Diagnostic Utility of Genetic and Immunohistochemical H3-3A Mutation Analysis in Giant Cell Tumour of Bone

To validate the reliability and implementation of an objective diagnostic method for giant cell tumour of bone (GCTB). H3-3A gene mutation testing was performed using two different methods, Sanger sequencing and immunohistochemical (IHC) assays. A total of 214 patients, including 120 with GCTB and 94 with other giant cell-rich bone lesions, participated in the study. Sanger sequencing and IHC with anti-histone H3.3 G34W and G34V antibodies were performed on formalin-fixed, paraffin-embedded tissues, which were previously decalcified in EDTA if needed. The sensitivity and specificity of the molecular method was 100% (95% CI: 96.97–100%) and 100% (95% CI: 96.15–100%), respectively. The sensitivity and specificity of IHC was 94.32% (95% CI: 87.24–98.13%) and 100% (95% CI: 93.94–100.0%), respectively. P.G35 mutations were discovered in 2/9 (22.2%) secondary malignant GCTBs and 9/13 (69.2%) GCTB after denosumab treatment. We confirmed in a large series of patients that evaluation of H3-3A mutational status using direct sequencing is a reliable tool for diagnosing GCTB, and it should be incorporated into the diagnostic algorithm. Additionally, we discovered IHC can be used as a screening tool. Proper tissue processing and decalcification are necessary. The presence of the H3-3A mutation did not exclude malignant GCTB. Denosumab did not eradicate the neoplastic cell population of GCTB.

High-resolution ultrasound in the diagnosis of failed carpal tunnel decompression: a study of 35 cases

We used high-resolution ultrasound to examine 35 median nerves (35 patients) with failed carpal tunnel decompression to identify the cause of failure. The carpal tunnel was examined before revision surgery, and the results were correlated with surgical findings. The cross-sectional area was measured, and nerve morphology was analysed at the sites of compression. We found persistent median nerve compression in 30 out of 35 patients. In 20 patients, the compression was caused by a residual transverse carpal ligament, in four by perineural fibrosis, in five by both of these causes and in one by tenosynovitis. In four patients, evidence of median nerve injury with an epineural/fascicular lesion was detected; and in one, no abnormalities were found. Surgical findings were consistent with the ultrasound findings except in one patient where tenosynovitis was associated with a giant cell tumour, which was missed by ultrasound. High-resolution ultrasound can provide helpful information in preoperative diagnosis of failed carpal tunnel decompression with good correlation between the ultrasound and surgical findings. Level of evidence: IV

En bloc resection and vascularized ulnar pedicle graft reconstruction with plate fixation for giant cell tumour of the distal radius

We retrospectively reviewed the medical records of ten patients (five men and five women) who were treated in our unit for Campanacci Grade III giant cell tumour of the distal radius between July 2017 and December 2019. Following en bloc resection of a giant cell tumour of the distal radius, the wrist was reconstructed by transposing a vascularized pedicle graft from the ipsilateral ulnar shaft. The graft was fixed to the radial shaft and proximal carpal row with plates. At a mean follow-up of 23.5 months (range 18 to 31), bony union was achieved in all cases and there were no tumour recurrences. All patients had a good range of pronation and supination, but flexion and extension of the wrist was limited. DASH scores ranged from 5 to 11. This reconstruction method is a safe and effective procedure that provides good aesthetic outcomes, removes the need for microvascular techniques and reduces donor site morbidity. Level of evidence: IV

Computerised tomography features of giant cell tumour of the knee are associated with local recurrence after extended curettage

Background Extended curettage has increasingly become the preferred treatment for giant cell tumour of bone (GCTB), but the high recurrence rate after curettage poses a major challenge for orthopaedic surgeons. Computed tomography (CT) is valuable in the evaluation of GCTB. Our aim was to identify specific features of GCTB around the knee in pre-operative CT images that might have prognostic value for local recurrence. Methods We retrospectively analyzed data from 124 patients with primary GCTB around the knee who underwent extended curettage from 2010 through 2019. We collected demographic, clinical, and therapeutic data along with several CT-derived tumour characteristics. CT-derived tumor characteristics included tumour size, the distance between the tumour edge and articular surface (DTA), and destruction of posterior cortical bone (DPC). Akaike information criterion (AIC) was used to select which variables to enter into multivariate logistic regression models and to determine significant factors affecting recurrence. Results The total recurrence rate was 21.0% (26/124), and the average follow-up time was 69.5 ± 31.2 months (24–127 months). Age, DTA (< 2 mm), and DPC were significantly related to recurrence, as determined by multivariate logistic regression. The C-index of the final model was 0.79 (95% CI: 0.71 to 0.88), representing a good model for predicting recurrence. Conclusion Identifying certain features of GCTB around the knee on CT has prognostic value for patients treated with extended curettage. A three-factor model predicts tumour recurrence well after extended curettage.

Gene of the month: H3F3A and H3F3B

H3F3A and H3F3B genes are located at 1q42.12 and 17q25.1, respectively, and encode identical H3.3 core histone proteins which form part of the histone hetero-octamer complex. Histones function by packaging DNA into small units, the nucleosome, and are highly susceptible to epigenetic post-translational modification. H3 K27 mutations have been shown to inhibit the polycomb repressive complex 2, which is normally involved in epigenetic gene silencing. Mutations in H3F3A and H3F3B are increasingly recognised in a variety of solid tumours. Point mutations in H3F3A have been described in giant cell tumour of bone and paediatric-type diffuse high-grade gliomas. Mutations in H3F3B have been described in chondroblastoma. Loss of trimethylation of H3 K27 is characteristic of most sporadic and radiation-associated malignant peripheral nerve sheath tumours. Immunohistochemistry with a variety of novel antibodies directed against specific mutations, as well as loss of H3K27me3 staining, may be useful in specific settings and in diagnostically challenging cases.

Recurrent giant cell tumour of the distal ulna after en bloc resection with preoperative denosumab use

In recent years, denosumab has been used to treat giant cell tumour of bone (GCTB) not only in cases where surgery is complicated but also preoperatively to decrease the preoperative grade or to facilitate surgery for Campanacci grade II and III cases. However, there are no clear protocols regarding the preoperative use of denosumab before en bloc resection. There are a few reports of recurrent cases after en bloc resection; however, the association with the use of denosumab is unknown. We present the clinical, radiological and histopathological findings of a case of Campanacci grade III GCTB at the distal end of the ulna, which resulted in soft tissue recurrence after en bloc resection with the preoperative use of denosumab.