Indu R Nair1*, Rajanbabu Anupama2, Prasad Chaya3, Sreedhar Sarala4
Institution Amrita Institute of
Medical Sciences, India
Institution Amrita Institute of
Medical Sciences, India
Gynecology, Institution Amrita
Institute of Medical Sciences, India
Institution Amrita Institute of
Medical Sciences, India
author: Indu R Nair, Department of Pathology,
Institute of Medical Sciences, India. Tel: + 919495901883;
Received Date: 17 December, 2018; Accepted Date: 04 January, 2019; Published Date: 11 January, 2019
1.1 Background: Teratomas constitute 95% of ovarian germ cell tumors. Though somatic neoplasms have been reported to arise in teratomas,very few studies had attempted to analyze the incidence and associated risk factors.
Methods: We report the incidence of teratomas and the somatic neoplasms arising
from them, over a 5 year period from January 2013 to December 2017,by
the cases treated in our
institute, which is an oncology center in South India.147 teratomas were
encountered, of which,13 were immature teratomas.9 cases had somatic tumors
arising in them, of which 2 were neuroectodermal tumors(one astrocytoma, one
oligodendroglia) and7 were carcinomas(5 squamous cell
carcinomas,1 thyroid carcinoma and 1 mucoepidermoid carcinoma).
We also attempted to study the associated risk
factors. All the carcinomas developed in women above 45 years;
with tumor size more than 10cm and solid area more than 2cm.Hence we suggest
that teratomas with these risk factors need to be thoroughly sampled to exclude
Germ cell tumours constitute 20-25 % of
all ovarian tumors.95
3. Materials and Methods
Records of all 840 ovarian neoplasms treated during the 5-year period from January 2013 to December 2017, in the departments of Gynaecology and Gynaecological Oncology in Amrita Institute of Medical Sciences, Kochi, India were retrieved. Tumours which had undergone torsion were excluded. Clinical data were collected from electronic medical records and the Pathology reports were reviewed for the relevant gross, microscopic and immunohistochemical findings.
155 germ cell tumours were encountered
during this period, which constituted 17.5 % of all ovarian neoplasms, 147 of
these were teratomas (95%). Among the rest eight, 5 were dysgerminomas and 3,
yolk sac tumours. 13 of the teratomas were immature teratomas, (twelve grade 1
, grade 2 in the
3-tier grading system).2 cases of neuroectodermal neoplasms were present, one
oligodendroglioma and the other, a low grade glioma, both in children less than
20 years. Seven cases of carcinomas arising in teratomas were seen.No skin
appendage or melanotic tumors were encountered. (Table-1)The
patients were in the age group ranging from 9 to 84 (mean age-34yrs).The mean
age of patients with benign teratomas was 30 yrs. All the patients with
immature teratoma were below 20 years of age (9-19 years, mean age -13 yrs.)
All carcinomas were encountered in women
above 45 years. (range 46-83, mean-56.4 yrs.) Most common clinical observation
was abdominal pain and lower abdominal fullness. Grossly the tumour size ranged
from 1.2 to 23 cms (mean diameter of 8.5cm), with a predominant cystic
component in 89%.Benign tumours had a mean size of 7.2cm.Malignant tumours were
larger than 10cms in size with a mean diameter of 11.4cm. All teratomas with
somatic tumours had fleshy solid areas and all carcinomas had solid
granular/friable areas more than 2cm in diameter
size ( Ranges
from 2.4 to10.6 cm with a mean of 5.6 cm).
4.1 Neuroectodermal Tumours
First case of neuroectodermal tumour was
of a 16year old girl with a 10 cm ovarian cyst showing mature teratoma with a
solid nodule in the wall measuring 2.4cm in greatest dimension. On microscopy
it showed sheets of cells with uniform oval nuclei and moderate cytoplasm
arranged in a fibrillary background. Admixed were seen many large cells
resembling ganglion cells, suggestive of a low grade glial neoplasm (figure-1). No mitosis/vascular proliferation/necrosis
were seen. The tumour cells were positive for GFAP and p53 with a proliferation
index of 8%. Adjuvant treatment was not given in view of the low grade disease
and patient is doing well 24 months after completion of surgery. The
oligodendroglioma was seen in the 11.2 cm sized ovarian cyst of an 11-year-old
girl. Grossly it was seen as soft solid grey white area
, mean 7.4cmwith a cerebriform appearance.
Microscopy showed a monotonous population of
round, uniform cells with a hyper chromatic nucleus and
perinuclear halo with the classical fried-egg appearance. Also seen was a fine
network of capillaries in the stroma. This was seen focally in an otherwise
encapsulated mature teratoma with an area of immature teratoma, grade2.
The neoplastic cells showed S100 positivity confirming the diagnosis. Ki
67index was 10%. Owing to the presence of immature teratoma, she was treated
with chemotherapy (6 cycles of Etoposide and platinum), and is now doing well 3
years post treatment completion.
Carcinomas constituted 4.7 % of germ cell
tumours, of which 5 were squamous cell carcinomas. One of the struma ovarii had
a differentiated thyroid carcinoma arising in it. The seventh was a
mucoepidermoid carcinoma. All 5 cases of squamous cell carcinomas (figure-2) showed mature cystic teratoma. The
clinicopathological characteristics were studied. (Table-2)Thyroid
carcinoma was seen in a83 year old lady with left ovarian
cyst mea 17cm, with a solid granular nodule mea 7cm.Microscopy showed struma
ovarii with a large partly capsulated nodule composed of closely packed
follicles lined by cuboidal cells with moderate cytoplasm and uniform round
vesicular nuclei. Nuclear features of papillary carcinoma were not seen. The
follicles were invading the capsule, infiltrating into the adjacent area of
fibrosis, adherent to the colon. With these microscopic features, a diagnosis
of follicular carcinoma was made (figure-3).
Owing to the advanced age and comorbidities, no further treatment was offered;
she was kept on follow up and died 4 months after the surgery. Seventh
carcinoma was in a 48-year-old lady with recurrent abdominal pain. She
underwent right ovarian cystectomy, which showed a solid mass mea 10.6cm.A
small cyst in the periphery showed lining by stratified squamous cells with
underlying appendages, suggestive of a mature teratoma. Solid areas showed
mucinous and epidermoid cells along with nests of intermediate cells. The
mucinous cells were positive for CK7 and CEA while the solid nests of
epidermoid cells were positive for p63 andCK5/6, confirming the diagnosis of
mucoepidermoid carcinoma, in a teratoma (figure-4).
While on adjuvant chemotherapy (after
one 1 of 6
cycles of Paclitaxel, Carboplatin chemotherapy regimen), she was found to have
a rectal wall mass suggestive of tumour recurrence at 4months. She was advised
for surgery for removing the recurrent lesion.
Majority of the germ cell tumours were
mature cystic teratomas. Among the monodermal teratomas, struma ovarii was the
most common, as stated inliterature.
the 2 cases of neuroectodermal tumours; one was a low grade glioma in a mature
teratoma and the other an oligodendroglioma, in an immature teratoma.Though
studies have reported neuroectodermal tumours, they are very rare (less than 50
cases) and include the primitive, differentiated and anaplastic types.Majority of the previously reported cases were
astrocytomas, though occasional high grade tumours like glioblastomas are also
described. These were found to arise mostly in mature teratomas; only7 cases
are reported to have developed in immature teratomas.Oligodendrogliomas arising
in teratomas are extremely rare, and to the best of our knowledge, only less
than 10 cases are reported so far with only one case in childhood. Though dysgerminomas are described as the most
common malignant tumours in literature 1, we found a
higher incidence of immature teratomas, mostly of grade 1 type. In a study from
Orissa India, by Pradhan et al ., both teratomas and dysgerminomas
contributed equally to the malignant ovarian germ cell tumours .The incidence of immature teratomas were slightly
more than dysgerminoma in paediatric patients in Kerala, as stated by Rajeswari
and co-workers .The difference in incidence
could be attributed to geographic variation. All immature teratomas occurred in
age group less than 20years, in concordance with other studies.
Malignancies in germ cell tumours can be malignant germ cell tumours like embryonal carcinoma or somatic malignancies arising in teratomas, like carcinomas or sarcomas. In observed patients, all the seven malignancies were carcinomas, no cases of sarcoma or melanoma were encountered. We also encountered a higher number of carcinomas than mentioned in the literature(4.7 % vs. 1-2%).
may be attributed referral bias, as our institute beinga gynaecological
oncology centre, suspected malignancy cases are
referred from outside hospitals. Squamous cell carcinomas were the commonest,
in concordance with the findings described by Kedar et al. from Indian
population.Other carcinomas described in
literature are adenocarcinoma (7%) and sarcomas of different types, like
leiomyosarcoma and angiosarcoma followed by rare tumours like melanoma, which
is often metastatic than primary .The
pathogenesis of squamous carcinomas in teratoma is not yet clear. An in situ
carcinomatous change similar to skin suggests squamous epithelial origin in
most of the tumours. Three of our cases showed full thickness dysplasia of the
cyst wall squamous epithelial lining, favouring this theory. Iwasa et al. had suggested the origin to be from
metaplastic columnar epithelium, supported by the IHC expression of CK18 more
than CK10 similar to that seen in lung and cervix squamous carcinomas where
metaplastic origin is proved  However, we have
not done the differential cytokeratins in any of our cases.
5-10% of struma can harbour thyroid carcinomas, most of which are papillary carcinomas, with the characteristic nuclear features.No definite criteria are described for follicular carcinoma, as mostly the capsule seen around the tumour might be ovarian tissue or capsule. Also, well established criteria for diagnosis are absent because of the rarity of cases .As high as37% of cases of struma ovarii can show malignancy, with metastasis in around 23% . The possible criteria proposed are the presence of infiltration by tumour cells into the surrounding ovarian tissue, or lymphovascular emboli or metastasis. The most acceptable feature of malignancy is extra ovarian spread, into the adjacent tissues or organs but most of the reported cases have not shown aggressive behavior.
Mucoepidermoid carcinoma is a type of salivary gland tumour, which is the least common to arise in a teratoma. A literature search showed less than five reported cases so far. It shows the typical morphology with mucinous, epidermoid and intermediate cell types, in varying combination, depending on the degree of differentiation. In our case all the 3 cell types were well appreciable.
The absence of keratinisation in the epidermoid cells and the presence of well differentiated mucinous cells and intermediate cells excluded a more common adenosquamous carcinoma.
Studies have shown postmenopausal age group and tumour size more than10 cm to be associated with the development of squamous cell carcinoma We also found advancing age to be a risk factor for the development of carcinoma (risk ratio 44.5, P value 0.012).Tumour size is another potential indicator of malignant transformation of teratomas [13,14]. According toKikkawa et al., who reviewed 277 cases from 64 studies, tumours with diameter larger than 9.9 cm or tumours demonstrating rapid growth were found to be associated with an increased risk for malignant transformation.All the carcinomas in our series had a tumour size of 10 cm or more, which was found to be a statistically significant risk factor for malignancy (Fischer’s exact test value 0.0004, p value 0.013).But most of the bulk in these large tumours is contributed by the benign cystic component. Enlargement may also be due to the secondary changes like necrosis and haemorrhage. Hence, an assessment of the size and consistency of the solid areas were done.
Teratomas with mono dermal components or
other tumours arising in them had solid areas, which were fleshy in benign
tumours like carcinoid and hemorrhagic, necrotic and friable in the malignant
ones. All malignant tumours had friable or granular solid areas more than 2cm
in size, unlike the benign ones, which were mostly cystic.Thus, size of fleshy
solid area, more than 2cm was found to be another risk factor in
(Fischer’s exact test value 0.0006, p value less than 0.04). These findings are
also in concordance with the risk factors observed by Park et al.
Carcinomas arising in teratomas being very
rare, there are no treatment guidelines established. Though several groups have
suggested different chemotherapy regimen, the treatment must be tailored to the
type of tumour. The therapy proposed is
multimodality treatment based on optimal cytoreduction, Cisplatin based
adjuvant chemotherapy and radiotherapy for disease localized in the pelvis.It
is recommended that after complete surgical staging, IA patients
need only follow up. Suboptimal surgery and advanced stages are considered to
be adverse prognostic factors. In our cases with squamous cell carcinomas,
four patients underwent complete staging surgery, two of which had
recurrence and other two were diagnosed with disease free. All
carcinomas except the thyroid carcinoma case were given 6 cycles of adjuvant chemotherapy, with cyclophosphamide and
platinum.Out of the two patients who developed recurrence,
one was at 8 months after completion of treatment whereas the other recurred at
6 months. Another patient had diagnosed with tumour recurrence at 9 months and
expired in12 months(Table 2).
Somatic tumours arising in teratomas are rare; comprising4.8%.Commonest malignancy was squamous cell carcinoma (4.7%).Risk factors associated with carcinomatous change in teratomas are age above 45 yrs, tumour size10cm or more and solid friable area, of size 2cm or more.
Though we encountered only seven cases of carcinoma, this proof-of-principle case study shows a significant association of carcinomatous growth with the gross size of the tumour as well as the solid area. In future, a study with a larger sample size might find a stronger association. We recommend that it might be worthwhile to sample extensively the solid areas in all teratomas occurring in the young, so as to ensure the absence of an immature component. Similarly, the friable or granular solid areas larger than 2cms, in large tumours(more than 10cm) occurring in women above 45 years may harbour carcinoma, hence needs to be thoroughly studied.
7.1 Source(s) of support: nil.
7.2 Presentation at a meeting: nil.
7.3 Conflicting Interest: nil.
Figure 1: glioma in teratoma-Hand E-40X.
Figure 2: Squamous cell carcinoma in teratoma-Hand E-40X.
Figure 3: Thyroid follicular carcinoma in struma ovarii-H and E-40X.