Following microscopic diagnosis of malignancy, several questions immediately arise: Is it carcinoma, sarcoma, or lymphoma? If carcinoma, is it squamous or glandular (adenocarcinoma)? If sarcoma, what is the tissue of origin? Is it primary or metastatic? If metastatic, what is the primary site (site of origin)?

In the majority of cases, the pathologist can differentiate carcinoma, sarcoma, and lymphoma and determine if a carcinoma is squamous or glandular. However, some tumors are poorly differentiated or the biopsy may be small or obtained in a tumor area that does not have unequivocal distinguishing features. In these cases, special tissue stains using antibodies against various cell antigens can often be of assistance. The majority of these antibodies are against some component of tissue intermediate filaments. Intermediate filaments are one of four major filamentous proteins that constitute the skeleton of cells. Intermediate filaments comprise most of the intracellular matrix and are intermediate in diameter compared to the other three filamentous structural proteins. Intermediate filaments contain five protein components: cytokeratin, vimentin, desmin, glial fibrillary acidic protein, and neurofilaments. A different one of these five predominates in each of the five histologic types of mammalian tissues (epithelial, mesenchymal, muscle, neuronal, and glial). This relationship is shown in Table 33-1. It was not long before investigators found so many tumor categories in each of the five intermediary filament subgroups (Table 33-2) that antibodies specific to individual tumor types and even subgroups were required. Since that time there has been a steady stream of new antibodies from several manufacturers that attempt to fill this need. Usually the new antibody is introduced as specific (or at least, “relatively specific”) for some tumor or tissue. Usually, over time, it is found that a certain number of patient neoplasms in tumor categories not expected to be reactive with the antibody were in fact reactive to greater or lesser degree (Table 33-3). Then the antibody is promoted as part of a “cocktail” or panel of antibodies rather than as a single clear-cut diagnostic reagent. The reader is cautioned that technical details (type of tissue fixation, correct technique, and experience with the procedure), selection of the most sensitive and strongest-reacting antibodies, and experience in interpreting the result all play a major role in final results. Antibodies from different manufacturers frequently do not behave exactly the same for various reasons, in some cases because the antibody recognizes a different antigen (epitope) within a group of antigens or reacts with more than one antigen. This may sometimes become a problem when one defines a tumor on the basis of reactivity with a single antibody, either alone or as part of a panel. In addition, although immunohistologic stains are able to solve (or at least partially solve) many diagnostic problems, there is well-documented variation of results, both positive and negative, between laboratories and different investigators, as well as some individual tumors that do not produce a recognizable antibody pattern or that produce one that does not fit the clinical or microscopic picture. Finally, the multiplicity of antibodies and manufacturer’s trade names for these antibodies is confusing to nonexperts attempting to understand consultation reports.

Original concepts of diagnosis by intermediate filament antibodies

Table 33-1 Original concepts of diagnosis by intermediate filament antibodies

Current diagnosis by intermediate filament antibodie

Table 33-2 Current diagnosis by intermediate filament antibodies

Some antibodies useful in tumor identification

Table 33-3 Some antibodies useful in tumor identification