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1110 Part VIII: Monocytes and Macrophages Chapter 71: Inflammatory and Malignant Histiocytosis 1111

Dendritic or Langerhans Cell Sarcomas TREATMENT, COURSE, AND PROGNOSIS
Histologic differentiation of dendritic-LC sarcomas from HS include Therapy for dendritic and LC sarcomas has usually been unsuccess-
long DC processes, convoluted nuclei, more intense S100 staining and ful. However, case reports of long-term remissions with oral thalido-
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weaker CD68 staining. These patients may have fever or weight loss. mide, 145,146 intravenous alemtuzumab, or intravenous MAID (mesna,
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They usually present with erythematous nodules or a skin rash, and may doxorubicin [Adriamycin], ifosfamide, and dacarbazine) have been
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also have involvement of bone, lymph nodes, lung, liver, or brain. 137,138 A published. In some instances, surgical resection of a localized mass with
series of histiocytic-DC sarcomas in patients with follicular lymphomas radiotherapy has been successful.
showed a clonal evolution from the B-cell lymphoma to myeloid-derived Interdigitating DC sarcomas, also, have been treated successfully
sarcomas. with surgery alone or a combination of surgery and radiotherapy, when
the tumor is localized. Patients with stage III/IV tumors generally do
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Extranodal Histiocytic Sarcomas not respond to multidrug chemotherapy, such as intravenous cyclo-
These tumors occur equally in males and females and present at a phosphamide, doxorubicin, and vincristine and oral prednisone with or
median age of 55 years. Tumors are found in the soft tissue of extrem- without the addition of intravenous actinomycin D.
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ities, the gastrointestinal tract, the nasal cavity, and the lung, sometimes
with involvement of regional lymph nodes. Gastrointestinal masses
were usually painful. Extremity tumors often present as painless masses.
Patients had symptoms or signs for 1 month to 2 years before diagnosis. MALIGNANT FIBROUS HISTIOCYTOMA
Most tumors are localized at the time of diagnosis. AND GIANT CELL TUMOR OF THE BONE

Interdigitating Dendritic Cell Sarcomas Gene-profiling experiments have shown that these tumors are not
Interdigitating DC sarcomas may occur as extranodal tumors in chil- derived from histiocytes, but are poorly differentiated fibrosarcomas,
dren and primarily affect lymph nodes in adults. A report of four myosarcomas, fibromyxosarcomas, or liposarcomas. 149–151 They are
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pediatric cases had involvement of the chest wall, vertebrae, lymph treated with a similar approach as are osteosarcomas. 152–154
nodes, marrow, and pelvic space. Of the other seven pediatric and 26
adult cases, 17 had extranodal presentations. Many of the 17 cases had
intestinal or mediastinal tumors. These tumors were very aggressive in
a third of cases. 141,142 ERDHEIM-CHESTER DISEASE
DEFINITION AND HISTORY
Follicular Dendritic Cell Tumors In 1930, two cases of “lipid granulomatosis” were described by William
The malignant cells in these patients are spindle to ovoid forming fasci- Chester and Jakob Erdheim and later designated as Erdheim-Chester
cles, storiform patterns and whorls which stain with CD21, CD23, and disease. The histopathologic characteristics of ECD overlap xantho-
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CD35. These malignancies affect males and females equally and present granuloma and distinctions between the two are made on the basis of
at a median age of 47 years (range: 14 to 77 years). Nodal and extran- clinical and radiologic findings. Lipid-laden histiocytes with foamy or
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odal sites can be affected. Most frequent nodal presentations are cervi- eosinophilic cytoplasm infiltrate bones and various organs and gener-
cal, axillary, and supraclavicular; mediastinal and mesenteric nodes can ate a fibroblastic response that leads to critical organ failure. The his-
also be affected. These tumors are usually slow growing and painless. tiocytes are CD68+, CD163+, factor XIIIa+, CD1a−, and S100−, and
Although local invasion is common, metastasis to sites other than the do not contain Birbeck granules. Touton-like giant cells are commonly
lungs is uncommon. found.

LABORATORY FINDINGS
Patients with diffuse disease may have pancytopenia, although leuko- EPIDEMIOLOGY/ETIOLOGY
cytosis occurs in some as a secondary response. Hemophagocytosis is This disease primarily affects adults (mean age: 53 years; range: 7 to 84
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occasionally seen in the marrow. An elevated lactate dehydrogenase and years) with a predominance of males (73 percent). There is no known
erythrocyte sedimentation rate may be found. etiology. Cells from ECD biopsies have been found to be clonal in three
of five cases tested and polyclonal in two. 157–159 Elevated levels of osteo-
pontin in ECD tissue have been found at diagnosis, which then declined
DIFFERENTIAL DIAGNOSIS after treatment with prednisolone. It is difficult to judge the exact role
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A diagnostic biopsy with a full immunophenotype panel should be of osteopontin in ECD as it has many functions as a noncollagenous,
done for these rare tumors, which have been mistaken for Hodg- extracellular matrix protein that may affect cell adhesion, migration,
kin lymphoma, anaplastic large cell lymphoma, or large cell lym- and other functions. Immunohistochemical staining of ECD tissue
phomas of T- or B-cell subtypes. The DC neoplasms do not express shows expression of CCL2 (monocyte chemotactic protein 1), CCL4
T- or B-lymphocyte markers and do not have rearrangements of (macrophage inflammatory protein-1β [MIP-1β]), CCL5 (RANTES
immunoglobulin or T-cell receptor genes. 133,142,143 Malignant fibrous [regulated upon activation, normal T-cell expressed and secreted]),
histiocytoma, fibrosarcoma, leiomyosarcoma, rhabdomyosarcoma, CCL20 (MIP-3α), and CCL19 (MIP-3β), along with their receptors
or melanoma may simulate interdigitating DC sarcoma, as well as CCR1, CCR2, CCR3, CCR5, CCR6, and CCR7. Elevated expression
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inflammatory pseudotumor. Although follicular DC sarcoma and of an IFN-γ–inducible protein, IL-6, and RANKL has been described.
histiocytic lymphoma may have a similar presentation, the specific The latter two factors are important for bone remodeling. Biopsies of 32
immunophenotype of the tumors helps differentiate them from inter- of 37 patients with ECD had prominent staining for the platelet-derived
digitating DC sarcoma. Thymomas, meningiomas, and malignant growth factor receptor-β. The inflammatory nature of ECD is indi-
fibrous histiocytomas can mimic follicular DC sarcoma, but they lack cated by an elevation of cytokines in a cohort of 37 patients. A T-helper
CD21 and CD35. type 1 (Th1)-associated signature in ECD patients was associated with

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