Pitfalls of Frozen Section in Gynecological Pathology: A Case of Ovarian Serous Surface Papillary Adenofibroma Imitating Malignancy

Introduction

Serous cystadenofibromas are uncommon benign ovarian lesions consisting of both fibrous and epithelial components. Though primarily cystic, internal solid areas and papillary excrescences may give rise to concern of malignancy on imaging.^1,2 Furthermore, lesions with gross and/or histological papillary architecture may lead the pathologist into considering a borderline or malignant diagnosis, particularly during frozen section. As frozen section is utilized to determine extent of procedure, an overcalling of malignancy might lead to unnecessarily extensive surgery. We recently encountered a rare variant of a serous cystadenofibroma with surface papillary excrescences, termed serous surface papillary adenofibroma. As most serous cystadenofibromas have smooth outer surfaces, this led to concern of a borderline lesion at the frozen section.

Case

A 45-year-old G0P0 female with a strong family history of colon and ovarian cancer was referred to our institution after being diagnosed with an ovarian mass on computed tomography scan with associated nausea and vomiting for several weeks. The computed tomography scan performed at our institution revealed 2 multiloculated cystic pelvic masses that measured 9.9 cm and 8.1 cm in the greatest dimension, respectively. Genetic testing was performed and was negative for BRCA 1 and 2, as well as mismatch repair genes and other associated hereditary breast and ovarian cancer genes. She did not desire fertility or reproductive preservation and had expressed strong desire for oophorectomy given her family history. She was taken to the operating room for surgical management. Examination under anesthesia was performed and was significant for fullness in the cul-de-sac. Intraoperatively, the surgical team found an 8-cm right ovarian cyst with papillary excrescences on the ovarian surface and a 7-cm left ovarian mass adherent to the pelvic wall. Intraoperative consultation of a 10.2 × 7.5 × 6.5 cm, 364-g right fallopian tube and ovary revealed a multiloculated cystic lesion with multiple internal and external papillary projections and clear, yellow fluid. Multiple sections of the tissue were submitted for frozen section and were interpreted as a serous cystadenoma with focal features suggestive of at least a borderline malignancy. Subsequently, the patient underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy, omentectomy, appendectomy, and biopsy of visualized peritoneal lesions. On permanent section of the right fallopian tube and ovary, extensive sampling demonstrated a serous surface papillary adenofibroma (Figures 1-3).

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Figure 1.

Frozen section slide demonstrates a papillary architecture with spindly fibrous stroma with areas of myxoid change and a simple epithelial lining.

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Figure 2.

Low-power magnification of hemoglobin and eosin stain shows simple papillary architecture with fibrous stroma lined by a single layer of cuboidal epithelium.

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Figure 3.

On high-power magnification, the single cuboidal epithelial layer is apparent and no nuclear atypia is visualized.

Discussion

Ovarian cystadenofibromas are uncommon benign lesions that fall under the category of surface epithelial-stromal neoplasms. They account for approximately 1.7% of all benign ovarian tumors. ¹ On imaging studies, some lesions possess a complex cystic appearance with thickened, irregular septae or a solid component, which can be interpreted as malignant characteristics. ¹ Serous surface papillary adenofibromas are a variant that are rare, and hence may be underrecognized, particularly during intraoperative consultation. They have papillary projections on their outer surface, which may trigger concern for malignancy. In this regard, they are not dissimilar to the finger-like projections seen in serous borderline ovarian lesions. ² Though the projections may be more extensive in borderline lesions and malignant lesions tend to be softer in consistency, as the epithelial elements predominate over the connective tissue, gross examination is not sufficient to make the distinction between benign and malignant entities.

Histologic characteristics of borderline ovarian tumors consist of branching papillae and pseudopapillae, which are lined by piled up epithelial cells that are primarily columnar with intermixed ciliated cells. ³ Nuclear features should include mild-to-moderate atypia and hyperchromasia. The epithelium tends to be multilayered and may give rise to tufts of detached cells.^3,4 Papillary adenofibromas, conversely, should not demonstrate any nuclear atypia or complex architecture. If a cystadenoma/cystadenofibroma contains greater than 10% of borderline histological features, it can be designated a borderline ovarian tumor. ³ Despite these defining features, making the diagnosis can prove to be more difficult than anticipated. One retrospective study by Avril et al ⁵ determined that ovarian cystadenomas/adenofibromas were overdiagnosed as serous borderline tumors at their institution. In our case, the tissue samples selected for frozen section had focal areas interpreted as suspicious for a borderline malignancy. However, on the permanent sections, the diagnosis of the benign copycat was made.

In summary, serous surface serous papillary adenofibromas are benign lesions that may be confused with malignant lesions on imaging, gross examination, and even on frozen section consultation. Consideration of this diagnosis may avoid the pitfall of over interpretation.