Massive Intra-abdominal Germ Cell Tumors: A Case Series and Review of Literature

Case Review Massive Intra-abdominal Germ Cell Tumors: A Case Series and Review of Literature Daniel G. Wong, Nirmish Singla, MD, Aditya Bagrodia, MD University of Texas Southwestern Medical Center, Dallas TX Intra-abdominal testes are at increased risk of malignant transformation and can manifest as large abdominal masses with a wide variation in presenting symptoms. In the setting of cryptorchid or nonpalpable testes, large abdominal masses are highly suspect for germ cell tumors. Without standard guidelines, management can vary extensively. Surgical management may not be trivial and can entail a major abdominal operation in the context of a multimodal approach. The use of biopsy and serum tumor markers may effectively guide sequence of management based upon expected histology. In advanced cases, neoadjuvant chemotherapy may be pursued, and retroperitoneal lymph node dissection may be accomplished at the time of orchiectomy to minimize morbidity. The development of these massive late stage tumors reaffirms current guidelines on the early correction of cryptorchidism. [Rev Urol. 2019;21(2/3):136–140] © 2019 MedReviews®, LLC KEY WORDS Testicular • Seminoma • Nonseminomatous O nly 5% of undescended testes (UDT) are estimated to be intra-abdominal.1 If these testes remain intra-abdominal, the risk of developing germ cell tumors is significantly increased.2,3 Intra-abdominal testicular tumors are rare and have variable symptomatic presentations. We discuss two cases in which the presentations were at opposite ends of the spectrum. One case presented almost completely asymptomatic, whereas the other 136 • Vol. 21 No. 2/3 • 2019 • Reviews in Urology presented with months of severe pain, weight loss, and night sweats. Due to a large potential for undetected growth in the abdominal cavity, these tumors are often discovered as huge late-stage malignancies and management can be complex. Definitive risk stratification and stage are difficult to determine without resection of the primary tumor. In the setting of a very large intra-abdominal mass, suspicious for testicular tumor, radical orchiectomy can be a Massive Intra-abdominal Germ Cell Tumors major, potentially morbid abdominal operation for both diagnosis and initial treatment. Furthermore, consideration for induction chemotherapy to improve resectability of the intra-abdominal mass (testes) may be warranted. With no standard guideline for the management of intra-abdominal testicular tumors, the treatment can vary extensively based on risk stratification and clinical expertise. We report our experience managing two unique cases of large germ cell tumors arising from intraabdominal testes and review related case series in the literature. Case Reports Patient 1 A 23-year-old man with a history of bilateral UDT presented with no symptoms except for mild abdominal fullness. Knowing his history of UDT, he was encouraged to go to the hospital by his newlywed spouse. Abdominal CT imaging was pursued and revealed a large multilobulated mass between the bladder and the sigmoid (Figure 1). A right inguinal testicle was also found in addition to prominent 1-cm paraaortic lymph node. Serum alphafetoprotein (AFP), human chorionic gonadotropin (hCG), and lactate dehydrogenase (LDH) levels were 221, 149, and 629, respectively. CT Figure 1. Abdominal CT imaging revealing a large multilobulated mass between the bladder and the sigmoid. A B Figure 2. (A) Final pathology of a mixed germ cell tumor. Atrophic right testis showed evidence of tumor invasion. (B) Composition involved 99% seminoma and 1% yolk sac tumor elements. chest imaging was negative for metastasis. Following discussion at multidisciplinary tumor board, surgical resection of primary tumor and retroperitoneal lymph node dissection was consensus management strategy. After appropriate counseling regarding sperm banking and lifelong testosterone supplementation, the patient agreed to undergo bilateral orchiectomy and retroperitoneal lymph node dissection (RPLND). Semen analysis yielded a total sperm count of 0, therefore sperm banking was not pursued despite the patient’s willingness. A midline laparotomy incision was made to enter the abdomen, and the mass was readily located. The right testicle was notably adherent to the mass. After bilateral ligation of the gonadal vessels and vasa deferentia, the mass was removed en bloc with the right testis and with grossly negative margins. The tumor appeared well encapsulated. Full-template primary bilateral nerve-sparing RPLND was then performed. The entire specimen weighed 1093 g and measured 17.5 3 9 3 6.5 cm with no normal left-sided testicular parenchyma identified. The right testis was atrophic and showed evidence of tumor invasion (Figure 2A). Histologically, the composition involved 99% seminoma and 1% yolk sac tumor elements (Figure 2B), with final pathologic stage pT2N0Mx. Postoperatively, his serum tumor markers (STMs) normalized, and he has demonstrated no relapse within 6 months of his surgery. Patient 2 A 31-year-old man with a history of prematurity and left cryptorchidism presented to the emergency room with a 1-month history of abdominal pain, weight loss, and night sweats. Abdominal CT showed a retroperitoneal mass measuring 11 3 8 3 8.5 cm and lower abdominal anterior mass measuring 11.8 3 16 3 19.3 cm (Figure 3). STMs revealed serum levels of 1221, 93, and 2 for LDH, hCG, and AFP, respectively. Ultrasoundguided percutaneous biopsy was pursued, demonstrating pure seminoma. Staging work-up revealed International Germ Cell Cancer Collaborative group good-risk clinical stage IIC disease (cTxN3M0Sx). Considering his histology and STMs, upfront chemotherapy with 3 cycles of bleomycin, etoposide, and cisplatin (BEP) were administered, with downstaging of the retroperitoneal mass to 3.7 3 1.4 cm and of his abdominal mass to 8.1 3 6.4 3 4.8 cm and normalization of STMs. He declined to undergo prechemotherapy sperm banking despite education on the risks of infertility. Fluorodeoxyglucose– positron emission tomography (FDG-PET) scan 8 weeks after treatment was obtained with minimal FDG uptake by the residual retroperitoneal mass. Given these Vol. 21 No. 2/3 • 2019 • Reviews in Urology • 137 Massive Intra-abdominal Germ Cell Tumors continued A B C Figure 3. (A, B) Intraoperative and surgical specimen photos. (C) Histologic evaluation revealed no viable tumor tissue (ypT0). results, surgical excision of the abdominal mass without RPLND was pursued following multidisciplinary evaluation and shared discussion regarding the associated Figure 4. Abdominal CT showed a retroperitoneal mass measuring 11 3 8 3 8.5 cm and lower abdominal anterior mass measuring 11.8 3 16 3 19.3 cm. risks, benefits, and alternatives with the patient. The operation was approached laparoscopically. The mass was readily identified and appeared non-adherent to surrounding structures (Figure 4A). The ipsilateral gonadal vessels and vas deferens were ligated and the mass was removed. The specimen weighed 107 g and measured 16.5 3 7.5 3 4.1 cm (Figure 4B). Histologic evaluation revealed no viable tumor tissue (ypT0) (Figure 4C). STMs remained normal at his 6-month postoperative visit, and he has since remained disease free. No FDG avid masses were seen on followup PET nor was there biochemical reoccurrence at 6 months. Discussion Etiology and Classification The relative risk for development of testicular germ cell tumor is between 2.75 to 8 among all cryptorchid testes when compared with case controls with no history of UDT.3 Only 5% of UDT are found in the abdomen, which confers an even higher risk of malignant transformation.1,4 Intra-abdominal malignancy in this setting is a rare phenomenon in light of current guidelines for the management and correction of cryptorchidism in early childhood. Only 9 such cases have been reported in the past 20 years, 5-11 7 of which were managed outside the United States. The average size of the abdominal testicular tumors reported in these 9 cases was 13.56 cm in greatest dimension, like our patients reported herein. This growth is largely driven by the often absent or nonspecific nature of symptoms. The occurrence of these aggressive late-stage malignancies effectively demonstrates the natural history of uncorrected UDT and reaffirms our current guidelines 138 • Vol. 21 No. 2/3 • 2019 • Reviews in Urology for the early correction of cryptorchidism. Though 95% of testicular cancer is considered curable,12 these advanced cases may entail extensive surgery, multimodal treatment, and long-term issues related to castration and infertility. Diagnosis Discovery of large pelvic and retroperitoneal masses in the setting of nonpalpable testes merits a high suspicion for intra-abdominal germ cell tumor. Considering the wide differential diagnosis, percutaneous biopsy may be indicated to establish diagnosis, whereas it is traditionally avoided in scrotal germ cell tumors due to theoretical fears of altering lymphatic drainage, and diagnosis is hence often established via radical orchiectomy.13 STMs are mandatory and may provide histologic insight. In the case of patient 1, biopsy was foregone because the STMs with an elevation of AFP were suggestive of non-seminomatous germ cell tumor (NSGCT), and the mass was felt to be resectable in conjunction with RPLND without the need for induction chemotherapy. In the case of patient 2, biopsy was pursued because the STMs did not effectively rule out pure seminoma, and the determination of NSGCT versus seminoma could affect the management approach considering post-chemotherapy residual masses. Specifically, if NSGCT was suspected all radiographically evident post-chemotherapy masses would have been resected. Whereas for pure seminomas, a more deliberate approach involving repeat staging, PET scan for masses .3 cm at least 12 weeks after treatment, and possible repeat PET/biopsy/RPLND/ salvage chemotherapy would be advised for PET-positive lesions. The caveat is that although biopsy can rule out seminoma, it cannot rule out NSGCT. As illustrated by Massive Intra-abdominal Germ Cell Tumors our cases and various approaches in the literature,8,9,11 the utility of biopsy can vary by accessibility and potential impact on management approaches, but it is not mandatory. Management Although traditionally radical orchiectomy serves both diagnostic and initial treatment purposes by providing risk stratification to guide subsequent treatment (chemotherapy, radiation, RPLND, or active surveillance), this treatment paradigm need not be strictly followed in the case of intra-abdominal malignant germ cell tumors. Resection of these massive intra-abdominal tumors requires a major abdominal procedure that can be accompanied by increased operative risk and difficulty. Furthermore, if RPLND is anticipated, it can be accomplished in the same setting as orchiectomy and may dictate the sequence of management. All 9 cases reported previously in the literature involved open laparotomy to explore the abdomen and resect testes (Table 1).5-11,14,15 Four of 9 cases were treated with subsequent chemotherapy at 6 months. As we showed in the case of patient 2, resection of even large masses can be accomplished in a minimally invasive manner. In selected patients with advanced disease, upfront chemotherapy and delayed orchiectomy may be considered to downsize the primary or metastatic masses and potentially treat or improve resectability of the cancer.16 This is perhaps even more viable for intra-abdominal germ cell tumors given that biopsy may be pursued without the threat of scrotal violation and the predisposition to discovering these tumors once they have grown to enormous proportions. Two of 9 cases in the literature utilized this approach.9,10 In both cases, biopsy revealed seminoma, and 4 cycles of BEP were administered followed by open orchiectomy and RPLND. Neither case had viable residual tumor cells on pathologic examination. In our series, patient 2 similarly responded well, as evidenced by ypT0 stage and lack of FDG uptake in retroperitoneal lymph nodes following chemotherapy. If we assume pure seminoma from biopsy results, this treatment sequence can add the benefit of avoiding RPLND given a favorable response on FDG-PET (,3 cm avid mass),17 effectively sparing the patient another high-risk procedure. If an FDG avid mass .3 cm was detected, RPLND would likely have been performed at the time of laparoscopic orchiectomy although a repeat PET scan and biopsy of the avid lesion would be very reasonable conservative options. Within the scheme of post-chemotherapy evaluation of retroperitoneal masses, FDG-PET scans are ordered secondary to positive findings of a residual mass .3 cm on first line MRI or CT. Residual masses without FDG uptake need not be resected, but should be followed with standard surveillance protocols. In the event of NSGCT, any residual mass .1 cm should be resected given the inability to accurately predict residual teratoma or viable germ cell tumor from fibrosis or necrosis. Conclusions Intra-abdominal testicular tumors can grow to extraordinary sizes before garnering medical attention, and orchiectomy can be a major abdominal procedure for these patients. There are multiple approaches to managing such masses, as we have shown in our unique case series, and the selected Main Points • Intra-abdominal testes are at increased risk of malignant transformation and can manifest as large abdominal masses with a wide variation in presenting symptoms. In the setting of cryptorchid or nonpalpable testes, large abdominal masses are highly suspect for germ cell tumors. • Without standard guidelines, management can vary extensively. Surgical management may not be trivial and can entail a major abdominal operation in the context of a multimodal approach. • The use of biopsy and serum tumor markers may effectively guide sequence of management based upon expected histology. • In advanced cases, neoadjuvant chemotherapy may be pursued and retroperitoneal lymph node dissection may be accomplished at the time of orchiectomy to minimize morbidity. • The development of these massive late stage tumors reaffirms current guidelines on the early correction of cryptorchidism. Vol. 21 No. 2/3 • 2019 • Reviews in Urology • 139 Massive Intra-abdominal Germ Cell Tumors continued TABLE 1 Similar Cases in the Literature Case Biopsy Chemotherapy/ Radiotherapy Neoadjuvant RPLND Operation Country Largest Dimension (cm) Pathology Diseasefree f/u Velez D et al (2015)9 Yes BEP Yes Yes Open lap USA 17 Seminoma 4 mo Sandikci F et al (2018)14 No BEP No No Open lap Turkey 14 Mixed 6 mo Rourke E et al (2018)8 Yes — No No Open lap USA 20 Seminoma — Tazi MF et al (2013)11 Yes BEP No No Open lap Morocco 10 Embryonal 18 mo Iwamura H et al (2013)10 Yes BEP Yes Yes Open lap Japan — Seminoma 17 mo Hussain S (2015)5 No BEP No No Open lap India 12 Seminoma — Alshyarba MH (2010)15 No Radiotherapy No No Open lap Saudi Arabia 18 Seminoma 18 mo Yoon CY et al (2006)6 No — No No Open lap Korea 7.5 Mixed 16 mo Singla A et al (2016)7 No BEP No No Open lap India 10 Mixed — BEP, bleomycin, etoposide, and cisplatin; RPLND, retroperitoneal lymph node dissection. approach must be tailored to the individual patient. 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