DISCUSSION:
Cystic teratoma is a common benign tumor found in 10%-20%of women in
their lifetime [5]. However, in rare cases, it might transform into
a malignant form. The most common malignant transformation is squamous
cell carcinoma, with an incidence of around 0.2%-0.8% [6]. We here
discuss a case of the 80-year-old female where mature cystic teratoma
has been transformed into undifferentiated carcinoma.
Any of the three germ layers, ectoderm, mesoderm, and endoderm, can be
the point of development of ovarian teratoma.[7] So malignant
transformation may occur from any of the three germ layers into
different histological tumor types like adenocarcinoma, squamous cell
carcinoma, melanoma, sarcoma, adenosquamous carcinoma, etc. The most
common malignant transformation from MCT is squamous cell carcinoma,
which is around 80% of all the cases of transformations.[8]
Clinically the patient with cystic teratoma usually presents with an
increase in abdominal girth, abdominal pain, abdominal distension, or
palpable pelvic or abdominal mass. Sometimes the patient remains
asymptomatic until the complication occurs. The most common
complications are ovarian torsion, rupture of the peritoneum, and
invasion of the adjacent structures.[9]The gastrointestinal or
urinary symptoms may arise if the tumor has invaded the adjacent organs
in the pelvic cavity.[10]In our case, the patient presented with
lower abdominal pain for two weeks and mild tenderness in the left iliac
region on physical examination.
Preoperative identification of the malignant transformation of the
mature cystic teratoma is difficult. Only 1–2% of the SCC cases can be
diagnosed preoperatively [10]. Multiple criteria have been proposed
to identify it. The criteria like age greater than 55, large tumor size
>10 cm, and radiological signs within revascularization are
most likely to represent the malignant transformation of the cystic
teratoma.[11] So CT scan and MRI are essential in identifying the
preoperative malignant transformation with the features like necrosis,
cystic wall growth, invasion to adjacent peritoneal organs, or
metastasis to the pelvic organs.[12]
Histologically, the undifferentiated tumor may show mesenchymal and
epithelial differentiation features and may show the immune reactivity
for markers such as cytokeratin, vimentin, and epithelial membrane
antigen [13]. In the present case, the undifferentiated area of the
tumor exhibited round to oval cells and did not take immunohistochemical
reagents like P40, SALL 4, Synaptophysin, Desmin, vimentin, CD20 except
for cytokeratin. So we consider our tumor to be an undifferentiated type
with features of epithelial differentiation. However, cytokeratin and
P40 were positive in the squamoid differentiated areas of carcinoma.
Therefore, considering the histomorphological features and
immunohistochemical findings, a final diagnosis of malignant
transformation of MCT into undifferentiated carcinoma and squamous cell
carcinoma was made.
The malignant transformation may be associated with the HPV infection or
due to the alternation in the tumor suppressor gene like p53 and p16.
[5, 14]. The malignant transformation usually has an association
with the level of tumor markers. Therefore, the tumor markers like SCC
antigen, CA125, CA19-9, and CEA are likely to be increased in patients
with this transformation. However, the FIGO stage and tumor size do not
determine the level of these markers. In our case, the level of Serum
CA125 was 200 IU/mL, and CEA was 63.62 µg/L [10].
The standard treatment of malignant transformation of MCTO is radical
surgery and chemotherapy. There is no fixed protocol for optimal
adjuvant therapy due to the rarity of the disease. Surgical treatment is
usually performed by hysterectomy with bilateral salpingo-oophorectomy,
omentectomy, peritoneal biopsy, and paraaortic lymph node dissection.
For chemotherapy, a wide range of therapeutic agents like
anthracyclines, alkylating agents, antimetabolites, platinum agents, and
vinca alkaloids are used.[12] Some scholars report the combination
of Paclitaxel with alkylating agents will improve the survival of the
patients with this transformation [5]. In the present case, the
patient underwent surgical treatment and adjuvant chemotherapy with
Paclitaxel and carboplatin 3 weekly (L1Cl completed).
The prognosis of the malignant transformation depends on factors like
age >55 years, large tumor size, high cancer grade, and
advanced stage of the disease. The cytoreductive surgery in combination
with chemotherapy is likely to improve the prognosis. [12]