Case 4 -

Serous Borderline Tumor Kristen Atkins

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Diagnosis: Serous Borderline Tumor Clinical History A 35-year-old woman with morbid obesity presents with abdominal pain. An ultrasound demonstrates a 9 cm unilateral cyst with several internal loculations but no solid component. The surgeons would rather not perform surgery if the cyst is benign so an ovarian cyst aspirate is performed. Case 4 - Figure 1A Ovarian cyst aspirate, Thin Prep slide, 400x (Papanicolou stains). Histiocytes and necrotic cells in the back ground. Case 4 - Figure 1B Ovarian cyst aspirate, Thin Prep slide, 400x (Papanicolou stains). Histiocytes and necrotic cells in the back ground. Case 4 - Figure 2 Ovarian cyst aspirate, Thin Prep slide, 200x (Papanicolaou stain). Papillary cluster of cells with variably sized cells with prominent nucleoli. Cytologic Diagnosis: Serous neoplasm, favor borderline tumor Histologic Diagnosis: Serous borderline tumor Cytologic Findings: Papillary clusters of cells devoid of mucin. The numerous histiocytes are characteristic of a cyst. The necrotic cells are unusual for a serous cystadenoma, which typically gives scant cellularity. The cells are variable sized and often have prominent nucleoli, features that are unusual for benign cystademonas. No glands or stroma are seen to support endometriosis. The solid cystoplasm (rather than granular) and lack of homogeneity argues against follicular cells (multiloculation is unusual for a follicular cyst unless in the setting of polycystic ovary disease). Differentiation from carcinoma is impossible based on cytologic grounds. However, given the radiographic impression and her age, a borderline tumor is favored. Histologic and Clinical Follow-up: Surgery was performed and revealed a serous borderline tumor. The majority of the histology was cystadenoma-like with several areas diagnostic of borderline tumor. Discussion: Ovarian cysts are visualized radiographically and an index of suspicion is calculated usually based on size, thickness of the cyst wall, solid components, number of loculations, and any other abdominal findings (such as abdominal implants or omental caking). For cysts that are thought to be benign in women of child bearing age, a watch and wait approach is often employed. A persistent cyst, slowly growing cyst or a cyst with a small solid component may prompt the clinician to sample the ovary. Some will aspirate a cyst for reassurance, particularly if thought to be benign. Other times, secondary to comorbidities, cyst aspirate may be done for malignant diagnosis confirmation. The differential of a cystic mass changes with age and the cytologist should be aware of these general age/ process distribution when assessing cyst aspirates. Differential diagnosis of Ovarian Masses <20 20-40 40-50 >50 Epithelial Cystadenoma x x o o Borderline o x o Carcinoma o x Germ Cell (malignant) x Teratoma x x x x Granulosa Cell Adult x x Juvenile x Fibroma o x Metastasis o x Functional Cysts x x o o - Occasionally x - Common Differential Diagnosis of Cystic Ovarian Masses in 20-40 year age range Functional cysts (most common) Corpus leuteum cyst, leuteoma of pregnancy, endometriosis, follicular cyst Neoplasms Serous/ mucinous cystadenoma, borderline tumors Teratoma Juvenile granulosa cell tumor (note: while these are often cystic, they almost always have a significant solid component, so the radiographic impression should lean towards neoplasm over functional cyst). As you can discern from this list, most of the time in this age group the differential diagnosis is between a functional cyst and a benign cystic neoplasm. Two important points should be highlighted. Serous Cystadenoma vs borderline tumor vs carcinoma Differentiating borderline tumor from well differentiated carcinoma is impossible, since the distinction relies on stromal invasion, a feature we can not detect cytologically (akin to follicular adenoma and carcinoma of the thyroid). However, this is probably not critical managerially anyway since both require surgical excision. Occasionally serous cystadenoma and borderline tumor may overlap cytologically. Serous cystadenomas are characterized by bland ciliated cells amidst numerous histiocytes. Occasional aggregates are seen but true papillae are rare. If the aspirate contains numerous papillae, a borderline tumor should remain in the differential. Mild to moderate cytologic atypia is not helpful, as long standing cysts can incite some atypia in the lining epithelium. Marked atypia is rare and should be noted with a cautionary note that a borderline tumor (or carcinoma) can not be excluded. This problematic distinction is echoed numerous times in the literature. Mucinous tumors In our experience, mucinous tumors that were aspirated were cystadenomas and radiographically benign cysts. If a cyst is aspirated that is over 10 cm and multiloculated, a diagnosis of mucinous cystic lesion is probably prudent. Endometriosis Endometriosis is a common aspirate. Luckily, these are usually suspected radiographically and the aspirate is done for diagnostic confirmation. It is not uncommon for endometriosis to have some mild to moderate atypia. However, when seen in a postmenopausal woman, caution should prevail as this is the age group most likely to develop endometrial carcinoma or clear cell carcinoma (and often in the setting of endometriosis). The final point is a cautionary one about the sensitivity and specificity of ovarian cyst aspirate. Many ovarian cyst aspirate studies are from a select population that does not reflect true clinical practice. Many are composed of intraoperative or bench aspirates from consecutive ovarian cysts. We can glean some information from these studies: It is extremely unusual to have a false positive diagnosis. [1, 2, 3, 4, 5] In this controlled manner of collection, differentiation of borderline from malignant neoplasms is challenging (see point #1 above) and benign epithelial cysts are often acellular. [1, 2, 5] Many benign cysts are acellular, therefore, radiographic correlation is paramount in assessing whether the cytology is sufficient. Some conclude that since most benign ovarian aspirates are acellular, it is a useless test, as the clinicians are left with a nondiagnostic result. Others ascertain that in the right clinical setting, an acellular aspirate is helpful in supporting the clinical suspicion of benign cyst as long as the clinician recognizes there is a remote chance that a malignancy was not sampled. The problem with 4c (above) is that many studies are not representative of the true clinical setting, making the significance (or lack of significance) of an acellular aspirate challenging. One study that reviewed 56 aspirates performed in real time on patients with a low risk of malignancy assessment radiographically, found that the majority of the aspirates (43) were devoid of epithelium. No malignancy was found in any case and no cases with subsequent cystectomy were malignant. [3] A prospective study on unilocular cysts with benign imaging characteristics also found no malignancies and 19/53 with no lining epithelium. [4] These studies and others support that malignancy in a unilocular cyst with benign radiographic findings is extremely rare. References (select): Ganjei P, Dickinson B, Harrison T, Nassiri M, Lu Y. Aspiration cytology of neoplastic and non-neoplastic ovarian cysts: is it accurate? Int J Gynecol Pathol. 1996 Apr;15(2):94-101. Martínez-Onsurbe P, Ruiz Villaespesa A, Sanz Anquela JM, Valenzuela Ruiz PL. Aspiration cytology of 147 adnexal cysts with histologic correlation. Acta Cytol. 2001 Nov-Dec;45(6):941-7. Monaghan H, Al-Nafussi A. Targeting the use of ovarian cyst aspirate cytology. J Clin Pathol. 2004 Nov;57(11):1232. Tahir Z, Yusuf NW, Ashraf M, Yusuf AW, Aziz F. Fine needle aspiration of unilocular ovarian cysts--a cytohistological correlation. J Pak Med Assoc. 2004 May;54(5):266-9. Wojcik EM, Selvaggi SM. Fine-needle aspiration cytology of cystic ovarian lesions. Diagn Cytopathol. 1994;11(1):9-14