Rosai–Dorfman disease is an uncommon benign proliferation of hematopoietic and fibrous tissue. Its initial manifestations most often include a roughly symmetric, painless, bilateral cervical adenopathy, fever, leukocytosis, and hypergammaglobulinemia, although extranodal disease may develop.1Rosai J. Dorfman R.F. Sinus histiocytosis with massive lymphadenopathy. A newly recognized benign clinicopathological entity.Arch Pathol. 1969; 87: 63-70PubMed Google Scholar, 2Carbone A. Passannante A. Gloghini A. Devaney K.O. Rinaldo A. Ferlito A. Review of sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease) of head and neck.Ann Otol Rhinol Laryngol. 1999; 108: 1095-1104Crossref PubMed Scopus (72) Google Scholar, 3Huang H.Y. Yang C.L. Chen W.J. Rosai–Dorfman disease with primary cutaneous manifestations—a case report.Ann Acad Med Singapore. 1998; 27: 589-593PubMed Google Scholar Rosai–Dorfman disease in HIV-infected patients has been previously reported in just three cases.4Delacretaz F. Meuge-Moraw C. Anwar D. Borisch B. Chave J.P. Sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease) in an HIV-positive patient.Virchows Arch A Pathol Anat Histopathol. 1991; 419: 251-254Crossref PubMed Scopus (27) Google Scholar, 5Perry B.P. Gregg C.M. Myers S. Lilly S. Mann K.P. Prieto V. Rosai–Dorfman disease (extranodal sinus histiocytosis) in a patient with HIV.Ear Nose Throat J. 1998; 77: 855-858PubMed Google Scholar, 6Pitamber H.V. Grayson W. Five cases of cutaneous Rosai–Dorfman disease.Clin Exp Dermatol. 2003; 28: 17-21Crossref PubMed Scopus (47) Google Scholar We report herein the case of a young Venezuelan woman, recently diagnosed with HIV, who had developed Rosai–Dorfman disease with maxillary and malar involvement. A 56-year-old woman was evaluated at the ear, nose and throat (ENT) service with a three-year history of hard palate swelling with compromise of the right genian region. Physical examination revealed a volume increase in the right side of the face. A considerable hard palate swelling was observed. Laboratory studies on presentation revealed HIV infection (HIV-1 and -2 ELISA tests were positive, and infection was confirmed with the Western-blot test). Multiple lesion biopsies were undertaken. Other laboratory studies were performed; no alterations in complete blood count or chemistry were evidenced. Serology for Coccidioides immitis, hepatitis B virus, Epstein–Barr virus (EBV), and cytomegalovirus were positive. The CD4 cell count was 350 cells/μl and the viral load was 10 000 copies of RNA/μl. CT-scans showed a significant compromise of the soft tissues in the right maxillary region (including a significant compromise of bone structures). A subtotal therapeutic maxillectomy and biopsy were carried out. The maxillary antrum lateral wall was found to have fibrohistiocytic lesions and inflammatory changes. In the resected tissues, a significant number of large, pale histiocytic cells that contained apparently engulfed lymphocytes or plasmocytes within their cellular borders was observed (emperipolesis; Figure 1). These distinctive large, pale cells – Rosai–Dorfman cells – were S-100 protein-positive by immunostaining and so differ from ordinary histiocytes (Figure 1). CD68 immunohistochemistry was also positive. Most cases of Rosai–Dorfman disease occur during the first or second decade of life, but any age group can be affected. The youngest patient on first series had congenital sinus histiocytosis with massive lymphadenopathy (SHML), and the oldest developed symptoms at age 74.7Foucar E. Rosai J. Dorfman R. Sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease): review of the entity.Semin Diagn Pathol. 1990; 27: 19-75Google Scholar, 8Marsh Jr., W.L. McCarrick J.P. Harlan D.M. Sinus histiocytosis with massive lymphadenopathy. Occurrence in identical twins with retroperitoneal disease.Arch Pathol Lab Med. 1988; 112: 298-301PubMed Google Scholar However, Rosai–Dorfman disease in HIV-infected patients has been previously reported in just three cases,4Delacretaz F. Meuge-Moraw C. Anwar D. Borisch B. Chave J.P. Sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease) in an HIV-positive patient.Virchows Arch A Pathol Anat Histopathol. 1991; 419: 251-254Crossref PubMed Scopus (27) Google Scholar, 5Perry B.P. Gregg C.M. Myers S. Lilly S. Mann K.P. Prieto V. Rosai–Dorfman disease (extranodal sinus histiocytosis) in a patient with HIV.Ear Nose Throat J. 1998; 77: 855-858PubMed Google Scholar, 6Pitamber H.V. Grayson W. Five cases of cutaneous Rosai–Dorfman disease.Clin Exp Dermatol. 2003; 28: 17-21Crossref PubMed Scopus (47) Google Scholar the first described in 1991. To our knowledge, this case is the fourth to be reported. Microscopically, there was a pronounced dilatation of the lymph nodes (see Figure 1). The sinuses were occupied by numerous histiocytic cells with a large vesicular nucleus and abundant clear cytoplasm, which may contain lipids and also lymphocytes and plasma cells. The histological key feature of Rosai–Dorfman disease is the presence of various numbers of large, pale histiocytic cells that contain within their cellular borders apparently engulfed lymphocytes or plasmocytes (emperipolesis); these distinctive large, pale cells – Rosai–Dorfman cells – are S-100 protein-positive by immunostaining and so differ from ordinary histiocytes. Despite its sometimes impressive clinical presentation, Rosai–Dorfman disease is a benign and self-limiting disease, whose treatment is aimed largely at controlling local manifestations (most often by surgical therapy). The microscopic differential diagnosis, particularly in extranodal disease, is at times challenging and can include Langerhans cell histiocytosis, Hodgkin's disease, non-Hodgkin's lymphoma, metastatic carcinoma, and metastatic malignant melanoma. Rosai–Dorfman disease with maxillary compromise has been previously reported in four cases (non HIV-infected patients),9Shemen L. D'Anton M. Klijian A. Toth I. Galantich P. Rosai–Dorfman disease involving the premaxilla.Ann Otol Rhinol Laryngol. 1991; 100: 845-851PubMed Google Scholar, 10Shemen L. Rosai–Dorfman disease involving the premaxilla.Ann Otol Rhinol Laryngol. 1992; 101: 798PubMed Google Scholar, 11Kademani D. Patel S.G. Prasad M.L. Huvos A.G. Shah J.P. Intraoral presentation of Rosai–Dorfman disease: a case report and review of the literature.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002; 93: 699-704Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar, 12Yoon A.J. Parisien M. Feldman F. Young-In Lee F. Extranodal Rosai–Dorfman disease of bone, subcutaneous tissue and paranasal sinus mucosa with a review of its pathogenesis.Skeletal Radiol. 2005; 34: 653-657Crossref PubMed Scopus (24) Google Scholar and no cases have been reported with malar compromise. In Venezuela, the first case of primary osseous Rosai–Dorfman disease was observed by us in 2002,13Mota Gamboa J.D. Caleiras E. Rosas-Uribe A. Extranodal Rosai–Dorfman disease. Clinical and pathological characteristics in a patient with a pseudotumor of bone.Pathol Res Pract. 2004; 200: 423-426Crossref PubMed Scopus (9) Google Scholar and to the best of our knowledge this pathology has not been reported again until our current case. Although numerous case reports concerning Rosai–Dorfman disease have been reported in the literature, few have documented an association with HIV/AIDS. Unfortunately, a consistent etiology for Rosai–Dorfman disease has not yet been found. Immunological relations between Rosai–Dorfman disease and viral infections (human herpesvirus 6 (HHV6) and EBV) have been suggested to explain its etiology;14Perez A. Rodriguez M. Febrer I. Aliaga A. Sinus histiocytosis confined to the skin. Case report and review of the literature.Am J Dermatopathol. 1995; 17: 384-388PubMed Google Scholar HIV could also be one such viral infection.4Delacretaz F. Meuge-Moraw C. Anwar D. Borisch B. Chave J.P. Sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease) in an HIV-positive patient.Virchows Arch A Pathol Anat Histopathol. 1991; 419: 251-254Crossref PubMed Scopus (27) Google Scholar Immunopathology of Rosai–Dorfman disease could be linked to viral infections that can create an immunologic environment that will result in the activation of the histiocyte–macrophage system. In this disease the immunohistochemical profile is similar to that of activated macrophages derived from circulating monocytes stimulated by T-lymphocytes following an immunologic challenge.5Perry B.P. Gregg C.M. Myers S. Lilly S. Mann K.P. Prieto V. Rosai–Dorfman disease (extranodal sinus histiocytosis) in a patient with HIV.Ear Nose Throat J. 1998; 77: 855-858PubMed Google Scholar, 14Perez A. Rodriguez M. Febrer I. Aliaga A. Sinus histiocytosis confined to the skin. Case report and review of the literature.Am J Dermatopathol. 1995; 17: 384-388PubMed Google Scholar, 15Eisen R.N. Buckley P.J. Rosai J. Immunophenotypic characterization of sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease).Semin Diagn Pathol. 1990; 7: 74-82PubMed Google Scholar Other studies have indicated that this immunological disturbance is associated with a chronic, but non-specific, infectious state,16Ngendahayo P. Roels H. Quatacker J. Boddaert J. Ntabomuvra V. Mbonyingabo P. Sinus histiocytosis with massive lymphadenopathy in Rwanda: report of eight cases with immunohistochemical and ultrastructural studies.Histopathology. 1983; 7: 49-63Crossref PubMed Scopus (16) Google Scholar the result of which could reflect an alteration in the process by which histiocytes contact T-lymphocytes for antigen presentation.17Bonetti F. Chilosi M. Menestrina F. Scarpa A. Pelicci P.G. Amorosi E. et al.Immunohistological analysis of Rosai–Dorfman histiocytosis. A disease of S-100 + CD1-histiocytes.Virchows Arch A Pathol Anat Histopathol. 1987; 411: 129-135Crossref PubMed Scopus (72) Google Scholar, 18Mir R. Aftalion B. Kahn L.B. Sinus histiocytosis with massive lymphadenopathy and unusual extranodal manifestations.Arch Pathol Lab Med. 1985; 109: 867-870PubMed Google Scholar The current interpretation of the immunostaining profile of Rosai–Dorfman disease is that SHML cells are functionally activated macrophages, perhaps recently derived from monocytes.15Eisen R.N. Buckley P.J. Rosai J. Immunophenotypic characterization of sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease).Semin Diagn Pathol. 1990; 7: 74-82PubMed Google Scholar Related pathologies have already been described in association with HIV, occurring in reactive histiocytosis with hemophagocytosis or in malignant histiocytosis.19Brynes R.K. Gill P.S. Clinical characteristics, immunologic abnormalities, and hematopathology of HIV infection.in: Joshi V.V. Pathology of AIDS and other manifestations of HIV infections. Igaku-Shoin, New York1990: 21-41Google Scholar, 20Salyer J. Craven C.M. Malignant histiocytosis in a patient with acquired immunodeficiency syndrome-related complex.Arch Pathol Lab Med. 1990; 114: 376-378PubMed Google Scholar In the past, Rosai–Dorfman disease associated with HIV infection has been described as coincidental because it has rarely been reported.4Delacretaz F. Meuge-Moraw C. Anwar D. Borisch B. Chave J.P. Sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease) in an HIV-positive patient.Virchows Arch A Pathol Anat Histopathol. 1991; 419: 251-254Crossref PubMed Scopus (27) Google Scholar But, whether or not related, some evidence supports the hypothesis of a relationship between the disease and HIV infection, as has been suggested in cases involving HHV6 or EBV. Immune-mediated diseases, associated with or preceding Rosai–Dorfman, are not rare.4Delacretaz F. Meuge-Moraw C. Anwar D. Borisch B. Chave J.P. Sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease) in an HIV-positive patient.Virchows Arch A Pathol Anat Histopathol. 1991; 419: 251-254Crossref PubMed Scopus (27) Google Scholar, 15Eisen R.N. Buckley P.J. Rosai J. Immunophenotypic characterization of sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease).Semin Diagn Pathol. 1990; 7: 74-82PubMed Google Scholar In some studies, about 12% of the patients with this pathology had clinical evidence of one or more immune disorders.12Yoon A.J. Parisien M. Feldman F. Young-In Lee F. Extranodal Rosai–Dorfman disease of bone, subcutaneous tissue and paranasal sinus mucosa with a review of its pathogenesis.Skeletal Radiol. 2005; 34: 653-657Crossref PubMed Scopus (24) Google Scholar As was suggested in the first report of an association, we believe that Rosai–Dorfman disease does represent an HIV-associated disease and should be further and more thoroughly studied; it should also be considered in the differential diagnosis of tumors complicating HIV infection. This work was presented in part as a poster at the 12th International Congress on Infectious Diseases, Lisbon, Portugal, June 15–18, 2006 (Abstract 5.002). Conflict of interest: No conflict of interest to declare.