Uterine Inflammatory Myofibroblastic Tumors: Proposed Risk Stratification Model Using Integrated Clinicopathologic and Molecular Analysis.
Journal
The American journal of surgical pathology
ISSN: 1532-0979
Titre abrégé: Am J Surg Pathol
Pays: United States
ID NLM: 7707904
Informations de publication
Date de publication:
01 02 2023
01 02 2023
Historique:
pubmed:
8
11
2022
medline:
18
1
2023
entrez:
7
11
2022
Statut:
ppublish
Résumé
Inflammatory myofibroblastic tumor (IMT) of the uterus is a rare mesenchymal tumor with largely benign behavior; however, a small subset demonstrate aggressive behavior. While clinicopathologic features have been previously associated with aggressive behavior, these reports are based on small series, and these features are imperfect predictors of clinical behavior. IMTs are most commonly driven by ALK fusions, with additional pathogenic molecular alterations being reported only in rare examples of extrauterine IMTs. In this study, a series of 11 uterine IMTs, 5 of which demonstrated aggressive behavior, were evaluated for clinicopathologic variables and additionally subjected to capture-based next-generation sequencing with or without whole-transcriptome RNA sequencing. In the 6 IMTs without aggressive behavior, ALK fusions were the sole pathogenic alteration. In contrast, all 5 aggressive IMTs harbored pathogenic molecular alterations and numerous copy number changes in addition to ALK fusions, with the majority of the additional alterations present in the primary tumors. We combined our series with cases previously reported in the literature and performed statistical analyses to propose a novel clinicopathologic risk stratification score assigning 1 point each for: age above 45 years, size≥5 cm,≥4 mitotic figures per 10 high-power field, and infiltrative borders. No tumors with 0 points had an aggressive outcome, while 21% of tumors with 1 to 2 points and all tumors with ≥3 points had aggressive outcomes. We propose a 2-step classification model that first uses the clinicopathologic risk stratification score to identify low-risk and high-risk tumors, and recommend molecular testing to further classify intermediate-risk tumors.
Identifiants
pubmed: 36344483
doi: 10.1097/PAS.0000000000001987
pii: 00000478-202302000-00002
doi:
Substances chimiques
Anaplastic Lymphoma Kinase
EC 2.7.10.1
Receptor Protein-Tyrosine Kinases
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
157-171Informations de copyright
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest and Source of Funding: This study was funded by the UCSF Department of Pathology Clinical Research Endowment awards granted to N.R.L., K.G., and S.E.U. J.T.R. reports that his spouse receives salary and stock options from Merck and Co. For the remaining authors none were declared.
Références
Pickett JL, Chou A, Andrici JA, et al. Inflammatory myofibroblastic tumors of the female genital tract are under-recognized: a low threshold for ALK immunohistochemistry is required. Am J Surg Pathol. 2017;41:1433–1442.
Devereaux KA, Kunder CA, Longacre TA. ALK-rearranged tumors are highly enriched in the STUMP subcategory of uterine tumors. Am J Surg Pathol. 2019;43:64–74.
Parra-Herran C, Schoolmeester JK, Yuan L, et al. Myxoid leiomyosarcoma of the uterus: a clinicopathologic analysis of 30 cases and review of the literature with reappraisal of its distinction from other uterine myxoid mesenchymal neoplasms. Am J Surg Pathol. 2016;40:285–301.
Mandato VD, Valli R, Mastrofilippo V, et al. Uterine inflammatory myofibroblastic tumor: more common than expected: case report and review. Medicine (Baltimore). 2017;96:e8974.
Subbiah V, McMahon C, Patel S, et al. STUMP un“stumped”: anti-tumor response to anaplastic lymphoma kinase (ALK) inhibitor based targeted therapy in uterine inflammatory myofibroblastic tumor with myxoid features harboring DCTN1-ALK fusion. J Hematol Oncol. 2015;8:66.
Parra-Herran C, Quick CM, Howitt BE, et al. Inflammatory myofibroblastic tumor of the uterus: clinical and pathologic review of 10 cases including a subset with aggressive clinical course. Am J Surg Pathol. 2015;39:157–168.
Bennett JA, Nardi V, Rouzbahman M, et al. Inflammatory myofibroblastic tumor of the uterus: a clinicopathological, immunohistochemical, and molecular analysis of 13 cases highlighting their broad morphologic spectrum. Mod Pathol. 2017;30:1489–1503.
Haimes JD, Stewart CJR, Kudlow BA, et al. Uterine inflammatory myofibroblastic tumors frequently harbor ALK fusions with IGFBP5 and THBS1. Am J Surg Pathol. 2017;41:773–780.
Devereaux KA, Fitzpatrick MB, Hartinger S, et al. Pregnancy-associated inflammatory myofibroblastic tumors of the uterus are clinically distinct and highly enriched for TIMP3-ALK and THBS1-ALK fusions. Am J Surg Pathol. 2020;44:970–981.
Cheek EH, Fadra N, Jackson RA, et al. Uterine inflammatory myofibroblastic tumors in pregnant women with and without involvement of the placenta: a study of 6 cases with identification of a novel TIMP3-RET fusion. Hum Pathol. 2020;97:29–39.
Makhdoum S, Nardi V, Devereaux KA, et al. Inflammatory myofibroblastic tumors associated with the placenta: a series of 9 cases. Hum Pathol. 2020;106:62–73.
Schoolmeester JK, Minn K, Sukov WR, et al. Uterine inflammatory myofibroblastic tumor involving the decidua of the extraplacental membranes: report of a case with a TIMP3-ROS1 gene fusion. Hum Pathol. 2020;100:45–46.
Homaei-Shandiz F, Jafarzadeh-Esfehani R, Moazzen N, et al. Inflammatory myofibroblastic tumor of salpinx: a very rare case treated with a less aggressive method. Iran J Cancer Prev. 2014;7:244–247.
Kushnir CL, Gerardi M, Banet N, et al. Extrauterine inflammatory myofibroblastic tumor: a case report. Gynecol Oncol Case Rep. 2013;6:39–41.
Markovic Vasiljkovic B, Plesinac Karapandzic V, Pejcic T, et al. Follow-up imaging of inflammatory myofibroblastic tumor of the uterus and its spontaneous regression. Iran J Radiol. 2016;13:e12991.
Olgan S, Saatli B, Okyay RE, et al. Hysteroscopic excision of inflammatory myofibroblastic tumor of the uterus: a case report and brief review. Eur J Obstet Gynecol Reprod Biol. 2011;157:234–236.
Sahnoun L, Elezzi O, Maazoun K, et al. Ovarian inflammatory myofibroblastic tumor in children. J Pediatr Adolesc Gynecol. 2007;20:365–366.
Rabban JT, Zaloudek CJ, Shekitka KM, et al. Inflammatory myofibroblastic tumor of the uterus: a clinicopathologic study of 6 cases emphasizing distinction from aggressive mesenchymal tumors. Am J Surg Pathol. 2005;29:1348–1355.
Fuehrer NE, Keeney GL, Ketterling RP, et al. ALK-1 protein expression and ALK gene rearrangements aid in the diagnosis of inflammatory myofibroblastic tumors of the female genital tract. Arch Pathol Lab Med. 2012;136:623–626.
Shintaku M, Fukushima A. Inflammatory myofibroblastic tumor of the uterus with prominent myxoid change. Pathol Int. 2006;56:625–628.
Coffin CM, Watterson J, Priest JR, et al. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor). A clinicopathologic and immunohistochemical study of 84 cases. Am J Surg Pathol. 1995;19:859–872.
Gupta N, Mittal S, Misra R. Inflammatory pseudotumor of uterus: an unusual pelvic mass. Eur J Obstet Gynecol Reprod Biol. 2011;156:118–119.
Fraggetta F, Doglioni C, Scollo P, et al. Uterine inflammatory myofibroblastic tumor in a 10-year-old girl presenting as polypoid mass. J Clin Oncol. 2015;33:e7–e10.
Banet N, Ning Y, Montgomery EA. Inflammatory myofibroblastic tumor of the placenta: a report of a novel lesion in 2 patients. Int J Gynecol Pathol. 2015;34:419–423.
Antonescu CR, Suurmeijer AJ, Zhang L, et al. Molecular characterization of inflammatory myofibroblastic tumors with frequent ALK and ROS1 gene fusions and rare novel RET rearrangement. Am J Surg Pathol. 2015;39:957–967.
Lovly CM, Gupta A, Lipson D, et al. Inflammatory myofibroblastic tumors harbor multiple potentially actionable kinase fusions. Cancer Discov. 2014;4:889–895.
Takahashi A, Kurosawa M, Uemura M, et al. Anaplastic lymphoma kinase-negative uterine inflammatory myofibroblastic tumor containing the ETV6-NTRK3 fusion gene: a case report. J Int Med Res. 2018;46:3498–3503.
Coffin CM, Hornick JL, Fletcher CD. Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases. Am J Surg Pathol. 2007;31:509–520.
Collins K, Ramalingam P, Euscher ED, et al. Uterine inflammatory myofibroblastic neoplasms with aggressive behavior, including an epithelioid inflammatory myofibroblastic sarcoma: a clinicopathologic study of 9 cases. Am J Surg Pathol. 2022;46:105–117.
Hou TC, Wu PS, Huang WY, et al. Over expression of CDK4 and MDM2 in a patient with recurrent ALK-negative mediastinal inflammatory myofibroblastic tumor: a case report. Medicine (Baltimore). 2020;99:e19577.
Marino-Enriquez A, Wang WL, Roy A, et al. Epithelioid inflammatory myofibroblastic sarcoma: an aggressive intra-abdominal variant of inflammatory myofibroblastic tumor with nuclear membrane or perinuclear ALK. Am J Surg Pathol. 2011;35:135–144.
Chen ST, Lee JC. An inflammatory myofibroblastic tumor in liver with ALK and RANBP2 gene rearrangement: combination of distinct morphologic, immunohistochemical, and genetic features. Hum Pathol. 2008;39:1854–1858.
Patel AS, Murphy KM, Hawkins AL, et al. RANBP2 and CLTC are involved in ALK rearrangements in inflammatory myofibroblastic tumors. Cancer Genet Cytogenet. 2007;176:107–114.
Fang H, Langstraat CL, Visscher DW, et al. Epithelioid inflammatory myofibroblastic sarcoma of the ovary with RANB2-ALK fusion: report of a case. Int J Gynecol Pathol. 2018;37:468–472.
Ma Z, Hill DA, Collins MH, et al. Fusion of ALK to the Ran-binding protein 2 (RANBP2) gene in inflammatory myofibroblastic tumor. Genes Chromosomes Cancer. 2003;37:98–105.
Parra-Herran C, Lee CH, Bennett JA, et al. Inflammatory myofibroblastic tumor. WHO Classification of Tumours Series, 5th ed. Lyon (France): International Agency for Research on Cancer; 2020:298–299.
Bennett JA, Croce S, Pesci A, et al. Inflammatory myofibroblastic tumor of the uterus: an immunohistochemical study of 23 cases. Am J Surg Pathol. 2020;44:1441–1449.
Ladwig NR, Schoolmeester JK, Weil L, et al. Inflammatory myofibroblastic tumor associated with the placenta: short tandem repeat genotyping confirms uterine site of origin. Am J Surg Pathol. 2018;42:807–812.
Parra-Herran C. ALK immunohistochemistry and molecular analysis in uterine inflammatory myofibroblastic tumor: proceedings of the ISGyP Companion Society Session at the 2020 USCAP Annual Meeting. Int J Gynecol Pathol. 2021;40:28–31.
Kobel M, Kang EY. The many uses of p53 immunohistochemistry in gynecological pathology: Proceedings of the ISGyP Companion Society Session at the 2020 USCAP Annual 9 Meeting. Int J Gynecol Pathol. 2021;40:32–40.
DePristo MA, Banks E, Poplin R, et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet. 2011;43:491–498.
Li H, Durbin R. Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics. 2010;26:589–595.
Li H, Handsaker B, Wysoker A, et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics. 2009;25:2078–2079.
Lin WY, Yi N, Zhi D, et al. Haplotype-based methods for detecting uncommon causal variants with common SNPs. Genet Epidemiol. 2012;36:572–582.
McKenna A, Hanna M, Banks E, et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20:1297–1303.
Rausch T, Zichner T, Schlattl A, et al. DELLY: structural variant discovery by integrated paired-end and split-read analysis. Bioinformatics. 2012;28:i333–i339.
Talevich E, Shain AH, Botton T, et al. CNVkit: genome-wide copy number detection and visualization from targeted DNA sequencing. PLoS Comput Biol. 2016;12:e1004873.
Van der Auwera GA, Carneiro MO, Hartl C, et al. From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline. Curr Protoc Bioinformatics. 2013;43:11 10 11–11 10 33. doi: 10.1002/0471250953.bi1110s43.
doi: 10.1002/0471250953.bi1110s43
Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010;38:e164.
Yang H, Wang K. Genomic variant annotation and prioritization with ANNOVAR and wANNOVAR. Nat Protoc. 2015;10:1556–1566.
Ye K, Schulz MH, Long Q, et al. Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads. Bioinformatics. 2009;25:2865–2871.
Genomes Project C, Abecasis GR, Altshuler D, et al. A map of human genome variation from population-scale sequencing. Nature. 2010;467:1061–1073.
Mohammad N, Stewart CJR, Chiang S, et al. p53 immunohistochemical analysis of fusion-positive uterine sarcomas. Histopathology. 2021;78:805–813.
Schaefer IM, Hornick JL, Sholl LM, et al. Abnormal p53 and p16 staining patterns distinguish uterine leiomyosarcoma from inflammatory myofibroblastic tumour. Histopathology. 2017;70:1138–1146.
Chudasama P, Mughal SS, Sanders MA, et al. Integrative genomic and transcriptomic analysis of leiomyosarcoma. Nat Commun. 2018;9:144.