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Dear Editor,

Although the role of fine needle aspiration (FNA) cytology is still under debate, its application in the precise diagnosis and management of selective ovarian malignancies is well emphasized. Most studies on the cytology of ovarian tumours deal with surface epithelial and germ cell tumours, with only a limited literature available on sex-cord stromal tumours. Granulosa cell tumour (GCT) is the most common sex-cord stromal tumour accounting for less than 3% of all ovarian tumours.[1] Clinically, an adult granulosa tumour (AGCT) is seen in postmenopausal women, whereas a juvenile granulosa tumour affects younger females. Although, histomorphology of GCT and its variants is well established, their cytodiagnosis can be challenging. Owing to the lack of a significant nuclear pleomorphism, an AGCT is often misdiagnosed or overlooked on cytology. We share our experience of an AGCT diagnosed pre-operatively on FNA and also discuss their close mimics.

A 65-year-old postmenopausal woman presented with abdominal pain of 3 months' duration. Abdominal ultrasound showed a solid and cystic right adnexal mass and moderate ascites. No omental deposits were detected. An ultrasound-guided FNA of the right adnexal mass was done: May-Grünwald Giemsa (MGG)- and Papanicolaou-stained smears were markedly cellular and revealed fairly monomorphic cells arranged in sheets, clusters and tissue fragments. Individual cells showed scanty to moderate cytoplasm, eccentrically placed, round to ovoid nuclei, uniformly distributed, granular chromatin and a single small and inconspicuous nucleolus (Figure 1). Minimal variation in nuclear size was attributable to mild degenerative change. Careful examination revealed rare rosettoid structures containing homogeneous, globular and eosinophilic material (Call-Exner bodies) while a few cells exhibited nuclear grooves (Figure 2) and mitotic activity. The tissue fragments showed arborizing vascular strands. Many cells, owing to an eccentrically placed nucleus, appeared plasmacytoid (Figure 1); none of them revealed cytoplasmic vacuoles. Rare clusters exhibited pseudo-stratification. A cytodiagnosis of an AGCT was given. After FNA diagnosis, a total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Gross examination of the surgical specimen showed a uniloculated right ovarian cystic mass, with solid areas, measuring 12 cm. Histopathological examination confirmed the cytodiagnosis. Histology of the endometrium revealed simple hyperplasia.

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Figure 1. Loosely cohesive monomorphic cells with round to oval nuclei, granular chromatin, inconspicuous nucleoli, scant to moderate amount of cytoplasm and a focal follicular pattern; many cells are plasmacytoid. The arrow shows a Call-Exner body (May-Grünwald Geimsa ×400).

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Figure 2. Call-Exner body showing central eosinophilic material and rossetoid arrangement of cells with pseudo-stratification; arrows and inset show nuclear grooves: May-Grünwald Geimsa ×400; inset ×1000).

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We have reported this case to emphasize that a definitive diagnosis of AGCT is possible solely on cytological examination of adequately sampled FNA material. The features that contributed to a cytodiagnosis of AGCT in our case are described and illustrated above. Rare nuclear grooves and occasional, but easily recognizable, Call-Exner bodies, are highly characteristic of AGCT. We also noted tissue fragments with prominent arborizing vessels; a finding which has been previously described by Lal et al.[2] A feature appreciated in our case, but not highlighted in any of the previous publications on AGCT, is the presence of cells with plasmacytoid morphology.

The differential diagnoses of AGCT include Brenner tumour, sex-cord stromal tumour with annular tubules (SCTAT), carcinoid and Sertoli-Leydig cell tumour. Nuclear grooves are described in Brenner tumour and in SCTAT. However, Brenner cells are larger than AGCT cells with a more abundant cytoplasm and the eosinophilic globules in the centre fuse giving a multilobated appearance.[3] The cells surrounding the Call-Exner bodies of AGCT are loosely cohesive, syncytial aggregates whereas those in the Brenner tumour are sheet-like strict aggregates.[4] SCTAT may show rosettes with or without a cellular central core composed of basement membrane material.[5] Rosettes in a carcinoid tumour are composed of cytoplasm and not the matrix material.5 Moreover, carcinoid cells lack nuclear grooves and show more cytoplasm than AGCT cells. Ovarian aspirates from younger women undergoing fertility treatment may mimic an AGCT as a result of heightened stimulation of the follicular cells. The younger age of a patient and a clinical history of treatment can avoid misdiagnosis in such situations. Moreover, an FNA is unlikely to be attempted in such cases.

Identification of AGCT on fluid cytology is more challenging, as it is difficult to appreciate nuclear grooves owing to tight clustering of AGCT cells in fluids. Failure to recognize them in peritoneal fluids may lead to under-staging of the tumour. However, Call-Exner bodies, if present, allow an easy diagnosis.[2] Both AGCT and mesothelial cells are immunopositive for calretinin, so its use may be misleading when the need for distinction between the two arises.

GCTs are usually indolent and more than 80% of cases present at stage 1. Rare cases are aggressive with early or late recurrence and metastasis. Increased mitotic activity, fewer Call-Exner bodies and nuclear atypia (pleomorphism, hyperchromasia and prominent nucleoli) indicate aggressiveness in AGCT.[6] A pathologist's comment on these features conveys the aggressive behaviour and chance of recurrence to the clinicians.

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