868 J Clin Pathol 1998;51:868–871 Malignant fibrothecomatous tumour of the ovary: J Clin Pathol: first published as 10.1136/jcp.51.11.868 on 1 November 1998. Downloaded from diagnostic value of anti-inhibin immunostaining W G McCluggage, J M Sloan, D D Boyle, P G Toner Abstract ultrasound scan, which also revealed free fluid Malignant ovarian tumours of the fibro- in the pelvic cavity. Serum CA-125 was mark- thecoma group are rare. The clinico- edly raised at 196 U/ml. A presumptive pathological features of a case of ovarian diagnosis of ovarian cancer was made. At malignant fibrothecoma in which there laparotomy, tumour masses were present in the was metastatic disease in the small intes- right ovary and in the terminal ileum. There tine and peritoneum at presentation are were also multiple tumour nodules throughout described. A number of diVerential diag- the abdominal peritoneum. The clinical im- noses were considered but positive immu- pression was of a primary lesion in the right nohistochemical staining of the resected ovary, with small intestinal and peritoneal ovarian and small intestinal neoplasms metastases. Total abdominal hysterectomy and with anti-inhibin was of value in confirm- bilateral salpingo-oophorectomy was per- ing a sex cord–stromal tumour and in formed, together with resection of a length of excluding other lesions. The two tumours terminal ileum. The postoperative period was were also ultrastructurally identical. Clas- unremarkable and the patient is currently sical malignant fibrothecomas are said to undergoing chemotherapy. show four or more mitotic figures per 10 high power fields (HPF). Although the intestinal secondary was mitotically ac- tive, the primary ovarian tumour con- tained only one to two mitoses per 10 HPF, Methods showing that formal mitotic counts are The surgical specimen was fixed in formalin not an absolute indicator of malignant and sections for histological examination were behaviour in this group of tumours. routinely processed in paraYn wax and stained (J Clin Pathol 1998;51:868–871) with haematoxylin and eosin. Reticulin and oil-red O stains were performed on representa- Keywords: ovarian tumour; fibrothecoma; inhibin; tive sections of the ovarian and small intestinal immunohistochemistry tumours. A formal mitotic count was carried out on all histological sections of the ovarian http://jcp.bmj.com/ and small intestinal neoplasms. This was done Malignant ovarian tumours of the fibro- 1–4 by counting the number of mitotic figures in 50 thecoma group are exceedingly rare. They are generally classified as fibrosarcomas and high power fields (HPF) and calculating the there is doubt as to whether a true malignant average per 10 HPF. form of thecoma exists. The main histological Immunohistochemistry was performed feature said to be of importance in distinguish- using a standard streptavidin biotin–peroxidase method (Dako). Sections were stained with the ing a cellular fibrothecoma from fibrosarcoma on September 28, 2021 by guest. Protected copyright. is the degree of mitotic activity in the primary following monoclonal antibodies: inhibin (Se- tumour.2 In this report we describe an ovarian rotec), vimentin (Dako), CAM 5.2 (Becton fibrothecomatous tumour with metastatic dis- Dickinson), CA-125 (CIS Biointernational), ease in the small intestine and peritoneum. desmin (Dako), S-100 protein (Diagnostic Royal Group of Products), and á smooth muscle actin (Sigma). Hospitals Trust, Both the primary ovarian neoplasm and the Belfast, UK: intestinal metastasis were histologically and The anti-inhibin antibody is a mouse mono- Department of ultrastructurally indistinguishable from a cellu- clonal antibody against the á subunit of human Pathology lar fibrothecoma. There were only scattered inhibin. Immunohistochemistry was per- W G McCluggage mitotic figures in the ovarian lesion, although formed using appropriate positive and negative J M Sloan the intestinal secondary was more mitotically controls. For anti-inhibin staining, positive P G Toner active. A number of diVerential diagnoses were controls comprised ovaries containing follicu- Department of considered. Positive immunohistochemical lar cysts or corpora lutea. For negative controls, Obstetrics and staining of both lesions with anti-inhibin the primary antiserum was replaced by mouse Gynaecology assisted in classifying the neoplasm as a malig- immunoglobulin (IgG, Dako) at a comparable DDBoyle nant ovarian sex cord–stromal tumour. protein concentration. For comparison, three Correspondence to: cases each of leiomyosarcoma and gastro- Dr W G McCluggage, Case report intestinal stromal tumour were also stained Department of Pathology, with anti-inhibin. Royal Group of Hospitals A 61 year old postmenopausal woman pre- Trust, Grosvenor Road, sented with a three month history of general Representative pieces of formalin fixed tissue Belfast BT12 6BL, Northern malaise and melaena. Rectal examination sug- from both the ovarian and small intestinal Ireland, UK. gested a pelvic mass and she was referred to a tumours were processed for examination by Accepted for publication gynaecologist. The presence of a large mass electron microscopy. Ultrathin sections were 23 June 1998 filling the pelvis was confirmed by transvaginal stained with uranyl acetate and lead citrate. Anti-inhibin immunostaining in ovarian tumour 869 showed a cellular lesion. Tumour cell nuclei J Clin Pathol: first published as 10.1136/jcp.51.11.868 on 1 November 1998. Downloaded from were ovoid to spindle shaped and contained evenly dispersed chromatin (fig 1A). Neither nuclear grooves nor Call-Exner bodies were identified and there was little nuclear pleomor- phism. Numerous hyalinised plaques were present and there were areas of oedema. There was no haemorrhage or necrosis. Scattered mitotic figures were identified (fig 1B), a formal mitotic count revealing one to two per 10 HPF. The reticulin stain revealed a pericel- lular arrangement of fibres and numerous cytoplasmic lipid droplets were seen with the oil-red O stain. The histological features were in keeping with a cellular fibrothecoma. Histological examination of the left ovary showed a few microscopic foci of tumour, similar to that in the right ovary, on the exter- nal surface. In areas, tumour cells had abundant eosinophilic cytoplasm, in keeping with luteinisation. Given their multifocality and location on the external surface, these were presumed to represent metastatic disease rather than independent primary tumours. The fallopian tubes were unremarkable. The en- dometrium showed definite proliferative activ- ity with nuclear stratification and mitotic activ- ity. However, there was no hyperplasia or malignancy. The presence of two benign intra- mural fibroids was confirmed. No microscopic abnormality was identified within the cervix. Histological examination of multiple sec- tions from the tumour in the small intestine confirmed that it was mainly located on the serosal surface, but also invaded the muscularis propria and submucosa and focally ulcerated the mucosa (fig 1C). There were areas of haemorrhage and necrosis. Tumour cell nuclei were similar to those in the right ovarian http://jcp.bmj.com/ neoplasm, but focally there was a much higher mitotic rate, a formal mitotic count revealing areas in which there were 12–15 mitoses per 10 HPF. Several microscopic foci of metastatic tumour were identified adjacent to the main secondary tumour mass. Figure 1 (A) Ovarian tumour showing a cellular spindle IMMUNOHISTOCHEMICAL FINDINGS on September 28, 2021 by guest. Protected copyright. cell lesion with hyalinised plaques. (B) Higher power of The immunophenotypes of the right ovarian ovarian tumour. An occasional mitotic figure (arrow) is and small intestinal neoplasms were identical. present. (C) Metastatic lesion in small intestine. Tumour is situated under the mucosal surface. There was positive cytoplasmic staining with anti-inhibin (fig 2) and vimentin, but no stain- Results ing with the other antibodies employed. The PATHOLOGICAL FINDINGS three leiomyosarcomas and the three gastro- The surgical specimen consisted of a uterus intestinal stromal tumours were all negative and cervix with attached ovaries and fallopian with anti-inhibin. tubes. An 8 cm length of small intestine was also received. The right ovary was replaced by ELECTRONMICROSCOPY a solid, yellow coloured tumour which weighed Ultrastructural examination of the ovarian and 80 g and measured 7 cm in maximum small intestinal tumours showed identical diameter. The left ovary weighed6gand features. Tumour cells contained ovoid to spin- measured 3 cm in maximum diameter. It was dle shaped nuclei and a moderate amount of grossly unremarkable. The uterus contained cytoplasm. Lipid droplets, both intracellular two intramural fibroids, both measuring 1 cm and extracellular, were easily identified. Poorly in maximum diameter. A 9 cm diameter formed adhesion specialisations were present partially necrotic tumour was present in the between adjacent cells. A discontinuous exter- small intestine. This was mainly located on the nal lamina appeared at the cell surface in some serosal surface, but infiltrated the wall and areas and there were scattered collagen fibrils focally ulcerated the mucosa. in the interstitium. There was no ultrastruc- Histological examination of multiple sec- tural evidence of smooth muscle or neural dif- tions from the tumour in the right ovary ferentiation. 870 McCluggage, Sloan, Boyle, et al designated cellular fibroma, and a malignant J Clin Pathol: first published as 10.1136/jcp.51.11.868
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