Presentation on theme: "D2-40 immunohistochemistry in the differential diagnosis of seminoma and embryonal carcinoma: a comparative immunohistochemical study with KIT (CD117)"— Presentation transcript:
1D2-40 immunohistochemistry in the differential diagnosis of seminoma and embryonal carcinoma: a comparative immunohistochemical study with KIT (CD117) and CD30Modern Pathology (2007) 20, 320–325Sean K Lau, Lawrence M Weiss and Peiguo G ChuDepartment of Pathology, City of Hope National Medical Center, Duarte, CA, USAIntern 鄭詩燕
3Germ Cell Tumors Seminoma Nonseminomatous localized to the testis extension to the epididymis, spermatic cord, or scrotal sacStageI or IIII or IIIMetastasisLymphaticlymphaticHematogenous to lung or liverTreatmentRadiotherapyChemotherapyPrognosisgoodDepend on the tumor typeStage I: Tumor confined to the testis, epididymis, or spermatic cord • Stage II: Distant spread confined to retroperitoneal nodes below the diaphragm • Stage III: Metastases outside the retroperitoneal nodes or above the diaphragm
4Seminoma Age: 15-35y/o 50% of germ cell tumor Painless swelling Dysgerminoma in ovary
5Seminoma Bulky masses, sometimes 10 times> the normal testis. Homogeneous, gray-white, lobulated cut surface, usually devoid of hemorrhage or necrosisMostly the entire testis is replaced.Occasionally, extension to the epididymis, spermatic cord, or scrotal sac
7SeminomaSeminoma Cell: large and round to polyhedral and has a distinct cell membraneA clear or watery-appearing cytoplasmA large, central nucleus with one or two prominent nucleoliThe cytoplasm contains varying amounts of glycogen.AFP(-) or HCG(-), placental alkaline phosphatase(+), 15%HCG(+)contain syncytiotrophoblasts
8SeminomaLow magnification shows clear seminoma cells divided into poorly demarcated lobules by delicate septa. B, Microscopic examination reveals large cells with distinct cell borders, pale nuclei, prominent nucleoli, and a sparse lymphocytic infiltrate.
9Embryonal carcinoma 20- to 30-year age group. Grow faster than seminomaPainfulMore aggressive than seminomas
10Embryonal carcinoma Size: smaller than seminoma Usually does not replace the entire testis.The mass is often variegated, poorly demarcated at the marginsPunctuated by foci of hemorrhage or necrosisExtension through the tunica albuginea into the epididymis or cord is not infrequent.
12Embryonal carcinomaThe cells: alveolar or tubular patterns, sometimes with papillary convolutionsUndifferentiated cells, epithelial appearanceHyperchromatic nuclei with prominent nucleoli.Indistinct cell border, variation in cell and nuclear size and shape, mitotic figuresHCG(+), AFP (+)
13Embryonal carcinomaundifferentiated cells as well as primitive glandular differentiation. The nuclei are large and hyperchromatic
14IntroductionSome seminomas : increased nuclear pleomorphism, cell crowding, and lack a lymphocytic infiltrate -> confusion with embryonal carcinoma.Limited biopsy specimen or poor tissue fixation.
16IntroductionD2-40Monoclonal antibody reacts with an oncofetal membrane antigen (M2A) which present in testis fetal germ cellsIntratubular germ cell neoplasia, seminoma(+),Embryonal carcinoma(-)
17Materials and methods 40 cases of testicular germ cell tumor Age 18-41, mean age: 30Pure germ cell tumor (26 cases)19 seminomas, 3 embryonal carcinomas,3 teratomas, 1 yolk sac tumorMixed germ cell tumors(14 cases)7 seminomas, 11 embryonal carcinomas, 10 teratomas, 2 yolk sac tumors, and 1 choriocarcinoma.
18Materials and methods Immunohistochemical staining: D2-40, KIT, CD30 Xylene (deparaffinized) and ethanol (dehydrated)Slide heating in EDTA buffer(pH8) in pressure cookerAutomated immunostainer -> antibody detection, counterstained with hematoxylin and coverslipped.
22Result (embryonal ca)during an automobile accident when the knees impact the dashboard.
23DiscussionD2-40 recognizes M2A antigen which present in fetal germ cells, lymphatic endothelium, and mesothelial cells.M2A antigen expression in all seminomas and seminomatous components of mixed germ cell tumors
24Discussion Present study: -- D2-40 in pure or mixed seminoma: 100% (26/26),(mixed) embryonal carcinoma 29% (4/14)-- Seminoma: diffuse membrane staining-- Embryonal carcinomas: focal and confined to theapical or luminal surfaces.Marks et al study-- D2-40 in seminomas 98%,embryonal carcinomas 69%.
25DiscussionDistinction between seminoma and embryonal carcinoma can be made on a morphologic basis using conventional histologic methods.Studies addressing the impact of central histopathologic review of previously diagnosed testicular tumors have demonstrated major discrepancy rates of 4–11%
26Discussion Immunohistochemical markers: keratins, KIT, and CD30. Antikeratin antibodies-- Embryonal carcinoma : keratin intermediatefilaments-- Seminomas lackedRecent study-- Keratin positive in seminomas 4 to 45%KIT and CD30: more effective immunohistochemical markers
27Discussion Previous study KIT expression in seminoma: 100% Present studyKIT expression in seminoma: 92%none in embryonal carcinomas or non seminomatous germ cell tumors
28DiscussionCD30: as a sensitive as well as a specific maker for embryonal carcinoma (93%)Focal CD30 expression has been described in a subset of seminomasLeroy et al CD30 in combination with KIT-- seminoma: KIT(-), CD30(+) impossible-- embryonal carcinoma: KIT(+), CD30(-)impossible
29Discussion Present study Sensitivity: D2-40 > KIT in seminomas Specific: D2-40 < KIT in seminomas (4/11 embryonal carcinomas +)D2-40 in seminomas: diffuse and membranousD2-40 in embryonal carcinomas: focal and limited to the apical or luminal surface of the cells.
30SummaryKIT and CD30: a useful markers that allows for seminoma to be distinguished from embryonal carcinoma.Although a highly sensitive marker of seminomas, focal D2-40 immunoreactivity can be seen in a subset of embryonal carcinomas, thus limiting the practical value of this marker for discriminating between these particular malignancies.