Management of Spinal Langerhans Cell Histiocytosis in Children: A Systematic Review

Macherla Haribabu Subramaniam; Victor Moirangthem; Muralidharan Venkatesan

doi:10.14444/8662

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Figure 1
Garg’s grading of radiographic collapse of the vertebral body.
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Figure 2
Literature search as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses-2020 guidelines.
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Figure 3
Mean time taken by various treatment modalities to completely restore vertebral body height. ROVE, reconstitution of vertebral body height.
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Figure 4
Comparison between the treatment modalities of systemic chemotherapy and surgery in children presenting with neurological symptoms.
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Figure 5
The proposed management algorithm for spinal Langerhans cell histiocytosis (LCH) in children aged 15 years or younger.
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Figure 6
Two-year-old boy with grade IIB spinal T11 Langerhans cell histiocytosis. (A and B) Radiographic picture. (C and D) CT images. (E) T2-weighted magnetic resonance imaging. (F and G) One-year follow-up following surgery. (H and I) Three years following surgery, 1 year following implant removal. Complete remodeling of vertebral body and near-total restoration of vertebral body height is seen. Reprinted with permission from Zheng et al.16

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Table 1

Assessment of bias among included studies—MINORS’ criteria.

Items	Peng et al, 200910	Jiang et al, 201111	Abdelaal et al, 202012	Nakamura et al, 201913	Zhou et al, 201714	Zheng et al, 202215	Zheng et al, 202216	Zhong et al, 201617
A clearly stated aim	2	2	2	2	2	2	2	2
Inclusion of consecutive patients	2	2	2	2	2	2	2	2
Prospective collection of data	2	2	2	2	2	2	2	2
Endpoints appropriate to the aim of the study	2	2	2	2	2	2	2	2
Unbiased assessment of the study endpoint	2	1	2	2	2	2	2	2
Follow-up period appropriate to the aim of the study	2	1	2	2	2	2	2	2
Loss of follow-up less than 5%	2	2	2	2	2	2	2	2
Prospective calculation of study size	0	0	0	0	0	0	0	0
An adequate control group	0	0	0	0	0	2	0	0
Contemporary groups	0	0	0	0	0	0	0	0
Baseline equivalence of groups	0	0	0	0	0	0	0	0
Adequate statistical analysis	1	1	1	1	1	2	2	1
Total	15	13	15	15	13	18	16	15
Risk	Low	Low	Low	Low	Low	Low	Low	Low

Abbreviation: MINORS, methodological index for non-randomized studies.
Note: 2 (green) is considered good, 1 (yellow) is considered moderate, and 0 (red) is no score.

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Table 2

The demographic characteristics of the patient population of the included studies.

Authors	No. of Patients	Mean Age	Mean Follow-Up	Site of Involvement	Clinical and Radiological Presentation
Peng et al10	9	7.7 y	30.3 mo	Cervical—2 Thoracic—5 Lumbar—1 Sacral—1	8 patients (88.9%) patients had neurological symptoms
Jiang et al11	5	18 y	7.2 y	Multiple sites	Neck pain and low back pain 2 patients had neurological symptoms
Abdelaal et al12	12—solitary site 3—multifocal sites	Not provided	49 mo	Cervical—5 Thoracic—8 Lumbar—4	Anterior wedging: 2 Vertebra plana picture:13
Nakamura et al13	5—solitary site 8—multifocal sites	3.6 y	10.2 y	Cervical—3 Thoracic—3 T-L junction—2 Lumbar—5	Not provided
Zhou et al14	31 (23 —solitary spinal site; 8—multifocal skeletal sites)	8.8 ± 2.8 y	2.9 ± 1.1 y	Cervical—8 Thoracic—11 Lumbar—4	Back pain or neck pain according to the location of the tumor Neurological symptoms: 8 patients Local kyphosis: 4 patients
Zheng et al15	9 patients	66.7 mo	26.7 mo	Thoracic—4 Lumbar—5	Vertebral collapse more than 50%
Zheng et al16	15 patients	74.3 ± 38.8 mo	2.9 y	Thoracic—9 Lumbar—6	Vertebral collapse more than 50% Asymmetrical destruction of vertebral body with collapse less than 50%
Zhong et al17	19 patients	9.9 ± 3.1 y	36.4 ± 13.7 mo	C1–C2: 7 patients C3–C7: 12 patients	1. Neck movements restriction 2. Neck pain 3. Neurological symptoms 4. Torticollis

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Table 3

The treatment modalities used in the studies relevant to Garg’s classification and salient findings of the studies.

Authors	Garg’s Classification	Treatment Modality	Assessed Outcome Parameters	Conclusion and Salient Findings
Peng et al10	Unclear about grades I or II; A: 3 patients; B: 5 patients; III: 1 patient	Chemotherapy: 8 patients; Chemotherapy + surgery: 1 patient	At last follow-up, MRI images revealed disappearance of soft tissue shadow.	Chemotherapy is safe and effective. Surgery is indicated for spinal instability or with severe neurological deficit.
Jiang L et al11	Not provided	Chemotherapy + local radiotherapy: 1 (case 1) Radiotherapy: 2 (cases 2 and 5) Surgery: 1 (case 3) radiotherapy + surgery: 1 (case 4)	Clinical symptoms resolved at last follow-up.	Chemotherapy is highly effective. Surgery in lesions causing neurology which are not amenable to chemotherapy or radiotherapy.
Abdelaal et al12	Unclear	Nonoperative treatment: 11 Surgery: 2 Died: 2 (by mean 27 months on nonoperative treatment)	Vertebral body height restoration.	Nonoperative treatment yields results. Surgery is indicated when the lesion is in cervical spine.
Nakamura et al13	Not provided	Brace: 9 patients, of which 8 patients had systemic chemotherapy + brace Supervised management: 4 patients	Anterior, posterior vertebral wall height restoration.	Vertebral body height restoration occurs eventually with treatment. It can be assessed by measuring the height of anterior, posterior vertebral body wall height.
Zhou et al14	Not provided	Surgery only: 6 Surgery + radiation therapy: 9 Surgery + chemotherapy: 4 Surgery + radiotherapy + chemotherapy: 4 Radiotherapy: 5 Chemotherapy: 1 Radiotherapy + chemotherapy: 2	Local pain relief and neurological improvement following surgery.	Surgery followed by postoperative low-dose radiation therapy or chemotherapy provides prompt local pain relief and early neurological improvement when compared with isolated radiation therapy or chemotherapy alone.
Zheng et al15	Grade II	Transpedicular curettage + short segment posterior instrumentation, balloon kyphoplasty, calcium sulfate cement injection	Better vertebral height restoration by 2-y follow-up when compared with historical cohort.	Active surgical treatment is recommended in patients with grade II lesions.
Zheng et al16	Grade IB and II	Transpedicular curettage + short segment posterior instrumentation, Instrumentation removal by 2 y	Better vertebral body height restoration by 1-y follow-up when compared with reference vertebral body height.	Active surgical treatment is recommended in patients with grade IB, II lesions to restore vertebral body height and spinal stability.
Zhong et al17	Not provided	C1–C2: Anterior resection of lesion and posterior instrumentation C3–C7: Vertebral body lesion: anterior excision, corpectomy, and fusion Posterior column lesion: posterior excision and instrumentation	Improvement in neurology and clinical symptoms.	Surgery can significantly improve neurological symptoms. However, it must be tailored according to the individual location of the lesion in cervical spine.