Mesenchymal tumors specific to the lung
2023-05-12 Paola Dal Cin, PhD , Yin (Rex) Hung, MD Affiliation1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)
2.Massachussetts General Hospital,Harvard Medical School, Boston (MA)
Classification
Definition
Mesenchymal tumors that arise in the lung are very rare. However, some of them can be found mainly in the lungs. Pulmonary hamartoma (PA) is the most common benign tumor of the lung (3% of all lung tumors). 1
| Mesenchymal tumors specific of the lung | Genetic marker(s) |
|---|---|
| Pulmonary hamartoma(PH) | Frequent 12q13-14 rearrangement , involving HMGA2, mainly as t(3;12)(q27-q28;q15) associated to HMGA2::LPP. 2-4 Less frequent invovement of 6p21 associated with HMGA1 rearrangement. 5-8 Similar aberrations have been reported in othere benign mesenchymal tumors. 9,10 |
| Pulmonary chondroma | Pulmonary chondroma is a component of Carney's triad, a non-hereditary tumor syndrome OMIM:604287, therfore, after definited diagnosis, it is necessary to exclude it.11 SDHB immunohistochemistry can be used as a surrogate marker to detectany componenet of SDH deficiency.12 Chromsome 1 losses were the most frequent in Carney triad tumors (gastric gastrointestinal stromal tumor, paraganglioma ,and pulmonary chondroma) OMIM:604287 , with the the minimal region been 1q12-> q21, a region that harbors the SDHC gene. 13 |
| Diffuse pulmonary lymphangiomatosis | No specific genetic findings so far |
| Pleuropulmonary blastoma (PPB) | Most common childhood primary lung tumor. Germline loss-of-function mutations in DICER1 in the majority of the cases, 14 known as DICER1 syndrome OMIM:606241. Biallelic DICER1 mutation in sporadic cases. 15,16 Frequent biallelic loss of TP53 was also reported 17 Gains in chromosome 8, especially as trisomy, is the most frequent aberration so far reported, among other gains/losses. IGF1R amplification (15q26) may indicate a later event in tumor progression. 18-20 |
| Pulmonary artery intimal sarcoma | Amplification and gains of 12q13-15 containing MDM2 and CDK4; amplificaton of PDGFRA and KIT in 4q12 detected by microarray, FISH analysis and quantitative PCR .21 EGFR ammplification/polysomy also reported. 22 |
| Congenital peribronchial myofibroblastic tumor (CPMT) | Althought morphologically, CPMT is very reminiscent of congenital fibrosarcoma ,but not ETV6::NTRK3 fusion was detected. 23 |
| Primary pulmonary myxoid sarcoma with EWSR1::CREB1 fusion (PPMS) | EWSR1::CREB1 fusion in the majority of the cases. 24,25 The same fusion EWSR1::CREB1 fusion have been also repored fin histopathologically and behaviorally diverse neoplasms26 |
| Lymphangiomatosis of the lung (LAM) | Bialleleic inactivating mutation in TSC2 ,less often in TSC1 in spoardic cases,27,28 Germline (or somatic mosaic) mutation in patients with TSC1 OMIM:605284 or TSC2 OMIM:191100 |
| PEComa | Loss of 16p and TSC2 mutations in 80% of case , with a concurrent TP53 mutation in the majority of the cases .29 TFE3 rearrangement in a subset of cases lacking TSC2 mutations, with SFPQ and IGFBP7 the most frequent partner gene. 30 Other non-recurrent fusion HTRA::ST3GAL1 and RASSF1::PDZRN3.29 |
| Clear cell stromal tumor of the lung with YAP1::TFE3 fusion (emerging entity) | Recurrent YAP1::TFE3 fusion has been described in clear cell (hemangioblastoma-like) stromal tumors of the lung.31-33 While YAP1::TFE3 fusion can be seen in other mesenchymal tumors (such as a subset of epithelioid hemangioendotheliomas), the fusion breakpoints of YAP1 and TFE3 appear to differ between clear cell stromal tumor of the lung and YAP1::TFE3 fusion-positive epithelioid hemangioendothelioma.32 |
Article Bibliography
| Reference Number | Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|---|
| 1 | 34302497 | 2021 | Pulmonary Hamartoma Associated With Lung Cancer (PHALC Study): Results of a Multicenter Study. | Fiorelli A et al |
| 2 | 7504517 | 1993 | Rearrangement of 12q14-15 in pulmonary chondroid hamartoma. | Dal Cin P et al |
| 3 | 7536462 | 1995 | Cytogenetic and histologic findings in 17 pulmonary chondroid hamartomas: evidence for a pathogenetic relationship with lipomas and leiomyomas. | Fletcher JA et al |
| 4 | 8637707 | 1996 | HMGI-C rearrangements as the molecular basis for the majority of pulmonary chondroid hamartomas: a survey of 30 tumors. | Kazmierczak B et al |
| 5 | 1423265 | 1992 | Clonal rearrangement of chromosome band 6p21 in the mesenchymal component of pulmonary chondroid hamartoma. | Fletcher JA et al |
| 6 | 8703850 | 1996 | Variant translocation t(6;10)(p21;q22) in pulmonary chondroid hamartoma. | Minoletti F et al |
| 7 | 9060828 | 1997 | HMGI(Y) activation by chromosome 6p21 rearrangements in multilineage mesenchymal cells from pulmonary hamartoma. | Xiao S et al |
| 8 | 11978964 | 2001 | Intragenic breakpoint within RAD51L1 in a t(6;14)(p21.3;q24) of a pulmonary chondroid hamartoma. | Blank C et al |
| 9 | 9824199 | 1998 | HMGIY is the target of 6p21.3 rearrangements in various benign mesenchymal tumors. | Kazmierczak B et al |
| 10 | 10744071 | 2000 | HMGI-C and HMGI(Y) immunoreactivity correlates with cytogenetic abnormalities in lipomas, pulmonary chondroid hamartomas, endometrial polyps, and uterine leiomyomas and is compatible with rearrangement of the HMGI-C and HMGI(Y) genes. | Tallini G et al |
| 11 | 18043038 | 2007 | Pulmonary chondroma: a tumor associated with Carney triad and different from pulmonary hamartoma. | Rodriguez FJ et al |
| 12 | 29239034 | 2018 | Succinate dehydrogenase (SDH)-deficient neoplasia. | Gill AJ et al |
| 13 | 28739378 | 2018 | Succinate dehydrogenase (SDH) deficiency, Carney triad and the epigenome. | Settas N et al |
| 14 | 34599283 | 2022 | DICER1 tumor predisposition syndrome: an evolving story initiated with the pleuropulmonary blastoma. | González IA et al |
| 15 | 24675358 | 2014 | Biallelic DICER1 mutations in sporadic pleuropulmonary blastoma. | Seki M et al |
| 16 | 26925222 | 2015 | Temporal order of RNase IIIb and loss-of-function mutations during development determines phenotype in pleuropulmonary blastoma / DICER1 syndrome: a unique variant of the two-hit tumor suppression model. | Brenneman M et al |
| 17 | 24909177 | 2014 | Exome sequencing of pleuropulmonary blastoma reveals frequent biallelic loss of TP53 and two hits in DICER1 resulting in retention of 5p-derived miRNA hairpin loop sequences. | Pugh TJ et al |
| 18 | 17163790 | 2006 | Pleuropulmonary blastoma: cytogenetic and spectral karyotype analysis. | Taube JM et al |
| 19 | 17873899 | 2007 | Gain of chromosome 8q is a frequent finding in pleuropulmonary blastoma. | de Krijger RR et al |
| 20 | 28382840 | 2017 | Strong Expression and Amplification of IGF1R in Pleuropulmonary Blastomas. | Vokuhl C et al |
| 21 | 31480474 | 2019 | Unique Aberrations in Intimal Sarcoma Identified by Next-Generation Sequencing as Potential Therapy Targets. | Roszik J et al |
| 22 | 24625414 | 2014 | Intimal sarcoma is the most frequent primary cardiac sarcoma: clinicopathologic and molecular retrospective analysis of 100 primary cardiac sarcomas. | Neuville A et al |
| 23 | 24117734 | 2014 | Congenital peribronchial myofibroblastic tumour with features of maturation in the older infant: report of two cases with a literature review. | Chang C et al |
| 24 | 21997693 | 2011 | Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion: a new tumor entity. | Thway K et al |
| 25 | 32039736 | 2020 | Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion: a case report and review of the literature. | Chen Z et al |
| 26 | 22510762 | 2012 | Tumors with EWSR1-CREB1 and EWSR1-ATF1 fusions: the current status. | Thway K et al |
| 27 | 10823953 | 2000 | Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis. | Carsillo T et al |
| 28 | 34461049 | 2021 | Lymphangioleiomyomatosis: pathogenesis, clinical features, diagnosis, and management. | McCarthy C et al |
| 29 | 25651471 | 2015 | Dichotomy of Genetic Abnormalities in PEComas With Therapeutic Implications. | Agaram NP et al |
| 30 | 26274027 | 2015 | PSF/SFPQ is a very common gene fusion partner in TFE3 rearrangement-associated perivascular epithelioid cell tumors (PEComas) and melanotic Xp11 translocation renal cancers: clinicopathologic, immunohistochemical, and molecular characteristics suggesting classification as a distinct entity. | Rao Q et al |
| 31 | 33899786 | 2021 | Recurrent YAP1-TFE3 Gene Fusions in Clear Cell Stromal Tumor of the Lung. | Agaimy A et al |
| 32 | 34156713 | 2021 | YAP1-TFE3 gene fusion variant in clear cell stromal tumour of lung: report of two cases in support of a distinct entity. | Dermawan JK et al |
| 33 | 35762906 | 2022 | Clear cell stromal tumour of the lung with YAP1::TFE3 fusion: four cases including a case with highly aggressive clinical course. | Dehner CA et al |
Citation
Paola Dal Cin, PhD ; Yin (Rex) Hung, MD
Mesenchymal tumors specific to the lung
Atlas Genet Cytogenet Oncol Haematol. 2023-05-12
Online version: http://atlasgeneticsoncology.org/solid-tumor/209137/mesenchymal-tumors-specific-to-the-lung
