Rosai–Dorfman disease (RDD) is a rare, usually self-limiting disease caused by a histiocytic proliferation of unknown aetiology in the lymph nodes sinuses and extranodal tissue. The condition usually presents with massive lymphadenopathy involving multiple lymph node groups in the body but is not always confined to the lymph nodes – it can also involve extranodal tissues such as the skin, liver, spleen and central nervous system. We present the case of a 50-year-old female with RDD with hepatosplenomegaly initially misdiagnosed with tuberculosis.
Keywords: Hepatosplenomegaly, Rosai–Dorfman disease, sinus histiocytosis
| Introduction|| |
Rosai–Dorfman disease (RDD; also known as sinus histiocytosis with massive lymphadenopathy) is a rare, benign, self-limiting proliferation of histiocytes in the sinusoids of lymph nodes and/or extranodal tissues that can mimic a lymphoproliferative disorder. Cervical lymph nodes are the most commonly involved lymph node group, and they often reach massive proportions. Extranodal involvement most commonly affects the skin; however, gastrointestinal, genitourinary, brain and bone tissues have also been affected. We present the first known case of RDD with lymphadenopathy and gastrointestinal involvement presented to our hospital.
| Case Report|| |
A 50-year-old female from Kohat presented to the outpatient department of the Medical “D” Unit of the Khyber teaching hospital in Peshawar. She reported a 6-month history of fever, generalised body aches and lymphadenopathy. The fever was high-grade, continuous and associated with rigors, chills and generalised body aches that were partially relieved with 1 g acetaminophen. She also had loss of appetite, weight loss and disturbed sleep. She reported painful swellings in the groin, axilla and cervical region. The swellings grew until a discharging sinus would form at the tip, then the swellings would disappear. The patient reported receiving multiple blood transfusions in the last 6 months to treat anaemia.
On examination, she was vitally stable and well oriented in time, place and person. She was anaemic with enlarged posterior cervical lymph nodes measuring 1 cm by 1.5 cm. We noted three enlarged lymph nodes in the left axilla measuring approximately 2 cm by 2 cm. A chest examination revealed reduced air entry and crepitations on the right side of her chest. Heart sounds on auscultation were normal. On abdominal examination, we noted non-tender hepatosplenomegaly with no other significant findings. She had normal reflexes in the upper and lower limbs. On fundoscopy, we noted the fundus was normal, and we found nothing abnormal during her cranial nerve examination.
The patient's laboratory investigations are presented in [Table 1]. The patient had hypochromic microcytic anaemia. Urine and blood cultures showed no microbial growth. The patient's liver function test results were normal. The tuberculin skin test results were negative. Serological test results for viral infections, including hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody, hepatitis C antibody, hepatitis A antibody (immunoglobulin M [IgM]), hepatitis E antibody (IgM) and viral-capsid antigen (IgM), were negative. The patient also tested negative for toxoplasmosis.
Echocardiography findings were unremarkable. We performed abdominal and pelvic ultrasound examinations which showed an enlarged liver measuring 19 cm and an enlarged spleen measuring approximately 17.5 cm. We also found multiple enlarged lymph nodes in the porta hepatis, pancreaticoduodenal and celiac regions.
A biopsy specimen from the cervical lymph nodes of the posterior triangle of the neck showed necrotising granulomatous inflammation. The patient was, therefore, started on antituberculous treatment (ATT) and low-dose steroids. However, her condition did not improve; however, we noted a reduction in the size of her lymph nodes.
After 3 months of ATT, she reported severe abdominal pain along with vomiting and reduced oral intake. The ATT was stopped, and a computed tomography (CT) scan (with contrast) of her chest, abdomen and pelvis was performed to determine the cause of her abdominal pain and the lack of response to ATT. The CT revealed focal ground-glass haze in both lungs, enlarged lymph nodes in the anterior mediastinum and bilateral axillae, mildly enlarged interaortocaval lymph nodes and left paraaortic lymph nodes along with hepatosplenomegaly [Figure 1]a and [Figure 1]b.
|Figure 1: (a) Computed tomography scan with contrast of abdomen showing hepato-splenomegaly. (b) Computed tomography scan with contrats of abdomen and pelvis showing enlarged para-aortic lymph nodes|
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Based on the CT scan findings, the patient underwent laparoscopy and biopsies of her mesenteric lymph node, and omentum was taken. The omentum showed acute on chronic inflammation while the biopsy of the lymph node revealed enlarged sinuses infiltrated with histiocytes. These histiocytes had normal lymphocytes and plasma cells within. No granuloma or necrosis was seen. Many of the histiocytes had intact lymphocytes within their cytoplasm [Figure 2] – an important diagnostic feature known as emperipolesis.
|Figure 2: Histopathology specimen of the lymph node showing enlarged sinuses infiltrated with histiocytes. These histicoytes had normal lymphocytes and plasma cells within. Many of the histiocytes had intact lymphocytes within their cytoplasm-an important diagnostic feature known as emperipolesis|
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Given the patient's history, examination, investigations and biopsy report, the diagnosis of sinus histiocytosis with lymphadenopathy (i.e., RDD) was made.
The patient was referred to an oncologist for further management who prescribed daily thalidomide (100 mg) along with steroids.
The patient was counselled regarding the prognosis of the disease and advised to maintain regular follow-up evaluations every 3 months to monitor the effectiveness of her medications, the development of complications and the progress of her disease.
| Discussion|| |
A Class II histiocytosis, RDD was described for the first time by Pierre-Paul Louis Lucien Destombes in 1965 and was labelled a distinct pathological entity by Rosai and Dorfman in 1969., RDD predominantly affects children under age 10 (66% of cases) and young adults under age 20 (80% of cases) with male predilection.
Although the exact aetiology of RDD is unknown, possible causes include viral infections (Epstein–Barr virus, parvovirus B19 and human herpes virus), immunodeficiency, autoimmune disease and neoplastic processes. Our patient had no evidence for any such infections both in history and on investigation.
The lymphatic disease affects the cervical lymph node group in 87% of the cases and are often bilateral and painless. The axillary, inguinal and mediastinal groups may also be affected in 23.7%, 25.7% and 14.5%, respectively, in proportions not as severe as seen in the cervical group. Our patient had cervical and axillary groups involved, along with anterior mediastinal, pancreaticoduodenal, porta hepatis and para-aortic lymphadenopathy which are very uncommon sites of lymphatic involvement in this disease.
Hepatosplenomegaly, a rare finding in RDD, was present in our patient and documented on ultrasound and CT scan., Patients may also report concerns of fever, night sweats and weight loss on presentation as our patient did.
Microscopic features have been described as dilated lymph node sinuses with a mixed cellular infiltrate composed of neutrophils, lymphocytes, plasma cells and medium-sized mononuclear cells with indented nuclei, and typically, numerous large and distinctive RD cells can be found. RD cells have abundant cytoplasm with round-to-oval, medium-to-large nuclei with a vesicular chromatin pattern. Nuclear atypia is unusual. Intact-appearing phagocytised lymphocytes are present in the cytoplasm of most RD cells (lymphocytophagocytosis or emperipolesis, i.e., ‘wandering about within’), which is a diagnostic feature. RD cells are S-100 protein-positive on immunohistochemistry. In extranodal involvement, the microscopic picture is exactly similar to the nodal disease and appears to have abnormal lymph node architecture. The histopathology of the biopsy specimen of our patient showed all the above features except S-100 protein on immunohistochemistry which could not be done due to facility constraints.
Common differential diagnoses include infectious lesions, reactive lymphoid hyperplasia with sinus histiocytosis, Langerhans cell histiocytosis, hemophagocytic syndrome and malignant lymphoma. A detailed history and careful physical examination usually prevent misdiagnosis.
Prognosis of RDD widely varies from spontaneous healing within weeks to months to persistence or recurrence following surgical excision or medical treatments. Regression is often spontaneous, and aggressive therapeutic measures are not recommended. A literature review showed that 50% of patients with RDD require no treatment, and 82% of untreated patients experience spontaneous and complete disease regression.
Due to the rarity of the disease, no standard treatment has yet been defined for RDD. However, since the condition is self-limiting, it is often unnecessary to intervene except when the airways are obstructed, or vital organs are compressed. Several treatment options have been described involving corticosteroids, chemotherapy combined with alkaloids, anthracyclines, antimetabolites and alkylating agents, interferon, antibiotics, radiotherapy and partial or total surgical resection.
The presentation of our patient with fever, weight loss and lymphadenopathy with poor general condition along with the high prevalence of tuberculosis in our region lead to a misdiagnosis of tuberculosis and initiation of ATT, which could have been avoided had RDD been kept in the differential diagnosis options.
| Conclusions|| |
This case report shows how a rare disease could be misdiagnosed and treated as another disease-carrying significant morbidity. RDD mainly presents in the first two decades of life as bilateral painless cervical lymphadenopathy, and some patients also have extranodal involvement on presentation. The aetiology is poorly understood, however, the diagnosis could be reached through histopathological examination of the affected tissues and immunohistochemical staining, thereby preventing the unnecessary exposure of patients to aggressive therapies.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
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Medical D Unit, Khyber Teaching Hospital, Peshawar
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]