| Abstract|| |
Mature cystic teratoma of the ovary (MCT) is rare in pre and postmenopausal age patients. Among various types of malignant transformation in MCT, adenocarcinoma is a rare subtype. Dual type tumors arising from ovarian MCT have been described in the literature very rarely. A 47-year-old postmenopausal female patient presented with abdominal mass for ten years. The radiological opinion was a dermoid cyst. Grossly, a 22 × 20 × 10 cm, unilocular cystic left ovarian mass with intact capsular surface and focal thickened wall measured 3.0 cm. Microscopically, it showed components of all three germ cell layers. In addition, features of colonic type adenocarcinoma and well-differentiated neuroendocrine tumor (carcinoid) were noted and confirmed by immunohistochemistry (IHC). We report this rare case of synchronous malignancy arising from an ovarian MCT with a clinicopathological review.
Keywords: Carcinoid, colonic type adenocarcinoma, mature cystic teratoma of ovary, postmenopausal age, well-differentiated neuroendocrine tumor
|How to cite this article:|
Ayyanar P, Begum J, Rout S, Mishra P. Synchronous colonic adenocarcinoma and well-differentiated neuroendocrine tumor arising in a mature cystic teratoma of ovary — rare presentation in a postmenopausal woman with literature review. Indian J Pathol Microbiol 2021;64:385-9
|How to cite this URL:|
Ayyanar P, Begum J, Rout S, Mishra P. Synchronous colonic adenocarcinoma and well-differentiated neuroendocrine tumor arising in a mature cystic teratoma of ovary — rare presentation in a postmenopausal woman with literature review. Indian J Pathol Microbiol [serial online] 2021 [cited 2021 May 8];64:385-9. Available from: https://www.ijpmonline.org/text.asp?2021/64/2/385/313289
| Background|| |
Mature cystic teratoma of the ovary (MCT) accounts for approximately 20% of all ovarian neoplasms. Malignant transformation in a mature cystic teratoma of the ovary is 1%–2%. Transformation to any type of adenocarcinoma accounts for 7% of cases, and intestinal adenocarcinoma is a rare subset of these transformations., We report this case because of its rarity and synchronous intestinal-type adenocarcinoma and well-differentiated neuroendocrine tumor arising in a postmenopausal ovarian MCT, which has not been described till date. It is important to differentiate the primary mucinous adenocarcinoma of ovary and intestinal-type adenocarcinoma arising from ovarian MCT.
| Case Details|| |
A 47-year-old female patient presented with intermittent lower abdomen pain for the past ten years and no other complaints. She attained menopause ten years back. Local examination showed an abdominal mass of 24 weeks size, of variable consistency with restricted mobility, normal cervix, and vagina. Transabdominal sonography revealed a large unilocular left ovarian mass had dots and dashes patterns, calcified components, and a large hyperechoic mural plug, creating intense acoustic shadowing without septations and vascularity. On imaging with transvaginal ultrasound, uterus was found to be atrophic, the right ovary imaging was normal, and the left ovary could not be localized. Based on simple descriptors of the International Ovarian Tumor Analysis guidelines (IOTA), a diagnosis of a dermoid tumor of the left ovary was made. All her blood investigations, tumor marker, and endometrial biopsy were normal. Because of a postmenopausal woman with a benign ovarian mass, she underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy. Intraoperatively, a 20 × 15 cm left ovarian cystic mass with smooth intact capsular surface and partial torsion, the right ovary was a cystic, small-sized uterus and normal bilateral fallopian tubes. No ascites or peritoneal spread was noted. The macroscopic examination of the left ovarian mass showed a cystic lesion measuring 22 × 20 × 10 cm. The outer surface was smooth, intact, and without capsular breach. The attached normal left fallopian tube measures 12 cm in length [Figure 1]a. The cut section showed an uninoculated cyst contained pultaceous material with a smooth inner surface and contained hair follicle. Cyst wall thickness was ranging from 0.1 to 3.0 cm. The thick portion of the cyst wall showed yellowish and grey-brown solid areas with mucinous material, foci of calcification, and bone formation [Figure 1]b and [Figure 1]c. Normal ovarian parenchyma was not seen. The right ovary showed an irregular bosselated smooth outer surface and measures 3.5 × 2.2 × 1.0 cm. Cut section showed multiple cysts with serous fluid, cyst measurement ranging from 1.5 to 0.5 cm in maximum dimension. Uterus and bilateral fallopian tubes were normal.
|Figure 1: (a) Ovarian mass with intact capsule and attached fallopian tube. (b) Uniloculated cystic mass with pultaceous material, smooth inner surface and focal thickened wall containing grey brown solid lesion with mucin. (c) Thicker part of cyst wall. Red arrow shows the tumor focus. (d) Keratinized squamous epithelium, pilosebaceous unit, hyaline cartilage and adipocytes, H&E 40X. Inset shows blood vessels of varying calibre, H&E 400X. (e) Pseudostratified ciliated columnar epithelium and adipose tissue, H&E 40X|
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Extensive sampling of the left ovarian cystic mass showed components of all three germ cell layers characterized by the squamous epithelium [Figure 1]d, pseudostratified ciliated columnar epithelium [Figure 1]e and [Figure 2]b, mucous glands [Figure 2]b, goblet cells [Figure 2]e, colonic type mucosa [Figure 2]e, mature glial tissue [Figure 2]c, parasympathetic ganglion [Figure 2]a, smooth muscle bundles [Figure 3]a, smooth muscle bundles [Figure 3]c sebaceous glands, hair follicle, eccrine and apocrine glands, hyaline cartilage [Figure 1]d, nerve bundles, adipose tissue [Figure 1]d and [Figure 3]a, blood vessels of varying calibers [Figure 1]d inset]], and calcification. No immature components were identified. Besides there were small areas of tumor, which were arranged in cribriform, papillary, and glandular pattern lined by dysplastic epithelial cells. Intraluminal necrosis was seen [Figure 2]e,[Figure 2]f,[Figure 2]g,[Figure 2]h. Adjacent colonic type mucosa showed low-grade dysplasia [Figure 2]f. This is one of the most important morphologic clues towards colonic type adenocarcinoma arising in a mature cystic teratoma because we noticed normal colonic mucosa, low-grade dysplasia focus, and well-differentiated colonic adenocarcinoma.
|Figure 2: (a) Ganglion, H&E 400X. (b) Subepithelial mucinous glands, H&E 400X. (c) Mature glial tissue, H&E 400X. (d) Transitional epithelium with surrounding fibrocollagenous tissue, H&E 100X. (e) Adenocarcinoma with adjacent normal colonic mucosa, H&E40X. (f) Low grade dysplasia of colonic epithelium, H&E 100X. (g and h) Adenocarcinoma, H&E 100X. (i and j) Diffuse and strong CK20, CDX2 positivity in tumor cells, IHC 100X. (k) Immunonegative for synaptophysin, chromogranin, PAX8, IHC 400X. Inset shows focal CK7 positivity, IHC, 400X|
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|Figure 3: (a) Adipose tissue, blood vessels and a tumor focus, H& E 40X. (b) Tumor cells are arranged in nest and rosettes, round nucleus with fine granular nuclear chromatin and scant to moderate amount of cytoplasm. H&E 400X. (c) Smooth muscle bundles with myenteric plexus, H&E 400X. (d-f) Tumor is infiltrating the smooth muscle bundles by single cells, cords and peripheral rosettes and also show adjacent normal colonic epithelium, H&E 100X. (g-i) Positivity for chromogranin, PanCK and Synaptophysin IHC 400X.|
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On further sections, another two foci of monotonous appearing round cells with scant cytoplasm, stippled nuclear chromatin were seen in small nests, rosettes, cords with a peripheral cleft [Figure 3]a, [Figure 3]b, [Figure 3]d,[Figure 3]e,[Figure 3]f. Mitotic activity was sparse, <1/10 HPF (MIB 1 labeling index is <1%). The adjacent area showed transitional epithelium [Figure 2]d and smooth muscle bundles. The attached fallopian tube was histologically within normal limits.
There was no evidence of capsular invasion.
IHC revealed caudal homeobox 2 (CDX- 2), cytokeratin (CK)-20 (diffuse), and CK7 (focal) positivity in the areas showing features of adenocarcinoma of colonic type and negative for synaptophysin, chromogranin, and paired box gene (PAX) 8 [Figure 2i],[Figure 2]j,[Figure 2]k. The neuroendocrine areas showed strong immunopositivity for chromogranin (cytoplasmic) and variable positivity for synaptophysin and pan-cytokeratin (Pan-CK) [Figure 3]g,[Figure 3]h,[Figure 3]i. MIB 1 labeling index was approximately <1% in the neuroendocrine morphology area.
Finally, we reported as synchronous well-differentiated colonic type adenocarcinoma and well-differentiated neuroendocrine tumor (carcinoid) arising in a mature cystic teratoma of the ovary in a postmenopausal patient. On further workup, colonoscopy was within normal limits. Contrast-enhanced computed tomography (CECT) did not reveal any regional lymphadenopathy or any evidence of distant metastasis. She was referred to the department of medical oncology for further treatment in our institute. The patient denied further treatment and is on follow up in a nearby medical center. On telephonic conversation the patient did not complain of any symptoms and was doing well after eight months of post-operative period.
| Discussion|| |
The most common form of malignant transformation of the MCT is squamous cell carcinoma. Other tumors arising in MCT include basal cell carcinoma, malignant melanoma, adenocarcinoma, sarcoma, and neuroectodermal tumor. Though it is uncommon, various types of adenocarcinoma can arise from ovarian MCT. It includes sweat glands, salivary glands, mammary glands, respiratory tract, gastro-intestinal, and thyroid glands.,,,, Gastro-intestinal type of adenocarcinoma arising from ovarian MCT is very rare, only less than twenty cases have been reported in the literature till date.,,,,,,,,,,,,
We reviewed the clinicopathological data of reported ovarian MCT with gastrointestinal type adenocarcinoma [Table 1]. The patients' median age was 44 years (ranged from 33 to 77 years). This finding indicates the perimenopausal and postmenopausal age group patients are more prone to malignant transformation. The maximum size of the tumor was ranging from more than 6.4 to 30 cm. All cases were unilateral ovarian mass. Microscopically the present case showed all the components of germ cell layers compared to previously reported cases, which showed fewer germ cell components. In addition, it also showed the normal colonic type epithelium, lamina propria, and muscularis propria layer, forming a proper colonic wall, and a transition from normal intestinal mucosa to high grade dysplasia of the mucosa and intraepithelial carcinoma to frank adenocarcinoma. This was mentioned in one of the reported cases. Another interesting finding was the concurrent presence of a well-differentiated neuroendocrine tumor (carcinoid). The role of IHC is important in such a scenario so as to render a correct diagnosis. First, we should exclude the possibility of primary mucinous carcinoma of the ovary. The second feature is to highlight the immunohistochemical nature of these two different morphologies of the tumors. Most of the cases have mentioned the strong and diffuse CK20 positivity and negative or weak CK7 positivity in cases of intestinal-type adenocarcinoma arising in MCT. This contrasts with mucinous tumors of the ovary, which usually show strong and diffuse expression of CK7, and are negative for CK20. Apart from these two IHC markers, CDX2 and PAX8 are of help in this diagnostic dilemma. IHC is an additional modality for confirmation because the morphological presence of mature cystic teratoma elements points towards a malignant transformation in an MCT. Most of the reported cases were in International Federation of Gynecology and Obstetrics (FIGO) stage I. In one of the review studies, out of 42 cases, 31 (74%) were in stage I. Some cases showed the capsular rupture with malignant ascites and in some nodal metastasis was noted.
|Table 1: Clinicopathological features of gastrointestinal type adenocarcinoma arising from ovarian MCTs|
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A single case of synchronous mucinous adenocarcinoma, goblet cell, and typical carcinoid tumor arising in a mature cystic teratoma of the mesentery has been reported. Regarding synchronous malignancies arising from ovarian MCT, only two such cases have been reported. One case is mucinous cystadenocarcinoma and carcinoid tumor arising from one of two bilateral MCT of both ovaries. In addition, this case also had synchronous non-keratinizing squamous cell carcinoma of the cervix. The other case is leiomyosarcoma and squamous cell carcinoma arising in a mature cystic teratoma of the ovary.Both were postmenopausal patients. Synchronous colonic type adenocarcinoma and carcinoid in an ovarian MCT have not yet been reported.
| Conclusion|| |
We conclude that the histopathological examination is an important diagnostic modality in a case of MCT occurring in the postmenopausal age group. Extensive sampling is needed to look for malignant transformation. One should keep in mind that synchronous malignancy can arise from an ovarian MCT.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
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| References|| |
Prat J, Cao D, Carinelli SG, Nogales FF, Vang R, Zaloudek CJ, editors. In Germ cell tumors. WHO Classification of Tumors of Female Reproductive Organs. 4th
ed. IARC Lyon; 2014. p. 57-62.
Takai M, Kanemura M, Kawaguchi H, Fujiwara S, Yoo S, Tanaka Y, et al
. Mucinous adenocarcinoma of the intestinal type arising from mature cystic teratoma of the ovary: A rare case report and review of the literature. J Ovarian Res 2012;5:41.
Min KJ, Jee BC, Lee HS, Kim YB: Intestinal adenocarcinoma arising in mature cystic teratoma of the ovary: A case report. Pathol Res Pract 2006; 202:531-5.
Clark ME, Will MD. Intestinal-type adenocarcinoma arising in a mature cystic teratoma of the ovary. Int J Gynecol Pathol 2016;35:352-6.
Sunitha S, Arundhathi S, Betigeri AM. Adenocarcinoma of intestinal type arising in mature cystic teratoma of ovary in a young female: An incidental finding. Indian J Pathol Oncol 2017;4:336-8.
Lee JM, Kim JW, Song JY, Lee JK, Lee NW, Kim SH, et al
. Adenocarcinoma arising in mature cystic teratoma: A case report. J Gynecol Oncol 2008;19:199-201.
Rim SY, Kim SM, Choi HS. Malignant transformation of ovarian mature cystic teratoma. Int J Gynecol Cancer 2006;16:140-4.
Sumi T, Ishiko O, Maeda K, Haba T, Wakasa K, Ogita S. Adenocarcinoma arising from respiratory ciliated epithelium in mature ovarian cystic teratoma. Arch Gynecol Obstet 2002;267:107-9.
Morimitsu Y, Nakashima O, Nakashima Y, Kojiro M, Shimokobe T. Apocrine adenocarcinoma arising in cystic teratoma of the ovary. Arch Pathol Lab Med 1993;117:647-9.
Ueda G, Fujita M, Ogawa H, Sawada M, Inoue M, Tanizawa O. Adenocarcinoma in a benign cystic teratoma of the ovary: Report of a case with a long survival period. Gynecol Oncol 1993;48:259-63.
Fishman A, Edelstein E, Altaras M, Beyth Y, Bernheim J. Adenocarcinoma arising from the gastrointestinal epithelium in benign cystic teratoma of the ovary. Gynecol Oncol 1998;70:418-20.
Levine DA, Villella JA, Poynor EA, Soslow RA. Gastrointestinal adenocarcinoma arising in a mature cystic teratoma of the ovary. Gynecol Oncol 2004;94:597-9.
Kushima M. Adenocarcinoma arising from mature cystic teratoma of the ovary. Pathol Int 2004;54:139-43.
Guney M, Oral B, Demir F, Ozsoy M, Kapucuoglu N. Mucinous adenocarcinoma arising from the gastrointestinal epithelium in benign cystic teratoma of the ovary–Case report. Eur J Gynaecol Oncol 2006;27:304-6.
McKenney JK, Soslow RA, Longacre TA. Ovarian mature teratomas with mucinous epithelial neoplasms: Morphologic heterogeneity and association with pseudomyxoma peritonei. A J Surg Pathol 2008;32:645-5.
Kavitha S, Kanchana MP, Babyvasumathi. Mucinous Adenocarcinoma Arising From Mature Cystic Teratoma with Nodal Metastasis IOSR Journal of Dental and Medical Sciences (IOSR-JDMS) e-ISSN: 2279-0853, p-ISSN: 2279-0861.Volume 15, Issue 9 Ver. I (September. 2016), PP 01-04
Miyasaka A, Nishikawa T, Kozawa E, Yasuda M, Fujiwara K, Hasegawa K. Advanced mucinous adenocarcinoma arising from a mature cystic teratoma: A case report and literature review. Case Rep Oncol 2016;9:331-7.
Roy S, Mukhopadhayay S, Gupta M, Chandramohan A. Mature Cystic Teratoma with Co-existent Mucinous Cystadenocarcinoma in the same Ovary-A Diagnostic Dilemma. J Clin Diagn Res 2016;10:ED11-ED13. doi: 10.7860/JCDR/2016/22150.9118.
Shin SJ,· Son EM, Sung CO, Kim KR. Mixed Carcinoid-Mucinous Adenocarcinoma Arising in Mature Teratoma of Mesentery. J Pathol and Trans Med 2015;49:61-5.
Kim SM, Choi HS, Byun JS, Kim YH, Kim KS, Rim SY, et al
. Mucinous adenocarcinoma and strumal carcinoid tumor arising in one mature cystic teratoma of the ovary with synchronous cervical cancer. J Obstet Gynaecol Res 2003;29:28-32.
Pongsuvareeyakul T, Sukpan K, Chaicharoen S, Khunamornpong S. Leiomyosarcoma and Squamous Cell Carcinoma Arising in Mature Cystic Teratoma of the Ovary. Case Rep Pathol. 2017;2017:7907359.
Additional Professor, Department of Pathology and Lab Medicine, All India Institute of Medical Sciences (AIIMS), Bhubaneswar- 751 019, Odisha
Source of Support: None, Conflict of Interest: None
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