Running Title: Utility of HCG Washout in Cervical LND FNA

Transcription

1 AACE Clinical Case Reports Rapid Electronic Articles in Press Rapid Electronic Articles in Press are preprinted manuscripts that have been reviewed and accepted for publication, but have yet to be edited, typeset and finalized. This version of the manuscript will be replaced with the final, published version after it has been published in the print edition of the journal. The final, published version may differ from this proof. Case Report ACCR DIAGNOSTIC UTILITY OF HCG WASHOUT IN CERVICAL LYMPH NODE FINE-NEEDLE ASPIRATION FOR METASTATIC TESTICULAR CANCER. Jamie Kaplan 1, BS, Helmi Khadra 1, MD, Andrew B. Sholl 2, MD; Emad Kandil 1, MD, MBA Running Title: Utility of HCG Washout in Cervical LND FNA From: 1 Division of Endocrine and Oncologic Surgery, Department of Surgery, Tulane University School of Medicine, New Orleans, LA; 2 Department of Pathology & Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA Corresponding Author: Emad Kandil, MD, MBA, FACS, FACE Edward G. Schlieder Chair in Surgical Oncology Professor of Surgery, Otolaryngology and Medicine Chief, Endocrine Surgery Section Department of Surgery, Tulane University School of Medicine hkhadra@tulane.edu

2 Objective: The objectives of this case report are to describe the first reported adjunct use of directly measuring the concentration of HCG in (fine needle aspiration) FNA washout for diagnosing metastatic nonseminomatous 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 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 2cm left supraclavicular mass. Upon ultrasound of the thyroid and soft tissues of the neck, a 1cm left thyroid nodule was revealed, as well as a 2.8cm 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 was non diagnostic. Due to the non-diagnostic FNA results, a re-aspiration with cytopathology and HCG evaluation washout was performed. The HCG aspirate came back with a value of 162mIU/ml, despite the patient s negative serum HCG results. Conclusion: This case demonstrates a novel way in diagnosing 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; NSGCT = nonseminomatous germ cell tumor; TG = thyroglobulin; PTH = parathyroid hormone; BEP = Bleomycin, Etoposide, and Platinum; RPLND = retroperitoneal lymph node dissection; CT = computed tomography; LDH = lactate dehydrogenase; AFP = alpha-fetoprotein.

3 INTRODUCTION Nearly nine thousand 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 77-95% and a specificity range of % (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 non-diagnostic 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 suspicious cystic lymph nodes, 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 two 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 (PTH) 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 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 nonseminomatous germ cell tumor (NSGCT) of the testicle presenting with cervical lymphadenopathy. CASE REPORT 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. 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 Bleomycin, Etoposide, and Platinum (BEP) that were completed in February of He was found to have a cystic mass on computed tomography (CT) of the neck with a subsequent left supraclavicular lymph node biopsy in March of 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 (RPLND) in April of In January of 2017, he was found to have a 2.7x1.5cm homogenous lesion of low attenuation in the left supraclavicular area on CT scan. Following this most recent CT scan 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 2cm 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

4 guidance. Upon ultrasound of the thyroid and soft tissues of the neck, a 1cm left thyroid nodule was revealed, as well as a 2.8cm 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 BRAF negative. The left level 4 lymph node FNA results were non-diagnostic and BRAF negative. Due to the nondiagnostic FNA results, a re-aspiration with cytopathology and HCG evaluation was offered to the patient. Repeat FNA was non-diagnostic, but showed an increase in size of the left level 4 lymph node from cm. The HCG aspirate came back with a value of 162mIU/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 PET scan, in addition to excising his left supraclavicular mass. The supraclavicular mass excision took place in July of 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 CT 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 (LDH), and alpha-fetoprotein (AFP) 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 ultrasound and FNA are the two 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 non-diagnostic 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-PTH 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 two ultrasound-guided FNA-cytology biopsies, with the first as solely FNAcytology and the second as a combination of FNA-cytology and FNA-HCG washout. Interestingly, both FNA-cytology biopsy results were non-diagnostic, however, the FNA- HCG washout demonstrated an increased HCG level of 162mIU/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 non-diagnostic 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 work-up 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. However, this case displays the potential utility of FNA-HCG washout to help direct excisional biopsy in the setting of a non-diagnostic or atypical FNA diagnosis with an

5 elevated HCG. In addition to HCG, a panel including LDH and AFP 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 AFP washout and FNA and HCG washout, respectively. Future studies are warranted to elucidate these findings. CONCLUSION: This case demonstrates a novel way in diagnosing metastatic testicular germ cell tumors utilizing FNA-HCG washout. Future prospective trials are needed to further elucidate this important finding. REFERENCES 1. Baird DC, Meyers GJ, Hu JS. Testicular Cancer: Diagnosis and Treatment. American Family Physician. 2018;97: Lee J, Fernandes R. Neck Masses: Evaluation and Diagnostic Approach. Oral and Maxillofacial Surgery Clinics of North America. 2008;20:

6 3. Smallman LA, Young JA, Oates J, et al. Fine needle aspiration cytology in the management ENT of patients. Journal of Laryngology & Otology. 1988;102: Strojan P, Ferlito A, Medina JE, et al. Contemporary management of lymph node metastases from an unknown primary to the neck: I. A review of diagnostic approaches. Head & Neck. 2011;35: Haugen BR, Alexander EK, Bible KC, et al American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26: Chung J, Kim EK, Lim H, et al. Optimal indication of thyroglobulin measurement in fine-needle aspiration for detecting lateral metastatic lymph nodes in patients with papillary thyroid carcinoma. Head & Neck. 2014;36: Abdelghani R, Noureldine S, Abbas A, et al. The diagnostic value of parathyroid hormone washout after fine-needle aspiration of suspicious cervical lesions in patients with hyperparathyroidism. The Laryngoscope. 2013;123: Trimboli P, Cremonini N, Ceriani L, et al. Calcitonin measurement in aspiration needle washout fluids has higher sensitivity than cytology in detecting medullary thyroid cancer: a retrospective multicentre study. Clinical Endocrinology. 2014;80: Cunha N, Rodrigues F, Curado F et al. Thyroglobulin detection in fine-needle aspirates of cervical lymph nodes: a technique for the diagnosis of metastatic differentiated thyroid cancer. Eur J Endocrinol. 2007;157: McGuirt WF, McCabe BF. Significance of node biopsy before definitive treatment of cervical metastatic carcinoma. Laryngoscope 1978;88:

7 11. Howitt BE, Berney DM. Tumors of the Testis. Surgical Pathology Clinics. 2015;8: