FDG-PET-CT in Growing Teratoma Syndrome with Non-Seminomatous Testicular Mixed Germ Cell Tumor

Non-seminomatous mixed (NSM) germ cell tumors (GCT) have varying percentages of malignant tumor (embryonal carcinoma, yolk sac tumor, choriocarcinoma) and teratoma (hair, teeth, bone; brain, thyroid, liver, lung tissue).¹ Radical orchiectomy is initial treatment and provides histologic characterization, treatment individualized by histology and if tumor markers [alpha fetoprotein (AFP), beta subunit of human chorionic gonadotropin (beta-hCG), and lactate dehydrogenase (LDH)] normalize after orchiectomy. Initial staging is computed tomography (CT) for retroperitoneal lymphadenopathy or distant lung metastasis. 2-deoxy-2-(¹⁸F)fluoro-D-glucose (FDG) positron emission tomography (PET), of limited utility in initial staging of GCT due to unacceptable negative predictive value (76%) for detection of lymph node involvement, is useful following initial adjuvant therapy and for evaluation of elevated tumor markers or residual masses – sensitivity/specificity of FDG-PET (80%/100%) superior to CT (70%/74%).² FDG-PET accurately identifies residual malignant germ cell masses, but cannot reliably distinguish mature teratoma from necrotic tumor.³ Growing Teratoma Syndrome, relatively uncommon (prevalence up to 7.6%), occurs when, during appropriate chemotherapy for NSMGCT with normalized tumor markers, an enlarging metastatic mass is present.⁴ These are benign mature well-differentiated teratomas that selectively grow after treatment of immature malignant cells, typically not accumulating FDG unless brain tissue is contained within the teratoma. These have potential for malignant transformation and recurrence if incompletely resected, but treatment is curative with prompt complete surgical resection.⁵ 16-year-old male, radical right orchiectomy for NSMGCT, embryonal carcinoma (70%), teratoma (20%), and yolk sac tumor (10%). Preoperative AFP and beta-hCG elevated. 3 months postoperative, tumor markers normalized, AFP 3.3 ng/mL (reference 0-8.1), beta-hCG <5 mIU/mL (reference 0-5), LDH 233 U/L (reference 120-246). Six months postoperative, tumor markers elevated (AFP 12.4, beta-hCG 22.2, LDH 1,257). FDG-PET/CT (Figure 1) – extensive active para-aortic, anterior mediastinal, left supraclavicular tumor. After 2 cycles of chemotherapy (bleomycin, etoposide, cisplatin) over 2 months, repeat FDG-PET/CT (Figure 2) – complete response; tumor markers normalized (AFP 2.7, beta-hCG <5). Non-FDG-avid aortocaval retroperitoneal cystic density, 1.1 cm craniocaudal x 1 cm anterior-posterior x 1.1 cm transverse, felt to be treated disease. After chemotherapy completion (4 cycles) over an additional 2 months, FDG-PET/CT (Figure 3) – increased size of non-FDG-avid aortocaval retroperitoneal cystic density (2.7 cm x 2 cm x 2.1 cm); normal tumor markers (AFP 3.3, beta-hCG <5); surveillance the chosen pathway. 4.5 years following orchiectomy, patient presented with right back pain, outside CT reporting enlarged aortocaval retroperitoneal cystic mass, normal tumor markers (AFP 2.7, beta-hCG <5, LDH 151). FDG-PET/CT (Figure 4) – further enlargement of non-FDG-avid aortocaval retroperitoneal cystic mass (5.6 cm x 3.5 cm x 4.4 cm), no sites of active tumor. Subsequent retroperitoneal tumor dissection – mature cystic teratoma, no malignancy. 2.5 years later, patient remains tumor free. Testicular cancer is the most common solid malignancy in males ages 15-35 years, and with appropriate treatment and surveillance, is highly curable, 5-year survival rate > 95%.⁶ A clinical conundrum uncommonly arises when an enlarging metastatic mass persists with normal tumor markers. FDG-PET/CT is useful in characterizing these as benign metastatic teratomas, and with no other FDG-PET/CT evidence of recurrent malignancy, surgical removal of the growing teratoma removes the potential for malignant transformation, providing ongoing curative therapy.