Metastatic seminoma presenting as neck and axillary lymphadenopathy in an elderly man

Abstract

A man in his 60s presented with a gradual progressive right-sided neck mass. Initial core biopsy was inconclusive and he was treated with a short course of oral prednisone for presumed sarcoidosis. Two months later, the patient developed worsening dysphagia, hoarseness of voice, dyspnea, and weight loss. Physical examination revealed bilateral cervical and right axillary lymphadenopathy. A right axillary lymph node excisional biopsy was performed and immunohistochemistry was diffusely positive for OCT4, SALL4, CD117, PLAP, confirming the diagnosis of metastatic seminoma. He received three cycles of bleomycin, etoposide, and cisplatin; bleomycin was omitted for the fourth cycle due to concern for toxicity. Restaging scans after four cycles of chemotherapy showed a favorable response to therapy. Unfortunately, the patient died from bleomycin pulmonary toxicity. This case illustrates a rare and atypical presentation of metastatic seminoma in an elderly patient.

Testicular germ cell tumor (GCT) is one of the most common solid tumors seen in young adults; however, it is rare in elderly men, accounting for only 4% of cases.¹ The incidence of testicular seminoma in men aged ≥50 years is increasing. When compared to Caucasians, Hispanics and African Americans have a lower probability of developing testicular cancer at an older age.² We present an interesting case of an elderly man with metastatic seminoma that presented with neck and axillary lymphadenopathy.

CASE PRESENTATION

A Hispanic man in his 60s presented with a 1-year history of a gradually progressive right-sided neck mass. Initial core biopsy showed fibrous tissue with a mild lymphohistiocytic infiltrate; acid-fast bacilli and Grocott’s methenamine silver stains were negative for acid-fast and fungal organisms, respectively. No overt features of malignancy were identified. He was started on oral prednisone for presumed sarcoidosis. Two months later, the neck mass significantly increased in size, and he developed dysphagia to solids, hoarseness of voice, anorexia, moderate weight loss, and shortness of breath. He denied fever, chills, night sweats, cough, chest pain, or palpitations. He was a nonsmoker. On examination, his vital signs were stable. He had no stridor. A hard, fixed 10 × 15 cm right neck mass and 3 × 4 cm left neck mass was palpable. No ulcers or lesions were noted in the oral cavity. He had enlarged right axillary lymph nodes but no inguinal or supraclavicular lymphadenopathy. He had no evidence of a testicular mass. Complete blood count, comprehensive metabolic panel, and erythrocyte sedimentation rate were within normal limits. Infectious workup for Epstein-Barr virus, cytomegalovirus, HIV, and fungal serologies was negative. A positron emission tomography (PET) scan is shown in Figure 1. The patient underwent right axillary lymph node (LN) excisional biopsy, showing sheets of large cells admixed with inflammatory cells; immunohistochemistry was diffusely positive for OCT4, SALL4, CD117, and PLAP (Figure 2).

Figure 1.

Right cervical lymphadenopathy measuring 15.0 × 11 cm with marked activity (max SUV of 18.1) and a few areas of necrosis. The mass extended into the right parapharyngeal, retropharyngeal, and right paraglottic space. The left cervical conglomerate measured 4.1 × 3.0 cm with a max SUV of 17.3. Right axillary 4.9 × 3.0 cm lymphadenopathy is noted with a max SUV of 15.6.

Figure 2.

(a) Hematoxylin and eosin stain shows sheets of large cells with eosinophilic cytoplasm and squared-off nuclei with prominent nucleoli admixed with background inflammatory cells (200× magnification). (b) OCT4 immunohistochemical stain shows a sheet of large cells with diffuse nuclear positivity (100× magnification).

Testicular ultrasound revealed bilateral testicular hypoechoic lesions and microlithiasis in the left testes. Serum alpha-fetoprotein was 1.3 ng/mL (reference range, 0–11), while lactate dehydrogenase (LDH) was 953 U/L (reference range, 98–192) and serum beta–human chorionic gonadotropin was 66.0 mIU/mL (reference range, <5). The diagnosis of metastatic seminoma was confirmed based on hematoxylin-eosin staining showing sheets of large cells with eosinophilic cytoplasm and prominent nucleoli admixed with background inflammatory cells. The immunohistochemical staining was diffusely positive for OCT4, SALL4, CD117, and PLAP with background inflammatory cells positive for CD45. The patient had intermediate-risk seminoma and we decided to treat him with four cycles of bleomycin, etoposide, and cisplatin (BEP) based on elevated LDH (>3 times the upper limit of normal). The patient received three cycles of BEP and tolerated it well. However, he developed a dry cough after cycle 3.

Computed tomography (CT) of the chest showed new patchy ground-glass opacities associated with ill-defined small consolidative opacities throughout the lungs with peripheral and basilar predominance concerning for bleomycin pulmonary toxicity. The main risk factor for this toxicity in our patient was age. He had no prior smoking history or underlying chronic lung disease. A pretreatment baseline pulmonary function study was normal (FEV/FEV1 84%, FEV1 82%, FVC 77%, DLCO 87%). He was treated with oral prednisone 1 mg/kg with significant improvement in symptoms. Bleomycin was omitted for cycle 4 and he received etoposide and cisplatin only. A PET/CT done 1 month after completing four cycles of chemotherapy showed a favorable response. The right neck mass had significantly decreased in size (6.0 × 2.1 cm with maximum standardized uptake value [SUV] of 2.4 compared to 15.0 ×11 cm and maximum SUV of 18.1 prior to treatment). The left level 2 A lymph node was non-FDG avid and measured 0.9 cm, significantly decreased from the initial scan showing 1.8 cm. Posttreatment LDH was still elevated at 508 U/L.

Two months after completing treatment, the patient presented with worsening shortness of breath, and CT of the chest showed bilateral diffuse ground glass, significantly progressed compared to the prior CT with some peripheral fibrotic changes. The patient was started on intravenous methylprednisone 1 mg/kg and placed on mechanical ventilation for worsening respiratory failure. Unfortunately, he died from multiorgan failure.

DISCUSSION

Seminoma is the most common (74%) malignant GCT in elderly men.^3,4 The histological variants of seminoma include classic (85%), anaplastic (5% to 15%), and spermatocytic seminoma, with the latter more common in the elderly.³ The differential diagnosis of an elderly man with cervical lymphadenopathy includes lymphoma, metastatic head and neck cancer, metastatic cancer from the aerodigestive tract, and infection. Testicular neoplasms usually present as a painless mass in the testicle or with a secondary hydrocele. Occasionally, the primary testicular GCT may be absent due to spontaneous regression or “burnt-out primary,” which is well recognized, and the only manifestation may be testicular microlithiasis.⁵

Cervical or axillary lymphadenopathy as the sole initial presentation of a testicular GCT is extremely rare. In a retrospective review of 665 patients with testicular cancer, only 23 patients (3.4%) had cervical LN metastases at initial diagnosis.⁶ Seminomas have a predilection for the cervical LN as they typically spread via lymphatics and follow the thoracic duct.⁷ Serum tumor markers provide important diagnostic and prognostic clues in testicular GCT. Elevated serum alpha-fetoprotein essentially rules out pure seminomas. Serum LDH ≥ 2.5 times the upper limit of normal is an independent poor prognostic factor.⁸

Metastatic seminomas are categorized as good risk if there is no metastasis to organs outside of LN and lungs. Intermediate-risk disease involves metastasis to organs other than lungs and LN. Cisplatin-based chemotherapy has changed the therapeutic landscape of testicular neoplasms. Seminomas are considered highly curable in younger patients, even in the metastatic setting, but the prognosis of older men (≥50 years) remains suboptimal, as they often have advanced disease at presentation and are at risk for treatment-related mortality.^3,4 For men with good risk disease, either three cycles of BEP or four cycles of EP is recommended, and the latter is preferred in men at risk for pulmonary toxicity. In patients with intermediate-risk disease, four cycles of BEP is recommended; however, four cycles of cisplatin, vinblastine, and ifosfamide is an alternative regimen that can be used in patients at risk for pulmonary toxicity.⁹ Single agent carboplatin (AUC of 10 given every 21 days) is a less toxic option that has shown promising results in a multicenter study of 216 patients (15% with age >60) achieving an impressive 3-year progression-free survival of 96.5% and 5-year disease-specific survival of 98.5%.¹⁰ Treatment response can be assessed by monitoring tumor markers on day 1 of each chemotherapy cycle. Clinical outcomes of metastatic seminoma have improved substantially in recent times with 5-year overall survival of up to 95% in good-risk disease and 88% in intermediate-risk disease.¹¹

In conclusion, this case highlights a rare presentation of metastatic seminoma in older individuals. Although rare, lymphadenopathy can be the sole initial presentation of testicular GCT and clinicians should consider this in the differential diagnosis of elderly men presenting with neck and axillary lymphadenopathy.

Disclosure statement/Funding

The authors report no funding or conflicts of interest. Informed consent was obtained from the patient for publication of this case.