A ruptured ovarian cystadenofibroma presenting with life-threatening sepsis and an incidental synchronous endometrial stromal sarcoma

Abstract

A woman in her 60s presented with a rare complication of an ovarian cyst which many clinicians may not consider at first presentation. She was admitted with life-threatening staphylococcus aureus sepsis. She presented shocked with a collapse following a 2-day history of diarrhoea, vomiting and pain in the right iliac fossa. She was taken to theatre where a ruptured, widely infarcted left ovarian serous cystadenofibroma was discovered with over 2 litres of purulent fluid exuding from the cyst into the abdomen. She had a left cyst removal, hysterectomy and bilateral salpingo-oophorectomy performed. Histological analysis and molecular gene testing of an incidentally discovered uterine neoplasm revealed an undifferentiated uterine sarcoma. She successfully recovered as an inpatient and was discharged under the care of an oncology team for ongoing management.

Background

Benign ovarian cysts are typically classified based on their cell of origin into three categories; epithelial, stromal and germ cell. Serous cystadenomas are a subtype of the epithelial cysts. A cystadenofibroma is a subtype of a cystadenoma which also contains a solid fibrous component in the cyst.¹

Serous ovarian cystadenofibromas are most often asymptomatic but if large would usually present with abdominal pain, menstrual disturbances or bladder and bowel pressure symptoms.² Infarction due to torsion occurs in large cysts. However, infection, with or without sepsis, is not a commonly recognised complication of ovarian cysts in modern times. The incidence of infected cysts has decreased due to a move away from therapeutic transabdominal puncture. This technique is now infrequently performed due to high reoccurrence rates of cysts.³ Since this time, although there have been reports of staphylococcus infected dermoid cysts, there have been very few reports of infected serous cystadenomas.⁴

Case presentation

A postmenopausal, gravida 0 para 0, female in her 60s presented with a 2-day history of diarrhoea, vomiting, abdominal distension and progressive right iliac fossa pain before collapse with shock. She had a non-tender, distended, tense abdomen and cold-mottled peripheries. She had no history of constitutional symptoms. Previously, she had a laparoscopic appendicectomy and a hospital admission with rheumatic fever aged 13 with no complications from this. She went through menarche aged 11 and menopause age 52 with early menarche being an established risk factor for endometrial sarcoma.⁵ She has never used any hormonal contraceptives nor other hormonal modulators such as tamoxifen. She has not attempted pregnancy and so fertility status is unknown. She has no other past medical, surgical or gynaecological history and no relevant family history of malignancy.

Investigations

Initial blood tests revealed a C-reactive protein of 380, a lactate of 10.9 and a procalcitonin of over 100. Blood cultures and an ascitic paracentesis grew staphylococcus aureus. Cancer Antigen-125 (CA-125) was 15 538. Her calculated P-Possum score predicted the likelihood of mortality as 35.0%.

A CT scan, shown in figure 1, demonstrated a 28×20 cm, adnexal, cystic structure arising from the pelvis. In addition to this, the CT scan demonstrated a fibroid uterus with an area of low density inferiorly but with no suspicious features of uterine malignancy. The microscopy of the adnexal cyst, shown in figure 2, revealed extensive necrosis and nodular projections lined by simple cubocolumnar epithelium and scattered ciliated cells. There was minimal cytological atypia with areas of calcification in a fibrotic stroma, diagnostic of an infarcted and ruptured left ovarian cystadenofibroma.

Figure 1.

A preoperative CT scan showing (A) the left ovarian cystadenofibroma and uterine body in sagittal view and (B) the presumed site of rupture of the ovarian cyst in axial view.

Figure 2.

(A) A photomicrograph of the ovarian serous cystadenofibroma demonstrating broad-based projections of fibrous stroma and inset showing simple cubocolumnar epithelium lining (H&E stain ×20 and ×200 magnification). (B) A macroscopic photograph of the left ovarian serous cystadenofibroma.

On histopathological examination, the uterus showed a large, 90-mm, intramural leiomyoma. The endometrial cavity was distended by a 65-mm soft necrotic mass with a yellow pink cut surface. This necrotic mass microscopically showed a high-grade neoplasm composed of sheets and fascicles of small epithelioid and spindle cells expressing moderate cytological atypia, bizarre nuclei, multinucleated giant cells and increased mitosis of 20 per 10 high power fields with extensive autolysis. This can be seen in figure 3.

Figure 3.

(A) A macroscopic photograph of the uterus including the undifferentiated endometrial stromal sarcoma (lower large yellowish mass inside uterine cavity) and two leiomyomas. (B) A photomicrograph of the endometrial stroma sarcoma showing epithelioid cells with moderate atypia, bizarre nuclei and multinucleated giant cells with increased mitosis (H&E stain at ×100 magnification).

Immunohistochemistry showed scattered strong staining for MNF116, AE1/AE3, CD56 and Vimentin with pale CD10 and a small number of cells stained for Desmin. Other stains: smooth muscle actin, Myogenin, H-Caldesmon, Calponin, CD34, CD99, CyclinD1, DOG1, S100, HMB45, Oestrogen Receptors, Progesterone Receptors, Inhibin, Calretinin, Chromogranin A and Synaptophysin were all negative. Ki67 was high up to 80% in hot spots. Molecular gene testing was found to be negative for YWHAE and BCOR gene fusions indicating it was most likely an undifferentiated endometrial stromal sarcoma.

Treatment

The woman was taken to theatre where she had a left cystectomy removing a ruptured ovarian cyst extending to the diaphragm. The ruptured cyst was exuding over 2 litres of purulent fluid into the abdomen which was drained. She also had a bilateral salpingo-oophorectomy and hysterectomy. She returned to the intensive care unit postoperatively where she required inotropic support and continuous veno-venous haemofiltration.

Outcome and follow-up

This woman was discharged from hospital to a rehabilitation facility where she successfully recovered. A follow-up PET-CT scan performed 5 months after surgery demonstrated a residual pelvic nodule which was indeterminate but radiologically suspicious for peritoneal metastasis. She is under active surveillance with her oncology team where she is having 3 monthly contrast CT scans to track the possible peritoneal disease. She is to continue these scans 3 monthly for 2 years. This would then be downgraded to 6 monthly for 3 years and then annually if disease did not progress. In the event of progression of disease, she would be offered single-agent doxorubicin-based chemotherapy in line with the Clinical Sarcoma Research guideline.⁶ There would be no role for radiotherapy or immunotherapy in multifocal disease.

Discussion

This case demonstrates first a rare complication of an ovarian cyst. It also displays a novel presentation of an ovarian serous cystadenofibroma associated with a synchronous uterine sarcoma. To the best of our knowledge, there are no reports of this tumour combination in the literature.^{7 8}

Superadded infection, with or without sepsis, is not a commonly recognised complication of ovarian cystadenofibromas. There have been reports of clostridium perfringens sepsis associated with uterine sarcomas but, to the best of our knowledge, no reports of sepsis secondary to serous ovarian cysts.⁹ Therefore, a ruptured cyst such as this one may not be considered as a differential for a patient presenting with a distended abdomen and life-threatening sepsis. A high index of suspicion is required to attribute this as the cause of sepsis and enable optimal management.

Sarcomas represent 4%–9% of all malignant uterine neoplasms. They are typically classified as carcinosarcomas, leiomyosarcomas or, as in this case, endometrial stromal sarcomas. The subtype differential for this case includes an undifferentiated uterine sarcoma or a high-grade endometrial stromal sarcoma. The median age of presentation of an undifferentiated uterine sarcoma is 61. Possible presenting features for these subtypes includes abdominal or pelvic pain, vaginal bleeding or a palpable pelvic mass. Both of these malignancies usually confer a poor prognosis.¹⁰

High-grade endometrial stromal sarcomas typically harbour YWHAE-NUTM2A/B, ZC3H7B-BCOR or BCOR-ITD gene fusions along with other rarer variants. Histopathologically, they demonstrate expansile, permeative or infiltrative growth patterns. Diagnostically, they should demonstrate monomorphic, high-grade, round or spindle cells with brisk mitotic activity. They should also demonstrate cyclin D1 and BCOR immunohistochemical positivity.¹¹

Undifferentiated uterine sarcomas represent less than 5% of uterine sarcomas and are diagnosed via exclusion.¹² The pathogenesis includes activation of RNA expression pathways associated with genital tract development, extracellular matrix and proliferation. They exhibit variable copy-number alterations with some tumours showing extensive chromosomal gains or losses while others are near diploid. Histopathologically, these tumours have a destructive pattern of myometrial invasion and consist of uniform or pleomorphic, high-grade mesenchymal cells with brisk mitotic activity.

The endometrial tumour in this case was negative for YWHAE-NUTM2A/B, ZC3H7B-BCOR and BCOR-ITD gene fusions when subjected to molecular gene testing. Combined with macroscopic and histopathological features, this tumour is therefore most likely an undifferentiated uterine sarcoma. This was managed surgically in accordance with current consensus of total abdominal hysterectomy and bilateral sapingo-oophorectomy without lymphadenectomy with follow-up under oncology for consideration of systemic treatment if required.^{13 14}

Learning points.

• A large, complicated, torted and infarcted ovarian cyst can present as the source of life-threatening intra-abdominal sepsis and a high index of suspicion is required to enable timely surgical management.

• This case demonstrates the diagnostic approach to an undifferentiated uterine sarcoma.

• This case also provides an opportunity to follow the management of a patient diagnosed with a rare undifferentiated uterine sarcoma managed surgically according to current guidelines.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).