215 555 2 PB

Vol. 5, No.
2, Jul-Dec 2021
ANDALAS OBSTETRICS AND GYNECOLOGY JOURNAL
Address for Correspondence:
Editorial Room Andalas Obstetrics and Gynecology Journal, 3rd floor of KSM of Obstetrics and Gynecology,
RSUP DR. M. Djamil Padang, Jl. Perintis Kemerdekaan Padang, Sumatera Barat 25127
Website:
eISSN : 2579-8324 pISSN : 2579-8323
http://jurnalobgin.fk.unand.ac.id/index.php/JOE
LITERATURE REVIEW
Immature Teratoma and Mature Cystic Teratoma
Nova Fenita Sari1, RZ Nizar2
Affiliation authors: 1. Anatomical Pathology Department, Faculty of Medicine, Andalas University,
Dr. M. Djamil Central General Hospital Padang, West Sumatera, Indonesia
Correspondence to: Nova Fenita Sari, email: [email protected], Hp: 085263885782
Abstract
Introduction : Germ cell tumors arise from primordial germ cells and account for about 30% of all
ovarian tumors. More than 95% of this group are benign dermoid cysts (mature cystic teratoma) and
the remaining 5% are malignant. Ovarian teratomas represent 15% to 20% of ovarian germ cell tumors.
Teratomas are classified as mature or immature and often consist of several embryological layers. While
the mature type is benign, the immature type is more aggressive.
Objective : Based on the above, this article will review about immature teratoma and mature cystic
teratoma of the ovary.
Material and methods : The method of writing this scientific paper is a literature review. The data used
are sourced from relevant literature and in accordance with the topics discussed.
Result : Teratomas are a common form of germ cell tumors. Teratomas are histologically defined as
tumors containing tissue derived from all germ cell layers: ectoderm, mesoderm, and endoderm.
Teratomas are classified as immature teratoma, mature teratoma and monodermal teratoma. Conclusion
: Teratomas are usually asymptomatic and if there are symptoms, they tend to be non-specific. In
patients with no residual tumor after surgery, the survival rate is 90-100%.
Keywords: Teratoma, Immature Teratoma, Mature Cystic Teratoma
BACKGROUNDS
Germ cell tumors are the second largest group of ovarian neoplasms after ovarian surface
epithelial tumors and account for about 30% of all ovarian neoplasms. Mature cystic teratoma
is the most common type (95%) with the majority occurring in adults and the remaining 5%
being malignant.1,2 Malignant germ cell tumor (MGCT) represents about 3% of all ovarian
cancers in Western countries and about 20% in Asian and African populations, where
epithelial cancer is less common.3
Malignant ovarian germ cell neoplasms account for less than 5% of ovarian cancers.
However, because these tumors mainly involve women during the reproductive years,
treatment with fertility preservation is an important issue. Germ cell neoplasms are
interesting because several processes are involved in their origin that are associated with
early embryonic development, reproduction, and sex determination. There are various types
of histologic types, including: dysgerminoma, immature teratoma, yolk sac tumor,
choriocarcinoma, polyembryoma, and mixed MOGCT. This group differs from ovarian
139
Received : June 9th, 2021
Accepted : June 19th, 2021
Correspondence : Nova Fenita Sari, email: [email protected]
Vol. 5, No. 2, Jul-Dec 2021
Website:
eISSN : 2579-8324 pISSN : 2579-8323
epithelial cancer, in two aspects, namely a younger age and good prognosis, due to the higher
number of diagnoses in the early stages and high chemosensitivity.4,5
Ovarian teratomas represent 15% to 20% of ovarian germ cell tumors. Teratomas are
classified as mature or immature and often consist of several embryological layers. While the
mature type is benign, the immature type is more aggressive. Mature cystic teratoma is the
most common type, 8-15% bilateral, but some cases are reported to be bilateral and
multiple.6
The origin of ovarian teratomas has been the subject of speculation and dispute for
centuries. The parthenogenetic theory, which states the origin of primordial germ cells, is now
more widely accepted than the theory of teratoma originating from blastomeres separated
at an early stage of embryonic development, or the theory of teratoma originating from rest
embryos.4,5
Based on the above and the number of cases found in daily practice, this article will
review this ovarian teratoma more deeply.
IMMATURE TERATOMA
Immature teratoma is a tumor consisting of tissue derived from three layers of embryonic
germ cells, ectoderm, mesoderm, and endoderm. In contrast to mature teratomas, immature
teratomas contain immature components (usually primitive/neuroectodermal embryonic
tissue) including in their most primitive form, embryoid bodies.7,8
Immature teratomas are the third most common germ cell tumor, accounting for 15-
20% of all primitive germ cell tumors and 3% of all ovarian teratomas. These tumors can occur
at any age, but are more common in the first two decades of life.9 The origin of teratomas has
been a matter of interest, speculation, and debate for centuries. The parthenogenic theory,
which suggests the origin of primordial germ cells, is now the most widely accepted.2
Immature teratomas usually present as a pelvic mass, increased abdominal
circumference, and vaginal bleeding. Isosexual precocity is rare, but serum markers,
particularly AFP and hCG, are generally elevated. Ultrasound usually distinguishes these
tumors from benign cystic teratomas, although some solid components such as goiter may
cause confusion.8
On ultrasound examination, the appearance of an immature teratoma is nonspecific,
although the tumor is usually heterogeneous, the lesion is partially solid, usually with
scattered calcifications. On CT and MRI imaging, immature teratomas usually have a large,
irregular solid component with calcifications. Small foci of fat help identify these tumors
(figure 1).10
140
Website:
eISSN : 2579-8324 pISSN : 2579-8323
Figure 1. Ultrasound and CT scan of immature teratoma10
These tumors are usually unilateral, large, predominantly solid, fleshy, gray in color
and may contain cysts, hemorrhages and necrosis. These tumors are usually unilateral, but
may coexist with a mature cystic teratoma, as seen in at least 10-15% of cases. Immature
teratoma size is usually larger than mature teratoma, with a reported range of 9 to 28 cm. It
may be a round, oval, or lobulated solid mass, soft or hard, which often contains a cystic
structure with solid areas within the cyst wall (Figure 2).2
Figure 2. Macroscopic immature teratoma3
Microscopically, immature teratomas are found to be immature embryonic variables,

mostly in the form of neuroectodermal tubules and rosettes, but occasionally with mitotically
active cellular components (glia), mixed with ectodermal elements and endodermal, with
varying degrees of maturation. The tubules are lined by overlapping, hyperchromatic cells
with multiple mitoses. Immature cartilage, adipose tissue, bone and skeletal muscle are often
found. The most primitive component of immature teratoma is in the form of embryoid
bodies formed from yolk sac epithelium whose epithelium resembles embryonal carcinoma
(dominant tumors composed of embryoids, which die are called polyembryoma). Extensive
proliferation of reactive blood vessels can be seen in immature teratomas. (figure 3).3,5,7
141
Website:
eISSN : 2579-8324 pISSN : 2579-8323
A B
Figure 3. Microscopy of immature teratomas. a). Immature neuroepithelial and mesenchymal
elements, b). glial tissue with neuroepithelial tubules3,5
O'Connor and Norris proposed that immature teratomas should be divided into two
classes, namely those with less immature grades (grade 1; low grade), those not treated with
combination chemotherapy, and those with more pronounced immaturity (grades 2 and 3;
high grade). (Table 1).2,7
Table 1. Grading immature teratoma

Grade Histological criteria
Grade 1 Tumours with rare foci of immature neuroepithelial tissue that copy <1 low power
field (40x) in any slide (kk
Grade 2 Tumours with similar elements, occupying 1-3 low power fieds (40x) in any slide
(highr grade)
Grade 3 Tumour with large amount of immature neuroepithelial tissue ocupying >3 low
power fields (40x) in any slide (high grade)
Various types of immunohistochemical examination can be performed on this

immature teratoma, including SALL4 positive in intestinal and nervous tissue (figure 1.4a).
SOX2 identifies more specific areas of immature nerves, and is useful for grading immature
teratomas (figure 1.4b). Glypican-3 may also exhibit unequal neuroepithelial
immunoreactivity.3,7
Figure 4. Immunohistochemistry. a) Tubules expressing SALL4, b) Neuroepithelial tubules

with strong SOX2 expression3,7
142
Website:
eISSN : 2579-8324 pISSN : 2579-8323
Management of immature teratoma, among others, in a young patient whose tumor

appears to be localized to one ovary (stage IA), unilateral and surgical salpingo-oophorectomy
should be performed. If fertility is not a problem, or the contralateral ovary or uterus is
involved, total abdominal hysterectomy and bilateral salpingo-oophorectomy should be
performed. Patients with stage IA, grade 1 tumors or who have exclusively mature glial
implants (grade 0) have an excellent prognosis and are treated with surgery alone. Patients
with grade 2 or 3, stage IA, or with immature implants should undergo combination
chemotherapy. VAC regimens have been replaced by platinum-containing regimens such as
cisplatin, etoposide, and bleomycin (BEP).11,12
In patients with no residual tumor after surgery, the survival rate is 90-100%. The
prognosis is less favorable for patients with residual tumor or recurrent immature teratomas.
After chemotherapy, the implant is usually lost, or replaced by mature, necrotic, or fibrotic
tissue.3
MATURE CYSTIC TERATOMA

Tumors consisting of mature tissue originate from two or three germ layers
(ectoderm, mesoderm and endoderm). Tumors are usually cystic (mature cystic teratoma),
but rarely solid (mature solid teratoma).7
Mature teratomas occur over a wide age range, from infancy to lifelong, even in the
ninth decade, although with the greatest incidence during the reproductive years, (80% or
more). Mature teratoma is an ovarian neoplasm that most often occurs in children under 15
years of age. Mature cystic teratoma is the only ovarian germ cell neoplasm that occurs in the
first year of childhood.5,7
Mature cystic teratomas are diploid, have a normal 46XX karyotype, and are ascribed
to germ cells after the first meiotic division. Mature ovarian teratoma differs from mature
postpubertal testicular teratoma which is malignant, aneuploid, having complex cytogenetic
abnormalities including 12p amplification. Ovarian cystic mature teratoma and testicular
prepubertal mature teratoma are similar in that they are both diploid, have normal and
benign karyotypes.4,13
Teratomas are usually asymptomatic and if there are symptoms, they tend to be non-
specific. Symptoms present in patients include abdominal pain, abdominal mass, most tumors
are incidental findings on imaging studies or at the time of surgery. Ten percent are bilateral.
Abdominal pain is the most common symptom, followed by abnormal uterine bleeding.
Complications include torsion, acute or subacute rupture (more common during pregnancy),
infection, idiopathic autoimmune hemolytic anemia, virilization.4,13
143
Website:
eISSN : 2579-8324 pISSN : 2579-8323
Ultrasonography most often shows a cystic lesion of a dense echogenic tubercle

(Rokitansky nodule) protruding into the lumen. The presence of bone confirms the diagnosis.
The second manifestation is a diffuse or partial echogenic mass with localized echogenicity
usually showing sebaceous material and hairs, whereas the third manifestation consists of
several thin echogenic bands caused by hairs in the cyst cavity. On CT scan, mature cystic
teratoma is seen as a complex mass with septal division, variable attenuation, calcification
and presence of fat. If the tumor contains fat, it can also be differentiated by MRI (figure 5).2,13
Figure 5. CT scan of mature cystic teratoma, spherical cystic mass with capsule2
Mature teratomas are almost always bilateral cystic tumors in about 15% of cases.
They range in size from 0.5 to 4cm (average 15cm), but are often <10 cm long, and have a
smooth, grayish-white surface. The cross section is a unilocular cyst or a multilocular cyst
covered with skin containing sebaceous material and hair. Dense nodules are composed of
fatty tissue. with teeth or bone usually protrudes into the lumen of the cyst (Rokitansky
bulge). Dermoid cysts can contain a variety of mature somatic tissue that can be seen with
the naked eye, such as brain tissue, bone, cartilage, adipose tissue, mucus cysts, and thyroid
(Figure 6).2,9
Figure 6. Macroscopic mature cystic teratoma. Cyst containing bone, teeth and hair2,9
144
Website:
eISSN : 2579-8324 pISSN : 2579-8323
Microscopically, mature cystic teratoma found tissue originating from the three germ
layers. The ectodermal tissue is represented by squamous epithelium and other skin adnexa,
usually the most abundant. Brain tissue, glia, nervous tissue, retina, choroid plexus, and
ganglia may also be encountered. Mesodermal tissue is represented by bone, cartilage,
smooth muscle, fibrous tissue and fat. Endodermal tissue is represented by gastrointestinal,
bronchial, glandular, thyroid, and salivary gland tissues. In a study of 100 cases, ectodermal
structures were found in 100%, mesodermal in 93%, and endodermal in 71% of cases. Rare
tissues, such as the prostate, have been found (Figure 7).9,16,17,18
Figure 7. Microscopy mature cystic teratoma, a). respiratory epithelial tissue and cartilage, b)
squamous epithelium and skin adnexa, c) brain tissue, d). salivary glands 2,3,5
Immunohistochemical examination of mature cystic teratoma, namely GFAP and

Nestin. Mature cystic teratomas (dermoid cysts) are treated conservatively, especially in
14
children and adolescent girls. Ovarian cystectomy is the treatment of choice. This tumor is a
benign tumor and most patients are young at the time of diagnosis, conservative surgery is
recommended, with complete resection of the cyst to avoid recurrence. Management should
include examination of the opposite ovary to determine involvement.3,15,16,17
These mature cystic teratomas are benign, unless malignant transformation occurs.
Overall about 4% of adult cystic teratomas recur, according to one study. Tumors that are
bilateral, involving women under 30 years of age, and those greater than 8 cm in diameter
are more likely to recur.5,7,19,20
145
Website:
eISSN : 2579-8324 pISSN : 2579-8323
CONCLUSION
Histologically, immature teratomas are graded according to WHO and AFIP. Immature
teratomas have 3 components with immature tissue, in contrast to mature teratomas which
have 3 components (ectoderm, mesoderm, endoderm) without immature tissue. Mature
cystic teratomas are benign, unless malignant transformation occurs whereas immature
teratomas are more aggressive.
REFERENCES
1. Eroschenko VP. Di Fiores Atlas of Histology with Functional Correlations. 11th Ed.
2008:455-62.
2. Blaustein A, Kurman RJ, editors. Blaustein’s pathology of the female genital tract. 6th
ed. New York, NY: Springer; 2011:1246 p.
3. Mutter GL, Prat J, editors. Pathology of the female reproductive tract. 3., rev. ed.
London: Churchill Livingstone; 2014:873 p.
4. Ghalleb M, Bouzaiene H, Slim S, Hadiji A, Hechiche M, Ben Hassouna J, et al. Fertility-
sparing surgery in advanced stage malignant ovarian germ cell tumor: a case report. J
Med Case Reports. 2017 Dec;11(1):350.
5. Wilkinson N. Pathology of the ovary, fallopian tube and peritoneum. New York:
Springer; 2014:292-97.
6. Long Y, Jing W, Guoping D. Management of giant ovaryan teratoma : a case series and
review literature. Oncology Letters 4. 2012: 672-676.
7. Kurman RJ, Carcangiu ML, Herrington CS, Young RH. WHO Classification of Tumours of
Female Reproductive Organs. 5th ed. 2020:119-21.
8. Kurman RJ, Ellenson RH, Ronnette BM. Blaustein’s pathology of the female genital
tract. 6th ed. 2011:869-91.
9. Nucci MR, Olivia E. Gynecologic Pathology (Foundations in Diagnostic Pathology
Series. Elsevier. 2009:520-35.
10. Goyal LD, Kaur S, Kawatra K. Malignant mixed germ cell tumour of ovaryan unusual
combination and review of literature. 2014;4.
11. Alwazzan AB, Popowich S, Dean E, Robinson C, Lotocki R, Altman AD. Pure Immature
Teratoma of the Ovary in Adults: Thirty-Year Experience of a Single Tertiary Care
Center. Int J Gynecol Cancer. 2015 Nov;25(9):1616–22.
12. Douay-Hauser N, Koskas M, Walker F, Luton D, Yazbeck C. Diagnosis and management
of an immature teratoma during ovarian stimulation: a case report. J Med Case
Reports. 2011 Dec;5(1):540.
13. Aloudek CJ. Pathology of Germ Cell Tumors. In: Soslow RA, Tornos C, editors.
Diagnostic Pathology of Ovarian Tumors [Internet]. New York, NY: Springer New York;
146
Website:
eISSN : 2579-8324 pISSN : 2579-8323
2011 [cited 2019 Jul 11]. p. 155–91. Available from:

http://link.springer.com/10.1007/978-1-4419-9751-7_13
14. Yoshikata R, Yamamoto T, Kobayashi M, Ota H. Immunohistochemical Characteristics
of Mature Ovarian Cystic Teratomas in Patients With Postoperative Recurrence:
International Journal of Gynecological Pathology. 2006 Jan;25(1):95–100.
15. Nucci MR, Oliva E, editors. Gynecologic pathology. Edinburgh: Churchill Livingstone;
(Foundations in diagnostic pathology). 2009. 710 p.
16. Park J-Y, Kim D-Y, Suh D-S, Kim J-H, Kim Y-M, Kim Y-T, et al. Analysis of outcomes and
prognostic factors after fertility-sparing surgery in malignant ovarian germ cell tumors.
Gynecol Oncol. 2017;145(3):513–8. doi: 10.1016/j.ygyno.2017.03.023.
17. Blumenfeld Z, Evron A. Preserving fertility when choosing chemotherapy regimens—
the role of gonadotropin-releasing hormone agonists. Expert Opin Pharmacother.
2015; 16: 1009– 1020
18. Patterson DM, Murugaesu N, Holden L, et al. A review of the close surveillance policy
for stage I female germ cell tumors of the ovary and other sites. Int J Gynecol Cancer.
2008; 18: 43– 50.
19. J.Y. Park, D.Y. Kim, D.S. Suh, J.H. Kim, Y.M. Kim, Y.T. Kim, et al., Outcomes of surgery
alone and surveillance strategy in young women with stage I malignant ovarian germ
cell tumors, Int. J. Gynecol. Cancer 26 (2016) 859–864.
20. Solheim, C.G. Trope, E. Rokkones, J. Kaern, T. Paulsen, H.B. Salvesen, et al., Fertility
and gonadal function after adjuvant therapy in women diagnosed with a malignant
ovarian germ cell tumor (MOGCT) during the “cisplatin era”, Gynecol. Oncol. 136
(2015) 224–229
147

215 555 2 PB

Uploaded by

Document Informationclick to expand document information

Copyright:

Available Formats

215 555 2 PB

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

215 555 2 PB

Uploaded by

Copyright:

Available Formats

Vol. 5, No.

Figure 1. Ultrasound and CT scan of immature teratoma10

Figure 2. Macroscopic immature teratoma3

Microscopically, immature teratomas are found to be immature embryonic variables,

Table 1. Grading immature teratoma

Various types of immunohistochemical examination can be performed on this

Figure 4. Immunohistochemistry. a) Tubules expressing SALL4, b) Neuroepithelial tubules

Management of immature teratoma, among others, in a young patient whose tumor

MATURE CYSTIC TERATOMA

Ultrasonography most often shows a cystic lesion of a dense echogenic tubercle

Immunohistochemical examination of mature cystic teratoma, namely GFAP and

2011 [cited 2019 Jul 11]. p. 155–91. Available from:

You might also like