Curettage or Resection? A Review on the Surgical Treatment of Low-Grade Chondrosarcomas.

Introduction Low-grade chondrosarcomas (LG-CS), including atypical cartilaginous tumors (ACT), are locally aggressive lesions. The focus of the discussion sits on the differential diagnosis between benign lesions or aggressive cartilaginous tumors and on their treatment: intralesional curettage or wide resection. This study presents the results obtained in the surgical treatment of 21 cases of LG-CS. Methods This retrospective study includes 21 consecutive patients from a single center with LG-CS who underwent surgery from 2013 to 2021. Fourteen were located in the appendicular skeleton, and seven in the axial (shoulder blade, spine, or pelvis). Mortality rate, recurrence, metastatic disease, overall survival, recurrence-free survival, and metastatic disease-free survival were analyzed for each type of procedure and each disease location. Operative complications and residual tumors were also recorded in cases where resection was performed. Survival was calculated using the Kaplan-Meier method. Results Thirteen patients underwent intralesional curettage (11 appendicular and 2 axial lesions), and eight underwent wide resection (5 axial and 3 appendicular). There were six recurrences during the follow-up, 43% of the axial lesions recurred, rising to 100% in axial curetted ones. Appendicular LG-CS recurred in 21% of cases, and only 18% of curetted appendicular lesions were not eradicated. The overall survival for the entire follow-up is 90.5%, and the 5-year survival rate is 83% (12 patients have adequate follow-up). Recurrence-free and metastasis-free survival were higher in resection cases, with 75% and 87.5%, vs. curettage 69.2% and 76.9%, respectively. In 9% of cases, the preoperative biopsy was inconsistent with the pathology of the surgical specimen. Discussion LG-CS and ACT are described as having high survival and low potential for metastatic disease. For this reason, these lesions are subject to a change in treatment philosophy to reflect these characteristics. Intra-lesional curettage is advocated as a less invasive technique for eradicating atypical cartilage tumors and has fewer and less severe complications, which was in accordance with our findings. Diagnosis, however, is challenging; misgrading is frequent and should be considered. Because of this risk of under-treating higher-grade lesions, some authors still defend wide-resection as the treatment of choice. We observed a trend towards longer survival, less recurrence, and metastatic disease with wide resection. Metastatic disease was higher than expected, present in 19% of cases, and always associated with local recurrence. Conclusion LG-CS is still a diagnostic and treatment challenge; patient selection is fundamental. Overall survival is high, independent of treatment choice or lesion location. We found a higher rate of metastatic disease than described in the literature; this, coupled with a misgrading rate of 9%, reflects the difficulty of preoperative diagnosis and the risk of treating high-grade chondrosarcomas as a low-grade lesion. More studies should be carried out with larger samples to obtain statistically robust results.

Microbial Disease Spectrum Linked to a Novel IL-12Rß1 N-Terminal Signal Peptide Stop-Gain Homozygous Mutation with Paradoxical Receptor Cell-Surface Expression.

Patients with Mendelian Susceptibility to Mycobacterial Diseases (MSMD) exhibit variable vulnerability to infections by mycobacteria and other intramacrophagic bacteria (e.g., Salmonella and Klebsiella) and fungi (e.g., Histoplasma, Candida, Paracoccidioides, Coccidioides, and Cryptococcus). The hallmark of MSMD is the inherited impaired production of interferon gamma (IFN-γ) or the lack of response to it. Mutations in the interleukin (IL)-12 receptor subunit beta 1 (IL12RB1) gene accounts for 38% of cases of MSMD. Most IL12RB1 pathogenic allele mutations, including ten known stop-gain variants, cause IL-12Rß1 complete deficiency (immunodeficiency-30, IMD30) by knocking out receptor cell-surface expression. IL12RB1 loss-of-function genotypes impair both IL-12 and IL-23 responses. Here, we assess the health effects of a rare, novel IL12RB1 stop-gain homozygous genotype with paradoxical IL-12Rß1 cell-surface expression. We appraise four MSMD children from three unrelated Brazilian kindreds by clinical consultation, medical records, and genetic and immunologic studies. The clinical spectrum narrowed down to Bacillus Calmette-Guerin (BCG) vaccine-related suppurative adenitis in all patients with one death, and recrudescence in two, histoplasmosis, and recurrence in one patient, extraintestinal salmonellosis in one child, and cutaneous vasculitis in another. In three patients, we established the homozygous Trp7Ter predicted loss-of-function inherited genotype and inferred it from the heterozygote parents of the fourth case. The Trp7Ter mutation maps to the predicted IL-12Rß1 N-terminal signal peptide sequence. BCG- or phytohemagglutinin-blasts from the three patients have reduced cell-surface expression of IL-12Rß1 with impaired production of IFN-γ and IL-17A. Screening of 227 unrelated healthy subjects from the same geographic region revealed one heterozygous genotype (allele frequency 0.0022) vs. one in over 841,883 public genome/exomes. We also show that the carriers bear European ancestry-informative alleles and share the extended CACCAGTCCGG IL12RB1 haplotype that occurs worldwide with a frequency of 8.4%. We conclude that the novel IL12RB1 N-terminal signal peptide stop-gain loss-of-function homozygous genotype confers IL-12Rß1 deficiency with varying severity and early-onset age through diminished cell-surface expression of an impaired IL-12Rß1 polypeptide. We firmly recommend attending to warning signs of IMD30 in children who are HIV-1 negative with a history of adverse effects to the BCG vaccine and presenting with recurrent Histoplasma spp. and extraintestinal Salmonella spp. infections.