Clinical characteristics according to BRAFV600E status
| . | BRAFV600E+ . | BRAFV600E− . | Odds ratio (95% confidence interval) . | P value . |
|---|---|---|---|---|
| Patients, n | 191 | 186 | ||
| Age at diagnosis, y, median (range) | 2.6 (0.0-17.6) | 5.7 (0.0-17.9) | N/A | <.001†† |
| Age <3 y, n (%) | 105 (55.0) | 66 (35.5) | 2.22 (1.47-3.36) | <.001†† |
| Age ≥3 y, n (%) | 86 (45.0) | 120 (64.5) | ||
| Sex, n (%) | ||||
| Male | 113 (59.2) | 109 (58.6) | 1.02 (0.68-1.54) | .92 |
| Female | 78 (40.8) | 77 (41.4) | ||
| Disease extent at diagnosis, n (%) | ||||
| MS | 64 (33.5) | 25 (13.4) | 3.25 (1.93-5.45) | <.001†† |
| SS | 127 (66.5) | 161 (86.6) | ||
| Detailed subtype, n (%)∗ | ||||
| MS-RO+ | 27 (14.1) | 7 (3.8) | 4.21 (1.79-9.93) | <.001†† |
| MS-RO− | 37 (19.4) | 18 (9.7) | 2.24 (1.23-4.10) | .009∗∗ |
| SS-bone | 109 (57.1) | 139 (74.7) | 0.45 (0.29-0.70) | <.001†† |
| • SS-UFB | 87 (45.5) | 97 (52.2) | 0.77 (0.51-1.15) | .22 |
| • SS-UFB, CNS-risk† | 16 (8.4) | 19 (10.2) | 0.80 (0.40-1.62) | .60 |
| • SS-MFB | 22 (11.5) | 42 (22.6) | 0.45 (0.26-0.78) | .006∗∗ |
| SS-skin | 18 (9.4) | 14 (7.5) | 1.28 (0.62-2.65) | .58 |
| SS-other | 0 (0.0) | 8 (4.3)¶ | N/A | .003∗∗ |
| Disease site(s) at diagnosis, n (%) | ||||
| Bone | 157 (82.2) | 159 (85.5) | 0.78 (0.45-1.36) | .41 |
| • MFB lesions | 56 (29.3) | 55 (29.6) | 0.99 (0.63-1.54) | 1 |
| • CNS-risk bone lesion(s)† | 64 (33.5) | 40 (21.5) | 1.84 (1.16-2.92) | .011∗∗ |
| • Spinal column lesion(s) | 18 (9.4) | 28 (15.1) | 0.59 (0.31-1.10) | .12 |
| Skin | 69 (36.1) | 24 (12.9) | 3.82 (2.27-6.43) | <.001†† |
| Liver‡ | 24 (12.6) | 5 (2.7) | 5.20 (1.94-13.95) | <.001†† |
| Hematopoietic system‡ | 19 (9.9) | 3 (1.6) | 6.74 (1.96-23.18) | .001†† |
| Spleen‡ | 15 (7.9) | 4 (2.2) | 3.88 (1.26-11.91) | .017∗∗ |
| Lymph node | 17 (8.9) | 17 (9.1) | 0.97 (0.48-1.97) | 1 |
| Lung | 10 (5.2) | 14 (7.5) | 0.68 (0.29-1.57) | .40 |
| CNS§ | 8 (4.2) | 4 (2.2) | 1.99 (0.59-6.72) | .38 |
| Gastrointestinal tract | 7 (3.7) | 0 (0.0) | N/A | .015∗∗ |
| Follow-up, y, median (range) | 4.0 (0.0-38.8) | 3.8 (0.0-36.0) | N/A | .61# |
| Permanent consequences developed during follow-up, n (%) | ||||
| DI | 23 (12.0) | 14 (7.5) | 1.68 (0.84-3.38) | .17 |
| ND-LCH‖ | 5 (2.6) | 0 (0.0) | N/A | .06 |
| Death, n | 4 | 4 | N/A | .97# |
| . | BRAFV600E+ . | BRAFV600E− . | Odds ratio (95% confidence interval) . | P value . |
|---|---|---|---|---|
| Patients, n | 191 | 186 | ||
| Age at diagnosis, y, median (range) | 2.6 (0.0-17.6) | 5.7 (0.0-17.9) | N/A | <.001†† |
| Age <3 y, n (%) | 105 (55.0) | 66 (35.5) | 2.22 (1.47-3.36) | <.001†† |
| Age ≥3 y, n (%) | 86 (45.0) | 120 (64.5) | ||
| Sex, n (%) | ||||
| Male | 113 (59.2) | 109 (58.6) | 1.02 (0.68-1.54) | .92 |
| Female | 78 (40.8) | 77 (41.4) | ||
| Disease extent at diagnosis, n (%) | ||||
| MS | 64 (33.5) | 25 (13.4) | 3.25 (1.93-5.45) | <.001†† |
| SS | 127 (66.5) | 161 (86.6) | ||
| Detailed subtype, n (%)∗ | ||||
| MS-RO+ | 27 (14.1) | 7 (3.8) | 4.21 (1.79-9.93) | <.001†† |
| MS-RO− | 37 (19.4) | 18 (9.7) | 2.24 (1.23-4.10) | .009∗∗ |
| SS-bone | 109 (57.1) | 139 (74.7) | 0.45 (0.29-0.70) | <.001†† |
| • SS-UFB | 87 (45.5) | 97 (52.2) | 0.77 (0.51-1.15) | .22 |
| • SS-UFB, CNS-risk† | 16 (8.4) | 19 (10.2) | 0.80 (0.40-1.62) | .60 |
| • SS-MFB | 22 (11.5) | 42 (22.6) | 0.45 (0.26-0.78) | .006∗∗ |
| SS-skin | 18 (9.4) | 14 (7.5) | 1.28 (0.62-2.65) | .58 |
| SS-other | 0 (0.0) | 8 (4.3)¶ | N/A | .003∗∗ |
| Disease site(s) at diagnosis, n (%) | ||||
| Bone | 157 (82.2) | 159 (85.5) | 0.78 (0.45-1.36) | .41 |
| • MFB lesions | 56 (29.3) | 55 (29.6) | 0.99 (0.63-1.54) | 1 |
| • CNS-risk bone lesion(s)† | 64 (33.5) | 40 (21.5) | 1.84 (1.16-2.92) | .011∗∗ |
| • Spinal column lesion(s) | 18 (9.4) | 28 (15.1) | 0.59 (0.31-1.10) | .12 |
| Skin | 69 (36.1) | 24 (12.9) | 3.82 (2.27-6.43) | <.001†† |
| Liver‡ | 24 (12.6) | 5 (2.7) | 5.20 (1.94-13.95) | <.001†† |
| Hematopoietic system‡ | 19 (9.9) | 3 (1.6) | 6.74 (1.96-23.18) | .001†† |
| Spleen‡ | 15 (7.9) | 4 (2.2) | 3.88 (1.26-11.91) | .017∗∗ |
| Lymph node | 17 (8.9) | 17 (9.1) | 0.97 (0.48-1.97) | 1 |
| Lung | 10 (5.2) | 14 (7.5) | 0.68 (0.29-1.57) | .40 |
| CNS§ | 8 (4.2) | 4 (2.2) | 1.99 (0.59-6.72) | .38 |
| Gastrointestinal tract | 7 (3.7) | 0 (0.0) | N/A | .015∗∗ |
| Follow-up, y, median (range) | 4.0 (0.0-38.8) | 3.8 (0.0-36.0) | N/A | .61# |
| Permanent consequences developed during follow-up, n (%) | ||||
| DI | 23 (12.0) | 14 (7.5) | 1.68 (0.84-3.38) | .17 |
| ND-LCH‖ | 5 (2.6) | 0 (0.0) | N/A | .06 |
| Death, n | 4 | 4 | N/A | .97# |
N/A, not available.
Fisher exact tests comparing patients with vs without a disease extent subtype are shown. Fisher-Freeman-Halton exact test comparing proportions in all different subgroups (a contingency table larger than 2 × 2) is not shown but was significant (P < .001).
Bone lesions affecting the orbital, temporal/mastoid, sphenoidal, zygomatic, or ethmoidal bones, the maxilla, paranasal sinuses, or anterior or middle cranial fossa.
These organs are considered ROs.
Given that the posterior pituitary and pituitary stalk are direct extensions of the hypothalamus, pituitary tumors are classified as CNS involvement. All 12 patients with CNS involvement at diagnosis had tumorous lesions, for example, pituitary stalk lesions.
Only patients with both clinical and radiologic ND-LCH are reported.
These 8 patients comprised 3 patients with SS-lung LCH, 3 patients with SS-lymph node LCH, and single cases with SS-soft tissue or (tumorous) SS-CNS disease.
Obtained with the log-rank test.
P < .05.
P < .00125 (Bonferroni correction for multiple testing; tests are shown in this table and supplemental Table 3).