Dataset Information

Phosphaturic Mesenchymal Tumors in the Head and Neck Demonstrate a Broad Clinical and Morphologic Spectrum.

ABSTRACT: Phosphaturic mesenchymal tumour (PMT) is a rare tumour that occurs in bone or soft tissue and is associated with production of fibroblast growth factor 23 (FGF23) leading to tumor-induced osteomalacia. We report three cases of PMT involving the head and neck that highlight the broad spectrum of clinical and histologic features of PMT. One of these lesions from the hard palate demonstrated an admixture of epithelial and mesenchymal elements, a feature that can pose a diagnostic challenge. The diagnostic utility of immunohistochemistry including FGF23, somatostatin receptor 2A, SATB2, ERG and CD56 is discussed. The biochemical pathway in the development of PMT associated tumor induced osteomalacia and its role in investigations and management of PMT is also described.

SUBMITTER: Hulme KR

PROVIDER: S-EPMC9424444 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Phosphaturic Mesenchymal Tumors in the Head and Neck Demonstrate a Broad Clinical and Morphologic Spectrum.

Hulme K R KR Mahar A A Campbell R G RG Clifton-Bligh R R Gill A J AJ Palme C E CE Gupta R R

Head and neck pathology 20220204 3

Phosphaturic mesenchymal tumour (PMT) is a rare tumour that occurs in bone or soft tissue and is associated with production of fibroblast growth factor 23 (FGF23) leading to tumor-induced osteomalacia. We report three cases of PMT involving the head and neck that highlight the broad spectrum of clinical and histologic features of PMT. One of these lesions from the hard palate demonstrated an admixture of epithelial and mesenchymal elements, a feature that can pose a diagnostic challenge. The dia ...[more]

PMID: 35119617

Similar Datasets

Project description:BackgroundThe diagnosis of phosphaturic mesenchymal tumors (PMT) is easily delayed clinically, and their surgical treatment is unstandardized. This study aimed to evaluate our experience in the diagnosis and treatment of PMT and provide a research basis for the accurate and standardized treatment of PMT.Materials and methodsTwelve patients diagnosed with PMT in our department and who underwent surgical treatment were included in this study. Preoperative demographic and clinical information were recorded. CT, MRI, and technetium-99m (Tc99m)-octreotide PET/CT imaging techniques were used to evaluate the general conditions and lesion boundaries of the tumors. Surgical treatment was performed using radical resection and microwave ablation-assisted extended curettage according to the lesion location and size. Patients were strictly followed up with and evaluated for oncological prognosis, radiological results, bone healing, serum ion levels, limb function, and pain level; the occurrence of complications was also recorded.ResultsThree patients underwent radical resection, and nine underwent microwave ablation-assisted extended curettage. The average duration of symptoms in this group was 1.5 years (9-35 months) before diagnosis. Serum phosphate and AKP levels returned to normal one and two weeks postoperatively, respectively. There was no apparent specificity in the pathological findings; however, the immunohistochemistry of FGF-23 was positive, and the original fracture sites were effectively healed during the follow-up. The limb function and pain scores were significantly improved. The MSTS score increased from 15.3 to 29.0, and the VAS score decreased from 5.3 to 0.4. All patients recovered, and 90% resumed their original jobs.ConclusionsAccurate diagnosis and standardized surgical treatment are crucial to achieving a clinical cure for PMT. Combining clinical manifestations, biochemical examinations, imaging characteristics, and pathological findings is an effective way to diagnose PMT accurately. Radical resection and microwave ablation-assisted extended curettage are reliable surgical treatment methods for PMT.

Project description:The gene CDC73 (previously known as HRPT2) encodes the protein parafibromin. Biallelic mutation of CDC73 is strongly associated with malignancy in parathyroid tumors. Heterozygous germline mutations cause hyperparathyroidism jaw tumor syndrome,which is associated with a high life-time risk of parathyroid carcinoma. Therefore loss of parafibromin expression by immunohistochemistry may triage genetic testing for hyperparathyroidism jaw tumor syndrome and be associated with malignant behavior in atypical parathyroid tumors. We share our experience that parafibromin-negative parathyroid tumors show distinctive morphology. We searched our institutional database for parathyroid tumors demonstrating complete loss of nuclear expression of parafibromin with internal positive controls. Forty-three parafibromin-negative tumors from 40 (5.1%) of 789 patients undergoing immunohistochemistry were identified. Thirty-three (77%) were external consultation cases; the estimated incidence in unselected tumors was 0.19%. Sixteen (37.2%) fulfilled World Health Organization 2017 criteria for parathyroid carcinoma and 63% had serum calcium greater than 3mmol/L. One of 27 (3.7%) noninvasive but parafibromin-negative tumors subsequently metastasized. Parafibromin-negative patients were younger (mean, 36 vs. 63 y; P<0.001) and had larger tumors (mean, 3.04 vs. 0.62 g; P<0.001). Not all patients had full testing, but 26 patients had pathogenic CDC73 mutation/deletions confirmed in tumor (n=23) and/or germline (n=16). Parafibromin-negative tumors demonstrated distinctive morphology including extensive sheet-like rather than acinar growth, eosinophilic cytoplasm, nuclear enlargement with distinctive coarse chromatin, perinuclear cytoplasmic clearing, a prominent arborizing vasculature, and, frequently, a thick capsule. Microcystic change was found in 21 (48.8%). In conclusion, there are previously unrecognized morphologic clues to parafibromin loss/CDC73 mutation in parathyroid tumors which, given the association with malignancy and syndromic disease, are important to recognize.

Project description:Phosphaturic mesenchymal tumours are a heterogeneous set of bone and soft tissue neoplasms that can cause a number of paraneoplastic syndromes such as tumour induced osteomalacia. The term phosphaturic comes from the common finding that these tumours secrete high levels of fibroblast growth factor 23 which causes renal phosphate wasting leading to hypophosphatemia. Phosphaturic mesenchymal tumours are rare and diagnosis is difficult. A very active 68 year old male presented with bone pain and muscle weakness. He was hypophosphataemic and total alkaline phosphatase was markedly elevated. The patient was placed on vitamin D supplementation but his condition progressed. In the fifth year of presentation the patient required the use of a wheelchair and described "explosive" bone pain on physical contact. Serum 1,25 dihydroxyvitamin D was low and serum fibroblast growth factor 23 was significantly elevated, raising suspicion of a phosphaturic mesenchymal tumour. A lesion was detected in his left femoral head and the patient underwent a total hip replacement. The patient displayed a rapid improvement to his condition and during a three year follow up period he returned to an active lifestyle. As molecular testing may help provide a robust diagnosis and is particularly useful in rare diseases we took a next generation sequencing approach to identify a differential expression of small RNAs in the resected tumour. Small RNAs are non-coding RNA molecules that play a key role in regulation of gene expression and can be used as specific biomarkers. We found an upregulation of miR-197. We also found a downregulation of miR-20b, miR-144 and miR-335 which is a small RNA profile typical of osteosarcoma. MiR-21, the most frequently upregulated microRNA in cancer, was downregulated. We conclude that the specific small RNA profile is typical of osteosarcoma except for the downregulation of oncogenic miR-21. Transcriptional plasticity of miR-197, which is computationally predicted to target fibroblast growth factor 23 messenger RNA, may be upregulated in a cellular effort to correct the ectopic expression of the protein.

Project description:A major breakthrough in the classification of soft tissue tumors has been the recent identification of NTRK-fusion related neoplasms which are amenable to highly effective targeted therapies. Despite these therapeutic opportunities, diagnostic challenges have emerged in recognizing tumors characterized by protein kinase fusions, as they are associated with a wide morphologic spectrum, variable risk of malignancy and a rather nonspecific immunoprofile. As such, NTRK-related fusions may occur in infantile fibrosarcoma, lipofibromatosis-like neural tumors (LPF-NTs), tumors resembling malignant peripheral nerve sheath tumors, etc. Triggered by an index case resembling LPF-NT but harboring RET gene rearrangement, we investigated our files for cases showing RET gene abnormalities to establish their clinicopathologic features. Tumors were tested with a combination of targeted RNA sequencing and fluorescence in situ hybridization methods. Six cases with RET gene rearrangements were identified, all except 1 occurred in children, including 4 infants. Their morphologic spectrum was quite diverse, but closely reproduced the phenotype of NTRK-fusion-positive tumors, including LPF-NTs (n=3), infantile fibrosarcoma-like tumor (n=2) and malignant peripheral nerve sheath tumor-like (n=1). Three cases showed coexpression of S100 and CD34, whereas the remaining 3 had a nonspecific immunoprofile. The tumors ranged morphologically and clinically from benign to highly malignant. None of the LPF-NT cases recurred, whereas 2 patients with malignant histology had a highly aggressive course with distant metastases to lung and other viscera. By targeted RNA sequencing these tumors harbored RET fusions with an identical break in exon 12, which retains the tyrosine kinase domain in the fusion oncoprotein and involving various gene partners (CLIP2, CCDC6, SPECC1L, MYH10, and NCOA4). Our results suggest that RET fusion-positive neoplasms share a similar phenotypic spectrum with the NTRK-positive tumors, displaying either fibroblastic or neural-like differentiation, and spanning a wide spectrum of clinical behavior. These findings open new avenues for targeted therapy with RET inhibitors currently available in clinical trials.

Dataset Information

Phosphaturic Mesenchymal Tumors in the Head and Neck Demonstrate a Broad Clinical and Morphologic Spectrum.

Publications

Phosphaturic Mesenchymal Tumors in the Head and Neck Demonstrate a Broad Clinical and Morphologic Spectrum.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets