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Differential Diagnosis Of Cervical Cancer

Abstract

In this case report, we discuss the potential diagnostic difficulty of identifying the cause or origin of a cervical swelling, a clinical situation often encountered in otolaryngology patients. A 30-year-old man came to us with a painless left cervical lump that he had noticed 8 weeks earlier. A series of examinations--including various biopsies, computed tomography, and extensive staging procedures--could not establish the diagnosis. We eventually identified the mass as an extragonadal germ-cell tumor. The diagnosis was established only after additional serologic testing and detection of tumor markers specific for extragonadal germ-cell tumor.

Introduction

The diagnosis and treatment of a cervical lump is a routine clinical undertaking for the ENT surgeon. The common differential diagnoses include metastases of malignancies primary to the head and neck, malignant lymphoma, and cancer of unknown primary site (CUP). Less common possibilities are manifestations of cancers primary to the stomach, breast, or lung. In this article, we describe the case of a patient with a cervical lump that was diagnosed as an extragonadal germ-cell tumor only after extensive investigation.

Case report

A 30-year-old man came to us with an 8-week history of a painless lump on the left side of his neck. He had no history of night sweats or fever. Our examination identified a palpable left supraclavicular mass approximately 5 cm in diameter. There were no signs of infection. Findings on the remainder of the physical examination, including the patient's ENT status, were normal.

Ultrasonography and computed tomography (CT) of the neck confirmed the presence of an inhomogeneous tumor that measured 37 x 58 x 69 mm (figure 1). Panendoscopic findings in the upper respiratory tract and esophagus were normal. A representative biopsy was taken from the mass, which was initially thought to be a malignant lymphoma. Histologic examination revealed the presence of a solid carcinoma. Immunohistochemical staining raised the possibility that the mass was a sinonasal carcinoma.

Further examination--including multiple nasopharyngeal biopsies and CT of the paranasal sinuses--failed to identify a carcinoma in this region. Likewise, thoracic and abdominal CT, gastroscopy, and positron-emission tomography (PET) all failed to provide information about the primary tumor (figure 2). The results of the urologic examination were normal. Additional serologic testing revealed that the patient's alpha-fetoprotein (AFP), human placental alkaline phosphatase, prostate-specific antigen, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), and thyroglobulin levels were within normal limits. However, three other levels were slightly elevated: aspartate aminotransferase: 19 U/L (normal: 3 to 18); alanine aminotransferase: 25 U/L (normal: 3 to 22); and lactate dehydrogenase: 264 U/L (normal: 40 to 240). Moreover, other levels were significantly elevated: human chorionic gonadotropin beta (hCG[beta]): 5,344 U/L (normal: <3); testosterone: 11.8 [mu]g/L (normal: 2.8 to 8.0); and free testo sterone: 44.2 ng/L (normal: 18 to 41); these values suggested a diagnosis of a malignant extragonadal germ-cell tumor.

Examination of the histologic specimen and immuno-histochemical staining for hCG[beta] confirmed that the mass was a nonseminomatous carcinoma. Because a complete restaging did not uncover a different primary tumor or a further metastasis, the diagnosis of nonseminomatous carcinoma primary to the supraclavicular lymph node was established.

The patient was started on cisplatin, etoposide, bleomyc in, and paclitaxel. Completion of four courses of chemotherapy led to a significant regression of the tumor (as seen on CT and PET imaging) and a normal hCG[beta] level. The residual mass was resected; histologic examination identified necrotic tissue, but no viable tumor cells.

Discussion

In a patient with a cervical lump, diagnostic procedures such as panendoscopy, biopsy, and staging will often, but riot always, identify the site of the primary tumor. When the primary site is not identified, the surgeon must undertake further staging. A metastasis that appears as a solid carcinoma on histologic analysis in a patient in whom the origin of the primary tumor is unidentified is usually classified as a CUP.

The routine treatment of CUP syndrome is surgical resection and radiation. But as demonstrated in this case, serologic testing of tumor markers followed by immunohistologic re-examination might in fact lead to a diagnosis that requires an entirely different therapeutic strategy. Extragonadal germ-cell tumors are very rare, accounting for as few as 2 to 5% of all germ-cell neoplasms) When they do occur, they usually do so in young men. The usual sites are the retroperitoneum and the mediastinum; occasionally they occur at more distant sites, such as the pineal gland, bladder, and stomach.

Primary extragonadal disease can occur in the absence of an occult neoplasm of the testes. (2) Like gonadal neoplasms, extragonadal germ-cell tumors are classified as either seminomatous or nonseminomatous. The latter is usually characterized by elevated levels of serum tumor markers, the most important being the AFP and hCG[beta] levels. In our patient, the high hCG[beta] level was diagnostic; on the other hand, his AFP level, which is elevated in approximately 80% of patients with an extragonadal germ-cell tumor, was within normal limits. When both AFP and hCG[beta] levels are normal in a patient with an extragonadal germ-cell tumor, measurement of CEA and CA 19-9 levels prior to the induction of chemotherapy has been shown to be useful?

There is no gold-standard treatment for extragonadal germ-cell carcinoma. (4) Intensive cisplatin-based chemotherapy followed by surgical removal of residual disease has been reported to result in an overall survival rate of 63% at 6.8 years? Elevated levels of the tumor markers AFP, hCGB, CEA, and CA 19-9 are apparently a negative indicator for survival. (5) Even so, the utility of various outcome predictors remains controversial.

References

(1.) Collins DH, Pugh RCB. Classification and frequency of testicular tumors. Br J Urol 1964;36:1-11.

(2.) Goss PE, Schwertfeger L, Btackstein ME, et at. Extragonadal germ cell tumors. A 14-year Toronto experience. Cancer 1994;73:1971-9.

(3.) Kitsukawa SI, Kin T, Tsukamoto T, et al. Extragonadal germ cell tomor of mediastinum with high serum level of carcinoesnbryonic antigen and carbohydrate antigen 19-9. J Urol 2000;163:912-3.

(4.) Hainsworth JD, Greco FA. Extragonadal germ cell tumors and unrecognized germ cell tumors. Semin Oncol 1992;19:119-27.

(5.) Jakob R, Ramadas K, Jyothirmayi R, et al. Extragonadal germcell tumors: A ten-year experience. Am J Clin Oncol 1998;21:198-202.

From the Department of Otorhinolaryngology--Head and Neck Surgery (Dr. Eickhoff and Dr. Jaehne) and the Department of Medical Oncology (Dr. Langer), University Hospital Hamburg--Eppendorf, University of Hamburg, Germany.

Reprint requests: Britta Eickhoff, MD, Department of Otorhinolaryngology--Head and Neck Surgery, University Hospital Hamburg--Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. Phone: +49-40-42803-2380; fax: +49-40-42803-4416; e-mail: brit_eickhoff@yahoo.com

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