Poorly Differentiated Carcinoma of the Mediastinum
John D. Hainsworth
F. Anthony Greco
The diagnosis of poorly differentiated carcinoma poses difficult problems for the clinician. Occasionally a patient with a mediastinal tumor has such a diagnosis rendered at the time of biopsy. Five of 38 patients (13%) with primary mediastinal tumors described by Adkins and associates1 had undifferentiated carcinoma. This diagnosis indicates a tumor with no histopathologic features allowing precise identification of the site of origin. Patients with poorly differentiated carcinoma in the mediastinum are sometimes treated with palliative radiation therapy or symptomatic treatment alone, because they are assumed to have metastatic lung cancer with an undetected primary lesion that is unresectable and incurable. However, this approach is not recommended, because optimal clinical and pathologic evaluation can establish a more 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.
The recommended pathologic evaluation, staging, and treatment of the patient with poorly differentiated carcinoma in the mediastinum is considered below. This is an area in which treatment recommendations are still developing, and many unanswered questions remain.
Pathologic Evaluation
Many types of cancer can involve the mediastinum, and some of these frequently have a poorly differentiated histology (Table 195-1). Because highly effective, specific treatments exist for some of these tumor types, it is essential to use all means possible to make a specific diagnosis before embarking on therapy. Optimal evaluation of these patients requires close communication between the clinician and pathologist. In some cases, the nonspecific diagnosis of poorly differentiated carcinoma or poorly differentiated neoplasm is given simply because the pathologist has a small, inadequate biopsy specimen to examine. Frequently in such a situation, a larger, adequately handled biopsy specimen is all that is necessary to make a more specific diagnosis. Fine-needle aspiration (FNA) biopsies are often inadequate to diagnose mediastinal tumors because they do not provide an adequate amount of tissue for histologic examination and special studies.
Immunoperoxidase Staining
When light microscopic examination of an adequate biopsy specimen fails to provide a specific diagnosis, specialized pathologic studies should be performed. Immunoperoxidase staining techniques are widely available and have become increasingly useful in the evaluation of poorly differentiated tumors. In evaluating such tumors in the mediastinum, immunoperoxidase staining can suggest the presence of (a) unsuspected lymphoma (positive common leukocyte antigen, negative keratin stains), (b) malignant germ cell tumor (positive human chorionic gonadotropin, positive alpha-fetoprotein stains), (c) poorly differentiated neuroendocrine carcinoma (positive neuron-specific enolase, chromogranin, synaptophysin stains), (d) poorly differentiated sarcoma (positive vimentin, positive desmin stains), and (e) melanoma (positive S-100 protein, positive HMB-45, negative keratin stains). In a large group of patients with poorly differentiated carcinoma (mediastinal and other metastatic sites), Hainsworth et al.12 performed immunoperoxidase staining that suggested specific diagnoses in 20% of their patients. In the remaining 80%, the diagnosis of poorly differentiated carcinoma was confirmed or the test results were in- conclusive.
Electron Microscopy
Electron microscopy is also a valuable adjunct to light microscopy. The examination of ultrastructural features is particularly useful when the initial diagnosis is poorly differentiated neoplasm, a nonspecific diagnosis given when the tumor may be either a poorly differentiated carcinoma, lymphoma, sarcoma, or melanoma. Electron microscopy is reliable in distinguishing lymphoma from carcinoma and can often establish a definitive diagnosis of melanoma or poorly differentiated sarcoma. Table 195-2 shows the results of electron microscopy in a large series of patients with poorly differentiated carcinoma of unknown primary site reported by Hainsworth and associates.11 Because electron microscopy is less readily available than immunoperoxidase staining and often requires another biopsy for special tissue
preparation, this technique should be reserved for patients in whom the diagnosis is unclear after immunoperoxidase staining has been performed.
preparation, this technique should be reserved for patients in whom the diagnosis is unclear after immunoperoxidase staining has been performed.
Table 195-1 Mediastinal Tumors with Poorly Differentiated Histologic Features | |
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Chromosomal Abnormalities
Several tumor types are associated with specific chromosomal abnormalities, allowing definitive diagnosis (Table 195-3). All of these tumor types have poorly differentiated histology and can occur in the mediastinum. Motzer and associates14 performed molecular genetic analysis on a group of 40 young men with poorly differentiated tumors involving the mediastinum. In none of these patients had other pathologic methods yielded a specific diagnosis. On the basis of specific chromosomal abnormalities, precise diagnoses were made in 17 patients (42%) as follows: germ cell tumor, 12 patients; lymphoma, 1 patient; peripheral neuroepithelioma, 1 patient; desmoplastic small cell tumor, 1 patient; and melanoma, 2 patients. The patients with germ cell tumors identified in this manner had excellent responses to appropriate chemotherapy.
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