| Poorly Differentiated Carcinoma of the Mediastinum
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John D. Hainsworth, MD; F. Anthony Greco, MD
Introduction
Occasionally, the biopsy diagnosis in a patient with a mediastinal tumor is "poorly differentiated carcinoma." This diagnosis poses difficult problems for the clinician, because it indicates a tumor with no histopathologic features specific enough to allow identification of the site of origin. Patients with poorly differentiated carcinoma in the mediastinum are sometimes assumed to have metastatic lung cancer with an undetectable primary lesion and are, therefore, assumed to be unresectable and incurable. In this setting, palliative radiation therapy is often administered. However, this approach is no longer adequate, because further clinical and pathologic evaluation can establish a definitive diagnosis with specific therapeutic implications in some of these patients. In addition, some patients with poorly differentiated carcinoma involving the mediastinum are curable with intensive cisplatin-based chemotherapy.
Pathologic Evaluation
Critical pathologic evaluation of mediastinal tumors is essential, because a variety of neoplasms with specific therapeutic implications can arise in this location (eg, mediastinal germ cell tumor, lymphoma, thymoma). In addition, effective therapy also exists for some neoplasms that commonly metastasize to the mediastinum (eg, small-cell lung cancer). Following light microscopic examination of an adequate biopsy specimen, immunoperoxidase staining and electron microscopy are useful in distinguishing between the various neoplasms occurring in the mediastinum. By using these methods, lymphoma and neuroendocrine tumors (including small-cell lung cancer) can be reliably identified, and appropriate therapeutic approaches can be defined. Molecular genetic analysis should also be performed, if possible, because identification of an i(12p) chromosomal abnormality is diagnostic of a germ cell tumor.
Diagnostic Evaluation and staging Work-Up
All patients should have CT scans of the chest and abdomen, as well as measurement of serum levels of HCG and ?-fetoprotein. Fiberoptic bronchoscopy should be performed if other studies are nondiagnostic. Small-cell lung cancer should be suspected when neuroendocrine features are found in patients with a previous history of cigarette smoking.
| Primary Germ Cell Tumors of the Thorax
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Treatment
The diagnostic evaluation defines specific therapy for some patients in this group. Patients with elevated levels of either HCG or ?-fetoprotein should be treated for a mediastinal nonseminomatous germ cell tumor, even if this diagnosis is not made by histologic examination. Patients who have an endobronchial lesion found at bronchoscopy probably have lung cancer; those with neuroendocrine features should receive therapy for small-cell lung cancer, while those lacking these features should be treated for non-small-cell lung cancer. Patients with poorly differentiated neuroendocrine carcinoma who lack risk factors and clinical features of small-cell lung cancer also have chemotherapy-sensitive tumors, and should be treated with platinum/ etoposide or paclitaxel/platinum/ etoposide regimens.
In a small percentage of patients, no evidence of tumor spread outside the mediastinum is detected. Surgical resection or local radiation therapy should be considered in these patients, usually in conjunction with empiric combination chemotherapy.
When mediastinal tumors are locally unresectable or have metastasized to distant sites, a trial of combination chemotherapy should be given to all patients with adequate performance status. We treated 43 patients with poorly differentiated carcinoma or poorly differentiated adenocarcinoma located predominantly in the mediastinum. These patients represented 19% of our entire group of patients with poorly differentiated carcinoma of unknown primary site. The median age was 38 years; 32 patients had other metastatic sites in addition to the mediastinum. Only 5 of 43 patients (12%) had elevated serum levels of HCG or α-fetoprotein. All patients received cisplatin-based chemotherapy; 13 patients (30%) had complete response, and 7 patients (16%) are long-term disease-free survivors. Review of the light microscopic features in these patients failed to reveal any previously unsuspected germ cell tumors or lymphomas.
In summary, patients with mediastinal tumors initially diagnosed as poorly differentiated carcinoma are a heterogeneous group. Some of these patients actually have well-defined tumor types that can be identified with additional pathologic or clinical evaluation. Patients in whom a specific tumor is identified should be treated according to standard guidelines for that tumor type. A trial of platinum/etoposide-based chemotherapy should be given to patients in whom no well-defined tumor type is recognized. Some of these patients have highly responsive neoplasms, and a minority appear to be cured with this treatment.
References
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