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Cytology samples and molecular biomarker testing in lung cancer—advantages and challenges

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Abstract

This review presents an overview on molecular diagnostic in lung cancer using cytologic samples. Every patient with advanced non-small cell lung cancer (NSCLC) should be tested for targetable driver mutations and gene arrangements. If a mutation is found, this may open an option for targeted therapy. As most of the NSCLC patients in advanced stage of disease are no candidates for surgery, these tests have to be performed on small biopsies or cytology samples. The most common and treatable gene alterations should be tested in every patient: EGFR, ALK, ROS1. A growing number of other genetic changes with targetable mutations may become treatable in the near future. To find patients who might profit from inclusion into clinical studies, relevant additional markers may be tested in an appropriate context. Another important approach for treatment is immunotherapy of lung cancer, which is guided by status of PD-L1 expression on tumour cells. The use of cytology samples carries considerable advantages: often, DNA of high quality is extracted thus enabling easy and precise analysis, and samples may be easily obtained. In case of effusions, effusion fluid seldom is not aspirated for immediate patient relief, so no additional dedicated procedure is needed. Some challenges exist: If the tumour cell count is low, mutations with a low allelic frequency may be missed. In cellblocks formalin-induced DNA, damage may obviate any DNA analysis. In very cellular smears, FISH may be impossible due to massive overlapping of nuclei. Autofluorescence may impede FISH analysis. Although there is no real universal test for genomic profiling for lung cancer, the pathology laboratory must be prepared to offer different assays on different specimens in order to address turnaround time and optimise detections of difficult tumour alterations such as gene fusions. The data from the literature demonstrate that cytology show consistent results, and it is a good alternative for lung cancer molecular testing.

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References

  1. Surveillance, Epidemiology, and End Results Program. Cancer stat facts: lung and bronchus cancer. https://seer.cancer.gov/statfacts/html/lungb.html. Accessed 14 March 2019

  2. Lindeman NI, Cagle PT, Beasley MB et al (2013) Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. Arch Pathol Lab Med 137:828–860

    Article  CAS  Google Scholar 

  3. Lindeman NI, Cagle PT, Aisner DL, Arcila ME, Beasley MB, Bernicker EH, Colasacco C, Dacic S, Hirsch FR, Kerr K, Kwiatkowski DJ, Ladanyi M, Nowak JA, Sholl L, Temple-Smolkin R, Solomon B, Souter LH, Thunnissen E, Tsao MS, Ventura CB, Wynes MW, Yatabe Y (2018) Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. Arch Pathol Lab Med 142(3):321–346. https://doi.org/10.5858/arpa.2017-0388-CP

    Article  CAS  PubMed  Google Scholar 

  4. Van Hoef MEHM (2018) Additional recommendations for ALK gene-rearranged non-small-cell lung cancer to the recently updated American Society of Clinical Oncology guideline for stage IV non-small-cell lung cancer. J Clin Oncol 36(4):427. https://doi.org/10.1200/JCO.2017.75.8367

    Article  PubMed  Google Scholar 

  5. Kerr KM, Bubendorf L, Edelman MJ, Marchetti A, Mok T, Novello S, O'Byrne K, Stahel R, Peters S, Felip E, Stahel R, Felip E, Peters S, Kerr K, Besse B, Vansteenkiste J, Eberhardt W, Edelman M, Mok T, O'Byrne K, Novello S, Bubendorf L, Marchetti A, Baas P, Reck M, Syrigos K, Paz-Ares L, Smit EF, Meldgaard P, Adjei A, Nicolson M, Crinò L, van Schil P, Senan S, Faivre-Finn C, Rocco G, Veronesi G, Douillard JY, Lim E, Dooms C, Weder W, de Ruysscher D, le Pechoux C, de Leyn P, Westeel V (2014) Second ESMO consensus conference on lung cancer: pathology and molecular biomarkers for non-small-cell lung cancer. Ann Oncol 25(9):1681–1690. https://doi.org/10.1093/annonc/mdu145

    Article  CAS  PubMed  Google Scholar 

  6. Bubendorf L, Lantuejoul S, de Langen AJ et al (2017) Nonsmall cell lung carcinoma: diagnostic difficulties in small biopsies and cytological specimens. Eur Respir Rev 26:170007. https://doi.org/10.1183/16000617.0007-2017]

    Article  PubMed  Google Scholar 

  7. Zakowski MF (2017) Analytic inquiry: molecular testing in lung cancer. Cancer Cytopathol 125:470–476. https://doi.org/10.1002/cncy.21866

    Article  PubMed  Google Scholar 

  8. Rosell R, Moran T, Queralt C, Porta R, Cardenal F, Camps C, Majem M, Lopez-Vivanco G, Isla D, Provencio M, Insa A, Massuti B, Gonzalez-Larriba JL, Paz-Ares L, Bover I, Garcia-Campelo R, Moreno MA, Catot S, Rolfo C, Reguart N, Palmero R, Sánchez JM, Bastus R, Mayo C, Bertran-Alamillo J, Molina MA, Sanchez JJ, Taron M (2009) Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 361:958–967

    Article  CAS  Google Scholar 

  9. Saito M, Shiraishi K, Kunitoh H, Takenoshita S, Yokota J, Kohno T (2016) Gene aberrations for precision medicine against lung adenocarcinoma. Cancer Sci 107:713–720. https://doi.org/10.1111/cas.12941

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Young K, da Cunha Santos G, Card P, Leighl N (2019) The role of cytology in molecular testing and personalized medicine in lung cancer: a clinical perspective. Cancer Cytopathol 127(2):72–78. https://doi.org/10.1002/cncy.22085

    Article  PubMed  Google Scholar 

  11. Pinto D, Schmitt F (2020) Current applications of molecular testing on body cavity fluids [published online ahead of print, 2020 Mar 30]. Diagn Cytopathol. https://doi.org/10.1002/dc.24410

  12. Sholl LM (2020) Molecular diagnostics in non-small cell lung carcinoma. Semin Respir Crit Care Med 41(3):386–399. https://doi.org/10.1055/s-0039-3399564

    Article  PubMed  Google Scholar 

  13. Sung S, Heymann JJ, Crapanzano JP, Moreira AL, Shu C, Bulman WA, Saqi A (2020) Lung cancer cytology and small biopsy specimens: diagnosis, predictive biomarker testing, acquisition, triage, and management. J Am Soc Cytopathol 9(5):332–345. https://doi.org/10.1016/j.jasc.2020.04.014

    Article  PubMed  Google Scholar 

  14. Sholl LM, Sun H, Butaney M, Zhang C, Lee C, Jänne PA, Rodig SJ (2013) ROS1 immunohistochemistry for detection of ROS1-rearranged lung adenocarcinomas. Am J Surg Pathol 37:1441–1449

    Article  Google Scholar 

  15. Vlajnic T, Savic S, Barascud A, Baschiera B, Bihl M, Grilli B, Herzog M, Rebetez J, Bubendorf L (2018) Detection of ROS1-positive non-small cell lung cancer on cytological specimens using immunocytochemistry. Cancer Cytopathol 126:421–429

    Article  CAS  Google Scholar 

  16. Conde E, Hernandez S, Martinez R, Angulo B, de Castro J, Collazo-Lorduy A, Jimenez B, Muriel A, Mate JL, Moran T, Aranda I, Massuti B, Rojo F, Domine M, Sansano I, Garcia F, Felip E, Mancheño N, Juan O, Sanz J, Gonzalez-Larriba JL, Atienza-Cuevas L, Arriola-Arellano E, Abdulkader I, Garcia-Gonzalez J, Camacho C, Rodriguez-Abreu D, Teixido C, Reguart N, Gonzalez-Piñeiro A, Lazaro-Quintela M, Lozano MD, Gurpide A, Gomez-Roman J, Lopez-Brea M, Pijuan L, Salido M, Arriola E, Company A, Insa A, Esteban-Rodriguez I, Saiz M, Azkona E, Alvarez R, Artal A, Plaza ML, Aguiar D, Enguita AB, Benito A, Paz-Ares L, Garrido P, Lopez-Rios F (2019) Assessment of a new ROS1 immunohistochemistry clone (SP384) for the identification of ROS1 rearrangements in patients with non-small cell lung carcinoma: the ROSING study. J Thorac Oncol 14:2120–2132

    Article  CAS  Google Scholar 

  17. Hofman V, Rouquette I, Long-Mira E, Piton N, Chamorey E, Heeke S, Vignaud JM, Yguel C, Mazières J, Lepage AL, Bibeau F, Begueret H, Lassalle S, Lalvée S, Zahaf K, Benzaquen J, Poudenx M, Marquette CH, Sabourin JC, Ilié M, Hofman P (2019) Multicenter evaluation of a novel ROS1 immunohistochemistry assay (SP384) for detection of ROS1 rearrangements in a large cohort of lung adenocarcinoma patients. J Thorac Oncol 14:1204–1212

    Article  CAS  Google Scholar 

  18. Huang RSP, Smith D, Le CH et al (2020) Correlation of ROS1 immunohistochemistry with ROS1 fusion status determined by fluorescence in situ hybridization. Arch Pathol Lab Med 144:735–741

    Article  CAS  Google Scholar 

  19. VanderLaan PA, Rangachari D, Costa DB (2020) Cancer Cytopathol. https://doi.org/10.1002/cncy.22334

  20. Solomon JP, Linkov I, Rosado A, Mullaney K, Rosen EY, Frosina D, Jungbluth AA, Zehir A, Benayed R, Drilon A, Hyman DM, Ladanyi M, Sireci AN, Hechtman JF (2020) NTRK fusion detection across multiple assays and 33,997 cases: diagnostic implications and pitfalls. Mod Pathol 33:38–46

    Article  CAS  Google Scholar 

  21. Cardarella S, Ogino A, Nishino M, Butaney M, Shen J, Lydon C, Yeap BY, Sholl LM, Johnson BE, Janne PA (2013) Clinical, pathologic, and biologic features associated with BRAF mutations in non-small cell lung cancer. Clin Cancer Res 19(16):4532–4540

    Article  CAS  Google Scholar 

  22. Smit E (2014) BRAF mutations in non-small-cell lung cancer. J Thorac Oncol 9(11):1594–1595

    Article  Google Scholar 

  23. Roy-Chowdhuri S, Aisner DL, Allen TC, Beasley MB, Borczuk A, Cagle PT, Capelozzi V, Dacic S, da Cunha Santos G, Hariri LP, Kerr KM, Lantuejoul S, Mino-Kenudson M, Moreira A, Raparia K, Rekhtman N, Sholl L, Thunnissen E, Tsao MS, Vivero M, Yatabe Y (2016) Biomarker testing in lung carcinoma cytology specimens: a perspective from members of the pulmonary pathology society. Arch Pathol Lab Med 140(11):1267–1272. https://doi.org/10.5858/arpa.2016-0091-SA

    Article  CAS  PubMed  Google Scholar 

  24. Liang H, Wang M (2020) MET oncogene in non-small cell lung cancer: mechanism of MET dysregulation and agents targeting the HGF/c-Met axis. Onco Targets Ther 13:2491–2510. Published 2020 Mar 25. https://doi.org/10.2147/OTT.S231257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Roy-Chowdhuri S (2020) Immunocytochemistry of cytology specimens for predictive biomarkers in lung cancer. Transl Lung Cancer Res 9(3):898–905. https://doi.org/10.21037/tlcr.2019.12.31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Thunnissen E, Allen TC, Adam J, Aisner DL, Beasley MB, Borczuk AC, Cagle PT, Capelozzi VL, Cooper W, Hariri LP, Kern I, Lantuejoul S, Miller R, Mino-Kenudson M, Radonic T, Raparia K, Rekhtman N, Roy-Chowdhuri S, Russell P, Schneider F, Sholl LM, Tsao MS, Vivero M, Yatabe Y (2018) Immunohistochemistry of pulmonary biomarkers: a perspective from members of the pulmonary pathology society. Arch Pathol Lab Med 142(3):408–419. https://doi.org/10.5858/arpa.2017-0106-SA

    Article  CAS  PubMed  Google Scholar 

  27. Grosu HB, Arriola A, Stewart J, Ma J, Bassett R, Hernandez M, Ost D, Roy-Chowdhuri S (2019) PD-L1 detection in histology specimens and matched pleural fluid cell blocks of patients with NSCLC. Respirology. 24(12):1198–1203

    Article  Google Scholar 

  28. Manucha V, Wang C, Huang Y (2012) Non-small-cell lung carcinoma subtyping on cytology without the use of immunohistochemistry - can we meet the challenge? Acta Cytol 56(4):413–418. https://doi.org/10.1159/000338517

    Article  PubMed  Google Scholar 

  29. Metovic J, Righi L, Delsedime L, Volante M, Papotti M (2020) Role of immunocytochemistry in the cytological diagnosis of pulmonary tumors. Acta Cytol 64(1–2):16–29. https://doi.org/10.1159/000496030

    Article  CAS  PubMed  Google Scholar 

  30. Sigel CS, Moreira AL, Travis WD, Zakowski MF, Thornton RH, Riely GJ, Rekhtman N (2011) Subtyping of non-small cell lung carcinoma: a comparison of small biopsy and cytology specimens. J Thorac Oncol 6(11):1849–1856. https://doi.org/10.1097/JTO.0b013e318227142d

    Article  PubMed  Google Scholar 

  31. Bellevicine C, Malapelle U, Vigliar E, Pisapia P, Vita G, Troncone G (2017) How to prepare cytological samples for molecular testing. J Clin Pathol 70(10):819–826

    Article  CAS  Google Scholar 

  32. Jain D, Roy-Chowdhuri S (2018) Molecular pathology of lung cancer cytology specimens: a concise review. Arch Pathol Lab Med 142(9):1127–1133

    Article  CAS  Google Scholar 

  33. da Cunha SG, Saieg MA, Troncone G, Zeppa P (2018) Cytological preparations for molecular analysis: a review of technical procedures, advantages and limitations for referring samples for testing. Cytopathology. 29(2):125–132

    Article  Google Scholar 

  34. Hannigan B, Ye W, Mehrotra M, Lam V, Bolivar A, Zalles S, Barkoh BA, Duose D, Hu PC, Broaddus R, Stewart J, Heymach J, Medeiros LJ, Wistuba I, Luthra R, Roy-Chowdhuri S (2019) Liquid biopsy assay for lung carcinoma using centrifuged supernatants from fine-needle aspiration specimens. Ann Oncol 30(6):963–969

    Article  CAS  Google Scholar 

  35. Villatoro S, Mayo-de-Las-Casas C, Jordana-Ariza N, Viteri-Ramírez S, Garzón-Ibañez M, Moya-Horno I, García-Peláez B, González-Cao M, Malapelle U, Balada-Bel A, Martínez-Bueno A, Campos R, Reguart N, Majem M, Blanco R, Blasco A, Catalán MJ, González X, Troncone G, Karachaliou N, Rosell R, Molina-Vila MA (2019) Prospective detection of mutations in cerebrospinal fluid, pleural effusion, and ascites of advanced cancer patients to guide treatment decisions. Mol Oncol 13(12):2633–2645

    Article  CAS  Google Scholar 

  36. Bubendorf L, Büttner R, Al-Dayel F et al (2016) Testing for ROS1 in non-small cell lung cancer: a review with recommendations. Virchows Arch 469(5):489–503

    Article  CAS  Google Scholar 

  37. Cao Z, Wu W, Zhang W, Li Z, Gao C, Huang Y, Zhang L (2020) ALK and ROS1 rearrangement tested by ARMS-PCR in non-small-cell lung cancer patients via cytology specimens: the experience of Shanghai pulmonary hospital. Diagn Cytopathol 48:524–530

    Article  Google Scholar 

  38. Jain D, Nambirajan A, Borczuk A, Chen G, Minami Y, Moreira AL, Motoi N, Papotti M, Rekhtman N, Russell PA, Savic Prince S, Yatabe Y, Bubendorf L, IASLC Pathology Committee (2019) Immunocytochemistry for predictive biomarker testing in lung cancer cytology. Cancer Cytopathol 127(5):325–339

    Article  CAS  Google Scholar 

  39. Thunissen E, Lissenberg-Witte BI, an den Heuvel MM et al (2019) ALK immunohistochemistry positive, FISH negative NSCLC is infrequent, but associated with impaired survival following treatment with crizotinib. Lung Cancer 138:13–18

    Article  Google Scholar 

  40. Roy-Chowdhuri S, Dacic S, Ghofrani M, Illei PB, Layfield LJ, Lee C, Michael CW, Miller RA, Mitchell JW, Nikolic B, Nowak JA, Pastis NJ Jr, Rauch CA, Sharma A, Souter L, Billman BL, Thomas NE, VanderLaan PA, Voss JS, Wahidi MM, Yarmus LB, Gilbert CR (2020) Collection and handling of thoracic small biopsy and cytology specimens for ancillary studies: guideline from the College of American Pathologists in collaboration with the American College of Chest Physicians, Association for Molecular Pathology, American Society of Cytopathology, American Thoracic Society, Pulmonary Pathology Society, Papanicolaou Society of Cytopathology, Society of Interventional Radiology, and Society of Thoracic Radiology. Arch Pathol Lab Med. https://doi.org/10.5858/arpa.2020-0119-CP

  41. Goyal S, Mohan H, Handa U, Saini V (2012) Rinse fluid and imprint smear cytology of bronchial biopsies in diagnosis of lung tumors. Diagn Cytopathol 40(2):98–103. https://doi.org/10.1002/dc.21502

    Article  PubMed  Google Scholar 

  42. Bodh A, Kaushal V, Kashyap S, Gulati A (2013) Cytohistological correlation in diagnosis of lung tumors by using fiberoptic bronchoscopy: study of 200 cases. Indian J Pathol Microbiol 56:84–88

    Article  Google Scholar 

  43. Saieg MA, Geddie WR, Boerner SL, Liu N, Tsao M, Zhang T, Kamel-Reid S, da Cunha Santos G (2012) The use of FTA cards for preserving unfixed cytological material for high-throughput molecular analysis. Cancer Cytopathol 120(3):206–214

    Article  CAS  Google Scholar 

  44. Layfield LJ, Roy-Chowdhuri S, Baloch Z, Ehya H, Geisinger K, Hsiao SJ, Lin O, Lindeman NI, Roh M, Schmitt F, Sidiropoulos N, VanderLaan PA (2016) Utilization of ancillary studies in the cytologic diagnosis of respiratory lesions. The Papanicolaou Society of Cytopathology. Consensus Recommendations for Respiratory Cytology. Diagn Cytopathol 44(12):1000–1009

    Article  Google Scholar 

  45. Jain D, Mathur SR, Iyer VK (2014) Cell blocks in cytopathology: a review of preparative methods, utility in diagnosis and role in ancillary studies. Cytopathology. 25(6):356–371

    CAS  PubMed  Google Scholar 

  46. Herth FJF, Bubendorf L, Gütz S, Morresi-Hauf A, Hummel M, Junker K, Lehmann U, Petersen I, Schnabel PA, Warth A (2013) Diagnose und prädiktive Analysen an zytologischen und bioptischen Tumorproben nicht-kleinzelliger Lungenkarzinome: Aktuelle Strategien und Herausforderungen. (Diagnostic and predictive analyses of cytological specimens of non-small cell lung cancer: strategies and challenges.) (in German). Pneumologie 67:198–204

    Article  CAS  Google Scholar 

  47. Gailey MP, Stence AA, Jensen CS, Ma D (2015) Multiplatform comparison of molecular oncology tests performed on cytology specimens and formalin-fixed, paraffin-embedded tissue. Cancer Cytopathol 123:30–39

    Article  CAS  Google Scholar 

  48. Roy-Chowdhuri S, Chen H, Singh RR, Krishnamurthy S, Patel KP, Routbort MJ, Manekia J, Barkoh BA, Yao H, Sabir S, Broaddus RR, Medeiros LJ, Staerkel G, Stewart J, Luthra R (2017) Concurrent fine needle aspirations and core needle biopsies: a comparative study of substrates for next-generation sequencing in solid organ malignancies. Mod Pathol 30:499–508

    Article  Google Scholar 

  49. Haentschel M, Boeckeler M, Bonzheim I, Schimmele F, Spengler W, Stanzel F, Petermann C, Darwiche K, Hagmeyer L, Buettner R, Tiemann M, Schildhaus HU, Muche R, Boesmueller H, Everinghoff F, Mueller R, Atique B, Lewis RA, Zender L, Fend F et al (2020) Influence of biopsy technique on molecular genetic tumor characterization in non-small cell lung cancer-the prospective, randomized, single-blinded, multicenter PROFILER study protocol. Diagnostics (Basel, Switzerland) 10(7):459. https://doi.org/10.3390/diagnostics10070459

    Article  CAS  Google Scholar 

  50. Haentschel M, Boeckeler M, Ehab A, Wagner R, Spengler W, Steger V, Boesmueller H, Horger M, Lewis RA, Fend F, Kanz L, Bonzheim I, Hetzel J (2020) Cryobiopsy increases the EGFR detection rate in non-small cell lung cancer. Lung Cancer 141:56–63. https://doi.org/10.1016/j.lungcan.2019.12.008

    Article  PubMed  Google Scholar 

  51. da Cunha Santos G, Schroder M, Zhu JB, Saieg MA et al (2013) Minimizing delays in DNA retrieval: the “freezer method” for glass coverslip removal. Letter to the Editor Regarding Comparative Study of Epidermal Growth Factor Receptor Mutation Analysis on Cytology Smears and Surgical Pathology Specimens from Primary and Metastatic Lung Carcinomas. Cancer Cytopathol 121(9):533

    Article  Google Scholar 

  52. Dejmek A, Zendehrokh N, Tomaszewska M, Edsjö A (2013) Preparation of DNA from cytological material: effects of fixation, staining, and mounting medium on DNA yield and quality. Cancer Cytopathol 121(7):344–353

    Article  CAS  Google Scholar 

  53. Savic S, Bubendorf L (2012) Role of fluorescence in situ hybridization in lung cancer cytology. Acta Cytol 56(6):611–621

    Article  CAS  Google Scholar 

  54. Savic S, Bubendorf L (2016) Common fluorescence in situ hybridization applications in cytology. Arch Pathol Lab Med 140(12):1323–1330

    Article  Google Scholar 

  55. Killian JK, Walker RL, Suuriniemi M, Jones L, Scurci S, Singh P, Cornelison R, Harmon S, Boisvert N, Zhu J, Wang Y, Bilke S, Davis S, Giaccone G, Smith WI Jr, Meltzer PS (2010) Archival fine-needle aspiration cytopathology (FNAC) samples untapped resource for clinical molecular profiling. J Mol Diagn 12(6):739–745

    Article  CAS  Google Scholar 

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Funding

This work was supported by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia—in the framework of a PhD grant to SC (SFRH/BD/147650/2019).

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  1. Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Rua Alfredo Allen, 208 4200-135, Porto, Portugal

    Sule Canberk

  2. Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal

    Sule Canberk

  3. Abel Salazar Biomedical Sciences Institute (ICBAS), University of Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313, Porto, Portugal

    Sule Canberk

  4. Institute of Pathology, University Hospital Cologne, Kerpener Str. 62,, 50924, Köln, Germany

    Marianne Engels

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Canberk, S., Engels, M. Cytology samples and molecular biomarker testing in lung cancer—advantages and challenges. Virchows Arch 478, 45–57 (2021). https://doi.org/10.1007/s00428-020-02995-2

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