Immature teratoma of the ovary: A clinicopathological study of 28 cases

Kedar K Deodhar; Pallavi Suryawanshi; Milap Shah; Bharat Rekhi; RF Chinoy

doi:10.4103/0377-4929.91508

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ORIGINAL ARTICLE

Year : 2011 | Volume : 54 | Issue : 4 | Page : 730-735

Immature teratoma of the ovary: A clinicopathological study of 28 cases

Kedar K Deodhar¹, Pallavi Suryawanshi¹, Milap Shah², Bharat Rekhi¹, RF Chinoy³
¹ Department of Pathology, Tata Memorial Hospital, Parel, Mumbai, India
² Junior Consultant Pathologist, SRL Diagnostics, Prince Aly Khan Hospital, Mumbai, India
³ Consultant Histopathologist, Prince Aly Khan Hospital, Mumbai, India

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Date of Web Publication

6-Jan-2012

Abstract

Aim: Immature teratoma (IT) of the ovary represents 1% of all ovarian cancers and 20% of malignant ovarian germ cell tumors. This retrospective study of 28 such cases aims to look at its morphological spectrum and to study the correlation of the grade and stage of the tumor with prognosis. Materials and Methods: A retrospective study of 28 cases of IT of the ovary was done. Neuroepithelium was graded as grade I, II and III according to the standard criteria. The presence of immature mesenchyme was also looked for and similarly graded. Results: The median age for the cases was 19 years and abdominal pain was the commonest symptom. Neuroepithelium was seen in 26 cases (6 were grade I, 13 were grade II, and 7 were grade III); and two showed immature mesenchymal tissue (IM) only. IM was seen in all 28 cases, but no correlation with the grade of the IT of the ovary is found. The follow up is available in 23 cases ranging from 6 months to 78 months (median 33 months). Of these, 13 were stage I, 3 were stage II and 7 were stage III ITs. Out of 23 patients, 17 patients were alive without evidence of disease recurrence during the last follow up. Adverse events in the form of death and local recurrence occurred in 6 patients. One patient died of the disease at 7 months duration from the disease onset (stage III, grade II IT). Conclusion: Morphological spectrum of IT of ovary is varied. Immature mesenchyme was seen in all the cases of IT of ovary and its presence should prompt a careful search for immature neuroepithelium. Stage I IT of ovary has better prognosis. Combination of surgery and chemotherapy can give longer survival even in recurrent disease.

Keywords: Alfa feto protein, immature teratoma, immature mesenchymal tissue, neuroepithelium, ovary, salpingo-opherectomy, yolk sac tumor

How to cite this article:
Deodhar KK, Suryawanshi P, Shah M, Rekhi B, Chinoy R F. Immature teratoma of the ovary: A clinicopathological study of 28 cases. Indian J Pathol Microbiol 2011;54:730-5

How to cite this URL:
Deodhar KK, Suryawanshi P, Shah M, Rekhi B, Chinoy R F. Immature teratoma of the ovary: A clinicopathological study of 28 cases. Indian J Pathol Microbiol [serial online] 2011 [cited 2023 Mar 30];54:730-5. Available from: https://www.ijpmonline.org/text.asp?2011/54/4/730/91508

Introduction

Immature teratoma (IT) represents 3% of all teratomas, 1% of all ovarian cancers and 20% of malignant ovarian germ cell tumors. It is found either in pure form or as a component of a mixed germ cell tumor. It occurs essentially during the first two decades of life. According to WHO, immature teratoma (IT) is defined as a teratoma containing a variable amount of immature embryonal type (generally) neuroectodermal tissue. ^[1] This study aims to look at the morphological spectrum of immature teratoma and to study the correlation of grade and stage of the tumor with prognosis.

Materials and Methods

This is a retrospective study. The case files from the year 2002 to 2008, showing a final diagnosis of immature teratoma for the patients, were looked up for from the Department of Pathology in our hospital, and a total of 28 such cases were retrieved. The cases with the diagnosis of mixed germ cell tumors were not included. During the same duration, a total of 242 ovarian germ cell tumors were seen, (thus IT of ovary comprised of 11.6% of all ovarian germ cell tumors at our institution from 2002 to 2008). 19 out of 28 cases being referred, the blocks and slides were sent from other institutes (material ranging from 2 to 25 blocks, mean 10 blocks). In the remaining cases, specimens were available. The gross findings were available in 10 cases. The tumor size ranged from 5 to 28 cm. Most of the cases showed solid and cystic foci, with mucoid, creamish and cartilaginous areas. The hematoxylin and eosin stained slides of all the cases were reviewed by two pathologists (KD and BR). Presence or absence of neuroepithelium was recorded. The ovarian immature teratomas were graded as per the accepted three tier grading system by Norris et al.^[2] Presence of immature mesenchyme was looked up for; and, grading was done by a method similar to the grading of the neuroepithelium. Relevant clinical, demographic and radiological information was extracted from the files and record forms of the patient. Staging of the tumors was done according to the International Federation of Gynaecologists and Obstetricians (FIGO) staging system for primary ovarian carcinomas, wherever possible. Follow up time was calculated from the day of surgery to the last day of contact with each patient.

Results

Our study included a total of 28 cases. As our centre is the tertiary referral centre, majority of our cases were operated elsewhere and were then referred for further advice and treatment.

Clinical Presentation

The age at presentation ranged from 4 years to 40 years with median age of 19 years. Seventeen patients were unmarried and 11 patients were married. None of our patients was pregnant at the time of presentation. Fifteen patients presented with abdominal pain, 13 patients presented with abdominal mass and in one case, the patient presented with secondary amenorrhea. Immature teratoma was unilateral in all these cases (right - 10, left - 15 and site not mentioned - 3). However in 2 cases contralateral ovary showed concurrent dermoid cyst. Preoperative tumor marker levels were available in 15 cases. Alfa feto protein (AFP) was raised in 10 cases (range 24-9283 ng/ml; in 4 cases less than 100 ng/ml) while cancer antigen 125 (CA125) was raised in 5 cases (ranging 33-112 units/ml). The tumor stage was available in 23 cases and the details are given in [Table 1].

Table 1: Summary of the findings of the retrospective study of 28 case files of immature teratoma of the ovary at the Institution from a period of 2002 to 2008

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Histomorphological Features

There were varied histomorphological features. A variety of mature elements were present [Figure 1] and [Figure 2]. Immature teratoma was 'pure' in 25 cases (absence of other malignant germ cell tumor component). In 3 cases, other germ cell tumor components were found (yolk sac tumor in 2 cases and dysgerminoma in 1 case). Twenty six immature teratomas were graded based upon the presence of immature neuroepithelium, [Figure 3] and [Figure 4] as per the standard defining criteria. Six were grade I, 13 were grade II and 7 were grade III immature teratomas. It was observed that grade I teratomas were associated with more mature elements like mature glial tissue and mature cartilage in contrast to grade III teratomas. In 2 cases immature neuroepithelium was not detected and these were considered as immature teratoma due to presence of abundant immature mesenchyme. In all 28 cases, we found immature mesenchyme defined as sparsely cellular, loose, primitive mesenchymal tissue [Figure 5] with mitotic figures. ^[1] We applied similar criteria (as applied to grade the neuroepithelium) to grade the immature mesenchyme. The findings are given in [Table 1]. It showed grade I immature mesenchyme in 11 cases, grade II in 12 cases and grade III in 5 cases. We did not find any significant correlation between immature mesenchyme grade and the grade of immature teratoma. Peritoneal implants of mature glial tissue (gliomatosis peritonei) were present in 3 cases.

Figure 1: (a) Mature epidermal and skin adnexal tissue in the immature teratoma upon histomorphological examination (Hematoxylin and Eosin stain, ×100). (b) Mature epidermal and glandular tissue in the immature teratoma upon histomorphological examination (Hematoxylin and Eosin stain, ×100). (c) Mature glial and choroid tissue in the immature teratoma upon histomorphological examination (Hematoxylin and Eosin stain, ×100). (d) Mature ganglion cells in the immature teratoma upon histomorphological examination (Hematoxylin and Eosin stain, ×200)

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Figure 2: (a) Mature glia in the immature teratoma upon histomorphological examination (Hematoxylin and Eosin stain, ×40). (b) Tooth anlage in the immature teratoma upon histomorphological examination (Hematoxylin and Eosin stain, ×100). (c) Mature cartilage in the immature teratoma upon histomorphological examination (Hematoxylin and Eosin stain, ×100). (d) Mature cartilage in the immature teratoma upon histomorphological examination (Hematoxylin and Eosin stain, ×200)

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Figure 3: (a) Immature neuroepithelium seen in the form of neuroepithelial rosettes in the immature teratoma upon histomorphological examination (Hematoxylin and Eosin stain, ×40). (b) Neuroepithelium, with melanin pigment in the immature teratoma upon histomorphological examination (Hematoxylin and Eosin stain, ×100). (c) Immature neuroepithelium seen in the form of neuroepithelial rosettes in the immature teratoma upon histomorphological examination (Hematoxylin and Eosin stain, ×100). (d) Immature neuroepithelium seen in the form of neuroepithelial rosettes in the immature teratoma upon histomorphological examination (Hematoxylin and Eosin stain, ×200)

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Figure 4: Immature neuroepithelium seen in the form of neuroepithelial rosettes in the immature teratoma upon histomorphological examination (Hematoxylin and Eosin stain, ×400)

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Figure 5: (a, b) Immature mesenchyme as sparsely cellular, loose, primitive mesenchymal tissue with mitotic figures in the immature teratoma upon histomorphological examination (Hematoxylin and Eosin stain, × 100). (c) Immature mesenchyme as sparsely cellular, loose, primitive mesenchymal tissue with mitotic Figures in the immature teratoma upon histomorphological examination (Hematoxylin and Eosin stain, ×200) with mature squamous epithelium on the left. (d) Immature cartilage, surrounded by immature mesenchyme in the immature teratoma upon histomorphological examination (Hematoxylin and Eosin stain, ×200)

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Treatment and Follow Up Details

Treatment details and follow up information was available in 23 cases. Of these, 13 were stage I, three were stage II and 7 were stage III ITs. Out of 13 in stage I immature teratomas, 4 grade I and only one grade II immature teratoma were treated by surgery alone consisting of unilateral salpingo-opherectomy (SO) without any chemotherapy. One case with dermoid cyst of contralateral ovary underwent bilateral salpingo-oophorectomy (without chemotherapy). Two grade III, 2 grade II and One grade I IT underwent SO with additional chemotherapy with bleomycin, etoposide and cisplatinum (BEP). One case with stage I, grade II IT of ovary underwent Total abdominal hysterectomy with salpingo-oophorectomy (TAHBSO), omentectomy and BEP chemotherapy; while one case of stage I, grade II IT underwent bilateral salpingo-oophorectomy (BSO), peritoneal biopsy and BEP chemotherapy.

There were 3 cases of stage II ITs, two being grade III tumors and one of grade I tumor. Out of these 3 stage II ITs, 2 cases of grade III and one patient of grade I IT underwent unilateral SO and BEP chemotherapy.

There were total 7 stage III ITs. Out of which 3 cases (grade II - 2, grade III - 1) underwent unilateral SO and BEP chemotherapy, 3 cases (grade II - 2, grade III - 1) underwent total abdominal hysterectomy with bilateral salpingo-opherectomy and BEP chemotherapy. In one case neuroepithelium was absent and it was treated by total abdominal hysterectomy with bilateral SO and BEP chemotherapy.

Follow up was ranging from 6 months to 78 months with median follow up of 33 months. Out of 23 patients, 17 patients were alive without evidence of disease at the last follow up. Adverse events in the form of death and local recurrence occurred in 6 patients. One patient died of the disease at 7 months (stage III, grade II IT). In this patient, there was a predominant component of yolk sac tumor along with immature teratoma and which was treated by total abdominal hysterectomy with BSO and BEP chemotherapy. Despite the chemotherapy, local recurrence in the form of pelvic mass occurred after 4 months and patient died after 3 months due to refractory disease. Five patients had local recurrences in the form of pelvic mass at the interval of 3 months, 12 months, 4 months, 4 months and 7 months, respectively. All these patients additionally received BEP chemotherapy and are kept on further follow up with radiology and tumor marker levels. They are doing well after 78, 16, 62, 6 and 78 months respectively.

Discussion

Clinical Presentation

The median age at presentation was 19 years, which was similar to other studies. ^[2],[3],[4] Abdominal pain was the most common presenting symptom followed by abdominal mass, compared to other studies where abdominal mass was the most common presenting symptom. ^[2],[3] Patients may sometimes present with paraneoplastic syndrome like limbic encephalitis; ^[5] however, this was seen in none of our cases. IT of the ovary is almost always unilateral as seen in the present study. ^[2],[3] Contralateral ovary showed dermoid cyst in 7.1% of cases (2/28). This observation is similar to the Norris et al. study (6.8% of cases showed dermoid cyst in the contralateral ovary), however, the frequency is less than what was seen in the study by Wisniewski et al.^[3] (two out of seven cases; 28.6%). ^[2]

Preoperative tumor marker levels were available in 15 cases. AFP was raised in 10 cases. Two of these cases (AFP values 8580 ng/ ml and 9283 ng/ml) showed an additional yolk sac tumor (YST) component. This component was not noted initially and was noted on review. These cases probably represent mixed germ cell tumors. The remaining 8 cases did not show yolk sac tumor. According to Heifetz et al.^[6] increased AFP levels almost always indicate the presence of foci of YST. The above lack of finding of YST could represent the sampling error. However, though AFP is widely used as a tumor marker level for IT, ^[7] it has been reported that the AFP level in IT is not correlated to either stage or grade. ^{[7],[8],[9],[10]}

In majority of these cases, the material available was referred material in the form of blocks and slides (mean of 10 blocks). This, at times, can be challenging and the above findings underline the fact that thorough sampling is crucial in ovarian germ cell tumors. CA125 was raised in 29.4% cases similar to other studies (30%). ^[7] In this study, the neuroepithelium was present in 93.1% cases. Many published articles state that IT is characterized by the presence of immature neural tissue. ^{[11],[12],[13]} It is noted that the amount of neuroepithelium correlates with survival and is the basis for grading these tumors. ^[2],[12]

The only type of neural tissue that should be counted in grading a tumor for immaturity is primitive neural tubes and immature rosettes. ^[6] These tissue simulate the various patterns of stroma poor undifferentiated neuroblastoma, primitive neuroectodermal tumor or peripheral neuroepithelioma. ^[6] The type of neural tissue most often misinterpreted as immature in the grading of IT are cellular areas of differentiating neural tissue. These are often more densely cellular areas with a negligible mitotic rate, and small nuclei and more distinct nuclear membranes than the truly significant immature neural cells. ^[6]

In this study, a variety of differentiated tissues were present in the tumors, e.g., skin and skin adnexal tissue, glandular tissue, mature glia, choroid plexus, tooth anlage, cartilage etc. We observed that differentiated ameloblastic epithelium closely resembles neuroepithelium and this can be a potential pitfall for an erroneous diagnosis of immature teratoma [Figure 6].

Figure 6: Ameloblastic epithelium (neuroepithelial mimic - which can be a potential pitfall for an erroneous diagnosis of immature teratoma) (Hematoxylin and Eosin stain, ×400)

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In 2 cases, immature neuroepithelium was absent and these were considered as immature teratoma due to presence of abundant immature mesenchyme. However according to a review article by Ulbright, ^[13] fetal type tissue (immature mesenchyme) alone is not sufficient for a diagnosis of IT. Immature mesenchyme is defined as sparsely cellular, loose, primitive mesenchymal tissue with mitotic figures. ^[2] The literature is sparse in discussing whether a significantly more cellular cartilage can be taken as immature mesenchyme. Cartilage with crowding of lacunae with cells (cellular cartilage) which is surrounded by immature mesenchyme is taken as immature cartilage. We, however, accept that there can be subjectivity in this assessment.

In all 28 cases, we found immature mesenchyme. This observation leads to the conclusion that presence of immature mesenchyme in an otherwise mature teratoma should lead to further sampling to search for the presence of neuroepithelium. This was a significant observation of the present study. However we did not find any significant correlation between immature mesenchyme grade and grade of IT. Gliomatosis peritonei were found in 10.7% of cases (3/28). The exact mechanism of gliomatosis peritonei is not known, but some authors suggest that it represents the teratoma induced metaplasia of submesothelial cells. ^[14] It does not adversely affect the prognosis of patients with IT. ^{[15],[16],[17],[18],[19]}

Treatment and Prognosis

IT of the ovary predominantly occurs in the young patients, and the preservation of fertility is an important factor in the management. In patients with grade I and FIGO stage I tumours, it is sufficient to perform a staging surgery with a unilateral oophorectomy. ^[20],[21] Patients with grade II or III tumors or a more advanced stage disease should be treated with adjuvant chemotherapy containing bleomycin, etoposide and cisplatin in addition to surgery. ^[22] In the natural history of IT of the ovary, the prognosis for patients' is dependent on the stage of the disease and grade of the tumor. ^[2] The current combination chemotherapy results in overall disease free survival rate of >95% and only in a small proportion it causes premature menopause. ^[21]

Summary and Conclusion

Morphological spectrum of immature teratoma of the ovary is varied, complex and offers diagnostic challenges. The literature suggests that presence of immature neuroepithelium is essential to make a diagnosis of immature teratoma (mere presence of immature mesenchyme is not sufficient). However, presence of immature mesenchyme should prompt a careful search for immature neuroepithelium.

There is considerable variation about the interpretation of what constitutes immature neuroepithelium. In grading of IT, primitive neural tubes and immature rosettes are counted. Such tissue simulates various patterns of stroma: poor undifferentiated neuroblastoma, primitive neuroectodermal tumour or peripheral neuroepithelioma. Literature suggests grade I IT have much better prognosis. Combination of surgery and chemotherapy can give longer survival even in recurrent disease. In this study, based on the follow up information, stage I tumors showed favourable outcome. We are unable to make a definitive comment about only the grade and survival due to less sample size and possibility of non uniformity in the treatment.

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