Metastatic seminoma with cervical lymphadenopathy as the initial manifestation.

Abstract

Advanced testicular germ cell tumors commonly involve cervical lymph nodes. In most circumstances, the diagnosis of germ cell tumor is established before the neck disease is noted. In rare cases, these tumors have been found along with cervical lymphadenopathy in patients with a previously undiagnosed primary tumor. In this article, we report the unusual case of a 71-year-old man whose metastatic seminoma initially manifested as an asymptomatic neck mass. This finding reinforces the need to include metastatic disease in the differential diagnosis of neck masses. Our discussion of this case focuses on the appropriate management of cervical metastases of germ cell tumors.

Introduction

The incidence of testicular tumors in the United States is approximately 6 per 100,000 males; these neoplasms are the most common tumors in males in the 15-to-34-year age group. (1) Germ cell tumors account for 98% of all testicular malignancies. (1) Among patients with testicular carcinoma, the incidence of neck metastasis has been reported to range from 4.5 to 15%; in an estimated 5% of these cases, a neck mass is the initial sign. (2,3) Although the presence of cervical metastasis is believed to be a marker for advanced disease, even advanced testicular cancer is thought to be curable with appropriate therapy. (4) Overall cure rates for germ cell tumors are in the range of 90 to 95%, but maintenance of these cure rates requires structured and timely approaches to therapy. (5)

When a cervical metastasis is present especially when the germ cell tumor manifests as a neck mass--the otolaryngologist may play a central role in the structured management of such a patient. In this article, we report an unusual case of metastatic seminoma that initially manifested as a neck mass. Our discussion of this case focuses on the evaluation and management of germ cell tumors with cervical metastases.

Case report

A 71-year-old white man presented with a chief complaint of a neck mass. The patient had noted a left supraclavicular neck mass 2 days earlier. The mass was asymptomatic. The patient had a history of papillary carcinoma of the thyroid, which had been treated with thyroidectomy 2 years earlier. The pathology report at that time indicated that there was no vascular invasion. When postoperative scanning identified some residual disease in the right lower neck and left upper neck, the patient was treated with radioactive iodine. The history and a review of systems also revealed that the patient had a congenitally atrophic right testicle as well as recent fatigue and weight loss. Findings on a head and neck review of systems were negative. The patient had not used any tobacco products for more than 35 years.

On physical examination, the patient was noted to be well developed and well nourished, and he communicated easily without assistance. His voice was somewhat hoarse and rather high-pitched. Findings on examination of the ears, nose, and oral cavity were normal. Further examination detected no suspicious lesions in the nasopharynx, oropharynx, or hypopharynx. Mirror examination revealed hypomobility of the right true vocal fold. The neck mass measured 5 cm in diameter and was located at the base of the neck just above the left clavicle. It was nontender and fixed. The carotid artery remained palpable medial to this mass. No other cervical lymphadenopathy was noted. Computed tomography (CT) at the level of the left clavicle revealed that the mass had displaced the trachea (figure 1).

[FIGURE 1 OMITTED] Needle aspiration biopsy yielded a moderate amount of mucoid material. Cytology demonstrated malignant cells consistent with a poorly differentiated epithelial malignancy (figure 2, A); on this basis, melanoma and lymphoma were ruled out. Immunohistochemical analysis revealed that the malignant cells were negative for pankeratin (AE1/AE3), S-100, HMB-45, CD30, and chromogranin; these cells were positive for keratin (CAM 5.2) and vimentin. Numerous lymphoid cells in the background were positive when stained for CD45, CD3, and CD20.

[FIGURE 2A OMITTED] Given the diagnosis of poorly differentiated epithelial malignancy on needle aspiration, excisional biopsy was performed to establish a definitive diagnosis. Upon exploration, it was noted that the mass was deep to the sternocleidomastoid and omohyoid muscles. The jugular vein was displaced anterior to the mass. The mass extended laterally into zone V and inferiorly beneath the clavicle; it appeared to partially encapsulate the carotid artery. Given the anticipated difficulty and morbidity associated with complete excision, representative portions of the mass were excised for pathologic diagnosis and the remainder of the mass was left in place.

Findings on histologic examination of the excised tumor were consistent with seminoma with atypical features (figure 2, B). The specimen contained large epithelioid malignant cells with large vesicular nuclei and prominent nucleoli. A moderate amount of variably vacuolated cytoplasm surrounded the nuclei. Mitotic figures were conspicuous. The neoplasm had a consistent lymphoid and granulomatous stroma. Nuclear pleomorphism was more striking than is the case in classic seminoma. The diagnosis of seminoma was confirmed by further immunohistochemical studies (figure 2, C), although the negative staining for placental alkaline phosphatase and CD 117 are considered to be atypical for seminoma.

[FIGURE 2B, 2C OMITTED] Following the diagnosis of the neck mass, testicular examination revealed the presence of an occult seminoma in the patient's atrophic right testicle. Further investigation revealed a collection of matted retroperitoneal lymph nodes as well as metastases beyond the retroperitoneum. The patient was diagnosed with stage-3 seminoma and began appropriate chemotherapy. He experienced a complete response to therapy, and at the 6-month follow-up, he had no evidence of disease. He subsequently died of an unrelated myocardial infarction. An autopsy was not performed.

Discussion

Testicular germ cell tumors can be split into two broad categories: seminomas and nonseminomatous germ cell tumors (NSGCTs). Seminomas account for approximately 60% of all testicular germ cell tumors. (6) The incidence of seminoma is highest among men aged 30 to 39 years, and it declines steadily with advancing age. (6) Such a tumor in a 71-year-old is exceedingly unusual; seminoma is rarely diagnosed in this age group. Treatment strategies are different for seminomas and NSGCTs; treatment can also vary according to the tumor stage in both categories. Clinicopathologic studies suggest that patients who have seminomas with atypical features tend to present at more advanced stages and that their tumors may behave more aggressively than seminomas without atypia. (7) Our patient was diagnosed with seminoma with atypical features. In light of the CT finding of a 5-cm collection of matted retroperitoneal lymph nodes and evidence of supradiaphragmatic disease, he was diagnosed as having a stage-3 seminoma.

The presence of cervical involvement is believed to be a marker for advanced disease, and most patients with testicular carcinomas present with other symptoms, such as a scrotal mass. When a neck mass is found to be a metastatic germ cell tumor, it is usually in the setting of a known primary tumor and other known metastatic disease, particularly beneath the diaphragm. (8)

Although some authors have estimated that as many as 5% of germ cell tumors initially manifest as a neck mass, (2,3) case reports of such a phenomenon are rare. Our superficial search of the MEDLINE database dating from 1966 turned up only a handful of previously reported cases of a metastatic germ cell tumor that initially manifested as a neck mass. Such a finding was described by Soboroff and Lederer (9) in a single case report, by Zeph et al (3) in 1 of 5 patients, and by Lee and Caleaterra (10) in 2 of 6 patients. None of these four patients was older than 34 years.

In extraordinarily unusual cases, a neck mass is the only manifestation of a germ cell tumor; no other primary tumor is ever found. In such a case, it is possible that the neck mass itself is the primary tumor or that the neck mass represents a metastatic deposit with spontaneous regression of the primary elsewhere; only four such cases have been described. (11) With respect to these cases, it is important to remember that as many as 10% of seminomas may be extragonadal in origin; such tumors typically occur in the anterior mediastinum, retroperitoneum, or pineal region. (12)

When germ cell tumors do metastasize to the cervical lymph nodes, such deposition may occur through either lymphatic or hematogenous channels. While all germ cell tumors have a propensity for lymphatic spread, NSGCTs are much more likely than seminomas to demonstrate hematogenous spread. (13,14) When lymphatic spread does occur, it follows characteristic lymphatic pathways. Both right-and left-sided testicular tumors spread first to the retroperitoneal nodes and then move superiorly along the thoracic duct. As a consequence, lymphatic metastases tend to be contiguous, spreading from the abdomen into the chest and finally into the neck. (14) Based on thoracic duct anatomy, cervical metastases from germ cell tumors are found almost exclusively within the left supraclavicular fossa, although aberrant crossover may occur. As for hematogenous spread, one possible mechanism includes metastatic reflux through Batson's paraspinal venous plexus, driven by transient increases in intra-abdominal and intrathoracic pressure. (15) This mechanism has been presumed to allow retroperitoneal renal cell cancers to metastasize to the head and neck. (16) The phenomenon of hematogenous spread may also explain the metastatic spread of seminoma to other areas of the head and neck, such as the orbit, sphenoid sinus, temporal bone, and jaw. (13)

Treatment strategies for advanced germ cell tumors continue to evolve. The treatment plan depends on the histology of the tumor (seminoma vs. NSGCT), the site of metastasis, and serum concentrations of tumor markers. (4,5,17) Once cervical lymph nodes are involved, the tumor is classified as stage 3 and initial treatment is generally chemotherapy. For NSGCTs, tumor markers may be followed; when tumor markers such as human chorionic gonadotropin or alpha-fetoprotein remain elevated, salvage chemotherapy is indicated. When tumor markers normalize but the neck mass persists, surgical resection is indicated to remove any recurrent disease, thereby eliminating the possibility of a reversion of mature teratoma to a more malignant phenotype and preventing further tumor spread. (2,3,10,18) In most cases, selective neck dissection is sufficient to provide adequate exposure for safe and aggressive resection of cervical disease. (2,3,18) Such neck dissection may be accompanied by simultaneous resection of retroperitoneal or thoracic disease if metastases persist in these areas as well. (19)

The management of seminoma is less clear and may be more controversial than that for NSGCT. (20) In seminoma, tumor markers may be negative at presentation (as was the case with our patient) and there fore may not be available to guide therapy. Also, seminomas tend to be more radiosensitive than are NSGCTs. Consequently, postchemotherapy management of residual masses (as studied in the retroperitoneum) might include radiotherapy, observation, or surgical resection; no studies address cervical seminoma specifically. However, researchers who did consider seminoma together with NSGCT in the more general category of germ cell tumors continue to recommend surgical resection of residual neck masses following chemotherapy. (2,10) Whether or not postchemotherapy resection is pursued, proper diagnosis necessitates that an otolaryngologist be aware that a metastatic germ cell tumor might manifest as a neck mass. As the case of our patient demonstrates, these tumors are occasionally found in an unexpected age group and even in the absence of a previously diagnosed primary tumor.

References

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From the Department of Otolaryngology and Communicative Disorders, The Cleveland Clinic, Cleveland, Ohio (Dr. Akst and Dr. Discolo), and the Division of Pathology and Laboratory Medicine (Dr. Dipasquale) and the Department of Otolaryngology and Communicative Disorders (Dr. Greene and Dr. Roberts), The Cleveland Clinic, Naples, Fla.

Reprint requests: David Greene, MD, Head, Department of Otolaryngology and Communicative Disorders, Cleveland Clinic Florida, 6101 Pine Ridge Rd., Naples FL 34119. Phone: [phone]; fax: [phone]; e-mail: [e-mail]