Immature teratoma

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Immature teratoma
Immature teratoma high mag.jpg
Micrograph of the primitive neuroepithelium of an immature teratoma. H&E stain.
Specialty Oncology

An immature teratoma is a teratoma that contains anaplastic immature elements, and is often synonymous with malignant teratoma. [1] A teratoma is a tumor of germ cell origin, containing tissues from more than one germ cell line, [2] [3] [4] It can be ovarian or testicular in its origin. [4] and are almost always benign. [5] An immature teratoma is thus a very rare tumor, representing 1% of all teratomas, 1% of all ovarian cancers, and 35.6% of malignant ovarian germ cell tumors. [6] It displays a specific age of incidence, occurring most frequently in the first two decades of life and almost never after menopause. [4] Unlike a mature cystic teratoma, an immature teratoma contains immature or embryonic structures. It can coexist with mature cystic teratomas and can constitute of a combination of both adult and embryonic tissue. [7] [8] The most common symptoms noted are abdominal distension and masses. [9] Prognosis and treatment options vary and largely depend on grade, stage and karyotype of the tumor itself.

Contents

Diagnosis

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. [10] It is usually filled with lipid constituents and therefore demonstrates fat density at CT and MRI. [10] Ultrasound appearance of an immature teratoma is nonspecific. It is highly heterogeneous with partially solid lesions and scattered calcifications. [11] [12]

Stage

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. [13] [14]

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. [15] [16] 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). [17]

Table 1: FIGO Staging System for Ovarian Cancers [16]
StageDescription
ICancer is completely limited to the ovary
IAinvolves one ovary, capsule intact, no tumor on ovarian surface, negative washings
IBinvolves both ovaries; capsule intact; no tumor on ovarian surface; negative washings
ICtumor involves one or both ovaries
IC1surgical spill
IC2capsule has ruptured or tumor on ovarian surface
IC3positive ascites or washings
IIpelvic extension of the tumor (must be confined to the pelvis) or primary peritoneal tumor, involves one or both ovaries
IIAtumor found on uterus or fallopian tubes
IIBtumor elsewhere in the pelvis
IIIcancer found outside the pelvis or in the retroperitoneal lymph nodes, involves one or both ovaries
IIIAmetastasis in retroperitoneal lymph nodes or microscopic extrapelvic metastasis
IIIA1metastasis in retroperitoneal lymph nodes
IIIA1(i)the metastasis is less than 10 mm in diameter
IIIA1(ii)the metastasis is greater than 10 mm in diameter
IIIA2microscopic metastasis in the peritoneum, regardless of retroperitoneal lymph node status
IIIBmetastasis in the peritoneum less than or equal to 2 cm in diameter, regardless of retroperitoneal lymph node status; or metastasis to liver or spleen capsule
IIICmetastasis in the peritoneum greater than 2 cm in diameter, regardless of retroperitoneal lymph node status; or metastasis to liver or spleen capsule
IVdistant metastasis (i.e. outside of the peritoneum)
IVApleural effusion containing cancer cells
IVBmetastasis to distant organs (including the parenchyma of the spleen or liver), or metastasis to the inguinal and extra-abdominal lymph nodes

Pathology

Ovarian tumors by incidence and risk of ovarian cancer, with immature teratoma at right. Ovarian tumors by incidence and cancer risk.png
Ovarian tumors by incidence and risk of ovarian cancer, with immature teratoma at right.

An immature teratoma contains varying compositions of adult and embryonic tissue. The most common embryonic component identified in immature teratomas is the neuroectoderm. [19] Occasionally, tumors may present neuroepithelium that resemble neuroblasts. [19] Tumors may also present embryonic components such as immature cartilage and skeletal muscle of mesodermal origin. [19] Immature teratomas composed of embryonic endodermal derivatives are rare. [19]

Often a mature cystic teratoma is misdiagnosed as its immature counterpart due to the misinterpretation of mature neural tissue as immature. [20] 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. [20] A recent study has identified the use of Oct-4 as a reliable biomarker for the diagnosis of highly malignant cases of immature teratomas. [21]

Grade

Thurlbeck and Scully devised a grading system for "pure" immature teratomas on the basis of differentiation of the cellular elements of the tumor. [22] The proportion of immature tissue elements defines the grade of immaturity. [22] This was later modified by Norris et al. (1976), who added a quantitative aspect to the degree of immaturity. [23]

Table 2: Identifying Tumor Grade in Immature Teratomas [22] [23]
GradeThurlbeck and Scully (1960)Norris et al. (1976)
0All cells are well differentiatedAll cells are mature; mitotic activity is rare or absent.
1Cells are well differentiated except in rare small foci of embryonic tissue; neuroepithelium is absent or rareNeuroepithelium absent or limited to fewer than one low-magnification field (x40) per slide
2Moderate quantities of embryonic tissue present; cells show atypicality and mitotic activityNeuroepithelium does not exceed more than three low-magnification fields (x40) per slide
3Large quantities of embryonic tissue present; cells show atypicality and mitotic activityNeuroepithelium exceeds more than three low-magnification fields (x40) per slide

Karyotype

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. [24] 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. [24]

Genetics

Ovarian immature teratomas have been classified as among the least mutated of all solid cancers. [25] 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. [25]

Prognosis

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. [23] [24] Once peritoneal spread has occurred, the grade of metastatic lesions or implants is the best determinant of prognosis. [23] [24] 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. [8] Gliomatosis peritonei, a rare condition often associated with immature ovarian teratoma, is characterized by the presence of mature glial implants in the peritoneum. [26] 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. [27]

A high degree of immaturity in the primary tumor, one that corresponds with a grade 3 diagnosis is a sign of poor prognosis. [23] [8] [28] [29] Grade 3 tumors often display chromosomal abnormalities, also an indication of poor prognosis. [24] Tumor grade is the most important factor for relapse in immature teratomas. [28] 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. [30] Among grade 3 patients, the stage was significantly associated with relapse. [30]

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. [23] However, these results antedate the use of multi-agent chemotherapy. [8] 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. [28]

Treatment

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. [28]

Surgery

Since the occurrence of immature teratoma is very rarely bilateral, current standard of care of unilateral salpingo-oophorectomy with wide sampling of peritoneal implants. [8] Total abdominal hysterectomy with bilateral salpingo-oophorectomy are not indicated as they do not influence outcomes. [8] Fertility-sparing surgery in the form of unilateral salpingo-oophorectomy is the primary treatment modality in young patients. [31] [32] [33] 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. [34] However, others caution against such an approach. [8]

Chemotherapy

Norris et al. (1976) observed an 18% recurrence rate in grade 2 tumors and 70% recurrence in grade 3 tumors. [23] 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. [35] 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. [28] 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. [36] 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. [36] However, the disease will recur in about 25% of well-staged patients treated with 6 months of VAC. [37]

See also

References

  1. ↑ Sun H, Ding H, Wang J, Zhang E, Fang Y, Li Z, et al. (April 2019). "The differences between gonadal and extra-gonadal malignant teratomas in both genders and the effects of chemotherapy". BMC Cancer. 19 (1): 408. doi: 10.1186/s12885-019-5598-0 . PMC   6492338 . PMID   31039746.
  2. ↑ "NCI Dictionary of Cancer Terms". National Cancer Institute. 2011-02-02. Retrieved 2018-04-20.
  3. ↑ Damjanov I (2009). Pathology secrets (3rd ed.). Philadelphia, PA: Mosby/Elsevier. ISBN   978-0-323-05594-9. OCLC   460883266.
  4. 1 2 3 Ulbright TM (January 2004). "Gonadal teratomas: a review and speculation". Advances in Anatomic Pathology. 11 (1): 10–23. doi:10.1097/00125480-200401000-00002. PMID   14676637.
  5. ↑ Schmidt D, Kommoss F (May 2007). "[Teratoma of the ovary. Clinical and pathological differences between mature and immature teratomas]". Der Pathologe (in German). 28 (3): 203–8. doi:10.1007/s00292-007-0909-7. PMID   17396268.
  6. ↑ Alwazzan AB, Popowich S, Dean E, Robinson C, Lotocki R, Altman AD (November 2015). "Pure Immature Teratoma of the Ovary in Adults: Thirty-Year Experience of a Single Tertiary Care Center". International Journal of Gynecological Cancer. 25 (9): 1616–22. doi:10.1097/IGC.0000000000000541. PMC   4623850 . PMID   26332392.
  7. ↑ Coran AG, Adzick NS (2012). Pediatric surgery (7th ed.). Philadelphia, PA: Elsevier Mosby. pp. 539–548. ISBN   978-0-323-07255-7. OCLC   778785699.
  8. 1 2 3 4 5 6 7 Di Saia PJ, Creasman WT (2012). Clinical gynecologic oncology (8th ed.). Philadelphia, PA: Elsevier/Saunders. pp. 329–356. ISBN   978-0-323-07419-3. OCLC   785577276.
  9. ↑ Ki EY, Byun SW, Choi YJ, Lee KH, Park JS, Lee SJ, Hur SY (2013-06-21). "Clinicopathologic review of ovarian masses in Korean premenarchal girls". International Journal of Medical Sciences. 10 (8): 1061–7. doi:10.7150/ijms.6216. PMC   3691806 . PMID   23801894.
  10. 1 2 Malkasian GD, Symmonds RE, Dockerty MB (June 1965). "Malignant Ovarina Teratomas. Report of 31 Cases". Obstetrics and Gynecology. 25: 810–4. PMID   14287472.
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  12. ↑ Moş C (2009). "Ovarian dermoid cysts: ultrasonographic findings" (PDF). Pictorial Essay Medical Ultrasonography. 11: 61–66. S2CID   5944732. Archived from the original (PDF) on 2018-04-20.
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  14. ↑ Brown KL, Barnett JC, Leath CA (March 2015). "Laparoscopic staging of ovarian immature teratomas: a report on three cases". Military Medicine. 180 (3): e365-8. doi: 10.7205/milmed-d-14-00288 . PMID   25735031.
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  18. ↑ - Vaidya S, Sharma P, KC S, Vaidya SA (2014). "Spectrum of ovarian tumors in a referral hospital in Nepal". Journal of Pathology of Nepal. 4 (7): 539–543. doi: 10.3126/jpn.v4i7.10295 . ISSN   2091-0908.
    - Minor adjustment for mature cystic teratomas (0.17 to 2% risk of ovarian cancer): Mandal S, Badhe BA (2012). "Malignant transformation in a mature teratoma with metastatic deposits in the omentum: a case report". Case Reports in Pathology. 2012 568062. doi: 10.1155/2012/568062 . PMC   3469088 . PMID   23082264.
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  21. ↑ Abiko K, Mandai M, Hamanishi J, Matsumura N, Baba T, Horiuchi A, et al. (December 2010). "Oct4 expression in immature teratoma of the ovary: relevance to histologic grade and degree of differentiation". The American Journal of Surgical Pathology. 34 (12): 1842–8. doi:10.1097/PAS.0b013e3181fcd707. PMID   21107090.
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  25. 1 2 Heskett MB, Sanborn JZ, Boniface C, Goode B, Chapman J, Garg K, et al. (June 2020). "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". Modern Pathology. 33 (6): 1193–1206. doi:10.1038/s41379-019-0446-y. PMC   7286805 . PMID   31911616.
  26. ↑ Liang L, Zhang Y, Malpica A, Ramalingam P, Euscher ED, Fuller GN, Liu J (December 2015). "Gliomatosis peritonei: a clinicopathologic and immunohistochemical study of 21 cases". Modern Pathology. 28 (12): 1613–20. doi:10.1038/modpathol.2015.116. PMC   4682736 . PMID   26564007.
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  28. 1 2 3 4 5 Pashankar F, Hale JP, Dang H, Krailo M, Brady WE, Rodriguez-Galindo C, et al. (January 2016). "Is adjuvant chemotherapy indicated in ovarian immature teratomas? A combined data analysis from the Malignant Germ Cell Tumor International Collaborative". Cancer. 122 (2): 230–7. doi:10.1002/cncr.29732. PMC   5134834 . PMID   26485622.
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  30. 1 2 Vicus D, Beiner ME, Clarke B, Klachook S, Le LW, Laframboise S, Mackay H (October 2011). "Ovarian immature teratoma: treatment and outcome in a single institutional cohort". Gynecologic Oncology. 123 (1): 50–3. doi:10.1016/j.ygyno.2011.06.037. PMID   21764111.
  31. ↑ Tay SK, Tan LK (January 2000). "Experience of a 2-day BEP regimen in postsurgical adjuvant chemotherapy of ovarian germ cell tumors". International Journal of Gynecological Cancer. 10 (1): 13–18. doi:10.1046/j.1525-1438.2000.00010.x. PMID   11240646.
  32. ↑ Kanazawa K, Suzuki T, Sakumoto K (June 2000). "Treatment of malignant ovarian germ cell tumors with preservation of fertility: reproductive performance after persistent remission". American Journal of Clinical Oncology. 23 (3): 244–8. doi:10.1097/00000421-200006000-00007. PMID   10857886.
  33. ↑ Low JJ, Perrin LC, Crandon AJ, Hacker NF (July 2000). "Conservative surgery to preserve ovarian function in patients with malignant ovarian germ cell tumors. A review of 74 cases". Cancer. 89 (2): 391–8. doi:10.1002/1097-0142(20000715)89:2<391::AID-CNCR26>3.0.CO;2-V. PMID   10918171.
  34. ↑ Zhao T, Liu Y, Wang X, Zhang H, Lu Y (April 2017). "Ovarian cystectomy in the treatment of apparent early-stage immature teratoma". The Journal of International Medical Research. 45 (2): 771–780. doi:10.1177/0300060517692149. PMC   5536676 . PMID   28415950.
  35. ↑ Gershenson DM, del Junco G, Silva EG, Copeland LJ, Wharton JT, Rutledge FN (November 1986). "Immature teratoma of the ovary". Obstetrics and Gynecology. 68 (5): 624–9. PMID   3763073.
  36. 1 2 Williams S, Blessing JA, Liao SY, Ball H, Hanjani P (April 1994). "Adjuvant therapy of ovarian germ cell tumors with cisplatin, etoposide, and bleomycin: a trial of the Gynecologic Oncology Group". Journal of Clinical Oncology. 12 (4): 701–6. doi:10.1200/JCO.1994.12.4.701. PMID   7512129.
  37. ↑ Slayton RE, Park RC, Silverberg SG, Shingleton H, Creasman WT, Blessing JA (July 1985). "Vincristine, dactinomycin, and cyclophosphamide in the treatment of malignant germ cell tumors of the ovary. A Gynecologic Oncology Group Study (a final report)". Cancer. 56 (2): 243–8. doi: 10.1002/1097-0142(19850715)56:2<243::AID-CNCR2820560206>3.0.CO;2-T . PMID   2988740.

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