Transcript 投影片 1
D2-40 immunohistochemistry in the
differential diagnosis of seminoma
and embryonal carcinoma: a
comparative immunohistochemical
study with KIT (CD117) and CD30
Modern Pathology (2007) 20, 320–325
Sean K Lau, Lawrence M Weiss and Peiguo G Chu
Department of Pathology, City of Hope National Medical Center, Duarte,
CA, USA
Intern 鄭詩燕
Testis: Germ Cell Tumors
Seminoma
Nonseminomatous
Embryonal carcinoma
Yolk sac (endodermal sinus)tumor
Choriocarcinoma
Teratoma
Germ Cell Tumors
Seminoma
Nonseminomatous
localized to the testis
extension to the epididymis,
spermatic cord, or scrotal sac
Stage
I or II
II or III
Metastasis
Lymphatic
lymphatic
Hematogenous to lung or
liver
Treatment
Radiotherapy
Chemotherapy
Prognosis
good
Depend on the tumor type
Seminoma
Age: 15-35y/o
50% of germ cell tumor
Painless swelling
Dysgerminoma in ovary
Seminoma
Bulky masses, sometimes 10 times> the
normal testis.
Homogeneous, gray-white, lobulated cut
surface, usually devoid of hemorrhage or
necrosis
Mostly the entire testis is replaced.
Occasionally, extension to the epididymis,
spermatic cord, or scrotal sac
Seminoma
Seminoma
Seminoma Cell: large and round to
polyhedral and has a distinct cell membrane
A clear or watery-appearing cytoplasm
A large, central nucleus with one or two
prominent nucleoli
The cytoplasm contains varying amounts of
glycogen.
AFP(-) or HCG(-), placental alkaline
phosphatase(+), 15%HCG(+)
Seminoma
Embryonal carcinoma
20- to 30-year age group.
Grow faster than seminoma
Painful
More aggressive than seminomas
Embryonal carcinoma
Size: smaller than seminoma
Usually does not replace the entire testis.
The mass is often variegated, poorly
demarcated at the margins
Punctuated by foci of hemorrhage or
necrosis
Extension through the tunica albuginea
into the epididymis or cord is not infrequent.
Embryonal carcinoma
Embryonal carcinoma
The cells: alveolar or tubular patterns,
sometimes with papillary convolutions
Undifferentiated cells, epithelial appearance
Hyperchromatic nuclei with prominent
nucleoli.
Indistinct cell border, variation in cell and
nuclear size and shape, mitotic figures
HCG(+), AFP (+)
Embryonal carcinoma
Introduction
Some seminomas : increased nuclear
pleomorphism, cell crowding, and lack a
lymphocytic infiltrate -> confusion with
embryonal carcinoma.
Limited biopsy specimen or poor tissue
fixation.
Introduction
Immunohistochemistry
CD 30: Embryonal carcinoma(+),
Seminoma(-),
Mixed germ cell tumors(+/-)
KIT(CD117): Seminoma(+),
Embryonal carcinoma(-)
Mixed germ cell tumors(+/-)
Introduction
D2-40
Monoclonal antibody reacts with an
oncofetal membrane antigen (M2A) which
present in testis fetal germ cells
Intratubular germ cell neoplasia, seminoma(+),
Embryonal carcinoma(-)
Materials and methods
40 cases of testicular germ cell tumor
Age 18-41, mean age: 30
Pure germ cell tumor (26 cases)
19 seminomas, 3 embryonal carcinomas,3
teratomas, 1 yolk sac tumor
Mixed germ cell tumors(14 cases)
7 seminomas, 11 embryonal carcinomas, 10
teratomas, 2 yolk sac tumors, and 1
choriocarcinoma.
Materials and methods
Immunohistochemical staining:
D2-40, KIT, CD30
Xylene (deparaffinized) and ethanol
(dehydrated)
Slide heating in EDTA buffer(pH8) in pressure
cooker
Automated immunostainer -> antibody
detection, counterstained with hematoxylin
and coverslipped.
Result
26
14
Result
D2-40 antibody
Seminoma
-- strong membranous
Embryonic carcinoma
-- weak, focal, distributed along the apical or
luminal surfaces of the cells.
Result (seminoma)
Result (embryonal ca)
Discussion
D2-40 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
Discussion
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 the
apical or luminal surfaces.
Marks et al study
-- D2-40 in seminomas 98%,
embryonal carcinomas 69%.
Discussion
Distinction 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%
Discussion
Immunohistochemical markers: keratins, KIT, and
CD30.
Antikeratin antibodies
-- Embryonal carcinoma : keratin intermediate
filaments
-- Seminomas lacked
Recent study
-- Keratin positive in seminomas 4 to 45%
KIT and CD30: more effective immunohistochemical
markers
Discussion
Previous study
KIT expression in seminoma: 100%
Present study
KIT expression in seminoma: 92%
none in embryonal carcinomas or non
seminomatous germ cell tumors
Discussion
CD30: as a sensitive as well as a specific
maker for embryonal carcinoma (93%)
Focal CD30 expression has been described
in a subset of seminomas
Leroy et al CD30 in combination with KIT
-- seminoma: KIT(-), CD30(+) impossible
-- embryonal carcinoma: KIT(+), CD30(-)
impossible
Discussion
Present study
Sensitivity: D2-40 > KIT in seminomas
Specific: D2-40 < KIT in seminomas
(4/11 embryonal carcinomas +)
D2-40 in seminomas: diffuse and
membranous
D2-40 in embryonal carcinomas: focal and
limited to the apical or luminal surface of the
cells.
Summary
KIT 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.