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Solid Pattern Yolk Sac Tumor: A Morphologic and Immunohistochemical Study of 52 Cases
(Am J Surg Pathol 2012;00:000–000)
Abstract: Yolk sac tumors may exhibit numerous patterns. One
that has received little attention overall, yet is not uncommon, is
a solid pattern, which is especially prone to misinterpretation,
usually as seminoma, in biopsy specimens from metastatic or
mediastinal sites. This distinction is of critical importance as the
2 tumors are treated differently. To determine features useful in
the diagnosis of solid yolk sac tumor we reviewed 52 germ cell
tumors (28 testicular primaries, 21 metastases from the testis,
and 3 mediastinal primaries) that had a yolk sac tumor
component with foci of solid growth, defined as a sheet-like
arrangement of tumor cells occupying >2mm2 and with no or
only rare microcysts. Solid yolk sac tumor was almost always
associated with other patterns, most commonly microcystic/
reticular (75%), glandular (35%), and myxoid (25%). The solid
foci consisted of sheets of cells with usually abundant cytoplasm
that was mostly (85%) pale to clear and frequently had
intercellular basement membrane deposits (75%), rare microcysts
(67%), significant nuclear pleomorphism (65%), and
hyaline globules (65%). In 2 cases (4%), the cells were small
with scant cytoplasm (blastema-like variant). A myxoid background
(39%), lymphocytic infiltrate (17%), and an applique´
pattern (8%) were sometimes observed. On immunostaining,
AE1/AE3 cytokeratin and glypican 3 provided the most intense
and diffuse reactivity for solid yolk sac tumor, whereas
a-fetoprotein was negative in 38%. CD117 stained 59%,
whereas only rare cells in 1 case (3%) were weakly reactive for
podoplanin; OCT3/4 was uniformly negative. We conclude that
solid yolk sac tumor can generally be recognized by careful
morphologic evaluation, especially its association with other
yolk sac tumor patterns, the presence of intercellular band-like
deposits of basement membrane, occasional microcysts, nuclear
pleomorphism, intracellular hyaline globules, and usual absence
of lymphocytes. In difficult cases a concise immunohistochemical
panel consisting of AE1/AE3, glypican 3, and OCT3/4
distinguishes solid yolk sac tumor from other neoplasms.
a-fetoprotein stains are commonly negative or weak and focal
in solid yolk sac tumor and cannot be solely relied on for
diagnosis. Common CD117 positivity in solid pattern yolk sac
tumors makes it an unreliable discriminator between yolk sac
tumor and seminoma.