In RDD the key factor that induces both chemotaxis of blood monocytes to the site of the lesion and the differentiation of these monocytes into RDD histiocytes is thought to be M-CSF (macrophage colony-stimulating factor). Monocytes are found in small amounts within the pulp of reactive lymph nodes and the interstitium of other organs that secrete M-CSF, which acts as chemotactic factor to recruit more blood monocytes to the site of the lesion. M-CSF stimulates blood monocytes to differentiate into mature macrophages capable of phagocytosis.4
The initial precipitating factor that leads to M-CSF production by resident monocytes, resulting in histiocytosis and potent phagocytosis, is yet to be discovered. This may be part of an immune-mediated disorder or a virus-mediated disorder.
Sinus histiocytosis is a diffuse, lymphoproliferative disorder involving numerous organs that occurs most often in children or young adults, although patients in their 7th decade have also been described. Associated symptoms and signs may be caused by specific organ involvement or may be constitutional, such as fever and weight loss. Laboratory findings include anemia, leukocytosis and serum polyclonal hypergammaglobulinemia. Although early descriptions concluded that nearly every case was marked exclusively by cervical lymph node involvement, other organ systems may be affected including the eye and eyelid, bone, central nervous system, ear, nose, throat, upper respiratory tract, liver, skin, salivary gland and testis. Coexistent lymphadenopathy, especially in retroperitoneal sites such as the para-aorta, iliac and inguinal lymph node chains has been noted in as many as 78% of patients. However, this disorder may also occur primarily, if not exclusively, in an extranodal site such as the facial skin or muscles, orbit, paranasal sinuses6
Kidney involvement is very uncommon, and therefore sinus histiocytosis is not frequently considered in the differential diagnosis of an infiltrative renal mass. Four cases of RDD in kidney cases have been reported with two of them diagnosed with adenocarcinoma of the prostate. None, including the one referred to us, had lymphadenopathy and all were in the same location within the kidney. The patients had been referred for renal masses and urinary conditions. Renal RDD accompanied by prostate adenocarcinoma warrants more study. In a rare case reported by Buchino et al, the kidney was only focally involved with a single small mass in the lower pole that contained an admixture of histiocytes, lymphocyte and plasma cells.8
In another case reported by Bechtold et al, a lobular irregularly enlarged kidney with distorted calyces associated with large matted para-aortic lymph nodes was described and the diagnosis was RDD.9
Some patients may experience spontaneous regression of the lesion, while others have a chronic course with stable or progressive disease.10
Grossly the masses are matted together by prominent perilesional fibrosis. Their cut surface varies from gray to golden yellow, depending on the amount of fat present. Microscopically there is an accumulation of lymphocytes, plasma cells (some containing Russell bodies), and most notably numerous cells of histiocytic appearance with a large vesicular nucleus and abundant clear cytoplasm that may contain large amounts of neutral lipids. Many of these histiocytes have within their cytoplasm numerous intact lymphocytes, a feature that has been designated as emperipolesis or lymphocyte phagocytosis.11
Although not specific to RDD, this is a constant feature of RDD and is therefore of great diagnostic significance. Sometimes other cell types are present within the cytoplasm of the histiocytes such as plasma cells and red blood cells. The histiocytes contain cytoplasmic fat and are strongly reactive for S100 protein, but negative for CD1a. The plasma cells show a polyclonal pattern of immunoglobulin expression. The lymphocytes present are an admixture of B and B and T cells.
The differential diagnosis of RDD in kidney includes malignant fibrous histiocytomas and histiocytic proliferations of infectious etiology (the presence of S100 is useful in discriminating these lesions), leukemia or lymphoma, especially when accompanied by lymphadenopathy (absent of emperipolesis and IHC profiles help to correct diagnosis). Other possible differential diagnoses include storage disease, tuberculosis or even renal cell carcinoma, a metastatic tumor such as malignant melanoma. RDD generally has a favorable prognosis, but involvement of a greater number of nodal groups and associated extranodal systems worsens the prognosis.11,12
A high mortality rate is associated with disseminated nodal disease, the presence of systemic immunological disorders and involvement of unusual sites such as the liver, kidney or lower respiratory tract. No intervention is necessary in most cases, but some patients may undergo surgery. In disseminated aggressive cases, chemotherapy and external may be used.