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1106 Part VIII: Monocytes and Macrophages Chapter 71: Inflammatory and Malignant Histiocytosis 1107

higher risk of initial treatment failure, and circulating cells with the Skull Lesions in the Mastoid, Temporal, Orbital or Base of Skull
BRAF V600E mutation to correlate with active disease, though these obser- Bones (CNS-Risk Lesions) The purpose of treating these patients with
vations remain to be validated in prospective trials. 5 systemic therapy is to decrease the risk of developing DI. In a large series
of patients with CNS-risk lesions who received little or no chemother-
DIFFERENTIAL DIAGNOSIS apy there was a 20 to 50 percent incidence of DI compared to incidence
52
It is not unusual for infants with LCH skin lesions to have symptoms for rates of 10 percent in patients treated with systemic chemotherapy.
longer than 1 year prior to having a diagnostic biopsy. The varied cuta- The current standard of care, based on the LCH-III study, is to treat
34
neous presentations of LCH may mimic a fungal diaper rash, seborrheic patients with single or multifocal lesions in CNS risk sites for 12 months
scalp rash or cradle cap, congenital viral infections, neuroblastoma, with intravenous vinblastine and oral prednisone: weekly intravenous
2
contact dermatitis, or psoriasis (see Fig. 71–1). Women or men with vinblastine (6 mg/m ) for 7 weeks, with daily oral prednisone (40 mg/
2
genital lesions may be thought to have a sexually transmitted disease or m ) for 4 weeks followed by a 2-week taper. If there is a good response
other infection. Oral lesions mimic other ulcerative conditions, gingival by 6 weeks, then vinblastine frequency is decreased to every 3 weeks.
infections, or dental caries. Copious white or green discharge from the After the first 6 weeks, oral prednisone is given for 5 days at 40 mg/m 2
ears resembles otitis externa. Lytic bone lesions are often thought to be every 3 weeks with the vinblastine intravenous. Patients with subop-
evidence of a malignancy such as neuroblastoma, rhabdomyosarcoma, timal responses by 6 weeks are given an additional 6 weeks of weekly
or Ewing sarcoma. Collapsed vertebrae from LCH may mimic tubercu- intravenous vinblastine. 39
losis bone disease, trauma, or osteomyelitis. The interstitial infiltrates Multiple Bone Lesions or Combinations of Skin, Lymph Node,
found in LCH patients with pulmonary involvement may resemble a or Pituitary Gland Involvement with or Without Bone Lesions
viral pneumonia. An enlarged thymus or mediastinal lymph nodes can Patients should be treated for 12 months with intravenous vinblastine
cause respiratory distress and wheezing similar to asthma. Enlarged and oral prednisone as outlined for the CNS-risk lesions. Both shorter
lymph nodes from LCH mimic any infiltrative condition such as lym- (<6 months) treatment strategies and treatment with only a single agent
phomas, other histiocytic diseases, infections, or immune-related con- (e.g., prednisone) are associated with inferior outcomes. A 37 percent
ditions. Likewise, hepatosplenomegaly of LCH patients can result from reactivation rate with a two-drug regimen has been reported, versus 50
the same conditions. Chronic diarrhea in LCH patients may initially to 80 percent with only surgery or single-drug treatments. 39,53,77
be considered to be an infectious or inflammatory bowel disease. Iso- Spleen, Liver, or Marrow (May or May Not Include Skin, Bone,
lated DI with enlargement of the pituitary may suggest a germinoma, Lymph Node, or Pituitary Gland Involvement) The standard therapy
lymphoma, or hypophysitis. LCH should be strongly considered when used for LCH in high-risk organs (spleen, liver, and/or marrow) is based
symptoms of other more common conditions do not respond to therapy. upon the LCH-III results in which oral mercaptopurine was added to
Occasionally infiltrates of LC are found in various malignancies intravenous vinblastine/oral prednisone regimen, outlined for the low-
39
and as such represent an attempt of the immune system to respond to risk patients above. The addition of oral or intravenous methotrexate
that disease. 65–67 Similarly LCH may be found in the thymus of patients did not improve the overall survival or risk of reactivation. Another
with myasthenia gravis. 68 more intensive regimen (JLSG-96) has been reported that includes
intravenous cytarabine, intravenous vincristine, oral prednisolone, and
TREATMENT methotrexate for good responders or a salvage therapy with intravenous
daunorubicin, intravenous cyclophosphamide, intravenous vincristine,
Pediatric Patients and oral prednisolone for poor responders. Both treatments lasted 7.5
78
The current optimal treatment of childhood and adults LCH patients, as months. Table 71–3 compares the results of the LCH-III and JLSG-96
with other rare conditions, is on clinical trials. The U.S. National Cancer trials.
Institute website (http://www.cancer.gov/cancertopics/pdq/treatment/ Central Nervous System Treatment of mass lesions, including
lchistio/HealthProfessional) and the Histiocytosis Association (http:// enlargement of the hypothalamic–pituitary axis, parenchymal mass
www.histio.org; 1–856–589–6606) also may be useful resources. lesions, and leptomeningeal involvement, with cladribine has been
Patients with only skin LCH, some single-bone lesions (non–CNS- effective. Doses of cladribine ranged from 5 to 13 mg/m given intrave-
2
risk), and isolated DI have not been studied in Histiocyte Society clini- nously at varying frequencies. 79
cal trials, but are discussed in this section.
Skin-Limited Lesions Skin-limited lesions may require therapy
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if they are symptomatic. One approach is topical glucocorticoids, TABLE 71–3. Comparison of Treatment Outcomes
although rarely effective. Other approaches with reported efficacy in High-Risk Langerhans Cell Histiocytosis Patients
69
include oral methotrexate (20 mg/m weekly) or oral thalidomide (50 LCH-III* JLSG-96
2
70
to 200 mg daily). Topical application of nitrogen mustard may be effec-
tive for cutaneous LCH that is resistant to oral therapies, but is contrain- Number of patients 235 59
71
dicated for large areas of skin. Psoralen plus long-wave ultraviolet A Median age at diagnosis 1.1 0.9
radiation (PUVA) has been used as well. The approach is limited by the Therapy duration (mo) 12 7.5
72
severity and distribution of the skin involvement.
Single Skull Lesions of the Frontal, Parietal, or Occipital Initial response 70–72* 76
Regions, or Single Lesions of Any Other Bone Curettage or curettage Reactivations 25–29 45
plus injection of methylprednisolone may be used. 73 Survival 88 97
Vertebral or Femoral Bone Lesions at Risk for Collapse Isolated
radiation therapy is indicated for patients with single bone lesions of a LCH-III, Histiocyte Society Langerhans cell histiocytosis treatment
vertebrae or the femoral neck, which are at risk of collapse. 74,75 When protocol III; JLSG-96, Japan Langerhans Cell Histiocytosis Study
instability of the cervical vertebrae and neurologic symptoms are pres- Group protocol 96.
76
ent, bracing or spinal fusion may be needed. Certain skull lesions, not *Arm A (velban/prednisone) vs. Arm B (velban/prednisone/
in the CNS-risk region, could also be considered for radiation therapy. methotrexate).

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