Inflammatory rhabdomyoblastic tumor is a recently introduced name for neoplasms currently included in the World Health Organization classification of soft tissue tumors under the rubric inflammatory leiomyosarcoma. Inflammatory rhabdomyoblastic tumor is an excellent example of how surgical pathologists working in conjunction with tumor biologists can greatly improve tumor classification to the benefit of patients. Over the last 28 years, understanding of this entity has undergone a fascinating evolution. This review serves as a summary of the latest findings in inflammatory rhabdomyoblastic tumor research and a diagnostic manual for the practicing surgical pathologist.
We examined the value of targeted molecular screening for the identification of uterine anaplastic lymphoma kinase (ALK)-rearranged mesenchymal tumors, including ALK immunohistochemistry followed by molecular genetic testing, in all uterine leiomyosarcomas and STUMPs (smooth muscle tumors of uncertain malignant potential). All leiomyosarcoma and STUMP cases diagnosed in a 10-year period (2006-2016) at Charles University Faculty of Medicine in Pilsen were retrieved and reviewed. Of 23 cases, one case (LMS [leiomyosarcoma]) was positive for ALK rearrangement, namely, PPP1CB-ALK fusion gene. No specific histologic features (i.e., lymphocytic infiltrate and stromal edema) were observed in this case. This suggests that inflammatory myofibroblastic tumor (IMT)-like histologic features may not be an initial reliable screening tool in identifying uterine IMT cases. Thus, we proposed a two-step IHC and molecular genetic testing (as a reflex test) for IMT in all uterine LMS and STUMP cases. This will enhance the proper detection of such tumors at the population level and ultimately offer patients available targeted therapies.
- MeSH
- anaplastická lymfomová kináza MeSH
- genetické testování metody MeSH
- genová přestavba * MeSH
- imunohistochemie MeSH
- leiomyosarkom diagnóza genetika metabolismus MeSH
- lidé MeSH
- nádor z hladké svalové tkáně diagnóza genetika metabolismus MeSH
- nádorové biomarkery genetika metabolismus MeSH
- nádory dělohy diagnóza genetika metabolismus MeSH
- retrospektivní studie MeSH
- tyrosinkinasové receptory genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The diagnosis of a uterine smooth muscle lesion is, in the majority of cases, straightforward. However, in a small number of cases, the morphological criteria used in such lesions cannot differentiate with certainty a benign from a malignant lesion and a diagnosis of smooth muscle tumor with uncertain malignant potential (STUMP) is made. Uterine leiomyosarcomas are often easy to diagnose but it is difficult or even impossible to identify a prognostic factor at the moment of the diagnosis with the exception of the stage. We hypothesize, for uterine smooth muscle lesions, that there is a gradient of genomic complexity that correlates to outcome. We first tested this hypothesis on STUMP lesions in a previous study and demonstrated that this 'gray category' could be split according to genomic index into two groups. A benign group, with a low to moderate alteration rate without recurrence and a malignant group, with a highly rearranged profile akin to uterine leiomyosarcomas. Here, we analyzed a large series of 77 uterine smooth muscle lesions (from 76 patients) morphologically classified as 19 leiomyomas, 14 STUMP and 44 leiomyosarcomas with clinicopathological and genomic correlations. We confirmed that genomic index with a cut-off=10 is a predictor of recurrence (P<0.0001) and with a cut-off=35 is a marker for poor overall survival (P=0.035). For the tumors confined to the uterus, stage as a prognostic factor was not useful in survival prediction. At stage I, among the tumors reclassified as molecular leiomyosarcomas (ie, genomic index ≥10), the poor prognostic markers were: 5p gain (overall survival P=0.0008), genomic index at cut-off=35 (overall survival P=0.0193), 13p loss including RB1 (overall survival P=0.0096) and 17p gain including MYOCD gain (overall survival P=0.0425). Based on these findings (and the feasibility of genomic profiling by array-comparative genomic hybridization), genomic index, 5p and 17p gains prognostic value could be evaluated in future prospective chemotherapy trials.
- MeSH
- analýza přežití MeSH
- dospělí MeSH
- leiomyom diagnóza genetika patologie MeSH
- leiomyosarkom diagnóza genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidské chromozomy, pár 13 genetika MeSH
- lidské chromozomy, pár 17 genetika MeSH
- lidské chromozomy, pár 5 genetika MeSH
- lokální recidiva nádoru MeSH
- nádor z hladké svalové tkáně diagnóza genetika patologie MeSH
- nádory dělohy diagnóza genetika patologie MeSH
- prognóza MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stanovení celkové genové exprese * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The diagnosis and management of uterine smooth muscle tumors with uncertain malignant potential (STUMP) is often challenging, and genomic data on these lesions as well as on uterine smooth muscle lesions are limited. We tested the hypothesis that genomic profile determination by array-CGH could split STUMP into a benign group with scarce chromosomal alterations akin to leiomyoma and a malignant group with high chromosomal instability akin to leiomyosarcoma. Array-CGH genomic profile analysis was conducted for a series of 29 cases of uterine STUMP. A group of ten uterine leiomyomas and ten uterine leiomyosarcomas served as controls. The mean age was 50 years (range, 24-85) and the follow-up ranged from 12 to 156 months (average 70 months). Since STUMP is a heterogenous group of tumors with genomic profiles that can harbor few to many chromosomal alterations, we compared genomic indices in leiomyomas and leiomyosarcomas and set a genomic index=10 threshold. Tumors with a genomic index <10 were classified as nonrecurring STUMPs and those with a genomic index >10 represented STUMPs with recurrences and unfavorable outcomes. Hence, the genomic index threshold splits the STUMP category into two groups of tumors with different outcomes: a group comparable to leiomyomas and another similar to leiomyosarcomas, but more indolent. In our STUMP series, genomic analysis by array-CGH is an innovative diagnostic tool for problematic smooth muscle uterine lesions, complementary to the morphological evaluation approach. We provide an improved classification method for distinguishing truly malignant tumors from benign lesions within the category of STUMP, especially those with equivocal morphological features.
- MeSH
- dospělí MeSH
- leiomyom diagnóza genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru genetika patologie MeSH
- mladý dospělý MeSH
- nádor z hladké svalové tkáně diagnóza genetika patologie MeSH
- nádory dělohy diagnóza genetika patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- srovnávací genomová hybridizace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- smíšený stromální-hladkosvalový nádor, myxoidní,
- MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- endometriální stromální sarkom diagnóza etiologie patologie MeSH
- financování organizované MeSH
- lidé MeSH
- nádor z hladké svalové tkáně diagnóza etiologie patologie MeSH
- nádory dělohy diagnóza etiologie patologie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
