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15 February 2017 - Case of the Week #417

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Thanks to Dr. Sandhya Sundaram, Professor & Senior Consultant, Sri Ramachandra Medical College & Research Institute, Chennai (India) for contributing this case and Dr. Belinda Lategan, St. Boniface Hospital (Canada) for writing the discussion. This case was reviewed in May 2020 by Dr. Jennifer Bennett, University of Chicago and Dr. Carlos Parra-Herran, University of Toronto. To contribute a Case of the Week, follow the guidelines on our main Case of the Week page.




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Case of the Week #417

Clinical history:
A 60 year old woman presented with rectal bleeding. Examination revealed a rectal mass. CT scan showed a soft tissue mass in the left hypochondrium which encircled the rectum. Multiple omental deposits were also seen. The ovaries and fallopian tubes were normal on imaging.

The rectal mass and an omental nodule were biopsied.


Radiology images:

CT Soft tissue mass in the left hypochondrium

Lesion seen encircling colon and rectum



Micro images:

Rectal tissue and a separate tumor fragment with papillary pattern x100

Papillary arrangement of tumor x200

Lining cells are pleomorphic and hyperchromatic x400


































Diagnosis:
High grade serous carcinoma (likely primary peritoneal)


Special Stains:

CK7 - strongly positive in tumor, negative in rectal mucosa

WTI - nuclear positivity in tumor and negative in rectal mucosa

CK20 - positivity in normal rectal mucosa, negative in tumor cells

CDX2 - nuclear positivity in normal rectal mucosa, negative in tumor cells



Test question (answer at the end):
Immunohistochemistry can reliably distinguish between serous carcinomas of ovarian, fallopian tube and peritoneal origin.

A. True
B. False

Discussion:

Histopathology from the rectal mass and omental nodule showed a malignant neoplasm arranged in a papillary pattern, lined by pleomorphic hyperchromatic cells with visible nucleoli. Mitotic figures are easily found. These features are typical of high grade serous carcinoma.

In terms of origin, high grade serous carcinoma of the upper genital tract is now divided as ovarian, tubal and primary peritoneal. It is known that most high grade serous carcinomas originate from a precursor in the tubal epithelium (namely serous tubal intraepithelial carcinoma - STIC). For this reason, for site of origin assignment, any STIC or tubal involvement by carcinoma suffices to classify the case as tubal. In the absence of tubal involvement, if the tumor involves one or both ovaries it is regarded as ovarian. The now rare primary peritoneal carcinoma is considered only if both tubes and ovaries are free of malignancy (Mod Pathol 2015;28:1101). The fallopian tubes can only be excluded as a site of origin after careful examination using the SEE-Fim-protocol (Mod Pathol 2014;27:1002) This distinction, while important for physio-pathologic and potentially epidemiologic purposes, is not clinically important as behavior and management are determined by grade and clinical stage, regardless of the site of origin (Mod Pathol 2015;28:1101)

Differential diagnosis and ancillary studies:
The differential diagnosis includes ovarian or fallopian tube serous tumors, mesothelial proliferations or peritoneal involvement by non-serous / non-Müllerian malignancy. Careful review of the clinical history, imaging, operative findings and ancillary studies is necessary to confirm the diagnosis.

Immunohistochemistry is not helpful in distinguishing the anatomic origin of high grade serous carcinoma, as the profiles are near identical. Malignant mesothelioma can be excluded by utilizing a panel of immunohistochemical studies. Both entities will usually express WT1, and the addition of Calretinin, PAX8, CK5/6 and ER may be helpful in the differentiation.

WT1PAX8CalretininCK5/6ER
Mesothelial proliferations+-/focal +++++++-
High grade serous carcinoma++++--/focal ++++


Other IHC markers can be included in the panel if non-Müllerian malignancies are also being considered. In this case, the differential diagnosis also included colon carcinoma. Immunohistochemistry was performed for CK7, CK20, WT1 and CDX2. CK7 and WT1 were strongly positive and CK20 and CDX2 were negative in the omental nodule and rectal mass, which ruled out a primary colorectal tumor. Imaging studies were reassessed for evidence of an ovarian origin; both ovaries were normal. A diagnosis of primary peritoneal serous carcinoma was rendered.

Primary peritoneal serous carcinoma presenting as a dominant rectal mass with clinical symptoms mimicking a primary rectal carcinoma is exceedingly rare. IHC proved useful for this diagnosis.

Test Question Answer:
B. False

Immunohistochemistry is not helpful in distinguishing PPSC from serous carcinoma arising in the ovary and fallopian tube, as the profiles are near identical. Careful review of the clinical history, imaging and operative findings is necessary to confirm the diagnosis. However, the distinction may not be critical as behavior and management is determined by grade and clinical stage, regardless of the site of origin.

Additional references:

J Clin Oncol 2015;33:2675, WHO classification of Tumours of the Female Reproductive Organs (4th ed. 2014), Gynecol Oncol Res Pract 2015;2:1

Image 01 Image 02