Pseudosarcomatous myofibroblastic proliferations of the genitourinary tract are genetically different from nodular fasciitis and lack USP6, ROS1 and ETV6 gene rearrangements

Jebastin, Judith; Smith, Steven C.; Perry, Kyle; Gupta, Nilesh; Alanee, Shaheen; Carskadon, Shannon; Chitale, Dhananjay; Palanisamy, Nallasivam; Williamson, Sean R.

doi:10.1111/his.13526

Cited by 15 publications

(10 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Myofibroblastic proliferations of the urinary bladder encompass several described lesions with overlapping morphology, including inflammatory myofibroblastic tumour (IMT) and postoperative spindle cell nodule (PSCN). 1 Whether these two lesions represent the same or different entities remains controversial. IMT seems to occur in virtually all locations, in adults most frequently in the lungs, 2,3 whereas in children, the urinary tract, gastrointestinal tract and soft tissue are more frequently involved.…”

Section: Introductionmentioning

confidence: 99%

TERT promoter mutation analysis as a surrogate to morphology and immunohistochemistry in problematic spindle cell lesions of the urinary bladder

et al. 2020

View full text Add to dashboard Cite

TERT promoter mutation analysis as a surrogate to morphology and immunohistochemistry in problematic spindle cell lesions of the urinary bladder Aims: Pseudosarcomatous myofibroblastic proliferations (PSMPs) of the urinary bladder are diagnostically challenging. Diagnostic difficulties are mainly due to frequent cytokeratin expression, variable ALK expression and worrisome morphological features suggestive of malignancy. Conversely, sarcomatoid urothelial carcinoma (UC) may show bland inflammatory myofibroblastic tumour (IMT)-like morphology. TERT promoter mutations are characteristic events in urothelial cancers, but have not been studied in PSMPs. Methods and results: We compared histomorphological and immunohistochemical features and TERT promoter status in 16 PSMPs and 18 sarcomatoid UC. In a subset of PSMPs, RNA sequencing was performed. At least focal IMT-like morphology was seen in nine of 17 sarcomatoid UC. Atypical mitoses, differentiated urothelial component and heterologous elements were the most reliable distinguishing histomorphological features of sarcomatoid UC, if present. A panel of immunohistochemistry (IHC) including ALK (clone D5F3), p53 pattern, p63 and GATA3 reliably distinguished PSMP from sarcomatoid UC. GATA3 (P = 0.001) and p53 patterns (mutant versus wildtype; P < 0.001) were differentially expressed between PSMPs and sarcomatoid UC. Diffuse pancytokeratin staining was significantly associated with PSMPs (10 of 13) compared to four of 14 sarcomatoid UCs (P = 0.012). TERT promoter mutations were found in 17 of 18 sarcomatoid UC versus none of 16 PSMPs (P < 0.001). RNA sequencing revealed ALK genetic rearrangements in one of two ALK-positive and one of 10 ALK-negative PSMPs, which revealed a novel FN1/RET gene fusion. Conclusion: Careful histomorphological analysis and differential IHC reliably distinguish the majority of PSMPs and sarcomatoid UC. In equivocal cases, TERT promoter mutation analysis and/or detection of ALK expression/rearrangements are valuable additional diagnostic adjuncts, strongly supporting sarcomatoid UC and PSMP, respectively.

show abstract

Section: Introductionmentioning

confidence: 99%

TERT promoter mutation analysis as a surrogate to morphology and immunohistochemistry in problematic spindle cell lesions of the urinary bladder

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Tissue sections were marked for the areas of variant histology and macrodissected from the slide, if not already shown to be pure by histological review. Briefly, this assay is a targeted sequencing assay that uses an anchored multiplex polymerase chain reaction to prepare target‐enriched cDNA libraries from RNA to detect fusions and other mutations in >50 genes linked to known solid tumours, with methods previously described 10 . The genes targeted by this assay include: AKT3 , ALK , ARHGAP26 , AXL , BRAF (fusion and V600E mutation), BRD3 , BRD4 , EGFR (fusion and mutation), ERG , ESR1 , ETV1 , ETV4 , ETV5 , ETV6 , EWSR1 , FGFR1 , FGFR2 , FGFR3 , FGR , INSR , MAML2 , MAST1 , MAST2 , MET (fusion and mutation), MSMB , MUSK , MYB , NOTCH1 , NOTCH2 , NRG1 , NTRK1 , NTRK2 , NTRK3 , NUMBL , NUTM1 , PDGFRA (fusion and mutation), PDGFRB , PIK3CA , PKN1 , PPARG , PRKCA , PRKCB , RAF1 , RELA , RET , ROS1 , RSPO2 , RSPO3 , TERT , TFE3 , TFE3 , TFEB , THADA , and TMPRSS2 .…”

Section: Methodsmentioning

confidence: 99%

“…Briefly, this assay is a targeted sequencing assay that uses an anchored multiplex polymerase chain reaction to prepare target-enriched cDNA libraries from RNA to detect fusions and other mutations in >50 genes linked to known solid tumours, with methods previously described. 10 The genes targeted by this assay include: AKT3, ALK, ARHGAP26, AXL, BRAF (fusion and V600E mutation), BRD3, BRD4, EGFR (fusion and mutation), ERG, ESR1, ETV1, ETV4, ETV5, ETV6, EWSR1, FGFR1, FGFR2, FGFR3, FGR, INSR, MAML2, MAST1, MAST2, MET (fusion and mutation), MSMB, MUSK, MYB, NOTCH1, NOTCH2, NRG1, NTRK1, NTRK2, NTRK3, NUMBL, NUTM1, PDGFRA (fusion and mutation), PDGFRB, PIK3CA, PKN1, PPARG, PRKCA, PRKCB, RAF1, RELA, RET, ROS1, RSPO2, RSPO3, TERT, TFE3, TFE3, TFEB, THADA, and TMPRSS2. Seventeen formalin-fixed paraffin-embedded tissue blocks of different tumours were tested with this method; four of them failed quality metrics, whereas the remaining 13 tumours were informative and yielded positive or negative results.…”

Section: N G Smentioning

confidence: 99%

Gene fusion characterisation of rare aggressive prostate cancer variants—adenosquamous carcinoma, pleomorphic giant‐cell carcinoma, and sarcomatoid carcinoma: an analysis of 19 cases

et al. 2020

Self Cite

View full text Add to dashboard Cite

Gene fusion characterisation of rare aggressive prostate cancer variants-adenosquamous carcinoma, pleomorphic giant-cell carcinoma, and sarcomatoid carcinoma: an analysis of 19 cases Aims: To evaluate the molecular underpinnings of the rare aggressive prostate cancer variants adenosquamous carcinoma, pleomorphic giant-cell carcinoma, and sarcomatoid carcinoma. Methods and results: We retrieved 19 tumours with one or more variant(s), and performed ERG immunohistochemistry, a next-generation sequencing assay targeting recurrent gene fusions, and fluorescence insitu hybridisation (FISH) for ERG and BRAF. Divergent differentiation included: sarcomatoid carcinoma (n = 10), adenosquamous carcinoma (n = 7), and pleomorphic giant-cell carcinoma (n = 7). Five patients had more than one variant. Four had variants only in metastases. ERG rearrangement was detected in nine (47%, seven via sequencing, showing TMPRSS2-ERG fusions and one GRHL2-ERG fusion, and two via FISH, showing rearrangement via deletion). ERG was immunohistochemically positive in the adenocarcinoma in eight of nine (89%) patients, but was immunohistochemically positive in the variant in only five of nine patients (56%, typically decreased). One patient had a false-positive ERG immunohistochemical result in the sarcomatoid component despite a negative FISH result. Two (11%) harboured BRAF fusions (FAM131A-BRAF and SND1-BRAF).

show abstract

“…USP6 break-apart probe fluorescence in situ hybridization was performed with methods previously described 3 and was negative for rearrangement ( Figure 1F). A multiplex RNA fusion panel (Archer FusionPlex Solid Tumor Kit) was run on RNA extracted from representative formalinfixed, paraffin-embedded tumor block.…”

Section: Molecular Findingsmentioning

confidence: 99%

A NovelCOL1A1-CAMTA1Rearrangement in Cranial Fasciitis

et al. 2020

Self Cite

View full text Add to dashboard Cite

Cranial fasciitis is an uncommon benign fibroblastic tumor, generally histologically identical to nodular fasciitis. It develops almost exclusively in children. Cranial fasciitis manifests clinically as a painless rapidly growing solitary nodule in the head and neck area, frequently eroding the underlying bone. Thus, this entity is often confused with aggressive lesions such as sarcomas, both clinically and radiologically. Histopathologic examination is essential to differentiate between cranial fasciitis and fibrohistiocytic or even sarcomatous lesions observed in children. In this article, we present a case of cranial fasciitis with intracranial extension in a 2-year-old boy. Although USP6 rearrangement has recently been recognized as a recurring alteration in nodular fasciitis, we present a novel COL1A1-CAMTA1 fusion in this lesion.

show abstract

Pseudosarcomatous myofibroblastic proliferations of the genitourinary tract are genetically different from nodular fasciitis and lack USP6, ROS1 and ETV6 gene rearrangements

Cited by 15 publications

References 25 publications

TERT promoter mutation analysis as a surrogate to morphology and immunohistochemistry in problematic spindle cell lesions of the urinary bladder

TERT promoter mutation analysis as a surrogate to morphology and immunohistochemistry in problematic spindle cell lesions of the urinary bladder

Gene fusion characterisation of rare aggressive prostate cancer variants—adenosquamous carcinoma, pleomorphic giant‐cell carcinoma, and sarcomatoid carcinoma: an analysis of 19 cases

A NovelCOL1A1-CAMTA1Rearrangement in Cranial Fasciitis

Contact Info

Product

Resources

About