Reetesh K. Pai, MD

Division Director, Anatomic Pathology at Presbyterian Hospital of UPMC, Director, Gastrointestinal Pathology Center of Excellence, Professor of Pathology

Dr. Pai is a Professor of Pathology at the University of Pittsburgh School of Medicine, Director of Anatomic Pathology at Presbyterian Hospital of UPMC, and Director of Gastrointestinal Pathology at UPMC. Dr. Pai is an experienced and internationally known GI pathologist with expertise in appendiceal and colorectal pathology.

Clinical Expertise

  • Appendix Pathology
  • Colorectal Pathology
  • Inflammatory Bowel Disease
  • Immunohistochemistry and ancillary testing in GI tumors
Education & Training
MD - University of New Mexico
Residency (Anatomic and Clinical Pathology) - University of New Mexico
Surgical Pathology Fellowship with focus in GI and Pancreatobiliary Pathology - Stanford University
Cytopathology Fellowship - Stanford University
Awards
John Yardley Investigator Award from the Roger C. Haggitt Gastrointestinal Pathology Society, 2020
Outstanding Faculty Research Mentor, University of Pittsburgh Department of Pathology, 2017
Outstanding Faculty Research Mentor, University of Pittsburgh Department of Pathology, 2015
Teaching Award in Anatomic Pathology, Stanford University, 2007
Alpha Omega Alpha, University of New Mexico, 2001
Research Interests

Dr. Pai’s research interests include the clinicopathologic analysis and evaluation of biomarkers for colorectal and appendiceal neoplasms and their correlation with clinical outcome. Dr. Pai’s research interests also include the characterization of inflammatory conditions of the colon and rectum.

Representative Publications

View Dr. Pai's publications on PubMed

Selected Publications

  1. Davison JM, Hartman DA, Singhi AD, Choudry HA, Ahrendt SA, Zureikat AH, Ramalingam L, Nikiforova M, Pai RK. Loss of SMAD4 protein expression is associated with high tumor grade and poor prognosis in disseminated appendiceal mucinous neoplasms. Am J Surg Pathol. 2014; 38:583-92.
  2. Davison JM, Choudry HA, Pingpank JF, Ahrendt SA, Holtzmann MP, Zureikat AH, Zeh HJ, Ramalingam L, Zhu B, Nikiforova M, Bartlett DL, Pai RK. Clinicopathologic and molecular analysis of disseminated appendiceal mucinous neoplasms: Identification of factors predicting survival and proposed criteria for a three-tiered assessment of tumor grade. Mod Pathol. 2014;27:1521-1539.
  3. Landau MA, Kuan SF, Chiosea S, Pai RK. BRAF-mutated microsatellite stable colorectal carcinoma: An aggressive adenocarcinoma with reduced CDX2 and increased cytokeratin 7 immunohistochemical expression. Hum Pathol 2014;45:1704-12.
  4. Singhi AD, Davison JM, Choudry HA, Pingpank JF, Ahrendt SA, Holtzman MP, Zureikat AH, Zeh HJ, Ramalingam L, Mantha G, Nikiforova M, Bartlett DL, Pai RK. GNAS is frequently mutated in both low-grade and high-grade disseminated appendiceal mucinous neoplasms but does not affect survival. Hum Pathol 2014;45:1737-43.
  5. Hartman DJ, Binion D, Regueiro M, Schraut W, Bahary N, Sun W, Nikiforova M, Pai RK. Isocitrate dehydrogenase-1 is mutated in inflammatory bowel disease-associated intestinal adenocarcinoma with low-grade tubuloglandular histology but not in sporadic intestinal adenocarcinoma. Am J Surg Pathol 2014;38:1147-1156.
  6. Dudley B, Brand RE, Thull D, Bahary N, Nikiforova MN, Pai RK. Germline MLH1 mutations are frequently identified in Lynch syndrome patients with colorectal and endometrial carcinoma demonstrating isolated loss of PMS2 immunohistochemical expression. Am J Surg Pathol 2015;39:1114-20.
  7. Mas-Moya J*, Dudley B, Brand RE, Thull D, Bahary N, Nikiforova M, Pai RK. Clinicopathologic comparison of colorectal and endometrial carcinoma in patients with Lynch syndrome versus patients with Lynch-like syndrome. Hum Pathol 2015;46:1616-25.
  8. Olevian DC*, Nikiforova M, Chiosea S, Sun W, Bahary W, Kuan S, Pai RK.  Colorectal poorly differentiated neuroendocrine carcinomas frequently exhibit BRAF mutations and are associated with poor overall survival. Hum Pathol. 2016;49:124-34.
  9. Farchoukh L*, Kuan S, Dudley B, Brand R, Nikiforova M, Pai RK. MLH1-deficient colorectal carcinoma with wild-type BRAF and MLH1 promoter hypermethylation harbor KRAS mutations and arise from conventional adenomas: Implications for the serrated neoplasia pathway. Am J Surg Pathol 2016;40:1390-9.
  10. Reuter JA, Spacek DV, Pai RK, Snyder MP. Comprehensive genome and transcriptome profiling through simultaneous DNA and RNA sequencing (Simul-seq). Nature Methods 2016;13:953-958.
  11. Pai RK, Chen Y, Jakubowski MA, Shadrach BL, Plesec TP, Pai RK. Colorectal carcinomas with submucosal invasion (pT1): Analysis of histopathologic and molecular factors predicting lymph node metastasis. Mod Pathol 2017;30:113-122. PMID 28252654.
  12. Kuan SF, Ren B, Nikiforova MN, Brand R, Dudley B, Pai RK. Neoadjuvant therapy in microsatellite stable colorectal carcinoma induces concomitant loss of MHS6 and Ki67 expression. Hum Pathol 2017;63:33-39. PMID 28232158.
  13. Carr NJ, Bibeau F, Bradley RF, Dartigues P, Feakins RM, Geisinger KR, Gui X, Isaac S, Milione M, Misdraji J, Pai RK, Rodriguez-Justo M, Sobin LH, van Velthyusen MF, Yantiss RK. The histopathologic classification, diagnosis, and differential diagnosis of mucinous appendiceal neoplasms, appendiceal adenocarcinoma, and pseudomyxoma peritonei. Histopathology 2017;71:847-858. PMID 28746986.
  14. Olevian DC*, Pai RK. Histologic features do not reliably predict mismatch repair protein deficiency in colorectal carcinoma: The results of a 5-year prospective evaluation. Appl Immunohistochem Mol Morphol 2018;26:231-238. PMID 29189259.
  15. Landau MA, Zhu B, Akwuole FN, Pai RK. Site-specific differences in colonic adenocarcinoma: KRAS mutations and high tumor budding are more frequent in cecal adenocarcinoma. Am J Surg Pathol 2018;42:351-358. PMID 29189259.
  16. Hartman DJ, Binion DG, Regueiro MD, Miller, C, Herbst C, Pai RK. Distinct histopathologic and molecular alterations in inflammatory bowel disease-associated intestinal adenocarcinoma: c-MYC amplification is common and associated with mucinous / signet ring cell differentiation. Inflamm Bowel Dis 2018;24:1780-1790. PMID 29788391.
  17. Choudry HA, Pai RK.  Management of mucinous appendiceal tumors. Ann Surg Oncol 2018;25:2135-2144. PMID 29717422.
  18. Pai RK, Dudley B, Karloski E, Brand RE, O’Callaghan N, Rosty C, Buchanan D, Jenkins M, Thibodeau S, French A, Lindor N, Pai RK. DNA mismatch repair protein deficient non-neoplastic colonic crypts: A novel indicator of Lynch syndrome. Mod Pathol 2018;31:1608-1618. PMID 29884888.
  19. Ma C, Olevian DC*, Lowenthal BM*, Jayachandran P, Kozak MM, Chang DT, Pai RK.  Loss of SATB2 expression in colorectal carcinoma is associated with DNA mismatch repair protein deficiency and BRAF mutation. Am J Surg Pathol 2018;42:1409-1417. PMID 30001238.
  20. Landau MA, Zhu B, Okwuole FN, Pai RK. Histopathologic predictors of recurrence in stage III colon cancer:  Reappraisal of tumor deposits and tumor budding using AJCC8 criteria. Int J Surg Pathol 2018;42:351-358. PMID 29992847.
  21. Jairath V, Peyrin-Biroulet L, Zou G, Mosli M, Van DeCasteele N, Pai RK, Valasek M, Marcal-Bressenot A, Stitt L, Shackelton L, Khanna R, D’Haens GR, Sandborn WJ, Olson A, Feagan BG, Pai RK.   Responsiveness of histological disease activity indices in ulcerative colitis: a post-hoc analysis using data from the Touchstone randomized controlled trial. Gut 2019;68:1162-1168. PMID 30076171.
  22. Ma C, Lowenthal BM, Pai RK. SATB2 is superior to CDX2 in distinguishing signet ring cell carcinoma of the upper gastrointestinal tract and lower gastrointestinal tract. Am J Surg Pathol 2018;42:1815-1722. PMID 30212392.
  23. Choudry MHA, Shuai Y, Jones HL, Pai RK, Pingpank JF, Ahrendt SS, Holtzman MP, Zeh HJ, Bartlett DJ. Postoperative complications independently predict cancer-related survival in peritoneal malignancies. Ann Surg Oncol 2018;25:3950-3959. PMID 30302637.
  24. Choudry HA, Bednar F, Shuai Y, Jones HL, Pai RK, Pingpank JF, Ahrendt SS, Holtzman MP, Zeh HJ, Bartlett DL. Repeat cytoreductive surgery-hyperthermic intraperitoneal chemoperfusion is feasible and offers survival benefit in select patients with peritoneal metastasis. Ann Surg Oncol 2019;26:1445-1453 (PMID 30825033).
  25. LaFramboise WA, Pai RK, Petrosko P, Belsky MA, Dhir A, Howard PG, Becich MJ, Holtzman MP, Ahrendt SA, Pingpank JF, Zeh HJ, Dhir R, Bartlett DL, Choudry HA. Discrimination of low and high grade appendiceal mucinous neoplasms by targeted sequencing of cancer related variants. Mod Pathol 2019;32:1197-1209 (PMID 30962504).
  26. Ma C, Olevian D, Miller C, Herbst C, Jayachandran P, Kozak MM, Chang DT, Pai RK. SATB2 and CDX2 are prognostic biomarkers in DNA mismatch repair deficient colon cancer. Mod Pathol 2019;32:1217-1231 (PMID 30962505).
  27. Choudry HA, Pai RK, Parimi A, Jones HL, Pingpank JF, Ahrendt SS, Holtzman MP, Bartlett DL. Discordant diagnostic terminology and pathologic grading of primary appendiceal mucinous neoplasms reviewed at a high-volume center. Ann Surg Oncol 2019;26:2607-2614 (PMID 31111354).
  28. Ma C, Henn P, Miller C, Herbst C, Hartman DJ, Pai RK. Loss of SATB2 expression is a biomarker of inflammatory bowel disease associated colorectal dysplasia and adenocarcinoma. Am J Surg Pathol 2019;43:1314-1322 (PMID 31318711).
  29. Gordon IO, Bettenworth D, Bokemeyer A, Srivastava A, Rosty C, Hertogh GE, Robert ME, Valasek MA, Mao R, Kurada S, Harpaz N, Borralho P, Pai RK, Pai RK, Odze R, Feakins R, Parker CE, Nguyen T, Jairath V, Baker ME, Bruining DH, Fletcher JG, Feagan BG, Rieder F; Stenosis Therapy and Anti-Fibrotic Research (STAR) Consortium. Histopathology Scoring Systems of Stenosis Associated With Small Bowel Crohn's Disease: A Systematic Review. Gastroenterology 2019;158:137-150. (PMID 31476299).
  30. Lowenthal BM, Nason KS, Pennathur A, Luketich JD, Pai RK, Davison JM, Ma C. Loss of ARID1A expression is associated with DNA mismatch repair protein deficiency and favorable prognosis in advanced stage surgically resected esophageal adenocarcinoma. Hum Pathol 2019; 94:1-10 (PMID 31655170).
  31. Pai RK, Hartman DJ, Ramos Rivers C, Regueiro M, Schwartz M, Binion DG, Pai RK. Complete resolution of mucosal neutrophils associates with improved long-term clinical outcomes in ulcerative colitis. Clin Gastroenterol Hepatol 2020;18:2510-2517. (PMID 31843598).
  32. Solomon D, Bekhor E, Leigh N, Maniar YM, Totin L, Hoftsedt M, Aycart SN, Carr J, Ballentine S, Magge DR, Golas BJ, Pai RK, Polydorides AD, Bartlett DL, Labow DM, Choudry HA, Sarpel U. Surveillance of low-grade appendiceal mucinous neoplasms with peritoneal metastases after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: Are 5 years enough? A multisite experience.  Ann Surg Oncol 2020;27:147-153 (PMID 31385130).
  33. Brand RE, Dudley B, Karloski E, Das R, Fuhrer K, Pai RK, Pai RK. Detection of DNA mismatch repair deficient crypts in random colonoscopic biopsies identifies Lynch syndrome patients. Fam Cancer 2020;19:168-175. (PMID 31997046).
  34. Villatoro TM, Ma C, Pai RK. SWI / SNF nucleosome complex-deficient colorectal carcinomas have distinct clinicopathologic features. Hum Pathol 2020;99:53-61. (PMID 32222462).
  35. Hartman DJ, Frank M, Siegh L, Choudry H, Pingpank J, Holtzman M, Bartlett D, Bahary N, Pantanowitz L, Pai RK. Automated quantitation of CD8-positive T cells predicts prognosis in colonic adenocarcinoma with mucinous, signet ring cell, or medullary differentiation independent of mismatch repair protein status. Am J Surg Pathol 2020;44:991-1001. (PMID 32205483).
  36. Chicago Consensus Working Group (Pai RK, member). The Chicago consensus on peritoneal surface malignancies: management of appendiceal neoplasms. Cancer 2020;126:2525-2533 and Ann Surg Oncol 2020;27:1753-60. (PMID 32282073 and PMID 32285275).
  37. Tokuyama M, Geisler D, Deitrick C, Fasanella K, Chennat JS, McGrath KM, Pai RK, Davison JM. Use of p53 immunohistochemistry in conjunction with routine histology improves risk stratification of patients with Barrett’s esophagus during routine clinical care. Histopathology 2020;77:481-491. (PMID 32431062).
  38. Shyu S, Choudry H, Hall L, Pingpank J, Holtzman M, Bartlett D, Pai RK. Clinicopathologic analysis of appendiceal goblet cell adenocarcinoma with peritoneal metastasis: World Health Organization grade predicts survival following cytoreductive surgery with intraperitoneal chemotherapy. Histopathology 2020;77:798-809. (PMID 32557796)
  39. Farchoukh L, Hartman DJ, Ma C, Celebrezze J, Medich D, Bahary N, Frank M, Pantanowitz L, Pai RK. Intratumoral budding and automated CD8-positive T-cell density in pretreatment biopsies can predict response to neoadjuvant therapy in rectal adenocarcinoma. Mod Pathol 2021;34:171-183. (PMID 32661298)
  40. Pai RK*, Pai RK*, Brown I, Choi W, Schaeffer D, Farnell D, Kumararasinghi MP, Gunawardena D, Kim B, Friedman M, Ghayouri M, Lauwers G. The significance of histologic activity measurements in immune checkpoint inhibitor colitis. Aliment Pharmacol Ther 2021;53:150-159.  (PMID 33146440) (*Authors contributed equally to manuscript)
  41. Almaradi A, Ma C, D’Haens GR, Sandborn WJ, Parker CE, Guizetti L, Borralho NP, De Hertogh G, Feakins RM, Khanna R, Lauwers GY, Mookhoek A, Pai RK, Peyrin-Biroulet L, Riddell R, Rosty C, Schaeffer DF, Valasek MA, Singh S, Crowley E, Feagan BG, Jairath V, Pai RK. An expert consensus to standardize the assessment of histological disease activity in Crohn’s disease clinical trials. Aliment Pharmacol Ther 2021;53:784-793. (PMID 33410551)
  42. Pai RK, Pai RK, Schaeffer DF, Choi WT, Kumarasinghe P, Brown I, Lauwers GY. Editorial: The microscope holds the key to predict need for biologic therapy in immunotherapy-checkpoint inhibitory colitis. Aliment Pharmacol Ther 2021;53:638-39. (PMID 33566423)
  43. Pai RK, Hartman D, Schaeffer DF, Rosty C, Shivji S, Kirsch R, Pai RK. Development and initial validation of a deep learning algorithm to quantify histologic features in colorectal carcinoma including tumour budding/poorly differentiated clusters. Histopathology 2021;79:391-405. (PMID 33590485).
  44. Almardi A, Ma C, D’Haens GR, Sandborn WJ, Parker CE, Guizzetti L, Borralho Nunes P, De Hertogh G, Feakins RM, Khanna R, Lauwers GY, Mookhoek A, Pai RK, Peyrin-Biroulet L, Riddell R, Rosty C, Schaeffer DF, Valasek MA, Singh S, Crowley E, Feagan BG, Jairath V, Pai RK. An expert consensus to standardize the assessment of histologic disease activity in Crohn’s disease clinical trials. Aliment Pharmacol Ther 2021;53:784-793 (PMID 33410551).
  45. Ma C, Sedano R, Almradi A, Casteele NV, Parker CE, Guizzetti L, Schaeffer DF, Riddell RH, Pai RK, Battat R, Sands BE, Rosty C, Dubinsky MC, Rieder F, Harpaz N, Abreu MT, Bryant RV, Lauwers GY, Kirsch R, Valasek MA, Crowley E, Sandborn WJ, Feagan BG, Pai RK, Jairath V. An international consensus to standardize integration of histopathology in ulcerative colitis clinical trials. Gastroenterology 2021;160:2291-2302. (PMID 33610533).
  46. Pai RK, Hartman DJ, Leighton JA, Pasha SF, Ramos Rivers C, Regueiro M, Binion DG, Pai RK. Validated indices for histopathologic activity predict development of colorectal neoplasia in ulcerative colitis. J Crohn’s Colitis 2021;15:1481-1490. (PMID 33687061)
  47. Hegazy S, Brand RE, Dudley B, Karloski E, Bhargava R, Elishaev E, Pai RK. DNA mismatch repair deficient non-neoplastic endometrial glands are common in Lynch syndrome patients and are present at a higher density compared to the colon. Histopathology 2021;79:573-583. (PMID 33847404)
  48. Van de Casteele N, Leighton JA, Pasha SF, Cusimano F, Mookhoek A, Hagen CE, Rosty C, Pai RK, Pai RK. Utilizing deep learning to analyze whole slide images of colonic biopsies for associations between eosinophil density and clinicopathologic features in active ulcerative colitis. Inflamm Bowel Dis 2021 (epub ahead of print) (PMID 34106260)
  49. Gordon IO, Bettenworth D, Bokemeyer A, Srivastava A, Rosty C, de Hertogh G, Robert ME, Valasek MA, Mao R, Li J, Harpaz N, Borralho P, Pai RK, Odze R, Feakins R, Parker CE, Guizzetti L, Nguyen T, Shackelton LM, Sandborn WJ, Jairath V, Baker M, Bruining D, Fletcher JG, Feagan BG, Pai RK, Rieder F (Stenosis Therapy and Anti-Fibrotic Research (STAR) Consortium). Gut 2021 (epub ahead of print). (PMID 33952604)
  50. Al Masri SS, Paniccia A, Hammad AY, Pai RK, Bahary N, Zureikat AH, Medich DS, Celebrezze JP, Choudry HA, Nassour I. The role of adjuvant chemotherapy following right hemicolectomy for non-metastatic mucinous and nonmucinous appendiceal adenocarcinoma. J Gastrointest Surg 2021 (epub ahead of print). (PMID 34291365)
  51. Chen W, Farchoukh L, Seigh L, Hartman DJ, Pai RK. Combined histopathologic risk score using TP53 protein expression, CD8+ T-cell density, and intratumoral budding is an independent predictor of neoadjuvant therapy response in rectal adenocarcinoma. Histopathology 2021;79:826-835. (PMID 34121230)
  52. Sehested A, Meade J, Scheie D, Ostrup O, Bertelsen B, Misiakou MA, Sarosiek T, Kessler E. Melchior LC, Munch-Petersen HF, Pai RK, Schmuth M, Gottschling H, Zschoke J, Gallon R, Wimmer K. Constitutional POLE variants causing a phenotype reminiscent of constitutional mismatch repair deficiency. Hum Mutat 2022;43:85-96. (PMID 34816535).
  53. Pai RK, Lauwers G, and Pai RK. Measuring histologic activity in inflammatory bowel disease: Why and how. Adv Anat Pathol 2022;29:37-47. (PMID 34879037)
  54. Kuang C, Park Y, Augustin RC, Lin Y, Hartman DJ, Seigh L, Pai RK, Sun W, Bahary N, Ohr J, Rhee JC, Marks SM, Beasley HS, Shuai Y, Herman JG, Zarour HM, Chu E, Lee JJ, Krishnamurthy A. Pembrolizumab plus azacitidine in patients with chemotherapy refractory metastatic colorectal cancer: a single-arm phase 2 trial and correlative biomarker analysis. Clin Epigenetics 2022;14:3 (PMID 34991708)
  55. Ma C, Pai RK, Schaeffer DF, Krell J, Guizzetti L, McFarlane SC, MacDonald JK, Choi WT, Feakins RM, Kirsch R, Lauwers GY, Pai RK, Rosty C, Srivastava A, Walsh JC, Feagan BG, Jairath V. Recommendations for standardizing biopsy acquisition and histological assessment of immune checkpoint inhibitor-associated colitis. J Immunother Cancer 2022;10:e004560 (PMID 35296560).
  56. Gonzalez RS, Carr NJ, Liao H, Pai RK, Aostinini-Vulaj D, Misdraji J. High-grade appendiceal mucinous neoplasm. Arch Pathol Lab Med 2022. (PMID 35472721)
  57. Bell PB and Pai RK. Goblet cell adenocarcinoma of the appendix: An update and practical approach to diagnosis and grading. Hum Pathol (epub).
  58. Bell PB and Pai RK. Immune response in colorectal carcinoma: A review of its significance as a predictive and prognostic biomarker. Histopathology (epub). 

Selected Book Chapters

  1. Misdraji J, Carr NJ, Pai RK. Appendix: Serrated polyps. In: WHO Classification of Tumours of the Digestive System, Fifth Edition, IARC Press 2019.
  2. Misdraji J, Carr NJ, Pai RK. Appendiceal mucinous neoplasm. In: WHO Classification of Tumours of the Digestive System, Fifth Edition IARC Press 2019.
  3. Misdraji J, Carr NJ, Pai RK. Appendix: Adenocarcinoma. In: WHO Classification of Tumours of the Digestive System, Fifth Edition, IARC Press 2019.
  4. Misdraji J, Carr NJ, Pai RK. Appendix: Goblet cell carcinoma. In: WHO Classification of Tumours of the Digestive System, Fifth Edition, IARC Press 2019.
  5. Misdraji J, Carr NJ, Vang R, Pai RK.  Peritoneal mucinous tumors. In: WHO Classification of Tumours of Female Genital Tract, Fifth Edition, IARC Press 2020.