|Year : 2015 | Volume
| Issue : 1 | Page : 211-215
Squamous carcinoma coexistent with teratoma of ovary: A clinicopathological study of 12 cases diagnosed over a 10-year period at a tertiary cancer referral center
Bharat Rekhi1, Pinki Parikh1, Kedar K Deodhar1, Santosh Menon1, Amita Maheshwari2, Rajendra Kerkar2, Sudeep Gupta3
1 Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India
2 Department of Surgical Oncology (Gynecology), Tata Memorial Hospital, Mumbai, Maharashtra, India
3 Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
|Date of Web Publication||16-Apr-2015|
Department of Pathology, Tata Memorial Hospital, Dr. EB Road, Parel, Mumbai - 400 012, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Somatic malignancy in an ovarian teratoma including a squamous carcinoma (SCC) is rare. Clinicopathological features of 12 ovarian teratomas with coexistent SCCs are presented.
Materials and Methods: Over a 10-year-period, 12 ovarian teratomas with coexistent SCCs were reviewed and analyzed.
Results: The age range was 31-68 years (median, 49), and the tumor size (nine cases) varied from 10 to 18 cm (mean, 12.4). Stage-wise (10 cases), 7 cases (70%) were in stage I; a single case (10%) in stage II, and two (20%) cases were in stage III. Microscopically, all 12 tumors revealed mature teratoma with SCC, as a discrete tumor (6, 50%), or arising from the epithelium of the teratoma in six (50%) cases. SCC component was commonly moderately differentiated (eight cases) or poorly differentiated (three cases). P63 immunostaining reinforced squamous differentiation in a single poorly differentiated SCC and CK5/6 in another tumor. All patients underwent surgery. Two cases revealed positive lymph nodes and contiguous colonic involvement. Three patients (stages II and III) underwent adjuvant chemotherapy (CT). Outcomes (seven patients) (3-58 months) included five patients who are free-of-disease (all stage I) and two patients who are alive-with-disease (stages I and III).
Conclusion: SCC and coexistent ovarian teratomas are rare. Most cases present at an early stage, commonly in perimenopausal women. Teratomas occurring in such patients should be optimally sampled for SCC. Teratomas coexistent with SCC are invariably mature-type. P63 is useful in differentiating poorly differentiated SCC from germ cell tumor components. Surgery forms the treatment mainstay. Adjuvant CT may be offered in high-stage that forms as an adverse prognostic parameter.
Keywords: Malignant transformation in a teratoma, ovarian teratoma, squamous carcinoma with ovarian teratoma
|How to cite this article:|
Rekhi B, Parikh P, Deodhar KK, Menon S, Maheshwari A, Kerkar R, Gupta S. Squamous carcinoma coexistent with teratoma of ovary: A clinicopathological study of 12 cases diagnosed over a 10-year period at a tertiary cancer referral center. J Can Res Ther 2015;11:211-5
|How to cite this URL:|
Rekhi B, Parikh P, Deodhar KK, Menon S, Maheshwari A, Kerkar R, Gupta S. Squamous carcinoma coexistent with teratoma of ovary: A clinicopathological study of 12 cases diagnosed over a 10-year period at a tertiary cancer referral center. J Can Res Ther [serial online] 2015 [cited 2019 Nov 19];11:211-5. Available from: http://www.cancerjournal.net/text.asp?2015/11/1/211/138083
| > Introduction|| |
Malignant transformation in an ovarian teratoma is very rare, with an incidence of <2%.  At our institution, nearly 400 ovarian cancer cases are diagnosed per year, accounting for 2.4% of total cancer cases.  Squamous carcinoma (SCC) is the most common somatic malignancy known to occur in a teratoma, followed by an adenocarcinoma and a melanoma. These tumors are invariably diagnosed postoperatively, as there are no well-described preoperative features that can help in predicting their exact diagnosis. Despite their rarity, there are sizable studies about this tumor type, except an occasional one from our country. ,,,,,,,,,,,,,,,, This study aims to characterize clinicopathological features of 12 cases of ovarian teratomas with coexisting SCCs, diagnosed over a 10-year-period at a single institution in our country.
| > Materials and methods|| |
During a 10-year period (2003-2013), we identified 290 cases of ovarian teratomas with 65 teratomas with coexisting malignancies, including somatic carcinomas, sarcomas, and germ cell-type of carcinomas, such as embryonal carcinomas and choriocarcinomas. The cases were searched from the hospital computerized search engine. After critical review by two authors (BR with PP), 12 cases of ovarian teratomas with coexisting SCCs were included in this study. Inclusion criteria were tumors containing both SCC and teratomatous components in the same ovary, either in the form of discrete tumors or as an integrated tumor component. We excluded two cases in which there was a SCC of ovary, but no identifiable teratomatous components. We also excluded any case of SCC with coexisting ovarian endometriosis. Certain immunohistochemical markers such as p63, CK5/6, and epithelial membrane antigen (EMA) were performed in individual cases. Critical review of all cases was performed by two authors. Clinical information was obtained from the hospital case files and electronic medical records.
| > Results|| |
Twelve cases were analyzed. The age range was 31-68 years (median, 49) and the tumor size in nine cases, varied from 10 to 18 cm (mean, 12.4). Stage-wise (10 cases), seven cases (70%) presented with stage I, and a single case (10%) presented with stage II and two cases (20%) presented with stage III disease.
Gross findings were available in eight cases (66.6%). In all eight cases, there were cystic ovarian masses with thickened cyst walls. In two out of eight cases, there were focal solid areas in the form of a mural nodule. In six out of eight cases, pultaceous material and hair structures, reminiscent of a dermoid cyst were identified [Figure 1].
|Figure 1: Gross specimen (fresh state). (a) Cut surface displaying predominantly cystic tumor with focal solid areas. A tooth is noted (arrow). (b) Fixed specimen of the same case showing cystic element and ragged cut surface with solid area (marked)|
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Microscopically, all 12 tumors contained "pure" mature teratoma in the form of a dermoid cyst as a distinct component. Cartilage was noted in three tumors. SCC was seen as a discrete tumor (six cases, 50%) and was seen arising from the teratomatous component in six cases (50%). In two cases origin of the SCC from the columnar epithelium, undergoing/squamous metaplasia, was identified. SCC was moderately differentiated in eight cases, poor in three cases, and well-differentiated in a single case. On immunohistochemical staining, p63 positivity reinforced squamous differentiation in a single poorly differentiated SCC. CK 5/6 and EMA reinforced carcinomatous differentiation in another single case each, respectively. In two tumors, lymphovascular emboli were identified, while in a single tumor, perineurial invasion was found. In two tumors, areas of necrosis were seen. A single case displayed squamous and glandular differentiation of the carcinomatous elements [Figure 2],[Figure 3] and [Figure 4].
|Figure 2: Microscopic findings of the above case. (a) Dermoid cyst/ mature cystic teratoma (H and E, ×200), (b) cystic areas within the dermoid displaying respiratory-type epithelium ((H and E, ×400), (c) mature cartilage (H and E, ×200), (d) poorly differentiated squamous carcinoma, displaying focal keratinization (arrow) ((H and E, ×400), and (e) diffuse p63 immunostaining reinforcing squamous differentiation (diaminobenzidine, ×200)|
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|Figure 3: Case 5. Microscopic findings: (a) Columnar epithelial lining of the dermoid cyst undergoing squamous metaplasia and dysplasia (H and E, ×200). (b) Squamous metaplasia and dysplasia seen at higher magnification. A single goblet cell reminiscent of columnar epithelium is noted (arrow) (H and E, ×400). (c) Areas of poorly differentiated squamous carcinoma (H and E, ×200). (d) Diffuse EMA positivity reinforcing carcinomatous differentiation (diaminobenzidine, ×400)|
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|Figure 4: (a) Single section displaying dermoid cyst (yellow arrow) and carcinomatous elements (red arrow) (H and E, ×40), (b) dermoid cyst (H and E, ×200), (c) squamous carcinoma (H and E, ×200), and (d) CK5/6 positivity reinforcing squamous differentiation (diaminobenzidine, ×400)|
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Therapeutically, all patients underwent surgical resection, mostly in the form of total abdominal hysterectomy with bilateral salpingo-oophorectomy with positive lymph nodes in two cases and colonic involvement in the same two cases. Three patients (stages II and III) underwent adjuvant chemotherapy (CT) including six cycles of platinum-based CT. Outcomes (seven patients during 3-58 months) included five free-of-disease (all stage I) and two alive-with-disease (stages I and stage III) [Table 1].
|Table 1: Clinicopathological features of 12 squamous cell carcinomas coexistent with ovarian teratomas|
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| > Discussion|| |
The reported incidence of malignant transformation in an ovary teratoma is <2%.  A malignant tumor can arise from any of three germ cell layers in a teratoma and is identified adjacent to both normal and metaplastic cells. , SCC is the most common transformation, although adenocarcinoma, adenosquamous carcinoma, sarcoma, carcinoid, and melanoma have also been reported, albeit rarely. ,,,,,,,,,,,,,,, The clinical presentation is similar to other ovarian tumors and includes abdominal pain and distension, secondary to a pelvic mass, and also in the form of bowel or bladder symptoms in locally advanced cases.  Ovarian teratomas with coexisting SCC comprise 0.3% cases of ovarian cancer cases at our institution.  This study forms the single largest documented descriptive series of ovarian teratomas coexisting with SCCs from our country , [Table 2].
|Table 2: Literature review of documented series of squamous cell carcinomas coexistent with ovarian teratomas/dermoid cysts|
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Preoperative suspicion of malignant transformation is difficult and poses great challenge and dilemma regarding a need for surgical management and adjuvant therapy.  In most cases, definitive diagnosis is invariably rendered postoperatively, as also noted in our study. Risk factors for malignancy in a teratoma include patient age, tumor size, imaging characteristics, and serum tumor marker levels. It has been observed that compared to a benign dermoid cyst, malignant transformation occurs in relatively older population; the mean age range reported being 45-60 years, as also observed in this study. As most cases have been reported in postmenopausal women, we, similar to Chiang et al.,  observed these tumors in relatively younger (i.e., perimenopausal women). Therein lays the need for optimal histopathological sampling to rule out malignant transformation, especially in a large-sized teratoma occurring in a patient after 45 years. 
Larger tumors correlate with increased risk of malignant transformation. Kikkawa et al.  observed that tumor diameter more than 9.9 cm associated with 86% sensitivity for malignant transformation.  In this study, the average tumor size in the largest dimension was 12.5 cm, corroborating with other studies. ,,,,,, One of the reasons for larger tumor size in this study also relates to ours being a tertiary cancer referral hospital, most patients present with large-sized tumors.
Importance of serum tumor markers has been cited in a few earlier studies. Kikkawa et al.  observed serum carcinoembryogenic antigen (CEA) was the best screening marker, followed by SCC antigen and both of these were superior to estimation of celomic antigen (CA)-125 and CA 19.9. It was finally recommended that measurement of CEA and SCC antigen would provide a good strategy for preoperative risk assessment and help in making differential diagnosis of teratoma and SCC arising from mature teratoma. , Mori et al.  reported that age above 40 years and serum SCC antigen levels above 2.5 ng/ml were 77% sensitive and 96% specific for malignant squamous transformation in a teratoma, therefore, useful in monitoring recurrent disease. 
In an attempt to identify radiographic features suspicious for a SCC in a mature teratoma, Kido et al.  observed the presence of a solid component with contrast enhancement, evidence of adherence to surrounding structures, and necrosis and hemorrhage as important parameters.
On gross pathological examination, a tumor arising on a background of an ovarian teratoma may appear as a polypoidal mass, mural nodule, or in the form of a mural plaque with areas of hemorrhage and necrosis, as observed in this study.
Microscopically, all cases in this study contained dermoids, except for a single tumor that contained cartilage and another tumor that showed foci of thyroid tissue (struma). We observed origin of SCC component mostly from squamous than columnar epithelium.
Regarding the origin of these tumors, two hypotheses have been proposed for the histogenesis of SCC in mature teratoma of the ovary. According to the first, it arises from the epidermis that has been supported by findings of a presence of Bowen's disease such as pattern of the skin. According to another hypothesis, it arises from the respiratory epithelium. This hypothesis is supported by findings indicating that SCC arises from the respiratory epithelium concomitant with squamous metaplasia as noted in one of our cases. ,,, Iwasa et al.  studied 24 cases of SCCs arising from teratomas, with intent to identify role of CK 10 and CK 18 to establish histogenesis. They found that only a minority of cases was CK10 positive, which is normally expressed in the squamous epithelium; whereas, the majority of the cases expressed CK18 positive, which is normally expressed in the columnar epithelium. These findings are very similar to those observed for SCCs of cervix and lung derived from squamous metaplasia derived from columnar epithelium, and they differ from those cases obtained in the case of SCC of vulva and skin derived from squamous epithelium. 
Genetically, underlying molecular mechanisms thought to be associated with malignant transformation in teratoma include alteration in both p53 and p16-Rb pathways. 
Because of rarity of this condition and its incidental nature, the optimal management approach remains unclear. The reported literature suggests that the surgical management for the described cases is performance of total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy, with additional steps as needed to ensure surgical debulking of all grossly visible disease. The role of adjuvant therapy is unclear. Limited experience suggests that surgical management with close follow-up alone would suffice for early-stage IA disease. Stage IC and above have been targeted with a variety of adjuvant regimens with variable outcomes. Relatively poor control has been noted with the conventional regimens to treat non-epithelial ovarian cancers, that is cisplatin, etoposide, bleomycin and vincristine . On the other hand, remarkable responses have been achieved with paclitaxel-based regimen in some cases. Radiotherapy has also been used with the rationale of SCC being a radiosensitive tumor and has brought forth variable results for cancers within antecedent dermoids. In the latest case series and review of literature, in cases of SCC arising from teratoma of the ovary, whole pelvis radiation and concurrent weekly platinum-based or paclitaxel-based CT following aggressive cytoreduction have been shown to be of benefit. 
| > Conclusion|| |
SCC and coexistent ovarian teratomas are rare. SCC, mostly moderately differentiated, is exclusively associated with "pure" mature teratomas/dermoids cysts, mostly seen in perimenopausal women. Teratomas in such patients, especially large-sized, should be carefully sampled for SCC that mostly occurs as a discrete tumor. P63 immunostaining is useful in differentiating poorly differentiated SCC from other germ cell tumor component. Surgery forms treatment mainstay. Adjuvant CT is offered in high-stage disease that in itself is an adverse prognostic parameter. SC antigen markers with CEA might help in preoperative assessment.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]