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).
A lengthy discussion ensued regarding treatment for the 3 cancers. The AJCC Cancer Staging Manual, 7th edition, was used as the framework for all staging. 1 The patient had a stage IIA (T1bN0MX), grade 3 sarcoma, which could be removed by neck dissection. He had a stage IIIB esophageal carcinoma (T3N2MX), which would require concurrent chemoradiation. His limited stage small cell lung cancer might have been amenable to a lobectomy if a mediastinoscopy was negative. The standard of care for limited stage small cell lung cancer is that if the cancer is precisely staged and the patient is a good surgical candidate, then surgery can be considered. The rationale for considering resection in this case was that if his other cancers could be cured, then surgery would be an excellent option. 2 These options were presented to the patient, who opted for chemotherapy. The oncologist treating the patient elected to target the small cell cancer initially, because it was likely the fastest growing cancer. The patient started treatment with etoposide/carboplatin shortly thereafter. Mr. F. was also referred to palliative care.
Discussion
When a patient presents with several tumor masses detected either clinically or radiologically, it is reasonable to assume, at least initially, that all the lesions can be attributed to the same disease (ie, a primary neoplasm and distant metastases). Based on this assumption, it is rational to establish a tissue diagnosis by sampling the most accessible lesion. In the correct clinical context, this may be sufficient to initiate an appropriate therapy. However, health care providers should be aware that unrelated neoplasms can develop simultaneously, and about 8% of patients have > 1 malignancy at presentation. 3
This patient presented with 3 different malignant neoplasms: esophageal adenocarcinoma, pulmonary small-cell carcinoma, and high-grade sarcoma. These types of tumors have completely different histogenesis. Esophageal adenocarcinoma develops from glandular cells of Barrett’s esophagus, small-cell carcinoma develops from neuroendocrine Kulchitsky cells, and sarcoma arises from mesenchymal cells. This constellation of neoplasms does not represent any known multicancer syndrome, such as Li-Fraumeni syndrome or Lynch syndrome. Whether these concomitant tumors represent coincidental neoplasms or have common underlying molecular alterations remains unknown.