By Bahram Robert Oliai, M.D.


Determination of the precise etiology of nodal follicular hyperplasia is often a frustrating exer-cise for both pathologists and our clinician col-leagues, as this common pattern of lymph node reaction is associated with myriad conditions, in-cluding Toxoplasmosis, syphilis, HIV, EBV, CMV (and other viral infections), histoplasmosis, cat scratch disease, Castleman’s disease, autoim-mune diseases of various types, and even focal involvement by various lymphomas (especially nodal marginal zone lymphoma, follicular lym-phoma, and Hodgkin’s disease).

Even with our current armamentarium of immu-nohistochemical stains, culture techniques, diag-nostic immunology, and molecular assays, many cases remain unresolved, resulting in an unsatis-fying descriptive pathologic diagnosis followed by a laundry list of differential possibilities and comment recommending clinical correlation.


In this month’s Focus newsletter we review re-cently published data describing the use of an immunohistochemical stain which seems to show great potential in the identification of follicular hyperplasia associated with HIV infection.

In the October 2007 issue of The American Jour-nal of Surigical Pathology, dePaiva et al. of the Universite Paul-Sabatier Department of Anat-omic Pathology and Infectious and Tropical Dis-eases described the use of an anti-p24-gag immu-nostain in a series of 240 patients diagnosed with follicular hyperplasia of unknown cause.  Briefly, p24-gag is one of the proteins encoded by HIV’s gag gene which makes up the viral capsid. It is one of the 3 proteins detected (in addition to gp120/160 complex and gp41) in the common Western Blot test for HIV infection.

Of the 240 cases examined with unexplained fol-licular hyperplasia (several of which were even-tually attributed to either autoimmune disease, toxoplasmosis, EBV, and CMV infection) only four cases/patient samples showed strong stain-ing with an anti-p24 immunoperoxidase stain in a follicular dendritic network distribution.  All four patients were not known to be HIV positive at the time of lymph node biopsy, and were sub-sequently shown to have HIV infection by HIV antibody (ELISA) testing with subsequent West-ern Blot confirmation!

Recently, thanks to the generosity of Dr. Lesa Ford of Anatomic Medical Laboratories in Denton, Texas (who provided us with positive control material), we have been able to success-fully optimize this antibody for paraffin sections and are now offering it for clinical use.

Generalized lymphadenopathy is a frequent find-ing in HIV infected patients, and it may be one of the earliest manifestations of infection (so-called “mononucleosis like syndrome”).  With-out a high index of clinical suspicion, the diag-nosis of HIV may be easily overlooked in such patients.  For this reason, we feel that p24-gag immunostains have great potential in identifying cases of clinically unrecognized HIV infection.  However, given the limited data regarding this im-munostain and the serious implications of an HIV diagnosis, we urge caution in interpreting positive results, reminding readers that this is not an alterna-tive diagnostic modality for HIV infection,  and that a diagnosis of HIV must ALWAYS be confirmed with more traditional diagnostic methods such as serology followed by Western Blot testing.



1. de Paiva GR, Laurent C, Godel A, et al.  Discovery of Human Immunodeficiency Virus Infection by Immunohistochemistry on Lymph Node Biopsies From Patients with Unexplained Follicular Hyper-plasia.  The American Journal of Surgical Pathol-ogy.  2007; 31(10):  1534-1538.



We would like to again thank Dr. Lesa Ford of Anatomic Medical Laboratories in Denton, Texas for her generosity in providing us with positive control tissue.


Date of last revision: December 2007.