Diagnostic tools in the differential diagnosis of giant cell-rich lesions of bone at biopsy

Rehkämper, Jan; Steinestel, Konrad; Jeiler, Birte; Elges, Sandra; Hekeler, Elena; Huss, Sebastian; Sperveslage, Jan; Hardes, Jendrik; Streitbürger, Arne; Gosheger, Georg; Wardelmann, Eva; Baumhoer, Daniel; Trautmann, Marcel; Hartmann, Wolfgang

doi:10.18632/oncotarget.25725

Cited by 22 publications

(19 citation statements)

References 32 publications

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“…that are commonly mutated in cancer. As described before [32][33][34] , Target enrichment was conducted by means of the GeneRead DNAseq Panel PCR V2 Kit (Qiagen). Purification and size selection steps were processed utilizing Agencourt AMPure XP magnetic beads (Beckman Coulter).…”

Section: Genes (Akt1 Alk Ar Braf Ctnnb1 Ddr2 Egfr Erbb2 Fgfr3mentioning

confidence: 99%

“…In silico tools to predict the potential deleterious impact of detected variants. The potential impact of NGS-detected variants in the coding regions was predicted using following in silico tools as reported [32][33][34] : PolyPhen-2 (v2.2.2r398) 35 , Protein Variation Effect Analyzer (PROVEAN; v1.1.3) 36 , Sorting Intolerant From Tolerant (SIFT; Ensembl 66) 37,38 , Mutation Assessor (release 3) 39 and Combined Annotation Dependent Depletion (CADD; v.1.3) 40 . The PolyPhen-2 method utilizes physical and evolutionary comparative considerations to predict amino acid changes on protein structure and function.…”

Section: Genes (Akt1 Alk Ar Braf Ctnnb1 Ddr2 Egfr Erbb2 Fgfr3mentioning

confidence: 99%

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Novel pathogenic alterations in pediatric and adult desmoid-type fibromatosis – A systematic analysis of 204 cases

Trautmann

Rehkämper

Gevensleben

et al. 2020

Sci Rep

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Desmoid-type fibromatosis (DTF, aggressive fibromatosis) is a non-metastasizing mesenchymal neoplasm of deep soft tissue with a tendency towards local recurrence. Genetic alterations affecting canonical Wnt/β-catenin signaling are reported in the majority of DTF. While most sporadic DTF harbor somatic mutations in CTNNB1, germline mutations in adenomatous polyposis coli (APC) are known to occur in hereditary DTF types (FAP, Gardner-Syndrome). Additional single nucleotide variants (SNVs) in AKT1 (E17K) and BRAF (V600E) were reported in pediatric DTF with potential clinical implications. We performed targeted next-generation sequencing (NGS) in a large cohort of 204 formalin-fixed DTF samples, comprising 22 pediatric cases (patients age ≤18 years). The mutational status was correlated with clinicopathological characteristics. Overall, deleterious CTNNB1 mutations were detected in 89% of DTF, most frequently affecting the serine/threonine phosphorylation sites T41 and S45 of β-catenin. While the T41A CTNNB1 mutation was significantly more often identified in the mesenterial localization, DTF originating from extra-intestinal sites more frequently harbored the S45P CTNNB1 alteration. Beyond common mutations in CTNNB1, additional SNVs were demonstrated in 7% of the DTF cohort and in 18% of the pediatric DTF subgroup. The mutational spectrum included deleterious mutations in AKT1 (G311S/D and T312I), ALK (R806H and G924S), AR (A159T), EGFR (P848L), ERBB2 (H174Y), IDH2 (H354Y), KIT (V559D), RET (T1038A), SDHA (R325M), and SDHD (R115W), as characterized by in silico prediction tools. In conclusion, our study indicates that DTF may harbor a broader mutational spectrum beyond CTNNB1 mutations, comprising targetable alterations including the herewith first reported imatinib-sensitive KIT V559D mutation in DTF. Desmoid-type fibromatosis (aggressive fibromatosis, desmoid tumor, DTF) is an infiltrating, locally aggressive myofibroblastic neoplasm of intermediate malignant potential highly prone to local recurrence without the potential for metastatic spread. The tumors typically arise in deep soft tissue compartments of intra-and extra-abdominal localization. Pediatric forms usually affect the extremities, while in adults also the mesenterium and the abdominal wall are commonly involved sites; the latter predominantly affected in women 1. The majority of DTF harbor mutations affecting the canonical Wnt/β-catenin signaling pathway 2. While in patients with familial adenomatous polyposis (FAP) β-catenin is not degraded through inactivating mutations in APC, most sporadic DTF harbor alterations in CTNNB1; both leading to a nuclear accumulation of β-catenin and an oncogenic activation of the Wnt/β-catenin signal transduction pathway 3-6. In the sporadic subtype, alterations in CTNNB1 seem to be focused on the serine/threonine phosphorylation sites T41 and S45 7,8 with a higher risk of local recurrence reported in association with the S45F CTNNB1 mutation 8,9. Currently, no evidence-based approach for the treatment of DTF is establ...

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Section: Genes (Akt1 Alk Ar Braf Ctnnb1 Ddr2 Egfr Erbb2 Fgfr3mentioning

confidence: 99%

Section: Genes (Akt1 Alk Ar Braf Ctnnb1 Ddr2 Egfr Erbb2 Fgfr3mentioning

confidence: 99%

Novel pathogenic alterations in pediatric and adult desmoid-type fibromatosis – A systematic analysis of 204 cases

Trautmann

Rehkämper

Gevensleben

et al. 2020

Sci Rep

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“…Differential diagnosis includes primarily giant cell tumor of bone. Recent genetic and immunohistochemistry studies [ 3 ] have defined a p.Lys36Met substitutions in H3F3B gene on chromosome 17 in about 98% of chondroblastomas, also resulting in the immunohistochemical expression of H3F3B, that distinguishes it from giant cell tumor of bone which presents a H3F3A [ 4 ] mutation and from other mimickers.…”

Section: Introductionmentioning

confidence: 99%

Chondroblastoma’s Lung Metastases Treated with Denosumab in Pediatric Patient

et al. 2021

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Chondroblastoma is a rare benign chondrogenic tumor that occurs in skeletally immature patients between ages 10 and 20 years old. In literature are reported few cases of lung metastases, mainly occurred after surgery or local recurrences. There is no evidence on the pathogenesis of lung metastasis, as well as pulmonary disease course. Few treatments for metastases with aggressive behavior were based on chemotherapy regimen employed in other sarcoma with no results or not satisfying ones. Denosumab is approved for treatment of giant cell tumors and it is under investigation for other giant cell-rich bone tumors. Here, we report a case of a 16-year-old male chondroblastoma of the left humerus with bilateral lung metastases at presentation and progressing during follow-up, treated with denosumab for almost 2 years. We confirm that denosumab treatment can be effective in controlling chondroblastoma metastasis and it has been a safe procedure in an adolescent patient.

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“…Another study by Rehkamper et al 23 A similar study done by Ali et al 20 , studied expression for DOG 1 and multiple other immunohistochemical markers in chondroblastoma, giant cell tumors and aneurysmal bone CYST. The study showed positive results for DOG 1 in all the 3 cases of chondroblastomas.…”

Section: Discussionmentioning

confidence: 93%

“…The large specimens show positivity in majority of the cases which may be focal or weak. However smaller biopsy samples can be negative for DOG 1 and clinical, radiological, and histological features remains the gold standard for the diagnosis of this entity with DOG 1 providing a supportive role in difficult cases 23 .…”

Section: Resultsmentioning

confidence: 99%

Dog 1 Expression in Differential Diagnosis of Chondroblastomas and Its Histological Mimickers

Nisar

Mushtaq

Hassan

et al. 2020

PAFMJ

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Objective: Chondroblastoma is rare benign cartilage forming tumor of bone predominantly in individuals less than 20 years of age. Recently immunohistochemical marker DOG 1 has been reported to help in the diagnosis in difficult cases where histological features overlap with other similar entities. Current study aims to assess the sensitivity and specificity of DOG 1 in the diagnosis of chondroblastomas. Study design: descriptive cross-sectional study Place and duration of study: The study was conducted from June 2015 to July 2017 in Department of Histopathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. Patients and methods: Total fifty-two patients were included in this study including 19 chondroblastomas, 21 giant cell tumors and 12 chondromyxoid fibromas. DOG 1 antibody was applied on all the cases Results: DOG 1 was positive in 100 % of cases of chondroblastomas. However, intensity and proportion of staining pattern was variable among them. 78% (n=15) cases showed diffuse moderate to strong expression while 22% (n=4) cases showed focal weak expression. Only 10% (n=2) cases of giant cell tumors and 33% (n=4) of chondromyxoid fibromas expressed focal weak expression for DOG 1. Conclusions: This study confirms 100 % expression of DOG 1 in cases of chondroblastomas but intensity and proportion of staining pattern was variable. Therefore DOG 1 may prove to be a useful immunohistochemical marker for diagnosis of chondroblastomas in the future in difficult cases in correlation with histological and radiological features.

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Diagnostic tools in the differential diagnosis of giant cell-rich lesions of bone at biopsy

Cited by 22 publications

References 32 publications

Novel pathogenic alterations in pediatric and adult desmoid-type fibromatosis – A systematic analysis of 204 cases

Novel pathogenic alterations in pediatric and adult desmoid-type fibromatosis – A systematic analysis of 204 cases

Chondroblastoma’s Lung Metastases Treated with Denosumab in Pediatric Patient

Dog 1 Expression in Differential Diagnosis of Chondroblastomas and Its Histological Mimickers

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