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Pathology – Research and Practice 202 (2006) 183–186

www.elsevier.de/prp

TEACHING CASE

Chemotherapy-induced alterations in ovarian sex cord tumor with annular

tubules (SCTAT): A diagnostic challenge

Mahmoud Khalifaa,�, Sharon Nofech-Mozesa, Mostafa Atrib, Allan Covensc

aDepartment of Pathology, Sunnybrook and Women’s College Health Sciences Center, 2075 Bayview Avenue, Room E-400,

Toronto, Ont., Canada M4N 3M5bDepartment of Medical Imaging, Sunnybrook and Women’s College Health Sciences Center, Toronto, Ont., Canada M4N 3M5cDivision of Gynecologic Oncology, Toronto-Sunnybrook Regional Cancer Center, Canada

Received 30 April 2003; accepted 15 December 2005

Abstract

We present a case of ovarian sex cord tumor with annular tubules (SCTAT) in a patient that received neoadjuvantchemotherapy with 3.5 years of follow-up. Neo-adjuvant chemotherapy is a common practice in advanced cases ofovarian carcinoma and is rarely applied in nonepithelial ovarian tumors. Chemotherapy-induced morphologicalterations of the subsequently resected tissue samples are well recognized; in this case, chemotherapy-inducedcytoarchitectural changes created diagnostic difficulties in the subsequently resected specimen.r 2006 Elsevier GmbH. All rights reserved.

Keywords: Ovarian sex cord tumor with annular tubules; Neoadjuvant chemotherapy

Introduction

Neo-adjuvant chemotherapy is a common treatmentin advanced cases of ovarian cancers. Chemotherapy-induced morphologic alterations of the subsequentlyresected tissue samples are well recognized and areknown to pose only minimal diagnostic difficulties in thecommon subtypes of ovarian neoplasms. We haveencountered an example of ovarian sex cord tumor withannular tubules (SCTAT), where chemotherapy-inducedcytoarchitectural changes created diagnostic difficultiesin the subsequently resected specimen.

e front matter r 2006 Elsevier GmbH. All rights reserved.

p.2005.12.004

ng author. Tel.: +1416 480 4987;

4271.

ss: Mahmoud.khalifa@sw.ca (M. Khalifa).

Case report

The patient was a 43-year-old nulliparous whopresented to her family doctor with vaginal bleedingand a 1-month history of generalized abdominal pain,bloating, and weight gain. The patient also reported along history of irregular periods and that she had notreceived any hormonal treatment for the previous 5years. She denied any problems with her bowel move-ments, and there was no family history of cancer. Anultrasonogram showed a 20-cm left adnexal mass andmoderate ascites. This was confirmed by a CT scan,which also showed the mass to be septated andsuggested intra-abdominal wall nodularities consistentwith ‘‘carcinomatosis’’.

The patient was referred to our cancer center forfurther management. Abdominal exam revealed amoderate amount of ascites, which made it difficult to

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Fig. 2. Complex annular tubules encircling hyaline material.

Note the unusual stromal separation. Tumor necrosis is not

shown in this photomicrograph (H&E � 400).

M. Khalifa et al. / Pathology – Research and Practice 202 (2006) 183–186184

delineate the pelvic mass. Recto-vaginal exam wasunremarkable. An endometrial biopsy was performedand revealed decidualized stroma with atrophic glandsconsistent with progesterone effect. Abdominal paracent-esis was performed, and the cytopathologic examinationof the ascitic fluid was negative for malignant cells. HerCA-125 was 1746, and the barium enema was negative.

Based on the CT scan findings, recurrent ascites andelevated CA-125, the pelvic mass was believed to be anepithelial ovarian cancer, and chemotherapy wasplanned to be followed by laparotomy. Following twocycles of carboplatin and paclitaxel, the patient reporteda significant subjective response to treatment, and herCA-125 dropped to 881. Due to an allergic reaction topaclitaxel, the patient was given a third course of single-agent carboplain followed 5 weeks later by debulkingsurgery consisting of total abdominal hysterectomy,bilateral salpingo-oophorectomy, and omentectomy.The uterus and right ovary appeared normal and, apartfrom large volume ascites, no gross tumor was evident atsurgery outside of the left ovarian mass. In retrospect,the abdominal CT scan was overcalled, probably due tothe misinterpretation of collapsed bowel as peritonealnodules. The CT was not reviewed prior to surgery.

The left ovarian mass was an intact 19.0� 15.5�8.0 cm, 1137 g multiloculated tumor with external sur-face fibrous adhesions. The cut surface featured multiplecystic spaces separated by thin septa and containinggray–yellow serous fluid, ranging from 0.1 to 1.4 cm indiameter (Fig. 1). The right ovary was 3.0 cm in greatestdimension, and the rest of the specimen was withinnormal limits.

On microscopic examination, more than 90% of thetumor was necrotic. Residual viable areas featured thecharacteristic complex communicating tubules encir-cling multiple hyalinized basement membrane-like eosi-nophilic material. Nests of neoplastic cells were

Fig. 1. The sectioned surface of the tumor displays multi-

loculated cystic neoplasm with thin septa.

surrounded by degenerated edematous stroma withspaces of artifactual separation. Neoplastic cells fea-tured abundant, occasionally vacuolated cytoplasm.Nuclei were mostly pyknotic (Fig. 2). Although themajority of the residual viable neoplastic tissue showed atypical SCTAT pattern, rare areas exhibited granulosacell differentiation. The tumor was inhibin-positive, andEMA- and cytokeratin-negative. The endometriumfeatured a normal proliferative phase pattern withoutdecidualization. The other ovary was normal. There wasno evidence of cervical neoplasia.

This was a diagnostically challenging case, primarilydue to the neoadjuvant, chemotherapy-induced changesdiscussed above. The unusual morphology warrantedthe examination of multiple sections and the inclusion ofa long list of other neoplasms in the differentialdiagnosis. Epithelial ovarian tumors, adenoid cysticcarcinoma, carcinoid, strumal carcinoid, and other sexcord tumors, such as granulosa cell tumor, all needed tobe considered in the differential diagnosis.

More recently, 29 months following her initialdebulking surgery, the patient presented abdominalrecurrence. She was treated by chemotherapy followedby surgery to release a small bowel obstruction. A2.5� 2.0� 0.8 cm irregular, bosselated yellow/tan pelvictumor was resected. Pathological evaluation of the masswas consistent with recurrent SCTAT. Ten monthsfollowing her second operation, the patient continues tobe stable with residual disease.

Discussion

SCTAT is a rare ovarian neoplasm which can be seenin two distinct clinical settings. The tumor was firstdescribed in patients with Peutz-Jeghers syndrome,

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where it is usually small, bilateral, and can be associatedwith endocervical neoplasia [2,9,10,12,15]. On the otherhand, sporadic cases are typically unilateral and mayattain relatively large sizes. The optimal therapy for sexcord/stromal tumors is unclear due to their rarity andtendency to remain localized at presentation [13,15].Chemotherapy is usually given at recurrence, rarely inan adjuvant setting.

Neo-adjuvant chemotherapy is typically used inadvanced epithelial ovarian cancer to reduce tumorvolume and to permit less aggressive debulking surgery.Appropriate candidates are patients who exhibit ex-cessive surgical risks from concomitant morbidity, poornutritional status, or are those with clearly unresectabledisease. In these settings, the available data suggest thatthe outcome is at least comparable to initial surgicalcytoreduction followed by adjuvant chemotherapy[1,4,7,11,14]. Platinum, taxanes, and anthracyclins arethe most commonly used agents. There is limited dataregarding the possible benefit of neoadjuvant che-motherapy in the management of non-epithelial ovariantumors [3,6], and its role in sex cord stromal tumors iseven less evident. Had this patient been suspected ofharboring a non-epithelial neoplasm, it is doubtful shewould have received neo-adjuvant chemotherapy.

Therefore, the current case is unique as it offers anopportunity to study the tumor’s morphology and itshormonal effects in its post-chemotherapy state. Tumornecrosis, stromal separation, and the predominance ofpyknotic nuclei are not typical features of the conven-tional examples of SCTAT. However, in its post-chemotherapy state, the current tumor exhibited thesefindings, thus presenting a diagnostic challenge. Themorphological effects of chemotherapy on epithelialovarian malignancies were described in detail [8]. Theseinclude architectural and cytological alterations in theneoplastic cells and adjacent stroma. Sections from post-chemotherapy specimens often reveal the presence ofsmall groups or single cells in fibrotic stroma associatedwith inflammation, foamy histiocytes, cholesterol clefts,hemosiderin deposits, dystrophic calcifications, includ-ing formation of psammoma bodies and fat necrosis.Neoplastic cells may include bizarre enlargement of thenuclei with hyperchromasia. Cytoplasmic changes arecharacterized by intense eosinophilia, vacuolation, orfoam cell changes. Administration of neoadjuvantchemotherapy may result in no residual disease or inextreme changes that limit the accuracy of typing andgrading of the original tumor [8]. It is noteworthy that inthe case presented here, the neoplastic cells did notexhibit the darkly stained, large, bizarre nuclei orabundant foamy cytoplasm commonly encountered inpost-chemotherapy epithelial tumors. Still, this tumorneeded to be distinguished from the other ovarianneoplasms included in the differential diagnosis listmentioned earlier. Its inhibin immunopositivity and its

negative reaction with any EMA and cytokeratinantibodies ruled out the possibilities of epithelial tumorsand adenoid cystic carcinoma. Its cytoarchitecturalfeatures also helped distinguish it from carcinoid andgranulosa cell tumors. The prevailing pattern was thatof complex communicating tubules encircling brighthyaline basement membrane-like eosinophilic materialrather than the characteristic microfollicular pattern ofgranulosa cell tumors where nuclei with longitudinalnuclear grooves exhibit a rosette-like arrangementaround faintly eosinophilic material.

In patients with SCTAT, endometrial glandularatrophy with stromal decidualization is a commonlyassociated finding indicative of the tumor’s ability tosecrete progesterone [13]. The pre-chemotherapy endo-metrial biopsy in this case, at the time when she was notreceiving hormonal therapy, showed a progesteroneeffect, while the post-chemotherapy endometrium in thehysterectomy specimen was proliferative. The noteddifference in the endometrial pattern could be attributedto the extensive tumor necrosis induced by chemother-apy, leading to a drop in serum progesterone levels. Thisis analogous to the described post-chemotherapy drop inserum estradiol levels in patients with advancedgranulosa cell tumors [5]. This functional observationcould reduce the diagnostic value of the often-describedendometrial progesterone pattern concomitantlyseen with SCTAT when a case is investigated in apost-chemotherapy setting.

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