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Gastrointestinal Cytology

  • Gabriela Oprea-Ilies
  • Momin T. Siddiqui
Chapter
Part of the Atlas of Anatomic Pathology book series (AAP)

Abstract

Cytology of the gastrointestinal (GI) tract, with a relatively timid start, continues to develop due to the use of flexible endoscopy. Cytology specimens can be obtained as exfoliative cytology from the oral cavity to the stomach and also from the anorectal area, using brushes, abrasive balloons, and lavage. Fine-needle aspiration (FNA) specimens obtained with flexible endoscopes, aided by high-resolution ultrasound probe, allow for real-time visualization and sampling of lesions of the four layers of the GI tract. As in most areas, cytology specimens and biopsy specimens are complementary and increase sensitivity and specificity in diagnosing GI lesions. Although GI cytology/endoscopy is not yet used for mass screening, one can foresee a time when this is going to change, similar to existing screening programs for pulmonary and airway lesions. Currently, only screening for anorectal squamous intraepithelial lesions is ongoing, with well-determined reporting criteria. GI cytology can be used to diagnose infectious processes and malignancy in immunocompromised patients, and it could be used in surveillance of patients with Barrett’s esophagus or with inflammatory bowel diseases. Being acquainted with the type of cells that normally line the GI tract—basically squamous and glandular cells—and with its wide possible pathology, the cytopathologist is an essential player in the clinical management team. In addition, tissue obtained by FNA as fresh specimens or cell blocks will surely be used for additional molecular studies in the era of molecular testing and personalized medicine.

Keywords

Brush cytology Balloon abrasive cytology Salvage cytology Oropharyngeal carcinoma Esophageal cytology Herpes esophagitis Barrett’s esophagus surveillance Squamous cell carcinoma of the esophagus Adenocarcinoma of the esophagus Gastric adenocarcinoma Neuroendocrine tumors of the stomach Gastric lymphoma Gastrointestinal stromal tumor cytology Duodenal cytology Colon cytology Anal cytology Low-grade squamous intraepithelial lesion High-grade squamous intraepithelial lesion HPV testing in anal cytology 

References

  1. 1.
    Chhieng DC, Stelow EB. Pancreatic cytopathology. New York: Springer; 2007.CrossRefGoogle Scholar
  2. 2.
    DeMay RM. The art and science of cytopathology. Exfoliative cytology, vol. I. 2nd ed. Chicago: American Society for Clinical Pathology Press; 2012.Google Scholar
  3. 3.
    Geisinger KR. Endoscopic biopsies and cytologic brushings of the esophagus are diagnostically complementary. Am J Clin Pathol. 1995;103:295–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Babshet M, Nandimath K, Pervatikar S, Naikmasur V. Efficacy of oral brush cytology in the evaluation of the oral premalignant and malignant lesions. J Cytol. 2011;28:165–72.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Yang H, Berner A, Mei Q, Giercksky KE, Warloe T, Yang G, et al. Cytologic screening for esophageal cancer in a high-risk population in Anyang County, China. Acta Cytol. 2002;46:445–52.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Patel AA, Strome M, Blitzer A. Directed balloon cytology of the esophagus: a novel device for obtaining circumferential cytologic sampling. Laryngoscope. 2017;127(5):1032.CrossRefPubMedGoogle Scholar
  7. 7.
    Graham DY, Spjut HJ. Salvage cytology: a new alternative fiberoptic technique. Gastrointest Endosc. 1979;25:137–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Caos A, Olson N, Willman C, Gogel HK. Endoscopic “salvage” cytology in neoplasms metastatic to the upper gastrointestinal tract. Acta Cytol. 1986;30:32–4.PubMedGoogle Scholar
  9. 9.
    Jhala NC, Jhala DN, Chhieng DC, Eloubeidi MA, Eltoum IA. Endoscopic ultrasound-guided fine-needle aspiration. A cytopathologist’s perspective. Am J Clin Pathol. 2003;120:351–67.CrossRefPubMedGoogle Scholar
  10. 10.
    Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomark Prev. 2005;14:467–75.CrossRefGoogle Scholar
  11. 11.
    D’Souza G, Fakhry C, Sugar EA, Seaberg EC, Weber K, Minkoff HL, et al. Six-month natural history of oral versus cervical human papillomavirus infection. Int J Cancer. 2007;121:143–50.CrossRefPubMedGoogle Scholar
  12. 12.
    Näsman A, Attner P, Hammarstedt L, Du J, Eriksson M, Giraud G, et al. Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma? Int J Cancer. 2009;125:362–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Afrogheh A, Wright CA, Sellars SL, Wetter J, Pelser A, Schubert PT, Hille J. An evaluation of the Shandon Papspin liquid-based oral test using a novel cytologic scoring system. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;113:799–807.CrossRefPubMedGoogle Scholar
  14. 14.
    Navone R, Burlo P, Pich A, Pentenero M, Broccoletti R, Marsico A, Gandolfo S. The impact of liquid-based oral cytology on the diagnosis of oral squamous dysplasia and carcinoma. Cytopathology. 2007;18:356–60.CrossRefPubMedGoogle Scholar
  15. 15.
    Glennie HR, Gilbert JG, Melcher DH, Linehan J, Wadsworth PV. The place of cytology in laryngeal diagnosis. Clin Otolaryngol. 1976;1:131–6.CrossRefPubMedGoogle Scholar
  16. 16.
    Loss R, Sandrin R, França BH, de Azevedo-Alanis LR, Grégio AM, Machado MÂ, de Lima AA. Cytological analysis of the epithelial cells in patients with oral candidiasis. Mycoses. 2011;54:e130–5.CrossRefPubMedGoogle Scholar
  17. 17.
    Barrett AP, Buckley DJ, Greenberg ML, Earl MJ. The value of exfoliative cytology in the diagnosis of oral herpes simplex infection in immunosuppressed patients. Oral Surg Oral Med Oral Pathol. 1986;62:175–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Napier SS, Speight PM. Natural history of potentially malignant oral lesions and conditions: an overview of the literature. J Oral Pathol Med. 2008;37:1–10.CrossRefPubMedGoogle Scholar
  19. 19.
    Warnakulasuriya S, Johnson NW, van der Waal I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med. 2007;36:575–80.CrossRefPubMedGoogle Scholar
  20. 20.
    Izumo T. Oral premalignant lesions: from the pathological viewpoint. Int J Clin Oncol. 2011;16:15–26.CrossRefPubMedGoogle Scholar
  21. 21.
    Gnepp DR. Diagnostic surgical pathology of the head and neck. 2nd ed. Philadelphia: W.B. Saunders; 2009.Google Scholar
  22. 22.
    Namala S, Guduru VS, Ananthaneni A, Devi S, Kuberappa PH, Udayashankar U. Cytological grading: an alternative to histological grading in oral squamous cell carcinoma. J Cytol. 2016;33:130–4.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    el-Naggar AK, Hurr K, Batsakis JG, Luna MA, Goepfert H, Huff V. Sequential loss of heterozygosity at microsatellite motifs in preinvasive and invasive head and neck squamous carcinoma. Cancer Res. 1995;55:2656–9.PubMedGoogle Scholar
  24. 24.
    Graveland AP, Bremmer JF, de Maaker M, Brink A, Cobussen P, Zwart M, et al. Molecular screening of oral precancer. Oral Oncol. 2013;49:1129–35.CrossRefPubMedGoogle Scholar
  25. 25.
    Vulliamy TJ, Marrone A, Knight SW, Walne A, Mason PJ, Dokal I. Mutations in dyskeratosis congenita: their impact on telomere length and the diversity of clinical presentation. Blood. 2006;107:2680–5.CrossRefPubMedGoogle Scholar
  26. 26.
    Lin BP, Harmata PA. Gastric and esophageal brush cytology. Pathology. 1983;15:393–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Grossi L, Ciccaglione AF, Marzio L. Esophagitis and its causes: who is “guilty” when acid is found “not guilty”? World J Gastroenterol. 2017;23:3011–6.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Buss DH, Scharyj MS. Herpesvirus infection of the esophagus and other visceral organs in adults. Am J Med. 1979;66:457–62.CrossRefPubMedGoogle Scholar
  29. 29.
    Eymard D, Martin L, Doummar G, Piché J. Herpes simplex esophagitis in immunocompetent hosts. Can J Infect Dis. 1997;8:351–3.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Wang HW, Kuo CJ, Lin WR, Hsu CM, Ho YP, Lin CJ, et al. The clinical characteristics and manifestations of cytomegalovirus esophagitis. Dis Esophagus. 2016;29:392–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Shaheen NJ, Falk GW, Iyer PG, Gerson LB, American College of Gastroenterology. ACG clinical guideline: diagnosis and management of Barrett’s esophagus. Am J Gastroenterol. 2016;111:30–50.CrossRefPubMedGoogle Scholar
  32. 32.
    Anderson LA, Watson RG, Murphy SJ, Johnston BT, Comber H, McGuigan J, et al. Risk factors for Barrett’s oesophagus and oesophageal adenocarcinoma: results from the FINBAR study. World J Gastroenterol. 2007;13:1585–94.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Falk GW. Risk factors for esophageal cancer development. Surg Oncol Clin N Am. 2009;18:469–85.CrossRefPubMedGoogle Scholar
  34. 34.
    Wani S, Falk G, Hall M, Gaddam S, Wang A, Gupta N, et al. Patients with nondysplastic Barrett’s esophagus have low risks for developing dysplasia or esophageal adenocarcinoma. Clin Gastroenterol Hepatol. 2011;9:220–7.CrossRefPubMedGoogle Scholar
  35. 35.
    Sikkema M, Looman CW, Steyerberg EW, Kerkhof M, Kastelein F, van Dekken H, et al. Predictors for neoplastic progression in patients with Barrett’s esophagus: a prospective cohort study. Am J Gastroenterol. 2011;106:1231–8.CrossRefPubMedGoogle Scholar
  36. 36.
    Kestens C, Offerhaus GJ, van Baal JW, Siersema PD. Patients with Barrett’s esophagus and persistent low-grade dysplasia have an increased risk for high-grade dysplasia and cancer. Clin Gastroenterol Hepatol. 2016;14:956–62.CrossRefPubMedGoogle Scholar
  37. 37.
    Verbeek RE, Leenders M, Ten Kate FJ, van Hillegersberg R, Vleggaar FP, van Baal JW, et al. Surveillance of Barrett’s esophagus and mortality from esophageal adenocarcinoma: a population-based cohort study. Am J Gastroenterol. 2014;109:1215–22.CrossRefPubMedGoogle Scholar
  38. 38.
    Kastelein F, van Olphen SH, Steyerberg EW, Spaander MC, Bruno MJ, ProBar-Study Group, Impact of surveillance for Barrett’s oesophagus on tumour stage and survival of patients with neoplastic progression. Gut. 2016;65:548–54.CrossRefPubMedGoogle Scholar
  39. 39.
    Schlemper RJ, Riddell RH, Kato Y, Borchard F, Cooper HS, Dawsey SM, et al. The Vienna classification of gastrointestinal epithelial neoplasia. Gut. 2000;47:251–5.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Montgomery E, Bronner MP, Goldblum JR, Greenson JK, Haber MM, Hart J, et al. Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation. Hum Pathol. 2001;32:368–78.CrossRefPubMedGoogle Scholar
  41. 41.
    Falk GW. Cytology in Barrett’s esophagus. Gastrointest Endosc Clin N Am. 2003;13:335–48.CrossRefPubMedGoogle Scholar
  42. 42.
    Dar M, Gramlich T, Falk G. Endoscopic brush cytology in Barrett’s esophagus: highly specific but less sensitive than previously reported [abstract]. Gastrointest Endosc. 2002;55:AB200.Google Scholar
  43. 43.
    Kumaravel A, Lopez R, Brainard J, Falk GW. Brush cytology vs. endoscopic biopsy for the surveillance of Barrett’s esophagus. Endoscopy. 2010;42:800–5.CrossRefPubMedGoogle Scholar
  44. 44.
    Ilhan M, Erbaydar T, Akdeniz N, Arslan S. Palmoplantar keratoderma is associated with esophagus squamous cell cancer in Van region of Turkey: a case control study. BMC Cancer. 2005;5:90.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Chang F, Syrjänen S, Shen Q, Cintorino M, Santopietro R, Tosi P, Syrjänen K. Human papillomavirus involvement in esophageal carcinogenesis in the high-incidence area of China. A study of 700 cases by screening and type-specific in situ hybridization. Scand J Gastroenterol. 2000;35:123–30.CrossRefPubMedGoogle Scholar
  46. 46.
    Cummings LC, Cooper GS. Descriptive epidemiology of esophageal carcinoma in the Ohio Cancer Registry. Cancer Detect Prev. 2008;32:87–92.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Ashktorab H, Nouri Z, Nouraie M, Razjouyan H, Lee EE, Dowlati E, et al. Esophageal carcinoma in African Americans: a five-decade experience. Dig Dis Sci. 2011;56:3577–82.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    The Cancer Genome Atlas Research Network. Integrated genomic characterization of oesophageal carcinoma. Nature. 2017;541:169–75.CrossRefPubMedCentralGoogle Scholar
  49. 49.
    Lin DC, Hao JJ, Nagata Y, Xu L, Shang L, Meng X, et al. Genomic and molecular characterization of esophageal squamous cell carcinoma. Nat Genet. 2014;46:467–73.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Bree RL, McGough MF, Schwab RE. CT or US-guided fine needle aspiration biopsy in gastric neoplasms. J Comput Assist Tomogr. 1991;15:565–9.CrossRefPubMedGoogle Scholar
  51. 51.
    Allen DC, Irwin ST. Fine needle aspiration cytology of gastric carcinoma. Ulster Med J. 1997;66:111–4.PubMedPubMedCentralGoogle Scholar
  52. 52.
    Hashemi MR, Rahnavardi M, Bikdeli B, Dehghani Zahedani M, Iranmanesh F. Touch cytology in diagnosing Helicobacter pylori: comparison of four staining methods. Cytopathology. 2008;19:179–84.CrossRefPubMedGoogle Scholar
  53. 53.
    The Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513:202–9.CrossRefGoogle Scholar
  54. 54.
    Borch K, Ahren B, Ahlman H, Falkmer S, Granerus G, Grimelius L. Gastric carcinoids: biologic behavior and prognosis after differentiated treatment in relation to type. Ann Surg. 2005;242:64–73.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. WHO classification of tumours of the digestive system. Geneva: WHO Press; 2010.Google Scholar
  56. 56.
    Chiu BC, Weisenburger DD. An update of the epidemiology of non-Hodgkin’s lymphoma. Clin Lymphoma. 2003;4:161–8.CrossRefPubMedGoogle Scholar
  57. 57.
    Herrmann R, Panahon AM, Barcos MP, Walsh D, Stutzman L. Gastrointestinal involvement in non-Hodgkin’s lymphoma. Cancer. 1980;46:215–22.CrossRefPubMedGoogle Scholar
  58. 58.
    Koch P, del Valle F, Berdel WE, Willich NA, Reers B, Hiddemann W, et al.; German Multicenter Study Group. Primary gastrointestinal non-Hodgkin’s lymphoma: I. Anatomic and histologic distribution, clinical features, and survival data of 371 patients registered in the German Multicenter Study GIT NHL 01/92. J Clin Oncol. 2001;19:3861–73.CrossRefPubMedGoogle Scholar
  59. 59.
    Ferrucci PF, Zucca E. Primary gastric lymphoma pathogenesis and treatment: what has changed over the past 10 years? Br J Haematol. 2007;136:521–38.CrossRefPubMedGoogle Scholar
  60. 60.
    Cavalli F, Isaacson PG, Gascoyne RD, Zucca E. MALT lymphomas. Hematology Am Soc Hematol Educ Program. 2001:241–58.CrossRefGoogle Scholar
  61. 61.
    Zucca E, Bertoni F. Another piece of the MALT lymphomas jigsaw. J Clin Oncol. 2005;23:4832–4.CrossRefPubMedGoogle Scholar
  62. 62.
    Rollinson S, Levene AP, Mensah FK, Roddam PL, Allan JM, Diss TC, et al. Gastric marginal zone lymphoma is associated with polymorphisms in genes involved in inflammatory response and antioxidative capacity. Blood. 2003;102:1007–11.CrossRefPubMedGoogle Scholar
  63. 63.
    Eck M, Schmausser B, Haas R, Greiner A, Czub S, Muller-Hermelink HK. MALT-type lymphoma of the stomach is associated with Helicobacter pylori strains expressing the CagA protein. Gastroenterology. 1997;112:1482–6.CrossRefPubMedGoogle Scholar
  64. 64.
    Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004;103:275–82.CrossRefPubMedGoogle Scholar
  65. 65.
    Offit K, Lococo F, Louie DC. Rearrangement of the bcl-6 gene as prognostic marker in diffuse large cell lymphoma. N Engl J Med. 1994;331:74–80.CrossRefPubMedGoogle Scholar
  66. 66.
    Chung KM, Chang ST, Huang WT, Lu CL, Wu HC, Hwang WS, et al. Bcl-6 expression and lactate dehydrogenase level predict prognosis of primary gastric diffuse large B-cell lymphoma. J Formos Med Assoc. 2013;112:382–9.CrossRefPubMedGoogle Scholar
  67. 67.
    Starostik P, Greiner A, Schwarz S, Patzner J, Schultz A, Müller-Hermelink HK. The role of microsatellite instability in gastric low- and high-grade lymphoma development. Am J Pathol. 2000;157:1129–36.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Hossain FS, Koak Y, Khan FH. Primary gastric Hodgkin’s lymphoma. World J Surg Oncol. 2007;5:119.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Carney JA, Stratakis CA. Familial paraganglioma and gastric stromal sarcoma: a new syndrome distinct from the carney triad. Am J Med Genet. 2002;108:132–9.CrossRefPubMedGoogle Scholar
  70. 70.
    Vij M, Agrawal V, Kumar A, Pandey R. Cytomorphology of gastrointestinal stromal tumors and extra-gastrointestinal stromal tumors: a comprehensive morphologic study. J Cytol. 2013;30:8–12.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Miettinen M, Wang ZF, Sarlomo-Rikala M, Osuch C, Rutkowski P, Lasota J. Succinate dehydrogenase-deficient GISTs: a clinicopathologic, immunohistochemical, and molecular genetic study of 66 gastric GISTs with predilection to young age. Am J Surg Pathol. 2011;35:1712–21.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Conrad R, Castelino-Prabhu S, Cobb C, Raza A. Role of cytopathology in the diagnosis and management of gastrointestinal tract cancers. J Gastrointest Oncol. 2012;3:285–98.PubMedPubMedCentralGoogle Scholar
  73. 73.
    Logrono R, Kurtycz DF, Molina CP, Trivedi VA, Wong JY, Block KP. Analysis of false negative diagnoses on endoscopic brush cytology of biliary and pancreatic duct strictures: the experience at 2 university hospitals. Arch Pathol Lab Med. 2000;124:387–92.PubMedGoogle Scholar
  74. 74.
    Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Kosary CL, et al., editors. SEER 18 2010–2014, all races, both sexes SEER cancer statistics review, 1975–2014. Bethesda, MD: National Cancer Institute. http://seer.cancer.gov/csr/1975_2014/, based on November 2016 SEER data submission, posted to the SEER web site, April 2017.
  75. 75.
    Centers for Disease Control and Prevention (CDC). Human papillomavirus-associated cancers—United States, 2004-2008. MMWR Morb Mortal Wkly Rep. 2012;61:258–61.Google Scholar
  76. 76.
    Silverberg MJ, Lau B, Justice AC, Engels E, Gill MJ, Goedert JJ, et al.; North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of IeDEA. Risk of anal cancer in HIV-infected and HIV-uninfected individuals in North America. Clin Infect Dis. 2012;54:1026–34.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Park IU, Palefsky JM. Evaluation and management of anal intraepithelial neoplasia in HIV-negative and HIV-positive men who have sex with men. Curr Infect Dis Rep. 2010;12:126–33.CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Zhao C, Domfeh AB, Austin RM. Histopathologic outcomes and clinical correlations for high-risk patients screened with anal cytology. Acta Cytol. 2012;56:62–7.CrossRefPubMedGoogle Scholar
  79. 79.
    Darragh TM, Winkler B, Souers RJ, Laucirica R, Zhao C, Moriarty AT, College of American Pathologists Cytopathology Committee. Room for improvement: initial experience with anal cytology: observations from the College of American Pathologists interlaboratory comparison program in nongynecologic cytology. Arch Pathol Lab Med. 2013;137:1550–4.CrossRefPubMedGoogle Scholar
  80. 80.
    Daragh TM, Palfsky JM. Anal cytology. In: Nayar R, Wilbur D, editors. The Bethesda system for reporting cervical cytology. Cham: Springer; 2015. p. 263–85.Google Scholar
  81. 81.
    Centers for Disease Control and Prevention. Stool specimens–intestinal parasites: comparative morphology tables. http://www.cdc.gov/dpdx/diagnosticProcedures/stool/morphcomp.html. Accessed 13 Jan 2018.
  82. 82.
    Wentzensen N, Follansbee S, Borgonovo S, Tokugawa D, Sahasrabuddhe VV, Chen J, et al. Analytic and clinical performance of cobas HPV testing in anal specimens from HIV-positive men who have sex with men. J Clin Microbiol. 2014;52:2892–7.CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Stier EA, Chigurupati NL, Fung L. Prophylactic HPV vaccination and anal cancer. Hum Vaccin Immunother. 2016;12:1348–51.CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pathology and laboratory MedicineEmory University School of MedicineAtlantaUSA
  2. 2.Weill-Cornell MedicineNew YorkUSA

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