Elevated HCG and retroperitoneal adenopathy after clomiphene therapy for infertility

Background

We believe this case emphasises that a closer interrogation of tumour marker trends, nodal imaging characteristics and retroperitoneal nodal histology is necessary prior to planning chemotherapy in similar patients with human chorionic gonadotropin (HCG) elevation on clomiphene citrate (CC).

Case presentation

We present a 37-year-old man with no prior significant medical or surgical history who presented with secondary subfertility. He had 1 live birth 3 years prior followed by two miscarriages, and despite trying to conceive for over 1 year was unsuccessful. He was a 6 pack-year smoker and discontinued smoking 7 years prior to presentation. Physical examination revealed bilateral normal sized descended testicles and normal secondary sexual characteristics. Blood investigations related to subfertility revealed elevated testosterone of 42.1 nmol/L and low follicle stimulating hormone (FSH) and luteinising hormone (LH) levels of 0.1 IU/L, respectively. Semen analysis parameters revealed volume of 3.8 mL (normal >1.5 mL), motility of 47% (normal >32%) and sperm concentration of 3.45 million per mL (normal 15 million/mL).1 In view of low FSH, LH levels and reduced sperm concentration the patient was started on CC at 25 mg every 2 days for 3 months. HCG testing was not performed prior to initiation of CC as it is not routine to do so.

After 2 months of therapy blood investigations revealed that testosterone had risen to 828 nmol/L with both FSH and LH remaining suppressed. HCG was elevated at 35 IU/L and CT scans of the abdomen and pelvis performed to asses for contributary adrenal abnormalities instead revealed enlarged retroperitoneal nodes with the largest measuring 18 mm at the left para-aortic region. There were smaller nodes at precaval and retrocaval region ranging from 7 to 8 mm (figure 1). It was noted that the nodes appeared to have significant fat content. There was no prior imaging for comparison. The adrenal glands were normal bilaterally. The patient was promptly referred to the multidisciplinary testicular cancer clinic and clomiphene was discontinued.

At the testicular cancer clinic, tumour markers were repeated demonstrating elevated HCG of 75 IU/L and normal alpha fetoprotein of 4.8 UG/L and lactate dehydrogenase of 195 U/L. Hormonal panel revealed elevated testosterone of 39.1 nmol/L and suppressed FSH and LH levels of 0.1 IU/L. CT of the chest revealed no metastasis. Ultrasound of the testes performed revealed normal sized testes bilaterally and while no discrete tumours were noted, extensive microlithiasis was observed on the right side and felt could be in keeping with an Azzopardi lesion of burnt out tumour (figure 2). His case was reviewed at our Multidisciplinary germ cell tumour rounds and it was felt he likely had a germ cell tumour. In line with European Association of Urology guidelines2 for stage IIA good risk non-seminomatous germ cell tumours counselling was performed for three cycles of bleomycin, etoposide and cisplatin chemotherapy. However, prior to proceeding, in view of the atypical nodal imaging findings a percutaneous biopsy of the largest left para-aortic node was performed. Histology returned as fibroadipose tissue with no malignancy seen. Additionally, his HCG levels had dropped down to 9 IU/L by 2 months after stopping clomiphene. This prompted a decision to defer the chemotherapy and continue surveillance.

Outcome and follow-up

A further 2 months later, his HCG had dropped to 4 IU/L. CT imaging revealed the retroperitoneal nodes to be regressing slightly with the largest now measuring 14 mm (figure 3). A repeat CT-guided percutaneous biopsy redemonstrated fibroadipose tissue with no malignancy noted. The patient remains well and asymptomatic. Tumour markers will be monitored again in 3 months’ time with interval imaging 6 months later. Table 1 illustrates the trend of tumour markers.