Pediatr Radiol (1990) 20:425432
Pediatric Radiology 9 Springer-Verlag 1990
Review
Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) W. H. McAlister 1, T. Herman 1 and L. P. Dehner 2 Departments of 1 Radiology and 2 Pathology,Division of Anatomic Pathology,Washington UniversitySchool of Medicine and St. Louis Children's Hospital, St. Louis, MO, USA Received: 4 December 1989;accepted: 4 December 1989
Sinus histiocytosis with massive lymphadenopathy (SHML) was initially described by Rosai and Dorfman in 1969 as a distinctive cfinicopathological entity differentiated from Langerhans' cell histiocytosis (LCH or histiocytosis X). Rosai-Dorfman disease is the generally applied eponym. Although the etiology remains unknown, the disease is thought to be a disorder of immune regulation or response to a presumed infectious agent with major manifestations in the lymph nodes with the resulting proliferation of sinusoidal histiocytes. Most efforts to identify a pathogen have culminated in indeterminant or negative results. In this and some other respects, SHML and LCH remain etiologic enigmas. The most frequent clinical manifestation of SHML is bilateral, nontender, painless, cervical lymphadenopathy; "proconsular" or "bull" neck is a term applied to the symmetrical cervical adenopathy which resembles the findings in Hodgkin's disease of the neck. Other nodal sites are involved as well including the mediastinal, retroperitoheal, and inguinal sites. Once SHML had been established as an entity in the lymph nodes, it soon became apparent that the disorder was not restricted to lymph nodes alone. In fact, of 40% of affected individuals have extranodal, multisystemic disease in a distribution not unlike LCH [1]. The purpose of this communication is to review the clinical, radiographic and pathological manifestations of SHML for the pediatric radiologist.
Histiocytoses Sinus histiocytosis with massive lymphadenopathy is but one of several histiocytic syndromes occurring predominantly in children. A brief consideration of these histiocytoses may help the understanding of a generally bewildering group of disorders. The differentiation of one histiocytic condition from another primarily relies upon the characterization of the type of "histiocyte" of which there are several mononuclear phagocytes including the Langerhans' cell, interdigitating reticulum cell and the
common phagocytic macrophage or histiocyte [2-4]. The Langerhans' cell, a dendritic cell normally found in the epidermis, is the diagnostic constitutent of histiocytosis X. Cytoplasmic Birbeck granules identifiable by electron microscopy and the expression of CD1 (T6 antigen) and H L A - D R on the cell membrane are the characteristic morphologic and immunophenotypic markers of the Langerhans' cell. The immunoreactivity for S-100 protein is not specific for Langerhans' cells although it is very useful when tissue is not available for the more specific studies [5]. In contrast to histiocytosis X, SHML is but one of a heterogenous group of histiocytic proliferations of the phagocytic or antigen processing cells. Infectious (Mycobacteria, Histoplasma) and metabolic etiologies (Gaucher's disease, Niemann-Pick disease) are examples of diseases with known etiologies whose histologic appearance is dominated by a histiocytic reaction. Erythroand lymphophagocytosis are the histologic hallmarks of infection (viral)-associated hemophagocytic syndrome (VAHS) and SHML. Epstein-Barr virus has been implicated in the pathogenesis, if not the direct etiology, of the VAHS. There are many similarities among the VAHS, familial erythrophagocytic histiocytosis and X-linked lymphoproliferative syndrome. In other words, the erythrophagocytosis is a nonspecific response to a variety of immunologic provocations. An immunologic pathogenesis is strongly suspected but unproven for both histiocytosis X and SHML. All of the histiocytoses which have been discussed to this point are regarded as benign processes of a probable reactive rather than of a neoplastic nature. Malignant histiocytosis (MH) and acute monoblastic leukemia are the two most familiar types of malignancies of mononuclear phagocytes. Recently, some questions have been raised about the differentiation of MH from peripheral T-cell lymphoma with a prominent histiocytic infiltrate; one example of the latter is the so-called Ki-1 lymphoma of childhood [6]. The extramedullary presentation of acute monoblastic leukemia may simulate MH.
426 Review of the literature
Clinicalfeatures Since the original description of SHML in 1969, a registry has been maintained by Rosai who has accumulated 365 cases as of 1988 [1]. The majority of patients present within the first two decades of life. There appears to be a slight predilection for blacks since 49% of cases occur in this race whereas the remainder are listed as caucasian (46%) or oriental (5%). Many of the black patients are from Africa and the Caribbean basin; the actual percentage of blacks with SHML may be higher because of infrequent reporting from these third world countries. In a series of 105 Nigerian children with persistent cervical lymphadenopathy, the incidence of SHML was 7.6% which is unlike the case in a group of children with similar symptoms from the St.Louis metropolitan area [7]. The male to female ratio is 1.4 to 1. Sixty-two percent of the patients are less than the age of 10 at presentation. However, the average age of patients in the registry is 19.7 years, including the large number of elderly patients with SHML [1, 8]. Perhaps a genetic predisposition exists as it has been described in two pairs of siblings and in a pair of identical twins [9]. Virtually all patients (97%) provide a history of bilateral cervical lymphadenopathy for a period of 39 months before medical attention is sought; the adenopathy may be asymmetric. Other nodal groups including the axillary, inguinal, hilar, a n d mediastinal lymph nodes are involved in 80% of patients; however, not all affected nodes are necessarily enlarged, but the microscopic changes of SHML are present in a biopsy. Extranodal disease has been reported in approximately 30% of cases with various sites in the head and neck region showing a particular predilection. The nasal cavity, salivary gland tissue, oral cavity, pharynx, tonsils, paranasal sinuses, trachea, orbit and eyelid are the specific affected locations [10]. Nasal obstruction and rhinorrhea due to mucosal infiltration by a mixture of histiocytes and chronic inflammatory cells are the clinical manifestations of a mass in the nasal cavity. Orbital involvement characteristically is manifested by proptosis. Two or more sites of SHML are seen in 50% of cases with extranodal head and neck disease [11]. When the trachea or bronchus is affected, stridor and even life threatening dyspnea may occur. Cutaneous infiltrates present as nodules or in some cases with a rash and may precede the lymphadenopathy. Subcutaneous lesions are less common than epidermal-based lesions but involvement may produce a panniculitis similar to Weber-Christian disease [12]. Bone pain or paralysis from an epidural lesion are other manifestations in a minority of patients [13]. Other than the presenting symptoms, the patients are generally in good health. Two-thirds of patients with SHML of the upper airway or oral cavity have infiltrative disease in other non-lymphoid sites (skin, bone, testes, orbits, eyelids, abdominal viscera, and central nervous system). Exclusive extrano-
W.H. McAlister et al.: Sinus histiocytosis(Rosai-Dorfman-disease) dal disease is more frequent in elderly individuals and in those with an underlying immune deficiency state. Cervical adenopathy is not an invariable finding in patients with extranodal involvement. When massive lymphadenopathy is present, often low grade fever (up to 102 ~ leukocytosis (up to 32 000), neutrophilia, and an elevated erythrocyte sedimentation rate are associated clinical and laboratory findings. Additionally, 80% of patients have a polyclonal hypergamma-globulinemia, and 65% have a hypochromic or normochromic normocytic anemia. The disease typically pursues an indolent clinical course. In approximately 50% of patients, the disease resolves without appreciable sequela, one-third have residual asymptomatic adenopathy and 17% have persistent symptomatology after 5 to 10years. Regression is usually heralded by diminution of the extranodal disease. The longest described clinical course has been 30 years [13]. The reported mortality is 7% and renal involvement has often been associated with a fatal outcome or an excessively prolonged course [14]. Seven percent of patients with SHML are found to have disorders such as Wiskott-Aldrich syndrome, circulating autoantibodies, rheumatoid arthritis, glomerulonephritis, brucellosis [15], amyloidosis, antiplatelet antibodies, joint disease or unusual infections of the lung, suggesting an underlying impaired immune system. These patients tend to be older, more frequently Western and white, and have more extensive mediastinal adenopathy. Evidence of an underlying immune deficiency disorder is a poor prognostic feature with a significantly increased mortality rate (43 %). Seven patients have been diagnosed with sinus histiocytosis at Children's Hospital. Five patients underwent spontaneous resolution of their lesions. Two were treated with chemotherapy, steroids and radiation therapy. All 7 are alive. One patient of particular interest is detailed below. He has been followed for 16 years and presented with bilateral proptosis and cervical adenopathy at age 3. One eye and some cervical nodes were biopsied. No therapy was given for 11/2years but because of keratitis and limitation of eye movements and lack of improvement he was given chemotherapy (vincristine and then chorambucil) for 2 years and responded. He had hypergammaglobulinemia and anemia. At age 13 years he developed massive abdominal lymphadenopathy and bilateral renal involvement. Both the kidney and retroperitoneal adenopathy were biopsied and confirmed to be SHML. He was placed back on systemic chemotherapy for 2 years and the adenopathy and renal involvement improved and the chemotherapy was discontinued. The kidneys have remained enlarged. He then developed bilateral lower extremity swelling and pain. Bone scintigraphy showed extensive skeletal abnormalities of increased uptake greatest around the joints of the lower extremities. Plain radiographs showed diffuse osteopenia. He was placed back on chemotherapy (Methotrexate) for 2 years and significantly improved. Except for short stature and anemia he is relatively asymptomtic at present.
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Fig.1. Sinushistiocytosiswithmassive lymphadenopathyshowingsinusoids distendedwithpale staininghistiocytes. H&E x 150/WIL89-2853F3
Figo2. Sinushistiocytosiswithmassive lymphadenopathyshowinginnumerable histiocyteswithintracytoplasmic lymphocytes(arrows). H&E x 150/WIL8254F0
Pathologicfeatures The diagnosis of SHML is readily established by the presence of the histologic alterations in an affected lymph node. When the disease is predominately manifested in an extranodal site, a pathologic diagnosis can be made but there is a greater likelihood of overlooking SHML in favor of nonspecific chronic inflammation and fibrosis, chronic osteomyelitis in the case of a bony lesion or one of several other entities producing histiocytic infiltrates in the skin. The possibility of SHML may not occur until a lymph node biopsy is performed and even then, there may be failure to appreciate the significance of the changes. When a group of lymph nodes are excised, they are generally matted together by thickened bands of capsular and pericapsular connective tissue. In this respect, the lymph nodes resemble those of nodular sclerosis Hodgkin's disease. However, the capsule may be a thin, delicate fibrous sheath. The architecture of the lymph node is in-
tact in respect to the corticomedullary areas, but there is accentuation of cortical follicles as a result of hyperplasia of the germinal centers and surrounding cortical mantle. Distention of the sinusoids by pale-staining histiocytes intermixed with variable numbers of mature plasma cells is the characteristic feature of SHML (Fig.l). Numerous plasma cells are also found in the paracortical tissues. The histiocytes tend to be loosely cohesive. Individual histiocytes contain one or more intact lymphocytes in the cytoplasm (Fig. 2). The lymphocytes show no evidence of fragmentation or degeneration which would be anticipated if these cells were simply phagocytized; rather the lymphocytes have penetrated the cytoplasm in a process known as emperipolesis where the lymphocytes continue to have free movement within the histiocyte. Because lymphocyte emperipolesis is thought to relate to antigen presentation, SHML may represent a derangement of the process by which histiocytes contact lymphocytes for antigen delivery. In extranodal sites, the presence of lymphocyte-
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Fig.3. A cervical adenopathy on this Tl-weighted coronal neck image in a young child. (Case courtesy of Dr. Walter Berdon.) Fig.4. Multiple cervical lymph nodes shown by sonography in a 6year-old boy Fig.5. Hilar adenopathy seen on a chest roentgenogram in an llyear-old girl Ng.6. Retroperitoneal adenopathy as shown on this transverse sonogram stretching the celiacartery in a 6-year-oldboy
when a biopsy has been obtained from an extranodal lesion. The differential diagnosis based upon the histologic examination is limited when the nodal biopsy shows the aforementioned changes. Virtually all histiocytic proliferative disorders have a common pattern of nodal involvement with expansion of the subcapsular and interfolicular sinusoids. Large mononuclear and occasional multinucleated cells with pale, eosinophilic cytoplasms and a reniform shaped nucleus with a cleft or groove across the nuclear membrane are diagnostic of Langerhans' cell histiocytosis. Ultrastructurally, the Langerhans' cell contains the cytoplasmic pentilaminar complex known as a Birbeck granule [2]. CD1 (T6) is expressed in the cell membrane, but in the case of SHML, the histiocytes are nonreactive. Both Langerhans' cells and the histiocytes of SHML are S-100 protein positive but the reaction is stronger in the Langerhans' cells [2, 4, 11]. The presence of lymphophagocytic histiocytes and S-100 protein positivity is regarded as diagnostic of SHML [4].
containing histiocytes is an important clue to the pathologic diagnosis. As SHML regresses, the affected lymph node becomes progressively fibrotic with replacement of the parenchyma by collagen deposition. At this stage, many of the diagnostic features and cells are less apparent. Nonspecific fibroinflammatory features are likely to result in an indeterminant diagnosis. This is especially problematic
W.H. McAlister et al.: Sinus histiocytosis (Rosai-Dorfman-disease)
Fig.7 a, b. Intrinsic renal involvement and retroperitoneal nodal involvement in a 13-year-oldboy. a Computed tomography delayed scan shows an enlarged right kidney with a small area of nephrogram, retroperitoneal nodes, and nephrogram defect in the left kidney. b Intravenous urography demonstrated enlarged kidneys with distorted collectingsystems especiallythe right and displacement of the ureters from lymph nodes Fig.8. Left orbital mass displacingthe globe laterally and destroying bone in this 5-year-old girl as shown on coronal computerized tomography
Imaging manifestations Since SHML is a multifocal and multisystemic condition in a substantial proportion of patients, the imaging features are occasionally confounding because of the differential diagnostic possibilities. As noted previously, the cervical lymphadenopathy is bilateral and often massive with individual nodes measuring up to 6 cm in diameter. All major lymph node groups in the neck may be involved, but there are no distinguishing features of the adenopathy by sonography, computed tomography (CT) or magnetic resonance imaging (MRI) (Fig. 3-4) [16]. The lymph nodes have the ability to uptake gallium [17]. Axillary and inguinal lymph nodes are enlarged in 38% and 44% of cases, respectively. These nodes are
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usually smaller than those in the neck and therefore, the scans may detect involvement which was less obvious on physical examination. Mediastinal and hilar adenopathy with a unilateral or bilateral distribution is present in 3040% of patients (Fig.5) [18]. When the lung parenchyma is involved, there is extension from the hila along vascular septae producing accentuated and widened interstitial markings. Reticulonodular infiltrates are unusual. Carpenter, et al. [19] described diminished perfusion of one lung on chest roentgenography which was probably secondary to hilar or bronchial mucosal infiltration. The retroperitoneal space is an infrequent site of disease. However, retroperitoneal lymphadenopathy may distort vessels (Fig.6) and is often accompanied by extrinsic ureteral obstruction and/or parenchymal involvement of the kidney. The distortion and displacement of the ureters by a fibrous reaction are similar to that seen in retroperitoneal fibrosis (Ormand's disease) and malignant lymphoma with sclerosis [9]. Sonography can demonstrate the enlarged lymph nodes and CT the extensive encasement of the kidneys by the nodal masses [9]. Enlargement of the kidneys with distortion of the collecting systems can be shown by intravenous urography, CT, MRI, or sonography (Fig.7a, b). When the kidneys are diffusely enlarged, the findings may be confused with leukemic or lymphomatous infiltrates [20]. The renal arteries can be stretched and splayed on arteriography. Retroperitoneal lymphangiography shows a reticular pattern in the enlarged lymph
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W.H. McAlister et al.: Sinus histiocytosis(Rosai-Dorfman-disease) Second in frequency to the upper aero-digestive tract for extranodal involvement by SHML is the orbit, globe and eyelid in 7-10% of patients [1, 23]. Extraconal soft tissue masses with proptosis are the major expression of orbital disease (Fig. 8). Enlargement of the orbits can be shown on plain radiographs (Fig. 9). The orbital and adjacent paranasal sinus masses are delineated by CT and MRI; the masses on CT are enhanced with iodinated contrast media. Infiltration of the intraorbital fat and muscle is also shown by CT [24]. The bones of the orbit may undergo osteolysis or sclerosis (Fig. 10) [25]. Very few cases of involvement of the globe have been reported [26]; masses in the cornea, epibulbar conjunctiva and uveal tract have been described [27]. There is a correlation between ophthalmic and nasal involvement
[28].
Fig.9. Expansion of the orbits and soft tissue orbital masses in a 4year-old boy with marked proptosis Fig. 10. Orbital sclerosisas seen on a roentgenogram in a 13-year-old boy nodes similar to the appearance in non-Hodgkin's lymphoma. Extranodal SHML in the head and neck region is present in approximately 75% of patients with evidence of disease extrinsic to the lymph nodes. Discrete polypoid masses or thickened nasal mucosa are noted on plain radiographs and CT. Masses may be identified in the paranasal sinuses, parotid and submandibular glands, oral cavity, pharynx, tonsil and larynx. The paranasal sinuses may be opacified and occasionally, the adjacent bone is eroded on plain radiographs and CT. Submucosal masses in the larynx, trachea and bronchi are uncommon, but can cause marked stridor, if not life threatening dyspnea [21]. Masses in the retropharyngeal space may compromise the airway as well. Extrinsic obstruction of trachea has been reported by Okada, et al. [16]; submucosa involvement of the trachea with sparing of the cartilagenous rings has been shown by MRI. Thyroid involvement is generally not accompanied by functional abnormalities. In a patient who was studied by sonography, the gland was diffusely enlarged with a mixed echogenic pattern, including prominent hypoechoic areas [22].
Skeletal manifestations are found in 5-10% of patients. Multiple small lytic lesions with sharply or poorly defined borders are more common than large, mixed or sclerotic lesions (Fig. 11) [29-31]. There is no predilection for a specific site in the bone nor for specific bones. Schweitzer and Bobier [32] reported a patient with multiple lyric lesions in the skull; irregular margins surrounded by halos of dense sclerotic bone were noted by plain radiographs. The differential diagnosis of these bony lesions in children include multifocal osteomyelitis, Langerhans' cell histiocytosis and metastatic neuroblastoma. Involvement of the central nervous system is usually confined to the intraspinal and intracranial subarachnoidal, subdural and epidural spaces [33]. Plaque-like lesions on the meninges simulate a meningioma [34]. Paraplegia from an extradural mass at the cervical and thoracic levels has been reported by Haas, et al. [35]. Dural-based lesions of the middle and posterior fossa produced erosion of the middle fossa and petrous bone. A contrast enhancing leptomeningeal mass with edema of the adjacent brain was shown by CT. High density intracranial masses are rare, but have been demonstrated by CT [35]. Hepatosplenomegaly is distinctly uncommon in SHML. A diffusely enlarged liver was reported in a 7year-old patient whose liver biopsy had lymphophagocytic histiocytes in the portal tracts [36]. However, imaging studies and radionucleide scans of the liver and spleen have a low yield in this disease. Other organs which have been sites of SHML are the thymus, testicle and heart. Thymic and cardiac involvement contribute to mediastinal enlargement.
Treatment
Because of SHML's frequently self-remitting course, the occasional good responses to therapy do not allow formulation of meaningful conclusions about therapy. Surgical resection of soft tissue masses, systemic chemotherapy, prednisone, radiation therapy have been associated with improvement in several patients, but only case reports have been described. No study of treatment efficacy is available.
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References
Fig.lla, b. Medullary poorly defined lyric lesions with focal sclerosis are seen in the radius and ulna. b Sclerotic lesions of the distal femoral epiphysis and proximal tibia are seen in a 9-year-old girl. (Contributed by T. C. Demos, M. D.; previous publication in Pediatr Radio115: 259,1985)
Summary Sinus histiocytosis with massive lymphadenopathy ( R o s a i - D o r f m a n disease) is a unique disease of u n k n o w n etiology with a childhood predilection. Reports have established the worldwide distribution of the disorder. A l t h o u g h peripheral l y m p h a d e n o p a t h y is the m o s t c o m m o n m o d e of presentation, n u m e r o u s studies and individual case reports have established the fact that 30-40% of affected individuals have extranodal manifestations particularly in the h e a d and neck region where the a d e n o p a t h y tends to b e concentrated. As yet, the pathogenesis of S H M L has n o t b e e n established but speculation relates the disorder to an aberrant response to an unspecified antigen, possibly an infectious organism. Because of the clinical manifestations, the radiographic features of S H M L are not p a t h o g n o m o n i c but rather e n g e n d e r a differential diagnosis which includes l y m p h o m a t o u s , p s e u d o l y m p h o m a t o u s and infectious conditions. A p p r o p r i a t e imaging of patients with S H M L d e p e n d s u p o n presenting s y m p t o m s and signs. Radionuclide b o n e scanning m a y be helpful in the evaluation of suspected skeletal lesions or joint symptoms. Gallium scanning is often positive in nodal disease and CT, M R I and s o n o g r a p h y are helpful in the evaluation of extranodal sites of i n v o l v e m e n t such as the orbit, eyelid, u p p e r aero-digestive tract and retroperitoneum.
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W. H. McAlister Mauinckrodt Institute of Radiology Washington University School of Medicine and St. Louis Children's Hospital 510 S. Kings Highway St.Louis, MO 63110 USA
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Delayed fontanelle closure in infants with cyanotic cardiopathy. [In germ.] Rusche, T. et al. (Klinik for Kinderheilkunde des Bereiches Med. der Wilhelm-Pieek-Univ., Rembrandtstr. 16/17, DDR-2500 Rostock, GDR) 202, 18 (1990) The portal system and the hepatic artery in children with an extrahepatic cystic artery. Part 1: sonographic and plain duplex sonographie parameters. [In germ.] Grunert, D. et al. (Univ.-Kinderklinik, Rtirnelinstr. 19-23, D7400 Tfibingen, FRG) 202, 24 (1990) Endocardial fibroelastosis of the left ventricle in a patient with Alagille's syndrome. [In germ.] Kotthoff, S. et al. (Univ.-Kinderklinik, Kinderkard., Waldweg 33, D-3400 GOttingen, FRG) 202, 50 (1990) Mediastinal teratocarcinoma and pituitary stalk germinoma in a patient with Klinefelter's syndrome. [In germ.] KOnig, R. et al. (Univ.-Kinderklinik, Langenbeckstr. 1, D-6500 Mainz, FRG) 202, 53 (1990) Monatsschrift Kinderheilkunde (Berlin)
Intraspinal cord astrocytoma in a 3-year old girl. [In germ.] Wilken, B. et al. (Klinik ffir Neurop~id., Med. Univ., Kahlhorststr. 31-35, D-2400 LiJbeck 1, FRG) 138, 38 (1990) Neuroradiology (Berlin)
MR imaging of the various stages of normal myelination during the first year of life. Van der Knapp, M. S., Valk, J. (Valk, J., Dept. of Diagn. Rad., and Neurorad., Free Univ. Hosp., EO. Box 7057, NL-1007 MB Amsterdam, The Netherlands) 31, 459 (1990) Posterior fossa arteriovenous malformations. Angioarchitecture in relation to their hemorrhagic episodes. Monaco, R. G. et al. (Lasjannias, R, H6pital, Unit6 de Neurorad., 78 G6n6ral Leclerc, F-94275 Kremlin Bic~tre Cedex, France) 31, 471 (1990) * Compiled by Professor E. Willich, Heidelberg
Venous anomalies and abnormalities of the posterior fossa. Goulao, A. et al. (Lasjaunias, E, Unit6 de Neurorad. vasculaire diagn, et therapeutique, H6pital, 78 rue du G1. Leclerc, F-94275 Kremlin Bic4tre Cedex, France) 31, 476 (1990) Ectasia of arteries beyond the Circle of Willis. Dervin, J., Kendall, B. E. (Kendall, B. E., Lysholm Rad. Dept., The National Hosp., Queen Square, London WC1N 3BG, England) 31, 483 (1990) Gadolinium-DTPA enhanced MR imaging in tuberous sclerosis. Martin, N. et al. (Dept. of Rad., H6pital Beaujon, 100 Blvd. de Gdndral Leclerc, F-92118 Clichy, France) 31, 492 (1990) Joubert syndrome: a clinico-radiological study. Kendall, B. et al. (Dept. of Neurorad., The Hosp. for Sick Children, Great Ormond St., London WCIN 3JH, England) 31, 502 (1990) Occult spinal dysraphism: neuroradiological study. Tortori-Donati, R et al. (Serv. di Neurorad., Ospedale San Martino, 1-16132 Genova, Italy) 31, 512 (1990) Resoiution of spinal epidural vascular pseudotumor following baUoon occlusion of a postoperative vertebral arteriovenous fistula. Johnson, C.E. et al. (Dept. of Rad., The Hosp., Cornell Univ. Med. Center 525 East 68 St., New York, NY 10021, USA) 31,529 (1990) Wyburn-Mason syndrome. Patel, U., Gupta, S. C. (Dept. of Rad., Royal Chip dren's Hosp., Pendelbury, Manchester M27 1HA, England) 31, 544 (1990) Clinical and radiographic response of Langerhans' cell histiocytosis with chemotherapy. S~nchez de Toledo, J. et al. (Unit of Ped. Oncology, Hosp. Infantil Valle de Hebron, Paseo Valle de Hebron s/n, E-08035 Barcelona, Spain) 31, 547 (1990) MR demonstration of paravertebral lumbar meningomyelocele with diastematomyelia. Gupta, R.K., Sharma, A. (Inst. of Nucl. Med. and Allied Sciences, Probyn Rd., Delhi-110054, India) 31, 554 (1990) Piidiatrische Praxis (Miinchen)
Htiftsonographie beim Neugeborenen. Graf, R. (Landessonderkrankenhaus, A-8852 Stolzalpe, Austria) 39,611 (1990) Die Adrenoleukodystrophie. yon Brenndorff, I.A. et al. (Kinderabt. des Kreiskrankenhauses, Postfach 1520, D-7920 Heidenheim, FRG) 39, 631 (1990) Die terminale Niereninsuffizienz im Kindesalter als Folge prim/~r urologischer Erkrankungen. Ulsh6fer, B. et al. (Urol. Klinik im Zentrum Operative Med. II der Univ., Baldingerstr., D-3550 Marburg, FRG) 39, 665 (1990) Transfontanellare Neurosonographie. Amato, M. (Univ.-Frauenklinik, Schanzeneckstr. 1, CH-3012 Bern, Switzerland) 39,701 (1990) Iatrogen bedingte Fehlerquellen bei R6ntgenuntersuchungen traumatisierter Kinder. Brinkmann, H. (Kinderrad. Abt. der Rad. Klinik, Zentralkrankenhaus St. Jiirgenstr., D-2800 Bremen, FRG) 39, 709 (1990) (continued on p. 436)
Pediatric Radiology 9 Springer-Verlag 1990
Review
Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) W. H. McAlister 1, T. Herman 1 and L. P. Dehner 2 Departments of 1 Radiology and 2 Pathology,Division of Anatomic Pathology,Washington UniversitySchool of Medicine and St. Louis Children's Hospital, St. Louis, MO, USA Received: 4 December 1989;accepted: 4 December 1989
Sinus histiocytosis with massive lymphadenopathy (SHML) was initially described by Rosai and Dorfman in 1969 as a distinctive cfinicopathological entity differentiated from Langerhans' cell histiocytosis (LCH or histiocytosis X). Rosai-Dorfman disease is the generally applied eponym. Although the etiology remains unknown, the disease is thought to be a disorder of immune regulation or response to a presumed infectious agent with major manifestations in the lymph nodes with the resulting proliferation of sinusoidal histiocytes. Most efforts to identify a pathogen have culminated in indeterminant or negative results. In this and some other respects, SHML and LCH remain etiologic enigmas. The most frequent clinical manifestation of SHML is bilateral, nontender, painless, cervical lymphadenopathy; "proconsular" or "bull" neck is a term applied to the symmetrical cervical adenopathy which resembles the findings in Hodgkin's disease of the neck. Other nodal sites are involved as well including the mediastinal, retroperitoheal, and inguinal sites. Once SHML had been established as an entity in the lymph nodes, it soon became apparent that the disorder was not restricted to lymph nodes alone. In fact, of 40% of affected individuals have extranodal, multisystemic disease in a distribution not unlike LCH [1]. The purpose of this communication is to review the clinical, radiographic and pathological manifestations of SHML for the pediatric radiologist.
Histiocytoses Sinus histiocytosis with massive lymphadenopathy is but one of several histiocytic syndromes occurring predominantly in children. A brief consideration of these histiocytoses may help the understanding of a generally bewildering group of disorders. The differentiation of one histiocytic condition from another primarily relies upon the characterization of the type of "histiocyte" of which there are several mononuclear phagocytes including the Langerhans' cell, interdigitating reticulum cell and the
common phagocytic macrophage or histiocyte [2-4]. The Langerhans' cell, a dendritic cell normally found in the epidermis, is the diagnostic constitutent of histiocytosis X. Cytoplasmic Birbeck granules identifiable by electron microscopy and the expression of CD1 (T6 antigen) and H L A - D R on the cell membrane are the characteristic morphologic and immunophenotypic markers of the Langerhans' cell. The immunoreactivity for S-100 protein is not specific for Langerhans' cells although it is very useful when tissue is not available for the more specific studies [5]. In contrast to histiocytosis X, SHML is but one of a heterogenous group of histiocytic proliferations of the phagocytic or antigen processing cells. Infectious (Mycobacteria, Histoplasma) and metabolic etiologies (Gaucher's disease, Niemann-Pick disease) are examples of diseases with known etiologies whose histologic appearance is dominated by a histiocytic reaction. Erythroand lymphophagocytosis are the histologic hallmarks of infection (viral)-associated hemophagocytic syndrome (VAHS) and SHML. Epstein-Barr virus has been implicated in the pathogenesis, if not the direct etiology, of the VAHS. There are many similarities among the VAHS, familial erythrophagocytic histiocytosis and X-linked lymphoproliferative syndrome. In other words, the erythrophagocytosis is a nonspecific response to a variety of immunologic provocations. An immunologic pathogenesis is strongly suspected but unproven for both histiocytosis X and SHML. All of the histiocytoses which have been discussed to this point are regarded as benign processes of a probable reactive rather than of a neoplastic nature. Malignant histiocytosis (MH) and acute monoblastic leukemia are the two most familiar types of malignancies of mononuclear phagocytes. Recently, some questions have been raised about the differentiation of MH from peripheral T-cell lymphoma with a prominent histiocytic infiltrate; one example of the latter is the so-called Ki-1 lymphoma of childhood [6]. The extramedullary presentation of acute monoblastic leukemia may simulate MH.
426 Review of the literature
Clinicalfeatures Since the original description of SHML in 1969, a registry has been maintained by Rosai who has accumulated 365 cases as of 1988 [1]. The majority of patients present within the first two decades of life. There appears to be a slight predilection for blacks since 49% of cases occur in this race whereas the remainder are listed as caucasian (46%) or oriental (5%). Many of the black patients are from Africa and the Caribbean basin; the actual percentage of blacks with SHML may be higher because of infrequent reporting from these third world countries. In a series of 105 Nigerian children with persistent cervical lymphadenopathy, the incidence of SHML was 7.6% which is unlike the case in a group of children with similar symptoms from the St.Louis metropolitan area [7]. The male to female ratio is 1.4 to 1. Sixty-two percent of the patients are less than the age of 10 at presentation. However, the average age of patients in the registry is 19.7 years, including the large number of elderly patients with SHML [1, 8]. Perhaps a genetic predisposition exists as it has been described in two pairs of siblings and in a pair of identical twins [9]. Virtually all patients (97%) provide a history of bilateral cervical lymphadenopathy for a period of 39 months before medical attention is sought; the adenopathy may be asymmetric. Other nodal groups including the axillary, inguinal, hilar, a n d mediastinal lymph nodes are involved in 80% of patients; however, not all affected nodes are necessarily enlarged, but the microscopic changes of SHML are present in a biopsy. Extranodal disease has been reported in approximately 30% of cases with various sites in the head and neck region showing a particular predilection. The nasal cavity, salivary gland tissue, oral cavity, pharynx, tonsils, paranasal sinuses, trachea, orbit and eyelid are the specific affected locations [10]. Nasal obstruction and rhinorrhea due to mucosal infiltration by a mixture of histiocytes and chronic inflammatory cells are the clinical manifestations of a mass in the nasal cavity. Orbital involvement characteristically is manifested by proptosis. Two or more sites of SHML are seen in 50% of cases with extranodal head and neck disease [11]. When the trachea or bronchus is affected, stridor and even life threatening dyspnea may occur. Cutaneous infiltrates present as nodules or in some cases with a rash and may precede the lymphadenopathy. Subcutaneous lesions are less common than epidermal-based lesions but involvement may produce a panniculitis similar to Weber-Christian disease [12]. Bone pain or paralysis from an epidural lesion are other manifestations in a minority of patients [13]. Other than the presenting symptoms, the patients are generally in good health. Two-thirds of patients with SHML of the upper airway or oral cavity have infiltrative disease in other non-lymphoid sites (skin, bone, testes, orbits, eyelids, abdominal viscera, and central nervous system). Exclusive extrano-
W.H. McAlister et al.: Sinus histiocytosis(Rosai-Dorfman-disease) dal disease is more frequent in elderly individuals and in those with an underlying immune deficiency state. Cervical adenopathy is not an invariable finding in patients with extranodal involvement. When massive lymphadenopathy is present, often low grade fever (up to 102 ~ leukocytosis (up to 32 000), neutrophilia, and an elevated erythrocyte sedimentation rate are associated clinical and laboratory findings. Additionally, 80% of patients have a polyclonal hypergamma-globulinemia, and 65% have a hypochromic or normochromic normocytic anemia. The disease typically pursues an indolent clinical course. In approximately 50% of patients, the disease resolves without appreciable sequela, one-third have residual asymptomatic adenopathy and 17% have persistent symptomatology after 5 to 10years. Regression is usually heralded by diminution of the extranodal disease. The longest described clinical course has been 30 years [13]. The reported mortality is 7% and renal involvement has often been associated with a fatal outcome or an excessively prolonged course [14]. Seven percent of patients with SHML are found to have disorders such as Wiskott-Aldrich syndrome, circulating autoantibodies, rheumatoid arthritis, glomerulonephritis, brucellosis [15], amyloidosis, antiplatelet antibodies, joint disease or unusual infections of the lung, suggesting an underlying impaired immune system. These patients tend to be older, more frequently Western and white, and have more extensive mediastinal adenopathy. Evidence of an underlying immune deficiency disorder is a poor prognostic feature with a significantly increased mortality rate (43 %). Seven patients have been diagnosed with sinus histiocytosis at Children's Hospital. Five patients underwent spontaneous resolution of their lesions. Two were treated with chemotherapy, steroids and radiation therapy. All 7 are alive. One patient of particular interest is detailed below. He has been followed for 16 years and presented with bilateral proptosis and cervical adenopathy at age 3. One eye and some cervical nodes were biopsied. No therapy was given for 11/2years but because of keratitis and limitation of eye movements and lack of improvement he was given chemotherapy (vincristine and then chorambucil) for 2 years and responded. He had hypergammaglobulinemia and anemia. At age 13 years he developed massive abdominal lymphadenopathy and bilateral renal involvement. Both the kidney and retroperitoneal adenopathy were biopsied and confirmed to be SHML. He was placed back on systemic chemotherapy for 2 years and the adenopathy and renal involvement improved and the chemotherapy was discontinued. The kidneys have remained enlarged. He then developed bilateral lower extremity swelling and pain. Bone scintigraphy showed extensive skeletal abnormalities of increased uptake greatest around the joints of the lower extremities. Plain radiographs showed diffuse osteopenia. He was placed back on chemotherapy (Methotrexate) for 2 years and significantly improved. Except for short stature and anemia he is relatively asymptomtic at present.
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Fig.1. Sinushistiocytosiswithmassive lymphadenopathyshowingsinusoids distendedwithpale staininghistiocytes. H&E x 150/WIL89-2853F3
Figo2. Sinushistiocytosiswithmassive lymphadenopathyshowinginnumerable histiocyteswithintracytoplasmic lymphocytes(arrows). H&E x 150/WIL8254F0
Pathologicfeatures The diagnosis of SHML is readily established by the presence of the histologic alterations in an affected lymph node. When the disease is predominately manifested in an extranodal site, a pathologic diagnosis can be made but there is a greater likelihood of overlooking SHML in favor of nonspecific chronic inflammation and fibrosis, chronic osteomyelitis in the case of a bony lesion or one of several other entities producing histiocytic infiltrates in the skin. The possibility of SHML may not occur until a lymph node biopsy is performed and even then, there may be failure to appreciate the significance of the changes. When a group of lymph nodes are excised, they are generally matted together by thickened bands of capsular and pericapsular connective tissue. In this respect, the lymph nodes resemble those of nodular sclerosis Hodgkin's disease. However, the capsule may be a thin, delicate fibrous sheath. The architecture of the lymph node is in-
tact in respect to the corticomedullary areas, but there is accentuation of cortical follicles as a result of hyperplasia of the germinal centers and surrounding cortical mantle. Distention of the sinusoids by pale-staining histiocytes intermixed with variable numbers of mature plasma cells is the characteristic feature of SHML (Fig.l). Numerous plasma cells are also found in the paracortical tissues. The histiocytes tend to be loosely cohesive. Individual histiocytes contain one or more intact lymphocytes in the cytoplasm (Fig. 2). The lymphocytes show no evidence of fragmentation or degeneration which would be anticipated if these cells were simply phagocytized; rather the lymphocytes have penetrated the cytoplasm in a process known as emperipolesis where the lymphocytes continue to have free movement within the histiocyte. Because lymphocyte emperipolesis is thought to relate to antigen presentation, SHML may represent a derangement of the process by which histiocytes contact lymphocytes for antigen delivery. In extranodal sites, the presence of lymphocyte-
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Fig.3. A cervical adenopathy on this Tl-weighted coronal neck image in a young child. (Case courtesy of Dr. Walter Berdon.) Fig.4. Multiple cervical lymph nodes shown by sonography in a 6year-old boy Fig.5. Hilar adenopathy seen on a chest roentgenogram in an llyear-old girl Ng.6. Retroperitoneal adenopathy as shown on this transverse sonogram stretching the celiacartery in a 6-year-oldboy
when a biopsy has been obtained from an extranodal lesion. The differential diagnosis based upon the histologic examination is limited when the nodal biopsy shows the aforementioned changes. Virtually all histiocytic proliferative disorders have a common pattern of nodal involvement with expansion of the subcapsular and interfolicular sinusoids. Large mononuclear and occasional multinucleated cells with pale, eosinophilic cytoplasms and a reniform shaped nucleus with a cleft or groove across the nuclear membrane are diagnostic of Langerhans' cell histiocytosis. Ultrastructurally, the Langerhans' cell contains the cytoplasmic pentilaminar complex known as a Birbeck granule [2]. CD1 (T6) is expressed in the cell membrane, but in the case of SHML, the histiocytes are nonreactive. Both Langerhans' cells and the histiocytes of SHML are S-100 protein positive but the reaction is stronger in the Langerhans' cells [2, 4, 11]. The presence of lymphophagocytic histiocytes and S-100 protein positivity is regarded as diagnostic of SHML [4].
containing histiocytes is an important clue to the pathologic diagnosis. As SHML regresses, the affected lymph node becomes progressively fibrotic with replacement of the parenchyma by collagen deposition. At this stage, many of the diagnostic features and cells are less apparent. Nonspecific fibroinflammatory features are likely to result in an indeterminant diagnosis. This is especially problematic
W.H. McAlister et al.: Sinus histiocytosis (Rosai-Dorfman-disease)
Fig.7 a, b. Intrinsic renal involvement and retroperitoneal nodal involvement in a 13-year-oldboy. a Computed tomography delayed scan shows an enlarged right kidney with a small area of nephrogram, retroperitoneal nodes, and nephrogram defect in the left kidney. b Intravenous urography demonstrated enlarged kidneys with distorted collectingsystems especiallythe right and displacement of the ureters from lymph nodes Fig.8. Left orbital mass displacingthe globe laterally and destroying bone in this 5-year-old girl as shown on coronal computerized tomography
Imaging manifestations Since SHML is a multifocal and multisystemic condition in a substantial proportion of patients, the imaging features are occasionally confounding because of the differential diagnostic possibilities. As noted previously, the cervical lymphadenopathy is bilateral and often massive with individual nodes measuring up to 6 cm in diameter. All major lymph node groups in the neck may be involved, but there are no distinguishing features of the adenopathy by sonography, computed tomography (CT) or magnetic resonance imaging (MRI) (Fig. 3-4) [16]. The lymph nodes have the ability to uptake gallium [17]. Axillary and inguinal lymph nodes are enlarged in 38% and 44% of cases, respectively. These nodes are
429
usually smaller than those in the neck and therefore, the scans may detect involvement which was less obvious on physical examination. Mediastinal and hilar adenopathy with a unilateral or bilateral distribution is present in 3040% of patients (Fig.5) [18]. When the lung parenchyma is involved, there is extension from the hila along vascular septae producing accentuated and widened interstitial markings. Reticulonodular infiltrates are unusual. Carpenter, et al. [19] described diminished perfusion of one lung on chest roentgenography which was probably secondary to hilar or bronchial mucosal infiltration. The retroperitoneal space is an infrequent site of disease. However, retroperitoneal lymphadenopathy may distort vessels (Fig.6) and is often accompanied by extrinsic ureteral obstruction and/or parenchymal involvement of the kidney. The distortion and displacement of the ureters by a fibrous reaction are similar to that seen in retroperitoneal fibrosis (Ormand's disease) and malignant lymphoma with sclerosis [9]. Sonography can demonstrate the enlarged lymph nodes and CT the extensive encasement of the kidneys by the nodal masses [9]. Enlargement of the kidneys with distortion of the collecting systems can be shown by intravenous urography, CT, MRI, or sonography (Fig.7a, b). When the kidneys are diffusely enlarged, the findings may be confused with leukemic or lymphomatous infiltrates [20]. The renal arteries can be stretched and splayed on arteriography. Retroperitoneal lymphangiography shows a reticular pattern in the enlarged lymph
430
W.H. McAlister et al.: Sinus histiocytosis(Rosai-Dorfman-disease) Second in frequency to the upper aero-digestive tract for extranodal involvement by SHML is the orbit, globe and eyelid in 7-10% of patients [1, 23]. Extraconal soft tissue masses with proptosis are the major expression of orbital disease (Fig. 8). Enlargement of the orbits can be shown on plain radiographs (Fig. 9). The orbital and adjacent paranasal sinus masses are delineated by CT and MRI; the masses on CT are enhanced with iodinated contrast media. Infiltration of the intraorbital fat and muscle is also shown by CT [24]. The bones of the orbit may undergo osteolysis or sclerosis (Fig. 10) [25]. Very few cases of involvement of the globe have been reported [26]; masses in the cornea, epibulbar conjunctiva and uveal tract have been described [27]. There is a correlation between ophthalmic and nasal involvement
[28].
Fig.9. Expansion of the orbits and soft tissue orbital masses in a 4year-old boy with marked proptosis Fig. 10. Orbital sclerosisas seen on a roentgenogram in a 13-year-old boy nodes similar to the appearance in non-Hodgkin's lymphoma. Extranodal SHML in the head and neck region is present in approximately 75% of patients with evidence of disease extrinsic to the lymph nodes. Discrete polypoid masses or thickened nasal mucosa are noted on plain radiographs and CT. Masses may be identified in the paranasal sinuses, parotid and submandibular glands, oral cavity, pharynx, tonsil and larynx. The paranasal sinuses may be opacified and occasionally, the adjacent bone is eroded on plain radiographs and CT. Submucosal masses in the larynx, trachea and bronchi are uncommon, but can cause marked stridor, if not life threatening dyspnea [21]. Masses in the retropharyngeal space may compromise the airway as well. Extrinsic obstruction of trachea has been reported by Okada, et al. [16]; submucosa involvement of the trachea with sparing of the cartilagenous rings has been shown by MRI. Thyroid involvement is generally not accompanied by functional abnormalities. In a patient who was studied by sonography, the gland was diffusely enlarged with a mixed echogenic pattern, including prominent hypoechoic areas [22].
Skeletal manifestations are found in 5-10% of patients. Multiple small lytic lesions with sharply or poorly defined borders are more common than large, mixed or sclerotic lesions (Fig. 11) [29-31]. There is no predilection for a specific site in the bone nor for specific bones. Schweitzer and Bobier [32] reported a patient with multiple lyric lesions in the skull; irregular margins surrounded by halos of dense sclerotic bone were noted by plain radiographs. The differential diagnosis of these bony lesions in children include multifocal osteomyelitis, Langerhans' cell histiocytosis and metastatic neuroblastoma. Involvement of the central nervous system is usually confined to the intraspinal and intracranial subarachnoidal, subdural and epidural spaces [33]. Plaque-like lesions on the meninges simulate a meningioma [34]. Paraplegia from an extradural mass at the cervical and thoracic levels has been reported by Haas, et al. [35]. Dural-based lesions of the middle and posterior fossa produced erosion of the middle fossa and petrous bone. A contrast enhancing leptomeningeal mass with edema of the adjacent brain was shown by CT. High density intracranial masses are rare, but have been demonstrated by CT [35]. Hepatosplenomegaly is distinctly uncommon in SHML. A diffusely enlarged liver was reported in a 7year-old patient whose liver biopsy had lymphophagocytic histiocytes in the portal tracts [36]. However, imaging studies and radionucleide scans of the liver and spleen have a low yield in this disease. Other organs which have been sites of SHML are the thymus, testicle and heart. Thymic and cardiac involvement contribute to mediastinal enlargement.
Treatment
Because of SHML's frequently self-remitting course, the occasional good responses to therapy do not allow formulation of meaningful conclusions about therapy. Surgical resection of soft tissue masses, systemic chemotherapy, prednisone, radiation therapy have been associated with improvement in several patients, but only case reports have been described. No study of treatment efficacy is available.
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References
Fig.lla, b. Medullary poorly defined lyric lesions with focal sclerosis are seen in the radius and ulna. b Sclerotic lesions of the distal femoral epiphysis and proximal tibia are seen in a 9-year-old girl. (Contributed by T. C. Demos, M. D.; previous publication in Pediatr Radio115: 259,1985)
Summary Sinus histiocytosis with massive lymphadenopathy ( R o s a i - D o r f m a n disease) is a unique disease of u n k n o w n etiology with a childhood predilection. Reports have established the worldwide distribution of the disorder. A l t h o u g h peripheral l y m p h a d e n o p a t h y is the m o s t c o m m o n m o d e of presentation, n u m e r o u s studies and individual case reports have established the fact that 30-40% of affected individuals have extranodal manifestations particularly in the h e a d and neck region where the a d e n o p a t h y tends to b e concentrated. As yet, the pathogenesis of S H M L has n o t b e e n established but speculation relates the disorder to an aberrant response to an unspecified antigen, possibly an infectious organism. Because of the clinical manifestations, the radiographic features of S H M L are not p a t h o g n o m o n i c but rather e n g e n d e r a differential diagnosis which includes l y m p h o m a t o u s , p s e u d o l y m p h o m a t o u s and infectious conditions. A p p r o p r i a t e imaging of patients with S H M L d e p e n d s u p o n presenting s y m p t o m s and signs. Radionuclide b o n e scanning m a y be helpful in the evaluation of suspected skeletal lesions or joint symptoms. Gallium scanning is often positive in nodal disease and CT, M R I and s o n o g r a p h y are helpful in the evaluation of extranodal sites of i n v o l v e m e n t such as the orbit, eyelid, u p p e r aero-digestive tract and retroperitoneum.
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23. Karcioglu ZA, Allam B, Insler MS (1988) Ocular involvement in sinus histiocytosis with massive lymphadenopathy. Br J Ophthalmol 8:153 24. Asai A, Matsutani M, Kohno T, Fujimaki T, Tanaka H, Kawaguchi K, Koike M, Takakura K (1988) Leptomeningeal and orbital benign lymphophagocytic histiocytosis. J Neurosurg 69:610 25. Siegel MJ, Shackelford GD; McAlister W H (1979) Sinus histiocytosis: some radiologic observations. A JR 132:783 26. Friendly DS, Font RL, Rao N A (1977) Orbital involvement in "Sinus" histiocytosis. Arch Ophthalmo195: 2006 27. Stopak SS, Dreizen NG, Zimmermann LE, O'Neill JF (1988) Sinus histiocytosis presenting as an epibulbar mass. Arch Ophthalmo1106:1426 28. FoucarE, RosaiJ, Dorfman RF (1979) The ophthalmologic manifestations of sinus histiocytosis with massive lymphadenopathy. A m J Ophthalmo187:354 29. Puczynski MS, Demos TC, Suarez CR (1985) Sinus histiocytosis with massive lymphadenopathy: skeletal involvement. Pediatr Radio115:259 30. Walker PD, Rosai J, Dorfman RF (1982) The osseous manifestations of sinus histiocytosis with massive lymphadenopathy. A m J Clin Path 75:131 31. U n n i K K (1988) Case report 457. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) presenting as lesion in the sacrum. Skeletal Radio117:129
32. SchweitzerVG, Bobier GD (1986) Sinus histiocytosis with massive cervical lymphadenopathy. Case report and literature review. Ann Otol Rhinol Laryngo195: 331 33. Carey MR Case CP (1987) Sinus histiocytosis with massive lymphadenopathy presenting as a meningioma. Neuropathol Appl Neurobio113:391 34. Mir R, Aftalion B, Kahn LB (1985) Sinus histiocytosis with massive lymphadenopathy and unusual extranodal manifestations. Arch Pathol Lab Med 109:867 35. Haas R J, Helmig MSE, Meister P (1981) Sinus histiocytosis with massive lymphadenopathy and epidural involvement. Hamatol Bluttransfus 27:239 36. Brown RE, D'Cruz C A (1987) Sinus histiocytosis massive lymphadenopathy syndrome: histiogenesis of the hepatic lesion. Ann Clin Lab Sci 17:162
W. H. McAlister Mauinckrodt Institute of Radiology Washington University School of Medicine and St. Louis Children's Hospital 510 S. Kings Highway St.Louis, MO 63110 USA
Literature in pediatric radiology* Fortschritte aufdem Gebiete der R/Jntgenstrahlen und der neuen bildgebenden Verfahren (Stuttgart)
Die Kriterien eines Shwachmau-Diamond-Syndroms bei zwei Brtidern. Henze, E., Hitzemann, T. (Inst. ffir R6ntgenol. und Strahlenheilkunde, Klinikum, Bismarckstr. 6, D-4950 Minden, FRG) 152,100 (1990) Acro-spondylar variant of punctate epiphyseal dysplasia (report of two cases) Kozlowski, K., Majewski, E (Royal Alexandra Hosp. for Children, Camper down, Pyrmont Bridge Rd., Sydney 2050 N.S.W., Australia) 152, 115 (1990) Klinische P/idiatrie (Stuttgart)
Delayed fontanelle closure in infants with cyanotic cardiopathy. [In germ.] Rusche, T. et al. (Klinik for Kinderheilkunde des Bereiches Med. der Wilhelm-Pieek-Univ., Rembrandtstr. 16/17, DDR-2500 Rostock, GDR) 202, 18 (1990) The portal system and the hepatic artery in children with an extrahepatic cystic artery. Part 1: sonographic and plain duplex sonographie parameters. [In germ.] Grunert, D. et al. (Univ.-Kinderklinik, Rtirnelinstr. 19-23, D7400 Tfibingen, FRG) 202, 24 (1990) Endocardial fibroelastosis of the left ventricle in a patient with Alagille's syndrome. [In germ.] Kotthoff, S. et al. (Univ.-Kinderklinik, Kinderkard., Waldweg 33, D-3400 GOttingen, FRG) 202, 50 (1990) Mediastinal teratocarcinoma and pituitary stalk germinoma in a patient with Klinefelter's syndrome. [In germ.] KOnig, R. et al. (Univ.-Kinderklinik, Langenbeckstr. 1, D-6500 Mainz, FRG) 202, 53 (1990) Monatsschrift Kinderheilkunde (Berlin)
Intraspinal cord astrocytoma in a 3-year old girl. [In germ.] Wilken, B. et al. (Klinik ffir Neurop~id., Med. Univ., Kahlhorststr. 31-35, D-2400 LiJbeck 1, FRG) 138, 38 (1990) Neuroradiology (Berlin)
MR imaging of the various stages of normal myelination during the first year of life. Van der Knapp, M. S., Valk, J. (Valk, J., Dept. of Diagn. Rad., and Neurorad., Free Univ. Hosp., EO. Box 7057, NL-1007 MB Amsterdam, The Netherlands) 31, 459 (1990) Posterior fossa arteriovenous malformations. Angioarchitecture in relation to their hemorrhagic episodes. Monaco, R. G. et al. (Lasjannias, R, H6pital, Unit6 de Neurorad., 78 G6n6ral Leclerc, F-94275 Kremlin Bic~tre Cedex, France) 31, 471 (1990) * Compiled by Professor E. Willich, Heidelberg
Venous anomalies and abnormalities of the posterior fossa. Goulao, A. et al. (Lasjaunias, E, Unit6 de Neurorad. vasculaire diagn, et therapeutique, H6pital, 78 rue du G1. Leclerc, F-94275 Kremlin Bic4tre Cedex, France) 31, 476 (1990) Ectasia of arteries beyond the Circle of Willis. Dervin, J., Kendall, B. E. (Kendall, B. E., Lysholm Rad. Dept., The National Hosp., Queen Square, London WC1N 3BG, England) 31, 483 (1990) Gadolinium-DTPA enhanced MR imaging in tuberous sclerosis. Martin, N. et al. (Dept. of Rad., H6pital Beaujon, 100 Blvd. de Gdndral Leclerc, F-92118 Clichy, France) 31, 492 (1990) Joubert syndrome: a clinico-radiological study. Kendall, B. et al. (Dept. of Neurorad., The Hosp. for Sick Children, Great Ormond St., London WCIN 3JH, England) 31, 502 (1990) Occult spinal dysraphism: neuroradiological study. Tortori-Donati, R et al. (Serv. di Neurorad., Ospedale San Martino, 1-16132 Genova, Italy) 31, 512 (1990) Resoiution of spinal epidural vascular pseudotumor following baUoon occlusion of a postoperative vertebral arteriovenous fistula. Johnson, C.E. et al. (Dept. of Rad., The Hosp., Cornell Univ. Med. Center 525 East 68 St., New York, NY 10021, USA) 31,529 (1990) Wyburn-Mason syndrome. Patel, U., Gupta, S. C. (Dept. of Rad., Royal Chip dren's Hosp., Pendelbury, Manchester M27 1HA, England) 31, 544 (1990) Clinical and radiographic response of Langerhans' cell histiocytosis with chemotherapy. S~nchez de Toledo, J. et al. (Unit of Ped. Oncology, Hosp. Infantil Valle de Hebron, Paseo Valle de Hebron s/n, E-08035 Barcelona, Spain) 31, 547 (1990) MR demonstration of paravertebral lumbar meningomyelocele with diastematomyelia. Gupta, R.K., Sharma, A. (Inst. of Nucl. Med. and Allied Sciences, Probyn Rd., Delhi-110054, India) 31, 554 (1990) Piidiatrische Praxis (Miinchen)
Htiftsonographie beim Neugeborenen. Graf, R. (Landessonderkrankenhaus, A-8852 Stolzalpe, Austria) 39,611 (1990) Die Adrenoleukodystrophie. yon Brenndorff, I.A. et al. (Kinderabt. des Kreiskrankenhauses, Postfach 1520, D-7920 Heidenheim, FRG) 39, 631 (1990) Die terminale Niereninsuffizienz im Kindesalter als Folge prim/~r urologischer Erkrankungen. Ulsh6fer, B. et al. (Urol. Klinik im Zentrum Operative Med. II der Univ., Baldingerstr., D-3550 Marburg, FRG) 39, 665 (1990) Transfontanellare Neurosonographie. Amato, M. (Univ.-Frauenklinik, Schanzeneckstr. 1, CH-3012 Bern, Switzerland) 39,701 (1990) Iatrogen bedingte Fehlerquellen bei R6ntgenuntersuchungen traumatisierter Kinder. Brinkmann, H. (Kinderrad. Abt. der Rad. Klinik, Zentralkrankenhaus St. Jiirgenstr., D-2800 Bremen, FRG) 39, 709 (1990) (continued on p. 436)
