Wendy L Frankel. Chair and Distinguished Professor

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1 1 Wendy L Frankel Chair and Distinguished Professor

2 Case 1 59 y/o woman Abdominal pain No personal or family history of cancer History of colon polyps Colonoscopy Polypoid rectosigmoid mass Biopsy

3 3

4 4 In-Situ Lesion

5 5 Rectal Resection for Colorectal Adenocarcinoma (CRC)

6 6

7 Diagnosis on Resection Transmural adenocarcinoma In-situ dysplasia 7/16 involved lymph nodes (LN) 3 tubular adenomas, 1 hyperplastic polyp Histology looks a little unusual Looks like endometrioid adenocarcinoma

8 Additional History TAH BSO 2005 No cancer Extensive endometriosis

9 Tumor Immunohistochemistry CDX2- PAX8+ 9

10 Tumor Immunohistochemistry ER+, Also CK20-, CK7+ 10

11 Diagnosis Müllerian cancer likely arising in endometriosis Unclear it if arose in peritoneum with secondary involvement of colorectum or within the colorectal wall 11

12 Differential Diagnosis: Primary CRC vs. Metastatic or Secondary Cancer Typical primary CRC Single polypoid mass In-situ lesion Mucosal involvement LN involvement in many Typical secondary tumor Serosal based if spread from serosal surface Regional LN involvement less likely Lymph vascular invasion if metastatic Multiple tumors 12

13 Secondary Tumors can Cause GI symptoms Single, polypoid GI mass Mucosal involvement Growth along basement membrane Mimic precursor Colonization can induce maturation LN involvement 13

14 Metastatic Tumors Involving GI Tract 100 GI resections with metastatic tumors compared to 29 primary small intestinal adenocarcinomas 42% metastases involved mucosal surface 26% resembled adenoma 62% regional LN involvement; 24% serosal based Metastasis from GI primaries colonized mucosal surfaces more often than those from other sites (60% vs. 20%) No significant differences in primary vs metastatic Growth along basement membrane, apparent precursor Lymph vascular invasion, LN involvement 14 Estrella, Am J Surg Pathol, 2011

15 Müllerian Adenocarcinoma Presenting in Colorectum 13 cases mimicked CRC Five misdiagnosed on biopsy Average age 64 No history gynecologic cancer Rectal bleeding, mass, pain, constipation Bulky mass colorectum, rectovaginal septum 9/13 endometriosis/endosalpingiosis in background Yang, Ann Diagn Pathol,

16 GI Endometriosis Associated Intestinal Tumors 2 reviews: 17 cases and 6 cases, age 30s to 50s Presentation- abdominal pain, melena, mass, obstructive symptoms Intestinal tumors Most endometrioid adenocarcinomas Some mixed müllerian tumors and stromal sarcomas Most rectosigmoid, followed by cecum and ileum History endometriosis and unopposed estrogen Malignant transformation rare Usually occurs in postmenopausal women 16 Yantiss, Am J Surg Pathol, 2000; Slavin, Hum Pathol, 2000

17 Immunohistochemistry Colon vs. Müllerian Colorectal typical CK7-, CK20+, CDX2+ CK7+, CK20-, CDX2- in some cases More often rectum Especially if MSI high Müllerian typical PAX8+, ER+, CK7+, CK20-, CDX2- Suggested panel CK7, CK20 (or CDX2), PAX8, ER 17

18 Tumors Arising in Endometriosis Endometriosis is risk factor for ovarian cancer (little evidence endometrial cancer) Unclear if causality or shared risk factors Most common types Endometrioid Clear cell More favorable behavior 18 Burghaus, BMC Cancer, 2015; Munksgaard, Gynecol Oncol, 2011; Van Gorp, Best Prac Res Clin Obstet Gynaecol, 2004

19 Lessons Learned Pitfalls Not considering the diagnosis Surface dysplasia does not rule out secondary tumor Clues Glands are not typical for CRC History of endometriosis Lesson Immunohistochemistry is helpful Sampling important for endometriosis 19

20 Other Challenges with Müllerian Lesions Endometriosis in a colorectal biopsy Endometriosis/endosalpingiosis with CRC and staging 20

21 35 y/o Woman with Abdominal Pain and Stricture Rectal biopsy

22 Diagnosis: Focal Acute Colitis Several colon biopsies normal Rectal biopsy Atypical gland Reactive change Focal acute inflammation 22

23 Colectomy for Stricture Continued symptoms Histology Endometrial glands Stroma Diagnosis- endometriosis 23

24 24 Review Biopsy PAX 8

25 Endometriosis Reproductive age women Pain, stricture, mass Pathology Endometrial glands Stroma Obvious Unapparent Decidualized Hemosiderin IHC +: PAX8, CD10, CK7, ER - : CDX2, CK20 25

26 26

27 CD10 CK7

28 28 Colorectal Resection after Neoadjuvant Chemoradiation Therapy for CRC

29 29 Deep Glands Beyond Muscularis Propria

30 Glands in Lymph Node

31 CRC Staging Challenge Malignant glands in submucosa Glands beyond muscularis propria with flattened epithelium-is it pt3? Glands in single lymph node- is it a metastasis, pn1a? IHC Rectal cancer in submucosa: CK20+, CDX2+, CK7-, PAX8-31

32 Malignant Glands in Submucosa 32 CDX2+

33 33 Deep Glands CK20, CDX2- ER+

34 Glands in Lymph Node CDX2, CK20- ER+

35 Summary- Take Home Message Secondary tumors can mimic primary CRC Red flags Funny histology History endometriosis Background endometriosis Histology can be deceiving Immunohistochemistry can be helpful Panel CK7, CK20 or CDX2 not enough Add PAX8, ER or PR Endometriosis can be challenging on GI biopsy Endometriosis can lead to upstaging CRC

36 Thanks for your Attention! Thanks to my GI team at OSU for cases 36

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