Presentation about the the second most common type of ovarian tumors which have a very unique property of being similar to the testicular germ cell tumors.

1. Germ cell tumors of ovary
Date- 10-02-16

2. Outline
• Introduction
– Terms, basis, classification, stats
• Primitive germ cell tumors
• Teratomas
– Mature
– Immature
• Mixed
– Gonadoblastoma

3. Introduction

4. Terms
• Germ cells-
– A germ cell is any biological cell that gives rise to
the gametes of an organism that reproduces
sexually.
• Germ cell tumors are composed of a number
of histologically different tumor types derived
from the primitive germ cells of the embryonic
gonad.

5. Basis of germ cell tumors
1. The common histogenesis of these neoplasms
2. The relatively frequent presence of histologically
different neoplastic elements within the same
tumor
3. The presence of histologically similar neoplasms in
extragonadal locations along the line of migration of
the primitive germ cells from the wall of the yolk
sac to the gonadal ridge
4. The remarkable homology between the various
tumors in the male and the female. Eg.seminoma to
dysgerminoma

6. • Germ cell tumors presumed to derived from
the pathogenic transformation of ovarian
germ cells being unique in the fact that they
recreate, however imperfectly, aspects of
human development.

9. The stats
• Germ cell tumors
– Second most common group of ovarian tumors
– All ages from infancy to old age
– Seen most frequently from the first to the sixth
decades(even during fetal life).
– In children and adolescents, more than 60% of ovarian
neoplasms are of germ cell origin, and one third are
malignant.
– In adults 95% are benign and consist of mature cystic
teratomas (dermoid cysts).
– Malignant ovarian germ cell tumors occur in the first
four decades and are rare thereafter.
– 90% are pure type and rest are mixed.

10. Primitive germ cell tumors

11. Dysgerminoma
• Most common of the primitive germ cell tumors / most common
malignant pure ovarian germ cell neoplasm
• Malignant
• Radiosensitive
• Common age <30 years (15-30)
• Composed entirely of germ cells that show morphologic,
ultrastructural, and histochemical similarity to primordial germ cells
• Most common presentation is abdominal enlargement and presence
of a mass in the lower abdomen, sometimes with abdominal pain
and weight loss.
• High risk -Abnormal gonads (due to gonadal
dysgenesis and androgen insensitivity syndrome)
• Ovarian counterpart of testicular seminoma.
• Elevated serum LDH at presentation

12. Dysgerminoma gross features
• Variable size
• Solid, capsulated
• Firm consistency
• Uniform, pale tan to gray-
pink cut surface
• Areas of cystic
degeneration, necrosis, and
hemorrhage are
occasionally present

13. Dysgerminoma microscopy
• Identical to
– Seminoma of the testis
– Germinoma of CNS
• Pattern-
– Composed of aggregates, islands, or strands of large uniform cells surrounded
by varying amounts of connective tissue stroma containing lymphocytes (T).
• Cell features-
– Cell-Large, oval or round with well defined cytoplasmic borders.
– Cytoplasm-ample amount of pale, slightly granular eosinophilic or clear
cytoplasm.
– Nucleus- large, central, round to oval, vesicular nucleus, sharp nuclear
membrane ,unevenly dispersed finely granular chromatin,
– Nucleoli one to two, prominent.
• Giant mononucleate tumor cells, resembling typical dysgerminoma
cells, may be seen.
• Mitoses- common.

14. • Tumor is composed of large aggregates of
uniform cells

15. • Tumor is composed of
trabeculae of tumor cells
surrounded by connective
tissue stroma containing
lymphocytes

16. • Tumor cells show centrally
placed nuclei with delicate
cytoplasmic membranes.
• Prominent nucleoli seen

17. • Special stain
– glycogen in cytoplasm of the tumor cells is PAS+
and removed by diastase digestion
• IHC stains
– PLAP (cytoplasmic and membrane staining)
– OCT4 i.e. Octamer-binding transcription factor
(nuclear staining),
– D2-40 (podoplanin), SALL4, CD117 (c-kit)
(membranous staining)
• Tumor marker
– Serum LDH increase
• Genetic abnormality associated
– Chromosome 12p

18. • 1-OCT4
• 2-CD 117
• 3- PLAP (placental
alk phos)
1, 2

19. Clinical behaviour
• Malignant, slow growing neoplasm, less aggressive
• Lymph node metastasis common to iliac artery and
abdominal nodes
• Direct extension by rupture of capsule, leading to
adhesions to nearby structures
• Hematogenous spread occurs late, to liver, lungs,
bones.
• It is highly chenosensitive and radiosensitive
• Good prognosis generally, 5 year survival>75%

20. Yolk sac tumor
• Also termed endodermal sinus tumor
• Malignant
• Develop as a result of differentiation of primitive malignant
germ cell elements in the direction of yolk sac or vitelline
structures.
• Second most common malignant ovarian germ cell neoplasm
• Common age-
– second and third decades
– first and fourth decades
• Usual presentation is abdominal pain with a large abdominal or
pelvic mass, commonly with extraovarian spread (peritoneum,
retroperitoneal nodes).
• Tumor marker- elevated serum AFP is almost always present; a
very high level is suggestive of the diagnosis

21. YST gross features
• Side- generally unilateral, bilateral indicates
metastatic spread
• Usually large, oval shaped, encapsulated, firm,
and gray-yellow.
• Cut surface- solid and cystic(containing
gelatinous fluid) with necrosis and
hemorrhage.
• Tumor may form adhesions to the surrounding
structures and invade them

23. YST microscopy patterns
Pattern Features
Microscystic or
reticular
Composed of a loose network of small cystic spaces forming a
honeycomb pattern. The microcysts are lined by flat cells with
pleomorphic,
hyperchromatic nuclei
Macrocystic
Myxomatous Small collections of epithelial-like cells forming strands or gland like
structures are seen within abundant myxomatous tissue
Solid
Endodermal sinus Composed of perivascular formations, consisting of a narrow band of
connective tissue with a capillary in the center and lined by a layer of
cuboidal or low columnar epithelial-like cells. The cells have large,
vesicular nuclei and prominent nucleoli. These structures are known as
sinuses of Duval or Schiller– Duval bodies. The presence of these
structures can be considered diagnostic of yolk sac tumor, but their
absence does not exclude the diagnosis.

24. YST microscopy patterns
Pattern Features
Alveolar-
glandular
Polyvesicular composed of numerous small vesicles surrounded by connective tissue
Papillary
Hepatoid Composed of solid aggregates or cords of polygonal cells with even or
granular eosinophilic cytoplasm resembling hepatocytes. Hyaline bodies may
be present.
Glandular or
primitive
endodermal

25. YST microscopy
• Cell features
– Cytoplasm-moderate amount, pale to clear
– Nucleus- hyperchromatic, irregular
– Nucleoli- prominent
– Mitoses common.
• The cells lining microcystic spaces may be flattened and less obviously
malignant in appearance.
• Schiller–Duval bodies (SDBs)
– in only 20% of tumors
– rounded to elongated papillae with a fibrovascular core ensheathed by
primitive columnar cells.
– The papilla may occupy a space lined by cuboidal, flat, or hobnail cells.
– SDBs are usually sparse, but when numerous, create a distinctive
‘endodermal sinus’ pattern.
• Eosinophilic, PAS-positive, diastase-resistant hyaline bodies of different sizes
are present in most YSTs, being most numerous in areas with a reticular or
hepatoid pattern.

26. • Microcystic pattern

27. • Schiller-Duvall bodies

28. • Special stains
– PAS-positive, diastase-resistant hyaline bodies
• IHC stains
– AFP-cytoplasmic,patchy
– Alpha antitrypsin1
– SALL4
– Glypican 3-cytoplasmic
– AE1/AE3-cytoplasmic
– LIN28
• Tumor marker
– Increased level of serum AFP

29. Clinical behaviour
• Highly malignant neoplasm, with early metastasis and
invasion of surrounding structures.
• Lymphatic spread -paraaortic and common iliac lymph nodes
and later supraclavicular nodes.
• Hematogenous spread- late to lungs, liver etc.
• Early recurrences common even after complete excision.
• Serial serum AFP measurements are used for monitoring
therapy and for early detection of metastasis and
recurrences.
• Adverse prognostic factors -stage II or greater, gross residual
tumor after cytoreductive surgery, and liver involvement.
• Complete cure for all stages in more than 80% of cases.
• Nawa et al. found the postchemotherapy survival rates for
stage I tumors to be 95%, but only 25% for stage IV tumors

30. Embryonal carcinoma
• The tumors similar to testicular embryonal
carcinoma
• Rare
• Age- first three decades of life
• Usually present with an adnexal mass, and in half
the cases, endocrine manifestations such as
isosexual pseudoprecocity, irregular bleeding,
amenorrhea, and hirsutism.
• Serum hCG and AFP levels are typically elevated.
• Extraovarian spread common.

31. Gross features
• Generally large, unilateral
• Cut surface is soft, white, tan–gray to yellow
tissue, cysts containing mucoid material, and
foci of hemorrhage and necrosis.

32. Microscopy features
• Pattern- Solid masses, glands, and papillae
• Cell features
– Large pleomorphic cells
– Cytoplasm -amphophilic.
– Nuclei-round and vesicular with coarse, irregular membranes,
– Nucleoli- 1 or more, prominent
– Mitoses common
• Hyaline bodies similar to those in YSTs may be present.
• Syncytiotrophoblastic giant cells (SGCs) are almost always
present, usually singly disposed within or at the periphery of
the tumor nests or within the stroma

34. • IHC Stains
– SGC are hCG positive
– CD30 positive
– PLAP
– NSE
– SALL4
• Tumor markers
– hCG (positive preganancy test)
– AFP

35. Clinical behaviour
• Highly malignant, locally aggressive neoplasm
with extensive spreading in the abdominal
cavity, and metastasizes early.
• Treated by surgical removal and
chemotherapy
• AFP and hCG levels monitored

36. Polyembryoma
• Very rare primitive germ cell tumor
• Gross- bulky, unilateral, and has a focally to extensively
hemorrhagic sectioned surface that is usually soft and
focally cystic.
• On microscopic examination the tumor is characterized
by numerous embryoid bodies mimicking normal early
embryos

37. Microscopic features
• Embryoid bodies
– The classic well-formed embryoid body consists of two
cavities (an amniotic cavity and a yolk sac) separated by
an embryonic germ disc.
– The latter is composed of epithelium resembling that of
embryonal carcinoma underlaid by thin flattened AFP+
epithelium of yolk sac type.
– Some may be imperfectly formed, particularly if the
embryonal-type or YST-type epithelium forms microscopic
carcinomas of those tumor types. 3mm size required.
• These are in a fibrous or edematous stroma.
• Mature and immature teratomatous elements are
usually present
• SGC may be present

38. • Yellow-amniotic cavity
• Blue-embryonic disc
• Purple-atypical yolk
sac

39. • Tumor markers -elevation of serum AFP and
hCG.
• IHC stains
– AFP in the cells lining the yolk sac cavities and
– hCG within the SGC present near the embryoid
bodies

40. Choriocarcinoma
• Rare malignant tumor
• Choriocarcinomatous elements are encountered
in many of mixed germ cell tumors
• Age-usually occur in children or young adults
• Presentation-adnexal mass, pain, and
occasionally, hemoperitoneum. Presentation
similar to ectopic or tubal pregnancy
• The serum hCG is elevated causing
– isosexual pseudoprecocity in children
– menstrual abnormalities, breast enlargement,
androgenic changes, in adults.

41. Gross features
• The tumor is usually large, solid, and
unilateral.
• The cut surface is friable and hemorrhagic

42. Microscopic features
• Cells present in varying amounts
– Syncytiotrophoblast
– Cytotrophoblast
• Cytotrophoblast
– Mononucleate, large, rounded cells with pale cytoplasm
– Present centrally in tumor mass
– Positive for hCG
• Syncytiotrophoblast
– large basophilic, multinucleated, vacuolated cells with
irregular outlines, varying shape.
– Nuclei are hyperchromatic, pleomorphic
• Pattern- biphasic usually plexiform
• Dilated vascular sinusoids, which are the source of the
massive hemorrhage are also present.
• Vascular invasion is prominent in some cases

44. • The cytotrophoblast is the more primitive
element, and the syncytiotrophoblast is
formed from it either directly or indirectly.
• The syncytiotrophoblast is the differentiated,
nondividing, hormone-secreting component.
• IHC stain- beta-hCG

45. Teratomas
• A tumor composed of tissues representing at least
two, but usually all three embryonic layers.
• Type of neoplastic tissue
– uniformly mature mature teratoma (almost always a
dermoid cyst);
– the presence of any immature tissue with an embryonal
appearance immature teratoma.
• Occasionally, a teratoma has a large component of a
single endodermal or ectodermal type of tissue or is
composed exclusively of such tissue
– type are referred to as monodermal teratomas

46. Dermoid cyst/ mature teratomas
• Commonest ovarian tumor
• Occur during the reproductive age
• Generally asymptomatic until complications
like torsion with perforation, bacterial
infection occur.

47. Gross features
• Variable size and weight
• The tumor is round, oval, or globular, with a smooth,
gray-white, and glistening surface
• It is usually freely mobile but occasionally may form
adhesions if perforated.
• The contents of the tumor are liquid at temperatures
above 34 deg cel and become solid at temperatures
below 25.
• Cut surface is uni to multilocular.
• The cut surface of the tumor reveals a cavity filled with
fatty material and hair surrounded by a firm capsule of
varying thickness. The fatty material is similar to
normal sebum.

48. • Arising from the cyst wall and projecting into the cavity
is a protuberance that may vary in size from a small
nodule to a rounded elevated mass.
• It is usually single but may be multiple and is frequently
solid but may be partly cystic.
• This protuberance has been variously termed dermoid
mamilla, dermoid protuberance, Rokitansky
protuberance, embryonic node, or dermoid nipple.
• The hair present in the tumor arises from this
protuberance, and when bone or teeth are present,
they tend to be located within this area.
• Bone, cartilage, mucinous cysts, adipose tissue, thyroid,
and soft brain tissue are visible grossly in some cases.

50. Microscopic features
• Adult-type tissues, usually representing all three germ layers, sometimes
arranged in an organoid fashion. Small foci of fetal-type tissues may
occur
• Ectodermal (predominate) -keratinized epidermis, sebaceous and sweat
glands, hair follicles, and neuroectodermal elements (glial and
peripheral nervous tissue, cerebrum, cerebellum, and choroid plexus).
• Mesodermal -smooth muscle, bone, teeth, cartilage, and fat.
• Endodermal -respiratory and gastrointestinal epithelium and thyroid
and salivary gland tissue. Rare tissues include retina, pancreas, thymus,
adrenal, pituitary, kidney, lung, breast, prostate, and seminal vesicle.
• The neuroectodermal elements can incite a florid vascular proliferation
identical to that described in immature teratomas and their implants.
• Escaped cyst contents elicit a characteristic lipogranulomatous response
in the wall of the cyst or the surrounding

52. Fetiform teratoma (homunculus)
• Extremely rare teratomas in
which an ovarian cyst contains a
structure resembling a
malformed human fetus
(homunculus).
• Most occur in the third or fourth
decade.
• Absence of umbilical cord and
normal extremities.

53. Immature teratoma
• Teratomas which contain immature or embryonal
structures (not neoplastic elements) along with
mature elements.
• These are uncommon tumors occurring most
commonly in the first 2 decades of life and being
almost unknown after the menopause.
• The tumor is usually asymptomatic until it enlarges.
• It tends to grow rapidly and forms a pelvic or lower
abdominal mass causing pressure symptoms, dull
pain, or it may undergo torsion, causing acute pain.
• Occasional patients have elevated serum AFP or hCG
levels

54. Gross features
• Generally larger than the mature type
• Round, oval, or lobulated, soft or firm solid mass, which frequently
contains cystic structures with solid areas present in the cyst wall
covered by an ill defined capsule.
• The cut surface is usually variegated, trabeculated, and lobulated,
varying in color from gray to dark brown.
• Foci of cartilage, bone, hair may be seen.
• Cystic spaces are usually filled with serous or mucinous fluid,
colloid, or fatty material

55. Microscopic features
• The immature, embryonic-type tissue varies from small foci to a
predominant component and is composed primarily of
neuroectodermal elements.
– Neuroepithelial rosettes and tubules, cellular foci of mitotically
active glia, and, occasionally, small areas resembling glioblastoma
multiforme or neuroblastoma.
• Immature or embryonal epithelium of various ectodermal and
endodermal types, as well as immature cartilage and skeletal muscle,
are frequently encountered, but the diagnosis of immature teratoma
is rarely based solely on the basis of the presence of these elements.
• Mature components of varying amounts also seen and so careful
examination and thorough sampling of the tumor is strongly
recommended

57. Important
• The sine qua non is the presence of
embryonic-appearing (not simply immature)
tissue that is usually predominantly
neuroectodermal, specifically neuroepithelial
rosettes and tubules and cellular foci of
mitotically active glia

58. • IHC stains (not required for diagnosis)
– GFAP
– GFRα-1
– OCT4
– LIN28
– PAX6
– CD56

59. Clinical behaviour
• Malignant neoplasm,grows rapidly, penetrates its
capsule, and forms adhesions
• Spreads throughout the peritoneal cavity by
implantation and metastasizes first to the
retroperitoneal, para-aortic, and more distant lymph
nodes and later to the lungs, liver, and other organs.
• Histologic appearances of the metastases and of the
peritoneal implants may or may not reflect the
appearances of the primary tumor.
• Very immature and poorly differentiated tumors have
been found to be associated with worse prognosis

60. • Glial implants in
peritoneum
(Gliomatosis
peritonei)

61. Grading immature teratomas
• Ovarian immature teratomas and their metastases should
be graded because the grade correlates with outcome and
determines which patients receive chemotherapy.
• O’Connor and Norris proposed that immature teratomas
should be divided into two grades,
– grade 1; low grade -a slight degree of immaturity which are not
treated with combination chemotherapy
– grades 2 and 3; high grade -those with a more marked degree
of immaturity which are treated.
• In order to ensure that the primary ovarian tumor has been
adequately sampled, one block of tissue per centimeter of
the greatest tumor dimension should be submitted.

62. Grading immature teratomas
• WHO currently follows AFIP grading system in
which the immature neuroepithelium is
graded.
• The grade is based on the aggregate amount
of immature neuroepithelium on any single
slide.

63. Struma ovarii
• Most common form of monodermal teratoma
• Term used for a teratoma in which the thyroid
tissue has overgrown all other tissues, or one in
which only the thyroid tissue has developed.
• No specific clinical or radiological findings are
present.

64. Gross features
• Appears as red, brown, or greenish-brown,
predominantly solid, soft tissue.
• It may be pure, or associated with another
tumor.
• Forms a uni- or multilocular cyst with colloid-
like contents

66. Microscopic features
• Composed of mature thyroid tissue consisting
of acini of various sizes, lined by a single layer
of columnar or flattened epithelium.
• The acini contain eosinophilic, PAS-positive
colloid.
• There may be a considerable variation in the
size of the acini.
• Colloid within follicles may contain calcium
oxalate crystals.

67. • Various patterns

68. • IHC stains-
– Thyroglobulin
– TTF 1
• Special stain
– PAS + colloid

69. Clinical behaviour
• Generally benign, rarely malignant
• If malignant, most common type is papillary carcinoma
• As struma has no true capsule but is surrounded only
by stroma, invasion of a capsule is not a criterion for
malignancy; also, vascular invasion is rare.
• Occasionally, there is extra-ovarian extension caused
either by rupture of the tumor or by local spread
where the peritoneal cavity contains tumor deposits,
composed of mature thyroid tissue.
– Peritoneal strumosis

70. Strumal carcinoid
• Coexistence of struma ovarii and a carcinoid
tumor. The carcinoid is a trabecular.

71. Mixed germ cell tumors
• These tumors are composed of two
or more neoplastic germ cell
components.
• Careful gross examination and
judicious sampling for microscopic
study.
• Each component and the proportion
of the tumor it represents should be
indicated in the pathology report, as
this may influence treatment and
prognosis.

72. Gonadoblastoma
• Mixed germ cell-sex cord stromal tumors
• Found almost exclusively in patients with an underlying gonadal disorder. The
presence of a Y chromosome is seen.
• The tumors may be soft and fleshy, firm and cartilaginous, flecked with calcium, or
totally calcified. Their color varies from brown to yellow to gray.
• Collections of cellular nests surrounded by fibrous stroma. The nests are solid,
usually small, and oval or round but occasionally may be larger and elongated.
• The cellular nests contain a mixture of germ cells and sex cord derivatives
resembling immature Sertoli and granulosa cells

73. S
u
m
m
a
r
y
• Germ cell tumors second most common of ovarian
tumors.
• The majority are mature cystic teratomas (dermoid cysts)
in women of reproductive age.
• The remainder occur in young women and children; in
these age groups, malignant tumor dominate.
• Immature teratomas are distinguished from mature
teratomas by the presence of immature elements, most
often consisting of primitive neuroepithelium.
• Germ cell tumors show various lines of differentiation
toward oogonia (dysgerminoma), extraembryonic yolk sac
(yolk sac tumors), placenta (choriocarcinoma), or multiple
germ layers (teratoma).

74. References
• Robbins and Cotran pathological basis of disease, 9th
ed (2014)
• Blausteins Pathology of female genital tract 6th ed
(2011)
• Diagnostic Histopathology of tumors Fletcher 4th ed
(2013)
• Various sources on internet