Mini case report: early serous carcinoma in fallopian tube in BRCA2 carrier
Posted Jan 04 2010 2:30pm
The patient is a 63 year-old woman with a family history of ovarian cancer in her mother and breast cancer in a sister. She has no personal history of cancer but is a BRCA2 mutation carrier . She is otherwise asymptomatic and presented for risk-reducing total hysterectomy with bilateral salpingo-oophrectomy.
The gross examination of the uterus was normal. Both fallopian tubes were also normal and both ovaries appeared atrophic with few simple cysts. The ovaries and fallopian tubes were examined and submitted for histology according to the SEE-FIM protocol where the ovaries and fallopian tubes are submitted in their entirety for histological examination. The H&E images below were found in one fibria from the distal end of one fallopian tube. (You can click on any of the images to open and enlarge them in a new window.)
The epithelial lining above is clearly abnormal compared to the normal single-layer ciliated epithelium below. There is nuclear stratification, nuclear enlargement, hyperchromasia, pleomorphism, and mitoses. The photomicrograph above shows pseudoinvasion but the same architectural and cytological features. Deeper levels from the block from which the above photomicrograph was taken shows continuity with the surface epithelium. Immunohistochemical stains for p53 and MIB-1 were performed to demonstrate the p53 signature of serous carcinogenesis and proliferation activity in serous carcinoma:
Compare the negative staining in the normal epithelium.
Based on these findings, my diagnosis is: occult serous tubal intraepithelial carcinoma associated with BRCA2 mutation.
An interesting but incidental histological finding in this case is a focus of transitional cell metaplasia in the contralateral fallopian tube which is notable for the comparison with the focus of carcinoma above.
This is the third specimen like this for risk-reducing surgery that I have examined within the last 6 weeks or so. I expect that these types of specimens will increase in frequency, especially in community hospital practice settings, so an awareness of handling these specimens is essential for appropriate patient care. Several recent papers concerning this subject have been published within the last 6 months, cited below, that are helpful but here is my summary of the major points based on recent literature and my own experience:
Occult carcinoma has been reported to be present in 2% to 17% of risk-reducing salpingo-oophectomy (RRSO) specimens--so a high index of suspicion for the presence of occult malignancy must be maintained.
These specimens must be processed according to a protocol. The most frequently cited one is the SEE-FIM ("seeing and extensively examining the fimbriated end") protocol published by Medeiros et al. in 2006. Particular attention must be paid to the distal end of the tube. In a study by Callahan et al., all 7 reported cases originated in the distal or fimbriated end of the tube, all were less than 1 cm, and 5 of 7 were not apparent on gross exam; one case involved only a single tubal plica.
Both p53 and Ki-67/MIB-1 must be used to evaluate histologically suspicious foci. A p53 signature without increased mitotic activity can be found in otherwise histologically benign foci, so it is essential to obtain both stains.
I have not seen any advocating doing these stains routinely on all specimens and would not recommend this myself; patient and critical examination of the routine H&E stained slides should guide the further evaluation of any suspicious foci with IHC stains and deeper levels.
Some of these tiny foci can be associated with (micro)invasion.
A variety of benign lesions (like transitional cell metaplasia) may mimic occult early serous carcinoma in the ovary in RRSO specimens and, since these patients may have had breast carcinoma or are so at risk, metastatic breast carcinoma to the ovaries must also be considered. The paper by Rabban et al. has an excellent discussion of this.
Use standardized terminology in reporting these cases.
Since there have been published cases of occult tubal intraepithelial carcinoma reported with positive peritoneal cytology--despite negative preoperative exams and the lack of an invasive component, we should discuss with our OB-GYN colleagues and departments about routinely including peritoneal washings as part of RRSO surgery.
Medeiros F, Muto MG, Lee Y, et al. The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome. Am J Surg Pathol 2006;30:230-236.
Kindelberger DW, Lee Y, Miron A, et al. Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship. Am J Surg Pathol 2007;31:161-169.
both of these papers are essential to begin with and have initiated the concept (still a bit controversial) of serous carcinogenesis beginning in the distal/fimbriated end of the fallopian tube
Callahan MJ, Crum CP, Medeiros F, et al. Primary fallopian tube malignancy in BRCA-positive women undergoing surgery for ovarian cancer risk reduction. J Clin Oncol 2007;25:3985-3990.
excellent survey of a series of BRCA mutation-positive patients
Gwin K, Wilcox R, Montag A. Insights into selected genetic diseases affecting the female reproductive tract and their implication for pathologic evaluation of gynecologic specimens. Arch Pathol Lab Med 2009;133:1041-1052.
a must read, excellent brief summary, also covers HNPCC-endometrial carcinoma and gonadal dysgenesis
Rabban JT, Barnes M, Chen L-M, et al. Ovarian pathology in risk-reducing salpigo-oophrectomies from women with BRCA mutations, emphasizing the differential diagnosis of occult primary and metastatic carcinoma. Am J Surg Pathol 2009;33:1125-1136.
as cited above--excellent presentation of various lesions that one might encounter in the ovary in generating a differential diagnosis and formulating a work-up
Semmel DR, Folkins AK, Hirsch MS, et al. Intercepting early pelvic serous carcinoma by routine pathological examination of the fimbria. Mod Pathol 2009;22:985-988.
a similar case report to my case, pictures illustrate nicely focal invasion; I also like the pro vs con arguments presented regarding submission of the entire fallopian tubes for histological examination