GijNHAN
J Oral Maxillofac 49:205-209.
205
ET AL
Surg
1991
Sinus Histiocytosis With Massive Lymphadenopathy: A Case With Facial Bones Involvement iiMER
GijNHAN,
DDS, PHD,* RIFKI FINCI, MD,t YILMAZ GUNAYDIN, AND IBRAHIM SOMUNCU, MD3
Sinus histiocytosis with massive lymphadenopathy (SHML) is a nonneoplastic, pseudolymphomatous disease with a broad clinical spectrum confined mainly to lymph nodes. Because it was first described in 1969 by Rosai and Dorfman,’ it is also known as Rosai-Dorfman disease. Most patients are children or young adults (mean age, 19.7; female/male ratio, 1.4:1) who present with painless cervical lymphadenopathy.’ Other lymph node groups often were also involved. This self-limited disease is usually accompanied by hypergamma-globulinemia, elevated erythrocyte sedimentation rate, neutrophilic leucocytosis, anemia, and fever. Clinically, the disease is characterized by its often protracted, although benign, clinical course, usually terminating in spontaneous resolution of the lesion. However, some cases are fatal (7%), with multisystem involvement and immunologic dysfunctions.’ No specific cause has been identified and it was speculated that the pathogenesis is related to infectious agents or disturbed immunologic functions.‘.4 The microscopic appearance of the involved lymph nodes is distinctive. There is capsular fibrosis and striking dilatation of the lymph node sinuses, with proliferation of histiocytes and plasma cells, and phagocytized lymphocytes (emperiopolesis) and erythrocytes.5 We report a unique case of SHML involving the mandible, maxilla, and zygomatic bones as well as the cervical, axillary. and inguinal lymph nodes and upper respiratory tract.
DDS, PHD,*
FIGURE I, Computed tomography scan showing upper respiratory tract and bone involvement (arrows).
Report of a Case A 20-year-old white man presented with a S-year history of pain and enlargement in the left mandible. He had also been complaining from bilateral nasal obstruction, rhinitis, epistaxis, and headache since 1976. Previously, he had been repeatedly treated for sinusitis and rhinitis with antibiotics and operated on (Caldwell-Luc in
Received from Giilhane Military Medical Academy and Medical School, Ankara, Turkey. * Associated Professor, Department of Pathology. t Professor and Chairman, Department of Pathology. f Associated Professor, Department of Oral Surgery. § Associated Professor, Department of Radiology. Address correspondence and reprint requests to Dr Giinhan: Giilhane Askeri Tip Akademisi. Patoloji Biiliimii, Etlik 06018, Ankara. Turkey. 0 1991 geons
American
Association
0278-2391191/4902-0020$3.00/O
of Oral
and Maxillofacial
Sur-
FIGURE 2. Computed tomography scan showing nasopharyngeal mass (arrows).
206
SHML WITH FACIAL BONES INVOLVEMENT
Microscopically, the lymph node biopsy specimen showed marked dilatation of the sinuses and proliferation of histiocytes, with vesicular nuclei, large nucleoli, and abundant pale eosinophilic cytoplasm. Mature lymphocytes and plasma cells accompanied the histiocytes. Lymphophagocytosis was evident. Infiltration affected the normal nodal architecture, although residual germinal centers were found (Figs 5 and 6). There was capsular fibrosis. The biopsy specimen of the nasal lesion (Fig 7) and mandibular bone (Fig 8) showed the presence of a similar infiltrate, including histiocytes, plasma cells, neutrophilic leucocytes, and lymphocytes. Necrosis, granulomatous infiltration, and giant cells were absent. There were no nuclear grooves in the histiocytes. The mandibular lesion showed slight fibrosis as well as histiocytic infiltration. Histologic stains did not show any storage in the histiocytes. Immunoperoxidase staining for S- 100 protein (avidinbiotin-peroxidase complex; Dako, Denmark) was carried out. The majority of the histiocytes were positively stained both in the lymph node and bone biopsies (Fig 9). With the diagnosis of SHML and extranodal involvement, the patient was treated with chemotherapy (prednisolone, 40 mg/d, and cyclophosphamide, 50 mg three times per day, for six periods of 14 days with ICday intervals between) and radiotherapy (total of 50 Gy to nasopharynx and paranasal sinuses only). After the treatment, the regional lymph nodes and the upper respiratory tract masses became smaller (Fig 10). There were no changes in the bone lesions. Because the air passages were opened, some complaints disappeared. Laboratory findings showed no significant difference, except the erythrocyte sedimentation rate showed a transient decrease. At the end of our 16 months of follow-up, the patient is alive with disease. were performed.
FIGURE 3. Lytic defects are seen in right and left mandibular corpus (arrows).
1978 and bilateral antrostomy in 1982) twice without establishment of a histologic diagnosis. Physical examination showed left mandibular and nasal masses, bilateral cervical, axillary and inguinal lymphadenopathy, and hepatosplenomegaly. The lymph nodes were firm and tender. There was a history of fatique, weight loss, fever, and joint pains (aspirin relieved the pain), the last developing recently. Radiologically, there were maxillary, ethmoidal, and sphenoidal sinus, nasal cavity, and nasopharyngeal softtissue involvement (Figs 1 and 2). The right and left mandibular corpus and ramus, and the maxillary and zygomatic bones were also involved (Figs 3 and 4). The osseous lesions were destructive, lytic, and ill-defined, without sclerotic margins. They were mainly medullary, but on the left side of the mandible, cortical destruction and soft-tissue involvement were noticed. Conventional radiographic and ultrasonographic investigations and computerized tomography (CT) showed no other bone, organ, or soft-tissue involvement. Table I lists the sites of nodal and extranodal involvement. Abnormal laboratory findings were as follows: erythrocyte sedimentation rate, 106 mm/h (normal, 20 mm/h); IgG, 2,650 mg/dL (normal, 800 to 1,800 mg/dL); albumin, 3.4 g/dL (normal, 4.5 to 5.5 g/dL); T helper cells, 22% (normal, 60%); T suppressor cells, 13% (normal, 35%). Bone marrow aspiration was normocellular. Inguinal lymph node, left mandibular, and nasal cavity biopsies
Discussion Sinus histiocytosis with massive lymphadenopathy has a very broad clinical spectrum, with outcomes varying from spontaneous remission to lethal infiltration of vital organs.396 There are 365 cases in Rosai’s established case registry.’ Because of the rarity of the disease, little progress has been made concerning the understanding of its pathogenesis.
FIGURE 4. Computed tomography scan of maxilla (A) and mandible (B) showing lytic, ill-defined lesions (arrows).
GUNHAN
207
ET AL
Table 1. Sites of Involvement in the Presented Case of SHML Lymph nodes (B) Cervical Axillary Inguinal* Extranodal tissues Nasal cavity* Sinuses (B) Maxillary Ethmoidal Sphenoidal Nasopharynx Liver Spleen Bone Mandible, corpus,*t Maxilla Zygoma (B)
and ramus (R and L)
FIGURE 6. The sinuses are filled with histiocytes containing phagocytized lymphocytes (emperiopolesis) (hematoxylin-eosin stain. original magnification X500).
The histology of the lymph nodes in SHML is typical and can be readily recognized. However, the appearance of the extranodal lesions presents difficulties in diagnosis and usually require the identification of the lesions from lymph nodes to establish the diagnosis.’ In extranodal involvement, the microscopic findings may be very similar to the lymph nodes presentations, with the presence of vascular proliferations and vessels highlighted by perivascular rows of plasma cells. I2 In some cases, the extranodal lesions may represent the predominant manifestation of the disease and precede the detection of the lymphadenopathy.879 The main complaints in the present case were related to extranodal manifestations and led to the bone, nasal, and lymph node biopsies.
The most frequent extranodal sites are the upper respiratory tract,’ orbit and eyelid,‘” and skin.’ Less frequent sites are bone,” the nervous system,” gastrointestinal tract,i3 salivary glands, tonsil, oral mucosa and tongue,’ lung,14 thyroid,” kidney,16 and testis. ” Sometimes there is widespread multisystem involvement.6”7 Table 1 summarizes the sites of nodal and extranodal involvement in the present case. Bone involvement is rare and usually multiple. Radius, ulna, tibia, femur, and Iibula are the most commonly affected long bones; the less frequently involved bones are skull, vertebral bodies, pelvis, phalanges, metacarpals, ribs, and maxilla.” The lesions usually are medullary, but cortical defect also may be present. No periosteal reaction is observed and central calcification is absent. In healing cases, lytic lesions may show a continuous decrease in size or may develop a sclerotic border.” Bone involvement is usually found together with other extranodal manifestations such as in the nasal and paranasal sinuses.” The present case is a prime ex-
FIGURE 5. SHML-produced changes in the architecture of a lymph node. There are only a few residual germinal centers (hematoxylin-eosin stain. original magnification X35).
FIGURE 7. Nasal cavity involvement by SHML. There is a large subepithelial collection of histiocytes, lymphocytes, and plasma cells (hematoxylin-eosin stain, original magnification X200).
Except for biopsied sites, involvement was based on clinical, radiologic. and ultrasonographic findings. Abbreviations: B, bilaterally; L. left: R, right. * Confirmed with biopsy. t Involvement of soft tissue on left.
208
FIGURE 8. Bone involvement by SHML. Note the area of proliferating histiocytes (hematoxylin-eosin stain, original magnification X200).
ample of the marked involvement of the facial bones, with the radiologic findings compatible with other reports.““* It is suggested that in the presence of extranodal involvement with histologic features that closely mimic SHML of lymph nodes makes a presumptive diagnosis possible.2 In the absence of the typical histiocytes and lymphophagocytosis, a positive diagnosis cannot be made. The microscopic appearance of the bone and nasal biopsy specimens in our case were very similar to what was seen in the lymph nodes and the diagnosis were made in the light of the latter findings. Some extranodal involvements, especially without distinctive nodal changes, may be confused with a variety of other histiocytic disorders. Re-
SHML WITH FACIAL BONES INVOLVEMENT
ports of cases of SHML show that histologic diagnosis is often confused with malignant histiocytosis, histiocytosis X, Hodgkins’ disease, granulomatous disease, xanthogranuloma, lipid storage disease, and nonspecific inflammations.7*9311’i9 Radiographically, bone involvement in SHML simulates histiocytosis X, metastatic malignancy, sarcoidosis, lipid storage disorders, and neurotibromatosis with osseous infiltration. ‘i Recently, immunohistochemical demonstration of S-100 protein positivity in histiocytes has provided a useful aid in the diagnosis of suspected SHML cases2 Although the nature and etiology of SHML are still questionable, the disease bears characteristics of a state of aberrant immune function. Sinus histiocytosis with massive lymphadenopathy histiocytes show S-100 protein and a-lantichymotrypsin positivity and lysozyme negativity.20 The “histiocytes” in this disease may not be mature histiocytes at all, but, rather, relatives of the interdigitating reticulum cells (IDRC) or t-zone histiocytes, more related to Langerhans’ cells or precursors of histiocytes than true histiocytes. As seen in Figure 9, histiocytes observed both in the lymph node and bone lesions showed strong cytoplasmic S-100 protein positivity. Extranodal disease is responsible from various symptoms, including neurologic manifestationsI related to compression, and nasal obstruction.7 Our patient had severe headaches for a long time that disappeared after treatment resulted in opening of the air passages. Repeated clinic laboratory testing showed consistently elevated polyclonal IgG val-
FIGURE 9. S-100 protein-positive histiocytes (arrows) in lymph node (Zefr) and bone (right) biopsies (avidin-biotin peroxidase immunostain with hematoxylin counterstain, original magnification X200).
209
GUNHAN ET AL
Acknowledgment The authors thank Dr J. Rosai (Yale University) for his kind comments about this case.
References I. Rosai J, Dorfman RF: Sinus histiocytosis
FIGURE 10. scan.
Posttreatment
opening of air passages seen on CT
ues, hypoalbuminemia, low T-subset ratios, and a high erythrocyte sedimentation rate. Except for the erythrocyte sedimentation rate, abnormal laboratory findings persisted despite the therapy. Approximately 10% of the patients with SHML have clinically significant hematologic and immunologic abnormalities such as glomerulonephritis, joint disease, Wiskott-Aldrich syndrome, unusual infections, and miscellaneous conditions (amyloidosis, increased serum viscosity, multiple myelomaIgA kappa, Raynaud’s phenomenon, and asthma).4 Fatality in patients with SHML is usually due to immunologic dysfunction and infectious complications. Foucar, Rosai, and Dorfman3 reported tindings in 14 patients who died with nodal and extranodal involvement, immunologic dysfunction, and unusual infections. Many patients have been subjected to delay in diagnosis.5.‘1V16 Similarly, our patient had been treated repeatedly for nonspecific inflammations of the nasal cavity and sinuses for 12 years. The final diagnosis was made with a combination of lymph node, nasal, and bone biopsies. Some cases of SHML show spontaneous resolution; some require therapy, especially ones with multisystem involvement and immunologic abnormalities. Reports about treatment mention from inconsistent results. Steroids, antibiotics, irradiation, and surgery have been used. Although the combined treatment in our patient relieved some complaints, the final results were not considered satisfactory.
with massive lymphadenopathy. A newly recognized benign clinicopathologic entity. Arch Path01 Lab Med 87:63, 1%9 2. Foucar E. Rosai J. Dorfman RF: Sinus histiocvtosis with massive lymphadenopathy. Current status and future directions. Arch Dermatol 124: 1211. 1988 3. Foucar E. Rosai J, Dorfman RF: Sinus histiocytosis with massive lymphadenopathy. An analysis of 14 deaths occuring in a patient registry. Cancer 54:1834. 1984 4. Foucar E, Rosai J, Dorfman RF: Immunologic abnormalities and their significance in sinus histiocytosis with massive lymphadenopathy. Am J Clin Path01 82:515. 1984 5. Rosai J, Dorfman RF: Sinus histiocytosis with massive lymphadenopathy: A pseudolymphomatous benign disorder. Cancer 30: 1174, 1972 6. Buchino JJ, Byrd RP. Kmetz DR: Disseminated sinus histiocytosis with massive lymphadenopathy. Its pathologic aspects. Arch Path01 Lab Med 106: 13, 1982 7. Foucar E. Rosai J. Dorfman RF: Sinus histiocytosis with massive lymphadenopathy. Ear, nose and throat manifestations. Arch Otolaryngol 104:687, 1978 8. Thawerani H, Sanchez RL, Rosai J, et al: The cutaneous manifestations of sinus histiocytosis with massive lymphadenopathy. Arch Dermatol 114: 191. 1978 9. Suster S. Cartagena N. Cabella-Inchausti B, et al: Histiocytic lymphophagocytic panniculitis. An unusual extranodal presentation of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). Arch Dermatol 124:1246, 1988 10. Foucar E. Rosai J. Dorfman RF: The ophthalmologic manifestations of sinus histiocytosis with massive lymphadenopathy. Am J Ophthalmol 87:354. 1979 11. Walker PD, Rosai J. Dorfman RF: Osseous manifestations of sinus histiocytosis with massive lymphadenopathy. Am J Clin Path01 75131, 1981 12. Foucar E, Rosai J. Dorfman RF, et al: The neurologic manifestations of sinus histiocytosis with massive lymphadenopathy. Neurology 32:365, 1982 13. Osborne BM, Hagemeister FB, Butler JJ: Extranodal gastrointestinal sinus histiocytosis with massive lymphadenopathy. Am J Surg Path01 5603, 1981 14. Carpenter RJ. Banks PM, McDonald TJ. Sanderson DR: Sinus histiocytosis with massive lymphadenopathy 1Rosai-Dorfman disease): Report of a case with respiratory tract involvement. Laryngoscope 88:1%3, 1978 15. Larkin DFP, Dervan PA. Munnely J. et al: Sinus histiocytosis with massive lymphadenopathy simulating subacute thyroiditis. Hum Path01 17:321. 1986 16. Mir R. Aftalion B, Kahn LB: Sinus histiocytosis with massive lymphadenopathy and unusual extranodal manifestations. Arch Path01 Lab Med 109:867, 1985 17. Azoury FJ. Reed RJ: Histiocytosis: Report of an unusual case. N Engi J Med 274:928, 1%6 18. Ramos CV: Widespread bone involvement in sinus histiocytosis. Arch Path01 Lab Med 10606, 1976 19. Marsh WL. MC Carrick JP, Harlan DM: Sinus histiocytosis with massive lymphadenopathy. Occurrence in identical twins with retroperitoneal disease. Arch Path01 Lab Med It2:298. 1988 20. Miettinen M, Paljakka P, Haveri P. et al: Sinus histiocytosis with massive lymphadenopathy. A nodal and extranodal proliferation of S-100 protein positive histiocytes. Am J Clin Path01 88:270, 1987
J Oral Maxillofac 49:205-209.
205
ET AL
Surg
1991
Sinus Histiocytosis With Massive Lymphadenopathy: A Case With Facial Bones Involvement iiMER
GijNHAN,
DDS, PHD,* RIFKI FINCI, MD,t YILMAZ GUNAYDIN, AND IBRAHIM SOMUNCU, MD3
Sinus histiocytosis with massive lymphadenopathy (SHML) is a nonneoplastic, pseudolymphomatous disease with a broad clinical spectrum confined mainly to lymph nodes. Because it was first described in 1969 by Rosai and Dorfman,’ it is also known as Rosai-Dorfman disease. Most patients are children or young adults (mean age, 19.7; female/male ratio, 1.4:1) who present with painless cervical lymphadenopathy.’ Other lymph node groups often were also involved. This self-limited disease is usually accompanied by hypergamma-globulinemia, elevated erythrocyte sedimentation rate, neutrophilic leucocytosis, anemia, and fever. Clinically, the disease is characterized by its often protracted, although benign, clinical course, usually terminating in spontaneous resolution of the lesion. However, some cases are fatal (7%), with multisystem involvement and immunologic dysfunctions.’ No specific cause has been identified and it was speculated that the pathogenesis is related to infectious agents or disturbed immunologic functions.‘.4 The microscopic appearance of the involved lymph nodes is distinctive. There is capsular fibrosis and striking dilatation of the lymph node sinuses, with proliferation of histiocytes and plasma cells, and phagocytized lymphocytes (emperiopolesis) and erythrocytes.5 We report a unique case of SHML involving the mandible, maxilla, and zygomatic bones as well as the cervical, axillary. and inguinal lymph nodes and upper respiratory tract.
DDS, PHD,*
FIGURE I, Computed tomography scan showing upper respiratory tract and bone involvement (arrows).
Report of a Case A 20-year-old white man presented with a S-year history of pain and enlargement in the left mandible. He had also been complaining from bilateral nasal obstruction, rhinitis, epistaxis, and headache since 1976. Previously, he had been repeatedly treated for sinusitis and rhinitis with antibiotics and operated on (Caldwell-Luc in
Received from Giilhane Military Medical Academy and Medical School, Ankara, Turkey. * Associated Professor, Department of Pathology. t Professor and Chairman, Department of Pathology. f Associated Professor, Department of Oral Surgery. § Associated Professor, Department of Radiology. Address correspondence and reprint requests to Dr Giinhan: Giilhane Askeri Tip Akademisi. Patoloji Biiliimii, Etlik 06018, Ankara. Turkey. 0 1991 geons
American
Association
0278-2391191/4902-0020$3.00/O
of Oral
and Maxillofacial
Sur-
FIGURE 2. Computed tomography scan showing nasopharyngeal mass (arrows).
206
SHML WITH FACIAL BONES INVOLVEMENT
Microscopically, the lymph node biopsy specimen showed marked dilatation of the sinuses and proliferation of histiocytes, with vesicular nuclei, large nucleoli, and abundant pale eosinophilic cytoplasm. Mature lymphocytes and plasma cells accompanied the histiocytes. Lymphophagocytosis was evident. Infiltration affected the normal nodal architecture, although residual germinal centers were found (Figs 5 and 6). There was capsular fibrosis. The biopsy specimen of the nasal lesion (Fig 7) and mandibular bone (Fig 8) showed the presence of a similar infiltrate, including histiocytes, plasma cells, neutrophilic leucocytes, and lymphocytes. Necrosis, granulomatous infiltration, and giant cells were absent. There were no nuclear grooves in the histiocytes. The mandibular lesion showed slight fibrosis as well as histiocytic infiltration. Histologic stains did not show any storage in the histiocytes. Immunoperoxidase staining for S- 100 protein (avidinbiotin-peroxidase complex; Dako, Denmark) was carried out. The majority of the histiocytes were positively stained both in the lymph node and bone biopsies (Fig 9). With the diagnosis of SHML and extranodal involvement, the patient was treated with chemotherapy (prednisolone, 40 mg/d, and cyclophosphamide, 50 mg three times per day, for six periods of 14 days with ICday intervals between) and radiotherapy (total of 50 Gy to nasopharynx and paranasal sinuses only). After the treatment, the regional lymph nodes and the upper respiratory tract masses became smaller (Fig 10). There were no changes in the bone lesions. Because the air passages were opened, some complaints disappeared. Laboratory findings showed no significant difference, except the erythrocyte sedimentation rate showed a transient decrease. At the end of our 16 months of follow-up, the patient is alive with disease. were performed.
FIGURE 3. Lytic defects are seen in right and left mandibular corpus (arrows).
1978 and bilateral antrostomy in 1982) twice without establishment of a histologic diagnosis. Physical examination showed left mandibular and nasal masses, bilateral cervical, axillary and inguinal lymphadenopathy, and hepatosplenomegaly. The lymph nodes were firm and tender. There was a history of fatique, weight loss, fever, and joint pains (aspirin relieved the pain), the last developing recently. Radiologically, there were maxillary, ethmoidal, and sphenoidal sinus, nasal cavity, and nasopharyngeal softtissue involvement (Figs 1 and 2). The right and left mandibular corpus and ramus, and the maxillary and zygomatic bones were also involved (Figs 3 and 4). The osseous lesions were destructive, lytic, and ill-defined, without sclerotic margins. They were mainly medullary, but on the left side of the mandible, cortical destruction and soft-tissue involvement were noticed. Conventional radiographic and ultrasonographic investigations and computerized tomography (CT) showed no other bone, organ, or soft-tissue involvement. Table I lists the sites of nodal and extranodal involvement. Abnormal laboratory findings were as follows: erythrocyte sedimentation rate, 106 mm/h (normal, 20 mm/h); IgG, 2,650 mg/dL (normal, 800 to 1,800 mg/dL); albumin, 3.4 g/dL (normal, 4.5 to 5.5 g/dL); T helper cells, 22% (normal, 60%); T suppressor cells, 13% (normal, 35%). Bone marrow aspiration was normocellular. Inguinal lymph node, left mandibular, and nasal cavity biopsies
Discussion Sinus histiocytosis with massive lymphadenopathy has a very broad clinical spectrum, with outcomes varying from spontaneous remission to lethal infiltration of vital organs.396 There are 365 cases in Rosai’s established case registry.’ Because of the rarity of the disease, little progress has been made concerning the understanding of its pathogenesis.
FIGURE 4. Computed tomography scan of maxilla (A) and mandible (B) showing lytic, ill-defined lesions (arrows).
GUNHAN
207
ET AL
Table 1. Sites of Involvement in the Presented Case of SHML Lymph nodes (B) Cervical Axillary Inguinal* Extranodal tissues Nasal cavity* Sinuses (B) Maxillary Ethmoidal Sphenoidal Nasopharynx Liver Spleen Bone Mandible, corpus,*t Maxilla Zygoma (B)
and ramus (R and L)
FIGURE 6. The sinuses are filled with histiocytes containing phagocytized lymphocytes (emperiopolesis) (hematoxylin-eosin stain. original magnification X500).
The histology of the lymph nodes in SHML is typical and can be readily recognized. However, the appearance of the extranodal lesions presents difficulties in diagnosis and usually require the identification of the lesions from lymph nodes to establish the diagnosis.’ In extranodal involvement, the microscopic findings may be very similar to the lymph nodes presentations, with the presence of vascular proliferations and vessels highlighted by perivascular rows of plasma cells. I2 In some cases, the extranodal lesions may represent the predominant manifestation of the disease and precede the detection of the lymphadenopathy.879 The main complaints in the present case were related to extranodal manifestations and led to the bone, nasal, and lymph node biopsies.
The most frequent extranodal sites are the upper respiratory tract,’ orbit and eyelid,‘” and skin.’ Less frequent sites are bone,” the nervous system,” gastrointestinal tract,i3 salivary glands, tonsil, oral mucosa and tongue,’ lung,14 thyroid,” kidney,16 and testis. ” Sometimes there is widespread multisystem involvement.6”7 Table 1 summarizes the sites of nodal and extranodal involvement in the present case. Bone involvement is rare and usually multiple. Radius, ulna, tibia, femur, and Iibula are the most commonly affected long bones; the less frequently involved bones are skull, vertebral bodies, pelvis, phalanges, metacarpals, ribs, and maxilla.” The lesions usually are medullary, but cortical defect also may be present. No periosteal reaction is observed and central calcification is absent. In healing cases, lytic lesions may show a continuous decrease in size or may develop a sclerotic border.” Bone involvement is usually found together with other extranodal manifestations such as in the nasal and paranasal sinuses.” The present case is a prime ex-
FIGURE 5. SHML-produced changes in the architecture of a lymph node. There are only a few residual germinal centers (hematoxylin-eosin stain. original magnification X35).
FIGURE 7. Nasal cavity involvement by SHML. There is a large subepithelial collection of histiocytes, lymphocytes, and plasma cells (hematoxylin-eosin stain, original magnification X200).
Except for biopsied sites, involvement was based on clinical, radiologic. and ultrasonographic findings. Abbreviations: B, bilaterally; L. left: R, right. * Confirmed with biopsy. t Involvement of soft tissue on left.
208
FIGURE 8. Bone involvement by SHML. Note the area of proliferating histiocytes (hematoxylin-eosin stain, original magnification X200).
ample of the marked involvement of the facial bones, with the radiologic findings compatible with other reports.““* It is suggested that in the presence of extranodal involvement with histologic features that closely mimic SHML of lymph nodes makes a presumptive diagnosis possible.2 In the absence of the typical histiocytes and lymphophagocytosis, a positive diagnosis cannot be made. The microscopic appearance of the bone and nasal biopsy specimens in our case were very similar to what was seen in the lymph nodes and the diagnosis were made in the light of the latter findings. Some extranodal involvements, especially without distinctive nodal changes, may be confused with a variety of other histiocytic disorders. Re-
SHML WITH FACIAL BONES INVOLVEMENT
ports of cases of SHML show that histologic diagnosis is often confused with malignant histiocytosis, histiocytosis X, Hodgkins’ disease, granulomatous disease, xanthogranuloma, lipid storage disease, and nonspecific inflammations.7*9311’i9 Radiographically, bone involvement in SHML simulates histiocytosis X, metastatic malignancy, sarcoidosis, lipid storage disorders, and neurotibromatosis with osseous infiltration. ‘i Recently, immunohistochemical demonstration of S-100 protein positivity in histiocytes has provided a useful aid in the diagnosis of suspected SHML cases2 Although the nature and etiology of SHML are still questionable, the disease bears characteristics of a state of aberrant immune function. Sinus histiocytosis with massive lymphadenopathy histiocytes show S-100 protein and a-lantichymotrypsin positivity and lysozyme negativity.20 The “histiocytes” in this disease may not be mature histiocytes at all, but, rather, relatives of the interdigitating reticulum cells (IDRC) or t-zone histiocytes, more related to Langerhans’ cells or precursors of histiocytes than true histiocytes. As seen in Figure 9, histiocytes observed both in the lymph node and bone lesions showed strong cytoplasmic S-100 protein positivity. Extranodal disease is responsible from various symptoms, including neurologic manifestationsI related to compression, and nasal obstruction.7 Our patient had severe headaches for a long time that disappeared after treatment resulted in opening of the air passages. Repeated clinic laboratory testing showed consistently elevated polyclonal IgG val-
FIGURE 9. S-100 protein-positive histiocytes (arrows) in lymph node (Zefr) and bone (right) biopsies (avidin-biotin peroxidase immunostain with hematoxylin counterstain, original magnification X200).
209
GUNHAN ET AL
Acknowledgment The authors thank Dr J. Rosai (Yale University) for his kind comments about this case.
References I. Rosai J, Dorfman RF: Sinus histiocytosis
FIGURE 10. scan.
Posttreatment
opening of air passages seen on CT
ues, hypoalbuminemia, low T-subset ratios, and a high erythrocyte sedimentation rate. Except for the erythrocyte sedimentation rate, abnormal laboratory findings persisted despite the therapy. Approximately 10% of the patients with SHML have clinically significant hematologic and immunologic abnormalities such as glomerulonephritis, joint disease, Wiskott-Aldrich syndrome, unusual infections, and miscellaneous conditions (amyloidosis, increased serum viscosity, multiple myelomaIgA kappa, Raynaud’s phenomenon, and asthma).4 Fatality in patients with SHML is usually due to immunologic dysfunction and infectious complications. Foucar, Rosai, and Dorfman3 reported tindings in 14 patients who died with nodal and extranodal involvement, immunologic dysfunction, and unusual infections. Many patients have been subjected to delay in diagnosis.5.‘1V16 Similarly, our patient had been treated repeatedly for nonspecific inflammations of the nasal cavity and sinuses for 12 years. The final diagnosis was made with a combination of lymph node, nasal, and bone biopsies. Some cases of SHML show spontaneous resolution; some require therapy, especially ones with multisystem involvement and immunologic abnormalities. Reports about treatment mention from inconsistent results. Steroids, antibiotics, irradiation, and surgery have been used. Although the combined treatment in our patient relieved some complaints, the final results were not considered satisfactory.
with massive lymphadenopathy. A newly recognized benign clinicopathologic entity. Arch Path01 Lab Med 87:63, 1%9 2. Foucar E. Rosai J. Dorfman RF: Sinus histiocvtosis with massive lymphadenopathy. Current status and future directions. Arch Dermatol 124: 1211. 1988 3. Foucar E. Rosai J, Dorfman RF: Sinus histiocytosis with massive lymphadenopathy. An analysis of 14 deaths occuring in a patient registry. Cancer 54:1834. 1984 4. Foucar E, Rosai J, Dorfman RF: Immunologic abnormalities and their significance in sinus histiocytosis with massive lymphadenopathy. Am J Clin Path01 82:515. 1984 5. Rosai J, Dorfman RF: Sinus histiocytosis with massive lymphadenopathy: A pseudolymphomatous benign disorder. Cancer 30: 1174, 1972 6. Buchino JJ, Byrd RP. Kmetz DR: Disseminated sinus histiocytosis with massive lymphadenopathy. Its pathologic aspects. Arch Path01 Lab Med 106: 13, 1982 7. Foucar E. Rosai J. Dorfman RF: Sinus histiocytosis with massive lymphadenopathy. Ear, nose and throat manifestations. Arch Otolaryngol 104:687, 1978 8. Thawerani H, Sanchez RL, Rosai J, et al: The cutaneous manifestations of sinus histiocytosis with massive lymphadenopathy. Arch Dermatol 114: 191. 1978 9. Suster S. Cartagena N. Cabella-Inchausti B, et al: Histiocytic lymphophagocytic panniculitis. An unusual extranodal presentation of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). Arch Dermatol 124:1246, 1988 10. Foucar E. Rosai J. Dorfman RF: The ophthalmologic manifestations of sinus histiocytosis with massive lymphadenopathy. Am J Ophthalmol 87:354. 1979 11. Walker PD, Rosai J. Dorfman RF: Osseous manifestations of sinus histiocytosis with massive lymphadenopathy. Am J Clin Path01 75131, 1981 12. Foucar E, Rosai J. Dorfman RF, et al: The neurologic manifestations of sinus histiocytosis with massive lymphadenopathy. Neurology 32:365, 1982 13. Osborne BM, Hagemeister FB, Butler JJ: Extranodal gastrointestinal sinus histiocytosis with massive lymphadenopathy. Am J Surg Path01 5603, 1981 14. Carpenter RJ. Banks PM, McDonald TJ. Sanderson DR: Sinus histiocytosis with massive lymphadenopathy 1Rosai-Dorfman disease): Report of a case with respiratory tract involvement. Laryngoscope 88:1%3, 1978 15. Larkin DFP, Dervan PA. Munnely J. et al: Sinus histiocytosis with massive lymphadenopathy simulating subacute thyroiditis. Hum Path01 17:321. 1986 16. Mir R. Aftalion B, Kahn LB: Sinus histiocytosis with massive lymphadenopathy and unusual extranodal manifestations. Arch Path01 Lab Med 109:867, 1985 17. Azoury FJ. Reed RJ: Histiocytosis: Report of an unusual case. N Engi J Med 274:928, 1%6 18. Ramos CV: Widespread bone involvement in sinus histiocytosis. Arch Path01 Lab Med 10606, 1976 19. Marsh WL. MC Carrick JP, Harlan DM: Sinus histiocytosis with massive lymphadenopathy. Occurrence in identical twins with retroperitoneal disease. Arch Path01 Lab Med It2:298. 1988 20. Miettinen M, Paljakka P, Haveri P. et al: Sinus histiocytosis with massive lymphadenopathy. A nodal and extranodal proliferation of S-100 protein positive histiocytes. Am J Clin Path01 88:270, 1987
