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.

• Klíčová slova
• Inflammatory leiomyosarcoma, Inflammatory rhabdomyoblastic tumor, Near haploidization, Rhabdomyosarcoma, Skeletal muscle tumor,
• MeSH
• kosterní svaly patologie   MeSH
• leiomyosarkom * diagnóza   patologie   MeSH
• lidé MeSH
• nádor z hladké svalové tkáně * diagnóza   patologie   MeSH
• nádory měkkých tkání * patologie   MeSH
• nádory svalů * patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Leiomyosarcoma with adipocytic differentiation or lipoleiomyosarcoma is an uncommon sarcoma of the female genital tract with only a few individual reports in the literature. We therefore performed a morphologic, immunohistochemical, MDM2 gene amplification and RNA and DNA sequencing analysis of a series of gynecologic lipoleiomyosarcoma to better define the clinicopathologic spectrum. Six tumors from 6 patients were identified and classified as spindled lipoleiomyosarcoma (n = 2), mixed spindled and myxoid lipoleiomyosarcoma (n = 1), epithelioid lipoleiomyosarcoma with focal myxoid features (n = 1) and mixed spindled and epithelioid lipoleiomyosarcoma (n = 2). Patient age ranged from 41 to 64 years (mean: 49; median: 50). Primary location included uterine corpus (3), uterine corpus/cervix (2) and broad ligament (1). Tumor size ranged from 4.5 to 22 cm (mean: 11.2; median: 9.8). Four patients had metastasis at presentation or subsequently developed recurrent or distant disease. Patient status was known for 5: 2 dead of disease, 2 alive with disease and 1 alive without evidence of disease. Immunohistochemical expression of smooth muscle markers, ER, PR and WT-1 showed patterns similar to non-adipocytic gynecologic leiomyosarcomas. MDM2 amplification fluorescence in situ hybridization performed on 2 tumors was negative in 1 and equivocal in 1. Sequencing studies performed on 3 tumors found TP53 mutations in 3, with 1 tumor also having an ATRX alteration. No gene fusions were identified. Although lipoleiomyosarcomas have a diverse morphologic spectrum, our findings suggest the smooth muscle component shares morphologic and immunohistochemical features with female genital tract non-adipocytic leiomyosarcomas. Lipoleiomyosarcomas also have genetic alterations associated with non-adipocytic gynecologic leiomyosarcomas.

• Klíčová slova
• Leiomyosarcoma, Leiomyosarcoma with adipocytic differentiation, Lipoleiomyosarcoma, Malignant smooth muscle tumor,
• MeSH
• dospělí MeSH
• hybridizace in situ fluorescenční MeSH
• imunohistochemie MeSH
• leiomyosarkom * patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• molekulární biologie MeSH
• nádor z hladké svalové tkáně * patologie   MeSH
• nádorové biomarkery genetika   analýza   MeSH
• protoonkogenní proteiny c-mdm2 genetika   MeSH
• ženské pohlavní orgány chemie   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• MDM2 protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• protoonkogenní proteiny c-mdm2 MeSH

OBJECTIVE: The aim of this study was to analyze the clinical and reproductive outcomes of patients treated with myomectomy who were histologically diagnosed with uterine smooth muscle tumor of uncertain malignant potential (STUMP). METHODS: Patients who were diagnosed with STUMP and underwent a myomectomy at our institution between October 2003 and October 2019 were identified. Variables of interest obtained from the institution's database included patient age, relevant medical history, pre-operative appearance of the tumor on ultrasound, parameters of the surgical procedure, histopathological analysis of the tumor, post-operative clinical course, and course of follow-up, including reinterventions and fertility outcomes. RESULTS: There were a total of 46 patients that fulfilled the criteria of STUMP. The median patient age was 36 years (range, 18-48 years) and the mean follow-up was 47.6 months (range, 7-149 months). Thirty-four patients underwent primary laparoscopic procedures. Power morcellation was used for specimen extraction in 19 cases (55.9% of laparoscopic procedures). Endobag retrieval was used in nine patients and six procedures were converted to an open approach due to the suspicious peri-operative appearance of the tumor. Five patients underwent elective laparotomy due to the size and/or number of tumors; three patients had vaginal myomectomy; two patients had the tumor removed during planned cesarean section; and two underwent hysteroscopic resection.There were 13 reinterventions (five myomectomies and eight hysterectomies) with benign histology in 11 cases and STUMP histology in two cases (4.3% of all patients). We did not observe any recurrence as leiomyosarcoma or other uterine malignancy. We did not observe any deaths related to the diagnosis. Twenty-two pregnancies were recorded among 17 women, which resulted in 18 uncomplicated deliveries (17 by cesarean section and one vaginal), two missed abortions, and two pregnancy terminations. CONCLUSIONS: Our study found that uterus-saving procedures and fertility-preservation strategies in women with STUMP are feasible, safe, and seem to be associated with a low risk of malignant recurrence, even while maintaining the mini-invasive laparoscopic approach.

• Klíčová slova
• Gynecologic Surgical Procedures, Pathology, Uterine Neoplasms,
• MeSH
• císařský řez MeSH
• fertilita MeSH
• kojenec MeSH
• laparoskopie * metody   MeSH
• lidé MeSH
• myomektomie * škodlivé účinky   MeSH
• nádor z hladké svalové tkáně * patologie   MeSH
• nádory dělohy * patologie   MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• těhotenství MeSH
• uterus patologie   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• předškolní dítě MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem 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

We report the case of a 73-year-old female with myxoid mixed low-grade endometrial stromal sarcoma and smooth muscle tumor of the uterus. Grossly, the tumor sized 130 x 130 x 100 mm involved the uterine corpus almost in its entirety. Histologically, the tumor consisted of two cell types. In some areas, the tumor cells showed typical features of endometrial stromal tumors and resembled stromal cells of proliferative endometrium. In other areas, however, the tumor showed smooth muscle features and consisted of larger mostly epitheloid cells with a moderate amount of cytoplasm. In all areas, myxoid changes and multiple hyalinizing giant rosettes were present. The tumor infiltrated the myometrium in a pattern typical of low-grade endometrial stromal sarcoma. Immunohistochemically, the tumor cells showed expression of vimentin, estrogen and progesterone receptors and variable expression of CD10, α-smooth muscle actin, desmin, h-caldesmon, and cytokeratin AE1/AE3. Other markers examined including CD99, α-inhibin, cytokeratin CAM5.2, S-100 protein, and HMB45 were negative. To the best of our knowledge, mixed low-grade endometrial stromal and smooth muscle tumor with myxoid changes has not been described to date.

• MeSH
• endometriální stromální sarkom diagnóza   patologie   MeSH
• lidé MeSH
• nádor z hladké svalové tkáně diagnóza   patologie   MeSH
• nádorové biomarkery analýza   MeSH
• nádory dělohy diagnóza   patologie   MeSH
• nádory endometria diagnóza   patologie   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• nádorové biomarkery MeSH

So-called dedifferentiation in mesenchymal neoplasms of the uterus is very rare. Among conventional low-grade stromal tumors only three cases of dedifferentiation were reported, whereas in mixed stromal-smooth muscle tumors the dedifferentiation was yet not described. Here we present such a case of low-grade mixed stromal-smooth muscle tumor with dedifferentiation. The tumor occurred in 52-years-old postmenopausal patient. The high-grade component representing a dedifferentiation showed morphology of undifferentiated sarcoma with myxoid change. The low-grade component with morphology of mixed stromal-smooth muscle tumor was limited to a few peripheral areas of the lesion. Immunohistochemically, the low-grade component showed typical positivity for CD10, estrogen receptor, progesterone receptor, and focal reactivity for myoid markers, whereas the dedifferentiated component expressed only vimentin, CD10 and estrogen receptor. This case demonstrates that low-grade mixed stromal-smooth muscle tumor of the uterus can dedifferentiate like a pure stromal tumor. It shows that extensive sampling/histological search may be needed for recognition of a minor component in a dedifferentiated tumor.

• MeSH
• endometriální stromální sarkom patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• maligní smíšený nádor patologie   MeSH
• nádor z hladké svalové tkáně patologie   MeSH
• nádory dělohy patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH