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Case Reports Indian Pediatrics 2002; 39:764-769 |
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Sinus Histiocytosis with Massive Lymphadenopathy in Children |
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Vasantha Thavaraj R. Dawar* L.S. Arya
Sinus histiocytosis with massive lymphadenopathy (SHML) is a unique disease of unknown etiology with a childhood predilection. It was initially described by Azoury and Reed(1); later it was described to have a benign course by Rosai and Dorfman(2) and is now widely known as Rosai-Dorfman disease or syndrome (RDD). This condition has been sporadically reported in Indian literature(3,4). We report six cases of RDD attending the pediatric oncology clinic at All India Institute of Medical Sciences, New Delhi from January 1990-December 2000. Case Reports The clinical profile of six patients with SHML is summarized in Table 1. Additional information is provided below: Case 1: Duration of illness was 8 months. Cervical nodes measured 2-4 cm in size, were bilateral, not matted and nontender. The contrast enhanced computerized tomography (CECT) of the chest and abdomen suggested bilateral hilar lymphadenopathy with consolidation of the left lower lobe with pleural effusion in the right major fissure. Case 2: The duration of illness was one and half years with a gradual increase in the size of the lymph nodes. The child was followed up for 9 months and the mass increased in size. He received prednisolone 30 mg daily for 3 weeks. The lymph nodes have completely regressed. Case 3: This child presented with fever for 3 months duration and swelling in the neck for two and half months. Fever was intermittent with no chills and rigors. There was a minimal cough with no expectoration. On examination, there were lymph nodes in the neck on both sides of the neck, 2-3 in number, 2-3 cm in size and submandibular and tonsillar lymph nodes. Case 4:
A two and half year old female child presented with fever and neck
swelling for 4 months. Fever was 102ºF, intermittent in nature with no
chills and rigors. The swelling in the neck slowly increased in size.
There was loss of appetite and weight. The patient also had difficulty in
breathing and swallowing. The submandibular lymph nodes and inguinal lymph
nodes were very big (4-5 cm) in size and matted. The hemoglobin was 4.6 g/dL.
The total leukocyte count was 15,000 cells/mm3. The Westergren erythrocyte
sedimentation rate was 70 mm in 1st hour. The child did not follow up
after the first visit. Table I- Clinical Profile of The Six patients with SHML (RDD)
N.P. = not palpabale; LN = Lymth nodes; FU-Follow up
Case 5: This child had swelling in the neck for two and half years. There was no fever or cough. The child was given anti-tubercular therapy by a private practitioner without any improvement. On examination, there was generalized lymphadenopathy, and mild pallor. The chest X-ray showed bulky bilateral hila with mediastinal widening. The CECT of chest and abdomen revealed mediastinal and bilateral hilar lymph nodes. There was extensive retroperitoneal lymph nodes with mild hepatomegaly. The child was given oral prednisolone 25 mg per day for a period of 60 days and then tapered off. The swelling in the neck subsided and the child was under follow up for 2 years. He again complained of swellings in the neck. X-ray chest revealed mediastinal enlargement of lymph nodes. The CECT chest and abdomen suggested mediastinal, bilateral hilar and axillary lymph nodes and retroperitoneal lymph nodes and hepatosplenomegaly. He was given three alternating ABVD (Adriamycin, Bleomycin, Vinblastin, Dacarbazine)/ COPP (Cyclophos-phamide, Vincristine, Prednisolone and Procarbazine) cycles of chemotherapy. Few lymphnodes of 0.5-1 cm size remain. He is under follow up.
Case 6: A 9 year old boy, the eldest of two children complained of bilateral neck swellings for the last 3 years and joint pains of small and large joints for 9 months. He also had some associated maculopapular rash. There was no history of fever, bony pain, weight loss or anemia. There was family history of tuberculosis. On examination the child had hypopigmented hair color with non tender cervical lymph nodes 3 to 4 in number (3 cm × 5 cm in size). A skeletal survey showed multiple osteolytic lesions of skull and long bones. The CECT chest showed no lymph nodes in the mediastinum. He was given prednisolone 2mg/kg/day for a period of six weeks. The lymph nodes did not regress in size and he continued to have fever. It was decided to treat him empirically with four alternating cycles of ABVD/COPP. He improved markedly and the cervical and axillary group of lymph nodes regressed. The repeat CECT of chest and abdomen showed no residual disease.
In the first 5 cases, the diagnosis of SHML was documented on biopsy of the lymph nodes (Figs. 1-2). In the last case, lymph node biopsy showed fibro collagenous tissue infiltrated by lymphocytes and histiocytes. The histiocytes were strongly S-100 protein positive on immunohistochemistry diag-nosing SHML. EB virus monospot test was negative in all cases. TORCH titers were within normal limits. Tuberculin test was not reactive in any of the cases. Discussion SHML or RDD is a well recognized benign syndrome but a rare cause of lymphadenopathy in the first decade of life. In the present report all the six cases had presented with cervical lymphadenopathy. The disease should be considered in the differential diagnosis of cervical lymphadenopathy. The extranodal involvement of SHML is seen in 30-40% of the cases. The involvement is reported in the ear, lacrimal sac and subglottis causing narrowing of subglottic area and retropharnyx(5). In extremely rare circumstances the central nervous system can be affected. Suprasellar involvement mimicking meningioma has been reported(6). Paraparesis due to a dural extramedullary mass on magnetic resonance imaging, and SHML proved by immunohistochemical studies of nodal lesions positive for S-100 protein has been reported(7). Osseous lesion can occur as part of SHML(5). We have seen osteolytic lesion in Case 6. The pathogenesis of RDD has not been established so far but speculation relates the disorder to be an aberrant response to an unspecified antigen possibly an infective agent. In the cases reported here the Montoux test for tuberculosis, the titer for EBV, Cytomegalovirus and Toxoplasma in the serum were negative. There is a report of SHML extranodal in skin in a patient infected with human immunodeficiency virus(8). RDD has been associated with elevated Epstein Barr virus (EBV) titers(9). RDD has been shown to respond to acyclovir(10). Using a broad panel of monoclonal and polyclonal antibodies the immunophenotype of the cell infiltrate of the lymph nodes of cases of RDD showed a heterogenity of cell markers. Immunoreactivity of the histiocytes for S-100 protein and CD-68 positive large histiocytes displaying lymphocyte phagocytosis are characteristically seen. The large histiocytes show prominent emperipolesis (documented by a halo round the cells) and may confirm the diagnosis(11,12). The review of literature has reported some series of cases besides sporadic cases. Montogomeri et al.(13) have reported a series of 23 cases of RDD from soft tissue lesions in adults in the age group 24-66 years. RDD entered in a case registry reported a series of 423 cases(14). Eventhough it is considered a benign disease, fatalities could happen due to cellular infiltrates of SHML. In a series of 14 known deaths due to SHML in a registry comprising of 215 patients, there were 4 children only. The causes of death due to SHML were reported to be a combination of cellular infiltration, mass forming ability of SHML and also may be due to defect in immune function(15). Most often the RDD takes a benign course and treatment is not necessary. Treatment is necessary only when the disorder becomes life threatening or organ threatening. Some patients have received surgery, radiation therapy and/or chemotherapy with a combination of vinca alkaloids, alkylating agents and corticosteriods (16-18). Palomera et al(19) have reported SHML showing a complete response to low dose interferon. Out of our 6 cases, 3 cases (case no 2,5 and 6) required treatment for recurring fever and lymphnode enlargement. In one case there was a spontaneous regression. Two cases were lost to follow up. SHML may respond dramatically to prednisolone but recurrence of lymphadenopathy may be seen after a few weeks of stopping steroids. Cases 2,5 and 6 were given a course of steroids following which the lymph node enlargement regressed. The lymph nodes were in remission for 5 years, 6 months and 1 year, respectively. In cases 5 and 6, the symptoms of fever and enlargement of lymph node recurred. We decided to give a multidrug regimen usually given in Hodgkin’s disease in these two cases because SHML has more recently been recorded as a focal finding in lymph nodes involved by Hodgkins lymphoma(20). It has also been reported that SHML may be associated with malignant lymphomas(21). The two cases 5 and 6, were treated with alternating COPP/ ABVD cycles following which the lymph nodes regressed. They are under follow-up for 1 year each with minimal palpable lymph nodes in the neck. The lymph nodes may persist for as long as 3 years(17) and a pattern of steroid dependence has been shown(18). Foucar et al(15) in a series of 215 patients with SHML reported that 34.5% of the cases had evidence of SHML present for five years. Only 23% appeared to be disease free. Horzeff et al(17) also had cited lymph node enlargement on tappering prednisolone. They treated the recurrent lymph nodes with low dose methotrexate and 6 mercaptopurine for 4 months and then the child was put on 6 mercaptopurine alone for 2 years, suggesting that some cases of SHML may require longer duration of treatment. Contributors: VKT and LSA are the Pediatric Oncologists who are registering, treating collecting data, analyzing and following up the cases in the clinic. RD is the histopathologist who provided the diagnosis through special stains. VKT will act as guarantor for the study. Funding: None. Competing interests: None stated.
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