An unusual mechanism of metastasis in serous carcinoma of the endometrium associated with BRCA1 mutation gene: A case report with clinical and immunohistochemical features

The current case report documented a uterine high-grade serous carcinoma in a 48-year-old woman with previous clinical history of breast cancer, BRCA1 gene mutation, and melanoma of the back. Uterine Serous Carcinoma (USC) was minimally invasive with fallopian tubes, ovaries, omentum, peritoneal surface and lymph node biopsy demonstrating no evidence of neoplasm at the time of total abdominal hysterectomy with bilateral salpingo-oophorectomy. In the peritoneal washing cytology and in the lumen of both fallopian tubes there were neoplastic cells which, on immunohistochemical analysis, showed immunoreactivity for p53 and p16 and negativity for WT1, supporting the endometrial origin of these malignant serous neoplastic cells. One year after surgery, the patient presented with recurrent peritoneal neoplastic nodules and metastases into intestinal lymphnodes. To detect neoplastic USC cells in the fallopian tube lumen and to prove a retrograde transtubal spread into the peritoneal cavity, it is mandatory to examine the fallopian tubes in their entirety according to the SEE-FIM (Sectioning and Extensively Examining the Fimbria) protocol. In addition, this case report highlights the importance of the peritoneal cytology and omentectomy during a total abdominal hysterectomy with bilateral salpingo-oophorectomy to establish adequate staging and future patient management, even in cases of minimally invasive serous endometrial carcinoma.

Uterine serous carcinoma; Peritoneal washing cytology; Sectioning and extensively examining the fallopian tube protocol; Retrograde trans-tubal spread.

[1] Hendrickson M., Ross J., Eifel P., Martinez A., Kempson R.: “Uterine papillary serous carcinoma: a highly malignant form of endometrial adenocarcinoma”. Am. J. Surg. Pathol. 1982, 6, 93-108.

[2] Benito V., Lubrano A., Arencibia O., Alvarez E.E., León L., Medina N., et al.: “Pure papillary serous tumors of the endometrium: a clinicopathological analysis of 61 cases from a single institution”. Int. J. Gynecol. Cancer, 2010, 19, 1364-1369.

[3] Hamilton C.A., Cheung M.K., Osann K., Chen L., Teng N.N., Longacre T.A., et al.: “Uterine papillary serous and clear cell carcinomas predict for poorer survival compared to grade 3 endometrioid corpus cancers”. Br. J. Cancer, 2006, 94, 642-646.

[4] Goff B.A., Kato D., Schmidt R.A., Ek M., Ferry J.A., Muntz H.G., et al.: “Uterine papillary serous carcinoma: patterns of metastatic spread”. Gynecol. Oncol., 1994, 54, 264-268.

[5] Carcangiu M.L., Chambers J.T.: “Uterine papillary serous carcinoma: a study on 108 cases with emphasis on the prognostic significance of associated endometrioid carcinoma, absence of invasion, and concomitant ovarian carcinoma”. Gynecol. Oncol., 1992, 47, 298-305.

[6] Chan J.K., Loizzi V., Youssef M., Osann K., Rutgers J., Vasilev S. A., et al.: “Significance of comprehensive surgical staging in non-invasive papillary serous carcinoma of the endometrium”. Gynecol. Oncol., 2003, 90, 181-185.

[7] de Jonge M.M., Mooyaart A.L., Vreeswijk M.P.G., de Kroon C.D., van Wezel T., van Asperen C.J., et al.: “Linking uterine serous carcinoma to BRCA1/2-associated cancer syndrome: A meta-analysis and case report”. Eur. J. Cancer, 2017, 72, 215-225.

[8] Colombo N., Creutzberg C., Amant F., Bosse T., González-Martín A., Ledermann J., et al.: “ESMO-ESGO-ESTRO consensus conference on endometrial cancer: Diagnosis, treatment and follow-up”. Ann. Oncol., 2016, 27, 16-41.

[9] Ballester M., Naoura I., Chéreau E., Seror J., Bats A., Bricou A., et al.: “Sentinel node biopsy upstages patients with presumed low-and intermediate-risk endometrial cancer: results of a multicenter study”. Ann. Surg. Oncol., 2013, 20, 407-412.

[10] Touhami O., Grégoire J., Renaud M., Sebastianelli A., Plante M.: “Performance of sentinel lymph node (SLN) mapping in high-risk endometrial cancer”. Gynecol. Oncol., 2017, 147, 549-553.

[11] Medeiros F., Muto M.G., Lee Y., Elvin J.A., Callahan M.J., Feltmate C., et al.: “The tubal fimbria is a preferred site for early adeno-carcinoma in women with familial ovarian cancer syndrome”. Am. J. Surg. Pathol., 2006, 30, 230-236.

[12] Abu-Rustum N.R.: “Update on sentinel node mapping in uterine cancer: 10-year experience at memorial sloan-kettering cancer center”. J. Obstet. Gynaecol. Res., 2015, 40, 327-334.

[13] Soslow R.A., Pirog E., Isacson C.: “Endometrial intraepithelial carcinoma with associated peritoneal carcinomatosis”. Am. J. Surg. Pathol., 2000, 24, 726-732.

[14] Zheng W., Schwartz P.E.: “Serous EIC as an early form of uter-ine papillary serous carcinoma: recent progress in understanding its pathogenesis and current opinions regarding pathologic and clinical management”. Gynecol. Oncol., 2005, 96, 579-582.

[15] Muto M.G., Welch W.R., Mok S.C., Bandera C.A., Fishbaugh P.M., Tsao S.W., et al.: “Evidence for a multifocal origin of papillary serous carcinoma of the peritoneum”. Cancer Res., 1995, 55, 490-492.

[16] Kupryjanczyk J., Thor A.D., Beauchamp R., Poremba C., Scully R. E., Yandell D.W.: “Ovarian, peritoneal, and endometrial serous carcinoma: clonal origin of multifocal disease”. Mod Pathol., 1996, 9, 166-173.

[17] Schorge J.O., Muto M.G., Welch W.R., Bandera C.A., Rubin S. C., Bell D.A., et al.: “Molecular evidence for multifocal papillary serous carcinoma of the peritoneum in patients with germline BRCA1 mutations”. J. Natl. Cancer Inst., 1998, 90, 841-845.

[18] Jarboe E.A., Miron A., Carlson J.W., Hirsch M.S., Kindelberger D., Mutter G.L., et al.: “Coexisting intraepithelial serous carcinomas of the endometrium and fallopian tube: frequency and potential significance”. Int. J. Gynecol. Pathol., 2009, 28, 308-315.

[19] Nair N., Schwartz M., Guzzardi L., Durlester N., Pan S., Overbey J. et al.: “Hysterectomy at the time of risk-reducing surgery in BRCA carriers”. Gynecol. Oncol. Rep., 2019, 26, 71-74.

[20] Goldstein N.S., Uzieblo A.: “WT1 immunoreactivity in uterine papillary serous carcinomas is different from ovarian serous carcinomas”. Am. J. Clin. Pathol., 2002, 117, 541-545.

[21] Hashi A., Yuminamochi T., Murata S., Iwamoto H., Honda T., Hoshi K.: “Wilms tumor gene immunoreactivity in primary serous carcinomas of the fallopian tube, ovary, endometrium, and peritoneum”. Int. J. Gynecol. Pathol., 2004, 22, 374-377.

[22] Sherman M.E., Bitterman P., Rosenshein N.B., Delgado G., Kur-man R.J.: “Uterine serous carcinoma. A morphologically diverse neoplasm with unifying clinicopathologic features”. Am. J. Surg. Pathol., 1992, 16, 600-610.

[23] Snyder M.J., Bentley R., Robboy S.J.: “Transtubal spread of serous adenocarcinoma of the endometrium: An underrecognized mechanism of metastasis”. Int. J. Gynecol. Pathol., 2006, 25, 155-160.

[24] Stewart C.S., Doherty D.A., Havlat D.M., Koay M.H., Leung Y.C., Naran A., et al.: “Transtubal spread of endometrial carcinoma: correlation of intraluminal cell with grade, peritoneal fluid cytology and extra-uterine metastasis”. Pathology, 2013, 45, 382-387.

[25] Felix A.S., Sinnott J.A., Vetter M.H., Rhoades J., Cohn D.E., Backes F. J., et al.: “Detection of endometrial cancer cell in the fallopian tube lumen is associated with adverse prognostic factor and reduce survival”. Gynecol. Oncol., 2018, 150, 38-43.