Atypical Location of a Granulosa Tumeur: A Case Report and Review of the Literature

Z. Benaboud*¹, F. Ouakka¹, K. Saoud¹, N. Mamouni¹, S. Errarhay¹, C. Bouchikhi¹, A. Banani¹, M. El  Mekhtoum ²

1. Obstetrics Gynecology Service I of the CHU HASSAN II, Faculty? of Medicine, Pharmacy and Dentistry of the University? Sidi Mohamed ben Abdellah, Morocco

2. Radiology Service of the CHU HASSAN II, Faculty? of Medicine, Pharmacy and Dentistry of the University? Sidi Mohamed ben Abdellah, Morocco.

Corresponding Author: Benaboud Zainab MD, Department of Gynaecology and Obstetrics I, CHU HASSAN II Fez, Morocco.

Copy Right: © 2023 Benaboud Zainab MD, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received Date: April 18, 2023

Published Date: May 01, 2023

Abstract

Context: Granulosa tumours account for 5% of ovarian malignancies and are the most common of the sex cord and stromal tumours . The adult form is the most common (95%). Adult granulosa tumours have few specific features apart from signs of hyperoestrogenism, increased inhibin B/AMH and Foxl2 mutation. These tumours have a good prognosis and require optimal surgery. However, the sometimes late relapses require close monitoring.

Observation: This is a 60 year old multiparous patient who underwent undocumented pelvic surgery in 2009 and consulted for abnormal uterine bleeding. Pelvic ultrasound and abdomino- pelvic CT scan revealed a left latero-uterine mass, a mass in the abdominal wall and endometrial thickening. The patient underwent an exploratory laparotomy. The procedure consisted of a left hysterectomy and adnexectomy (right adnexa not found), and resection of the abdominal mass. Anatomopathology, immunohistochemistry and FoxL2 mutation testing concluded that the tumour was a granulosa tumour in the abdominal wall. Following the multidisciplinary meeting, the decision was made to discuss adjuvant chemotherapy and to establish close monitoring by tumour markers.

Conclusion: Our case highlights the difficulties in the diagnosis of adult granulosa tumours. The present study reviews diagnostic methods, histological features and therapeutic recommendations.

Introduction

Stromal tumours of the sex cords of the ovary are rare (3-5% of all ovarian malignancies). Granulosa cell tumours (GCTs) account for 70-90% of these tumours [1]. The two subtypes are differentiated by their clinical and histopathological features. The more common adult granulosa cell tumours (AGCT) have the following characteristics: onset around or after the perimenopausal period, early detection, hyperestrogenism [1,2] and association with a FOXL2 gene mutation [3]. Early stage or complete cytoreductive surgery is indicative of a better prognosis.

With a relatively indolent behaviour, the tumour sometimes recurs several years after the initial diagnosis. There is no consensus on adjuvant treatment or post-operative monitoring, partly because of the low incidence of this tumour. Recurrences can occur at different stages and mainly involve the abdominopelvic cavity [1,2]. As AGCT rarely presents with alarming elevations of specific tumour markers or causes troublesome symptoms such as increasing ascites, the management of recurrent AGCT can be difficult. We present a case of relapsed AGCT detected by imaging studies and currently undergoing chemotherapy.

Observation

We report the case of Mrs H.Z, 60 years old, multiparous (7EV/AVB), postmenopausal, followed for hypothyroidism on levothyrox for 02 months, operated in 2009 for an undocumented right latero- uterine mass who was initially admitted for management of postmenopausal metrorrhagia.

The initial clinical examination found a conscious patient, hemodynamically and respiratorily stable, and the gynecological examination was unremarkable except for the presence of an abdominal mass measuring 7 cm in long axis and appearing to be dependent on the rectus.

Ultrasound revealed a left latero-uterine mass measuring 15x16x10 cm, associated with endometrial thickening measured at 20mm, and a parietal mass appearing to be dependent on the right rectus measuring 7cm long.

Abdominal-pelvic MRI showed a thickened and irregular endometrium measuring 21mm in maximum thickness with the presence of a left latero uterine mass in hypo T1 hypersignal T2 unenhanced after injection of contrast medium and unrestricted thin walled lobulated without septum or vegetation of homogeneous signal measuring 150x 142x95mm associated with the presence at the level of the left lateral sub umbilical abdominal wall of an oval formation well limited encapsulated in hypoT1 signal and T2 iso-signal strongly enhanced after injection of contrast medium measuring 89x58x91mm suggesting in the first instance a fibrous tumour.

The patient underwent a diagnostic hysteroscopy and then surgery with anatomical study of the presence of foci of complex atypical hyperplasia, given the symptomatology and thickening observed on ultrasound and MRI.

An exploratory laparotomy was performed and revealed a left parietal paral mass 10 cm long, adherent to the rectus abdominis muscle, an enlarged uterus 10 SA and a flaccid left latero-uterine cystic mass adherent to the uterus and the bowels 15 cm long. The right adnexa was not found during the exploration (probably resected in 2014).

We proceeded to resect the parietal mass and then performed a total hysterectomy with left adnexectomy and cystectomy.

The definitive pathological study of the mass which developed opposite the rectus came back in favour of a tumour of the granulosa confirmed by immunohistochemical and molecular study. Polypoid hyperplasia of the entire endometrium with foci of complex atypical hyperplasia were found on the hysterectomy specimen. The left ovary was unremarkable except for a simple serous cyst.

Discussion

Although AGCT has a low potential for malignancy, it is described as recurrent in 20-25% of patients, with an average of 4-6 years between initial treatment and recurrence. Several reports have suggested checking serum levels of oestradiol, human chorionic gonadotropin, alpha- fetoprotein, lactate dehydrogenase, inhibin and anti-mullerian hormone (AMH) [4-5].

While a meta-analysis of 70 AGCT cases and 351 controls demonstrated that serum AMH was a useful biomarker [5], a series of AGCT cases (n = 30) did not find a relationship between serum oestradiol and disease recurrence [6]. Serum inhibin levels, in contrast, are readily available as a routine clinical laboratory test.

Efforts have been made to identify predictive features of recurrence, such as age, initial tumour stage, tumour size and residual tumour [2-3]. A retrospective study using the National Cancer Database 1998-2013 for ovarian AGCT (n = 2680) showed that older age, more comorbidities, previous tumour, higher grade, higher stage, larger tumour size, incomplete surgical staging and residual disease at the surgical margin were independently associated with a higher risk of death [7]. As AGCT rarely induces prominent symptoms, imaging findings of any new or enlarging lesion should raise alarm and require further investigation.

Most systemic reviews or population-based studies have not found a benefit to postoperative adjuvant chemotherapy or radiotherapy [2,7,10]. Five patients with GCT (4 AGCT, 1 juvenile GCT) were treated with the PD-1 inhibitor pembrolizumab in a phase II trial, but unfortunately no objective response was observed, although two patients had stable disease for ≥12 months [11]. In a Gynecologic Oncology Group phase II trial of bevacizumab in recurrent ovarian sex cord tumours (32 GCTs, 4 unclassified SCSTs), 16.7% of patients achieved a partial response and 77.8% had stable disease [12].

Conclusion

In the light of this work, we aim to add to the literature regarding the early management of recurrent AGCT, which remains early detection and surgical intervention. Laboratory data should be integrated with caution, as recent data have not indicated a specific tumour marker suitable for serial follow-up. Imaging studies, such as ultrasound, CT, PET and others, should be performed routinely and whenever recurrence is suspected. There is an urgent need for further studies on AGCT to assess the long-term efficacy of endocrine therapies, but also of other therapeutic agents, and to establish biomarkers for monitoring responses.

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