

Serous Ovarian Carcinoma

Low-grade serous ovarian carcinoma and its high-grade serous ovarian carcinoma counterpart differ in their precursor lesions, molecular profile, natural history, and response to therapies. As such, low-grade serous ovarian carcinoma needs to be studied separately from high-grade serous ovarian carcinoma, despite challenges stemming from its rarity. A deeper understanding of the pathogenesis of low-grade serous ovarian carcinoma and the most common molecular defects and pathways involved in the carcinogenesis of the ovarian epithelium from normal to serous borderline ovarian tumors to low-grade serous ovarian carcinoma will help develop better therapies. By adopting targeted approaches there may be an opportunity to integrate novel therapies without the need for robust numbers in clinical trials. This manuscript will discuss low-grade serous ovarian carcinoma and focus on the arising treatments being developed with an improved understanding of the pathogenesis of this disease.

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A Case of Biphasic Pulmonary Blastoma (High-grade Adenocarcinoma of Fetal Lung Type with a Sarcomatous Component).

Haigan ◽

10.2482/haigan.37.249 ◽

1997 ◽

Vol 37 (2) ◽

pp. 249-254 ◽

Cited By ~ 2

Author(s):

Kazuhiko Date ◽

Shinji Kato ◽

Kazuo Kondo ◽

Masashi Yoshihara ◽

Kazushige Beppu ◽

...

Keyword(s):

Fetal Lung ◽

Pulmonary Blastoma ◽

High Grade ◽

Sarcomatous Component

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Aggressive Clear Cell Chondrosarcomas: Do Distinctive Characteristics Exist?: A Report of 4 Cases

Archives of Pathology & Laboratory Medicine ◽

10.5858/2006-130-1673-acccdd ◽

2006 ◽

Vol 130 (11) ◽

pp. 1673-1679 ◽

Cited By ~ 2

Author(s):

Domenico Corradi ◽

Patrizia Bacchini ◽

Nicoletta Campanini ◽

Franco Bertoni

Keyword(s):

Clear Cell ◽

Low Grade ◽

Common Symptom ◽

High Grade ◽

Clinicopathologic Features ◽

Immunohistochemical Expression ◽

Clear Cell Chondrosarcoma ◽

Aggressive Tumors ◽

Synchronous Lesion ◽

Conventional Light Microscopy

Abstract Context.—Clear cell chondrosarcoma (CCC) is commonly considered to be a low-grade subtype of chondrosarcoma. However, a few cases of CCC behave as high-grade lesions (with early metastases or multiple/synchronous locations). Objective.—To investigate morphologic features that can help predict the aggressiveness of these CCCs. Design.—To investigate possible hallmarks of this aggressiveness, we are presenting the clinicopathologic features of 6 cases of CCC, 4 of which presented aggressive features and 2 low-grade behavior. The patients were 5 men and 1 woman; their ages ranged from 22 to 47 years. Histologic appearance, ultrastructure, and immunohistochemical expression of metalloproteinase 1 and 2 and their inhibitors were evaluated in all 6 cases. Results.—Pain was the most common symptom; the lesions were located in the femur (4), humerus (2), and vertebral body (1), with 1 patient presenting a double/synchronous lesion. Although no major differences were detected using conventional light microscopy, an ultrastructural analysis—at variance with usual cases—showed a lack of superficial microvilli in more than 50% of neoplastic cells in the aggressive cases, therefore suggesting a less differentiated phenotype. In addition, metalloproteinase 2 was more diffusely expressed in the aggressive tumors than in the conventional CCCs, whereas p53 labeling was always negative. Conclusions.—The aggressive behavior of some CCCs may be, at least in part, correlated to a lesser degree of cell differentiation and to the expression of tumor cell proteins, such as metalloproteinase 2, which are able to favor neoplastic spreading.

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The immunologic tumor microenvironment in endometrioid endometrial cancer in the morphomolecular context: mutual correlations and prognostic impact depending on molecular alterations

Cancer Immunology Immunotherapy ◽

10.1007/s00262-020-02813-3 ◽

2020 ◽

Author(s):

Barbara Willvonseder ◽

Fabian Stögbauer ◽

Katja Steiger ◽

Moritz Jesinghaus ◽

Peer-Hendrik Kuhn ◽

...

Keyword(s):

T Cells ◽

Endometrial Cancer ◽

Prognostic Biomarker ◽

High Density ◽

Molecular Profile ◽

Low Grade ◽

Prognostic Impact ◽

High Grade ◽

Molecular Subgroups ◽

Histopathological Grading

Abstract Objective POLE-mutant, microsatellite-instable (MSI), p53-mutant and non-specific molecular profile (NSMP) are TCGA-defined molecular subgroups of endometrial cancer (EC). Hypothesizing that morphology and tumor immunology might differ depending on molecular background concerning composition and prognostic impact, we aimed to comprehensively interconnect morphologic, immunologic and molecular data. Methods TCGA-defined molecular groups were determined by immunohistochemistry and sequencing in n = 142 endometrioid EC. WHO-defined histopathological grading was performed. The immunologic microenvironment (iTME) was characterised by the quantification of intraepithelial and stromal populations of tumor-infiltrating lymphocytes (TIL: overall T-cells; T-Killer cells; regulatory T-cells (Treg)). Immunologic parameters were correlated with WHO-grading, TCGA-subgroups and prognosis. Results High density TIL were significantly more frequent in high-grade (G3) compared to low-grade (G1/2) EC in the whole cohort and in the subgroup of POLE-wildtype-/microsatellite-stable-EC. MSI was associated with high-level TIL-infiltration when taking into account the type of mismatch repair defect (MLH1/PMS2; MSH2/MSH6). Prognostic impact of biomarkers depended on molecular subgroups: In p53-mutant EC, Treg were independently prognostic, in NSMP, the unique independently prognostic biomarker was WHO-grading. Conclusions EC morphology and immunology differ depending on genetics. Our study delineated two molecularly distinct subgroups of immunogenic EC characterized by high-density TIL-infiltration: MSI EC and high-grade POLE-wildtype/microsatellite-stable-EC. Prognostic impact of TIL-populations relied on TCGA-subgroups indicating specific roles for TIL depending on molecular background. In NSMP, histopathological grading was the only prognostic biomarker demonstrating the relevance of WHO-grading in an era of molecular subtyping.

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