Clear cell tumors of unknown nature and origin: a systematic approach to diagnosis

Not infrequently, surgical pathologists encounter malignant neoplasms composed of clear cells, the sources and natures of which are indeterminate on the basis of conventional morphological study. In this context, it is frustrating that tumors of completely dissimilar lineage can show strikingly similar microscopic appearances; moreover, anatomic location provides few if any definitive clues to the likely final diagnosis in many cases of clear cell neoplasia. Because of these factors, it is necessary to systematically pursue the same approach to the pathological assessment of clear cell tumors, routinely considering not only clinical and radiologic details but also the possible application of immunohistology, electron microscopy, and cytogenetics. This review provides algorithmic schemes by which such techniques can be applied, as well as their potential drawbacks and limitations.