医网情深：第一次带教的美国医学毕业生的病理实习作业——在美国行医之路系列 （刀评：美国医学院毕业生Erina同学终于完成了4周的病理实习，即将奔赴亚特兰大另一个见习单位。周五晚上，在手把手教学第二次实践操作中学会了冰冻切片，做的还不错了。周六结业的最后一天，在办公室让她先自己阅读片子给出初步诊断，然后给她评点指出对错和精确的诊断术语和语句。大部分都准确诊断。这是我带的第一个AMG实习医生，也可能是最后一个。很高兴经过实习，她初步了解了外科病理而且坚定了转向申请病理住院医生。这对于她和我，都是一种全新的体验……） My pathology externship experience at NY EM, MD Throughout my post-graduate externship rotation, I gained valuable experience in preparation for my future role as a pathologist-in-training. I learned to quickly identify gastrointestinal diagnoses including tubular adenoma, hyperplastic polyp, sessile serrated adenoma, reactive gastropathy, reflux esophagitis and Barrett’s esophagitis via microscopic findings. Diverse specimens from specialty areas such as gastrointestinal, skin, prostate, and gynecology were grossed by my own hands. Frozen sectioning techniques were practiced to obtain a head-start for surgical pathology rotations. Reverse transcriptase polymerase chain reaction testing for severe acute respiratory syndrome coronavirus 2 was observed to gain knowledge regarding clinical pathology practice. Priceless advice regarding the interview process was also provided. When the question “Why do you want to be a pathologist?” is asked, the response “I love the diagnostic process” is a very weak answer. A strong response requires both a unique and genuine answer which is validated by experiences the applicant can share with the interviewer. During this externship experience, I learned that pathology is the right career choice for me because I enjoy determining the cause of a patient’s illness rather than blindly reading a report or following “evidence-based” screening guidelines which have been generated by someone else. As a physician, I hold the responsibility to determine the optimal treatment course to determine the fate of patients. Therefore, I know that comprehensive training incorporating not only treatment guidelines but also disease pathogenesis and the materials and methods utilized to generate them is necessary for me to become the best physician possible. I initially became interested in pathology because I love gross specimen dissection, autopsies, zebra cases and the sensation of looking at something from “outer space” when initially examining a microscopic slide for diagnostic findings. However, understanding pathology’s past contributions and present potential to impact the future of medicine overall has cemented my passion for the field. Through my discussions with Dr. He, I learned how the knowledge and work of pathologists has been essential to developing vaccines, medications, and diagnostic markers to beneficially impact the prognosis of patients everywhere. A recent event includes the discovery of programmed death molecule-1 on T cells and the translational development of antibody therapies for treatment of cancer. Other breakthroughs include the identification of erb-b2 receptor kinase 2 gene amplification in malignancies outside of the breast and the potential for treatment with trastuzumab for bladder, gastric, and gastroesophageal cancers. In medical school I learned that the pathologist is the “doctor’s doctor” who guides the surgeon’s hand to ensure that margins are clear and clarifies diagnostic findings to clinicians to verify that appropriate treatment is administered. This externship directly enhanced my understanding of pathology by directly allowing me to participate in microscopic identification, diagnostic report documentation, differential diagnosis generation, and discussions regarding prognosis/treatment implications. It also provided multiple opportunities to collaborate not only with the pathologist but also with other students and laboratory employees. I am very grateful to have found this opportunity to demonstrate my interest in pathology and cultivate my knowledge for a very unique field which requires physicians to serve the role of not only clinician but also teacher and researcher as well. The following Q&A involves a case of great educational value which was discussed during my last day of the externship. I have discovered that incorporating the diagnostic findings in images encountered with an educational objective presented in the format of a question is a very effective learning method for me. Question: The following biopsy specimens (A, B) were obtained from a 52-year-old male with an ascending colon mass. Immunohistochemistry was positive for MSH2 (C) and MSH6 (D) but negative for MLH1 (E) and PMS2 (F). Is further testing indicated?

Answer: Tubulovillous adenoma with high grade dysplasia and intramucosal glandular invasion (formerly carcinoma-in-situ) This adenoma contains both tubular (straight or branched crypts) and villous (finger-like projections of lamina propria lined by neoplastic epithelium) components. High-grade dysplasia is present and characterized by irregular, elongated, hyperchromatic nuclei, atypical mitotic figures, and complete loss of surface columnar maturation. An area of intramucosal glandular invasion of the stroma is noted. Ancillary testing with immunohistochemistry was performed to evaluate for mismatch repair (MMR) protein expression. When MMR proteins are functioning, nuclear expression of MLH1, PMS2, MSH2, and MSH6 is intact. Negative staining with a positive internal control for mononuclear cells and stroma indicates an MMR pathway deficiency. Loss of MLH1 and PMS2 nuclear expression, as in this patient, suggests an increased risk for progression to colorectal carcinoma secondary to sporadic or Lynch-associated mutations. In sporadic cases, there is both BRAF mutation and MLH1 promoter hypermethylation. In Lynch syndrome, germline MMR genes are mutated but the MLH1 promoter is nonmethylated and BRAF is wild-type. Therefore, BRAF mutation analysis and/or hypermethylation testing is necessary. It is noteworthy to add that lack of MSH2 with loss of MSH6 nuclear expression or isolated absence of PMS2 expression can also be associated with Lynch syndrome-associated colorectal cancer. Germline mutation testing is indicated for these patients as well. 6/6/2021 Sources: Conventional (Tubular, Villous, Tubulovillous) Adenoma. Yantiss, R.K. Accessed via ExpertPath by Elselvier on June 6th, 2021. Colorectal Adenocarcinoma and Precancerous Lesions. Hanson, J.A. Accessed via ExpertPath by Elselvier on June 6th, 2021. Lynch Syndrome. Yantiss, R.K. Accessed via ExpertPath by Elselvier on June 6th, 2021.