As we move further into 2020, we want to highlight areas of interest and trends that are affecting pathologists or will soon become a larger part of their professional scope. We sat down with an expert for their take on these topics. 

Elizabeth Anne Montgomery, MD, is a professor of pathology, oncology and orthopedic surgery at the Johns Hopkins School of Medicine in Baltimore.  She specializes in gastrointestinal pathology and soft tissue pathology. She reviews biopsy specimens from patients at Johns Hopkins and from around the world.

Q. What are the most important clinical trends pathologists need to be aware of for 2020, and how would you advise pathologists to respond to them? 

A.  Look for efforts to detect “targetable” fusions in unexpected tumors. For example, NTRK fusions are targetable and are not limited to sarcomas¹. Also look for refinements in staging with accumulated data ². Assessment of tumor infiltrating lymphocytes and “immunoscoring” of tumors will escalate in importance. Some commercial enterprises are attempting to convince us that a complicated system is needed for this, but probably using CD3 and CD8 alone will be sufficient ³. This may be the sort of assessment that is perfect for AI20 since tedious counting, which bores a human, is perfect for a computer! For the moment, we should be assessing “targets” in neoplasms as needed and thinking about how we might be assessing immune cells in neoplasms.

Q. What are you seeing in the area of precision medicine and the microbiome? 

A. Each week brings us new “targetable” molecules in cancer treatment using next generation sequencing and methods that detect characteristic gene fusions in tumors. Drug discovery is also progressing at a rapid pace. For example, recently an inhibitor was found that is active against the DNAJB1-PRKACA fusions detected in fibrolamellar hepatocellular carcinoma and a subset of pancreatic lesions ^{4 5 6}. Similarly, our understanding of the role of the microbiome, even the biome of fungal organisms, is progressing at a rapid pace and informs obesity treatment, treatment of inflammatory bowel disease, and even possibly treatment of some neoplasms ⁷. These rapidly exploding areas of investigation will increase in importance to daily practice. 

^[1] Chou A, Fraser T, Ahadi M, Fuchs T, Sioson L, Clarkson A, Sheen A, Singh N, Corless CL, Gill AJ. NTRK gene rearrangements are highly enriched in MLH1/PMS2 deficient, BRAF wild-type colorectal carcinomas-a study of 4569 cases. Mod Pathol. 2019 Dec 2. doi: 10.1038/s41379-019-0417-3. [Epub ahead of print] PubMed PMID: 31792356

^[2] Scolyer RA, Rawson RV, Gershenwald JE, Ferguson PM, Prieto VG. Melanoma pathology reporting and staging. Mod Pathol. 2019 Nov 22. doi: 10.1038/s41379-019-0402-x. [Epub ahead of print] Review. PubMed PMID: 31758078

^[3] Trabelsi M, Farah F, Zouari B, Jaafoura MH, Kharrat M. An Immunoscore System Based On CD3(+) And CD8(+) Infiltrating Lymphocytes Densities To Predict The Outcome Of Patients With Colorectal Adenocarcinoma. Onco Targets Ther. 2019 Oct 21;12:8663-8673. doi: 10.2147/OTT.S211048. eCollection 2019. PubMed PMID:31695425

^[4] Singhi AD, Wood LD, Parks E, Torbenson MS, Felsenstein M, Hruban RH, Nikiforova MN, Wald AI, Kaya C, Nikiforov YE, Favazza L, He J, McGrath K, Fasanella KE, Brand RE, Lennon AM, Furlan A, Dasyam AK, Zureikat AH, Zeh HJ, Lee K, Bartlett DL, Slivka A. Recurrent Rearrangements in PRKACA and PRKACB in Intraductal Oncocytic Papillary Neoplasms of the Pancreas and Bile Duct.

Gastroenterology. 2019 Oct 30. pii: S0016-5085(19)41481-9.

PubMed PMID: 31678302.

^[5] Vyas M, Hechtman JF, Zhang Y, Benayed R, Yavas A, Askan G, Shia J, Klimstra DS, Basturk O. DNAJB1-PRKACA fusions occur in oncocytic pancreatic and biliary neoplasms and are not specific for fibrolamellar hepatocellular carcinoma. Mod Pathol. 2019 Nov 1. PubMed

PMID: 31676785

^[6] Graham RP, Yeh MM, Lam-Himlin D, Roberts LR, Terracciano L, Cruise MW, Greipp  PT, Zreik RT, Jain D, Zaid N, Salaria SN, Jin L, Wang X, Rustin JG, Kerr SE, Sukov WR, Solomon DA, Kakar S, Waterhouse E, Gill RM, Ferrell L, Alves VA, Nart D, Yilmaz F, Roessler S, Longerich T, Schirmacher P, Torbenson MS. Molecular testing for the clinical diagnosis of fibrolamellar carcinoma. Mod Pathol. 2018 Jan;31(1):141-149. doi: 10.1038/modpathol.2017.103. Epub 2017 Sep 1. PubMed PMID: 28862261; PubMed Central PMCID: PMC5758901

^[7] Aykut B, Pushalkar S, Chen R, Li Q, Abengozar R, Kim JI, Shadaloey SA, Wu D, Preiss P, Verma N, Guo Y, Saxena A, Vardhan M, Diskin B, Wang W, Leinwand J, Kurz E, Kochen Rossi JA, Hundeyin M, Zambrinis C, Li X, Saxena D, Miller G. The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL. Nature. 2019 Oct;574(7777):264-267. PubMed PMID: 31578522; PubMed Central PMCID: PMC6858566.