Malignancy in an Undescended Intra-abdominal Testis: a Single Institution Experience (2024)

Abstract

Cryptorchidism is one of the most common congenital anomalies of the genitourinary tract, encountered in 1% of men. The cancer risk in an ectopic testis is 40 times higher than a scrotal testis. However, not much literature is available on the management of this rare presentation of testicular cancer. A retrospective analysis was conducted at our institute of patients who were diagnosed with carcinoma in an undescended intra-abdominal testis between 2014 and 2019. Patients with an intra-abdominal mass with an empty hemiscrotum/scrotum were included in the study. In all 10 patients were identified with a mean age of 32years. Four patients were non-seminomatous germ cell tumors, and other 6 were seminomatous tumors. Five were in stage I, two in stage II, and three in stage III. Six patients received induction chemotherapy with bleomycin, etoposide, and cisplatin, and four had complete response. Five patients underwent laparoscopic excision, and five underwent open surgery. Two patients with bilateral (B/L) cryptorchidism underwent contralateral orchidopexy. Two patients with B/L intra-abdominal gonads and uterus underwent excision of the malignant testicular mass with removal of atrophic uterus and contralateral dysgenetic gonad. One patient developed peritoneal recurrence within 3months of completion of surgery. Both recurrence-free and overall survival were 90% after a median follow-up of 35months. Malignancy in an undescended intra-abdominal testis is a rare presentation of testicular cancer, diagnosis of which requires a sharp correlation between clinical and radiological findings. There management and prognosis remains similar to classical testicular cancer.

Keywords: Testicular cancer, Undescended testis, Intra-abdominal testis

Introduction

Around 0.4% males have cryptorchidism [1]. It is seen in approximately 5–6% of full-term infants and 25% of preterm infants [2, 3] and is one of the most common congenital anomalies of genito urinary tract [4]. Of all the complications that can arise in an undescended testis, the most dreaded is development of malignancy, as it is frequently recognized later in the course of disease. Testicular cancer is the most common solid tumor seen in males aged 25 to 40years [2]. The probability of development of malignancy in an undescended testis (UDT) is 40 timesthan that in a normal testis [5]. Although management is similar to that of a normally descended testis [6], rarity of this presentation means no definite guidelines exist at present. Coupled with this, the unusual presentation of such tumors (especially so when present in intra-abdominal location) gives rise to significant dilemma to the treating physician as to how to proceed with their management. Here we present a series on malignancy in an undescended intra-abdominal testis with respect to their management and treatment outcomes.

Material and Methods

A retrospective analysis was conducted at our institute of patients who presented with carcinoma testis in an undescended intra-abdominal testis between July 2014 and July 2019. Inclusion criteria included patients with presence of an intra-abdominal mass and an empty hemiscrotum on clinical evaluation. Biopsy from abdominal mass was not compulsory to make a diagnosis. Patients were evaluated with a contrast enhanced computerized tomography (CECT) scan of the abdomen and pelvis to look for the mass and its relation to surrounding structures, confirm no other position of ectopic testis, look for any retroperitoneal lymphnodes (RPLNs), and rule out other site of metastasis. Patients with bulky retroperitoneal nodes also underwent CT scan of the chest. Laboratory investigations including hematological profile and biochemistry tests were performed. Serum tumor markers including serum AFP (alpha-fetoprotein), serum B HCG (human chorionic gonadotropin), and serum LDH (lactate dehydrogenase) were done on diagnosis, followed by 3weeks after completion of chemotherapy, if given and again 3weeks following surgery. Patients were classified as seminoma and non-seminoma depending upon the biopsy if done and tumor markers and were staged according to 8th edition TNM staging [7] depending on lymph node status, serum tumor markers, and presence of distant metastasis.

Extent of surgery varied depending upon stage at presentation. Induction chemotherapy was given after discussion in multidisciplinary tumor board. Post chemotherapy at a 6-week interval, a CECT of the chest, abdomen, and pelvis was performed. On CECT, we assessed the chemotherapy response of abdominal testicular mass and retroperitoneal lymph nodes (if present at the initial presentation). For non-seminomatous germ cell tumors (NSGCT), the decision to operate the RPLNs was based on whether the size is more than or less than 1cm. Any patient with size less than 1cm was placed on close surveillance for retroperitoneum. For seminoma, the protocol to operate retroperitoneum was depending upon whether the size is less than or more than 3cm. Surgery was performed laparoscopically or open depending upon size of the mass and requirement of retroperitoneal lymph node dissection (RPLND), as assessed by the operating surgeon (Fig.1). The aim was to deliver the mass outside without any rupture. During surgery the mass was identified, and cord structures were traced and ligated at the deep ring. The gonadal vein was ligated in the retroperitoneum close to the insertion with left renal vein for left-sided mass and IVC for the right-sided mass. Following laparoscopic surgery, the specimen was placed in endobag and retrieved through apfannenstiel incision. Patients were discharged when fit and planned for adjuvant chemotherapy depending upon decision in MDT.

Patients were followed up every 3months for first 2years and every 6months thereafter with clinical examination, serum tumor markers, and radiological examination depending upon stage of disease. Patients were assessed for the type of surgery performed (open/laparoscopic), complication (intraoperative or postoperative), final histopathology report, chemotherapy given, response to chemotherapy, and long-term oncological outcomes including disease-free survival and overall survival.

Results

During the time period of 2014 and 2019, a total of 104 patients underwent surgery for testicular cancer in our department. Ten patients out of this had malignancy in an undescended intra-abdominal testis and were included in our analysis. The clinical features are summarized in Table ​Table1.1. The mean age was 32years. Four patients were non-seminomatous germ cell tumors, and 6 others were seminomas. Six patients received preoperative induction chemotherapy with bleomycin, etoposide, and cisplatin (BEP) ranging from 2 to 4 cycles, and four others were operated upfront. Of the 6 seminomas, 3 had raised serum LDH and one patient had raised B HCG. All NSGCT patients had raised S. AFP, S. BHCG, and S. LDH (2 were in S1 range and 2 were in S2 range). Five patients underwent laparoscopic excision, and other 5 underwent open excision of testicular mass. Two patients underwent RPLND along with excision of testicular mass. Two patients had bilateral (B/L) cryptorchidism for which they underwent contralateral orchidopexy at the same time. Two patients with B/L intra-abdominal gonads with uterus underwent excision of testicular mass with removal of uterus and contralateral dysgenetic gonad (Fig.2); both patients were phenotypically male (one patient had associated coronal hypospadias).

Discussion

Undescended testis (UDT) occurs with an incidence of 1 in every 500 men and may give rise to complications including cancer, ischemia, and infertility [1]. Cryptorchidism is associated with a higher risk of malignancy (relative risk of 3.7–7.5 times) than that of scrotal testis. Around 5–10% of men who developed testicular malignancy have cryptorchidism [8]. Malignant change typically peaks in 3rd to 4th decade of life [9]. The median age of patients in our series was 32years, which is comparable to other reported series [10, 11]. Due to its extra scrotal location, malignant UDT may become symptomatic much later in the course of illness. As a result, many present at a higher stage, treatment of which is challenging [12]. On the other hand, testicular germ cell tumors (TGCT) are most frequently diagnosed in men between 15 and 44years of age [1, 13], present at an early clinical stage, and are often cured by radical orchidectomy. More commonly tumors in UDT are seminoma [10], accounting for around 50–60% [5] of cases. In our series, the number of seminomatous tumors (60%) was more than the number of NSGCT (40%) similar to that seen by Raina et al. [14]. Few patients may be asymptomatic and diagnosed on routine checkup or evaluation for another problem, while others may present with acute symptoms due to torsion and hemorrhage [15]. Pain in abdomen was the most common symptom seen in our patients (8 patients), followed by abdominal mass in 5 (50%), difficulty in micturition, and constipation in one patient each. Diagnosis is often difficult as many patients are not aware of their cryptorchid status, and few others may have had a scrotal scar bur are not sure about the surgery that was performed. Three patients in our series were initially worked up as retroperitoneal tumor elsewhere and referred to our hospital. Only on further clinical evaluation, the diagnosis of intra-abdominal testicular tumor made.

There are two proposed theories for development of tumors in an UDT. Raised core temperature within an ectopic testis is pro-carcinogenic which is the first hypothesis. Abnormally high temperature in which UDT develops impairs both transformation of the neonatal gonocytes into spermatogonia and causes apoptosis of remaining gonocytes, allowing some to persist to become a possible source of carcinoma in situ (CIS) and malignancy after puberty [16, 17]. Thus early orchidopexy of a cryptorchid testis into scrotal sac may prevent development of malignancy. On the other hand, the 2nd hypothesis considers underlying hormonal changes that occur during intra-uterine and perinatal testicular development as responsible for cryptorchidism and malignant change in testis. Thus early orchidopexy may not always prevent development of cancer according to this hypothesis [18]. This may also account for slightly higher incidence for malignancy in the normally descended contralateral testis [19]. Like TGCTs, carcinoma in situ also occurs with a higher incidence in cryptorchid testis [20]. Overall incidence of CIS has been seen to be higher in men with macroscopic testicular atrophy [16], with bilateral cryptorchidism, with intra-abdominal testes, and those with abnormal genitalia or an abnormal karyotype [13, 21] .

The incidence of malignancy following correction of UDT varies from 2.23 to 5.4%, depending upon whether surgery is performed before or after 13years of age, respectively [12]. Based on the available data, the recommended age for the correction of cryptorchidism is before completion of 2years [12]. On the other hand, others have not found significant correlation between age of correction and risk of TGCT [22]. Whereas orchidopexy may not prevent development of cancer in all patients, it certainly makes its early detection feasible [15, 23]. Two patients in our series underwent orchidopexy of contralateral undescended testis, one in dartos pouch and the other in superficial inguinal ring. Few patients may present with testicular cancer in bilateral UDS. Two patients in our series had bilateral undescended intra-abdominal testis. Intraoperatively they were found to have intra-abdominal malignant gonadal mass with contralateral dysgenetic gonad and an atrophic uterus. In both these patients, the atrophic uterus and contralateral dysgenetic gonad was not apparent on CT scan but was an intraoperative finding, later confirmed by histopathology. They underwent excision of testicular mass, dysgenic gonad, and uterus. The final HPR came as NSGCT in one patient and SGCT in other. Overall gonadoblastoma is more common in some disorders of sex development (DSD), which present in UDT with gonadal dysgenesis [13, 20, 21, 24]. The risk of TGCT is greater in patients with intra-abdominal and bilateral UDT [21, 25].

Stage by stage tumors in an undescended testis present in more advanced stages than a normally descended testis [5, 11]. Overall management remains similar to testicular germ cell tumors, but there are certain differences. Firstly because of rarity of intra-abdominal presentation, treatment strategy needs to be individualized for each patient. For a normally descended testis, testicular mass excision itself serves as the biopsy to plan further treatment. For UDT patients with stage II or higher stage disease who will require multimodality approach, treatment needs to be sequenced while planning surgery. The main constraint to proceed with excision of mass first is its abdominal location, which will entail a laparotomy. Thus instead of doing laparotomy twice in case patient requires RPLND, one can give chemotherapy and then plan subsequent excision of mass with or without RPLND. Few published case reports have done the excision of intra-abdominal testicular mass first with confirmation of histology followed by chemotherapy [26, 27]. At least 2 large case series on malignant intra-abdominal testis with bulky RPLNs have recommended induction chemotherapy first followed later by excision of mass and residual LNs as a single step approach [28, 29]. This might ensure better compliance and also make surgery less challenging [28, 29].

Secondly the stage grouping in NSGCT is a matter of concern, since often S category is allotted before removal of testicular mass. The tumor markers may be erroneously elevated and so is the “S” stage. Stage 2 patients will be upstaged to stage 3, if the tumor markers increase from S1 to S2 or S3 range. Two NSGCT patients in our series had N1 disease but were upstaged to stage III due to higher S stage. Both these patients underwent biopsy from the mass followed by 4 cycles of BEP and lastly excision of mass as they had no residual nodes. Thirdly, should these patients undergo sampling of RP nodes during excision of mass upfront or following induction chemotherapy even when not indicated is questionable, as there are no set guidelines to guide in management of such scenarios. One patient in our study with stage IA, SGCT had subcentimeter lymph nodes on preoperative CT scan, which were sampled during excision of mass. This might be tempting as anyways laparotomy needs to be done for excision of primary. Although this may probably help in better staging in some cases, it is not bereft of complications [30]. Therefore decision for RPLND should be individualized for each patient taking into account the type of GCT, response to chemotherapy if given, as well as radiological and intraoperative findings.

Survival depends upon the stage at presentation and the histology of malignant mass. In series of 21 patients with undescended testis by Kulkarni et al, 6 patients had intra-abdominal location. The 3- and 5-year survival in their study for the entire group was 70% and 69%, respectively. They showed 100% 5-year survival in stage I and II and 33% in stage IV disease [11]. Seminomas perform better than NSGCTs as shown in studies by Husseiny et al. [6] and Thyavihally et al. [31]. Batata et al. also found higher survival and lower recurrences in seminomas versus NSGCT. They also found similar 5-year survival irrespective of whether the UDT was corrected surgically (61%) or uncorrected (63%) [10]. Prior studies trying to compare survival following surgery in normally descended testis versus that in a cryptorchid testis have not found any significant difference [14]. Our study with a median follow-up of 35months had one patient with systemic recurrence, who subsequently died of disease. The median disease-free and overall survival in our study was 90%, being 100% for seminomas and 75% for NSGCT. Rarity of this presentation means not enough literature exists on this group of patients. In the absence of adequate literature, our study definitely adds to existing scarce literature and should be a motivation to conduct further larger studies to answer doubts raised by our study.

Conclusion

Malignancy in an undescended intra-abdominal testis is a rare presentation of testicular cancer, diagnosis of which requires sharp correlation between clinical and radiological findings. There management and prognosis remains similar to classical testicular cancer.

Compliance with Ethical Standards

The data of the present study were collected in the course of common clinical practice, and accordingly, the signed informed consent was obtained from each patient for any surgical and clinical procedure. The study protocol was in accordance with the ethical standards of the institutional research committee and the 1964 Helsinki Declaration and its later amendments. Because this was a retrospective study, formal consent for this study is not required and no approval of the institutional research committee was needed.

Footnotes

References