DIAGNOSTIC UTILITY OF HUMAN CHORIONIC GONADOTROPIN WASHOUT IN CERVICAL LYMPH NODE FINE-NEEDLE ASPIRATION FOR METASTATIC TESTICULAR CANCER

Abstract

Objective:

This case report will describe the first adjunct use of directly measuring the concentration of human chorionic gonadotropin (HCG) in fine-needle aspiration (FNA) washout for diagnosing metastatic non-semi-nomatous germ cell tumor (NSGCT) of the testicle in a patient with cervical lymphadenopathy.

Methods:

We present the clinical, laboratory, imaging, and pathologic findings, along with a review of the literature.

Results:

A 23-year-old, otherwise healthy man who first presented with left testicular discomfort and swelling was diagnosed with NSGCT after undergoing a left orchiectomy. A few years later, the patient presented with a 2-cm left supraclavicular mass. Upon ultrasound of the thyroid and soft tissues of the neck, a 1-cm left thyroid nodule was revealed, as well as a 2.8-cm left supraclavicular lymph node, which was cystic in nature and worrisome for metastatic disease given the patient's history of metastatic NSGCT. The results of the FNA of the left thyroid nodule were benign, however the results from the supraclavicular mass were nondiagnostic. Due to the nondiagnostic FNA results, another aspiration with cytopathology and HCG evaluation washout was performed. The HCG aspirate came back with a value of 162 mIU/mL, despite the patient's negative serum HCG results.

Conclusion:

This case demonstrates a novel way to diagnose metastatic testicular germ cell tumors utilizing FNA-HCG washout. Future prospective trials are needed to further elucidate this important finding.

INTRODUCTION

Nearly 9,000 new testicular cancer diagnoses were made in 2017, with germ cell tumors encompassing close to 95% of all diagnoses (1). Fine-needle aspiration (FNA) biopsy is an extremely useful procedure for the diagnosis of metastatic germ cell tumors. Most of the subtypes can be easily recognized and differentiated from other subtypes, allowing for accurate diagnosis and staging. The accuracy of FNA biopsy fluctuates within the literature, with a sensitivity range of 77 to 95% and a specificity range of 93 to 100% (2,3). To stratify and effectively treat patients with metastatic disease, the first line of diagnostic testing includes FNA of draining lymph nodes. Excisional biopsy is only required in the setting of multiple nondiagnostic FNA attempts (4).

An innovative technique has been described in the endocrine surgery literature measuring thyroglobulin (TG) in FNA washout fluids for the assessment of metastatic thyroid carcinoma. The 2015 American Thyroid Association guidelines report the usefulness of FNA-TG washout for suspicious cystic lymph nodes after insufficient cytologic evaluation or differing ultrasonographic and cytologic assessments (5,6). A retrospective study involving 220 patients revealed FNA-TG washout was beneficial in metastatic disease in a lymph node with 2 or less suspicious characteristics on ultrasonography (6). A recent study reported that FNA-TG washout improves FNA biopsy sensitivity and specificity, as well as reliability in patients with recurrent papillary thyroid cancer. In addition, studies have shown that parathyroid hormone washouts are highly specific and reliable in verifying parathyroid lesions (7). FNA washout of calcitonin has also demonstrated higher sensitivity in discovering medullary thyroid cancer compared to cytology alone (8).

The adjunct use of directly measuring the concentration of human chorionic gonadotropin (HCG) in the washout for diagnosing metastatic germ cell tumors has not been reported in the literature. We propose to improve the diagnostic yield of cytology in these difficult cases. In the following case report, FNA-HCG washout was performed in a patient with a history of metastatic non-seminomatous germ cell tumor (NSGCT) of the testicle presenting with cervical lymphadenopathy.

CASE REPORT

A 23-year-old, otherwise healthy man first presented with left testicular discomfort and swelling. He was diagnosed with NSGCT after undergoing a left orchiectomy. The final pathology was stage IIIa, with 21 lymph nodes taken and all 21 lymph nodes negative for viable germ cell tumor. The patient underwent 3 cycles of chemotherapy with bleomycin, etoposide, and platinum that were completed in February of 2014. He was found to have a cystic mass on computed tomography of the neck with a subsequent left supraclavicular lymph node biopsy in March of 2014. Histopathology exhibited considerable necrotic tumor within the lymph node, revealing consistency with the metastatic nature of the left NSGCT diagnosis. The patient underwent retroperitoneal lymph node dissection in April of 2014. In January of 2017, he was found to have a 2.7 × 1.5-cm homogenous lesion of low attenuation in the left supraclavicular area on computed tomography scan.

Following this most recent finding, the patient was referred by his medical oncologist to our clinic for further evaluation. At this time, the patient had no other complaints. On physical exam, he exhibited a 2-cm left supraclavicular mass located in the supraclavicular fossa, without any additional cervical masses or lymphadenopathy. It was decided to further evaluate the supraclavicular mass with FNA with ultrasonography guidance.

Upon ultrasound of the thyroid and soft tissues of the neck, a 1-cm left thyroid nodule was revealed, as well as a 2.8-cm left supraclavicular lymph node, which was cystic in nature and worrisome for metastatic disease given the patient's history of metastatic NSGCT. The results of the FNA of the left thyroid nodule were benign and negative for the protein called B-Raf. The left level 4 lymph node FNA results were nondiagnostic and also B-Raf negative. Due to the nondiagnostic FNA results, another aspiration with cytopathology and HCG evaluation was offered to the patient. Repeat FNA was nondiagnostic, but showed an increase in size of the left level 4 lymph node from 2.8 to 3.1 cm. The HCG aspirate came back with a value of 162 mIU/mL, despite the patient's negative serum HCG results.

At this point in time, treatment options were discussed with the patient and he decided to undergo a positron emission tomography scan, in addition to excising his left supraclavicular mass. The supraclavicular mass excision took place in July of 2017. Final pathology results showed the lymph node with metastatic mature teratoma, consistent with origin from a testicular germ cell neoplasm. The patient did not require any additional treatment. A follow-up computed tomography scan was obtained 6 months later that did not show any recurrence or new metastatic implants.

DISCUSSION

In regards to testicular cancer, there are certain tumor markers that can be measured pre- and post-orchiectomy. Specifically, beta-HCG, lactate dehydrogenase, and alpha-fetoprotein are common markers that can provide important diagnostic information (1). In addition to tumor markers, and especially when discussing metastatic disease involving cervical lymphadenopathy, unification of ultra-sound and FNA are the 2 diagnostic modalities of choice for detection and assessment. Although FNA-cytology has displayed an appropriate level of accuracy in regards to recurrence of the primary tumor, as well as metastatic disease to cervical lymph nodes, there are still many nondiagnostic and false negative results (9).

As mentioned above, a recent study demonstrated the value of FNA-TG washout in conjunction with FNA-cytology, resulting in an improvement of both sensitivity and specificity for discovery of metastasis in a population of patients with papillary thyroid cancer recurrence. Studies have also exhibited the usefulness in FNA-parathyroid hormone washouts for parathyroid lesions, as well as FNA-calcitonin washouts for medullary thyroid cancer detection (7,8).

This is the first reported case utilizing FNA-HCG washout for detecting recurrent metastatic testicular cancer in a patient with cervical lymphadenopathy. Our patient underwent 2 ultrasound-guided FNA-cytology biopsies, with the first as solely FNA-cytology and the second as a combination of FNA-cytology and FNA-HCG washout. Interestingly, both FNA-cytology biopsy results were nondiagnostic, however, the FNA-HCG washout demonstrated an increased HCG level of 162 mIU/mL in the second specimen.

This case demonstrates the promising utility of FNA-HCG washout in patients with NSGCT with a component that produces HCG. An HCG washout has the potential to guide excisional biopsy in the setting of a nondiagnostic FNA. Although reports have established the escalated risks involved with open excisional biopsy of cervical lymphadenopathy, such as a heightened likelihood of local complications (4,10), excisional biopsy is still an important component of the diagnostic workup in NSGCT. The diagnosis of NSGCT encompasses many entities, such as embryonal carcinoma, yolk sac tumor, teratoma, and choriocarcinoma, among others (11), thus necessitating the use of an excisional biopsy.

Importantly, this case displays the potential utility of FNA-HCG washout to help direct excisional biopsy in the setting of a nondiagnostic or atypical FNA diagnosis with an elevated HCG. In addition to HCG, a panel including lactate dehydrogenase and alpha-fetoprotein washout may be beneficial in the setting of suspicious lymph nodes in patients with a history of NSGCT. Potential possibilities for a patient with a known specific history of yolk sac tumor or choriocarcinoma may comprise FNA and alpha-fetoprotein washout and FNA and HCG washout, respectively. Future studies are warranted to elucidate these findings.

CONCLUSION

This case demonstrates a novel way to diagnose metastatic testicular germ cell tumors utilizing FNA-HCG washout. Future prospective trials are needed to further elucidate this important finding.

Abbreviations:

FNA

fine-needle aspiration

HCG

human chorionic gonadotropin

NSGCT

non-seminomatous germ cell tumor

TG

thyroglobulin