immature teratoma

At CT and MRI, an immature teratoma possesses characteristic appearance. It is typically large (12–25 cm) and has prominent solid components with cystic elements.{{cite journal | vauthors = Malkasian GD, Symmonds RE, Dockerty MB | title = Malignant Ovarina Teratomas. Report of 31 Cases | journal = Obstetrics and Gynecology | volume = 25 | pages = 810–4 | date = June 1965 | pmid = 14287472 }} It is usually filled with lipid constituents and therefore demonstrates fat density at CT and MRI. Ultrasound appearance of an immature teratoma is nonspecific. It is highly heterogeneous with partially solid lesions and scattered calcifications.{{cite journal | vauthors = Brammer HM, Buck JL, Hayes WS, Sheth S, Tavassoli FA | title = From the archives of the AFIP. Malignant germ cell tumors of the ovary: radiologic-pathologic correlation | journal = Radiographics | volume = 10 | issue = 4 | pages = 715–24 | date = July 1990 | pmid = 2165627 | doi = 10.1148/radiographics.10.4.2165627 | doi-access = free }}{{Cite journal| vauthors = Moş C |date=2009|title=Ovarian dermoid cysts: ultrasonographic findings | url = https://pdfs.semanticscholar.org/befa/7bdce97184467581d36af9ba9f7316804d7f.pdf | archive-url = https://web.archive.org/web/20180420140124/https://pdfs.semanticscholar.org/befa/7bdce97184467581d36af9ba9f7316804d7f.pdf | url-status = dead | archive-date = 2018-04-20 |journal=Pictorial Essay Medical Ultrasonography|volume=11|pages=61–66|s2cid=5944732 }}

Traditionally, comprehensive surgical staging is performed via exploratory laparotomy with cytologic washings, peritoneal biopsies, an omental assessment (either biopsy or rarely a full omentectomy), and both pelvic and aortic lymph node dissection. Laproscopy is often suggested as an alternative to surgically stage patients with immature teratoma.{{cite journal | vauthors = Nishida M, Kawano Y, Yuge A, Nasu K, Matsumoto H, Narahara H | title = Three cases of immature teratoma diagnosed after laparoscopic operation | journal = Clinical Medicine Insights: Case Reports | volume = 7 | pages = 91–4 | date = 2014-09-03 | pmid = 25232281 | pmc = 4159361 | doi = 10.4137/CCRep.S17455 }}{{cite journal | vauthors = Brown KL, Barnett JC, Leath CA | title = Laparoscopic staging of ovarian immature teratomas: a report on three cases | journal = Military Medicine | volume = 180 | issue = 3 | pages = e365-8 | date = March 2015 | pmid = 25735031 | doi = 10.7205/milmed-d-14-00288 | doi-access = free }}

Ovarian cancer is staged using the FIGO staging system and uses information obtained after surgery, which can include a total abdominal hysterectomy via midline laparotomy, unilateral (or bilateral) salpingo-oophorectomy, pelvic (peritoneal) washings, assessment of retroperitoneal lymph nodes and/or appendectomy.{{Cite book |title=Harrison's principles of internal medicine |date=2012 |publisher=McGraw-Hill | vauthors = Longo DL |isbn=9780071748896 |edition=18th |location=New York |oclc=288932926}}{{cite journal | vauthors = Jayson GC, Kohn EC, Kitchener HC, Ledermann JA | title = Ovarian cancer | journal = Lancet | volume = 384 | issue = 9951 | pages = 1376–88 | date = October 2014 | pmid = 24767708 | doi = 10.1016/s0140-6736(13)62146-7 }} The AJCC staging system, identical to the FIGO staging system, describes the extent of tumor (T), the presence of absences of metastases to lymph nodes (N), the presence or absence of distant metastases (M).{{Cite web|url=https://www.cancer.org/cancer/ovarian-cancer/detection-diagnosis-staging/staging.html|title=How is Ovarian Cancer Staged?|website=American Cancer Society}}

File:Ovarian tumors by incidence and cancer risk.pngs by incidence and risk of ovarian cancer, with immature teratoma at right.- {{cite journal| vauthors = Vaidya S, Sharma P, KC S, Vaidya SA |title=Spectrum of ovarian tumors in a referral hospital in Nepal|journal=Journal of Pathology of Nepal|volume=4|issue=7|year=2014|pages=539–543|issn=2091-0908|doi=10.3126/jpn.v4i7.10295|doi-access=free}}
- Minor adjustment for mature cystic teratomas (0.17 to 2% risk of ovarian cancer): {{cite journal | vauthors = Mandal S, Badhe BA | title = Malignant transformation in a mature teratoma with metastatic deposits in the omentum: a case report | journal = Case Reports in Pathology | volume = 2012 | pages = 568062 | year = 2012 | pmid = 23082264 | doi = 10.1155/2012/568062 |pmc=3469088 | doi-access = free }}]]

An immature teratoma contains varying compositions of adult and embryonic tissue. The most common embryonic component identified in immature teratomas is the neuroectoderm.{{Cite book |title=Modern surgical pathology |date=2009 |publisher=Saunders/Elsevier | vauthors = Weidner N |isbn=9781416039662 |edition=2nd |location=Philadelphia, PA |oclc=460883320}} Occasionally, tumors may present neuroepithelium that resemble neuroblasts. Tumors may also present embryonic components such as immature cartilage and skeletal muscle of mesodermal origin. Immature teratomas composed of embryonic endodermal derivatives are rare.

Often a mature cystic teratoma is misdiagnosed as its immature counterpart due to the misinterpretation of mature neural tissue as immature.{{Cite book |title=Gynecologic pathology : a volume in the series foundations in diagnostic pathology |date=2009 |publisher=Churchill Livingstone/Elservier | vauthors = Nucci MR, Oliva E |isbn=9780443069208 |location=Edinburgh |pages=501–538 |oclc=460883296}} While mature neural cells have nuclei with uniformly dense chromatin and neither exhibit apoptotic or mitotic activity, immature neural cells have nuclei with vesicular chromatin and exhibit both apoptotic and mitotic activity. A recent study has identified the use of Oct-4 as a reliable biomarker for the diagnosis of highly malignant cases of immature teratomas.{{cite journal | vauthors = Abiko K, Mandai M, Hamanishi J, Matsumura N, Baba T, Horiuchi A, Mikami Y, Yoshioka S, Wakasa T, Shiozawa T, Konishi I | display-authors = 6 | title = Oct4 expression in immature teratoma of the ovary: relevance to histologic grade and degree of differentiation | journal = The American Journal of Surgical Pathology | volume = 34 | issue = 12 | pages = 1842–8 | date = December 2010 | pmid = 21107090 | doi = 10.1097/PAS.0b013e3181fcd707 }}

Thurlbeck and Scully devised a grading system for “pure” immature teratomas on the basis of differentiation of the cellular elements of the tumor.{{cite journal | vauthors = Thurlbeck WM, Scully RE | title = Solid teratoma of the ovary. A clinicopathological analysis of 9 cases | journal = Cancer | volume = 13 | issue = 4 | pages = 804–11 | date = July 1960 | pmid = 13838271 | doi = 10.1002/1097-0142(196007/08)13:4<804::AID-CNCR2820130423>3.0.CO;2-V | doi-access = free }} The proportion of immature tissue elements defines the grade of immaturity. This was later modified by Norris et al. (1976), who added a quantitative aspect to the degree of immaturity.{{cite journal | vauthors = Norris HJ, Zirkin HJ, Benson WL | title = Immature (malignant) teratoma of the ovary: a clinical and pathologic study of 58 cases | journal = Cancer | volume = 37 | issue = 5 | pages = 2359–72 | date = May 1976 | pmid = 1260722 | doi = 10.1002/1097-0142(197605)37:5<2359::AID-CNCR2820370528>3.0.CO;2-Q | doi-access = free }}

An ovarian immature teratoma is karyotypically normal 46,XX or near-normal. Grade 1 or 2 tumors exhibit 46,XX normal karyotype, whereas grade 3 tumors show a variety of abnormal karyotypes.{{cite journal | vauthors = Ihara T, Ohama K, Satoh H, Fujii T, Nomura K, Fujiwara A | title = Histologic grade and karyotype of immature teratoma of the ovary | journal = Cancer | volume = 54 | issue = 12 | pages = 2988–94 | date = December 1984 | pmid = 6498772 | doi = 10.1002/1097-0142(19841215)54:12<2988::AID-CNCR2820541229>3.0.CO;2-U | doi-access = free }} Though immature teratoma cells show a normal karyotype, there may still be detectable alterations in the gene level and that these aberrations may influence the stability of chromosome status.

Ovarian immature teratomas have been classified as among the least mutated of all solid cancers.{{cite journal | vauthors = Heskett MB, Sanborn JZ, Boniface C, Goode B, Chapman J, Garg K, Rabban JT, Zaloudek C, Benz SC, Spellman PT, Solomon DA, Cho RJ | display-authors = 6 | title = Multiregion exome sequencing of ovarian immature teratomas reveals 2N near-diploid genomes, paucity of somatic mutations, and extensive allelic imbalances shared across mature, immature, and disseminated components | journal = Modern Pathology | volume = 33 | issue = 6 | pages = 1193–1206 | date = June 2020 | pmid = 31911616 | pmc = 7286805 | doi = 10.1038/s41379-019-0446-y | url = }} Immature teratomas originate from germ cells that undergo one of several meiotic failures, leading to a tumor genome with high levels of copy neutral loss of heterozygosity.

Though several studies have shown that size and stage of the primary tumor are related to survival, the grade of the tumor is the best determinant of prognosis prior to peritoneal spread. Once peritoneal spread has occurred, the grade of metastatic lesions or implants is the best determinant of prognosis. Multiple sections of the primary tumor and wide sampling of the implants are necessary to properly grade the tumor. In most cases, the implants are better differentiated than the primary tumors. Gliomatosis peritonei, a rare condition often associated with immature ovarian teratoma, is characterized by the presence of mature glial implants in the peritoneum.{{cite journal | vauthors = Liang L, Zhang Y, Malpica A, Ramalingam P, Euscher ED, Fuller GN, Liu J | title = Gliomatosis peritonei: a clinicopathologic and immunohistochemical study of 21 cases | journal = Modern Pathology | volume = 28 | issue = 12 | pages = 1613–20 | date = December 2015 | pmid = 26564007 | pmc = 4682736 | doi = 10.1038/modpathol.2015.116 }} Yoon et al. (2012), reported that immature ovarian teratoma patients with Gliomatosis peritonei have larger tumors, more frequent recurrence and higher CA-125 levels than immature ovarian teratoma patients without gliomatosis peritonei.{{cite journal | vauthors = Yoon NR, Lee JW, Kim BG, Bae DS, Sohn I, Sung CO, Song SY | title = Gliomatosis peritonei is associated with frequent recurrence, but does not affect overall survival in patients with ovarian immature teratoma | journal = Virchows Archiv | volume = 461 | issue = 3 | pages = 299–304 | date = September 2012 | pmid = 22820986 | doi = 10.1007/s00428-012-1285-0 }}

A high degree of immaturity in the primary tumor, one that corresponds with a grade 3 diagnosis is a sign of poor prognosis.{{cite journal | vauthors = Pashankar F, Hale JP, Dang H, Krailo M, Brady WE, Rodriguez-Galindo C, Nicholson JC, Murray MJ, Bilmire DF, Stoneham S, Arul GS, Olson TA, Stark D, Shaikh F, Amatruda JF, Covens A, Gershenson DM, Frazier AL | display-authors = 6 | title = Is adjuvant chemotherapy indicated in ovarian immature teratomas? A combined data analysis from the Malignant Germ Cell Tumor International Collaborative | journal = Cancer | volume = 122 | issue = 2 | pages = 230–7 | date = January 2016 | pmid = 26485622 | pmc = 5134834 | doi = 10.1002/cncr.29732 }}{{cite journal | vauthors = Nogales FF, Favara BE, Major FJ, Silverberg SG | title = Immature teratoma of the ovary with a neural component ("solid" teratoma). A clinicopathologic study of 20 cases | journal = Human Pathology | volume = 7 | issue = 6 | pages = 625–42 | date = November 1976 | pmid = 992645 | doi = 10.1016/S0046-8177(76)80076-7 }} Grade 3 tumors often display chromosomal abnormalities, also an indication of poor prognosis. Tumor grade is the most important factor for relapse in immature teratomas. Vicus et al. (2011), reported that grade 2 or 3 tumors are associated with a greater chance of relapse that can be fatal, predominantly within 2 years of diagnosis.{{cite journal | vauthors = Vicus D, Beiner ME, Clarke B, Klachook S, Le LW, Laframboise S, Mackay H | title = Ovarian immature teratoma: treatment and outcome in a single institutional cohort | journal = Gynecologic Oncology | volume = 123 | issue = 1 | pages = 50–3 | date = October 2011 | pmid = 21764111 | doi = 10.1016/j.ygyno.2011.06.037 }} Among grade 3 patients, the stage was significantly associated with relapse.

In the past, survival rates were low for high-grade immature teratomas. Norris et al. (1976), reported a survival rate of 82% for patients with grade 1 tumors, 62% for grade 2 and 30% for grade 3 tumors. However, these results antedate the use of multi-agent chemotherapy. With the advent of multiagent chemotherapy after surgical resection, long-term remission and increased survival rates have been achieved. Pashankar et al. (2016), reported that the estimated 5-year overall survival rate for grade 3 Stage I and II disease was 91% compared with 88% for grade 3, Stage III and IV disease.

Histologic grade and fertility desires of the patient are key considerations in determining treatment options. In adult women postoperative adjuvant chemotherapy is standard except for stage I /grade 1 disease. In pediatric patients, surgery alone is standard.

Since the occurrence of immature teratoma is very rarely bilateral, current standard of care of unilateral salpingo-oophorectomy with wide sampling of peritoneal implants. Total abdominal hysterectomy with bilateral salpingo-oophorectomy are not indicated as they do not influence outcomes. Fertility-sparing surgery in the form of unilateral salpingo-oophorectomy is the primary treatment modality in young patients.{{cite journal | vauthors = Tay SK, Tan LK | title = Experience of a 2-day BEP regimen in postsurgical adjuvant chemotherapy of ovarian germ cell tumors | journal = International Journal of Gynecological Cancer | volume = 10 | issue = 1 | pages = 13–18 | date = January 2000 | pmid = 11240646 | doi = 10.1046/j.1525-1438.2000.00010.x }}{{cite journal | vauthors = Kanazawa K, Suzuki T, Sakumoto K | title = Treatment of malignant ovarian germ cell tumors with preservation of fertility: reproductive performance after persistent remission | journal = American Journal of Clinical Oncology | volume = 23 | issue = 3 | pages = 244–8 | date = June 2000 | pmid = 10857886 | doi = 10.1097/00000421-200006000-00007 }}{{cite journal | vauthors = Low JJ, Perrin LC, Crandon AJ, Hacker NF | title = Conservative surgery to preserve ovarian function in patients with malignant ovarian germ cell tumors. A review of 74 cases | journal = Cancer | volume = 89 | issue = 2 | pages = 391–8 | date = July 2000 | pmid = 10918171 | doi = 10.1002/1097-0142(20000715)89:2<391::AID-CNCR26>3.0.CO;2-V }} Some physicians recommend ovarian cystectomy alone, rather than a unilateral salpingo-oophorectomy for patients with an early stage low grade disease. Zhao et al. (2017), reported no significant differences in survival rates or post-operative fertility outcomes between the two treatment options.{{cite journal | vauthors = Zhao T, Liu Y, Wang X, Zhang H, Lu Y | title = Ovarian cystectomy in the treatment of apparent early-stage immature teratoma | journal = The Journal of International Medical Research | volume = 45 | issue = 2 | pages = 771–780 | date = April 2017 | pmid = 28415950 | pmc = 5536676 | doi = 10.1177/0300060517692149 }} However, others caution against such an approach.

Norris et al. (1976) observed an 18% recurrence rate in grade 2 tumors and 70% recurrence in grade 3 tumors. Gershenson et al. (1986), reported outcomes of 41 patients with Stage I-IV disease and observed recurrences in 94% of patients treated with surgery alone compared with 14% in patients treated with surgery and chemotherapy.{{cite journal | vauthors = Gershenson DM, del Junco G, Silva EG, Copeland LJ, Wharton JT, Rutledge FN | title = Immature teratoma of the ovary | journal = Obstetrics and Gynecology | volume = 68 | issue = 5 | pages = 624–9 | date = November 1986 | pmid = 3763073 }} Studies like these resulted in the recommendation to use chemotherapy for grade 2 and 3 tumors. Currently, the use of multi agent chemotherapy for adult patients with ovarian immature teratoma is standard of care except for grade 1, stage I tumors. There is considerable experience with a combination of vincristine, dactinomycin, and cyclophosphamide (VAC) given in an adjuvant setting; however, combinations containing cisplatin, etoposide, and bleomycin (BEP) are now preferred because of a lower relapse rate and shorter treatment time.{{cite journal | vauthors = Williams S, Blessing JA, Liao SY, Ball H, Hanjani P | title = Adjuvant therapy of ovarian germ cell tumors with cisplatin, etoposide, and bleomycin: a trial of the Gynecologic Oncology Group | journal = Journal of Clinical Oncology | volume = 12 | issue = 4 | pages = 701–6 | date = April 1994 | pmid = 7512129 | doi = 10.1200/JCO.1994.12.4.701 }} While a prospective comparison of VAC versus BEP has not been performed, in well-staged patients with completely resected tumors, relapse is essentially unheard of following platinum-based chemotherapy. However, the disease will recur in about 25% of well-staged patients treated with 6 months of VAC.{{cite journal | vauthors = Slayton RE, Park RC, Silverberg SG, Shingleton H, Creasman WT, Blessing JA | title = Vincristine, dactinomycin, and cyclophosphamide in the treatment of malignant germ cell tumors of the ovary. A Gynecologic Oncology Group Study (a final report) | journal = Cancer | volume = 56 | issue = 2 | pages = 243–8 | date = July 1985 | pmid = 2988740 | doi = 10.1002/1097-0142(19850715)56:2<243::AID-CNCR2820560206>3.0.CO;2-T | doi-access = free }}

• Teratoma
• Ovarian Cancer
• Germ Cell Tumor

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• [http://www.cancer.gov/dictionary?CdrID=443576 Immature teratoma] entry in the public domain NCI Dictionary of Cancer Terms

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Category:Germ cell neoplasia