Page 1137 - Williams Hematology ( PDFDrive )

1112 Part VIII: Monocytes and Macrophages Chapter 71: Inflammatory and Malignant Histiocytosis 1113

EPIDEMIOLOGY THERAPY
Children with solitary lesions have a median age of onset of 2 years Patients with a single or only a few lesions need no therapy. An exci-
with a male-to-female ratio of 1.5:1. Children with multiple lesions sional biopsy can be used, if desired for cosmetic reasons. For the rare
have a median age of onset of 5 months and have a male-to-female patients who have systemic disease and require treatment a wide variety
ratio of 12:1. No population study of JXG has been reported, so the of chemotherapy and radiotherapy regimens have been reported. 191–193
precise incidence is unknown. However, a review of JXG from the Kiel Inclusion of a vinca alkaloid and a glucocorticoid is associated with bet-
Pediatric Tumor Registry recorded 129 (0.52 percent) cases of JXG and ter overall response rates than single agents. A child with CNS JXG who
800 (3.3 percent) cases of LCH among 24,600 children over a 36-year failed to respond to vinblastine was successfully treated with cladrib-
period. ine. A series of four children with systemic and CNS JXG were suc-
194
cessfully treated with clofarabine. 84
ETIOLOGY AND PATHOGENESIS COURSE AND PROGNOSIS
There is no known cause of JXG. Patients with JXG and neurofibroma- Patients with only skin or soft-tissue involvement all survive and in a
tosis types 1 and 2, as well as the triad of the aforementioned diseases majority of cases, the lesions spontaneously disappear over time. Infants
with juvenile chronic myelogenous leukemia, have been reported. 185–187 with large retroperitoneal masses, liver, marrow, or CNS involvement
These and other cases have suggested an increased risk of leukemia in usually survive with chemotherapy treatment. Two of 17 patients with
neurofibromatosis patients with JXG, but there is no rigorous proof for multisystem JXG reported in the literature died despite multiagent
this association. 188,189 chemotherapy. 192

CLINICAL FEATURES
The majority of patients are children younger than 2 years of age who SINUS HISTIOCYTOSIS WITH MASSIVE
have solitary skin nodules on their head, neck, or trunk. 184,190 The lesion LYMPHADENOPATHY (ROSAI-
is most often the same color as surrounding skin, but may be erythe-
matous or yellowish. Rarely, nodules may be in the subcutaneous fat, DORFMAN DISEASE)
deep soft tissue, or skeletal muscle. Organ involvement is rare, but has
been reported in the soft tissue, CNS, bone, lung, liver, spleen, pancreas, DEFINITION AND HISTORY
adrenal, intestines, kidneys, lymph nodes, marrow, and heart. 184,190,191 Rosai and Dorfman recognized this nonmalignant proliferation of his-
Systemic symptoms and signs occur only if these organ systems are tiocytes as a unique histopathologic entity, which is part of the differen-
involved. tial diagnosis of massive lymphadenopathy. Although this disease is
195
self-limited in some patients, others with airway obstruction, multiple
bone lesions, orbital or brain tumors require therapy. 84,196
LABORATORY FEATURES
Immunohistochemical staining of biopsies is necessary to differentiate EPIDEMIOLOGY
JXG from other histiocytic lesions. JXG classically stains with a mac-
rophage marker such as antibodies to CD68 or Ki-M1P, factor XIIIa, RDD is found throughout the world as a disease of children and young
fascin, vimentin, and often CD4. They are negative for S100 and anti- adults (mean age: 20.6 years). Most of our knowledge about it is the result
CD1a. There are three characteristic histologic patterns: early JXG, clas- of analysis of the 423 cases in the registry developed by Rosai and Dorf-
sic JXG, and transitional JXG. Early JXG is characterized by small- to man in which there was no gender, ethnic, or socioeconomic predilec-
190
intermediate-size mononuclear histiocytes in sheet-like infiltrates. The tion. Persons of African and European descent are equally represented;
cells in this category have only small quantities of lipid in the cyto- people of Asian descent less so. In cases of digestive system disease,
197
plasm and Touton-type giant cells are absent. This type has relatively males and persons of African descent were more commonly affected.
more mitoses than the others, but there is no cytologic atypia. Classic Intracranial disease is found in patients with a mean age of 37.5 years.
JXG exhibits abundant vacuolated, foamy histiocytes with Touton giant There is an apparent increase in rheumatologic disorders and hemolytic
cells (lipid-laden histiocytes with multiple nuclei and a small amount anemia among these patients. 198,199 Germline mutations in the nucleoside
of centrally oriented cytoplasm). Transitional JXG has a predominance transporter SLC29A3 have been described in patients with rare familial
of spindle-shaped cells resembling benign fibrous histiocytoma with syndromes that include lymphadenopathy characteristic of RDD. 200
foamy histiocytes and occasional giant cells. Biopsies also contain
190
lymphocytes, eosinophils, and occasionally Charcot-Leyden crystals. If ETIOLOGY AND PATHOGENESIS
the marrow is involved, patients may have cytopenias. Liver infiltration
may cause elevation of liver enzymes, hypoalbuminemia, and an ele- Although associations with various herpes virus infections have been
vated erythrocyte sedimentation rate. Pituitary involvement may lead reported, these most likely represent detection of lymphocytes or macro-
to DI. Hypercalcemia has been reported. CNS lesions can lead to hydro- phages harboring these viruses with no relation to etiology. A model for
cephalus, seizures, and developmental delay. the key histopathologic finding, emperipolesis of lymphocytes by mac-
rophages, has been proposed. These authors hypothesized that mac-
201
DIFFERENTIAL DIAGNOSIS rophage-activating cytokines could stimulate the macrophages to ingest
lymphocytes. The cells in the lesions of this disorder are polyclonal.
202
LCH is the disease most often confused with JXG. Other disorders
to be considered include fibrohistiocytic lesion not otherwise spec-
ified, reticulohistiocytoma, hemangioendothelioma, Spitz nevus, CLINICAL FEATURES
malignant fibrous histiocytoma, and rhabdomyosarcoma or other Massive, painless bilateral cervical adenopathy is the presenting finding
malignancies. in 87 percent of patients. Some have fever, night sweats, malaise, and

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