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Year : 2017  |  Volume : 60  |  Issue : 1  |  Page : 125-127
Squash cytodiagnosis of synchronous papillary serous carcinoma of ovary and endometrium with demonstration of serous tubal intraepithelial carcinoma as a precursor lesion

1 Department of Pathology, S.C.B. Medical College, Cuttack, Odisha, India
2 Department of Obstetrics and Gynecology, VIMSAR, Burla, Odish, India
3 Department of Pathology, AHRCC, Cuttack, Odisha, India

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Date of Web Publication14-Feb-2017

How to cite this article:
Kar A, Kar T, Dha I, Panda S. Squash cytodiagnosis of synchronous papillary serous carcinoma of ovary and endometrium with demonstration of serous tubal intraepithelial carcinoma as a precursor lesion. Indian J Pathol Microbiol 2017;60:125-7

How to cite this URL:
Kar A, Kar T, Dha I, Panda S. Squash cytodiagnosis of synchronous papillary serous carcinoma of ovary and endometrium with demonstration of serous tubal intraepithelial carcinoma as a precursor lesion. Indian J Pathol Microbiol [serial online] 2017 [cited 2020 Jul 2];60:125-7. Available from: http://www.ijpmonline.org/text.asp?2017/60/1/125/200039

Intraoperative cytodiagnosis is a very useful, simple, rapid, and cheap adjunctive technique for the intraoperative consultation of ovarian lesions.[1] In patients with suspected ovarian malignancy, it frequently can assist in performing optimum surgical management. Simultaneously occurring primary cancers of the female genital tract is a rare phenomenon accounting for 1%–6% of genital neoplasms. But out of these, synchronous endometrial and ovarian malignancies are frequently seen.[2] The two tumors can have similar morphology or may be of different types. It is extremely difficult to decide which one is primary and/or metastatic even though there are hypotheses suggesting either. The recent concept of ovarian serous carcinogenesis has changed over the last few decades and had nullified the previous theory of surface epithelial inclusion cysts. The  Fallopian tube More Details has emerged as the culprit and more studies are being done to prove it without doubt. We describe here a case of synchronous ovarian and endometrial papillary serous carcinoma (high-grade) which was diagnosed intraoperatively by squash cytology. The case was followed up, and serous tubal intraepithelial carcinoma (STIC) was demonstrated in both the fallopian tubes by histomorphology and immnuohistochemistry which could be the precursor lesion of ovarian serous carcinoma.

A 55-year-old female presented with bleeding per vaginum and abdominal discomfort. Her cervical cytology examination revealed features suggestive of glandular epithelial abnormality, i.e. adenocarcinoma possibly of endometrial origin. Ultrasonography showed enlarged bilateral ovaries of 6 cm × 4 cm and 4.5 cm × 3.8 cm with heterogeneous mass lesion measuring 2.3 cm × 1.8 cm in endometrial cavity. She had ascites. Per abdominal examination showed swelling of lower abdomen. Her serum CA-125 level was increased (760 mg/dl). Lactic dehydrogenase and b-human chorionic gonadotropin were not raised. Routine investigations were within normal limits. Hysteroscopy revealed irregular endometrial cavity, normal fundus, and ostium with an irregular mass in the right lateral uterine wall. Mammography was done and did not reveal any mass in the breast.

Endometrial curettage and biopsy were done along with a punch biopsy from cervix. Hematoxylin and eosin stained section of endometrium showed papillary structures lined by stratified neoplastic endometrial cells with stromal invasion. The cells were pleomorphic and hyperchromatic with prominent nucleoli. Cervical sample showed features of chronic cervicitis without any evidence of dysplasia or malignancy. Examination of ascitic fluid did not reveal any malignant cells. The patient was planned for laparotomy and total hysterectomy with bilateral salpingo-oophorectomy was done. Intraoperative squash cytology of endometrial and both ovarian masses was done. Endometrial squash cytosmear showed high cellularity with tumor cells arranged in thin papillary pattern with cuboidal to polygonal pleomorphic cells having scanty to moderate amount of eosinophilic cytoplasm, high N:C ratio [Figure 1]a and [Figure 1]b. Clearing of cytoplasm and hobnailing were absent. Squash smears from both the ovarian lesions showed similar features [Figure 2]a.
Figure 1: (a) Squash cytology of papillary serous carcinoma of endometrium (H and E, ×100). (b) Clusters of pleomorphic cells (H and E, ×400). (c) Histomorphology of papillary serous carcinoma of endometrium (H and E, ×100). (d) Superficial myometrial invasion by neoplastic glands (H and E, ×400)

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Figure 2: (a) Cytomorphology of ovarian serous carcinoma (H and E, ×400). (b) Photomicrograph showing papillae lined by stratified neoplastic cells in ovarian serous carcinoma (H and E, ×400). (c) Tubal structure with intraepithelial carcinoma (H and E, ×400). (d) Strong positivity of epithelial cells in fallopian tube (IHCp53, ×400). (e) Ki-67 immunostain in fallopian tube (×400)

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Hence, a diagnosis of adenocarcinoma probably of papillary serous type was rendered. Moreover, the operation was extended to include omentectomy and pelvic lymphadenectomy. The formalin preserved gross specimen was cut opened uterus and cervix with bilateral appendages measuring 6 cm × 10 cm × 4 cm. Uterine cavity showed a diffuse friable mass of 3 cm × 2 cm × 2 cm [Figure 3]. Ovarian masses were enlarged of around 6 cm × 4 cm × 3 cm, unencapsulated, friable with areas of necrosis and smooth surface. Tubes were of normal length and thickness. Sections were taken from endometrial mass, myometrium (to look for myometrial invasion), cervix, ovaries, omentum, and lymph nodes. Section from endometrial growth showed features of papillary serous carcinoma [Figure 1]c. Superficial myometrial invasion was noted [Figure 1]d. Multiple sections taken from both ovarian masses showed complex branching papillae with nuclear stratification, high mitotic activity, and high-grade nuclear features [Figure 2]b.
Figure 3: Gross photograph of uterus and both ovaries with mass lesion

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Sections from omentum and lymph nodes did not show any evidence of metastasis. Both ovaries were small without multinodularity, endometrial mass was also not very big, there was superficial myometrial invasion. Hence, in the absence of definite features, no lesion could be decided as metastatic. Therefore, a diagnosis of synchronous primary papillary serous adenocarcinoma of endometrium and ovary was rendered. Then both fallopian tubes were sectioned according to sectioning and extensively examining the FIMbriated end protocol.[3],[4] The fimbrial segments were amputated, and sagittal sectioning was done and subjected for histopathological study. There were stratification, loss of polarity, high N:C ratio, nuclear pleomorphism, secretory cell outgrowth with loss of cilia in the tubal mucosa [Figure 2]c. Stromal invasion was absent. Immunohistochemistry with p53 was done, and it showed strong nuclear positivity of tubal epithelial cells [Figure 2]d. Ki-67 was also done, and positivity was seen indicating high (20% Ki-67 positive cells) proliferative activity [Figure 2]e. So, the presence of STIC was confirmed in both tubes.

Synchronous primary endometrial and ovarian cancers coexist in approximately 10% of all females with ovarian cancer and 5% of all females with endometrial cancer.[2] When both the tumors are of similar morphology, the possibilities can be – (i) Independent primary tumors in endometrium and ovary, (ii) Metastases from endometrial carcinoma into ovary, and (iii) Metastases from ovarian carcinoma to endometrium. It often is a great challenge for surgical pathologists to differentiate synchronous tumor from metastasis to one another. In these situations, clinical presentation, sonographic, gross, and microscopic findings can guide toward a correct diagnosis.

In the present case, small lesion in endometrial cavity without deep myometrial and vascular or lymphatic invasion, the absence of involvement of tubal lumen excluded the possibility of endometrial lesion as primary. Ovarian lesions were also small, without multinodular configuration. CA-125 was raised in the patient suggesting primary ovarian involvement. Hence, a diagnosis of synchronous primary papillary serous carcinoma of endometrium and ovaries was made. In the present case, diagnosis was done by intraoperative squash cytology in both endometrial and ovarian lesions. The presence of papillae with occasional clustering of pleomorphic cells having scanty cytoplasm and high-grade nuclear features suggested a probable diagnosis of adenocarcinoma of papillary type.

The previous theory of ovarian carcinogenesis has changed since late 1990s. There is now evidence that instead of ovarian surface epithelium, a putative precursor to pelvic serous carcinomas exists in the fimbria of fallopian tubes. This is the area where serous carcinomas arise.[5] The range of epithelial alterations in fallopian tube associated with strong p53 accumulation can be divided into three categories which are together known as SCAT (Serous carcinogenesis at tube). They can be p53 signature, STIC and intermediate p53 positive foci (serous tubal intraepithelial lesion).[5] STIC is characterized by the presence of malignant cells replacing the tubal epithelium with secretory cell outgrowth (decrease in ciliated cells), high N:C ratio, nuclear pleomorphism, high mitotic index, and loss of polarity. All the features were detected in both the tubes in the above case. According to Crum's study, strong positivity for p53 protein by immunohistochemistry is suggestive of early serous cancer (intraepithelial) in tube.[6] Histomorphology and p53 immunohistochemistry in the present case proved the presence of STIC in both the fallopian tubes. Summarizing, there were serous carcinomas in both the ovaries, endometrium along with STIC in the fallopian tubes. A study done by Tang et al. demonstrated that STIC is exclusively associated with 19% and 29% of ovarian and peritoneal serous carcinomas respectively, and 14% of endometrial serous carcinomas.[7] STIC was neither identified in any nonserous ovarian, endometrial, and cervical malignancies nor any other conditions. Hence, the authors raised the possibility that STIC may be the potential source endometrial serous carcinoma with ovaries in this patient. She received postoperative platinum-based adjuvant chemotherapy; her ascites has subsided, and she is doing well after 10 months of the operation.

The authors have tried to convey three messages through this case study:

  • There is a simultaneous occurrence of carcinoma of endometrium and both ovaries which are a challenging situation for surgical pathologists to decide which one is primary and/or metastatic or both are primaries
  • The diagnosis of both malignancies is made by squash cytology which though advantageous is not regularly practiced. Moreover, authors have advocated in favor of it as this is rapid, cheap, and with comparable accuracy like histopathology
  • The presence of simultaneous occurrence of carcinoma in endometrium and both ovaries have prompted the authors to look for a precursor lesion in tube as this is evolving as the recent concept of pathogenesis of ovarian malignancy and can be used as a screening procedure and is a torch bearer for reducing the incidence of pelvic high-grade serous carcinoma.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Shahid M, Zaheer S, Mubeen A, Rahman K, Sherwani RK. The role of intraoperative cytology in the diagnostic evaluation of ovarian neoplasms. Acta Cytol 2012;56:467-73.  Back to cited text no. 1
Zaino R, Whitney C, Brady MF, De Geest K, Burger RA, Buller RE. Simultaneously detected endometrial and ovarian carcinomas a prospective clinico-pathological study of 74 cases; a gynaecologic oncology group study. Gynecol Oncol 2001;83:355-62.  Back to cited text no. 2
Kindelberger DW, Lee Y, Miron A, Hirsch MS, Feltmate C, Medeiros F, et al. Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: Evidence for a causal relationship. Am J Surg Pathol 2007;31:161-9.  Back to cited text no. 3
Medeiros F, Muto MG, Lee Y, Elvin JA, Callahan MJ, Feltmate C, et al. The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome. Am J Surg Pathol 2006;30:230-6.  Back to cited text no. 4
Mehrad M, Ning G, Chen EY, Mehra KK, Crum CP. A pathologist's road map to benign, precancerous, and malignant intraepithelial proliferations in the fallopian tube. Adv Anat Pathol 2010;17:293-302.  Back to cited text no. 5
Crum CP, Drapkin R, Kindelberger D, Medeiros F, Miron A, Lee Y. Lessons from BRCA: The tubal fimbria emerges as an origin for pelvic serous cancer. Clin Med Res 2007;5:35-44.  Back to cited text no. 6
Tang S, Onuma K, Deb P, Wang E, Lytwyn A, Sur M, et al. Frequency of serous tubal intraepithelial carcinoma in various gynecological malignancies: A study of 300 consecutive cases. Int J Gynecol Pathol 2012;31:103-9.  Back to cited text no. 7

Correspondence Address:
Dr. Asaranti Kar
Qrs. No. JO/1, S.C.B. Medical College Campus, Cuttack - 753 007, Odisha
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.200039

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