R H Young

Nottinghamshire Healthcare NHS Trust, Nottigham, England, United Kingdom

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Publications (3)6.71 Total impact

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    ABSTRACT: 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.
    International Journal of Gynecological Pathology 11/2004; 23(4):330-6. · 1.41 Impact Factor
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    W G McCluggage, R H Young
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    ABSTRACT: To describe six cases seen in consultation in which artefactual vascular involvement within the ovary by benign granulosa cells caused diagnostic confusion. In five cases, the initial favoured diagnoses of the submitting pathologists were metastatic carcinoma (three cases) and immature neural elements within a teratoma (two cases). In two cases, the ovary contained a benign cystic teratoma (one with struma ovarii), in two cases endometriosis, in one case follicular cysts, and in the other no pathological lesion was present. In all cases, several small ovarian vascular channels contained cohesive groups of cells with mildly atypical nuclei and cytoplasm, which varied from scant to abundant and eosinophilic. In four cases, mitotic figures were identified. The cells were morphologically consistent with benign granulosa cells and were associated in four cases with a nearby follicle lined by similar cells. There was no evidence of a mass lesion, grossly or histologically, to suggest a granulosa cell tumour. The nature of the cells was confirmed using immunohistochemistry for alpha inhibin and calretinin in one case. This phenomenon is probably an artefact secondary to surgical trauma or sectioning within the laboratory; alternatively, it could be related to ovulation. It is important that this benign process is not misinterpreted as cancer, either primary or metastatic, which may prompt inappropriate treatment or investigations that are not needed.
    Journal of Clinical Pathology 03/2004; 57(2):151-4. · 2.44 Impact Factor
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    ABSTRACT: 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. 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. 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.
    Histopathology 09/2003; 43(2):144-50. · 2.86 Impact Factor

Publication Stats

102 Citations
6.71 Total Impact Points

Institutions

  • 2003–2004
    • Nottinghamshire Healthcare NHS Trust
      Nottigham, England, United Kingdom
    • Harvard Medical School
      Boston, Massachusetts, United States