Joseph Misdraji, M.D. GI pathology Unit Massachusetts General Hospital
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1 Joseph Misdraji, M.D. GI pathology Unit Massachusetts General Hospital
2 Low-grade appendiceal mucinous neoplasm (LAMN) High-grade appendiceal mucinous neoplasm (HAMN) Adenocarcinoma
3 40 year old man. In 2013, undergoing work up for abdominal pain and constipation, and found to have pseudomyxoma on CT. Undergoes cytoreduction and HIPEC. Ultimately, he would develop recurrent disease and within 2 years was placed on comfort measures only.
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8 Low-grade mucinous epithelial proliferation that can be flat or villous. Characterized by pushing invasion: Destruction of muscularis mucosae and m. propria with fibrosis, or dissection of the wall by tumor as diverticula, herniations, and rupture. Despite the bland morphology, the tumor has the potential to disseminate to the peritoneal cavity as pseudomyxoma peritonei. Alternative terminologies are no longer recommended Mucinous cystadenoma Implies a benign tumor. Adenocarcinoma Requires infiltrative type invasion.
9 53 year old woman. In 1999, she complained of left lower quadrant abdominal pain. A CT showed a complex ovarian mass. At surgery she was found to have widespread pseudomyxoma, including a mass of tumor incorporating the right ovary and appendix together. The left ovary was spared. She had debulking and chemotherapy. Today, she is disease free.
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14 KRAS and GNAS mutations. Mutations typical of colorectal carcinoma (APC, p53, and SMAD4) are not common. Microsatellite instability, BRAF mutations, and loss of expression of DNA mismatch repair proteins are not features of LAMNs. Practically speaking, appendiceal tumors with pushing invasion and/or pseudomyxoma peritonei are LAMNs, not serrated tumors.
15 53 year old woman. In 2018 reported bloating, upset stomach, early satiety, and weight loss. CT showed large complex loculated fluid collection present in the pelvic region centered on the left ovary, measuring 14.9 x 18.3 x 12 cm. Diagnostic laparoscopy showed diffuse and extensive mucinous carcinomatosis and a large right ovarian mass. The appendix could not be visualized due to extensive disease. Received platinum based chemo, but had radiologic progression and increase in tumor markers. At definitive surgery, she had extensive carcinomatosis involving all peritoneal surfaces and multiple visceral organs, as well as a 23 cm right ovarian mass and 9 cm left ovarian mass. Complete cytoreduction could not be performed; only palliative debulking. Due to the lack of available treatments, HIPEC was performed.
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18 T stage Tis(LAMN) LAMN confined by the muscularis propria T3 LAMN that extends to subserosa. T4a - Tumor invades visceral peritoneum, including acellular or cellular mucin on the serosa of the appendix or mesoappendix. M stage M1a: Intraperitoneal acellular mucin M1b: Intraperitoneal mucinous deposits with tumor cells. M1c: Metastasis to sites other than peritoneum.
19 What is the best approach to stage this tumor? Tis(LAMN) M1b TX M1b
20 Extent of tumor spread in appendectomy TNM stages Prognosis Tumor is confined to the appendix: serosa intact, no mucin or tumor outside appendix Tumor perforates serosa with acellular mucin on the serosa or in the peritoneum Tumor perforates serosa with cellular mucin on the serosa LAMN Tis or T3 T4 T4 Almost certainly cured by appendectomy Low-risk of recurrence as pseudomyxoma High-risk of recurrence as pseudomyxoma Ultimately, it is critical to describe the extent of spread of tumor and mucin, emphasizing whether there is acellular or cell mucin on the appendix serosa
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22 72 year old woman with appendiceal mass.
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28 Pushing invasion, like LAMN, but unequivocal high-grade cytology. May have complex architecture (micropapillary or cribriform). Most tumors with high-grade cytology are invasive cancers; evaluate the entire tumor before concluding it is a HAMN. T stages the same as adenocarcinoma. Tis(LAMN) does not apply. Tumor pushing into muscle is T2. If the tumor is confined to the appendix and not ruptured, then the grade is probably not significant. Whether it is more likely than LAMN to disseminate once it ruptures is unclear.
29 45 year old woman. In 2012, presented with abdominal bloating. CT scan showed omental cake and bilateral adnexal masses. She underwent resection with HIPEC, followed by adjuvant chemotherapy. One year later, she had recurrent disease that was treated with systemic chemotherapy, with progression. 6 months later, repeat attempt at resection was aborted as it was found to be unresectable. Additional chemotherapy was implemented over the next 3 years, including atezolizumab. The patient ultimately died in 2018.
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35 62 year old man with appendix mass, sent in consultation to decide if this was an invasive tumor or HAMN. Patient had acellular mucin in the omentum.
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42 Characterized by infiltrative invasion Some areas may appear to be pushing invasion, especially in cystic cancers. Even focal unequivocal invasion warrants a diagnosis of adenocarcinoma. Subtypes Mucinous adenocarcinoma About 40% of appendix adenocarcinomas Adenocarcinoma, NOS Signet ring cell adenocarcinoma Precursor lesions include colonic type villous adenomas, serrated lesions, or LAMN-like lesions (hypermucinous proliferations). Right hemicolectomy for staging purposes. Frequent KRAS and GNAS mutations, and occasionally p53, SMAD4, and other mutations. Microsatellite instability is rare.
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Joseph Misdraji, M.D. GI pathology Unit Massachusetts General Hospital
Joseph Misdraji, M.D. GI pathology Unit Massachusetts General Hospital jmisdraji@partners.org Adenoma Low-grade appendiceal mucinous neoplasm High-grade appendiceal mucinous neoplasm Adenocarcinoma Serrated
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