This leader reviews recent advances in immunohistochemistry that are useful in the diagnosis of ovarian neoplasms. These include the value of different anticytokeratin antibodies in the distinction ...between a primary ovarian adenocarcinoma and a metastatic adenocarcinoma, especially of colorectal origin. These antibodies have also helped to clarify the origin of the peritoneal disease in most cases of pseudomyxoma peritonei. The value of antibodies against so called tumour specific antigens, such as CA125 and HAM56, in determining the ovarian origin of an adenocarcinoma is also reviewed. In recent years, several studies have investigated the value of a variety of monoclonal antibodies in the diagnosis of ovarian sex cord stromal tumours and in the distinction between these neoplasms and their histological mimics. These antibodies include those directed against inhibin, CD99, Mullerian inhibiting substance, relaxin like factor, melan A, and calretinin. Of these, anti-α inhibin appears to be of most diagnostic value. It is stressed that these antibodies should always be used as part of a larger panel and not in isolation.J Clin Pathol(J Clin Pathol 2000;53:327–334)
The incidence of malignant and premalignant endocervical glandular lesions is increasing. This review covers controversial and difficult aspects regarding the categorisation and diagnosis of these ...lesions. The terminology of premalignant endocervical glandular lesions is discussed because of the differences between the UK terminology and the widely used World Health Organisation classification. The morphology and histological subtypes of premalignant endocervical glandular lesions are described. Early invasive adenocarcinoma and difficulties in the diagnosis and recognition of this entity are covered, as is the measurement of early invasion within cervical adenocarcinoma. Several benign endocervical glandular lesions can mimic malignant and premalignant endocervical glandular lesions, and the distinction of these benign mimics from premalignant and malignant lesions using ancillary immunohistochemical studies is also covered. Antibodies used to distinguish between endometrial and endocervical adenocarcinoma, in the diagnosis of cervical minimal deviation adenocarcinoma of mucinous type (adenoma malignum), and in the diagnosis of cervical mesonephric lesions are also reviewed.
Immunohistochemical staining for calretinin is useful in the diagnosis of ovarian sex cord–stromal tumours
Aims: Ovarian sex cord–stromal tumours are a heterogeneous group of neoplasms which may be ...confused morphologically with a wide variety of tumours. Calretinin positivity has previously been demonstrated in a small number of ovarian sex cord–stromal tumours. The aim of this study was to investigate calretinin staining in a series of these tumours and their histological mimics in order to determine the value of calretinin staining in a diagnostic setting.
Methods and results: Seventy‐two neoplasms, including 37 ovarian sex cord–stromal tumours and 35 miscellaneous neoplasms which may enter into the differential diagnosis, were stained with a commercially available polyclonal antibody against calretinin. All sex cord–stromal tumours exhibited positivity except for a single fibrothecoma. In this group of tumours staining was generally diffuse and strong. Small numbers of the miscellaneous group of neoplasms exhibited positivity but this tended to be focal and weak, although this was not always the case. There was consistent strong positive staining of granulosa cells in follicular cysts and corpora lutea. There was also positive staining of luteinized stromal cells in two cases of ovarian stromal hyperplasia and hyperthecosis.
Conclusions: Calretinin is a sensitive immunohistochemical marker of ovarian sex cord–stromal tumours and may be useful in a diagnostic setting. However, the value is somewhat limited since occasional neoplasms which enter into the morphological differential diagnosis may be positive. Be that as it may, calretinin positivity may be of value in the diagnosis of an ovarian sex cord–stromal tumour and its differentiation from other neoplasms. In this regard, calretinin should always be used as part of a larger panel.
Aims: Preinvasive endocervical glandular lesions, termed cervical glandular intraepithelial neoplasia, are increasing in incidence. The distinction of cervical glandular intraepithelial neoplasia ...from benign mimics, especially tubo‐endometrial metaplasia, endometriosis and microglandular hyperplasia, can be difficult. This study investigates the value of immunohistochemical staining with MIB1, bcl2 and p16 in the distinction of cervical glandular intraepithelial neoplasia from these benign mimics.
Methods and results: Immunohistochemical staining using the monoclonal antibodies MIB1, bcl2 and p16 was performed on cases of cervical glandular intraepithelial neoplasia (n=21), tubo‐endometrial metaplasia (n=13), endometriosis (n=7) and microglandular hyperplasia (n=14). With tubo‐endometrial metaplasia and microglandular hyperplasia staining with MIB1 was either negative or involved <10% of cells, while with cervical glandular intraepithelial neoplasia the majority of cases (86%) exhibited >10% positive cells. Two cases of endometriosis exhibited a MIB1 index of 10–30% while in the other cases <10% cells stained. With bcl2 the cells of microglandular hyperplasia were negative although there was staining of associated reserve cells in 43% of cases. All cases of tubo‐endometrial metaplasia except one and all cases of endometriosis stained diffusely positive with bcl2. Cases of cervical glandular intraepithelial neoplasia were negative or exhibited focal staining. With p16 all cases of cervical glandular intraepithelial neoplasia exhibited diffuse strong positivity, generally involving 100% of cells, while all cases of microglandular hyperplasia were negative. Sixty‐two percent of cases of tubo‐endometrial metaplasia showed focal positivity, the remainder being negative. Cases of tubo‐endometrial metaplasia were never diffusely positive with p16. In three cases of endometriosis there was staining of >50% of cells while the other cases were either focally positive or negative.
Conclusions: A panel of antibodies, comprising MIB1, bcl2 and p16, is a useful adjunct to histology in distinguishing cervical glandular intraepithelial neoplasia from tubo‐endometrial metaplasia, endometriosis and microglandular hyperplasia. Cases of cervical glandular intraepithelial neoplasia are diffusely positive for p16 and generally exhibit a high proliferation index with MIB1, while bcl2 is negative or, at most, focally positive. Tubo‐endometrial metaplasia and endometriosis are characterized by strong diffuse positivity with bcl2 and a low proliferation index with MIB1 (although occasional cases of endometriosis show moderate proliferative activity). p16 is negative or exhibits focal positivity in tubo‐endometrial metaplasia but in endometriosis there may be quite widespread positivity. Microglandular hyperplasia shows a low proliferation index with MIB1 and is negative for bcl2 and p16.
Recent years have seen the publication of many articles investigating the value of antibodies against inhibin in diagnostic surgical pathology. This review concentrates on the uses of inhibin ...staining in gynecological pathology. alpha-inhibin is diagnostically the most useful antibody and is a sensitive immunohistochemical marker of most ovarian sex cord-stromal tumors and, as such, is of value in the diagnosis of this heterogeneous group of neoplasms that can be confused morphologically with a wide range of other tumors. Because the antibody is not entirely specific for ovarian sex cord-stromal tumors, it should always be used as part of a larger panel. alpha-inhibin staining may also be of value in confirming late recurrence or metastasis of an ovarian sex cord-stromal tumor, especially a granulosa cell tumor. Sex cord-like elements within uterine tumors resembling ovarian sex cord tumors are also commonly immunoreactive with alpha-inhibin, perhaps indicating true sex cord differentiation. alpha-inhibin staining may also be of value in cytological preparations in confirming a functional cyst and excluding a cyst or cystadenoma of epithelial origin. Syncytiotrophoblastic cells are also immunoreactive, as are most trophoblastic tumors. Thus, positive staining may be of value in confirming an intrauterine gestation or in the diagnosis of a trophoblastic neoplasm. Another gynecological neoplasm that is commonly positive with alpha-inhibin is the so-called female adnexal tumor of probable wolffian origin, and, therefore, the antibody is of no value in the distinction of this neoplasm from a sex cord-stromal tumor, tumors that are often in the differential diagnosis.
Aims: In the female genital tract CD10 has been used to assist in the evaluation of mesenchymal tumours of the uterus and in determining whether endometrial stroma is present. CD10 positivity has ...also been shown in cervical mesonephric remnants and this antibody has been suggested as a useful immunohistochemical marker of mesonephric lesions in the female genital tract. Calretinin has also been shown to be positive in mesonephric lesions. In this study the specificity of these two antibodies in evaluating cervical and uterine glandular lesions and the value of CD10 in determining whether stroma is endometriotic or not were investigated.
Methods and results: Cases of cervical tubo‐endometrial metaplasia (TEM) (n = 11), microglandular hyperplasia (MGH) (n = 10), endometriosis (n = 8), mesonephric remnants/hyperplasia (n = 12), endocervical adenocarcinoma, usual type (n = 15), mucinous variant of minimal deviation adenocarcinoma (MDA) (n = 7) and mesonephric adenocarcinoma (n = 3) were stained with antibodies against CD10 and calretinin. Nine cases of endometrial adenocarcinoma of endometrioid type were also stained. In all the cervical cases normal endocervical glands were negative with both antibodies except for one case with strong positive luminal staining with CD10. All cases of TEM, MGH and endometriosis were negative with CD10 and calretinin except for focal staining with CD10 in one case each of MGH (cytoplasmic staining) and endometriosis (luminal staining). Most usual endocervical adenocarcinomas were negative with both antibodies, although one exhibited focal cytoplasmic staining with calretinin and five exhibited limited luminal positivity with CD10. All MDAs were negative with both antibodies. Ten of 12 mesonephric remnants/hyperplasia showed luminal positivity with CD10 and one exhibited cytoplasmic and nuclear staining with calretinin. Two of three mesonephric adenocarcinomas showed luminal positivity with CD10 and nuclear and cytoplasmic positivity with calretinin. Seven of nine endometrial adenocarcinomas were positive with CD10 (four cytoplasmic, two membranous and cytoplasmic, one luminal and cytoplasmic) and three with calretinin (two cytoplasmic, one nuclear and cytoplasmic). Positive staining of endometriotic stroma with CD10 was present in all endometriosis cases but normal cervical stroma was also strongly positive, especially around glands. Endometriotic stroma and cervical stroma were negative with calretinin.
Conclusions: We conclude that most endocervical glandular lesions, including mesonephric remnants/ hyperplasia, are negative with calretinin. However, the focal nuclear and cytoplasmic positivity with calretinin in two of three mesonephric adenocarcinomas suggests that this may be a useful indicator of a mesonephric origin of a cervical adenocarcinoma. Most mesonephric remnants/hyperplasias exhibit luminal positivity with CD10, although this is not invariable and staining is usually focal. Positive luminal staining of a benign endocervical glandular lesion with CD10 may help confirm mesonephric remnants. Although positive staining with CD10 was found in two of three mesonephric adenocarcinomas, the observed immunoreactivity of several conventional cervical adenocarcinomas limits the diagnostic value of CD10 in confirming a mesonephric origin for an adenocarcinoma. Since all cervical MDAs were negative with CD10, positivity with this antibody may be of value in distinguishing mesonephric hyperplasia from MDA, although this distinction rarely necessitates immunohistochemistry. Most endometrial adenocarcinomas of endometrioid type stain with CD10 and thus positivity with this antibody is not specific for a mesonephric origin of an endometrial adenocarcinoma. Positivity of normal cervical stroma limits the value of CD10 staining in confirming a diagnosis of cervical endometriosis.
Aims—Aggressive angiomyxoma of pelvic parts is a distinctive soft tissue tumour that chiefly involves the vulvar and perineal region of female patients. Several previous reports have demonstrated ...oestrogen receptor (ER) and/or progesterone receptor (PR) positivity in this neoplasm. The aim of this study was to confirm whether ER and/or PR positivity is present in aggressive angiomyxoma. We also wished to ascertain whether positivity may be found in the stromal cells of normal vulval skin and in other lesions at this site that can cause diagnostic confusion with aggressive angiomyxoma. Methods—Five aggressive angiomyxomas in female patients and one involving male pelvic soft parts were stained immunohistochemically with antibodies against ER and PR. Other samples studied were normal vulval skin (n = 7), fibroepithelial polyps of vulva (n = 7), vulval smooth muscle neoplasms (n = 5), vulval nerve sheath tumours (n = 2), vaginal angiomyofibroblastoma (n = 1), and pelvic myxoma (n = 1). Nuclear staining was classified as negative, weak, moderate, or strong and the proportion of positively staining cells was categorised as 0, < 10%, 10–50%, or > 50%. Results—All five cases of aggressive angiomyxoma in female patients were positive for ER (two with weak intensity involving < 10% of cells and three with moderate intensity involving 10–50% of cells) and four of five cases were strongly positive for PR in > 50% of cells. The other case was negative for PR. There was no staining with antibodies to ER or PR in the single male patient with aggressive angiomyxoma. Other samples exhibiting positivity of the stromal cells for either ER or PR were normal vulval skin (five of seven, ER; two of seven, PR), fibroepithelial polyps (four of seven, ER; five of seven, PR), smooth muscle neoplasms (three of five, ER; four of five, PR), nerve sheath tumours (one of two, ER; one of two, PR), angiomyofibroblastoma (one of one, ER; one of one, PR), and pelvic myxoma (one of one, PR). Conclusions—All cases of aggressive angiomyxoma of pelvic soft parts in female patients exhibited positivity for ER and/or PR. Because of its propensity to occur in female patients during the reproductive years, it is possible that aggressive angiomyxoma is a hormonally responsive neoplasm. However, dermal fibroblasts in normal vulval skin and stromal cells in a variety of vulval lesions can also be positive. ER or PR immunoreactivity cannot be used to distinguish aggressive angiomyxoma and its histological mimics.
Aims : To describe the clinical and pathological features of 12 further cases (in 11 patients) of superficial cervicovaginal myofibroblastomas (SCVM), rare tumours that hitherto have been described ...only in a single series of cases involving the cervix and vagina.
Methods and results : The patients' ages ranged from 23 to 80 years. Ten tumours were located in the vagina and two in the vulva. Three patients had been taking tamoxifen. The tumours ranged in size from 2 to 45 mm and morphologically were well‐circumscribed lesions composed of bland ovoid to spindle‐shaped cells, often with wavy nuclei. These cells were arranged in a variety of architectural patterns and were set in a finely collagenous stroma. Five cases exhibited stromal oedema or myxoid change and in eight cases hyalinized areas with thick, dense collagen bundles were present. Immunohistochemically, there was positivity with vimentin (11 of 11 cases tested), CD34 (six of 12 cases), desmin (nine of 12 cases) and oestrogen receptor (nine of 11 cases). All cases tested were negative for smooth muscle actin, S100, h‐caldesmon, HMB45, and CD31. In this study we expand on the morphological spectrum of these rare lesions and reiterate their association with tamoxifen.
Conculsions : Since these lesions may occur on the vulva, as well as the cervix and vagina, we propose the term ‘superficial myofibroblastoma of the lower female genital tract’.
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