Recurrent EGFR alterations in NTRK3 fusion negative congenital mesoblastic nephroma.
Practical laboratory medicine
2020; 21: e00164
Myelin bodies in LMX1B-associated nephropathy: potential for misdiagnosis.
Pediatric nephrology (Berlin, Germany)
Objectives: To identify oncogenic driver mutations in congenital mesoblastic nephroma (CMN) cases lacking ETV6-NTRK3 fusion and discuss their diagnostic value.Design: The institutional pathology database was queried for cases with a morphologic diagnosis of CMN. Cases positive for ETV6 rearrangement or with unavailable blocks were excluded. Four cases met the inclusion criteria and were sequenced by next-generation sequencing. Three additional cases were contributed by our collaborators.Results: Three of four internal cases harbor an EGFR kinase domain duplication (KDD), which is known to be oncogenic yet exceedingly rare in other histologies. All three outside cases are positive for EGFR alterations, including KDD in two and a splicing site mutation in one. The splicing site mutation is predicted to be EGFR activating. One of the outside cases was a retroperitoneal mass without a clear site of origin. A diagnosis of CMN is suggested based on exclusion of differential diagnoses by expert consultation and detection of EGFR KDD.Conclusions: EGFR activation, predominantly via EGFR KDD, is a common recurrent genetic alteration in CMN lacking NTRK3 fusions. CMN can be molecularly classified into NTRK3 fusion type, EGFR activation type and others.
View details for DOI 10.1016/j.plabm.2020.e00164
View details for PubMedID 32490123
Short tau inversion recovery magnetic resonance imaging for staging and screening in myxoid liposarcoma.
Journal of orthopaedics
2019; 16 (3): 206–10
BACKGROUND: Myelin figures, or zebra bodies, seen on electron microscopy were historically considered pathognomonic of Fabry disease, a rare lysosomal storage disorder caused by alpha-galactosidase A deficiency and associated with X-linked recessive mode of inheritance. More recently, iatrogenic phospholipidosis has emerged as an important alternate cause of myelin figures in the kidney.METHODS: We report two families with autosomal dominant nephropathy presenting with proteinuria and microscopic hematuria, and the kidney biopsies were notable for the presence of myelin figures and zebra bodies.RESULTS: Laboratory and genetic work-up for Fabry disease was negative. Genetic testing in both families revealed the same heterozygous missense mutation in LMX1B (C.737G>A, p.Arg246Gln). LMX1B mutations are known to cause nail-patella syndrome, featuring dysplastic nails and patella with or without nephropathy, as well as isolated LMX1B-associated nephropathy in the absence of extrarenal manifestations.CONCLUSIONS: LMX1B mutation-associated nephropathy should be considered in hereditary cases of proteinuria and/or hematuria, even in the absence of unique glomerular basement membrane changes indicative of nail-patella syndrome. In addition, LMX1B mutation should be included in the differential diagnosis of myelin figures and zebra bodies on kidney biopsy, so as to avoid a misdiagnosis.
View details for DOI 10.1007/s00467-020-04564-w
View details for PubMedID 32356190
Synchronous primary lung adenocarcinomas harboring distinct MET Exon 14 splice site mutations.
Lung cancer (Amsterdam, Netherlands)
2018; 122: 187–91
Purpose: Myxoid liposarcoma has a propensity to metastasize to bone. MRI is the preferred modality for detecting bone disease. We evaluated multiple MRI sequences to determine an optimal screening method.Methods: Whole body MRI was performed on all patients. The number and locations of metastases found by imaging and round cell component of the sites sampled were evaluated.Results: We found a total of 68 osseous lesions. Whole body MRI utilizing STIR only sequences decreased imaging time by 83.6% and demonstrated the lesions the best.Conclusions: STIR sequences can be exclusively used during staging and screening of myxoid liposarcoma.
View details for PubMedID 30906124
When a patient is found to have multiple lung tumors, distinguishing whether they represent metastatic nodules or separate primary cancers is crucial for staging and therapy. We report the case of a 79-year-old patient with two surgically resected synchronous left upper lobe adenocarcinomas initially pathologically staged as T3 (IIB), indicating adjuvant chemotherapy should be recommended. However, the tumors appeared radiographically distinct, so next-generation sequencing was performed on each nodule. Each tumor harbored a different mesenchymal-to-epithelial transition (MET) exon 14 skipping mutation, an emerging targetable mutation, suggestive of distinct clonality. While the in frame protein deletion was the same in each tumor, the nucleotide base substitutions were different. Thus, the patient was down-staged to having two separate IA tumors, spared of adjuvant chemotherapy, and routine surveillance was recommended. This case highlights the utility of using molecular analysis in diagnosing and treating multifocal lung tumors, and the process of convergent molecular evolution toward a common oncogenic driver mutation. This is the first case of multiple synchronous lung tumors each harboring a distinct MET exon 14 splice site mutation.
View details for PubMedID 30032829