R H Young

The Bracton Centre, Oxleas NHS Trust, Дартфорде, England, United Kingdom

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Publications (190)666.97 Total impact

  • [Show abstract] [Hide abstract]
    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. DOI:10.1097/01.pgp.0000139644.38835.9d · 1.63 Impact Factor
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    ABSTRACT: Basaloid proliferations of the prostate with morphologic patterns other than usual basal cell hyperplasia are rare, and the distinction between benign and malignant lesions has been difficult. We describe 23 such lesions and classify them into two groups: adenoid cystic-like hyperplasia and adenoid cystic or basaloid carcinoma. Adenoid cystic-like hyperplasia (n = 19) was characterized by an older age at presentation (mean, 71.8 years), transition zone location with background of nodular hyperplasia, multifocality, lobulation, circumscription, and small acini with occasional hyalinization. A cribriform pattern limited to small- and medium-sized glands, squamous metaplasia, and hypercellular myxoid stroma were occasionally seen. Adenoid cystic carcinoma (n = 3) was characterized by a younger age at presentation (mean, 46.0 years), peripheral zone involvement, and large acini that were often dilated and exhibited extensive interanastomoses, prominent intraglandular hyalinization, perineural invasion , and extraprostatic extension. Basaloid carcinoma (n = 1) showed infiltration between normal glands, perineural invasion, and extraprostatic extension but lacked a cribriform architecture. The degree of cytologic atypia and mitotic rate overlapped between the hyperplasia and carcinoma cases. Both hyperplastic lesions and adenoid cystic carcinomas showed a basal cell phenotype with strong immunoreactivity to cytokeratins 14 and 34betaE12, but the basaloid carcinoma was negative for these markers. In all cases, the proliferating basal cells were nonreactive for myoepithelial and prostatic secretory cell markers. The 8 patients with adenoid cystic-like hyperplasia with available follow-up information had no progression of disease (mean follow-up period, 8.6 years). One patient with adenoid cystic carcinoma died with widespread metastases, but the 3 other patients with carcinomas had no disease progression (mean follow-up period, 7.0 years). In conclusion, most florid basaloid proliferations of the prostate fall into one of two categories. In the first, there is a clear association with nodular hyperplasia (adenoid cystic-like hyperplasia) and, although cytologic atypia and mitoses may be seen, they are present within a lesion that retains an orderly, vaguely nodular (noninfiltrative) pattern. The second group of cases (adenoid cystic and basaloid carcinoma) shows a widespread, haphazard infiltrative growth pattern. This study suggests that adenoid cystic carcinomas are biologically indolent following prostatectomy but have a low risk of distant metastasis.
    American Journal of Surgical Pathology 10/2004; 28(10):1289-1298. DOI:10.1097/01.pas.0000138180.95581.e1 · 4.59 Impact Factor
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    ABSTRACT: To test whether alpha-methylacyl-CoA racemase (AMACR) is a sensitive and specific marker of prostate cancer. The expression levels of AMACR mRNA were measured by real-time polymerase chain reaction. A total of 807 prostatic specimens were further examined by immunohistochemistry specific for AMACR. Quantitative immunostaining analyses were carried out by using the ChromaVision Automated Cellular Imaging System and the Ariol SL-50 Imaging System, respectively. AMACR mRNA levels measured in prostatic adenocarcinoma were 55 times higher than those in benign prostate tissue. Of 454 cases of prostatic adenocarcinoma, 441 were positive for AMACR, while 254 of 277 cases of benign prostate were negative for AMACR. The sensitivity and specificity of AMACR immunodetection of prostatic adenocarcinomas were 97% and 92%, respectively. Both positive and negative predictive values were 95%. By automatic imaging analyses, the AMACR immunostaining intensity and percentage in prostatic adenocarcinomas were also significantly higher than those in benign prostatic tissue (105.9 versus 16.1 for intensity, 45.7% versus 0.02% and 35.03% versus 4.64% for percentage, respectively). We have demonstrated the promising features of AMACR as a biomarker for prostate cancer in this large series and the potential to develop automated quantitative diagnostic tests.
    Histopathology 10/2004; 45(3):218-25. DOI:10.1111/j.1365-2559.2004.01930.x · 3.30 Impact Factor
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    ABSTRACT: A heterogeneous spectrum of epithelial alterations and atypical lesions affect the squamous epithelium of penile mucosal anatomical compartments. Analogous to other genital sites, the terminology utilized to define the lesions is variable. The few pathologic studies of penile precancerous lesions are mostly related to carcinoma in situ and human papilloma Virus (HPV), and the information on low-grade atypical lesions is limited. The objective of this study was to comprehensively describe the morphologic features of all epithelial alterations, benign and atypical, low grade and high grade, associated with invasive squamous cell carcinoma of the penis and to investigate their relation with each other and with subtypes of invasive carcinoma. We also propose herein a simple and reproducible nomenclature for penile precancerous abnormalities until more biological, molecular, or epidemiologic information on the lesions is available. Two hundred and eighty-eight penectomy and circumcision specimens with invasive squamous cell carcinoma were pathologically evaluated. Carcinomas were classified as usual, verrucous, papillary not otherwise specified, warty (condylomatous), basaloid, and mixed. Associated lesions were classified as squamous hyperplasia and squamous intraepithelial lesions of low and high grade (LGSIL and HGSIL). In LGSIL, atypia was confined to the lower third, and in HGSIL, atypical cells affected at least two thirds of the squamous epithelium. Subtypes of SIL were squamous, warty, basaloid, warty-basaloid, and papillary. Squamous hyperplasia, the most common lesion, was found in 83% of the cases, followed by LGSIL (59%) and HGSIL (44%). In 62% of the cases more than 1 associated lesion was present per specimen. A sequence from squamous hyperplasia to low-grade to high-grade SIL was seen frequently. Squamous hyperplasia was more commonly associated with usual squamous, papillary, and verrucous than with warty and basaloid invasive carcinomas. LGSIL was associated with all types of squamous cell carcinoma but was rarely present adjacent to basaloid or verrucous tumors. HGSIL was present in two thirds of invasive warty, basaloid, and mixed warty-basaloid tumors, in about half of usual squamous cell carcinomas, and was absent in papillary and verrucous carcinomas. Correlation of special types of invasive carcinomas with subtypes of SIL revealed morphologic correspondence of invasive tumor and the associated intraepithelial lesion. Squamous LGSIL was preferentially associated with verrucons, papillary, an usual squamous cell carcinomas; warty LGSIL, with invasive warty and mixed warty-basaloid carcinomas. High-grade SIL of the squamous type was frequently found in squamous cell carcinoma of usual type but was rarely present with warty or basaloid carcinomas. Basaloid HGSIL was associated with basaloid carcinoma, and HGSIL of warty type, with either warty or mixed warty-basaloid carcinomas. The high frequency of squamous hyperplasia and LGSIL and preferential association with usual, verrucous, and papillary carcinomas plus the subtle morphologic differences of the 2 lesions suggest that, despite its benign appearance, squamous hyperplasia is a precursor of the aforementioned carcinomas. The association and histologic similarities between high-grade SIL of the basaloid, warty, or mixed forms with their invasive counterparts indicate these lesions are their likely precursors.
    International Journal of Surgical Pathology 10/2004; 12(4):351-364. DOI:10.1177/106689690401200408 · 0.96 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. DOI:10.1136/jcp.2003.011338 · 2.55 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. DOI:10.1046/j.1365-2559.2003.01684.x · 3.30 Impact Factor
  • R H Young, P B Clement
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    ABSTRACT: Adenocarcinoma of the uterine cervix and its variants account for a much greater number of cases in routine practice of histopathology than they did several decades ago. The varied morphology of these tumours results in diverse problems in differential diagnosis. The overall area of glandular pathology of the cervix, of which invasive adenocarcinoma is only one subset, is further complicated by the fact that there are many benign glandular proliferations of the cervix that can potentially be misinterpreted as adenocarcinoma. In this review the histopathology of endocervical adenocarcinoma and its variants is presented with the emphasis on evaluation of routinely stained sections, still the bedrock of routine practice, relatively little aid being provided by immunohistochemistry or other new techniques, contrary to what is sometimes implied in the literature. Description of the appearance of each subtype of adenocarcinoma or variant thereof is followed by a section on their differential diagnosis. Eighty percent of endocervical carcinomas are of the so-called usual type being characterized by cells with eosinophilic cytoplasm and generally brisk mitotic activity. It is sometimes stated that endocervical adenocarcinomas are mucinous but the usual form just noted often has little or no mucin. Pure or almost pure mucinous adenocarcinoma do occur, however, and have an important subtype, the so-called adenoma malignum (minimal deviation adenocarcinoma). Although treacherous because of its bland cytological features and sometimes deceptive pattern, a cone biopsy or hysterectomy specimen showing this neoplasm typically has easily recognizable features that indicate the presence of an infiltrative adenocarcinoma. An important variant of usual endocervical adenocarcinoma is the well differentiated villoglandular papillary adenocarcinoma, a designation that should be reserved for tumours with grade 1 cytologic features as usual endocervical adenocarcinoma, which is typically grade 2, may have papillae. In our opinion all other variants of pure adenocarcinoma, including endometrioid, are rare and include in addition to the latter clear cell, serous and mesonephric neoplasms. Tumours with a glandular and nonglandular component are also reviewed: adenosquamous carcinoma, glassy cell carcinoma, adenoid basal carcinoma, 'adenoid cystic' carcinoma and adenocarcinoma admixed with a neuroendocrine tumour.
    Histopathology 10/2002; 41(3):185-207. DOI:10.1046/j.1365-2559.2002.01462.x · 3.30 Impact Factor
  • E Oliva, P. B Clement, R. H Young
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    ABSTRACT: Smooth muscle tumours and endometrial stromal tumours represent the two main categories of mesenchymal tumours of the uterus. Although their diagnosis is straightforward in most cases, difficulties arise with particular leiomyoma variants, especially highly cellular leiomyoma (often confused with an endometrial stromal tumour) and leiomyoma with bizarre nuclei, mitotically active leiomyoma, and leiomyomas with hydropic or myxoid change, which may cause concern for leiomyosarcoma. Endometrial stromal tumours including several recently described variants, those with smooth muscle, sex-cord-like or glandular differentiation, or a fibrous-myxoid background are responsible for their own subset of diagnostic problems as are two other entities considered here: high-grade endometrial sarcomas and uterine tumours resembling ovarian sex-cord tumours. This review highlights useful morphologic features as well as immunohistochemical findings that may help in the classification of these often confusing tumours.
    Current Diagnostic Pathology 08/2002; 8(4):268-282. DOI:10.1054/cdip.2002.0126
  • R H Young, R E Scully
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    ABSTRACT: The differential diagnosis of ovarian tumors is reviewed based on their patterns and cell types. This approach, which differs from the standard textbook discussion of each neoplasm as an entity, has practical value as differential diagnosis depends largely on the pattern or patterns and cell type or types of tumors. Awareness of the broad range of lesions that may exhibit particular patterns or contain one or more cell types is crucial in formulating a differential diagnosis. The following patterns are considered: moderate-to-large-glandular and hollow-tubular; solid tubular and pseudotubular; cords and ribbons; insular; trabecular; slit-like and reticular spaces; microglandular and microfollicular; macrofollicular and pseudomacrofollicular; papillary; diffuse; fibromatous-thecomatous; and biphasic and pseudobiphasic. The following cell types are considered: small round cells; spindle cells; mucinous cells, comprising columnar, goblet cell and signet ring cell subtypes; clear cells; hobnail cells; oxyphil cells; and transitional cells. The morphologic diversity of ovarian tumors poses many challenges; knowledge of the occurrence and frequency of these patterns and cell types in various tumors and tumor-like lesions is of paramount diagnostic importance. A specific diagnosis can usually be made by evaluating routinely stained slides, but much less often, special staining, immunohistochemical staining or, very rarely, ultrastructural examination is also required. Finally, clinical data, operative findings, and gross features of the lesions may provide important, and at times decisive diagnostic clues.
    Seminars in Diagnostic Pathology 09/2001; 18(3):161-235. · 1.80 Impact Factor
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    J H Eichhorn, R H Young
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    ABSTRACT: Neuroendocrine tumors are more common in the female than male genital tract; most are uterine small cell carcinomas or ovarian carcinoids. Primary ovarian carcinoids are divided into insular, trabecular, strumal, and mucinous types; most are benign. Carcinoids metastatic to the ovary are more aggressive; most arise in the gastrointestinal tract. Scattered neuroendocrine cells are seen in a variety of ovarian surface epithelial tumors; sporadic mucinous cystic tumors with neuroendocrine cells have been associated with Zollinger-Ellison syndrome. Frank neuroendocrine carcinomas in the ovary include small cell carcinoma and large cell neuroendocrine carcinoma, each with a poor prognosis and often associated with a conventional surface epithelial tumor Such carcinomas also occur in the endometrium and cervix. Uterine carcinoids are rare if strict criteria are applied. Small cell neuroendocrine carcinomas also occur rarely in the vagina and vulva. Most male genital tract neuroendocrine tumors are prostatic small cell carcinomas or testicular carcinoids. Extragonadal carcinoids of the male genital tract are rare. Testicular carcinoids should be distinguishedfrom metastatic tumors. It is important to distinguish prostatic small cell carcinoma from poorly differentiated adenocarcinoma with small cells. Small cell neuroendocrine carcinomas also occur rarely in the scrotum, penis, and penile urethra.
    American Journal of Clinical Pathology 07/2001; 115 Suppl:S94-112. DOI:10.1309/64CW-WKGK-49EF-BYD1 · 3.01 Impact Factor
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    ABSTRACT: Only rare primary mucinous (goblet cell) carcinoids of the ovary have been reported, and their clinicopathologic features have not been well delineated. The authors studied 17 examples from patients 14 to 74 years of age. The clinical presentations were similar to those of ovarian neoplasms in general. The tumors ranged from 0.8 to 30 cm in diameter. In six cases the tumor was in the wall of a mature cystic teratoma, appearing grossly as solid nodules or areas of thickening in four of them, six tumors were entirely solid, and five were solid associated with other types of cystic tumor. The tumors were divided into three groups on the basis of their microscopic features. Six neoplasms, designated "well differentiated," were composed of small glands, many of which floated in pools of mucin. The glands were lined by goblet cells and columnar cells, some of which were of neuroendocrine type. Three tumors, designated "atypical," were characterized by crowded glands, some of which were confluent, small islands with a cribriform pattern, and scattered microcystic glands. The glands were lined by cuboidal to columnar cells, some of them neuroendocrine, admixed with goblet cells. Eight tumors, designated "carcinoma arising in mucinous carcinoid," contained islands and larger nodules of tumor cells, or closely packed glands, as well as single cells, mainly of the signet ring cell type. Most of the cells were devoid of mucin and were severely atypical with marked mitotic activity. Necrosis was present in all eight tumors. Seven of the eight tumors with a carcinomatous component contained at least minor foci of well-differentiated mucinous carcinoid; the eighth contained only foci of atypical mucinous carcinoid. The neuroendocrine nature of a variable proportion of the cells in all three groups was demonstrated by staining for neuroendocrine markers. The mucinous nature of other cells was confirmed by mucicarmine or Alcian blue stains. The ovary contained an intrinsic component of trabecular and insular carcinoid, and of strumal carcinoid in one case each, an adjacent mature cystic teratoma in six cases, mucinous cystadenocarcinoma in three cases, and borderline mucinous cystic tumor, borderline Brenner tumor, and epidermoid cyst in one case each. Fifteen tumors were stage I, one was stage II, and one was stage III. The last two tumors had a carcinomatous component. Follow-up data were available for 15 patients; 12 were alive and free of tumor 2.3 to 14 years (average, 4.7 years) after the ovarian tumor was excised. One patient, whose tumor had a carcinomatous component, died 3 years postoperatively of unrelated causes. Two patients, both of whom had a carcinomatous component in their tumor, died 9 and 12 months postoperatively. Primary mucinous carcinoids must be distinguished from metastatic mucinous carcinoid tumors from the appendix or elsewhere. Features supporting an ovarian origin are the additional presence in the specimen of teratoma or an ovarian surface epithelial tumor, an absence of blood vessel or lymphatic space invasion, and confinement to a single ovary. Similar features help to distinguish mucinous carcinoids from Krukenberg tumors. Mucinous carcinoids should also be distinguished from strumal carcinoids, which can contain mucinous glands, and insular carcinoid tumors that arise rarely in the wall of a mucinous cystic neoplasm. Although the number of cases in this series is small, the follow-up data suggest that the degree of differentiation, particularly the presence of frank carcinoma, is an important prognostic factor.
    American Journal of Surgical Pathology 06/2001; 25(5):557-68. DOI:10.1097/00000478-200105000-00001 · 4.59 Impact Factor
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    ABSTRACT: Objective: The expression of Mullerian inhibiting substance (MIS), CD99 (MIC-2 gene product), and HEA125 in ovarian tumors is potentially useful for diagnostic purposes. Methods: We studied the expression of MIS, CD99, and an epithelial cell-associated antigen recognized by antibody HEA125 in a series of 179 ovarian tumors using monoclonal or polyclonal antibodies and standard immunohistochemical techniques. Results: MIS was consistently detected in primary and metastatic sex cord tumors with annular tubules (SCTAT) (n=9). 3 of 9 adult granulosa cell tumors (AGCT) 4 of 8 juvenile granulosa cell tumors (JGCT), 3 of 9 Sertoli cell tumors (SCT), 2 of 2 unclassified sex cord tumors, 2 of 7 steroid cell tumors, 1 of 1 gonadoblastoma (sex cord cells positive, germ cells negative), 3 of S female adnexal tumors of probable wolffian origin (FATPWO), and 2 of 4 small cell carcinomas of the hypercalcemic type (SCCHCT) were also MIS positive. In contrast, 9 thecomas, 10 fibromas, 10 fibrosarcomas, S sclerosing stromal tumors (SST), and 6 Sertoli-Leydig cell tumors (SLCT) were MIS negative. All 11 primary and metastatic JGCT were CD19 positive. In addition, 1 of 13 AGCTs, 3 of II thecomas, 3 of II SSTs, 3 of 11 SCTs, 2 of 10 SLCTs, 2 of 12 SCTATs, 1 of 1 gynandroblastoma, 1, of 2 unclassified sex cord tumors, and 4 of 12 SCCHCTs were also CD99 positive. However, 11 fibromas, 10 fibrosarcomas, 9 steroid cell tumors, 5 gonadoblastomas, and 10 FATPWOs were CD99 negative. Likewise, except for weak focal CD99 immunostaining in 1 of 3 yolk sac tumors (YST), all 16 remaining germ cell tumors and all 18 borderline or malignant epithelial-stromal tumors were negative. HEA125 immunoreactivity was detected in 2 of 11 thecomas, 1 of 11 SCTs, 4 of 10 SLCTs, 1 of 2 unclassified sex cord tumors, 1 of 10 FATPWOs, 4 of 12 SCCHCTs as well as in most germ cell tumors and epithelial-stromal tumors. 13 AGCTs, 11 JGCTs, 11 fibromas, 10 fibrosarcomas, 11 SSTs, 12 SCTATs, 1 gynandroblastoma, 9 steroid cell tumors, and 5 gonadoblastomas were HEA125 negative. Conclusion: Our findings indicate that MIS is a marker of sex-cord differentiation and may be useful as a serum tumor marker for certain sex cord tumors, especially SCTAT. Although the detection of MIS and CD99 in some SCCHCTs and FATPWOs might argue in favor of a sex cord origin, the histogenesis of these tumors remains unclear. Although inhibin-cr has previously been shown to be a more sensitive marker of sex-cord differentiation, a panel of immunohistochemical markers including MIS, CD99 and HEA125 may be helpful in the differential diagnosis of certain ovarian neoplasms.
    Geburtshilfe und Frauenheilkunde 05/2001; 61(5):274-279. DOI:10.1055/s-2001-14147 · 0.96 Impact Factor
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    ABSTRACT: A retrospective review of the clinical and pathologic features of 61 cases of penile squamous cell carcinoma (SCC), all treated by primary surgical resection at the Memorial Sloan Kettering Cancer Center during the period 1949-1992, was undertaken. Inguinal lymph node dissection material was evaluated in 40 cases. All carcinomas were of squamous cell type and were classified as follows: usual type, 36 cases (59%); papillary, not otherwise specified (NOS), 9 cases (15%), basaloid, 6 cases (10%); warty (condylomatous), 6 cases (10%); verrucous, 2 cases (3%), and sarcomatoid, 2 cases (3%). A high rate of nodal metastasis and poor survival were found for the basaloid and sarcomatoid neoplasms (5 of 7 patients with metastasis, 71%, and 5 of 8 dead of disease, 63%). Only 1 patient with a verruciform tumor (defined as a tumor of nonspecific papillary, warty, or verrucous type) had inguinal node metastasis and none died from penile cancer. An intermediate rate of metastasis and mortality (14 of 26, 54%, and 13 of 36, 36%, respectively) was found for typical SCC. Penile carcinomas are morphologically heterogeneous, and there is a correlation of histologic type and biologic behavior. This mandates accurate histologic subtyping by the pathologist.
    International Journal of Surgical Pathology 05/2001; 9(2):111-20. DOI:10.1177/106689690100900204 · 0.96 Impact Factor
  • R K Yantiss, P B Clement, R H Young
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    ABSTRACT: Endometriosis of the intestinal tract may mimic a number of diseases both clinically and pathologically. The authors evaluated 44 cases of intestinal endometriosis in which endometriosis was the primary pathologic diagnosis, and evaluated them for a variety of gross and histologic changes. Cases with preneoplastic or neoplastic changes were excluded specifically because they were the subject of a previous study. The patients ranged in age from 28 to 56 years (mean age, 44 years), and presenting complaints included abdominal pain (n = 15), an abdominal mass (n = 12), obstruction (n = 8), rectal bleeding (n = 2), infertility (n = 3), diarrhea (n = 2), and increasing urinary frequency (n = 1). The clinical differential diagnoses included diverticulitis, appendicitis, Crohn's disease, tubo-ovarian abscess, irritable bowel syndrome, carcinoma, and lymphoma. Forty-two patients underwent resection of the diseased intestine and two patients underwent endoscopic biopsies. In 13 patients there were predominantly mural masses, which were multiple in two patients (mean size, 2.6 cm). In addition, 11 cases had luminal stenosis or strictures, six had mucosal polyps, four had submucosal masses that ulcerated the mucosa (sometimes simulating carcinoma), three had serosal adhesions, one had deep fissures in the mucosa, and one was associated with appendiceal intussusception. Involvement of the lamina propria or submucosa was identified in 29 cases (66%) and, of these, 19 had features of chronic injury including architectural distortion (n = 19), dense lymphoplasmacytic infiltrates (n = 7), pyloric metaplasia of the ileum (n = 1), and fissures (n = 1). Three cases had features of mucosal prolapse (7%), ischemic changes were seen in four (9%), and segmental acute colitis and ulceration were seen in four and six cases (9% and 13%) respectively. In 14 patients, endometriosis formed irregular congeries of glands involving the intestinal surface epithelium, mimicking adenomatous changes. Mural changes included marked concentric smooth muscle hyperplasia and hypertrophy, neuronal hypertrophy and hyperplasia, and fibrosis of the muscularis propria with serositis. Follow-up of 20 patients (range, 1-30 years; mean, 7.8 years) revealed that only two patients had recurrent symptoms. None of the patients developed inflammatory bowel disease. Endometriosis can involve the intestinal tract extensively, causing a variety of clinical symptoms, and can result in a spectrum of mucosal alterations. Because the endometriotic foci may be inaccessible to endoscopic biopsy or may not be sampled because of their focality, clinicians and pathologists should be aware of the potential of this condition to mimic other intestinal diseases.
    American Journal of Surgical Pathology 05/2001; 25(4):445-54. · 4.59 Impact Factor
  • M W Datta, T M Ulbright, R H Young
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    ABSTRACT: Five cases of renal cell carcinoma metastatic to the testis or its adnexa are described, including 3 that represented the initial presentation and mimicked primary testicular neoplasms. The patients ranged from 46 to 85 years of age. Three presented with self-identified testicular masses. One patient was investigated because of fever of unknown origin and was found to have a left rib metastasis. Further work-up led to the discovery of a testicular mass. The final patient had a tumor of the spermatic cord that was examined without knowledge that he had a prior renal neoplasm. All the tumors were unilateral. They ranged from 1.8 to 5.0 cm; multiple tumor nodules were present in one of them but the others were discrete solitary masses. Four tumors were yellow/yellow-tan, and one was gray. On microscopic examination all the tumors were of the clear cell type. Patterns included solid sheets, acini, cysts, alveoli, and trabeculae. Two had prominent vascular invasion. Diagnoses initially entertained in these cases included Sertoli cell tumor, Sertoli-Leydig cell tumor, and clear cell cystadenoma of the epididymis. In 3 cases a kidney tumor was discovered 2 to 4 weeks after the diagnosis of renal cell carcinoma metastatic to the testis was rendered. On follow-up two patients died of tumor, and two were alive (5 months and 1 year) after orchiectomy. The diagnosis of renal cell carcinoma metastatic to the testis should be considered in evaluating a clear cell tumor of the testis, particularly in an older male or if the appearance suggests a Sertoli cell tumor. The differences in survival between metastatic renal cell carcinoma and sex cord-stromal tumors indicate the importance of considering the former in the differential.
    International Journal of Surgical Pathology 02/2001; 9(1):49-56. DOI:10.1177/106689690100900108 · 0.96 Impact Factor
  • E Oliva, R H Young
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    ABSTRACT: The diverse non-neoplastic lesions that occur in the paratesticular region and may potentially mimic neoplasms are considered. These include some aspects of normal histology such as a cribriform pattern of the epididymis, bizarre nuclear atypia within epididymal epithelial cells and the presence of Leydig cells outside the testicular parenchyma. Inflammatory changes associated with a hydrocele and a variety of granulomatous and nongranulomatous infectious disorders may mimic a neoplasm on gross evaluation, but should be readily distinguished from them microscopically. This is also the case with malakoplakia and sarcoidosis, which rarely form a paratesticular mass. Other lesions considered are changes associated with vasculitis, the recently described entities inflammatory pseudotumor and fibromuscular hyperplasia and the well-known processes sperm granuloma, spermatocele, vasitis nodosa, fibrous pseudotumor, meconium periorchitis, mesothelial hyperplasia, the testicular tumor of the adrenogenital syndrome, sclerosing lipogranuloma, and splenic-gonadal fusion. Features that aid in the microscopic distinction of these lesions from neoplasms are emphasized.
    Seminars in Diagnostic Pathology 12/2000; 17(4):340-58. · 1.80 Impact Factor
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    ABSTRACT: Little is known about pathology residents' ability to Gleason grade or their ability to learn surgical pathology using Internet-based technology. A free Web-based program (available at www.pathology. jhu.edu/prostate) was developed that consisted of 20 pretutorial images for grading, 24 tutorial images, and the same 20 posttutorial images for Gleason grading. The grading images were selected from cases that had a consensus Gleason grade from 10 uropathology experts. In 2.5 months, 255 residents visited the website, and 151 (59%) completed it. Of those who completed the website, their year in training was known in 85 (56%): 1st year, 25.8%; 2nd year, 20%; 3rd year, 22.3%; 4th year, 14.1%; 5th year, 15.3%; and 6th year, 2.4%. Eighty percent learned Gleason grading in residency versus being self-taught, and 66% were male. In a multivariate analysis, higher pretutorial scores were associated with both their year in training (P = .001) and their hospital size (P = .003). Improvements in grading posttutorial were not related to the residents' year in training. Overall, the website significantly improved grading in 11 of 20 images and had no effect in 9 of 20 images. Improvements were noted in 1 of 1 Gleason score 4; 2 of 7 Gleason score 5 to 6; 2 of 6 Gleason score 7; and 6 of 6 Gleason score above 7 tumors. In summary, a Web-based tutorial improved Gleason grading accuracy by pathology residents to an equal extent regardless of their year in training. It is more difficult to teach residents to grade Gleason scores 5 to 7 tumors, and additional training should be concentrated in this area.
    Human Pathlogy 10/2000; 31(9):1044-50. DOI:10.1053/hupa.2000.16278 · 2.81 Impact Factor
  • M R Nucci, J A Ferry, R H Young
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    ABSTRACT: We report four examples of prostatic tissue occurring in the uterine cervix of patients aged 22, 25, 31, and 77 years. Three were incidental findings in loop excisions (two patients) and cone biopsy (one patient) of the cervix for high-grade squamous dysplasia. One presented as a cervical mass, clinically suspected to represent a fibroid. The prostatic tissue consisted of ducts and acini, some of which had papillary or cribriform patterns. Squamous metaplasia was prominent in all cases. No Wolffian duct tissue was present. The glandular epithelium in all cases was positive for prostatic acid phosphatase and prostate-specific antigen. High molecular weight keratin, performed in two cases, highlighted basal cells in a manner similar to the normal prostate. These unusual cases, only one of which is documented previously, further complicate the often-challenging area of interpretation of benign glandular lesions of the cervix. The unusual phenomenon of ectopic prostate tissue in general is reviewed.
    American Journal of Surgical Pathology 10/2000; 24(9):1224-30. · 4.59 Impact Factor
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    ABSTRACT: The clinical and pathologic features of 15 primary urethral melanomas occurring in patients (nine women and six men) age 44 to 96 years (mean age, 73 yrs) are described. In the men the tumor involved the distal urethra. In eight women it involved the distal urethra, usually the meatus; both the distal and proximal urethra were involved in one woman. The tumors were typically polypoid and ranged from 0.8 to 6 cm (mean, 2.6 cm) in maximum dimension. A vertical growth phase was present in all tumors, with a prominent nodular component in seven of them. A radial growth phase was seen in nine tumors. The depth of invasion ranged from 2 to 17 mm. The tumors had diffuse, nested, storiform, or mixed growth patterns. The neoplastic cells typically had abundant eosinophilic cytoplasm, large nuclei with prominent nucleoli, and brisk mitotic activity. Melanin pigment was seen in 12 tumors but was conspicuous in only six. At the time of diagnosis, 13 tumors were confined to the urethra and two patients had lymph node metastasis. Nine patients died of disease 13 to 56 months after initial diagnosis and treatment, and one patient had a local recurrence at 4 years and subsequently died of sepsis 1 year later. Three patients were alive and well at 11 months, 23 months, and 7 years. One patient died at the time of the initial operation, and one died of a ruptured aortic aneurysm at 3 years without evidence of melanoma at autopsy. Primary malignant melanomas of the urethra, one fifth of which are amelanotic, must be included in the differential diagnosis of a number of primary neoplasms that involve the urethra, including transitional cell carcinoma, sarcomatoid carcinoma, and sarcomas. Conventional prognostic factors, such as depth of invasion or tumor stage, do not seem to play as important a role in predicting survival as the mucosal location and the nodular growth present frequently in these tumors.
    American Journal of Surgical Pathology 07/2000; 24(6):785-96. · 4.59 Impact Factor
  • P M Baker, R H Young
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    ABSTRACT: Four cases of radiation cystitis that caused diagnostic difficulty because of an epithelial proliferation with architectural complexity and reactive cytologic atypia are described. The patients, 2 male, 2 female, were from 43 to 77 years of age. Two presented with hematuria. Cystoscopy disclosed abnormalities in 3 patients. Microscopic examination showed irregularly shaped and arranged aggregates of epithelial cells in the upper and mid zones of the lamina propria. The cells, which typically showed at least mild, and sometimes severe, pleomorphism, were usually transitional, but squamous differentiation was seen focally in 3 cases. Ulceration of the overlying epithelium was present in all cases and was prominent and associated with conspicuous fibrin and hemorrhage in one of them. Edema of the lamina propria was present in 3 cases, whereas lamina propria fibrosis and chronic inflammation were present in all cases. The presence in all 4 cases of vascular ectasia and other changes characteristic of radiation injury, such as atypical fibroblasts, prompted investigation of the clinical history in 2 cases in which the pathologist was unaware that the patient had received radiation. Pseudocarcinomatous proliferations in the bladder caused by radiation injury have received limited attention in the literature. Our cases illustrate the potential diagnostic errors with which these lesions may be associated.
    Human Pathlogy 07/2000; 31(6):678-83. DOI:10.1053/hupa.2000.7894 · 2.81 Impact Factor

Publication Stats

6k Citations
666.97 Total Impact Points


  • 2004
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 1985–2004
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1980–2004
    • Harvard Medical School
      • Department of Pathology
      Boston, Massachusetts, United States
  • 1991–2001
    • Massachusetts General Hospital
      • Department of Pathology
      Boston, MA, United States
  • 1989–1999
    • University of British Columbia - Vancouver
      Vancouver, British Columbia, Canada
  • 1998
    • Johannes Gutenberg-Universität Mainz
      Mayence, Rheinland-Pfalz, Germany
  • 1996–1997
    • Henry Ford Hospital
      • Surgery
      Detroit, Michigan, United States
    • University of Toronto
      Toronto, Ontario, Canada
  • 1990–1997
    • Maine Medical Center
      Portland, Maine, United States
    • Johns Hopkins University
      • Department of Gynecology & Obstetrics
      Baltimore, Maryland, United States
  • 1989–1997
    • Indiana University-Purdue University Indianapolis
      • Department of Pathology and Laboratory Medicine
      Indianapolis, IN, United States
  • 1987–1996
    • Vancouver General Hospital
      • Department of Pathology and Laboratory Medicine (UBC)
      Vancouver, British Columbia, Canada
  • 1994
    • Jefferson College
      Хиллсборо, Missouri, United States