Triple synchronous tumour of female genital tract: cervical squamous cell carcinoma, right ovarian dermoid cyst and left ovarian benign Brenner tumour

Abstract

Synchronous tumours of two different histological type are not uncommon in the female genital tract. But triple synchronous tumours of three or more different histological types is extremely rare. We describe a case of a 48-year-old female patient who presented with cervical growth and bilateral ovarian masses. Pathological evaluation of the surgical specimen revealed synchronous cervical squamous cell carcinoma, right ovarian dermoid cyst and left ovarian benign Brenner tumour. The patient was treated as per the carcinoma cervix protocol and is disease free at 1-year follow-up. To our knowledge this is the first report of such an occurrence. This occurrence cannot be related to any known hereditary syndromes, hence may be considered a chance association. Although rare, awareness of such an occurrence is important for the surgeon, radiologist and the surgical pathologist for proper diagnosis and management.

Background

Synchronous tumours of two different histological type account for 0.6%–5.4% malignancies of the female genital tract.¹ Most common synchronous malignancy is that of endometrial and ovarian carcinoma.² Synchronous existence of benign tumours such as teratoma of ovary and Brenner tumour of ovary with mucinous tumours occurring either in the same ovary or contralateral ovary are also well documented.^3–5 However the association of Squamous cell carcinoma of cervix with primary benign ovarian teratoma and Brenner tumours has not been reported. To our knowledge this is the first report of such an occurrence.

Case presentation

A 48-year-old woman presented with bleeding per vaginum and abdominal discomfort of 2 months duration. There were no feminising or virilising symptoms. There was no relevant medical history, family history or risk factors. Per speculum examination revealed an infiltrative firm to hard growth in the cervix. Routine investigations such as complete blood count, renal function tests and liver function tests were within normal limits. Ultrasonography of abdomen and pelvis showed bilateral adnexal masses. Serum tumour markers such as CA125, CA19.9, CEA, AFP, beta HCG were not elevated. Biopsy of the cervical growth revealed a squamous cell carcinoma. A clinical diagnosis of cervical carcinoma metastasising to both ovaries was made and the patient underwent hysterectomy with bilateral salpingo-ophorectomy and pelvic lymph node dissection.

Investigations

Gross evaluation of the specimen revealed enlarged uterus with an infiltrative growth in the cervix. The growth measured 1.9×1 cm. Cut surface of the growth was greyish white. The tumour was confined to the cervix without any extension into the uterine wall, vagina or parametria. There was no pelvic lymph node metastasis. The uterine cavity was dilated and filled with pus and necrotic material (figure 1). The right ovary was replaced by a uniloculated cystic mass filled with cheesy material and hair shaft. No solid areas were found (figure 2). The left ovary was also replaced by a mass of 6×4×3 cm. Cut surface of the mass was solid, homogenous, firm and greyish white (figure 3). Microscopic evaluation revealed an infiltrating squamous cells carcinoma of cervix (figure 4). The endometrium showed features of severe acute and chronic endometritis. It was not involved by tumour. The right ovarian mass showed features of a dermoid cyst (figure 5). The cyst showed squamous lining epithelium and lumen was filled with keratin. The cyst wall showed hair follicles and sebaceous glands. There was no evidence of any other germ cell components or malignancy. The left ovarian mass showed the characteristic features of a benign Brenner tumour. The tumour cells were arranged in nests within a fibrotic stroma. The cells showed round to oval nuclei with longitudinal nuclear grooves (figure 6).

Figure 1.

Gross photograph of uterus showing an infiltrative growth in the cervix with dilated uterine cavity and greyish white granular appearing endometrial surface.

Figure 2.

Right ovarian unicystic mass filled with cheesy material and hair,.

Figure 3.

Left ovarian mass showing a solid, homogeneous, firm greyish cut surface.

Figure 4.

Photomicrograph of cervical tumour showing features of a squamous cell carcinoma, H&E stain, ×400 original magnification.

Figure 5.

Section of right ovary showing a dermoid cyst lined by squamous epithelium with hair follicles and sebaceous glands, H&E stain, ×400 original magnification.

Figure 6.

Section of left ovarian mass showing features of a Benign Brenner tumour with islands of tumour cells within a fibrotic stroma. H&E stain, ×200 original magnification.

Differential diagnosis

The most important differential diagnosis in such cases is multiple metastasis from a single primary. The generally accepted criteria for diagnosis of multiple synchronous tumours is that the tumours must be diagnosed simultaneously, the tumours must be of different histological subtypes and metastasis from a single primary must be ruled out. In our case, the diagnosis of triple synchronous tumours was easy as all the three tumours were of different histological types.

Outcome and follow-up

The patient did not have any tumour recurrence or metastasis at the end of 1-year follow-up.

Discussion

Triple synchronous tumours of the female genital tract are rare. Rare occurrences of quadruple tumours are also reported.^6–19 Study of these reported cases suggest that most common combination of triple synchronous tumours are adenocarcinomas of endometrium, ovary and cervix (table 1). Synchronous existence of cervical invasive squamous cell carcinoma with endometrial and ovarian malignancy has been reported only once⁶ and there is only one reported case of synchronous cervical squamous cell carcinoma with bilateral ovarian benign tumours (Brenner tumour and granulosa cell tumour).¹³ However the coexistence of cervical squamous cell carcinoma with a benign Brenner tumour and benign mature cystic teratoma of ovary has never been documented.

Table 1.

List of triple synchronous tumours of female genital tract in literature

Author	Year of publication	Sites involved	Histological type of tumour
Abu-Zaid et al6	2017	Ovary Endometrium Cervix	Clear cell carcinoma Endometrioid carcinoma Squamous cell carcinoma
Kan et al18	2017	Salpinx Ovary Endometrium	Serous Cystadenocarcinoma in situ Mucinous Adenocarcinoma Adenocarcinoma
Chiofalo et al7	2016	Ovary Endometrium Endocervix	Mucinous carcinoma Endometrioid carcinoma Mucinous adenocarcinoma
Takatori et al8	2014	Ovary Endometrium Cervix	Serous carcinoma Endometrioid carcinoma Endometrioid carcinoma
Kambi et al19	2013	Salpinx Ovary Cervix	Papillary Cystadenocarcinoma Papillary Cystadenocarcinoma Adenosquamous carcinoma
Zhang and Lerwill9	2011	Ovary Endometrium Myometrium	Leydig cell tumour Mucinous adenocarcinoma Leiomyosarcoma
Hale et al10	2011	Ovary Endometrium Cervix	Mixed (Mucinous+clear cell+endometrioid) Endometrioid carcinoma Endometrioid carcinoma
Pekin et al13	2007	Right ovary Left ovary Cervix	Brenner tumour Granulosa tumour Squamous cell carcinoma
Işin Doğan Ekici et al15	2006	Ovary Endometrium Myometrium	Mucinous cystadenocarcinoma Endometrioid carcinoma Leiomyosarcoma
Jobo et al17	1997	Ovary Endometrium Cervix	Endometrioid adenocarcinoma Endometrioid adenocarcinoma Carcinoma in situ
Ayhan et al16	1992	Ovary Endometrium Cervix	Mucinous cystadenocarcinoma Endometrioid adenocarcinoma Carcinoma in situ
Present case		Right ovary Left ovary Cervix	Dermoid cyst Brenner tumour Squamous cell carcinoma

Synchronic neoplasms pose difficulty with regard to tumour staging and treatment and it is essential to distinguish them from multiple metastasis of a single primary. In the present case, extensive sampling of both ovarian masses was undertaken, and the possibility of any mixed components was ruled out. The possibility of cervical squamous cell carcinoma metastasising to both ovaries was also ruled out. In our case the tumours were at three different sites and showed three different histology, hence it was easy to label them as synchronous tumours.

The pathogenesis of synchronous tumours in the female genital tract is poorly understood. It is postulated that the cells of Mullerian tract having the same embryological origin, having the same genetic structure respond to environmental exposure in the same way to produce concurrent neoplasms.¹⁶ However this theory does not explain the concurrent occurrence of neoplasms of divergent cell lines such as epithelial and germ cell lines. Coexistence of mature cystic teratoma with benign Brenner tumour has been described in the literature.³Benign Brenner tumour may coexist with mature cystic teratoma or Struma ovary within the same mass supporting the theory of its germ cell origin. However, Brenner tumour associated with benign mucinous cystadenomas are also well documented in literature, supporting the alternate theory of its celomic epithelial origin.

The management of multiple synchronic neoplasm is not well defined. It depends upon several factors including the patients age, general status, histological type and local aggressiveness of the neoplasms, surgical respectability and distant spread. In our case, the treatment was directed towards the malignant tumour, that is, squamous cell carcinoma of cervix as detailed above. The ovarian tumours were benign and hence surgical excision was enough. The patient did not have any tumour recurrence or metastasis at 1-year follow-up. However, for multiple synchronous malignant tumours, the current literature suggests that each tumour be treated as primary tumour with local excision or chemo/radiotherapy wherever applicable. Moreover, in such patients the follow-up period must be prolonged.

In conclusion, we report the first case of triple synchronous neoplasm of female genital tract composing of invasive squamous cell carcinoma of the cervix, mature cystic teratoma of one ovary and benign Brenner tumour of another ovary. Awareness of such an occurrence is important for the surgeon, radiologist and the surgical pathologist for proper diagnosis and management.

Patient’s perspective.

I was having abdominal discomfort and bleeding from vagina. When I went to see my doctor, he said that I had a growth in the cervix which looked like a cancer. I was shocked at the news. Then a lot of other tests and investigations were performed, and it was found that I had enlarged ovaries on both sides. The surgeon believed that the ovarian enlargement was due to spread of tumour from cervix. However, the radiologists had a doubt that the ovarian enlargement could be due to some other cause. They decided to operate on me and removed my uterus with both side ovaries. The biopsy of my specimen showed that the ovarian masses were two different benign tumours without any relation to the main tumour of the cervix. The tumour of the cervix was found to be a malignant tumour. I thank god that the ovarian tumour was not metastatic deposit. There was significant dilemma among the doctors as to how to treat me. I was told that I had a very rare condition of triple synchronous tumour of my genital tract, and the treatment of such cases are not well described in medical literature.

Learning points.

• Triple synchronous malignant tumours of female genital tract are not uncommon. However, the occurrence of synchronous bilateral benign tumours of ovaries of different histological types and a malignant tumour of cervix is extremely rare.

• Benign tumours of bilateral ovary may coexist with malignant tumour of cervix and must not be confused as metastatic deposits.

• Treatment of such cases should be directed to the malignant tumour.