Müllerian adenosarcomas are tumours of low malignant potential with proliferation of benign glands and low grade endometrial stromal sarcoma (LGESS). Unusually, the latter may include foci of uterine tumours resembling ovarian sex-cord tumours (UTROSCT). Two cases of uterine adenosarcomas massively overgrown by UTROSCT are reported, for the first time. The patients, aged 71 and 64, one receiving tamoxifen, presented with intracavitary polypoid adenosarcomas; each was overgrown by an immunopathologically characteristic UTROSCT that constituted more than 75% of its volume. Periglandular CD10+LGESS represented less than 25%. Both are alive and well after 5 and 3 years, respectively. Compared to the poor prognosis of adenosarcomas overgrown by high grade sarcomata, the cases reported here had a benign behaviour. Quantitative assessment of volume percentage of the potentially aggressive LGESS, CD10+ areas should be considered as a relevant prognostic histological parameter in these tumours.
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Müllerian adenosarcomas are mixed uterine and ovarian tumours of low malignant potential, usually consisting of a proliferation of benign glands and a low grade endometrial stromal sarcoma (LGESS),1 which may be occasionally overgrown by various types of aggressive, high grade sarcomas.2 ,3 ,4 Unusual stromal differentiations can include foci of sex-cord-like areas similar to the rare, benign uterine tumours resembling ovarian sex-cord tumours (UTROSCT).5 ,6
We report, for the first time, two cases of adenosarcoma of the uterus, one of them occurring in a patient treated with tamoxifen, which had undergone a massive stromal overgrowth by UTROSCT and were associated with a benign clinical course.
Patients were aged 71 and 64 years and both presented with abnormal vaginal bleeding. Ultrasound showed in both cases large intracavitary polypoid masses. The second patient had previously been diagnosed with an infiltrating ductal mammary carcinoma; she was treated with mastectomy followed by adjuvant chemotherapy. She also received tamoxifen, 20 mg daily, for 4 years. Total hysterectomy with bilateral salpingo-oophorectomy was performed in each patient; no further treatment was indicated. Both patients are alive and well 5 and 3 years, respectively, after surgery.
Macroscopy revealed polypoid intracavitary tumours measuring 2.5 and 8 cm, respectively, that obliterated the uterine cavity. On cut section they had a soft, gelatinous tissue, yellow to tan in colour, that was arranged in grape-like lobules stippled with numerous small cystic formations (fig 1). In both cases, their limits with the normal myometrium were well delineated without any invasive features.
Eight and 17 tissue blocks, respectively, were available for microscopy, which showed tumours composed of an admixture of epithelial and mesenchymal components. The former consisted of cystically dilated tubular glands (fig 2A), that often showed intraglandular, folliaceous, blunt papillary projections (fig 2B) which were lined by a benign, regular endometrial epithelium that presented frequent areas of mucinous, squamous, eosinophilic and tubal metaplasia. The bulk of the tumour corresponded to an UTROSCT that replaced the stroma and occupied more than 75% of the tumour volume and was arranged in sheets (fig 3A), cords or tubules (fig 3B), often positive for CAM 5.2. There were also abundant nests of bland polygonal cells with a CD56, α-inhibin (fig 4A) and calretinin positive eosinophilic or foamy cytoplasm that resembled ovarian luteinised cells. These cells, additionally, showed focal, inconstant positivity for androgen and progestogen receptors and α-actin. Other myoid markers such as desmin, calponin and h-caldesmon were negative.
Glands were surrounded by thin cuffs of an endometrial stromal condensation of LGESS type that had mild pleomorphism and infrequent mitoses (1 per 10 high power fields) and represented less than 25% of the total tumour volume. These periglandular areas were highlighted at low microscopic power by strong positivity to CD10 (fig 4B), which contrasted with the CD10 negative bulk of the neoplasm.
Müllerian adenosarcomas usually have LGESS as their mesenchymal component. However, in a subset of cases, the stroma becomes overgrown by various types of high grade sarcomata such as fibrosarcoma,2 rhabdomyosarcoma, leiomyosarcoma, angiosarcoma3 ,4 and undifferentiated sarcoma. These cases are associated with a substantially poorer prognosis than usual adenosarcoma.
Areas resembling ovarian sex-cord elements (UTROSCT) have been reported in one cervical5 and eight endometrial adenosarcomas.6 However, minor sex-cord-like elements can be found in adenosarcomas, this component occurring as a differentiation from their sarcomatous endometrial stromal component. In three quarters of the reported cases, UTROSCT areas usually representing less than 25% of the tumour’s volume, ranging from minor foci comprising less than 5% of the tumour to a mass of 40% of the tumour, attaining 50% in only two instances. In contrast, our cases are exceptional since they comprise over 75% of the bulk of the neoplasm, thus representing a yet unreported overgrowth of this usually benign component.
Clinicopathologically, all the nine previously reported cases of adenosarcoma with UTROSCT elements behaved in a benign fashion, with the exception of one tumour in an 85-year-old patient which presented only a small component of sex-cord elements and which recurred, presumably, as an LGESS. When assessing the malignant potential of the different areas present in our tumours, we believe that the predominant ones corresponding to a luteinised UTROSCT component have a negligible malignant potential compared with the minor component of LGESS, present only in the periglandular cuffs. This LGESS component represented in our cases less than 20% of tumour volume and was clearly identifiable both by its histology, periglandular topography and a characteristic CD10 positivity, which facilitated assessment of the relative amounts of each component at low microscopic power. Thus, we believe that the volume percentage of CD10 positive, potentially aggressive, LGESS areas should be considered as the main prognostic histological parameter in these tumours.
From the viewpoint of tumour pathogenesis, the massive UTROSCT component present in our cases should not be considered a phenomenon of dedifferentiation as it occurs in adenosarcomas with sarcomatous overgrowth, but rather as a benign, secondary differentiation associated to the LGESS component of adenosarcoma. Our cases had a benign behaviour since they had only surgery and both are alive and well after 5 and 3 years, respectively.
Immunohistochemically, the UTROSCT component had a characteristic ovarian sex-cord tumour phenotype with concurrent positivity of markers such as α-inhibin, calretinin and CD56. This immunophenotype is absent in cases of pure adenosarcoma and indeed, a recent comprehensive immunohistochemical study of 35 cases only revealed focal α-inhibin positivity in one case.2
The association of long term administration of tamoxifen and various types of hormonal therapy, including hormonal contraception9 with both adenosarcomas of usual type7 and those with sarcomatous overgrowth8 is well known, implying that prolonged hyperoestrinism may be related to its pathogenesis, although this may be coincidental. However, no cases of adenosarcomas with UTROSCT elements similar to our case 2 have been previously reported in association with long term tamoxifen treatment.
Uterine adenosarcomas can be extensively overgrown by sex-cord-like tumours that develop from their low grade stromal sarcoma component.
The overgrowth by sex-cord-like tumour has a morphology and immunohistochemistry similar to ovarian sex-cord neoplasms.
Sex-cord-like tumours usually behave in a benign fashion.
Since low grade stromal sarcoma may behave aggressively, quantitative assessment of CD10 positive areas may represent a prognostic histological parameter in these tumours.
Competing interests None.
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