| OCR Text |
Show Journal of Nemo- Ophthalmology 18( 4): 270- 275, 1998. © 1998 Lippincott Williams & Wilkins, Philadelphia Sinus Histiocytosis With Massive Lymphadenopathy Involving the Orbit: Reversal of Compressive Optic Neuropathy After Chemotherapy Sharon Goldberg, M. D., Panna Mahadevia, M. D., Michael Lipton, M. D., and Pearl S. Rosenbaum, M. D. A 38- year- old woman from Antigua had compressive optic neuropathy of the right eye caused by orbital involvement with sinus histiocytosis. There was also nasal sinus involvement and massive cervical lymphadenopathy resulting in radiographic compression of the airway and carotid sheath. Because of the compressive optic neuropathy and threat to the airway and carotid perfusion, the patient underwent a 6- month chemothera-pcutic regimen of cyclophosphamide, vincristine, and prednisone. After chemotherapy, the visual dysfunction resolved in correlation with diminution of the orbital mass, and marked regression of the cervical lymphadenopathy. This case demonstrates the potential efficacy of chemotherapy in the treatment of compressive oplic neuropathy in cases of orbital sinus histiocytosis with massive lymphadenopathy. Key Words: Chemotherapy- Optic neuropathy- Rosai- Dorfman disease- Sinus histocytosis with massive lymphadenopathy. Sinus histiocytosis with massive lymphadenopathy ( SHML) is a benign pseudolymphomatous disorder defined by the characteristic histopathologic features of sinusal histiocytic proliferation and lymphocytophagocy-tosis ( 1,2). Rosai- Dorfman disease ( RDD) is used synonymously with SHML or is considered the preferred eponym for soft- tissue involvement by sinus histiocytosis in the absence of lymphadenopathy ( 3,4). Although several case reports had been published previously ( 5- 8), Rosai and Dorfman established SHML as a well-recognized clinicopathologic entity with their description of four cases in 1969 ( 1) and documentation of 30 addi- Manuscript received May 22, 1998; accepted July 8, 1998. From the Departments of Ophthalmology and Visual Sciences ( S. G., P. S. R.), Pathology ( P. M., P. S. R.), and Radiology ( M. L.), Monlefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York. Supported by an unrestricted grant to the Department of Ophthalmology and Visual Sciences, Monlefiore Medical Center, Albert Einstein College of Medicine, from Research to Prevent Blindness, New York, New York. Address correspondence and reprint requests to Pearl S. Rosenbaum, M. D., Department of Ophthalmology and Visual Sciences, Montefiore Medical Center, 1 11 East 210 Street, Bronx, NY 10467, U. S. A. tional cases in 1972. By 1990, Foucar et al. ( 2) identified 423 patients with this disease. SHML has been reported worldwide, typically occurring in the first two decades of life. The age of onset may range, however, from birth to the eighth decade. Patients with extranodal SHML are generally older at the time of disease onset ( 40 years) ( 3). Overall, blacks and whites are equally affected, and there is a slight male predominance ( 58%). Typically, patients are in otherwise good health and exhibit slowly progressive, painless, bilateral lymphadenopathy. Systemic manifestations variably include fever and weight loss. Anemia, neutrophilia, polyclonal hyper-globulinemia, and elevated erythrocyte sedimentation rate are the most commonly associated laboratory findings.( 2,3,10) The cervical lymph nodes are most often involved. Occasionally there is enlargement of the axillary, mediastinal, and inguinal chains ( 1,2). Extranodal sites of involvement are noted in approximately 40% of patients, with the most frequent sites being the skin, nasal cavity and paranasal sinuses, soft tissue, eyelid, orbit, and bone.( 2) CASE REPORT A 38- year- old woman from Antigua described an 8- month history of blurring of vision on the right. She denied trauma, diplopia, or eye pain. Simultaneously, she also noted a gradually enlarging, nontender mass on the right side of her neck. Two months after the onset of her visual symptoms, there was right nasal congestion and epistaxis. Review of systems was otherwise negative. Physical examination showed a well- developed and well- nourished woman with a firm, nontender mass posterior to the right sternocleidomastoid muscle, measuring 8 x 5 cm. On ophthalmologic examination, best corrected visual acuity measured 20/ 40 OD and 20/ 20 OS. There was 2 mm of proptosis on the right. The motility examination produced normal findings. Static visual field testing using a Humphrey perimeter revealed an inferior altitudinal defect on the right and a full visual field on the left. On color vision testing ( Ishihara 15 270 SINUS HISTIOCYTOSIS WITH MASSIVE LYMPHADENOPATHY 27/ plates) the patient could identify 3 plates with the right eye and 15 with the left eye. There was 25% red and brightness desaturation in the right eye. Intraocular pressures by applanation tonometry were normal. The pupils were reactive to light, but the right pupil was sluggish. Slit lamp and dilated fundus examinations were unremarkable. The results of laboratory studies showed only mild FIG. 1. Axial computed tomogram of the head discloses proptosis of the right globe, soft tissue infiltration of the posterior portion of the right orbit extending to the apex, as well as opacification of the right ethmoid and sphenoid sinuses ( A). Coronal T1 - weighted magnetic resonance image ( B) and axial computed tomogram ( C) demonstrate massive posterior triangle and deep cervical lymphadenopathy ( open arrows). Mass effect on the carotid artery ( arrowheads) and airway ( A) as well as compression of the right internal jugular vein ( arrow) are evident. J Neiim- Oplilluilinol. Vol. IS. No. 4. 199ft 272 S. GOLDBERG ET AL. anemia. Contrast- enhanced computed tomography ( CT) of the head and neck demonstrated an enhancing mass within the posterior portion of the right orbit, extending to the apex, and infiltration and expansion of the right ethmoid sinus with bowing of its lateral wall into the orbit ( Fig. 1A). Opacification of the right sphenoid sinus was also present. There was massive posterior triangle and deep cervical lymphadenopathy extending interiorly to the level of the supraclavicular fossa. This lesion caused compression of the right internal jugular vein, medial deviation of the right carotid artery, and mass effect on the airway ( Figs. IB, 1C). An open exploration of the right neck mass was performed, resulting in incisional biopsy of one of the massively enlarged cervical lymph nodes. Punch biopsies of the right ethmoid sinus were also performed. PATHOLOGIC FINDINGS Histopathologic examination of the lymph node specimen showed marked distortion and obliteration of the normal sinus architecture by significant intranodal fibrosis. There was heavy cellular infiltration, in part lymphoid, of the biopsy tissue, divided into nodules or incomplete lobules by thick bands of collagen. Rare lymphoid follicles with germinal centers were noted ( Fig. 2). The cellular infiltrate consisted of small, mature lympho- FIG. 2. Light microscopy of the lymph node showing obliteration of the normal sinus architecture by extensive fibrosis and nodular infiltration. A lymphoid follicle is present ( arrowhead). FIG. 3. The cellular infiltrate consists of numerous plasma cells, occasional Russell bodies and lymphocytes ( hematoxylin- eosin; original magnification, x63). cytes, plasma cells, Russell bodies, and histiocytes ( Fig. 3). The histiocytes often formed sheets and characteristically contained a single, vesicular nucleus, small nucleolus, and abundant pale vacuolated cytoplasm. Em-peripolesis- that is, intracytoplasmic sequestration of apparently viable cells of hematopoietic origin- was prominent. There were numerous histiocytes containing predominantly lymphocytes as well as a few plasma cells, neutrophils, and erythrocytes. Touch preparations of the lymph node also showed prominent emperipolesis ( Fig. 4). The histiocytes exhibited strong cytoplasmic immunopositivity for S- 100 protein and for macrophage markers ( lysozyme, MAC- 387; Fig. 5). Plasma cell infiltration was most prominent in areas of fibrosis and collagenization. Congo red stain was negative for amyloid and the frozen section and cytospin immunophenotyping studies showed polyclonality, thus excluding the possibility of a plasma cell disorder with amyloid deposits. Examination of specimens obtained in punch biopsy of the right ethmoid sinus showed heavy lymphoplasma-cytic and histiocytic proliferation, without evidence of micro- organisms. A diagnosis of sinus histiocytosis with massive lymphadenopathy was made. CLINICAL COURSE Because of the optic neuropathy and airway compression, the patient underwent treatment with a 6- month course of combination chemotherapy consisting of Cytoxan, vincristine, and prednisone. Subsequent to the chemotherapy, there was marked diminution of the cervical lymphadenopathy to 1 cm x 1 cm. There was resolution of the compressive optic neuropathy. The visual acuity improved to 20/ 20 OD and repeat static testing revealed a full field on the right. Color vision improved so that the patient could identify 13/ 15 Ishihara plates OD. There was no red or brightness desaturation, and the pupils were equally reactive. Computed tomographic scan evaluation three months after the completion of chemotherapy demonstrated significant resolution of the ,/ Neum- Oplulmlmol, Vol. 18, No. 4. 199H SINUS HISTIOCYTOSIS WITH MASSIVE LYMPHADENOPATHY 273 FIG. 4. Prominent emperipolesis as seen on touch preparation ( A) and tissue sections ( B) of the lymph node. The histiocytes ( arrowheads) shown here sequester lymphocytes within their cytoplasm. Infiltration by lymphocytes and plasma cells is also seen ( A, Giemsa; original magnification, x100; B, hematoxylin- eosin; original magnification, x100). right orbital infiltrate ( Fig. 6A) and cervical lymphade-nopathy ( Fig. 6B). Ethmoidal opacification persisted. The patient remained stable when last examined 5 months after the completion of chemotherapy, after which time she was lost to follow- up. DISCUSSION Of the 423 patients reported in the 1990 registry, 36 had documented ophthalmologic involvement as follows: eyelid ( 5 patients), orbit ( 22 patients), or both ( 9 patients) ( 2). The majority of cases involving the orbit were reported in black men ( 2). Patients with orbital involvement often have other sites of extranodal disease, including the nasal cavity, paranasal sinuses, skin, lower respiratory tract, and liver ( 2), with the presence of nasal sinus or nasal mucosal involvement being the most common ( 2,11). Ophthalmic disease generally localizes to the peripheral orbital soft tissues rather than to the muscle cone ( 10,12). Eyelid involvement occurs either as an extension of orbital involvement or as an isolated ophthalmologic finding ( 10,13- 15). Ocular involvement in the form of unilateral anterior uveitis ( 16), panuveitis ( 10), or epibulbar limbic infiltration ( 17) has also been reported. The reported signs and symptoms of orbital SHML include exophthalmos ( most frequent) ( 2,12,18), lagoph-thalmos, blurred vision, diplopia, conjunctival injection, dry eye, and ocular irritation ( 10). Major ocular morbidity relates to the sequelae of proptosis: exposure keratopathy, corneal ulceration, endophthalmitis, and ultimately, loss of the eye ( 10,12,13). There are rare reports of visual impairment ( 11); however, the precise cause of the deficit is not recorded. Histopathologically, a cellular infiltrate of plasma cells and histiocytes is seen in orbital SHML, similar to that seen in nodal SHML. Histiocytic proliferation in cords and nests simulates the sinusal pattern of the lymph node. In extranodal SHML, however, fibrosis is more common ( 2) and lymphocytophagocytosis is less frequent ( 10). The prognosis of patients with SHML correlates with the number of nodal and extranodal areas involved ( 2). The disease course is generally protracted but self-limiting, with eventual spontaneous regression of lymph-adenopathy and extranodal disease within several months to years ( 9). Medical or surgical intervention is reserved for those cases in which the disease threatens life or organ function. To date, no specific treatment protocol has been established. However, chemotherapeu-tic ( 10,14,18- 21) and surgical ( 4,10,12,22) approaches have been used to treat the disease successfully in a limited number of cases. A combination of Vinca alkaloid, alkylating agent, and corticosteroid seems to be the most effective chemotherapeutic regimen ( 14,19,21). An isolated report of successful resolution of disease using acyclovir has been reported ( 20). Although radiotherapy has decreased mass size in some patients ( 13), many FIG. 5. The histiocytes show strong cytoplasmic immunoreactiv-ity to MAC- 387, outlining the sequestered lymphocytes ( trypsin pretreated, avidin- biotin complex method, DAB chromogen, hematoxylin counterstain; original magnification, x160). J Neiiro- Oplillmlnwl, Vol. IX, No. 4, I99X 274 S. GOLDBERG ET AL. FIG. 6. Contrast enhanced axial computed tomography of the head ( A) and neck ( B) 3 months subsequent to the completion of chemotherapy. The right orbital infiltrate has largely resolved ( A), and the sphenoid sinus is clear. Persistent opacification of the ethmoid sinus is seen. Marked regression of the lymphadenopathy ( B, open arrows) resulted in symmetry of the airway ( A), carotid arteries, and jugular veins. clinicians report only limited success with this treatment ( 9,20). Surgical excision has most successfully been employed for disease eradication in patients with discrete and isolated masses ( 4,10,19,22). Despite medical or surgical intervention, occasional deaths have been reported, but few were attributed directly to SHML ( 2,9). The presence of immune- mediated disease ( e. g., autoimmune hemolytic anemia, arthritis, severe systemic infections, glomerulonephritis, asthma, and juvenile- onset diabetes mellitus) in association with SHML is an unfavorable prognostic indicator and is associated with increased mortality ( 2). The patient described in our case clinically manifested compressive optic neuropathy and compression of the airway and carotid sheath. She was therefore treated with combination chemotherapy consisting of a Vinca alkaloid ( vincristine), alkylating agent ( cytoxan), and corticosteroid ( prednisone). As documented in other cases, our patient responded to chemotherapy with significant resolution of the lymphadenopathy and decreased orbital infiltration ( 14,21,23). Of particular clinical significance in our case was the reversal of the compressive optic neuropathy after chemotherapy, correlating with the diminution of the orbital infiltrate, demonstrated by computed tomography. The potential efficacy of chemotherapy in the treatment of compressive optic neuropathy due to orbital involvement in SHML is thus illustrated. REFERENCES I. Rosai .1, Dorfman R. Sinus histiocytosis with massive lymphadenopathy. Arch Pathol 1969; 87: 63- 70. 2. Foucar E, Rosai J, Dorfman R. Sinus histiocytosis with massive lymphadenopathy ( Rosai- Dorfman disease): Review of the entity. Semin Diagn Pathol 1990; 7: 19- 73. 3. Foucar E, Rosai J, Dorfman R. Sinus histiocytosis with massive lymphadenopathy: current status and future directions. Arch Dermatol 1988; 124: 1211^ 1. 4. Shemen L, D'Anton M, Klijian A, Toth I, Galantich P. Rosai Dorfman disease involving the premaxilla. Ann Otorhinolaryngol 1991; 100: 845- 51. 5. Azouri F. 1, Reed RJ. Histiocytosis: report of an unusual case. N Engl J Med 1966; 274: 928- 30. 6. Vincent TN, Micrcourt R. Histiocytosis of the eyelid. Penrose Cancer Hosp Bull 1967; 3: 246- 50. 7. Marie J, Bernard J, Nezelof C, et al. Adenopathieschronique avee reticulohistiocytaire et surchage lipidique. Arm Pediatr ( Paris) 1966; 42: 2689- 98. 8. Destombes P. Adenites avec surchage lipidique dc 1' enfant ou de 1' adulte jeunne, observees aux Antilles et au Mali ( quatre observations). Bull Soc Pathol Exot 1965; 58: 1169- 75. 9. Rosai J, Dorfman R. Sinus histiocytosis with massive lymphadenopathy: a pseudolymphomatous benign disorder. Cancer 1972; 30: 1174- 88. 10. Foucar E, Rosai J, Dorfman R. The ophthalmic manifestations of the sinus histiocytosis with massive lymphadenopathy. Am J Ophthalmol 1979; 87: 354- 67. 11. Wenig B, Abbondanzo SL, Childers EL, Kapadia S, Heffner D. Extranodal sinus histiocytosis with massive lymphadenopathy ( Rosai- Dorfman disease) of the head and neck. Hum Pathol 1993; 24: 483- 92. 12. Friendly DS, Font RL, Rao NA. Orbital involvement in " sinus" histiocytosis. Arch Ophthalmol 1977; 95: 2006- 11. 13. Codling BS, Soni KC, Barry DR, Martin- Walker W. Histiocytosis presenting as swelling of orbit and eyelid. Br J Ophthalmol 1972; 56: 517- 30. 14. Levinger S, Pe'er J, Aker M, Okon E. Rosai- Dorfman disease involving four eyelids [ letter]. Am J Ophthalmol 1993; 116: 382- 4. 15. Murray JC, Rossman SN, Chintagumpala M. Pathological case of the month: sinus histiocytosis with massive lymphadenopathy ( Rosai- Dorfman disease). Arch Pediatr Adolesc Med 1995; 149: 57- 8. ./ Nam,- Ophthalmol. Vol. IS, No. 4. 1998 SINUS HISTIOCYTOSIS WITH MASSIVE LYMPHADENOPATHY 275 16. Berger L, Gait J, Allansmith MR. Globe involvement in sinus histiocytosis. Am J Ophthalmol 1983; 95: 124- 5. 17. Zimmerman LE, Hidayat AA, Grantham RL, et al. Atypical cases of sinus histiocytosis ( Rosai- Dorfman disease) with ophthalmological manifestations. Trans Am Ophthalmol Soc 1988; 86: 113- 35. 18. Brau R, Sosa I, Marcial- Seoane MA. Sinus histiocytosis with massive lymphadcnopathy ( Rosai- Dorfman disease) and extranodal involvement of the orbit. P R Health Sci J 1995; 14: 145- 9. 19. Komp D. The treatment of sinus histiocytosis with massive lymphadcnopathy ( Rosai Doii'man disease). Semin Diagn Pathol 1990; 7: 83- 6. 20. Baildam EM, Ewing CI, D'Souza SW, Stevens RF. Sinus histiocytosis with massive lymphadcnopathy ( Rosai- Dorfman disease): response to acyclovir. ./ R Soc Med 1992; 85: 179- 80. 21. Picco P, Buoncompagni A, Pisloia V, et al. Difficulties and positive therapeutic response in a patient wilh sinus histiocytosis with massive lymphadcnopathy. Eur J Pediatr 1993; 152: 699- 702. 22. Gregor RT, Ninnin D. Sinus histiocytosis: a rare tumor involving the paranasal sinuses. Ear Nose Throat J 1993; 72: 291- 5. 23. Foucar D, Rosai J, Doii'man RE. Sinus histiocytosis with massive lymphadenopathy: ear, nose, and throat manifestations. Arch Otolaryngol 1978; 104: 687- 93. ./ Neuro- Ophtlwlmol, Vol. IH. No. 4, 199H |
