Cystadenofibroma case report: The chameleon of cancer.

Patel Shamim, Sara Bernardez-Lai, Stefano Leone, Sebastian Villamil, Anthony Walcott drafted and edited the manuscript

This study was exempted from ethical approval at our institution (Humboldt Park Health, Chicago).

This case report was not funded.

Written informed consent was obtained from the patient for publication and any accompanying images.

Patel Shamim, Anthony Walcott, Sara Bernardez-Lai, Stefano Leone, Sebastian Villamil, Anthony Walcott

Ovarian cystadenofibromas are rare benign ovarian tumors with clinical and imaging characteristics that often mimic malignancy. Their rarity and diverse presentations necessitate a thorough diagnostic approach that integrates imaging studies, tumor markers, and histopathological analysis for definitive diagnosis. Recognizing the potential for misdiagnosis and employing a multidisciplinary approach are crucial for optimizing patient outcomes. Continued research is needed to refine diagnostic algorithms and therapeutic strategies for these rare ovarian neoplasms.

Ovarian cystadenofibroma is a rare benign ovarian tumor that accounts for approximately 1.7 % of benign ovarian neoplasms [ 2 ]. Despite being benign, cystadenofibromas exhibit macroscopic and histopathological features that may mimic ovarian cancers, which can lead to misdiagnosis and inappropriate aggressive surgical management [ [3] , [4] , [5] ]. The rarity of this tumor and its resemblance to malignant lesions can complicate preoperative diagnosis. Typically cystadenofibromas present as unilateral adnexal masses in women aged 40–50 years-old [ 3 ], although cases of bilaterality have been reported [ 4 , 7 , 8 ]. In utero exposure to diethylstilbestrol may be associated with earlier onset [ 9 ]. Although often asymptomatic, large cystadenofibromas can cause pelvic pain, changes in bowel or urinary habits, and increased abdominal girth [ [9] , [10] , [11] , [12] , [13] ]. Rarely, they may secrete estrogen, leading to symptoms such as metrorrhagia [ 7 , 14 ]. Histologically, cystadenofibromas are composed of cystic, fibrous, and glandular epithelial components, which can sometimes exhibit atypical features mimicking malignancy. Grossly, these tumors are cystic-to-solid, with the majority being predominantly cystic [ 15 ]. They often present as unilocular complex cystic tumors with papillary projections or solid nodules that may exhibit increased vascularity [ 5 ]. Cystadenofibromas can be serous or mucinous, with serous variants being more common [ 6 , 7 ]. The presence of solid components, thick or irregular septa, and suspicious intracystic fluid can contribute to their misdiagnosis as malignant [ 14 , 16 , 17 ]. In contrast to the diagnosis of other ovarian tumors, for which ultrasonography is considered the gold standard, T2-weighted MRI is best able to characterize ovarian cystadenofibromas [ 18 ]. On T2 weighted imaging, the fibrogenous epithelial component of these lesions exhibits low signal intensity, similar to skeletal muscle [ 19 ]. Their cystic components may show high signal, contributing to a “black sponge” appearance [ 20 ]. A recent study indicates that additional MRI findings include a “dark-dark appearance” (T2-weighted hypointensity without diffusion-weighted imaging restrictions) and a slow, gradual enhancement following gadolinium contrast [ 21 ]. In contrast, malignant tumors tend to exhibit high-intensity signals on diffusion-weighted imaging according to a high impact study [ 22 ]. The absence of enhancement on MRI imaging can aid in distinguishing cystadenofibromas from ovarian malignancies. The imaging findings of our patient were consistent with those reported in the literature for cystadenofibromas, demonstrating minimal enhancement on T2-weighted MRI. While malignant transformation is extremely rare, it can occur, resulting in the development of cystadenocarcinofibromas (CACFs), which have a greater solid component, higher T2-MRI signal intensity, and stronger enhancement on imaging compared to benign cystadenofibromas. The subtlety of differences in imaging characteristics and the rarity of both these lesions make CACFs challenging to distinguish from benign cystadenofibromas preoperatively.

Ovarian cystadenofibroma is an uncommon benign ovarian neoplasm characterized by clinical and radiological features that can mimic malignant ovarian tumors, complicating its diagnosis. These tumors are often discovered incidentally or due to symptoms related to mass effect, such as abdominal pain or distension. The main diagnostic difficulty challenge is to differentiate cystadenofibromas from malignant ovarian neoplasm ( Table 1 ). This case report describes a hemorrhagic serous cystadenofibroma in a 36-year-old woman , emphasizing the clinical presentation, diagnostic evaluation, and histopathological features crucial for accurate diagnosis and management. To facilitate this, peer-reviewed studies of both pre- and post-menopausal populations with ovarian neoplasms were utilized. This allowed for adequate comparison of the literature and validation of our diagnostic approach. High-impact and recent studies were used to explore imaging modalities that best differentiate between benign and malignant ovarian masses. This case report has been reported in line with the SCARE Criteria [ 1 ]. Table 1 A table showing the diagnostic algorithm for ovarian masses using ACOG guidelines. Table 1 Step Clinical/imaging findings Next step Differential diagnoses 1. History & Physical Exam Pelvic pain, bloating, fullness, abnormal bleeding, palpable mass Perform pelvic exam and assess risk factors (age, family history, menstrual history) Functional cyst, endometrioma, fibroma, malignancy 2. Initial Imaging Transvaginal ultrasound (TVUS): preferred first-line tool Evaluate morphology: size, wall thickness, septations, solid components, Doppler blood flow Simple cyst, complex cyst, hemorrhagic cyst, teratoma, endometrioma 3A. Simple Cyst (5 cm or symptomatic Functional cyst, follicular cyst 3B. Simple Cyst (2 cm Serous cystadenoma, benign cyst 3C. Complex or Solid Mass Thick septations, mural nodules, papillary projections, Doppler flow, ascites Order CA-125 and consider MRI/CT; refer to GYN-oncology if suspicious features present Endometrioma, dermoid cyst, epithelial ovarian carcinoma 4. Tumor Markers CA-125 (especially in postmenopausal); AFP, β-hCG, LDH (in young women); Inhibin, Estradiol (if hormonally active mass) Interpret CA-125 carefully: • >35 U/mL in postmenopausal = concern • >200 U/mL in premenopausal = concerning Other markers based on age/hormonal activity Epithelial ovarian cancer, germ cell tumors, sex cord-stromal tumors (e.g., granulosa cell) 5. High-Risk Criteria for Malignancy (ACOG Referral) - Ascites - Nodular/fixed pelvic mass - Evidence of metastasis - CA-125 > 200 (premenopausal) - CA-125 > 35 (postmenopausal) - Elevated HE4 or ROMA score Refer to GYN-Oncology Referral improves survival and outcomes Malignant ovarian tumor, peritoneal carcinomatosis, metastatic disease 6. Surgical Evaluation Persistent or suspicious mass, rising tumor markers Laparoscopy or laparotomy with frozen section if malignancy suspected Histological classification: benign, borderline, or malignant 7. Final Diagnosis & Management Based on intraoperative findings and pathology • Benign: cystectomy or oophorectomy • Malignant: staging surgery, cytoreductive surgery, adjuvant chemotherapy Benign: serous cystadenoma, dermoid Malignant: serous/mucinous carcinoma, granulosa tumor, metastasis A table showing the diagnostic algorithm for ovarian masses using ACOG guidelines.

The patient is a 36-year-old obese female (P1; BMI 34.6 kg/m 2 ) who presented to the emergency department with acute abdominal pain localized to the right lower quadrant, accompanied by a one-day history of nausea and unspecified episodes of vomiting. Patient reported post-coital spotting earlier in the week and regular monthly menses, with the last menstrual period occurring two weeks prior. The patient denied menstrual irregularities or gastrointestinal symptoms. The patient's medical history included hypertension (with non-compliance to antihypertensive medication, Amlodipine 5 mg orally daily) and an uncomplicated C-section in 2017. The patient denied relevant family and social history, and the review of systems was otherwise negative. On physical examination, the patient was afebrile with stable vital signs. The abdominal examination revealed right lower quadrant and right flank tenderness with guarding but no rebound tenderness. Initial diagnostic evaluation included imaging studies (CT abdomen and pelvis [CTAP], transvaginal ultrasound [TVUS], and abdomen and pelvis Magnetic Resonance Imaging [MRI]) and laboratory tests. CTAP showed a lesion with solid and predominantly cystic components, likely originating from the right ovary, measuring 13 × 14 cm. Incidental findings included right hydronephrosis, likely secondary to compression of the right ureter by the pelvic mass. There was no evidence of adenopathy or ascites. TVUS confirmed the presence of a complex right adnexal mass with thick-walled septations measuring 12.0 × 10.0 × 14.0 cm ( Fig. 1 ). MRI revealed a 15.8 × 14.1 × 12.3 cm mixed cystic and solid adnexal mass concerning for malignancy ( Fig. 2 ). A bedside urine pregnancy test was negative, and tumor markers Cancer Antigen 125 (CA-125) and Human Epididymis Protein 4 (HE4) were within normal limits. No other tumor markers were ordered. Despite the use of appropriate imaging modalities, the clinical rarity and ambiguous gross morphological findings posed significant diagnostic challenges. At this point, the findings were a large cystic mass concerning for malignancy. Fig. 1 Transvaginal ultrasound showing right adnexal mass with thick-walled septations. Fig. 1 Fig. 2 MRI showing cross-sectional view of cystic septated pelvic mass. Fig. 2 Transvaginal ultrasound showing right adnexal mass with thick-walled septations. MRI showing cross-sectional view of cystic septated pelvic mass. Given the patient's presentation, operative management was deemed necessary. Preoperatively, the patient was optimized with anti-emetics, pain management, and blood pressure control. She was placed on nil by mouth restrictions at midnight prior to surgery. Two grams of Cefazolin were administered as infection prophylaxis immediately before the procedure. The patient was placed in a lithotomy position under general anesthesia for laparoscopy. A laparoscopic procedure was performed that included extensive adhesiolysis to address scar tissue and endometriosis, and removal of the 15 cm ovarian lesion with right salpingo-oophorectomy ( Fig. 3 , Fig. 4 ). During the procedure, the right ovary was found to be necrotic and twisted around the infundibulopelvic ligament, suggestive of hemorrhagic ovarian torsion which necessitated its removal. This was deemed to be the cause of the patient's acute abdominal pain. To avoid potential intraperitoneal seeding, the large lesion was placed in a 15 cm laparoscopic specimen retrieval bag, drained within the bag, and then removed through the trocar site. Fig. 3 Intraoperative image showing a 15 cm ovarian lesion. Fig. 3 Fig. 4 Intraoperative image showing omental adhesions. Fig. 4 Intraoperative image showing a 15 cm ovarian lesion. Intraoperative image showing omental adhesions. Postoperatively, the patient was prophylaxed with Pantoprazole for gastrointestinal protection and sequential compression devices to prevent thromboembolic events. Pain management included ibuprofen, acetaminophen, and morphine. The operative and pathology reports described the lesion as a hemorrhagic cystic mass, with the final histopathological diagnosis being hemorrhagic serous cystadenofibroma. ( Fig. 5 ). The early postoperative period was unremarkable. The patient's pain was well controlled, diet was tolerated, she had normal bowel movements and was discharged after three days of hospitalization. Fig. 5 Cyst wall showing epithelial proliferation. Fig. 5 Cyst wall showing epithelial proliferation. .The patient had two follow-up visits within three weeks. No complications were noted.

There is no conflict of interest.