Histopathologic and molecular characteristics of ALK-positive histiocytoses
| No. . | ALK rearrangement . | Analysis method(s) . | Classic XG-like . | Emperipolesis . | ALK IHC . | |
|---|---|---|---|---|---|---|
| Staining . | Staining pattern . | |||||
| Group 1A | ||||||
| 1 | Not confirmed | ALK-FISH negative; KIF5B-ALK RT-PCR negative; no RNA-seq (insufficient material) | No | Yes | Positive | Light cytoplasmic; membranous |
| 2 | ALK-FISH+ | FISH | No | Yes abundant | Positive | Diffuse cytoplasmic; membranous |
| 3 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | No | No | Positive | Granular cytoplasmic with focal Golgi dot-like accentuation; no membranous |
| 4 | Not confirmed | ALK-FISH negative; no RNA-seq (insufficient material) | Yes | Yes abundant | Positive | Scant cytoplasmic; strong membranous |
| 5 | ALK-FISH+ | FISH | Yes | Yes | Positive | Weak cytoplasmic; strong membranous |
| 6 | CLTC-ALK | Archer FusionPlex targeted RNA-seq | No | Yes | Positive | Diffuse dark cytoplasmic (clone 5A4) to more light granular cytoplasmic (clone ALK1); membranous (both) |
| Group 1B | ||||||
| 7 | TPM3-ALK | Archer FusionPlex targeted RNA-seq | Yes | Yes | Positive | Diffuse cytoplasmic with Golgi dot-like accentuation; membranous |
| 8 | ALK-FISH+ | FISH | No | No | Positive | Diffuse granular cytoplasmic with rare Golgi dot-like accentuation; no membranous |
| 9 | KIF5B-ALK | Illumina Childhood Cancer targeted RNA-seq | No | No | Weak | Very weak diffuse cytoplasmic; no membranous |
| 10 | KIF5B-ALK | Illumina Trusight targeted RNA-seq | No | No | Positive | Diffuse dark cytoplasmic (clone D5F3) to more light, granular cytoplasmic with Golgi dot-like accentuation (clone ALK1); no membranous |
| 11 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | No | No | Positive | Diffuse cytoplasmic; no membranous |
| 12 | KIF5B-ALK | KIF5B-ALK RT-PCT positive | No | No | Exclusive dot-like | Golgi dot-like cytoplasmic only; no membranous |
| 13 | TFG-ALK | Archer FusionPlex targeted RNA-seq | Yes | No | Focal, weak | Very weak cytoplasmic blush to negative; no membranous |
| 14 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | No | No | Positive | Granular cytoplasmic with Golgi dot-like accentuation; no membranous |
| 15 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | Yes | Yes | Positive | Diffuse cytoplasmic with Golgi dot-like accentuation; no membranous |
| 16 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | No | No | Positive | Granular cytoplasmic with rare Golgi dot-like accentuation; no membranous |
| Group 2: neurological involvement | ||||||
| 17 | KIF5B-ALK | FoundationOne Heme targeted RNA-seq | No | No | Positive | Granular cytoplasmic with Golgi dot-like accentuation in some cells; no membranous |
| 18 | ALK-FISH+ | FISH | No | No | Positive | Diffuse cytoplasmic with Golgi dot-like accentuation; membranous |
| 19 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | No | No | Positive | Diffuse cytoplasmic; no membranous |
| 20 | KIF5B-ALK | FoundationOne Heme targeted RNA-seq | No | No | Focal, weak | Focal, weak diffuse cytoplasmic with Golgi dot-like accentuation; no membranous |
| 21 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | Yes | Yes | Positive | Diffuse cytoplasmic with Golgi dot-like accentuation; no membranous |
| 22 | KIF5B-ALK | Whole transcriptome RNA-seq | No | No | Positive | Diffuse granular cytoplasmic; no membranous |
| 23 | KIF5B-ALK | Whole transcriptome RNA-seq | No | No | Positive | Diffuse granular cytoplasmic; no membranous |
| 24 | ALK-FISH+ | FISH | Yes* | No | Positive | Diffuse granular cytoplasmic; no membranous |
| 25 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | Yes | Yes abundant | Positive | Diffuse cytoplasmic with Golgi dot-like accentuation; membranous |
| 26 | KIF5B-ALK | Ion Ampliseq RNA Fusion Lung Cancer targeted RNA-seq; whole transcriptome RNA-seq | No | Yes abundant | Positive | Diffuse cytoplasmic with Golgi dot-like accentuation; no membranous |
| 27 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | Yes | No | Positive | Diffuse granular cytoplasmic; no membranous |
| 28 | KIF5B-ALK | FoundationOne Heme targeted RNA-seq | No | No | Focal, weak | Variable focal, weak cytoplasmic to negative; no membranous |
| Group 2: nonneurological involvement | ||||||
| 29 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | No | No | Positive | Diffuse cytoplasmic with Golgi dot-like accentuation; no membranous |
| 30 | KIF5B-ALK | Oncomine Comprehensive Assay Plus targeted RNA-seq | No | No | Positive | Diffuse granular cytoplasmic with Golgi dot-like accentuation; no membranous |
| 31 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | No | No | Positive | Diffuse granular cytoplasmic; no membranous |
| 32 | KIF5B-ALK | Whole transcriptome RNA-seq | No | No | Positive | Diffuse dark cytoplasmic; subset possibly nuclear; no membranous (clone 5A4, lung staining protocol). Focal/Golgi dot-like cytoplasmic; no nuclear or membranous (clone 5A4, lymphoma staining protocol) |
| 33 | KIF5B-ALK | Illumina Trusight targeted RNA-seq | No | Yes | Positive | Diffuse light granular cytoplasmic with dark Golgi-dot like accentuation; no membranous |
| 34 | KIF5B-ALK | Illumina Trusight targeted RNA-seq | No | No | Exclusive dot-like | Golgi dot-like cytoplasmic only (focal weak); no membranous |
| 35 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | No | No | Positive | Diffuse granular cytoplasmic with Golgi dot-like accentuation; no membranous |
| 36 | KIF5B-ALK | FoundationOne Heme targeted RNA-seq | No | No | Exclusive dot-like | Golgi dot-like cytoplasmic only (focal weak); no membranous |
| 37 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | Yes | Yes | Positive | Diffuse cytoplasmic with Golgi dot-like accentuation; membranous |
| 38 | EML4-ALK | Archer FusionPlex targeted RNA-seq | Yes | No | Positive | Diffuse granular cytoplasmic; membranous |
| 39 | DCTN1-ALK | Archer FusionPlex targeted RNA-seq | Yes | Yes abundant | Positive | Diffuse cytoplasmic with Golgi dot-like accentuation; membranous |
| No. . | ALK rearrangement . | Analysis method(s) . | Classic XG-like . | Emperipolesis . | ALK IHC . | |
|---|---|---|---|---|---|---|
| Staining . | Staining pattern . | |||||
| Group 1A | ||||||
| 1 | Not confirmed | ALK-FISH negative; KIF5B-ALK RT-PCR negative; no RNA-seq (insufficient material) | No | Yes | Positive | Light cytoplasmic; membranous |
| 2 | ALK-FISH+ | FISH | No | Yes abundant | Positive | Diffuse cytoplasmic; membranous |
| 3 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | No | No | Positive | Granular cytoplasmic with focal Golgi dot-like accentuation; no membranous |
| 4 | Not confirmed | ALK-FISH negative; no RNA-seq (insufficient material) | Yes | Yes abundant | Positive | Scant cytoplasmic; strong membranous |
| 5 | ALK-FISH+ | FISH | Yes | Yes | Positive | Weak cytoplasmic; strong membranous |
| 6 | CLTC-ALK | Archer FusionPlex targeted RNA-seq | No | Yes | Positive | Diffuse dark cytoplasmic (clone 5A4) to more light granular cytoplasmic (clone ALK1); membranous (both) |
| Group 1B | ||||||
| 7 | TPM3-ALK | Archer FusionPlex targeted RNA-seq | Yes | Yes | Positive | Diffuse cytoplasmic with Golgi dot-like accentuation; membranous |
| 8 | ALK-FISH+ | FISH | No | No | Positive | Diffuse granular cytoplasmic with rare Golgi dot-like accentuation; no membranous |
| 9 | KIF5B-ALK | Illumina Childhood Cancer targeted RNA-seq | No | No | Weak | Very weak diffuse cytoplasmic; no membranous |
| 10 | KIF5B-ALK | Illumina Trusight targeted RNA-seq | No | No | Positive | Diffuse dark cytoplasmic (clone D5F3) to more light, granular cytoplasmic with Golgi dot-like accentuation (clone ALK1); no membranous |
| 11 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | No | No | Positive | Diffuse cytoplasmic; no membranous |
| 12 | KIF5B-ALK | KIF5B-ALK RT-PCT positive | No | No | Exclusive dot-like | Golgi dot-like cytoplasmic only; no membranous |
| 13 | TFG-ALK | Archer FusionPlex targeted RNA-seq | Yes | No | Focal, weak | Very weak cytoplasmic blush to negative; no membranous |
| 14 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | No | No | Positive | Granular cytoplasmic with Golgi dot-like accentuation; no membranous |
| 15 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | Yes | Yes | Positive | Diffuse cytoplasmic with Golgi dot-like accentuation; no membranous |
| 16 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | No | No | Positive | Granular cytoplasmic with rare Golgi dot-like accentuation; no membranous |
| Group 2: neurological involvement | ||||||
| 17 | KIF5B-ALK | FoundationOne Heme targeted RNA-seq | No | No | Positive | Granular cytoplasmic with Golgi dot-like accentuation in some cells; no membranous |
| 18 | ALK-FISH+ | FISH | No | No | Positive | Diffuse cytoplasmic with Golgi dot-like accentuation; membranous |
| 19 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | No | No | Positive | Diffuse cytoplasmic; no membranous |
| 20 | KIF5B-ALK | FoundationOne Heme targeted RNA-seq | No | No | Focal, weak | Focal, weak diffuse cytoplasmic with Golgi dot-like accentuation; no membranous |
| 21 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | Yes | Yes | Positive | Diffuse cytoplasmic with Golgi dot-like accentuation; no membranous |
| 22 | KIF5B-ALK | Whole transcriptome RNA-seq | No | No | Positive | Diffuse granular cytoplasmic; no membranous |
| 23 | KIF5B-ALK | Whole transcriptome RNA-seq | No | No | Positive | Diffuse granular cytoplasmic; no membranous |
| 24 | ALK-FISH+ | FISH | Yes* | No | Positive | Diffuse granular cytoplasmic; no membranous |
| 25 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | Yes | Yes abundant | Positive | Diffuse cytoplasmic with Golgi dot-like accentuation; membranous |
| 26 | KIF5B-ALK | Ion Ampliseq RNA Fusion Lung Cancer targeted RNA-seq; whole transcriptome RNA-seq | No | Yes abundant | Positive | Diffuse cytoplasmic with Golgi dot-like accentuation; no membranous |
| 27 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | Yes | No | Positive | Diffuse granular cytoplasmic; no membranous |
| 28 | KIF5B-ALK | FoundationOne Heme targeted RNA-seq | No | No | Focal, weak | Variable focal, weak cytoplasmic to negative; no membranous |
| Group 2: nonneurological involvement | ||||||
| 29 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | No | No | Positive | Diffuse cytoplasmic with Golgi dot-like accentuation; no membranous |
| 30 | KIF5B-ALK | Oncomine Comprehensive Assay Plus targeted RNA-seq | No | No | Positive | Diffuse granular cytoplasmic with Golgi dot-like accentuation; no membranous |
| 31 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | No | No | Positive | Diffuse granular cytoplasmic; no membranous |
| 32 | KIF5B-ALK | Whole transcriptome RNA-seq | No | No | Positive | Diffuse dark cytoplasmic; subset possibly nuclear; no membranous (clone 5A4, lung staining protocol). Focal/Golgi dot-like cytoplasmic; no nuclear or membranous (clone 5A4, lymphoma staining protocol) |
| 33 | KIF5B-ALK | Illumina Trusight targeted RNA-seq | No | Yes | Positive | Diffuse light granular cytoplasmic with dark Golgi-dot like accentuation; no membranous |
| 34 | KIF5B-ALK | Illumina Trusight targeted RNA-seq | No | No | Exclusive dot-like | Golgi dot-like cytoplasmic only (focal weak); no membranous |
| 35 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | No | No | Positive | Diffuse granular cytoplasmic with Golgi dot-like accentuation; no membranous |
| 36 | KIF5B-ALK | FoundationOne Heme targeted RNA-seq | No | No | Exclusive dot-like | Golgi dot-like cytoplasmic only (focal weak); no membranous |
| 37 | KIF5B-ALK | Archer FusionPlex targeted RNA-seq | Yes | Yes | Positive | Diffuse cytoplasmic with Golgi dot-like accentuation; membranous |
| 38 | EML4-ALK | Archer FusionPlex targeted RNA-seq | Yes | No | Positive | Diffuse granular cytoplasmic; membranous |
| 39 | DCTN1-ALK | Archer FusionPlex targeted RNA-seq | Yes | Yes abundant | Positive | Diffuse cytoplasmic with Golgi dot-like accentuation; membranous |
RT-PCR, reverse transcription polymerase chain reaction; XG, xanthogranuloma.
Multiple areas with xanthomatous histiocytes and Touton giant cells were observed; however, a significant part consisted of an infiltration of spindly cells.