Malignant mixed ovarian germ cell tumor composed of immature teratoma, yolk sac tumor and embryonal carcinoma harboring an EGFR mutation: a case report

Abstract

Malignant mixed ovarian germ cell tumors are very rare, accounting for ~5.3% of all malignant ovarian germ cell tumors (MOGCTs), with a very high degree of malignancy. The treatment of patients with persistent, refractory, or platinum-resistant MOGCT is not well defined. The objective of this case report was to analyze the importance of chemotherapy, salvage surgery and target therapy in the treatment of a patient with refractory OGCT after first-line chemotherapy failure. We reported a 34 year-old woman suffered from advanced refractory MOGCT after first-line chemotherapy, cytoreductive surgery, and a series of chemotherapy. The genetic test shows she is a carrier of EGFR: p.L858R mutation. Based on genetic testing result, she received icotinib which targeted for EGFR mutation, but the tumor progressed. After a secondary cytoreductive surgery, she exhibited a partial response and continued to receive chemotherapy. This suggests that salvage surgery may be considered for patients with persistent or refractory MOGCTs when no effective systemic treatment option is available. Targeted therapies based on gene sequencing may provide a new option; however, its efficacy and related resistance mechanisms still need to be verified by further study.

Keywords: EGFR mutation; mixed ovarian germ cell tumor; next-generation sequencing; salvage surgery; target therapy.

Figure 1

Changes of residual lesions showed by PET-CT. Notes: (A) March 10, 2017, before chemotherapy and cytoreductive surgery; (B) September 19 2017, after cytoreductive surgery and nine courses of chemotherapy; (C) April 4, 2018, before secondary cytoreductive surgery. Abbreviation: PET-CT, positron emission tomography-computed tomography.

Figure 2

Some specimens at first cytoreductive surgery. Notes: (A) Metastases located between spleen and descending colon; (B) omentum.

Figure 3

Changes of residual lesions by cytoreductive surgery. Notes: The yellow arrows represent metastases. Most metastases disappeared after cytoreductive surgery (left: before cytoreductive surgery; right: after cytoreductive surgery).

Figure 4

Postoperative pathology proved the tumor was a MOGCT with immature teratoma (G2), small amount of YST and embryonal carcinoma. Notes: (A) immature teratoma component (HE, 100×); (B) YST and embryonal carcinoma component (HE, 400×); (C) AFP immunostain diffusely positive in YST component (400×); (D) SALL-4 positive in YST and embryonal carcinoma component; (E) SOX2 positive in embryonal carcinoma; (F) AE1/AE3 positive in YST and embryonal carcinoma component. Abbreviations: MOGCT, malignant ovarian germ cell tumor; YST, yolk sac tumor.

Figure 5

The result of comprehensive genomic profiling revealed an EGFR somatic mutation (p.L858R).

Figure 6

CT scan revealed multiple metastases. Notes: The yellow arrows represent metastases. Metastases were mainly located in the subcapsular area of the liver and in the right attachment area.

Figure 7

Metastases between liver and diaphragm.

Figure 8

Serum AFP and β-HCG levels during treatment. Abbreviation: A, actinomycin D; AFP, alpha fetoprotein; B, bleomycin; Be, bevacizumab; C, cyclophosphamide; CRS, cytoreductive surgery; D, docetaxel; E, etoposide; F, FUDR; Ge, gemcitabine; I, ifosfamide; M, methotrexate; P, cisplatin; RCRS, re-cytoreductive surgery; RFA, radiofrequency ablation; T, taxol; V, vincristine.