http://informahealthcare.com/gye ISSN: 0951-3590 (print), 1473-0766 (electronic) Gynecol Endocrinol, 2014; 30(3): 187–191 ! 2014 Informa UK Ltd. DOI: 10.3109/09513590.2013.860122
THYROID CARCINOMA IN OVARIAN TERATOMA
Conservative treatment of a young patient with thyroid carcinoma in adult ovarian teratoma – case report Aneta Cymbaluk-Ploska1, Anita Chudecka-Głaz1, Maria Chosia2, Olgierd Ashuryk3, and Janusz Menkiszak1 Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, 2Department of Pathology, and 3Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland Abstract
Keywords
The cystic mature teratomas, including dermoid cysts, are one of the most frequently occurring benign ovarian tumors diagnosed in female patients. The process of neoplastic transformation in mature dermoid cysts is applicable only to 1–2% of cases. In our article, we present a rare case of thyroid carcinoma development in adult teratoma in 21-year-old patient. The young age, certain pathomorphological features and clinical data (small size of neoplastic lesion, correct values of tumour markers, unilateral character, regular levels of thyreoglobulin and absence of any significant deviations in imaging examinations), were the basis for attempting to apply the conservative treatment both in the scope of gynecological surgery and in the supplemental endocrinological therapy. In the patient, the one-sided adnexectomy was performed, considering pathological lesions on the adnexa, as well as the other ovary dermoid cyst was enucleated, without the hysteroctomy procedure. Considering the lack of any morphological lesions and functional changes relating to thyroid gland, the treatment was not radicalised in this scope, either. At present, one year after the primary operation treatment, the patient does not manifest any disease symptoms, whereas the other ovary, in the follow-up ultrasound examinations, shows normal size and echostructure. The thyroid-stimulating hormone (TSH) suppression keeps being applied.
Adult teratoma, ovary, thyroid carcinoma
Introduction The cystic mature teratomas, including dermoid cysts, are one of the most frequently occurring benign ovarian tumours diagnosed in female patients that may constitute up to 10–20% of all the neoplastic tumours of this organ. In 1–3%, they may undergo malignant transformation. This phenomenon occurs more often in postmenopausal women, mainly in the 5th and 6th life decade(s) [1,2]. In 75% of neoplastic transformations, the squamous epithelial carcinomas are diagnosed, whereas the percentage of the occurring sarcomas and adenomas is similar and it is equal to ca. 7% [3]. The majority of cases of malignant neoplastic lesions in mature teratomas are found incidentally by pathomorphologists, because in the macroscopic picture there are no exponents of the malignant neoplastic process. The prognosis in dermoid cysts with malignant transformation is serious but it is conditional upon several factors, and first of all on the kind of the malignant component, the stage of the clinical progression of the neoplasm, the age of the patient as well as the adequate operation treatment [2]. The aim of this article is to present a rare case of the occurrence of papillary carcinoma of the thyroid gland in the adult dermoid ovarian cyst in a young woman, taking into Address for correspondence: Aneta Cymbaluk-Ploska, MD, PhD, Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, Al. Powstan´co´w Wielkopolskich 72, 70-111 Szczecin, Poland. E-mail: [email protected]
History Received 11 June 2013 Revised 14 October 2013 Accepted 24 October 2013 Published online 7 January 2014
particular account the conservative treatment both in the scope of gynecological surgery and that of thyroid gland.
Case report A 21-year old woman without any complaints came to a gynaecologist for a routine gynaecological examination. In a bimanual gynaecological examination, a thickening of blurred borders on the right side adnexa and the presence of tuberous lesion of ca. 7 cm diameter in the projection of the left adnexa were reported. The Douglas sinus was painless and not lowered. Additionally in the vaginal speculum examination, the ectopic glandular tissue was reported on the vaginal part disc. The result of the cytological examination from the uterine cervix was correct – no features of intraepithelial neoplasia or carcinoma were found. The ultrasonographic examination (USG) was performed during which solid-cystic bilateral ovarian tumours were diagnosed. The tumour had no divisions and the cystic part contained fluid of high density. The risk malignancy index (RMI) calculated on the basis of the available data was equal to 69.6. That is, assuming that the cut off point value for benign and malignant tumours is 200, they were recognised as the benign lesions in the ovary. The patient was qualified as eligible for laparoscopy during which a 5-cm tumour was detected in the right ovary, and a 8-cm tumour with uneven surface in the left ovary. Considering the size of tumours, the high probability of causing injury of the capsule during the laparoscopy and the lack of any certainty as for the benign character of the lesion, the decision was made on the laparoscopy procedure conversion to laparotomy, during which both tumours were enucleated. In both cases, the remaining part
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of the ovary was stitched with continuous sutures obtaining full hemostasis. No free fluid was detected in the peritoneal cavity. After thorough macroscopic evaluation of tumours, in which solid cystic lesions were diagnosed, with a sebum mass component in the right adnexa tumour, they were recognised as adult dermoid ovarian cysts which do not require the intraoperational examination. In the postoperative histopathological examination, the following was diagnosed: in the right adnexa tumour – teratoma adultum cysticum. In the teratoma tissue, the mature forms of tissues: cartilaginous, neuroglia, epithelium of the respiratory system and fragment of cutis are noticeable, whereas in the left adnexa tumour – teratoma adultum cysticum with visible solid cystic nodule of 12 mm diameter, which morphologically and immunophenotypically corresponded to carcinoma papillare thyreoides [papillary thyroid carcinoma]. The tumour was built mainly of structure typical of dermoid cysts, i.e. the skin tissue with skin appendages and hair and certain small areas of other mature tissues: cylindrical glandular epithelium, cartilaginous tissue, nervous tissue, and neuroglia. The diagnosed papillary carcinoma within this tumour was built of solid papillary structures, with a small liquid space. The cancer cells included oval or round overlapping nuclei, of minimum cellular atypy and of ground glass appearance (or ‘‘orphan Annie’’ nuclei], with visible nuclear grooves. The mitotic activity index was low: 1/10 HPF. Necrosis was absent. In the performed immunohistochemical examinations, the following results were obtained: CK AE 1/ AE 3þ, Vimentinþ, thyroid transcription factor-1 (TTF-1) þ, HBME-1þKi-67þ (55% of cells) (Figure 1). After obtaining the result, in order to exclude the metastatic lesions in the abdominal cavity, the computer tomography scanning was carried out, in which the following was diagnosed: in the right ovary projection – visible solid – cystic lesion of 4 3 2 cm dimensions – the image suggesting that the ovarian structure was regular, with numerous Graffian follicles, and with haemorrhagic cyst of the corpus luteum – which was verified by conducting transvaginal ultrasonografic examination. The homogenous liver was without any perceptible focal lesions. The pancreas, spleen, adrenal glands, kidneys, inferior caval vein, aorta and retroperitoneal space were normal. No enlarged lymph nodes were disclosed in the intra-abdominal space and in the retroperitoneal space. In order to exclude the primary focus occurrence, the USG of thyroid was performed, in which the thyroid gland was reported as positioned typically, not enlarged, of reduced and heterogenic echogenicity. The dexter thyroid lobe of 45 19 14 mm dimensions, the sinister thyroid lobe of 39 16 11 mm dimensions. The isthmus was 3 mm thick. No focal lesions were disclosed in the thyroid gland. Along the sternum – clavicle – breast muscle, on both sides of the neck, there are several lymph nodes with preserved vascular hilus; on the right side of the neck, the biggest one up to 9 mm, and on the left side of the neck up to 12 mm. In the left submandibular region, a lymph node of 17 6 mm dimensions. The whole examination of the thyroid gland might have suggested the chronic autoimmune process occurrence in the thyroid gland. Prior to the operation, the routine determination of only CA125 and HE4 markers was carried out. Both markers’ values were within the normal range: CA125 – 11.6 IU/ml and HE4 – 63.3 pmol/l, respectively. Other markers, characteristic of germinal tumours, as well as parameters of thyroid gland functions were determined after receiving the histopathological examination result. The obtained results were as follows: beta HCG 50.1 mU/ml, AFP 1.19 ng/ml, thyroidstimulating hormone (TSH) – 2.32 mU/ml, ft3 – 3.85 pg/ml, fT4 – 1.49 ng/dl, thyroglobulin 16.3 ng/ml, chromogranin A – 58.3 ng/ml, aTG – 17.4 IU/ml, aTPO – 34.6 IU/ml. Only the
Gynecol Endocrinol, 2014; 30(3): 187–191
Figure 1. The microscopic image of the papillary thyroid carcinoma in the cystic mature teratoma tissue. (A) Histological image of the whole tumour in small enlargement (staining H&E). (B) Histological image in big enlargement. The n (staining H&E). (C) Positive immunohistochemical reaction in nuclei of carcinoma cells in the presence of thyroid transcription factor-1 (TTF-1).
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DOI: 10.3109/09513590.2013.860122
concentration of SHBG was slightly increased and it was equal to 147.2 nmol/l. In view of the lack of pathological deviations in the computer tomography scanning result, the young age of the patient and having no children, as well as considering pathomorphological features of the tumour, the decision was made on applying the maximally conservative treatment both as regards the gynaecological surgical procedure and the endocrinological treatment. In view of the too conservative procedure taken during the first operation, consisting only in enucleation of the dermoid cyst, in which next, in the pathomorphological examination, the thyroid carcinoma was diagnosed in addition, a decision was made on relaparotomy, for the treatment radicalisation. Relaparotomy is not routine procedure. We decided to exercise it because the patient was of young age and planned saving treatment. We needed a full staging for this saving treatment which was not done during the first surgery because ovarian cysts macroscopically looked as mature teratoma without raising the suspicion of malignancy. Full staging was impossible to carry out with laparoscopy again. The laparotomy was carried out, during which the left adnexectomy and omentectomy were performed, the right ovary cyst was enucleated, biopsy specimens were collected from peritoneum, and the washing was performed. In the postoperative histopathological and cytological examination(s), no deviations from normal condition were found. In the removed adnexa on the left side, the ovary tissue with corpus albicans, follicular cysts, and numerous resorptive granulomas were reported, with no neoplastic tissue. The ovarian tissue was without any substantial morphological lesions. In the removed right ovarian cyst, the haemorrhagic cyst of corpus luteum was reported. The omentum and peritoneal biopsy specimens were without any traits of neoplastic cell proliferation. In washings from peritoneal cavity, the absence of any neoplastic cells was observed. Due to the lack of any focal lesions in thyroid gland ultrasound image as well as considering the absence of any significant deviations in biochemical test results, the decision was made to leave the thyroid unoperated, introducing, however, the hormonotherapy with Levothyroxine, so as to cause TSH suppression. The patient has been under the care and control at the Endocrinology, Metabolic Diseases and Internal Diseases of PMU. In the PET CT examination conducted six months after the operation, no traits of the neoplastic process recurrence were disclosed. The patient has been taking hormonal contraception. The thyreglobulin levels are normal. The dexter ovary, despite the hemorrhagic cyst enucleation, shows normal dimensions and echostructure.
Discussion The cystic mature teratomas, including adult ovarian teratomas, and among them, the most frequently occurring dermoid cysts, rarely undergo malignant transformation. The malignant transformation in tumours of these types concerns mainly the epithelial component, most often in the form of squamous epithelial carcinoma, but the following ones are also reported: adenocarcinomas, sarcomas, germinal tumours, malignant melanomas, neuro-endocrine tumours (NET) and thyroid carcinomas. While the thyroid carcinomas in struma ovarii-type tumours are not rare, in adult teratoma they occur incidentally. Rather seldom, since only in 0.1–0.3% of cases, the occurrences of thyroid carcinomas are reported in cystic mature [adult] teratomas, most frequently in dermoid cysts. Until now only 15 such cases have been reported in the world. Only in two cases, the patient’s age was not over 30 years [4]. The prevailing clinical
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symptom in the majority of patients was the hypogastric pain. Only in one case reported by Krnojelac et al. [5], like in our patient, the tumour was not accompanied by any symptoms. In five cases, the conservative operations were performed on reproductive organs [4–7]. In all the reported 15 cases, the thyroid carcinoma was of papillary type, and in it – in six cases, it was follicular variation. Most of the thyroid carcinoma cases in adult teratoma are diagnosed postoperatively. In the medical literature, it is reported that prior to operation there appear certain characteristics that may prove the malignancy of ovarian lesions. Among them the following are listed: at first place, the elevation of thyroglobulin level, clinical and biochemical hyperthyreosis, which, however, occurs only in 5–8% of patients, the ‘‘struma pearls’’ ultrasound image, occurrence of partitions and their thickness in USG [8,9]. Considering the fact that during the first operation, the macroscopic image, in the majority of cases, has no features proving the malignant character of the occurring lesions, the full oncological procedure (staging), or the intraoperational examination, is not performed (especially, that the image of the adult teratoma is characteristic, and neoplastic transformations in it are very rare). Apart from extremely rarely occurring thyroid carcinoma cases in adult teratoma, more frequently the struma ovarii-type tumours occur, which are diagnosed when more than 50% of the tumour tissue is made by the thyroid tissue. In 5–10% of cases, within the struma ovarii area, it may come to malignant transformation [10]. Most frequently, it is the papillary carcinoma (ca. 70% of cases) and the follicular carcinoma [9]. The morphological image and immunophenotypic profile of papillary thyroid carcinoma in the thyroid gland and within the ovarian teratormas are similar. In patients with the thyroid carcinoma in adult teratomas, the BRAF, RET, and RAS mutations occur with a different frequency, which also proves the genetic similarity to thyroid carcinomas occurring in the thyroid gland [8,9,11]. In the differential diagnostics, one should also take into account the extremely rarely encountered metastases of the papillary thyroid carcinoma to the ovary, which causes the diagnostic difficulties both of clinical and of pathological nature [12]. In the case reported by us, the possibility of metastates occurrence was excluded. The procedure in the malignant variation of the struma ovarii type tumour is quite widely reported, considering higher frequency of occurrence. Therefore, part of the authors reporting the cases of the occurrences thyroid carcinoma in dermoid cyst(s) have assumed the procedure reported in the malignant variations of struma ovarii. Makani et al. [13], among 39 cases of struma ovarii with neoplastic transformation diagnosed, the metastases in nine patients which represented 23% of the reported group. In the same publication, he reported six cases of the neoplastic process recurrences which occurred on the average within time period up to four years from establishing the diagnosis. Therefore, he recommend the four-year-follow-up in patients with malignant struma ovarii variant, consisting in the scintigraphy of the whole body with J131 and in determining the thyroglobulin level. He recommends that in patients in whose ultrasonographic imaging examinations, or during labelling with radioactive iodine, are premises for the recurrence of neoplastic process, the thyroglobulin level monitoring shall be performed for a period up to 10 years from establishing the diagnosis [13]. In the available literature, the reports on the said recurrence in patients with thyroid carcinoma cases in the adult teratoma are missing. Lee et al. in 2008 carried out the additional radical surgery in a 35-year-old patient two months after the laparoscopic adnexectomy procedure. Decision on extending the scope of the procedure was made due to lack of the oncological purity
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(fragmentation of cyst, after sucking of the liquid part) during the laparoscopic procedure. The postoperative masses and the staging performed did not demonstrate any dissemination of the disease. The authors of the article emphasise that the laparoscopic procedures should be performed very carefully in order to guarantee the intact cyst removal [14]. Lataifeh et al. [7], who in a 39-year-old patient with the papillary thyroid carcinoma in adult teratoma, carried out the laparoscopic adnexectomy procedure, draw our attention to the fact that such conservative treatment should be performed in young patients who are about to maintain their fertility, with low initial staging and, first of all, in medical centres specialising in endoscopic operations. Dane et al. reported a case of a patient similar to ours. However, due to the fact that it was a large-sized tumour, the operation was conducted from the very beginning with laparotomy applied. The tumour masses were removed, leaving the ovarian tissue remains hoping for its regeneration. In our case, we performed the left adnexectomy on the side of the earlier
Gynecol Endocrinol, 2014; 30(3): 187–191
diagnosed thyroid carcinoma and we enucleated the benign lesion from the right ovary, trying to conserve as much as possible of the intact ovarian tissue. Owing to such a conservative procedure, in the follow-up examinations, we can observe in the right ovary, the correctly functioning ovarian tissue, with numerous Graffian follicles (Figure 2). The authors [4,5,7] decided, in patients with diagnosed papillary thyroid carcinoma in mature teratoma, to carry out total thyroidectomy when there were visible nodules in USG image. After the thyroidectomy, the patient was supplemented with thyroid hormones, so as to cause TSH suppression. Dane is of the opinion that thyroidectomy is important due to two reasons. First, it enables the correct clinical evaluation (thyroid carcinoma with metastases to ovary, or occurrence of papillary carcinoma in teratoma, independent of thyroid carcinoma). Second, in order to conduct effective treatment with radioiodine, the thyroidectomy is necessary. In case of the patient reported by us, the lack of any lesions in the USG image of thyroid gland, the pathomorphological features of the thyroid carcinoma and the low-concentration level of thyroglobulin gave the grounds for the conservative treatment of thyroid gland. The negligible number of the reported cases of the occurrences thyroid carcinoma in mature dermoid cyst(s) does not permit to establish the unequivocal algorithms of procedures. It seems that due to the histopathological similarity the method of treatment, reported in the malignant struma ovarii-type tumours, can be partly extrapolated. It is worthwhile to emphasise that the small tumour size (510 cm diameter), the absence of necrosis, and the low mitotic activity (55/10 HPF) are associated with favourable prognosis [15]. We are of the opinion that the young age of the patient, certain clinical features, and pathomorphological data should be the basis for considering the maximally conservative procedure.
Declaration of interest The authors report no conflicts of interest.
References
Figure 2. Imaging examinations in the period of observation after treatment.
1. Kido A, Togashi K, Konishi I, et al. Dermoid cysts of the ovary with malignant transformation: MR appearance. Am J Roentgenol 1999; 172:445–9. 2. Sakuma M, Otsuki T, Yoshinaga K. Malignant transformation arising from mature cystic teratoma of the ovary: a retrospective study of 20 cases. Int J Gynecol Cancer 2010;20:766–71. 3. Hanada M, Tsujimura T, Shimizu H. Multiple malignancies (squamous cell carcinoma and sarcoma) arising in a dermoid cyst of the ovary. Acta Pathol Jpn 1981;31:681–8. 4. Dane C, Ekmez M, Karaca A, et al. Follicular variant of papillary thyroid carcinoma arising from a dermoid cyst: a rare malignancy in young women and review of the literature. Taiwan J Obstet Gynecol 2012;51:421–5. 5. Krnojelac D, Hadzic B, Curcin N, et al. Malignant transformation of thyroid tissue in an ovarian dermoid cyst: case report. Med Pregl 1999;52:395–8. 6. Ryder M, Yuri E, Nikiforov J, Fagin A. Follicular variant papillary thyroid carcinoma arising within an ovarian teratoma. Thyroid 2007; 17:179–80. 7. Lataifeh I, Abdel-Hadi M, Morcos B, et al. Papillary thyroid carcinoma arising from mature cystic teratoma of the ovary. Obstet Gynecol 2010;30:884–6. 8. Wolff EF, Hughes M, Merino MJ, et al. Expression of benign and malignant thyroid tissue in ovarian teratomas and the importance of multimodal management as illustrated by a BRAF-positive follicular variant of papillary thyroid cancer. Thyroid 2010;20: 981–7. 9. Salman WD, Mayuri Singh, Twaii Z. A case of papillary carcinoma in struma ovarii and review of the literature. Patholog Res Int 2010;2010:352476.
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10. Steinman RA, De Castro IO, Shrayyef M, et al. Two cases of malignant struma ovarii with metastasis to pelvic bone. Gynecol Obstet Invest 2013;75:139–44. 11. Schmidt J, Derr V, Heinrich MC, et al. BRAF in papillary thyroid carcinoma of ovary (struma ovarii). Am J Surg Pathol 2007;31: 1337–43. 12. Logani S, Baloch ZW, Snyder PJ, et al. Cystic ovarian metastasis from papillary thyroid carcinoma: a case report. Thyroid 2001;11: 1073–5.
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13. Makani S, Kim W, Gaba AR. Struma ovarii with a focus of papillary thyroid cancer: a case report and review of the literature. Gynecol Oncol 2004;94:835–9. 14. Lee SH, Lee KB, Shin JW, et al. Ovarian malignant melanoma without evidence of teratoma. Obstet Gynecol 2010;36:898–901. 15. Shaco-Levy R, Bean SM, Bentley RC, Robboy SJ. Natural history of biologically malignant struma ovarii: analysis of 27 cases with extraovarian spread. Int J Gynecol Pathol 2010;29:212–27.
THYROID CARCINOMA IN OVARIAN TERATOMA
Conservative treatment of a young patient with thyroid carcinoma in adult ovarian teratoma – case report Aneta Cymbaluk-Ploska1, Anita Chudecka-Głaz1, Maria Chosia2, Olgierd Ashuryk3, and Janusz Menkiszak1 Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, 2Department of Pathology, and 3Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland Abstract
Keywords
The cystic mature teratomas, including dermoid cysts, are one of the most frequently occurring benign ovarian tumors diagnosed in female patients. The process of neoplastic transformation in mature dermoid cysts is applicable only to 1–2% of cases. In our article, we present a rare case of thyroid carcinoma development in adult teratoma in 21-year-old patient. The young age, certain pathomorphological features and clinical data (small size of neoplastic lesion, correct values of tumour markers, unilateral character, regular levels of thyreoglobulin and absence of any significant deviations in imaging examinations), were the basis for attempting to apply the conservative treatment both in the scope of gynecological surgery and in the supplemental endocrinological therapy. In the patient, the one-sided adnexectomy was performed, considering pathological lesions on the adnexa, as well as the other ovary dermoid cyst was enucleated, without the hysteroctomy procedure. Considering the lack of any morphological lesions and functional changes relating to thyroid gland, the treatment was not radicalised in this scope, either. At present, one year after the primary operation treatment, the patient does not manifest any disease symptoms, whereas the other ovary, in the follow-up ultrasound examinations, shows normal size and echostructure. The thyroid-stimulating hormone (TSH) suppression keeps being applied.
Adult teratoma, ovary, thyroid carcinoma
Introduction The cystic mature teratomas, including dermoid cysts, are one of the most frequently occurring benign ovarian tumours diagnosed in female patients that may constitute up to 10–20% of all the neoplastic tumours of this organ. In 1–3%, they may undergo malignant transformation. This phenomenon occurs more often in postmenopausal women, mainly in the 5th and 6th life decade(s) [1,2]. In 75% of neoplastic transformations, the squamous epithelial carcinomas are diagnosed, whereas the percentage of the occurring sarcomas and adenomas is similar and it is equal to ca. 7% [3]. The majority of cases of malignant neoplastic lesions in mature teratomas are found incidentally by pathomorphologists, because in the macroscopic picture there are no exponents of the malignant neoplastic process. The prognosis in dermoid cysts with malignant transformation is serious but it is conditional upon several factors, and first of all on the kind of the malignant component, the stage of the clinical progression of the neoplasm, the age of the patient as well as the adequate operation treatment [2]. The aim of this article is to present a rare case of the occurrence of papillary carcinoma of the thyroid gland in the adult dermoid ovarian cyst in a young woman, taking into Address for correspondence: Aneta Cymbaluk-Ploska, MD, PhD, Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, Al. Powstan´co´w Wielkopolskich 72, 70-111 Szczecin, Poland. E-mail: [email protected]
History Received 11 June 2013 Revised 14 October 2013 Accepted 24 October 2013 Published online 7 January 2014
particular account the conservative treatment both in the scope of gynecological surgery and that of thyroid gland.
Case report A 21-year old woman without any complaints came to a gynaecologist for a routine gynaecological examination. In a bimanual gynaecological examination, a thickening of blurred borders on the right side adnexa and the presence of tuberous lesion of ca. 7 cm diameter in the projection of the left adnexa were reported. The Douglas sinus was painless and not lowered. Additionally in the vaginal speculum examination, the ectopic glandular tissue was reported on the vaginal part disc. The result of the cytological examination from the uterine cervix was correct – no features of intraepithelial neoplasia or carcinoma were found. The ultrasonographic examination (USG) was performed during which solid-cystic bilateral ovarian tumours were diagnosed. The tumour had no divisions and the cystic part contained fluid of high density. The risk malignancy index (RMI) calculated on the basis of the available data was equal to 69.6. That is, assuming that the cut off point value for benign and malignant tumours is 200, they were recognised as the benign lesions in the ovary. The patient was qualified as eligible for laparoscopy during which a 5-cm tumour was detected in the right ovary, and a 8-cm tumour with uneven surface in the left ovary. Considering the size of tumours, the high probability of causing injury of the capsule during the laparoscopy and the lack of any certainty as for the benign character of the lesion, the decision was made on the laparoscopy procedure conversion to laparotomy, during which both tumours were enucleated. In both cases, the remaining part
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of the ovary was stitched with continuous sutures obtaining full hemostasis. No free fluid was detected in the peritoneal cavity. After thorough macroscopic evaluation of tumours, in which solid cystic lesions were diagnosed, with a sebum mass component in the right adnexa tumour, they were recognised as adult dermoid ovarian cysts which do not require the intraoperational examination. In the postoperative histopathological examination, the following was diagnosed: in the right adnexa tumour – teratoma adultum cysticum. In the teratoma tissue, the mature forms of tissues: cartilaginous, neuroglia, epithelium of the respiratory system and fragment of cutis are noticeable, whereas in the left adnexa tumour – teratoma adultum cysticum with visible solid cystic nodule of 12 mm diameter, which morphologically and immunophenotypically corresponded to carcinoma papillare thyreoides [papillary thyroid carcinoma]. The tumour was built mainly of structure typical of dermoid cysts, i.e. the skin tissue with skin appendages and hair and certain small areas of other mature tissues: cylindrical glandular epithelium, cartilaginous tissue, nervous tissue, and neuroglia. The diagnosed papillary carcinoma within this tumour was built of solid papillary structures, with a small liquid space. The cancer cells included oval or round overlapping nuclei, of minimum cellular atypy and of ground glass appearance (or ‘‘orphan Annie’’ nuclei], with visible nuclear grooves. The mitotic activity index was low: 1/10 HPF. Necrosis was absent. In the performed immunohistochemical examinations, the following results were obtained: CK AE 1/ AE 3þ, Vimentinþ, thyroid transcription factor-1 (TTF-1) þ, HBME-1þKi-67þ (55% of cells) (Figure 1). After obtaining the result, in order to exclude the metastatic lesions in the abdominal cavity, the computer tomography scanning was carried out, in which the following was diagnosed: in the right ovary projection – visible solid – cystic lesion of 4 3 2 cm dimensions – the image suggesting that the ovarian structure was regular, with numerous Graffian follicles, and with haemorrhagic cyst of the corpus luteum – which was verified by conducting transvaginal ultrasonografic examination. The homogenous liver was without any perceptible focal lesions. The pancreas, spleen, adrenal glands, kidneys, inferior caval vein, aorta and retroperitoneal space were normal. No enlarged lymph nodes were disclosed in the intra-abdominal space and in the retroperitoneal space. In order to exclude the primary focus occurrence, the USG of thyroid was performed, in which the thyroid gland was reported as positioned typically, not enlarged, of reduced and heterogenic echogenicity. The dexter thyroid lobe of 45 19 14 mm dimensions, the sinister thyroid lobe of 39 16 11 mm dimensions. The isthmus was 3 mm thick. No focal lesions were disclosed in the thyroid gland. Along the sternum – clavicle – breast muscle, on both sides of the neck, there are several lymph nodes with preserved vascular hilus; on the right side of the neck, the biggest one up to 9 mm, and on the left side of the neck up to 12 mm. In the left submandibular region, a lymph node of 17 6 mm dimensions. The whole examination of the thyroid gland might have suggested the chronic autoimmune process occurrence in the thyroid gland. Prior to the operation, the routine determination of only CA125 and HE4 markers was carried out. Both markers’ values were within the normal range: CA125 – 11.6 IU/ml and HE4 – 63.3 pmol/l, respectively. Other markers, characteristic of germinal tumours, as well as parameters of thyroid gland functions were determined after receiving the histopathological examination result. The obtained results were as follows: beta HCG 50.1 mU/ml, AFP 1.19 ng/ml, thyroidstimulating hormone (TSH) – 2.32 mU/ml, ft3 – 3.85 pg/ml, fT4 – 1.49 ng/dl, thyroglobulin 16.3 ng/ml, chromogranin A – 58.3 ng/ml, aTG – 17.4 IU/ml, aTPO – 34.6 IU/ml. Only the
Gynecol Endocrinol, 2014; 30(3): 187–191
Figure 1. The microscopic image of the papillary thyroid carcinoma in the cystic mature teratoma tissue. (A) Histological image of the whole tumour in small enlargement (staining H&E). (B) Histological image in big enlargement. The n (staining H&E). (C) Positive immunohistochemical reaction in nuclei of carcinoma cells in the presence of thyroid transcription factor-1 (TTF-1).
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DOI: 10.3109/09513590.2013.860122
concentration of SHBG was slightly increased and it was equal to 147.2 nmol/l. In view of the lack of pathological deviations in the computer tomography scanning result, the young age of the patient and having no children, as well as considering pathomorphological features of the tumour, the decision was made on applying the maximally conservative treatment both as regards the gynaecological surgical procedure and the endocrinological treatment. In view of the too conservative procedure taken during the first operation, consisting only in enucleation of the dermoid cyst, in which next, in the pathomorphological examination, the thyroid carcinoma was diagnosed in addition, a decision was made on relaparotomy, for the treatment radicalisation. Relaparotomy is not routine procedure. We decided to exercise it because the patient was of young age and planned saving treatment. We needed a full staging for this saving treatment which was not done during the first surgery because ovarian cysts macroscopically looked as mature teratoma without raising the suspicion of malignancy. Full staging was impossible to carry out with laparoscopy again. The laparotomy was carried out, during which the left adnexectomy and omentectomy were performed, the right ovary cyst was enucleated, biopsy specimens were collected from peritoneum, and the washing was performed. In the postoperative histopathological and cytological examination(s), no deviations from normal condition were found. In the removed adnexa on the left side, the ovary tissue with corpus albicans, follicular cysts, and numerous resorptive granulomas were reported, with no neoplastic tissue. The ovarian tissue was without any substantial morphological lesions. In the removed right ovarian cyst, the haemorrhagic cyst of corpus luteum was reported. The omentum and peritoneal biopsy specimens were without any traits of neoplastic cell proliferation. In washings from peritoneal cavity, the absence of any neoplastic cells was observed. Due to the lack of any focal lesions in thyroid gland ultrasound image as well as considering the absence of any significant deviations in biochemical test results, the decision was made to leave the thyroid unoperated, introducing, however, the hormonotherapy with Levothyroxine, so as to cause TSH suppression. The patient has been under the care and control at the Endocrinology, Metabolic Diseases and Internal Diseases of PMU. In the PET CT examination conducted six months after the operation, no traits of the neoplastic process recurrence were disclosed. The patient has been taking hormonal contraception. The thyreglobulin levels are normal. The dexter ovary, despite the hemorrhagic cyst enucleation, shows normal dimensions and echostructure.
Discussion The cystic mature teratomas, including adult ovarian teratomas, and among them, the most frequently occurring dermoid cysts, rarely undergo malignant transformation. The malignant transformation in tumours of these types concerns mainly the epithelial component, most often in the form of squamous epithelial carcinoma, but the following ones are also reported: adenocarcinomas, sarcomas, germinal tumours, malignant melanomas, neuro-endocrine tumours (NET) and thyroid carcinomas. While the thyroid carcinomas in struma ovarii-type tumours are not rare, in adult teratoma they occur incidentally. Rather seldom, since only in 0.1–0.3% of cases, the occurrences of thyroid carcinomas are reported in cystic mature [adult] teratomas, most frequently in dermoid cysts. Until now only 15 such cases have been reported in the world. Only in two cases, the patient’s age was not over 30 years [4]. The prevailing clinical
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symptom in the majority of patients was the hypogastric pain. Only in one case reported by Krnojelac et al. [5], like in our patient, the tumour was not accompanied by any symptoms. In five cases, the conservative operations were performed on reproductive organs [4–7]. In all the reported 15 cases, the thyroid carcinoma was of papillary type, and in it – in six cases, it was follicular variation. Most of the thyroid carcinoma cases in adult teratoma are diagnosed postoperatively. In the medical literature, it is reported that prior to operation there appear certain characteristics that may prove the malignancy of ovarian lesions. Among them the following are listed: at first place, the elevation of thyroglobulin level, clinical and biochemical hyperthyreosis, which, however, occurs only in 5–8% of patients, the ‘‘struma pearls’’ ultrasound image, occurrence of partitions and their thickness in USG [8,9]. Considering the fact that during the first operation, the macroscopic image, in the majority of cases, has no features proving the malignant character of the occurring lesions, the full oncological procedure (staging), or the intraoperational examination, is not performed (especially, that the image of the adult teratoma is characteristic, and neoplastic transformations in it are very rare). Apart from extremely rarely occurring thyroid carcinoma cases in adult teratoma, more frequently the struma ovarii-type tumours occur, which are diagnosed when more than 50% of the tumour tissue is made by the thyroid tissue. In 5–10% of cases, within the struma ovarii area, it may come to malignant transformation [10]. Most frequently, it is the papillary carcinoma (ca. 70% of cases) and the follicular carcinoma [9]. The morphological image and immunophenotypic profile of papillary thyroid carcinoma in the thyroid gland and within the ovarian teratormas are similar. In patients with the thyroid carcinoma in adult teratomas, the BRAF, RET, and RAS mutations occur with a different frequency, which also proves the genetic similarity to thyroid carcinomas occurring in the thyroid gland [8,9,11]. In the differential diagnostics, one should also take into account the extremely rarely encountered metastases of the papillary thyroid carcinoma to the ovary, which causes the diagnostic difficulties both of clinical and of pathological nature [12]. In the case reported by us, the possibility of metastates occurrence was excluded. The procedure in the malignant variation of the struma ovarii type tumour is quite widely reported, considering higher frequency of occurrence. Therefore, part of the authors reporting the cases of the occurrences thyroid carcinoma in dermoid cyst(s) have assumed the procedure reported in the malignant variations of struma ovarii. Makani et al. [13], among 39 cases of struma ovarii with neoplastic transformation diagnosed, the metastases in nine patients which represented 23% of the reported group. In the same publication, he reported six cases of the neoplastic process recurrences which occurred on the average within time period up to four years from establishing the diagnosis. Therefore, he recommend the four-year-follow-up in patients with malignant struma ovarii variant, consisting in the scintigraphy of the whole body with J131 and in determining the thyroglobulin level. He recommends that in patients in whose ultrasonographic imaging examinations, or during labelling with radioactive iodine, are premises for the recurrence of neoplastic process, the thyroglobulin level monitoring shall be performed for a period up to 10 years from establishing the diagnosis [13]. In the available literature, the reports on the said recurrence in patients with thyroid carcinoma cases in the adult teratoma are missing. Lee et al. in 2008 carried out the additional radical surgery in a 35-year-old patient two months after the laparoscopic adnexectomy procedure. Decision on extending the scope of the procedure was made due to lack of the oncological purity
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(fragmentation of cyst, after sucking of the liquid part) during the laparoscopic procedure. The postoperative masses and the staging performed did not demonstrate any dissemination of the disease. The authors of the article emphasise that the laparoscopic procedures should be performed very carefully in order to guarantee the intact cyst removal [14]. Lataifeh et al. [7], who in a 39-year-old patient with the papillary thyroid carcinoma in adult teratoma, carried out the laparoscopic adnexectomy procedure, draw our attention to the fact that such conservative treatment should be performed in young patients who are about to maintain their fertility, with low initial staging and, first of all, in medical centres specialising in endoscopic operations. Dane et al. reported a case of a patient similar to ours. However, due to the fact that it was a large-sized tumour, the operation was conducted from the very beginning with laparotomy applied. The tumour masses were removed, leaving the ovarian tissue remains hoping for its regeneration. In our case, we performed the left adnexectomy on the side of the earlier
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diagnosed thyroid carcinoma and we enucleated the benign lesion from the right ovary, trying to conserve as much as possible of the intact ovarian tissue. Owing to such a conservative procedure, in the follow-up examinations, we can observe in the right ovary, the correctly functioning ovarian tissue, with numerous Graffian follicles (Figure 2). The authors [4,5,7] decided, in patients with diagnosed papillary thyroid carcinoma in mature teratoma, to carry out total thyroidectomy when there were visible nodules in USG image. After the thyroidectomy, the patient was supplemented with thyroid hormones, so as to cause TSH suppression. Dane is of the opinion that thyroidectomy is important due to two reasons. First, it enables the correct clinical evaluation (thyroid carcinoma with metastases to ovary, or occurrence of papillary carcinoma in teratoma, independent of thyroid carcinoma). Second, in order to conduct effective treatment with radioiodine, the thyroidectomy is necessary. In case of the patient reported by us, the lack of any lesions in the USG image of thyroid gland, the pathomorphological features of the thyroid carcinoma and the low-concentration level of thyroglobulin gave the grounds for the conservative treatment of thyroid gland. The negligible number of the reported cases of the occurrences thyroid carcinoma in mature dermoid cyst(s) does not permit to establish the unequivocal algorithms of procedures. It seems that due to the histopathological similarity the method of treatment, reported in the malignant struma ovarii-type tumours, can be partly extrapolated. It is worthwhile to emphasise that the small tumour size (510 cm diameter), the absence of necrosis, and the low mitotic activity (55/10 HPF) are associated with favourable prognosis [15]. We are of the opinion that the young age of the patient, certain clinical features, and pathomorphological data should be the basis for considering the maximally conservative procedure.
Declaration of interest The authors report no conflicts of interest.
References
Figure 2. Imaging examinations in the period of observation after treatment.
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