Bilateral Granulosa Cell Tumours in a Pregnant Mare: Reproductive Implications and Long-Term Outcome

Granulosa cell tumours (GCTs) are the most commonly diagnosed ovarian neoplasms in mares and are typically associated with behavioural abnormalities, anoestrus, or stallion-like behaviour^1,2. However, this case presented an unusual scenario involving bilateral GCTs in a pregnant mare that developed life-threatening haemoperitoneum. 

More remarkably, the mare successfully maintained pregnancy following bilateral ovariectomy performed at approximately 70 days of gestation. 

An Unusual Clinical Presentation 

An 8-year-old pregnant Warmblood-cross mare was initially presented with mild intermittent colic. Unlike most mares diagnosed with GCTs, she showed¹: 

• No behavioural abnormalities  

• No reproductive irregularities prior to breeding  

• No history of systemic illness  

• A viable 60-day pregnancy  

Transrectal ultrasonography revealed progressive bilateral ovarian enlargement with large, reticulated structures suggestive of haemorrhagic ovarian pathology. 

Initially, ovarian haematoma was considered the most likely diagnosis because pregnancy-associated ovarian enlargement can occur during peak equine chorionic gonadotropin (eCG) activity between 60–80 days gestation³. 

However, rapid enlargement of both ovaries and progressive haemoperitoneum later raised suspicion for ovarian neoplasia. 

Histopathological Findings 

Following emergency bilateral ovariectomy, both ovaries were found to be markedly enlarged with irregular hyperaemic surfaces and extensive haemorrhage. 

Histopathology demonstrated¹: 

• Multiple large follicular structures  

• Polygonal neoplastic granulosa cells  

• Multifocal haemorrhage  

• Thrombosed blood vessels  

• Extensive fibrin accumulation  

These findings confirmed bilateral macrofollicular granulosa cell tumours with associated subacute haemorrhage. 

Bilateral Granulosa Cell Tumours 

Most equine GCTs are unilateral, although bilateral cases have been reported. In one review, bilateral involvement was identified in approximately 27% of cases¹. 

Why This Case Was Unusual 

This mare demonstrated several atypical features¹: 

• Bilateral ovarian involvement  

• Pregnancy at diagnosis  

• Absence of behavioural signs  

• Severe haemoperitoneum as the primary presentation  

The authors suggested that pregnancy-associated hormonal stimulation may have contributed to rapid tumour growth and subsequent ovarian rupture. 

Why the Tumours Ruptured 

Previous reports have proposed that rapid enlargement of GCTs may predispose tumours to rupture due to vascular compromise and capsular tearing⁴. 

In this mare: 

• Both ovaries enlarged rapidly  

• Serosal tearing was evident  

• Active bilateral haemorrhage developed  

The combination of pregnancy-related hormonal stimulation and expanding neoplastic tissue likely contributed to ovarian rupture and severe intra-abdominal bleeding. 

Hormonal Findings 

Postoperative hormonal testing supported the diagnosis of hormonally active GCTs. 

Findings included: 

• Increased Anti-Müllerian hormone  

• Elevated testosterone concentration  

• Increased oestrogen levels  

• Persistently elevated progesterone associated with pregnancy  

These hormonal abnormalities are consistent with granulosa-theca cell tumour activity in mares². 

Pregnancy After Bilateral Ovariectomy 

One of the most remarkable aspects of this case was the successful continuation of pregnancy after removal of both ovaries. 

Traditionally, bilateral ovariectomy during early pregnancy is expected to compromise progesterone support and potentially result in pregnancy loss. However, pregnancy maintenance in mares depends on several evolving endocrine mechanisms¹. 

Understanding Pregnancy Maintenance in the Mare 

Between approximately Days 35–120 of gestation: 

• Endometrial cups produce equine chorionic gonadotropin (eCG)  

• Secondary corpora lutea develop  

• Progesterone production increases  

As pregnancy progresses, the fetoplacental unit gradually assumes responsibility for steroid hormone production¹. 

Because this mare underwent ovariectomy at approximately 70 days gestation, sufficient endocrine support likely already existed to maintain pregnancy through secondary corpora lutea activity and developing fetoplacental steroidogenesis¹. 

Role of Medical Therapy 

Medical therapy likely also contributed to preservation of pregnancy. 

Treatments Included: 

• Altrenogest  

• Flunixin meglumine  

Altrenogest provided exogenous progesterone support, while flunixin meglumine may have reduced prostaglandin-mediated pregnancy loss associated with systemic inflammation and stress^1,3. 

Long-Term Outcome 

The mare recovered well following surgery and intensive supportive care. 

At 335 days gestation: 

• She delivered a healthy filly foal  

• Parturition was unassisted  

• No major postpartum complications occurred  

This successful outcome demonstrated that pregnancy can continue normally following bilateral ovariectomy when adequate hormonal support has already developed. 

Practical Clinical Takeaways 

This case highlights several important lessons for equine reproductive practitioners: 

Pregnancy Does Not Exclude Ovarian Neoplasia 

GCTs should remain a differential diagnosis even in pregnant mares. 

Bilateral Disease Can Occur 

Rapid enlargement of both ovaries warrants aggressive investigation. 

Behavioural Changes May Be Absent 

Not all mares with GCTs exhibit classic reproductive or behavioural abnormalities. 

Pregnancy Can Continue After Bilateral Ovariectomy 

Successful pregnancy maintenance is possible beyond early gestation under appropriate endocrine conditions. 

Serial Monitoring Is Essential 

Repeated ultrasonography and cardiovascular assessment are critical in mares with ovarian enlargement and suspected haemorrhage. 

Conclusion 

This unusual case highlights the complex interaction between ovarian neoplasia, pregnancy physiology, and haemoperitoneum in mares. 

Bilateral granulosa cell tumours should remain an important differential diagnosis in pregnant mares presenting with ovarian enlargement and intra-abdominal haemorrhage. The case also demonstrates that successful pregnancy maintenance following bilateral ovariectomy is possible once sufficient hormonal support from secondary corpora lutea and the fetoplacental unit has developed. 

References  

1. Sinovich M, Archer DC, Kane‐Smyth J, Scarabelli S, Ritchie A, Kelly PG. Haemoperitoneum associated with bilateral granulosa cell tumours in a pregnant mare treated by standing ovariectomy. Equine Veterinary Education. 2022 Dec;34(12):e526-32. https://beva.onlinelibrary.wiley.com/doi/pdfdirect/10.1111/eve.13612  

2. Sherlock CE, Lott‐Ellis K, Bergren A, Withers JM, Fews D, Mair TS. Granulosa cell tumours in the mare: A review of 52 cases. Equine Veterinary Education. 2016 Feb;28(2):75-82. https://doi.org/10.1111/eve.12449 

3. Beachler TM, Bailey CS, McKelvey KA, Davis JL, Edwards A, Diaw M, Vasgaard JM, Whitacre MD. Haemoperitoneum in a pregnant mare with an ovarian haematoma. Equine Veterinary Education. 2016 Jul;28(7):359-63. https://doi.org/10.1111/eve.12211 

4. Worsman FC, Barakzai SZ, de Bont MP, Turner S, Rubio‐Martínez LM. Treatment of haemoperitoneum secondary to ruptured granulosa cell tumours in two mares. Equine Veterinary Education. 2020 Feb;32(2):71-7. https://doi.org/10.1111/eve.12929