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Cancers May 2024The Wnt receptor ROR1 has generated increased interest as a cancer therapeutic target. Research on several therapeutic approaches involving this receptor is ongoing;...
The Wnt receptor ROR1 has generated increased interest as a cancer therapeutic target. Research on several therapeutic approaches involving this receptor is ongoing; however, ROR1 tissue expression remains understudied. We performed an immunohistochemistry analysis of ROR1 protein expression in a large cohort of multiple tumor and histologic types. We analyzed 12 anonymized multi-tumor tissue microarrays (TMAs), including mesothelioma, esophageal and upper gastrointestinal carcinomas, and uterine endometrioid carcinoma, among other tumor types. Additionally, we studied 5 different sarcoma types of TMAs and 6 patient-derived xenografts (PDX) TMAs developed from 19 different anatomic sites and tumor histologic types. A total of 1142 patient cases from different histologic types and 140 PDXs placed in TMAs were evaluated. Pathologists assessed the percentage of tumor cells in each case that were positive for ROR1 and the intensity of staining. For determining the prevalence of staining for each tumor type, a case was considered positive if >1% of its tumor cells showed ROR1 staining. Our immunohistochemistry assays revealed a heterogeneous ROR1 expression profile. A high prevalence of ROR1 expression was found in mesothelioma (84.6%), liposarcoma (36.1%), gastrointestinal stromal tumors (33.3%), and uterine endometrioid carcinoma (28.9%). Other histologic types such as breast, lung, renal cell, hepatocellular, urothelial carcinoma, and colon carcinomas; glioblastoma; cholangiocarcinoma; and leiomyosarcoma showed less ROR1 overall expression, ranging between 0.9 and 13%. No ROR1 expression was seen in mesenchymal chondrosarcoma, rhabdomyosarcoma, or gastric adenocarcinoma cases. Overall, ROR1 expression was relatively infrequent and low in most tumor types investigated; however, ROR1 expression was infrequent but high in selected tumor types, such as gastroesophageal GIST, suggesting that ROR1 prescreening may be preferable for those indications. Further, mesothelioma exhibited frequent and high levels of ROR1 expression, which represents a previously unrecognized therapeutic opportunity. These findings can contribute to the development of ROR1-targeted therapies.
PubMed: 38791952
DOI: 10.3390/cancers16101874 -
Child's Nervous System : ChNS :... May 2024Intracranial mesenchymal chondrosarcoma (IMC) is a rare malignant tumor in pediatric population. IMC can present as extra- or intra-axial lesion in pediatric patients,... (Review)
Review
BACKGROUND
Intracranial mesenchymal chondrosarcoma (IMC) is a rare malignant tumor in pediatric population. IMC can present as extra- or intra-axial lesion in pediatric patients, though the former is commoner causing raised intracranial pressure (ICP). Radiological diagnosis is a challenge in these cases, as is it difficult to differentiate these from other extra-axial neoplasms due to the wide differential diagnosis in pediatric population. We aim to systematically review the literature and present a rare case of extraskeletal intracranial mesenchymal chondrosarcoma treated with safe maximal resection.
METHODS
A systematic review of literature was conducted in accordance with PRISMA guidelines. PubMed and Scopus databases were queried using the search terms, "primary intracranial chondrosarcoma", "extraskeletal mesenchymal chondrosarcoma", "mesenchymal chondrosarcoma" and "pediatric". Presentation, surgical management and outcome of a 15-year-old male with an extraskeletal IMC are also described.
RESULTS
The search yielded 25 articles which met the inclusion criteria. These published records consisted of 33 IMC cases with mean age at presentation of 9.81 ± 5.2 years (range 2 months to 18 years). Frontal region was the commonest locations (11, 33.3%). Most common presentation was headache (14, 42.4%). All patients underwent surgical intervention: gross total resection (20, 60.6%), subtotal resection (9, 27.3%) and no extent mentioned (4, 12.1%). No adjuvant therapy was received in 15 patients (45.5%). On latest follow-up, 11 patients (33.3%) are on remission, 5 patients (15.2%) are symptom free, 3 patients (9.1%) had recurrence, 2 patients (6.1%) had metastasis and 9 patients (27.3%) expired.
CONCLUSION
IMC is a rare entity in pediatric population with imaging findings which are non-characteristic leading to its diagnostic challenge. It can masquerade as other extra-axial intracranial neoplasm (meningioma or hemangiopericytoma). Combination of clinico-radiological and pathological examination can help in accurate diagnosis. Safe Maximal resection followed by radiotherapy is the preferred treatment strategy.
PubMed: 38762839
DOI: 10.1007/s00381-024-06452-2 -
Journal of Cancer Research and... Apr 2024Bone sarcomas encompass a group of spontaneous mesenchymal malignancies, among which osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma are the most common... (Review)
Review
Bone sarcomas encompass a group of spontaneous mesenchymal malignancies, among which osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma are the most common subtypes. Chondrosarcoma, a relatively prevalent malignant bone tumor that originates from chondrocytes, is characterized by endogenous cartilage ossification within the tumor tissue. Despite the use of aggressive treatment approaches involving extensive surgical resection, chemotherapy, and radiotherapy for patients with osteosarcoma, chondrosarcoma, and chordoma, limited improvements in patient outcomes have been observed. Furthermore, resistance to chemotherapy and radiation therapy has been observed in chondrosarcoma and chordoma cases. Consequently, novel therapeutic approaches for bone sarcomas, including chondrosarcoma, need to be uncovered. Recently, the emergence of immunotherapy and immune checkpoint inhibitors has garnered attention given their clinical success in various diverse types of cancer, thereby prompting investigations into their potential for managing chondrosarcoma. Considering that circumvention of immune surveillance is considered a key factor in the malignant progression of tumors and that immune checkpoints play an important role in modulating antitumor immune effects, blockers or inhibitors targeting these immune checkpoints have become effective therapeutic tools for patients with tumors. One such checkpoint receptor implicated in this process is programmed cell death protein-1 (PD-1). The association between PD-1 and programmed cell death ligand-1 (PD-L1) and cancer progression in humans has been extensively studied, highlighting their remarkable potential as biomarkers for cancer treatment. This review comprehensively examines available studies on current chondrosarcoma treatments and advancements in anti-PD-1/PD-L1 blockade therapy for chondrosarcoma.
Topics: Humans; Chondrosarcoma; B7-H1 Antigen; Programmed Cell Death 1 Receptor; Bone Neoplasms; Immune Checkpoint Inhibitors; Immunotherapy
PubMed: 38687921
DOI: 10.4103/jcrt.jcrt_2269_23 -
Clinical Orthopaedics and Related... Apr 2024Malignancies involving the pelvic ring present numerous challenges, especially in the periacetabular area. Extensive resection of the pelvic region without...
BACKGROUND
Malignancies involving the pelvic ring present numerous challenges, especially in the periacetabular area. Extensive resection of the pelvic region without reconstruction can lead to severe functional impairment. Numerous reconstructive options exist, but all have drawbacks. Extracorporeally irradiated autografts are one option for reconstruction after periacetabular resections; they offer the potential advantages of eliminating the risk of allogeneic reactions associated with allografts and preserving local anatomy. However, little is known about the durability and risks of this approach in pelvic reconstruction.
QUESTIONS/PURPOSES
(1) What are the survival rates of the autograft used, and if there is graft loss, what is the extent of this loss? (2) What are the functional outcomes after the implementation of this method? (3) What is the rate and nature of complications associated with this approach?
METHODS
This is a retrospective case series from one subspecialty tumor unit that evaluated patients treated between January 2005 to January 2022. During that time, three surgeons treated 48 patients with Type II resections (defined as resection of periacetabular area). Patients treated with isolated Type II resections were eligible, as were those treated either with Type I+II resections, Type II+III resections, Type I+II+III resections, and Type I+II+III+IV resections. Of those, 21% (10 of 48) were treated primarily with a cone prosthesis, 13% (6 of 48) were treated without femoral reconstruction, 10% (5 of 48) were treated with resection without reconstruction, and 6% (3 of 48) had a THA on the sacrum, leaving 50% (24 of 48) of patients who were treated with femoral and acetabular reconstruction using extracorporeally irradiated autograft and total hip replacement; those patients were potentially eligible for this study. During that time span, we used this approach in all Type II pelvic resection procedures, when a part of the hemipelvis could be preserved without resection (other than Type I+II+III+IV) and where we predicted that there would be sufficient bone stock after tumor removal. Of those, 21% (5 of 24) were lost to follow-up before 2 years, and 13% (3 of 24) died within 2 years with the reconstruction intact and without any reoperation or graft loss, leaving 67% (16 of 24) for analysis here. Demographic characteristics, type of tumor, tumor origin site, type of applied resection, and extent of applied surgical procedure were noted. Of 16 patients, 12 were male, with a mean age of 38 ± 21 years. Tumor types included chondrosarcoma in eight patients, malignant mesenchymal tumor in four patients, osteosarcoma in two patients, and Ewing sarcoma in two patients. Among these, 10 patients had tumors originating from the pelvis, whereas six patients had tumors originating from the proximal femur. We used a Kaplan-Meier estimator to calculate survivorship free from total or partial graft removal at 72 months. To measure functional results, the Musculoskeletal Tumor Society (MSTS) scoring system was utilized at most recent follow-up so as to be able to evaluate the impact of complications (if any) on the ultimate result. The MSTS score ranges from a minimum of 0 points to a maximum of 30 points, where a higher score reflects lower pain and higher functional and emotional capacity. Related complications, time of complications, secondary interventions, and mortality rates were also ascertained from chart review.
RESULTS
Graft survival rate at 72 months after initial reconstruction, free from partial or total graft removal, was 50% (95% CI 26% to 75%). Kaplan-Meier analyses revealed estimated mean time of graft removal as 43 months (95% CI 28 to 58). The graft was protected in eight patients on their final follow-up radiographs. The median (range) MSTS score was 18 (6 to 25) of 30 points at most-recent follow-up (these scores include patients who have had their grafts removed). In all, 15 of 16 patients had 17 complications; 16 were major complications (defined as those substantial enough to result in further surgery or a life- or limb-threatening event). A total of 14 of those 15 patients underwent one or more secondary procedures (a total of 21 unplanned additional procedures were performed in those patients). Deep infection was the most common complication, occurring in eight patients. Prosthesis dislocation occurred in four patients. Three patients developed aseptic acetabular component loosening, two had graft fractures, and one patient developed heterotopic ossification.
CONCLUSION
Composite reconstruction with extracorporeal irradiated autografts plus total hip replacement is a feasible reconstruction technique after Type II pelvic resections, although complications and reoperations were common. Although no reconstruction technique has been proven superior to other alternatives, the high risk of complications and reoperations associated with this technique should be considered when selecting from among possible alternative reconstruction methods.
LEVEL OF EVIDENCE
Level IV, therapeutic study.
PubMed: 38666740
DOI: 10.1097/CORR.0000000000003097 -
Oncology Letters Jun 2024Sarcoma is derived from mesenchymal neoplasms and has numerous subtypes, accounting for 1% of all adult malignancies and 15% of childhood malignancies. The prognosis of...
Sarcoma is derived from mesenchymal neoplasms and has numerous subtypes, accounting for 1% of all adult malignancies and 15% of childhood malignancies. The prognosis of metastatic or recurrent sarcoma remains poor. The current study presents two cases of sarcoma enrolled in a phase I dose escalation trial for solid tumor, who had previously failed all standard therapies. These patients were treated with VG161, an immune-stimulating herpes simplex virus type 1 oncolytic virus with payloads of IL-12, IL-15 and IL-15 receptor α unit, and a programmed cell death 1 (PD-1)/PD-1 ligand 1 blocking peptide. Both cases demonstrated stable disease as the best response, accompanied by a noteworthy prolongation of progression-free survival (11.8 months for chondrosarcoma and 11.9 months for soft tissue sarcoma, respectively) at a dose of 2.5×10 PFU/cycle. In addition, the treatment led to the activation of anti-cancer immunity, as evident from cytokine, lymphocyte subset and related pathway analyses of peripheral blood and/or tumor biopsy samples. These promising results suggest that VG161 monotherapy holds promise as an effective treatment for sarcoma and warrants further investigation through clinical trials. The two reported patients were part of a phase I clinical trial conducted and registered on the Australian New Zealand Clinical Trials Registry in Australia (registration no. ACTRN12620000244909; registration date, 26 February, 2020).
PubMed: 38638849
DOI: 10.3892/ol.2024.14377 -
Cureus Feb 2024Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the gastrointestinal tract and is most commonly seen in the stomach. The standard treatment...
Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the gastrointestinal tract and is most commonly seen in the stomach. The standard treatment for patients with advanced GISTs include both surgical resection and imatinib therapy. There have been cases that document the alterations of patients' GIST histomorphology both with primary GIST prior to imatinib therapy and with recurrent GIST after imatinib therapy. However, there has been no documented case of a patient who has recurrent GIST with chondroid differentiation at the primary site after imatinib therapy. In this article, we report an incidental finding of a 58-year-old patient who had two treatments of imatinib therapy prior to surgical resection of her recurrent GIST in her stomach. We also explore through a mini-literature review the various cases of GIST with chondroid differentiation that have been reported to compare the histomorphology, immunophenotype, and patient demographic of these cases. This article is significant for reporting a rare finding of GIST after imatinib therapy and highlights the various presentations that GIST could acquire after imatinib therapy that exclude another malignant process, such as chondrosarcoma.
PubMed: 38533168
DOI: 10.7759/cureus.54842 -
Modern Pathology : An Official Journal... May 2024Extraskeletal myxoid chondrosarcoma (EMC) is an uncommon mesenchymal neoplasm characteristically composed of uniform-appearing round to spindle-shaped cells with...
Extraskeletal myxoid chondrosarcoma (EMC) is an uncommon mesenchymal neoplasm characteristically composed of uniform-appearing round to spindle-shaped cells with eosinophilic cytoplasm and abundant myxoid extracellular matrix. Although the majority of cases harbor a pathognomonic t(9;22) translocation that fuses EWSR1 with the orphan nuclear receptor NR4A3, there are less common variants that partner NR4A3 with TAF15, TCF12, or TFG. By immunohistochemistry, EMC has features of both cartilaginous and neuroendocrine differentiation, as evidenced by inconsistent expression of S100 protein and synaptophysin or INSM1, respectively, in a subset of cases. Given the limitations of available immunohistochemical stains for the diagnosis of EMC, we analyzed genome-wide gene expression microarray data to identify candidate biomarkers based on differential expression in EMC in comparison with other mesenchymal neoplasms. This analysis pointed to CHRNA6 as the gene with the highest relative expression in EMC (96-fold; P = 8.2 × 10) and the only gene with >50-fold increased expression in EMC compared with other tumors. Using RNA chromogenic in situ hybridization, we observed strong and diffuse expression of CHRNA6 in 25 cases of EMC, including both EWSR1-rearranged and TAF15-rearranged variants. All examined cases of histologic mimics were negative for CHRNA6 overexpression; however, limited CHRNA6 expression, not reaching a threshold of >5 puncta or 1 aggregate of chromogen in >25% of cells, was observed in 69 of 685 mimics (10.1%), spanning an array of mesenchymal tumors. Taken together, these findings suggest that, with careful interpretation and the use of appropriate thresholds, CHRNA6 RNA chromogenic in situ hybridization is a potentially useful ancillary histologic tool for the diagnosis of EMC.
Topics: Humans; Biomarkers, Tumor; Chondrosarcoma; Neoplasms, Connective and Soft Tissue; Female; Male; Middle Aged; Aged; In Situ Hybridization; Adult; Receptors, Nicotinic; Neoplasms, Connective Tissue; Aged, 80 and over; Immunohistochemistry
PubMed: 38447752
DOI: 10.1016/j.modpat.2024.100464 -
Indian Journal of Pathology &... Jul 2023
PubMed: 38391341
DOI: 10.4103/ijpm.ijpm_299_22