Aims: To describe the clinicopathological and immunohistochemical findings in four cases of uterine tumour resembling ovarian sex cord tumour (UTROSCT). Methods: Four UTROSCTs were stained with a ...wide range of antibodies, including epithelial (AE1/3, epithelial membrane antigen), myoid (desmin, α smooth muscle actin, h-caldesmon), sex cord (α inhibin, calretinin, melan A, CD99) and neuroendocrine (chromogranin, CD56) markers as well as hormone receptors (oestrogen receptor, progesterone receptor, androgen receptor), vimentin, CD10, WT1 and HMB45. Results: The tumours ranged from 0.8 to 19.5 cm. Three were relatively well circumscribed intramural myometrial lesions; the other was a pedunculated mass attached to the uterine serosa. The tumours were variably composed of solid, corded, trabecular, nested, glandular and retiform arrangements of tumour cells. In three cases, cells with eccentric nuclei and abundant eosinophilic cytoplasm, resulting in a rhabdoid appearance, were a prominent feature. Three cases were diffusely positive with AE1/3 and all with epithelial membrane antigen. Positivity with myoid markers was common with 3, 4 and 1 case respectively staining with desmin, α smooth muscle actin and h-caldesmon; 2, 4, 1 and 2 cases respectively were positive with α inhibin, calretinin, melan A and CD99. All were chromogranin negative and exhibited diffuse strong staining with CD56. All were diffusely positive with oestrogen receptor, progesterone receptor, vimentin and WT1. Three cases were androgen receptor positive and all were CD10 and HMB45 negative. Conclusions: UTROSCT exhibits a polyphenotypic immunophenotype with coexpression of markers of epithelial, myoid and sex cord lineage as well as hormone receptors.
Aims: It has been suggested that p16 is overexpressed in uterine leiomyosarcomas in comparison with leiomyomas. In this study, p16 immunohistochemical expression was assessed in a variety of uterine ...smooth muscle tumours, including usual leiomyomas, leiomyoma variants, smooth muscle tumours of uncertain malignant potential (STUMPs) and leiomyosarcomas. The aim was to ascertain whether there are differences in p16 expression between these groups and whether p16 is of potential value in the assessment of problematic uterine smooth muscle neoplasms. p16 expression was also compared with that of p53 and MIB1.
Methods and results: Cases of usual leiomyoma (n = 10), leiomyoma variants (n = 27), STUMP (n = 4) and leiomyosarcoma (n = 22) were subject to p16, p53 and MIB1 immunohistochemistry. For p16, cases were evaluated with respect to both staining distribution and intensity. There was a statistically significant difference in p16 distribution (P < 0.001) and intensity (P = 0.001) between leiomyosarcomas and the other groups. There was no difference in p16 expression between usual leiomyomas, leiomyoma variants and STUMPs. There were also statistically significant differences in p53 (P = 0.014) and MIB1 (P < 0.001) immunoreactivity between leiomyosarcomas and the other groups.
Conclusions: p16 is overexpressed in uterine leiomyosarcomas compared with leiomyomas, benign leiomyoma variants and STUMPs, suggesting that p16 may be implicated in the pathogenesis of malignant uterine smooth muscle neoplasms. p16, in combination with p53 and MIB1, may be of value as an adjunct to morphological examination in the assessment of problematic uterine smooth muscle tumours, although further large‐scale studies with follow‐up are necessary to confirm this.
The distinction between an endometrial and an endocervical origin of an adenocarcinoma may be difficult, especially with small biopsy specimens or when tumor is present in both endometrial and ...cervical specimens. Previous studies have investigated the value of antibodies such as carcinoembryonic antigen, estrogen receptor, and vimentin in making this distinction. We investigated the value of p16 immunohistochemistry for distinguishing between an endometrial and an endocervical origin of an adenocarcinoma. Cases included in the study were endometrial adenocarcinomas of endometrioid type (n=29) and cervical adenocarcinomas of endocervical type (n=23). Cases were scored on a scale from 0 to 5 depending on the percentage of positive tumor cells: 0 (negative or occasional cells positive); 1 (<5% cells positive); 2 (5-20% cells positive); 3 (21-50% cells positive); 4 (51-99% cells positive); 5 (100% cells positive). Twenty-two of 23 (96%) endocervical adenocarcinomas were scored 5; the other was scored 0. The numbers of endometrial adenocarcinomas with scores of 0 to 5, respectively, were 1, 7, 4, 9, 5, and 3. Most primary endocervical adenocarcinomas were characterized by strong, diffuse positivity of 100% of cells with p16. Endometrial adenocarcinomas are usually positive, but positivity is generally focal and commonly involves <50% of cells. However, occasional endometrial adenocarcinomas exhibit 100% positivity. Diffuse, strong positivity with p16 suggests an endocervical rather than an endometrial origin of an adenocarcinoma. When there is morphological doubt this antibody may be of value as part of a panel for ascertaining the origin of an adenocarcinoma. Diffuse, strong positivity with p16 in endocervical adenocarcinomas is likely caused by inactivation of the retinoblastoma protein by the E7 human papillomavirus oncoprotein, which acts as a p16 transcript repressor.
Aggressive angiomyxoma (AA) is a vulvovaginal mesenchymal neoplasm with a marked tendency to local recurrence but which usually does not metastasise. Most cases exhibit positive immunohistochemical ...staining with oestrogen receptor (ER) and, or, progesterone receptor (PR).
We report a case of AA which exhibited positive immunohistochemical staining with ER and in which radiological examination following resection showed extensive residual tumour. The patient was commenced on gonadotropin-releasing hormone (GnRH) agonist therapy which resulted in complete radiological remission with replacement by scar tissue. The patient is currently maintained on a GnRH agonist.
The present case, together with several others reported in the literature, suggests that GnRH agonists may be of value in managing cases of AA, either primary or recurrent, which are not amenable to surgical excision. These agents may also be used to effect a reduction in size, so that more conservative surgery can be undertaken.
Recent advances in immunohistochemistry in gynaecological pathology
Recent years have witnessed significant developments in the use of immunohistochemistry in diagnostic gynaecological pathology. ...This review details the most significant of these. In ovarian pathology, differential cytokeratin staining (CK7 and 20) assists in distinguishing between a primary ovarian adenocarcinoma and a metastatic adenocarcinoma, especially of colorectal origin. The development of markers characteristic of ovarian sex cord‐stromal tumours (especially α‐inhibin) facilitates diagnosis of these neoplasms which is often difficult by morphology alone due to the wide differential diagnosis. In the uterus, the distinction between a primary endometrial and endocervical adenocarcinoma may be facilitated by use of a small panel of antibodies, including CEA, ER and vimentin. Newly developed antibodies such as CD10 and h‐caldesmon may be of use in the diagnosis of uterine mesenchymal lesions, especially in the distinction between endometrial stromal and smooth muscle lesions. Proliferation markers, such as MIB1, are of value in the cervix in the diagnosis of preinvasive squamous and glandular lesions. Recent studies have shown that cervical adenoma malignum exhibits a gastric phenotype. Advances have also been made in trophoblastic disease with the development of antibodies reactive against trophoblast such as α‐inhibin, mel‐Cam and p57. A newly developed monoclonal antibody HMGIC which is expressed in vulvovaginal aggressive angiomyxoma may prove to be of value in the often difficult distinction of this lesion from its histological mimics.
It is generally considered that an unequivocal histological diagnosis of endometriosis requires the presence of endometrioid-type glands and endometrioid-type stroma. However, small nodules or ...plaques of endometrioid-type stroma without glands have been noticed by the authors in repeated peritoneal biopsies performed for suspected endometriosis. These are often, but not always, accompanied by typical endometriosis with glands. This form of endometriosis has been previously referred to as stromal or micronodular stromal endometriosis. However, there has been little reference to this condition in the literature.
In this study, there was a review of a large series (n = 274) of peritoneal biopsies with a diagnosis of endometriosis with a view to ascertaining the frequency of stromal endometriosis.
Stromal endometriosis, characterised histologically by small microscopic nodules or plaques of endometrioid-type stroma, sometimes with a whorled pattern and prominent vascularity and erythrocyte extravasation, was identified in 44.9% of the biopsies. In 6.6% of the biopsies, stromal endometriosis occurred without typical endometriosis. The foci of stromal endometriosis usually had a superficial location just beneath the mesothelial surface or protruding above this. Associated histological features present in some cases included reactive mesothelial proliferation, inflammation, giant cell or granuloma formation, haemosiderin pigment deposition, microcalcification and decidualisation and myxoid change.
Stromal endometriosis, usually in the form of superficial nodules or plaques, is a relatively common form of endometriosis which typically occurs in association with typical endometriosis but occasionally on its own. Pathologists should be aware of the existence of this form of endometriosis, the morphological features of which may be subtle. The typical location, intimately associated with surface mesothelium, may suggest that stromal endometriosis derives from mesothelial or submesothelial cells via a metaplastic process.
Objective Malignant transformation in a dermoid cyst of the ovary is a rare complication, occurring in only 1–2% of cases, with squamous cell carcinoma being the most common type. Preoperative ...diagnosis is difficult because of the lack of specific symptoms and signs to suggest malignancy. Because of the small numbers of women involved, our knowledge of this rare tumour type is limited. This study aims to further characterise the population of women affected, the disease itself and the most appropriate management strategy.
Design We identified 14 women with this diagnosis between 1989 and 2006. This is a descriptive study, looking at the patient characteristics, mode of presentation and the role of tumour markers and radiological imaging in diagnosis. We also examined the stage and pathological features of the tumour at presentation and the subsequent course of the disease. We have also described our experiences using surgery, chemotherapy and radiotherapy in the management of these women.
Results We found that these tumours present at an age older than that of mature teratomas and that there are no reliable diagnostic tools or prognostic indicators. The behaviour of these tumours is unpredictable, and the role of chemotherapy and radiotherapy remains unclear. We suggest that repeated surgical resection of disease at the time of relapse could give a very durable response in selected women.
Ovarian small cell carcinoma of hypercalcemic type (OSCCHT) is a rare neoplasm with an aggressive behavior, broad differential diagnosis, and unknown histogenesis. To add to knowledge concerning the ...possible aid of immunohistochemistry in resolving problems in differential diagnosis and to further explore whether that modality points to any specific histogenesis, we undertook an immunohistochemical study of this neoplasm. Fifteen OSCCHTs (including four of the ''large cell" variant) were stained with a range of antibodies, some of which have not been investigated previously in this neoplasm. Cases were stained with AE1/3, EMA, BerEP4, CK5/6, calretinin, WT1, chromogranin, CD56, synaptophysin, CD99, NB84, desmin, S100, CD10, alpha inhibin, TTFI, and p53. Staining was classified as 0 (negative), 1+ (<5% cells positive), 2+ (5% to 25% cells positive), 3+ (26% to 50% cells positive), or 4+ (>50% cells positive). All cases were positive with p53 (two 1+, five 3+, eight 4+), 14 of 15 cases were positive with WT1 (one 1+, thirteen 4+), 14 of 15 with CD10 (three 1+, four 2+, two 3+, five 4+), 13 of 15 with EMA (three 1+, three 2+, two 3+, five 4+), 11 of 15 with calretinin (nine 1+, one 3+, one 4+), 9 of 15 with AE1/3 (eight 1+, one 2+), 4 of 15 with CD56 (one 1+, two 2+, one 4+), 3 of 15 with BerEP4 (two 2+, one 4+), 2 of 15 with synaptophysin (two 1+), and 1 of 15 with S100 (4+). All cases were negative with CK5/6, chromogranin, CD99, NB84, desmin, alpha inhibin, and TTF1. The only noticeable difference in the immunophenotype between typical OSCCHT and the large cell variant was that there was 4 +EMA positivity in three of four cases of large cell variant compared with two of 11 cases of typical OSCCHT. OSCCHT is characteristically positive with AE1/3, EMA, CD10, calretinin, WT1, and p53. Combined EMA and WT1 positivity, the latter usually intense and diffuse, may be of diagnostic value, inasmuch as only a few of the neoplasms in the differential diagnosis are positive with both antibodies. Negative staining with CD99, desmin, NB84, alpha-inhibin, and TTF1 may aid in the cases in which primitive neuroectodermal tumor, rhabdomyosarcoma, intraabdominal desmoplastic small round cell tumor, neuroblastoma, a sex cord-stromal tumor, and metastatic pulmonary small cell carcinoma are in the differential. Calretinin positivity precludes its use in the differential with granulosa cell tumors. The results of this investigation do not settle the issue of histogenesis, which remains enigmatic. The typical age distribution, follicle formation, and calretinin positivity are consistent with a sex cord origin. On the other hand, WT1 and EMA positivity and negative staining with alpha-inhibin would be unusual in a sex cord-stromal neoplasm and can be used as an argument for a surface epithelial origin. Germ cell and neuroendocrine origins seem highly unlikely.
Most cases of cervical adenocarcinoma in situ (AIS) and adenocarcinoma are of the usual or endocervical type. However, intestinal types of AIS and adenocarcinoma exist. With an intestinal-type ...adenocarcinoma in the cervix, the question may arise as to whether one is dealing with a primary cervical neoplasm or direct or secondary spread from an intestinal adenocarcinoma. In organs such as the ovary, urinary bladder, esophagus, and gallbladder, intestinal-type glandular epithelium often expresses enteric markers, but this has hardly been studied in the cervix. The purpose of this study was to investigate whether intestinal-type AIS and adenocarcinoma in the cervix express enteric markers and to ascertain whether these antibodies are of value in the distinction from a metastatic intestinal adenocarcinoma. We compared the immunophenotype of these lesions with that of usual-type AIS and adenocarcinomain the cervix. Cases included were AIS of usual type (n = 6), primary cervical adenocarcinoma of usual type (n = 6), AIS of intestinal type (n = 21), primary cervical adenocarcinoma of intestinal type (n = 3), primary cervical adenocarcinoma with signet ring cells (n = 2), and colorectal adenocarcinoma involving the cervix (n = 5). All cases were stained with cytokeratin (CK) 7, CK20, monoclonal carcinoembryonic antigen (CEA), p16, and CDX2. Staining was categorized as negative, focally positive (<50% cells), or diffusely positive (50% or more cells). Usual-type AIS was always diffusely CK7 positive, typically diffusely CEA and p16 positive, and always CK20 negative. CDX2 was positive in 1 case. All usual cervical adenocarcinomas were diffusely CK7 and p16 positive, and all were immunoreactive with CEA. Five and 2 cases were CK20 and CDX2 positive, respectively. Intestinal-type AIS was diffusely CK7 positive (all cases) and typically CK20 negative and diffusely CEA and p16 positive. All but 1 case exhibited diffuse nuclear positivity with CDX2. In addition, usual-type AIS adjacent to intestinal type was CDX2 positive in 13 of 21 cases. The 3 cases of primary cervical intestinal-type adenocarcinoma were diffusely CK7 positive, focally or diffusely positive with CK20 and CDX2, and focally positive with CEA. One case was diffusely p16 positive, 1 focal and 1 negative. The foci of signet ring cells in the 2 primary cervical adenocarcinomas were diffusely CK7 and p16 positive and negative with CK20 and CDX2. Colorectal adenocarcinomas involving the cervix were typically diffusely positive with CK20, CEA, and CDX2; negative with CK7; and negative or focally positive with p16. Intestinal types of cervical AIS and adenocarcinoma exhibit a partial enteric immunophenotype, usually with diffuse expression of CDX2 and, in some cases, staining with CK20. They maintain their CK7 immunoreactivity and are usually p16 positive. Although there is immunophenotypic overlap, focal staining with CK20 together with diffuse CK7 and sometimes p16 positivity helps to distinguish intestinal types of cervical adenocarcinoma from involvement by a colorectal adenocarcinoma; CEA and CDX2 are of no value in this regard. CDX2 positivity in usual-type AIS adjacent to intestinal type and in occasional cases of pure usual-type AIS may be a reflection of early intestinal differentiation before this is morphologically apparent. Using a set of cases of AIS diagnosed in a single institution over a 7-year period (77 usual type; 13 intestinal type), intestinal type was more likely to be associated with early invasive adenocarcinoma than usual type (31% vs 17%), suggesting that intestinal differentiation may be a risk factor for invasion in premalignant cervical glandular lesions.
Prostatic tissue has rarely been described in the lower female genital tract. We describe 6 cases of ectopic prostatic tissue: 5 involving the cervix and 1 the vagina. The latter is the first ...reported example of benign prostatic tissue in the vagina. The age of the patients ranged from 21 to 65 years; and in all cases, the prostatic tissue was located within the cervical or vaginal stroma without involvement of the surface. In all cases, there were both glandular and squamous elements, which varied in prominence. In some cases, the squamous elements predominated to such an extent that the underlying glandular component was easily overlooked. In the glandular areas, a double cell layer of luminal and basal cells was focally apparent. There was little cytologic atypia or mitotic activity. Immunohistochemically, 3 of 6 cases were positive with prostate specific antigen (PSA) and all 6 cases marked with prostatic acid phosphatase (PSAP). In some of the positive cases, staining was focal. Positive staining with prostatic markers was confined to the glandular elements with no staining of the squamous areas. Immunohistochemical staining with the high molecular weight cytokeratin 34betaE12 highlighted the basal cell layer, which often extended into the center of the cellular islands, reminiscent of basal cell hyperplasia involving the prostate gland. All cases tested were CD10 positive (largely restricted to the basal cell layer), alpha-methylacyl-CoA racemase positive, and p16 negative. Estrogen receptor (ER) and progesterone receptor (PR) were negative in the glandular areas, but ER was positive in the squamous elements in all cases and PR was positive in 1 case. All cases tested were androgen receptor positive and exhibited a low MIB-1 proliferation index with only scattered positive nuclei. The presence of ectopic prostatic tissue in the lower female genital tract may be more common than is appreciated. Once the possibility is considered, the diagnosis is easily confirmed using immunohistochemistry, although staining with prostatic markers may be focal and PSA may be negative. Ectopic prostatic tissue in the lower female genital tract is almost certainly a benign condition, based on the morphology, including the presence of a double cell layer, although follow-up of larger numbers of cases is required. Possible theories of histogenesis include a developmental anomaly, metaplasia of preexisting endocervical glands, and derivation from mesonephric remnants.
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