Molecular and clinical features of included patients
| No. . | Genetic alteration(s) . | Detection method . | Age . | Sex . | Disease extent . | Organ(s) . | Disease site(s) . | Description . | Therapy . | Outcome . | Status (follow-up duration) . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| XG of soft tissue | |||||||||||
| 1 | CSF1R exon 12 deletion | TLC-NGS | 0.1 y (C) | M | SS unifocal | Soft tissue and skin | Chest | Large tumor (3 cm) ventral of the clavicle, restricted to the skin and subcutaneous tissue, and with recurrent ulceration | Subtotal resection | Relapse in scar (1.2 × 0.7 cm) with slow spontaneous regression | Alive with minor disease in scar (2.6 y) |
| 2 | CLTC::SYK fusion | TLC-NGS | 0.2 y (C) | M | SS unifocal | Soft tissue | Forearm | Large forearm tumor (7 × 5.5 cm) | Active monitoring | Spontaneous regression of lesion | Alive with NED (12.1 y) |
| 3 | CSF1R exon 12 indel | TLC-NGS | 0.2 y (C) | M | SS multifocal | Soft tissue and skin | Neck and upper leg | Two subcutaneous tumors; 1 in the neck and 1 on the upper leg | Resection neck tumor; active monitoring of the lesion on the leg | Spontaneous regression of leg lesion∗ | Alive with NED (2.4 y) |
| 4 | CSF1R exon 12 indel | TLC-NGS | 0.2 y | M | SS unifocal | Soft tissue | Scalp | Large extra/intracranial tumor of the frontal, temporal and parietal skull | Resection | N/A | Alive with disease (0.1 y) |
| 5 | CSF1R exon 12 indel | TLC-NGS | 0.3 y (C) | M | SS unifocal | Soft tissue and skin | Forearm | Subcutaneous forearm tumor (2.8 × 1.6 × 4.2 cm), extending inward between the flexor digitorum superficialis and profundus | Active monitoring | Spontaneous regression of lesion | Alive with NED (11.8 y) |
| 6 | MRC1::PDGFRB fusion and CSF1R deletion of exons 21-22 | TLC-NGS | 0.3 y | F | SS multifocal | Soft tissue | Abdomen | Large tumor involving the greater omentum; small lesions on intestinal walls and in the liver hilum | Subtotal resection | Complete remission | Alive with NED (24.9 y) |
| 7 | CSF1R exon 12 indel | TLC-NGS | 0.4 y | M | SS multifocal | Soft tissue/muscle | Scalp and back | Subcutaneous mass scalp; intramuscular tumor below the scapula | Subtotal resections scalp lesion (3× within 4 months); resection tumor below the scapula | Relapse of scalp lesion in scar; complete remission after re-resections | Alive with NED (9.8 y) |
| 8 | CLTC::SYK fusion | TLC-NGS | 0.4 y | F | SS unifocal | Soft tissue | Scalp | Parietal tumor | Subtotal resection | Complete remission | Alive with NED (25.3 y) |
| 9 | CLTC::SYK fusion | TLC-NGS and WTS | 0.4 y | F | SS unifocal | Soft tissue/muscle | Inguinal region | Intramuscular tumor in the vastus medialis of the quadriceps muscle group | Resection | Complete remission | Alive with NED (0.03 y) |
| 10 | CLTC::SYK fusion | TLC-NGS and WTS | 0.6 y | F | SS unifocal | Soft tissue | Thoracic wall | Parasternal tumor below the pectoralis major with extension between the second and third rib to the parietal pleura (2.7 × 2 × 3.2 cm) | Subtotal resection† | Complete remission | Alive with NED (13.5 y) |
| 11 | CLTC::SYK fusion | TLC-NGS | 0.8 y | M | SS unifocal | Soft tissue/muscle | Abdominal wall | Tumor on the fascia of the abdominal external oblique muscle | Resection | Complete remission | Alive with NED (0.6 y) |
| 12 | CLTC::SYK fusion | TLC-NGS and WTS | 1.1 y | M | SS unifocal | Soft tissue | Upper leg | Subcutaneous nodule in the lateral upper leg positioned just above the fascia of the underlying muscle | Resection | Complete remission | Alive with NED (0.03 y) |
| 13 | CSF1R exons 9-10 missense mutations | WES (clinical) | 1.2 y | M | SS unifocal | Soft tissue | Trachea | Midendotracheal pedunculated tumor, originating from the anterior wall | Resection | Complete remission | Alive with NED (2.2 y) |
| 14 | TBL1XR1::BOD1L1 fusion | TLC-NGS and WTS | 18.9 y | F | SS unifocal | Soft tissue | Nasopharynx | Large submucosal tumor of the nasopharynx (3.7 × 2.5 cm) with invasion of prevertebral muscles | 1. Corticosteroid injection 2. Debulking surgery 3. Resection | Complete remission | Alive with NED (11.8 y) |
| 15 | None detected | TLC-NGS | 36.6 y | M | SS unifocal | Soft tissue | Paranasal sinus | Submucosal tumor left paranasal sinus | Resection | N/A | N/A |
| 16 | None detected | TLC-NGS | 47 y | M | SS unifocal | Soft tissue | Pubic region | Large tumor (5.5 cm) in the proximal upper leg, adjacent to the pectineal line of the pubis | Resection | N/A | N/A |
| 17 | None detected | TLC-NGS | 58.2 y | F | SS unifocal | Soft tissue | Scalp | Parietal subcutaneous soft tissue tumor with bone destruction | Resection‡ | Complete remission | Alive with NED (5.2 y) |
| No. . | Genetic alteration(s) . | Detection method . | Age . | Sex . | Disease extent . | Organ(s) . | Disease site(s) . | Description . | Therapy . | Outcome . | Status (follow-up duration) . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| XG of soft tissue | |||||||||||
| 1 | CSF1R exon 12 deletion | TLC-NGS | 0.1 y (C) | M | SS unifocal | Soft tissue and skin | Chest | Large tumor (3 cm) ventral of the clavicle, restricted to the skin and subcutaneous tissue, and with recurrent ulceration | Subtotal resection | Relapse in scar (1.2 × 0.7 cm) with slow spontaneous regression | Alive with minor disease in scar (2.6 y) |
| 2 | CLTC::SYK fusion | TLC-NGS | 0.2 y (C) | M | SS unifocal | Soft tissue | Forearm | Large forearm tumor (7 × 5.5 cm) | Active monitoring | Spontaneous regression of lesion | Alive with NED (12.1 y) |
| 3 | CSF1R exon 12 indel | TLC-NGS | 0.2 y (C) | M | SS multifocal | Soft tissue and skin | Neck and upper leg | Two subcutaneous tumors; 1 in the neck and 1 on the upper leg | Resection neck tumor; active monitoring of the lesion on the leg | Spontaneous regression of leg lesion∗ | Alive with NED (2.4 y) |
| 4 | CSF1R exon 12 indel | TLC-NGS | 0.2 y | M | SS unifocal | Soft tissue | Scalp | Large extra/intracranial tumor of the frontal, temporal and parietal skull | Resection | N/A | Alive with disease (0.1 y) |
| 5 | CSF1R exon 12 indel | TLC-NGS | 0.3 y (C) | M | SS unifocal | Soft tissue and skin | Forearm | Subcutaneous forearm tumor (2.8 × 1.6 × 4.2 cm), extending inward between the flexor digitorum superficialis and profundus | Active monitoring | Spontaneous regression of lesion | Alive with NED (11.8 y) |
| 6 | MRC1::PDGFRB fusion and CSF1R deletion of exons 21-22 | TLC-NGS | 0.3 y | F | SS multifocal | Soft tissue | Abdomen | Large tumor involving the greater omentum; small lesions on intestinal walls and in the liver hilum | Subtotal resection | Complete remission | Alive with NED (24.9 y) |
| 7 | CSF1R exon 12 indel | TLC-NGS | 0.4 y | M | SS multifocal | Soft tissue/muscle | Scalp and back | Subcutaneous mass scalp; intramuscular tumor below the scapula | Subtotal resections scalp lesion (3× within 4 months); resection tumor below the scapula | Relapse of scalp lesion in scar; complete remission after re-resections | Alive with NED (9.8 y) |
| 8 | CLTC::SYK fusion | TLC-NGS | 0.4 y | F | SS unifocal | Soft tissue | Scalp | Parietal tumor | Subtotal resection | Complete remission | Alive with NED (25.3 y) |
| 9 | CLTC::SYK fusion | TLC-NGS and WTS | 0.4 y | F | SS unifocal | Soft tissue/muscle | Inguinal region | Intramuscular tumor in the vastus medialis of the quadriceps muscle group | Resection | Complete remission | Alive with NED (0.03 y) |
| 10 | CLTC::SYK fusion | TLC-NGS and WTS | 0.6 y | F | SS unifocal | Soft tissue | Thoracic wall | Parasternal tumor below the pectoralis major with extension between the second and third rib to the parietal pleura (2.7 × 2 × 3.2 cm) | Subtotal resection† | Complete remission | Alive with NED (13.5 y) |
| 11 | CLTC::SYK fusion | TLC-NGS | 0.8 y | M | SS unifocal | Soft tissue/muscle | Abdominal wall | Tumor on the fascia of the abdominal external oblique muscle | Resection | Complete remission | Alive with NED (0.6 y) |
| 12 | CLTC::SYK fusion | TLC-NGS and WTS | 1.1 y | M | SS unifocal | Soft tissue | Upper leg | Subcutaneous nodule in the lateral upper leg positioned just above the fascia of the underlying muscle | Resection | Complete remission | Alive with NED (0.03 y) |
| 13 | CSF1R exons 9-10 missense mutations | WES (clinical) | 1.2 y | M | SS unifocal | Soft tissue | Trachea | Midendotracheal pedunculated tumor, originating from the anterior wall | Resection | Complete remission | Alive with NED (2.2 y) |
| 14 | TBL1XR1::BOD1L1 fusion | TLC-NGS and WTS | 18.9 y | F | SS unifocal | Soft tissue | Nasopharynx | Large submucosal tumor of the nasopharynx (3.7 × 2.5 cm) with invasion of prevertebral muscles | 1. Corticosteroid injection 2. Debulking surgery 3. Resection | Complete remission | Alive with NED (11.8 y) |
| 15 | None detected | TLC-NGS | 36.6 y | M | SS unifocal | Soft tissue | Paranasal sinus | Submucosal tumor left paranasal sinus | Resection | N/A | N/A |
| 16 | None detected | TLC-NGS | 47 y | M | SS unifocal | Soft tissue | Pubic region | Large tumor (5.5 cm) in the proximal upper leg, adjacent to the pectineal line of the pubis | Resection | N/A | N/A |
| 17 | None detected | TLC-NGS | 58.2 y | F | SS unifocal | Soft tissue | Scalp | Parietal subcutaneous soft tissue tumor with bone destruction | Resection‡ | Complete remission | Alive with NED (5.2 y) |
| No. . | Genetic alteration(s) . | Detection method . | Age . | Sex . | Disease extent . | Organ(s) . | Description . | Therapy . | Outcome . | Status (follow-up duration) . |
|---|---|---|---|---|---|---|---|---|---|---|
| Isolated CNS-XG | ||||||||||
| 18 | BRAF p.V600E | NGS (clinical) | 0.5 y | F | SS unifocal | CNS | Intramedullary spinal cord tumor at level Th9-L1 | Dabrafenib (initially + trametinib) | Complete remission while on targeted therapy | Alive with NED (4.3 y) |
| 19 | BRAF p.V600E | PCR (clinical) and TLC-NGS | 50.2 y | F | SS multifocal | CNS | Multifocal brain and spinal cord tumors | 1. Subtotal resection; 2. Steroids (MPS); 3. 2-CDA (2 courses), followed by MPS; 4. Vemurafenib (0.5 y; lost access); 5. PEG-IFN-α; 6. Steroids (MPS); 7. Vemurafenib | Progressive disease with conventional therapy; partial remission with vemurafenib | Alive with disease (9.6 y) |
| Systemic JXG | ||||||||||
| 20 | TPM3::NTRK1 fusion and MAP3K1 exon 20 deletion | TLC-NGS | 0.02 y (C) | F | MS | Hematopoietic system, liver, skin, spleen | Anemia, trombocytopenia, and hepatosplenomegaly (with calcifications in the spleen, which was 10 cm in length); an unifocal skin nodule on the right shoulder | Supportive care (including transfusions) | Spontaneous regression of the skin lesion, cytopenias, and hepatosplenomegaly | Alive with NED (0.6 y) |
| 21 | MAP2K1 exon 2 deletion | TLC-NGS | 2.8 y | F | MS | Pituitary, lungs, lymph nodes, skin | Thickened pituitary; bilateral lung consolidations; bilateral enlarged mediastinal lymph nodes (maximum size of lymph node collection: 3.8 cm); papular skin lesions on the trunk, legs, arms, and face | Active monitoring | Slow spontaneous regression of skin lesions, lung abnormalities and enlarged lymph nodes; persistent thickened pituitary stalk | Alive in clinical remission (15.7 y) |
| No. . | Genetic alteration(s) . | Detection method . | Age . | Sex . | Disease extent . | Organ(s) . | Description . | Therapy . | Outcome . | Status (follow-up duration) . |
|---|---|---|---|---|---|---|---|---|---|---|
| Isolated CNS-XG | ||||||||||
| 18 | BRAF p.V600E | NGS (clinical) | 0.5 y | F | SS unifocal | CNS | Intramedullary spinal cord tumor at level Th9-L1 | Dabrafenib (initially + trametinib) | Complete remission while on targeted therapy | Alive with NED (4.3 y) |
| 19 | BRAF p.V600E | PCR (clinical) and TLC-NGS | 50.2 y | F | SS multifocal | CNS | Multifocal brain and spinal cord tumors | 1. Subtotal resection; 2. Steroids (MPS); 3. 2-CDA (2 courses), followed by MPS; 4. Vemurafenib (0.5 y; lost access); 5. PEG-IFN-α; 6. Steroids (MPS); 7. Vemurafenib | Progressive disease with conventional therapy; partial remission with vemurafenib | Alive with disease (9.6 y) |
| Systemic JXG | ||||||||||
| 20 | TPM3::NTRK1 fusion and MAP3K1 exon 20 deletion | TLC-NGS | 0.02 y (C) | F | MS | Hematopoietic system, liver, skin, spleen | Anemia, trombocytopenia, and hepatosplenomegaly (with calcifications in the spleen, which was 10 cm in length); an unifocal skin nodule on the right shoulder | Supportive care (including transfusions) | Spontaneous regression of the skin lesion, cytopenias, and hepatosplenomegaly | Alive with NED (0.6 y) |
| 21 | MAP2K1 exon 2 deletion | TLC-NGS | 2.8 y | F | MS | Pituitary, lungs, lymph nodes, skin | Thickened pituitary; bilateral lung consolidations; bilateral enlarged mediastinal lymph nodes (maximum size of lymph node collection: 3.8 cm); papular skin lesions on the trunk, legs, arms, and face | Active monitoring | Slow spontaneous regression of skin lesions, lung abnormalities and enlarged lymph nodes; persistent thickened pituitary stalk | Alive in clinical remission (15.7 y) |
2-CDA, cladribine; C, congenital; F, female; indel, insertion-deletion; L, lumbar; M, male; MPS, methylprednisolone; MS, multisystem; N/A, not available; NED, no evidence of disease; PEG-IFN-α, pegylated interferon alfa; SS, single system; Th, thoracic; TLC, targeted locus capture; WES, whole exome sequencing; WTS, whole transcriptome sequencing.
After diagnosis, both lesions progressed (Figure 1B). The tumor in the neck limited the child and was therefore resected. The upper leg lesion continued to grow for several months, but eventually regressed spontaneously.
Initially, a diagnosis of self-limiting sternal tumor of childhood was assumed, and the patient was managed by active monitoring. However, ultrasound revealed slow progression of the parasternal lesion during follow-up; therefore, subtotal resection was performed at 6.5 months after presentation.
Initially, an active monitoring strategy was pursued. The lesion slowly progressed; therefore, resection was performed 7.5 months after the diagnostic biopsy.