Clinical Topics & News

Complex Malignancies: A Diagnostic and Therapeutic Trilemma

A patient presented with esophageal adenocarcinoma, pulmonary small-cell carcinoma, and high-grade carcinoma, which is a rare occurrence that required a staged multidisciplinary approach to treatment.

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Mr. F. is a 67-year-old man with a medical history significant for hypertension, hyperlipidemia, gastroesophageal reflux disease, abdominal aortic aneurysm repair, and lung nodules (8-mm nodules in his right lower lobe and left upper lobe) since 2009 for which he had been followed in the pulmonary clinic. His last radiologic imaging had been performed in November 2010. The patient had failed to show for a serial scan and follow-up pulmonary appointments. He had seen his primary care practitioner annually. He reporteded a 60 pack-year smoking history and drank up to 10 to 15 beers a day, 3 days a week. He also reported exposure to asbestos while in the U.S. Navy as well as having worked in a sheet metal yard. He reported no family history of lung cancer.

In January 2014, Mr. F. presented to his primary care doctor with a nonpainful neck lump noted by the patient for a few months. On physical examination, the patient appeared healthy and without change in weight, loss of appetite, dysphagia, hemoptysis, or any other remarkable symptoms except for the pain in the left-sided neck mass. On oral examination, the patient did not have any oral lesions but was noted to have poor dentition. He had decreased breath sounds on the right side but no adventitious breath sounds. His cardiac status was within normal limits with a regular heart rate, warm skin, and well-perfused extremities. His abdomen was soft and nontender with good bowel sounds.

A neck computed tomography (CT) done on January 17, 2014, showed 2 left neck masses in the tail of the parotid gland or in level 2 adjacent to the parotid gland. The ear, nose, and throat (ENT) clinic noted that he had a 3-cm level 2 mass, which was mobile and nontender. A fine needle aspiration biopsy showed poorly differentiated rare malignant cells, but the small size of the biopsy precluded identification of the cells. For that reason, the patient was scheduled for an operative laryngoscopy.

A combined positron emission tomography and CT (PET/CT) scan on February 5, 2014, showed multiple areas of hypermetabolic activity. A highly metabolic 2.6 x 1.9-cm mass was noted in the left neck inseparable from the inferior border of the left parotid gland; whether this represented a parotid neoplasm or neoplastic lymph node could not be determined. Positive level 5 neck lymph nodes were suggestive of metastatic disease. There were also 2 foci of mild nonspecific metabolic activity in the right parotid gland. A spiculated mass in the right lower lung, measuring 2.3 x 3.5 cm, demonstrated intense fludeoxyglucose F 18 (FDG) uptake with maximum standardized uptake value (SUV) of 12.7, which was consistent with neoplasm. Thickening of the middistal esophageal wall with intense FDG uptake (SUV of 7.9) was suggestive of esophageal carcinoma.

The patient underwent an endoscopic ultrasound (EUS) esophageal biopsy, which demonstrated poorly differentiated adenocarcinoma (Figure 1). The tumor seemed to have originated at this site, as the biopsy fragments also contained foci of Barrett’s metaplasia and in situ carcinoma. He was presented in the hospital tumor board about whether he should undergo a high-risk lung biopsy due to the location of the mass or have his left neck mass rebiopsied, assuming that he had metastatic esophageal cancer in both the lung and neck. The safer procedure of redoing the neck biopsy in the Ear, Nose, and Throat clinic was pursued, and the patient underwent a biopsy and surgical excision of his left neck mass with positive pathology of high-grade sarcoma (Figure 2).

The tumor consisted of spindle and epithelioid cell proliferation within a lymph node. The neoplastic cells exhibited prominent nuclear atypia, multinucleation, frequent mitoses, and focal necrosis. By immunohistochemistry, the tumor cells were diffusely positive for vimentin, CD68, and CD34 and were negative for pankeratin, CK7, CAM 5.2, CD30, CD15, tyrosine, melan-a, HMB-45, epithelial membrane antigen, keratin 903, desmin protein, CD56, CD99, actin protein, and CD1a. A differential diagnosis included malignant fibrous histiocytoma and histiocytic sarcoma.

Knowing the patient had 2 tumors, a percutaneous lung biopsy was scheduled. It was assumed that the lung mass would be metastatic from esophagus vs sarcoma, but the biopsy showed small cell cancer (Figure 3). The tumor was composed of small cells with finely granular chromatin and a sparse amount of cytoplasm. By immunohistochemistry, the tumor cells were positive for TTF-1, CK7, CAM 5.2, CD56, and synaptophysin and were negative for CK5, CK6, and p63. The patient was represented at the tumor board with diagnostic recommendations to undergo a magnetic resonance imaging of the brain (negative for metastasis) and a PET/CT scan (stable disease).

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