A 46-year-old woman with a distant history of malignant melanoma and no known history of asbestos exposure presented with a unilateral pleural effusion. A biopsy was performed and the resultant specimen is seen at low-power below.
There are two distinct populations of epithelioid cells. The cells on the left are smaller with smaller, more dense nuclei. Those on the right are clearly larger with larger "powdery" nuclei and small nucleoli. The latter population was the dominant one in this biopsy and these cells can be seen to better advantage in the image below.
What is your diagnosis?
Immunohistochemical stains were performed. The results of a cytokeratin cocktail are shown below.
Although somewhat difficult to appreciate at this magnification, the smaller epithelioid cells and some spindled sub-pleural fibroblasts reacted strongly for cytokeratins. The larger epithelioid cells were virtually all cytokeratin negative. The cytokeratin positive cells also reacted for a variety of mesothelial markers and these cells were interpreted as a component of reactive mesothelial hyperplasia. The larger epithelioid cells were negative for melanoma markers but reacted strongly for endothelial markers including CD34 (not shown), and the more specific marker CD31, shown below.
Although this tumor lacks virtually any obvious evidence of vasoformation, I believe that it represents and epithelioid vascular neoplasm. Because of it cytologic uniformity, low mitotic rate, and involvement of the pleura, it was classified as most likely representing an epithelioid hemangioendothelioma, rather than an overt angiosarcoma.
Like malignant melanomas, epithelioid hemangioendotheliomas are great pathologic mimickers at many sites throughout the body. In the lungs they were initially considered by Dail and Liebow to be intravascular epithelial neoplasms (IVBAT), in the liver they have been confused with cholangiocarcinomas, in the pleura as in this case they can quite easily be confused with malignant mesotheliomas.
Epitheloid hemangioendotheliomas occupy the middle position in a histologic spectrum of epithelioid vascular neoplasms. At the benign end of the spectrum are epithelioid hemangiomas (also known as histiocytoid hemangiomas, pseudopyogenic granulomas, and angiolymphoid hyperplasia with eosinophilia, as well as other terms). At the more malignant end are epithelioid angiosarcomas. All three of these tumors can be very diagnostically difficult. Like other epithelioid stromal tumors they may occasionally express cytokeratins which can add to the diagnostic confusion. The pleural lesions are especially treacherous and this diagnosis should always be considered.
The clinical course for these tumors is variable and dependent on the anatomic location. Unfortunately, many of those with pleural lesions pursue a course similar to that of mesothelioma.