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Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): two case reports
International Journal of Pediatric Otorhinolaryngology 61 (2001) 243– 247 www.elsevier.com/locate/ijporl
Case report
Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): two case reports Asma El Kohen a,*, Xavier Planquart c, Zitouna Al Hamany b, Laurent Bienvenu d, Mohamed Kzadri a, Denis Herman c a
Department of Otorhinolaryngology and Maxillofacial Surgery, A6icenne’s Hospital, Faculty of Medicine and Uni6ersity Hospital of Rabat, Rabat, Morocco b Department of Pediatric’s Pathology, Children’s Hospital, Faculty of Medicine and Uni6ersity Hospital of Rabat, Rabat, Morocco c Department of Otorhinolaryngology Surgery, Robert Ballanger’s Hospital, Aulnay sous Bois, France d Department of Pathology, Robert Ballanger’s Hospital, Aulnay sous Bois, France Received 28 September 2000; received in revised form 26 May 2001; accepted 27 May 2001
Abstract Sinus histiocytosis with massive lymphadenopathy or Destombes-Rosai-Dorfman’s syndrome is a rare benign disease of unknown etiology , usually seen in younger patients. The cases reported concerned a 15-month old Caucasian boy and an 8 year old black boy with unilateral cervical enlargement, occasional fever and without any extranodal involvement. Diagnosis was performed by superficial lymph node biopsy. No immunodeficiency was found. The patients received no therapy and a complete spontaneous resolution was seen after a few months in the two cases. The clinical presentation, histologic characteristics, pathogenesis and treatment of the Destombes-RosaiDorfman’s syndrome are discussed. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Rosai-Dorfman disease; Cervical lymphadenopathy; Sinus histiocytosis; Child
1. First case report
Abbre6iations: SHML, sinus histiocytosis with massive lymphadenopathy; EBV, Epstein Barr virus; ESR, sedimentation rate; MGG, May Grunwald Giemsa. * Corresponding author. Villa No. 136 OLM SOUISSI II, Rabat, Morocco. Tel.: + 212-377-52295. E-mail address: [email protected] (A. El Kohen).
A 15 months old Caucasian boy presented with 3 months history of enlarging and painless unilateral cervical and submandibular lymphadenopathy. He was asymptomatic except for occasional fever (temperature to 38.5 °C). Physical examination revealed large, unilateral, non-tender lymph node conglomerates in the anterior cervical chain
0165-5876/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 1 6 5 - 5 8 7 6 ( 0 1 ) 0 0 5 2 3 - 7
244
A. El Kohen et al. / Int. J. Pediatr. Otorhinolaryngol. 61 (2001) 243–247
and submandibular area. No lymphadenopathy in other regions or extranodal involvement were detected. Routine laboratory investigations, including a complete blood count, sedimentation rate (ESR) and serum protein electrophoresis, were made. Values obtained were WBC: 7200/mm3, hemoglobin 9.1 g/dl, MCMH: 0.31 g/l, ESR: 43 mm/h, a-1-globulin: 0.1 g/dl, a-2-globulin: 1.2 g/dl, b-globulin: 1.2 g/dl, g-globulin: 2.9 g/dl. The serological viral investigations were negative for toxoplasmosis, infectious mononucleosis and catscratch. Since there had been no improvement in the lymphadenopathy after several courses of oral antibiotics, a lymph node biopsy was performed. It showed histologically expanded sinuses packed with large histiocytes. Their cytoplasm often engulfs lymphocytes and less frequently erythrocytes and plasma cells (Figs. 1– 3 and 5) The patient received no therapy. We noted spontaneous regression of the lymphadenopathy with no evidence of recurrence during 22 months of follow up.
Fig. 2. Lymph node biopsy: expanded sinuses packed with large histiocytes which had ample pale cytoplasm and single round vesicular nuclei. Their cytoplasm engulfs lymphocytes, erythrocytes and plasma cells. Hematoxylin and eosin stain × 250.
The second case concerned an 8 years old black boy with large unilateral lymph node involvement in the anterior cervical chain and recurrent fever.
There was no history of weight loss, dysphagia or arthralgias. Physical examination revealed no lymphadenopathy by palpation in other regions and the remainder of the examination was normal. The chest X-ray was normal. A routine laboratory work up showed an elevated sedimentation rate (50 mm/h, normal B 15 mm/h) and a mild normochromic anemia (9.5 g/dl, MCMH: 0.3 g/l). Quantitative serum IgA and IgG were elevated [8.2 g/l (normal: 0.4–4.2 g/l) and 30.1 g/l (normal:
Fig. 1. Lymph node biopsy: expanded sinuses packed with large histiocytes which had ample pale cytoplasm and single round vesicular nuclei. Their cytoplasm engulfs lymphocytes, erythrocytes and plasma cells. Hematoxylin and eosin stain × 100.
Fig. 3. Lymph node biopsy: expanded sinuses packed with large histiocytes which had ample pale cytoplasm and single round vesicular nuclei. Their cytoplasm engulfs lymphocytes, erythrocytes and plasma cells. Hematoxylin and eosin stain × 400.
2. Second case report
A. El Kohen et al. / Int. J. Pediatr. Otorhinolaryngol. 61 (2001) 243–247
Fig. 4. Immunostaining by S 100 protein ( ×100): showing histiocytic cells S 100 protein positive.
7.3– 15 g/l) respectively]. Serologic tests for toxoplasmosis, infectious mononucleosis, cat-scratch and human immunodeficiency virus disease were negative. We noted elevated Epstein Barr virus serum antibody titers. The histopathology was characteristic of SHML, and histiocytic cells were S-100 protein positive by immunostaining (Fig. 4) (and anti-cytokeratine and EMA anti-epithelial membrane antigen negative). The lymphadenopathy had completely and spontaneously regressed after 6 months of follow up.
3. Discussion Sinus histiocytosis with massive lymphadenopathy (SHML), also known as the Destombes-Rosai-Dorfman syndrome, is a rare and benign disorder described in 1969 [1] as a newly benign histioproliferative disease in which lymphadenopathy results from infiltration and dilatation of lymph node sinuses by large histiocytes actively phagocytosing autologous lymphocytes. All ages are affected but the disorder occurs usually in the first or second decade, most commonly in black and male patients. Ninety percent of the patients tend to have a chronic bilateral painless cervical lymphadenopathy usually of massive proportions [2]. The cervical region (submandibular in particular) is the most prominent site of involvement [3].
245
Other peripheral or central lymph node groups (axillary, inguinal, hilar or mediastinal) can be affected with or without cervical disease [4]. Commonly associated findings were noted such as fever, leukocytosis, normochromic anemia, polyclonal hypergammaglobulinemia and elevated erythrocyte sedimentation rate [2,5]. One third of the patients have evidence of extranodal involvement in sites such as eyes, head and neck, upper respiratory tract, skin, salivary gland, abdominal viscera, testicles, meninges of the cranium and spine, and central nervous system. Head and neck sites involved included the nasal cavity, paranasal sinuses, nasopharynx, parotid and submandibular glands, larynx and temporal bone [1,6,7]. Occasionally extranodal disease represents the predominant or even exclusive manifestation of the disease [2,8]. In some patients immunological abnormalities can be noted including leukocytosis, altered T4/T8 ratios, decreased lymphocyte mitogenic responses, and hypergammaglobulinemia. In these cases, extranodal involvement is present in about half of cases [9]. Cellular immunological abnormalities can disappear after a few months. Infectious adenitis, specific (tuberculosis) or non specific seems to be the most frequent cause of cervical lymphadenopathy in children, particularly in our country. Cases of progressive lymph node enlargement with failure to regress after appropriate antibacterial therapy should indicate the possibility of non infectious process, which included Hodgkin’s and non-Hodgkin’s lymphoma and SHML [2]. Diagnosis of Rosai-Dorfman disease is based on morphological characteristics. The gross morphologic characteristics include large, lobulated masses with the presence of fibrous septa between the lymph nodes. The microscopic features are distinguished by engorgement of dilated nodal sinus, with large distinctive histiocytes which possess ample pale cytoplasm, round vesicular nuclei and distinct nucleoli. Lymphophagocytosis (emperipolesis) is seen and plasma cell, neutrophils or erythrocytes may be engulfed as well (Figs. 1, 2 and 5). In extranodal sites, identical cellular infiltrates are seen, but the presence of cellular phagocytosis is less constant.
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A. El Kohen et al. / Int. J. Pediatr. Otorhinolaryngol. 61 (2001) 243–247
We can find a predominance of histiocytes in other disease entities such as leukemia, lipid storage disease and histiocytosis X [4]. However emperipolesis seems to be a phenomenon which makes Rosai-Dorfman disease easily distinguishable, and also appears to be requisite for the diagnosis, whereas emperipolesis is not a unique phenomenon to Rosai Dorfman [1,5]. The histiocytes stained strongly for S 100 protein. The group of xanthohistiocytic proliferation expressing a S 100 protein includes also histiocytosis X and congenital self healing reticulohistiocytosis [10,11]. These diseases show, in contrast with Rosai Dorfman, many eosinophils and destructive cells with convulted ‘Kidney shaped’ nucleus. The origin, the pathogenesis of the disease and the histogenesis of the proliferating cell are still unknown or uncertain. The cell of Rosai-Dorfman disease can still not be classified as a Langherans type dendritic cell or as a non Langherans phagocytic histiocyte [10]. The two most popular theories implicate an infectious cause and an immunodeficiency state. Human herpes virus 6 genome was demonstrated by in situ hybridization in biopsy specimens [12]. This virus, however, is commonly demonstrated in variant forms of lymphadenopathy. Some authors also suggest that Rosai-Dorfman disease may result from an aberrant histiocytic response to Epstein Barr Virus (EBV) infection or direct EBV infection of histiocytes. But the implication
of EBV as the aetiological agent of Rosai Dorfman disease is still not proved and there was no evidence of latent or lytic EBV carriage in the histiocytes and lymphocytes. Serological evidence of EBV documented in over half of the cases, especially those with associated immune disorders, may represent only an epiphenomenon of EBV superinfection or reactivation in the presence of the immune disturbance found commonly in such patients [13]. The disease is often benign and self limiting. The natural history and outcome are variable, usually indolent, characterized by remissions and exacerbations over many months to years. The lymphadenopathy generally resolves spontaneously and is not influenced by treatment. One third of SHML patients have evidence of disease for 5 years, and fatal outcomes occur in 7% of cases, usually in patients with immunological deficiencies [2]. SHML is not a premalignant lymph node condition. Although the literature contains no indications for an effective treatment protocol, various modalities of therapy have been tried with little effect on the disease course [14,15]. Radiation therapy and chemotherapic regimens can be used when disease manifestation becomes severe and progressive. Symptomatic progressive RosaiDorfman disease may require an approach similar to that commonly employed with low grade lymphomas with results indicating a related long survival. However the role of chemotherapy in Rosai-Dorfman disease is still not clarified. Surgical treatment has been used in localized forms, when nodal or extranodal deposits cause tracheal obstruction or in cases of spinal epidural and intracranial involvement [16]. Our patients who had clinical and histopathologic features classic for SHML have received no therapy and the disease state has been stable for several months.
4. Conclusion Fig. 5. Lymph node biopsy [May Grunwald Giemsa stain (MGG)× 400]: showing a population of large histiocytic cells with phagocytosed lymphocytes.
We describe additional cases of SHML presenting with the typical manifestations of cervical lymphadenopathy. Biopsy of the lymph nodes is
A. El Kohen et al. / Int. J. Pediatr. Otorhinolaryngol. 61 (2001) 243–247
necessary in order to differentiate this potentially benign disorder from neoplastic or inflammatory process. SHML can have extranodal spread with associated morbidity and mortality. The fatal cases demonstrated immune dysfunction.
References [1] J. Rosai, R.F. Dorfman, Sinus histiocytosis with massive lymphadenopathy: a newly recognised benign clinicopatological entity, Arch. Pathol. 87 (1969) 63 – 70. [2] J.C. Murray, S.N. Rossmann, Pathological case of the month. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease), Arch. Pediatr. Adolesc. Med. 149 (1995) 57 – 58. [3] A. Carbone, A. Passannante, A. Gloghini, Review of sinus histiosytosis with massive lymphadenopathy (RosaiDorfman disease) of the head and neck, Ann. Otol. Rhinol. Laryngol. 108 (11 Pt. 1) (1999) 1095 –1104 [4] V.G. Schweitzer, G.D. Bobier, Sinus histiocytosis with massive lymphadenopathy: case report and literature review, Ann. Otol. Rhinol. Laryngol. 95 (1986) 331 – 335. [5] M. Kim, J. Provias, Rosai-Dorfman disease mimicking multiple meningioma: case report, Neurosurgery 36 (6) (1995) 1185 – 1187. [6] J.W. Goodnignt, M.B. Wang, J.A. Sercarz, Y.S. Fu, Extranodal Rosai-Dorfman disease of the head and neck, Laryngoscope 106 (3 Pt. 1) (1996) 253 –256. [7] B.M. Wenig, S.L. Abbondanzo, E.L. Childers, Extranodal sinus histiosytosis with massive lymphadenopathy (Rosai-Dorfman disease) of the head and neck, Human
247
Pathol. 24 (5) (1993) 483 – 492. [8] R. Sanchez, J. Rosai, R.F. Dorfman, Sinus histiocytosis with massive lymphadenopathy: an analysis of 113 cases with special emphasis on its extranodal manifestations, Lab. Invest. 36 (1977) 349 – 350. [9] E. Foucar, J. Rosai, R. Dorfman, Immunological abnormalities and their significance in sinus histiocytosis with massive lymphadenopathy, Am. J. Clin. Pathol. 82 (1984) 515 – 525. [10] F. Mac-Moune Lai, W.Y. Lam, Cutaneous Rosai-Dorfman disease presenting as a suspicious breast mass, J. Cutan Pathol. 21 (4) (1994) 377 – 382. [11] M. Miettinen, P. Paljakka, P. Haveri, E. Saxen, Sinus histiocytosis with massive lymphadenopathy. A nodal and extranodal proliferation of S-100 protein positive histiocytes?, Am. J. Clin. Pathol. 88 (1987) 270. [12] P.H. Levine, N. Jahan, Detection of human herpesvirus 6 in tissues involved by sinus histiocytosis with massive lymphadenopathy (Rosai Dorfman disease), J. Infect. Dis. 166 (1992) 291 – 295. [13] W.Y.W. Tsang, T.T.C. Yip, The Rosai-Dorfman disease histiocytes are not infected by Epstein-Barr virus, Histopathology 25 (1) (1994) 88 – 90. [14] M. Colleoni, F. Gaion, Evidence of responsiveness to chemotherapy in aggressive Rosai-Dorfman Disease, Eur. J. Cancer 31A (3) (1995) 424. [15] F. Boman-Ferrand, J. Floquet, Histiocytose sinusale avec lymphade´ nopathie massive, Syndrome de Destombes-Rosai-Dorfman, Ann. Pathol. 10 (3) (1990) 152 – 160. [16] E. Kessler, C. Srulijes, Sinus histiocytosis with massive lymphadenopathy and spinal epidural involvement. A case report and review of the literature, Cancer 38 (1976) 1614 – 1618.
Case report
Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): two case reports Asma El Kohen a,*, Xavier Planquart c, Zitouna Al Hamany b, Laurent Bienvenu d, Mohamed Kzadri a, Denis Herman c a
Department of Otorhinolaryngology and Maxillofacial Surgery, A6icenne’s Hospital, Faculty of Medicine and Uni6ersity Hospital of Rabat, Rabat, Morocco b Department of Pediatric’s Pathology, Children’s Hospital, Faculty of Medicine and Uni6ersity Hospital of Rabat, Rabat, Morocco c Department of Otorhinolaryngology Surgery, Robert Ballanger’s Hospital, Aulnay sous Bois, France d Department of Pathology, Robert Ballanger’s Hospital, Aulnay sous Bois, France Received 28 September 2000; received in revised form 26 May 2001; accepted 27 May 2001
Abstract Sinus histiocytosis with massive lymphadenopathy or Destombes-Rosai-Dorfman’s syndrome is a rare benign disease of unknown etiology , usually seen in younger patients. The cases reported concerned a 15-month old Caucasian boy and an 8 year old black boy with unilateral cervical enlargement, occasional fever and without any extranodal involvement. Diagnosis was performed by superficial lymph node biopsy. No immunodeficiency was found. The patients received no therapy and a complete spontaneous resolution was seen after a few months in the two cases. The clinical presentation, histologic characteristics, pathogenesis and treatment of the Destombes-RosaiDorfman’s syndrome are discussed. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Rosai-Dorfman disease; Cervical lymphadenopathy; Sinus histiocytosis; Child
1. First case report
Abbre6iations: SHML, sinus histiocytosis with massive lymphadenopathy; EBV, Epstein Barr virus; ESR, sedimentation rate; MGG, May Grunwald Giemsa. * Corresponding author. Villa No. 136 OLM SOUISSI II, Rabat, Morocco. Tel.: + 212-377-52295. E-mail address: [email protected] (A. El Kohen).
A 15 months old Caucasian boy presented with 3 months history of enlarging and painless unilateral cervical and submandibular lymphadenopathy. He was asymptomatic except for occasional fever (temperature to 38.5 °C). Physical examination revealed large, unilateral, non-tender lymph node conglomerates in the anterior cervical chain
0165-5876/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 1 6 5 - 5 8 7 6 ( 0 1 ) 0 0 5 2 3 - 7
244
A. El Kohen et al. / Int. J. Pediatr. Otorhinolaryngol. 61 (2001) 243–247
and submandibular area. No lymphadenopathy in other regions or extranodal involvement were detected. Routine laboratory investigations, including a complete blood count, sedimentation rate (ESR) and serum protein electrophoresis, were made. Values obtained were WBC: 7200/mm3, hemoglobin 9.1 g/dl, MCMH: 0.31 g/l, ESR: 43 mm/h, a-1-globulin: 0.1 g/dl, a-2-globulin: 1.2 g/dl, b-globulin: 1.2 g/dl, g-globulin: 2.9 g/dl. The serological viral investigations were negative for toxoplasmosis, infectious mononucleosis and catscratch. Since there had been no improvement in the lymphadenopathy after several courses of oral antibiotics, a lymph node biopsy was performed. It showed histologically expanded sinuses packed with large histiocytes. Their cytoplasm often engulfs lymphocytes and less frequently erythrocytes and plasma cells (Figs. 1– 3 and 5) The patient received no therapy. We noted spontaneous regression of the lymphadenopathy with no evidence of recurrence during 22 months of follow up.
Fig. 2. Lymph node biopsy: expanded sinuses packed with large histiocytes which had ample pale cytoplasm and single round vesicular nuclei. Their cytoplasm engulfs lymphocytes, erythrocytes and plasma cells. Hematoxylin and eosin stain × 250.
The second case concerned an 8 years old black boy with large unilateral lymph node involvement in the anterior cervical chain and recurrent fever.
There was no history of weight loss, dysphagia or arthralgias. Physical examination revealed no lymphadenopathy by palpation in other regions and the remainder of the examination was normal. The chest X-ray was normal. A routine laboratory work up showed an elevated sedimentation rate (50 mm/h, normal B 15 mm/h) and a mild normochromic anemia (9.5 g/dl, MCMH: 0.3 g/l). Quantitative serum IgA and IgG were elevated [8.2 g/l (normal: 0.4–4.2 g/l) and 30.1 g/l (normal:
Fig. 1. Lymph node biopsy: expanded sinuses packed with large histiocytes which had ample pale cytoplasm and single round vesicular nuclei. Their cytoplasm engulfs lymphocytes, erythrocytes and plasma cells. Hematoxylin and eosin stain × 100.
Fig. 3. Lymph node biopsy: expanded sinuses packed with large histiocytes which had ample pale cytoplasm and single round vesicular nuclei. Their cytoplasm engulfs lymphocytes, erythrocytes and plasma cells. Hematoxylin and eosin stain × 400.
2. Second case report
A. El Kohen et al. / Int. J. Pediatr. Otorhinolaryngol. 61 (2001) 243–247
Fig. 4. Immunostaining by S 100 protein ( ×100): showing histiocytic cells S 100 protein positive.
7.3– 15 g/l) respectively]. Serologic tests for toxoplasmosis, infectious mononucleosis, cat-scratch and human immunodeficiency virus disease were negative. We noted elevated Epstein Barr virus serum antibody titers. The histopathology was characteristic of SHML, and histiocytic cells were S-100 protein positive by immunostaining (Fig. 4) (and anti-cytokeratine and EMA anti-epithelial membrane antigen negative). The lymphadenopathy had completely and spontaneously regressed after 6 months of follow up.
3. Discussion Sinus histiocytosis with massive lymphadenopathy (SHML), also known as the Destombes-Rosai-Dorfman syndrome, is a rare and benign disorder described in 1969 [1] as a newly benign histioproliferative disease in which lymphadenopathy results from infiltration and dilatation of lymph node sinuses by large histiocytes actively phagocytosing autologous lymphocytes. All ages are affected but the disorder occurs usually in the first or second decade, most commonly in black and male patients. Ninety percent of the patients tend to have a chronic bilateral painless cervical lymphadenopathy usually of massive proportions [2]. The cervical region (submandibular in particular) is the most prominent site of involvement [3].
245
Other peripheral or central lymph node groups (axillary, inguinal, hilar or mediastinal) can be affected with or without cervical disease [4]. Commonly associated findings were noted such as fever, leukocytosis, normochromic anemia, polyclonal hypergammaglobulinemia and elevated erythrocyte sedimentation rate [2,5]. One third of the patients have evidence of extranodal involvement in sites such as eyes, head and neck, upper respiratory tract, skin, salivary gland, abdominal viscera, testicles, meninges of the cranium and spine, and central nervous system. Head and neck sites involved included the nasal cavity, paranasal sinuses, nasopharynx, parotid and submandibular glands, larynx and temporal bone [1,6,7]. Occasionally extranodal disease represents the predominant or even exclusive manifestation of the disease [2,8]. In some patients immunological abnormalities can be noted including leukocytosis, altered T4/T8 ratios, decreased lymphocyte mitogenic responses, and hypergammaglobulinemia. In these cases, extranodal involvement is present in about half of cases [9]. Cellular immunological abnormalities can disappear after a few months. Infectious adenitis, specific (tuberculosis) or non specific seems to be the most frequent cause of cervical lymphadenopathy in children, particularly in our country. Cases of progressive lymph node enlargement with failure to regress after appropriate antibacterial therapy should indicate the possibility of non infectious process, which included Hodgkin’s and non-Hodgkin’s lymphoma and SHML [2]. Diagnosis of Rosai-Dorfman disease is based on morphological characteristics. The gross morphologic characteristics include large, lobulated masses with the presence of fibrous septa between the lymph nodes. The microscopic features are distinguished by engorgement of dilated nodal sinus, with large distinctive histiocytes which possess ample pale cytoplasm, round vesicular nuclei and distinct nucleoli. Lymphophagocytosis (emperipolesis) is seen and plasma cell, neutrophils or erythrocytes may be engulfed as well (Figs. 1, 2 and 5). In extranodal sites, identical cellular infiltrates are seen, but the presence of cellular phagocytosis is less constant.
246
A. El Kohen et al. / Int. J. Pediatr. Otorhinolaryngol. 61 (2001) 243–247
We can find a predominance of histiocytes in other disease entities such as leukemia, lipid storage disease and histiocytosis X [4]. However emperipolesis seems to be a phenomenon which makes Rosai-Dorfman disease easily distinguishable, and also appears to be requisite for the diagnosis, whereas emperipolesis is not a unique phenomenon to Rosai Dorfman [1,5]. The histiocytes stained strongly for S 100 protein. The group of xanthohistiocytic proliferation expressing a S 100 protein includes also histiocytosis X and congenital self healing reticulohistiocytosis [10,11]. These diseases show, in contrast with Rosai Dorfman, many eosinophils and destructive cells with convulted ‘Kidney shaped’ nucleus. The origin, the pathogenesis of the disease and the histogenesis of the proliferating cell are still unknown or uncertain. The cell of Rosai-Dorfman disease can still not be classified as a Langherans type dendritic cell or as a non Langherans phagocytic histiocyte [10]. The two most popular theories implicate an infectious cause and an immunodeficiency state. Human herpes virus 6 genome was demonstrated by in situ hybridization in biopsy specimens [12]. This virus, however, is commonly demonstrated in variant forms of lymphadenopathy. Some authors also suggest that Rosai-Dorfman disease may result from an aberrant histiocytic response to Epstein Barr Virus (EBV) infection or direct EBV infection of histiocytes. But the implication
of EBV as the aetiological agent of Rosai Dorfman disease is still not proved and there was no evidence of latent or lytic EBV carriage in the histiocytes and lymphocytes. Serological evidence of EBV documented in over half of the cases, especially those with associated immune disorders, may represent only an epiphenomenon of EBV superinfection or reactivation in the presence of the immune disturbance found commonly in such patients [13]. The disease is often benign and self limiting. The natural history and outcome are variable, usually indolent, characterized by remissions and exacerbations over many months to years. The lymphadenopathy generally resolves spontaneously and is not influenced by treatment. One third of SHML patients have evidence of disease for 5 years, and fatal outcomes occur in 7% of cases, usually in patients with immunological deficiencies [2]. SHML is not a premalignant lymph node condition. Although the literature contains no indications for an effective treatment protocol, various modalities of therapy have been tried with little effect on the disease course [14,15]. Radiation therapy and chemotherapic regimens can be used when disease manifestation becomes severe and progressive. Symptomatic progressive RosaiDorfman disease may require an approach similar to that commonly employed with low grade lymphomas with results indicating a related long survival. However the role of chemotherapy in Rosai-Dorfman disease is still not clarified. Surgical treatment has been used in localized forms, when nodal or extranodal deposits cause tracheal obstruction or in cases of spinal epidural and intracranial involvement [16]. Our patients who had clinical and histopathologic features classic for SHML have received no therapy and the disease state has been stable for several months.
4. Conclusion Fig. 5. Lymph node biopsy [May Grunwald Giemsa stain (MGG)× 400]: showing a population of large histiocytic cells with phagocytosed lymphocytes.
We describe additional cases of SHML presenting with the typical manifestations of cervical lymphadenopathy. Biopsy of the lymph nodes is
A. El Kohen et al. / Int. J. Pediatr. Otorhinolaryngol. 61 (2001) 243–247
necessary in order to differentiate this potentially benign disorder from neoplastic or inflammatory process. SHML can have extranodal spread with associated morbidity and mortality. The fatal cases demonstrated immune dysfunction.
References [1] J. Rosai, R.F. Dorfman, Sinus histiocytosis with massive lymphadenopathy: a newly recognised benign clinicopatological entity, Arch. Pathol. 87 (1969) 63 – 70. [2] J.C. Murray, S.N. Rossmann, Pathological case of the month. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease), Arch. Pediatr. Adolesc. Med. 149 (1995) 57 – 58. [3] A. Carbone, A. Passannante, A. Gloghini, Review of sinus histiosytosis with massive lymphadenopathy (RosaiDorfman disease) of the head and neck, Ann. Otol. Rhinol. Laryngol. 108 (11 Pt. 1) (1999) 1095 –1104 [4] V.G. Schweitzer, G.D. Bobier, Sinus histiocytosis with massive lymphadenopathy: case report and literature review, Ann. Otol. Rhinol. Laryngol. 95 (1986) 331 – 335. [5] M. Kim, J. Provias, Rosai-Dorfman disease mimicking multiple meningioma: case report, Neurosurgery 36 (6) (1995) 1185 – 1187. [6] J.W. Goodnignt, M.B. Wang, J.A. Sercarz, Y.S. Fu, Extranodal Rosai-Dorfman disease of the head and neck, Laryngoscope 106 (3 Pt. 1) (1996) 253 –256. [7] B.M. Wenig, S.L. Abbondanzo, E.L. Childers, Extranodal sinus histiosytosis with massive lymphadenopathy (Rosai-Dorfman disease) of the head and neck, Human
247
Pathol. 24 (5) (1993) 483 – 492. [8] R. Sanchez, J. Rosai, R.F. Dorfman, Sinus histiocytosis with massive lymphadenopathy: an analysis of 113 cases with special emphasis on its extranodal manifestations, Lab. Invest. 36 (1977) 349 – 350. [9] E. Foucar, J. Rosai, R. Dorfman, Immunological abnormalities and their significance in sinus histiocytosis with massive lymphadenopathy, Am. J. Clin. Pathol. 82 (1984) 515 – 525. [10] F. Mac-Moune Lai, W.Y. Lam, Cutaneous Rosai-Dorfman disease presenting as a suspicious breast mass, J. Cutan Pathol. 21 (4) (1994) 377 – 382. [11] M. Miettinen, P. Paljakka, P. Haveri, E. Saxen, Sinus histiocytosis with massive lymphadenopathy. A nodal and extranodal proliferation of S-100 protein positive histiocytes?, Am. J. Clin. Pathol. 88 (1987) 270. [12] P.H. Levine, N. Jahan, Detection of human herpesvirus 6 in tissues involved by sinus histiocytosis with massive lymphadenopathy (Rosai Dorfman disease), J. Infect. Dis. 166 (1992) 291 – 295. [13] W.Y.W. Tsang, T.T.C. Yip, The Rosai-Dorfman disease histiocytes are not infected by Epstein-Barr virus, Histopathology 25 (1) (1994) 88 – 90. [14] M. Colleoni, F. Gaion, Evidence of responsiveness to chemotherapy in aggressive Rosai-Dorfman Disease, Eur. J. Cancer 31A (3) (1995) 424. [15] F. Boman-Ferrand, J. Floquet, Histiocytose sinusale avec lymphade´ nopathie massive, Syndrome de Destombes-Rosai-Dorfman, Ann. Pathol. 10 (3) (1990) 152 – 160. [16] E. Kessler, C. Srulijes, Sinus histiocytosis with massive lymphadenopathy and spinal epidural involvement. A case report and review of the literature, Cancer 38 (1976) 1614 – 1618.