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.

• MeSH
• Muscle, Skeletal pathology   MeSH
• Leiomyosarcoma * diagnosis   pathology   MeSH
• Humans MeSH
• Smooth Muscle Tumor * diagnosis   pathology   MeSH
• Soft Tissue Neoplasms * pathology   MeSH
• Muscle Neoplasms * pathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

PLAG1 gene fusions were recently identified in a subset of uterine myxoid leiomyosarcomas (M-LMS). However, we have encountered cases of PLAG1-rearranged uterine sarcomas lacking M-LMS-like morphology and/or any expression of smooth muscle markers. To better characterize their clinicopathologic features, we performed a multiinstitutional search that yielded 11 cases. The patients ranged in age from 34 to 72 years (mean, 57 years). All tumors arose in the uterine corpus, ranging in size from 6.5 to 32 cm (mean, 15 cm). The most common stage at presentation was pT1b (n = 6), and 3 cases had stage pT1 (unspecified), and 1 case each presented in stages pT2a and pT3b. Most were treated only with hysterectomy and adnexectomy. The follow-up (range, 7-71 months; median, 39 months) was available for 7 patients. Three cases (7-21 months of follow-up) had no evidence of disease. Three of the 4 remaining patients died of disease within 55 to 71 months, while peritoneal spread developed in the last patient, and the patient was transferred for palliative care at 39 months. Morphologically, the tumors showed a high intertumoral and intratumoral heterogeneity. M-LMS-like and epithelioid leiomyosarcoma-like morphology were present in 3 and 5 primary tumors, respectively, the remaining mostly presented as nondescript ovoid or spindle cell sarcomas. Unusual morphologic findings included prominently hyalinized stroma (n = 3), adipocytic differentiation with areas mimicking myxoid liposarcoma (n = 2), osteosarcomatous differentiation (n = 1), and undifferentiated pleomorphic sarcoma-like areas (n = 1). The mitotic activity ranged from 3 to 24 mitoses per 10 high-power fields (mean, 9); 3 of 10 cases showed necrosis. In 3 of 11 cases, no expression of smooth muscle actin, h-caldesmon, or desmin was noted, whereas 5 of 5 cases expressed PLAG1. By RNA sequencing, the following fusion partners were identified: PUM1, CHCHD7 (each n = 2), C15orf29, CD44, MYOCD, FRMD6, PTK2, and TRPS1 (each n = 1). One case only showed PLAG1 gene break by fluorescence in situ hybridization. Our study documents a much broader morphologic spectrum of PLAG1-rearranged uterine sarcomas than previously reported, encompassing but not limited to M-LMS-like morphology with occasional heterologous (particularly adipocytic) differentiation. As it is currently difficult to precisely define their line of differentiation, for the time being, we suggest using a descriptive name "PLAG1-rearranged uterine sarcoma."

• MeSH
• DNA-Binding Proteins * genetics   MeSH
• Adult MeSH
• Phenotype MeSH
• Gene Rearrangement * MeSH
• Immunohistochemistry MeSH
• Leiomyosarcoma * genetics   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Biomarkers, Tumor genetics   MeSH
• Uterine Neoplasms * genetics   pathology   MeSH
• Sarcoma * genetics   pathology   MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

V roce 2023 vydávaná 5. edice WHO klasifikace nádorů kůže doznala v sekci mezenchymálních nádorů několika změn, přičemž mezi nejvýznamnější, jako již tradičně, patří zařazení nově identifikovaných nádorových jednotek, kterými se tento přehledový článek bude zabývat především. Konkrétně se jedná o tři nové kožní mezenchymální tumory s melanocytární diferenciací a rearanžemi genů CRTC1::TRIM11, ACTIN::MITF a MITF::CREM. Dále byly nově zařazeny EWSR1::SMAD3- rearanžované fibroblastické tumory, superficiální CD34 pozitivní fibroblastické tumory a NTRK-rearanžované vřetenobuněčné neoplazie. Z dalších změn budou krátce zmíněny pouze ty nejvýznamnější.

The section on mesenchymal tumors in 5th edition of WHO classification of skin tumors has undergone several changes, the most important of which, as usual, is the inclusion of newly identified tumor entities, which will be the main focus of this review article. These specifically include three novel cutaneous mesenchymal tumors with melanocytic differentiation, and rearrangements of the CRTC1::TRIM11, ACTIN::MITF, and MITF::CREM genes. In addition, EWSR1::SMAD3-rearranged fibroblastic tumors, superficial CD34-positive fibroblastic tumors, and NTRK-rearranged spindle cell neoplasms were newly included. Of the other changes, only the most important ones will be briefly mentioned

• Keywords
• mezenchymální nádory,
• MeSH
• Antigens, CD34 analysis   MeSH
• Diagnosis, Differential MeSH
• Cancer-Associated Fibroblasts classification   pathology   MeSH
• Carcinoma classification   pathology   MeSH
• Melanocytes pathology   MeSH
• Skin Neoplasms * genetics   classification   pathology   MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Clear cell mesothelioma is uncommon and shows predominance of clear cells with resemblance to clear cell carcinomas. Clinicopathologic and molecular descriptions of clear cell mesothelioma remained limited. In this study, we identified an index patient with clear cell mesothelioma, confirmed by immunohistochemical and ultrastructural studies. Targeted next-generation sequencing revealed the presence of an inactivating VHL mutation. We then systematically searched for VHL-mutant mesotheliomas in a comprehensive genomic profiling database of 1532 mesotheliomas. Collectively, we identified a cohort of four VHL-mutant clear cell mesotheliomas, including three peritoneal and one pleural tumors from three females and one male, with age range of 47-68 (median 63) years. Histologically, each tumor showed a microcystic to tubulopapillary architecture with prominent clear cells. By next-generation DNA sequencing, each of the four clear cell mesotheliomas harbored inactivating VHL mutations, while lacking other alterations typical of mesotheliomas such as BAP1, NF2, SETD2, CDKN2A, CDKN2B, TP53, and PTEN. By using low-pass whole genome sequencing on the index case and targeted next-generation sequencing on the remaining three cases, we identified extensive loss of heterozygosity throughout the genome but consistently sparing chromosomes 5, 7, and 20, characteristic of genomic near-haploidization. In summary, clear cell mesotheliomas were characterized by inactivating VHL mutations and genomic near-haploidization and appeared to represent a distinct clinicopathologic and molecular category of mesotheliomas. Our findings implicate VHL in the pathogenesis of a subset of mesotheliomas, particularly those with clear cell morphology.

• MeSH
• Chromosome Aberrations MeSH
• Genomics MeSH
• Haploidy MeSH
• Middle Aged MeSH
• Humans MeSH
• Mesothelioma, Malignant * MeSH
• Mesothelioma * genetics   MeSH
• Mutation MeSH
• Von Hippel-Lindau Tumor Suppressor Protein genetics   MeSH
• Lung Neoplasms * genetics   MeSH
• Aged MeSH
• Ubiquitin Thiolesterase genetics   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Systematic Review MeSH

This article presents 2 cases of TFG::MET-rearranged mesenchymal tumor, an extremely rare molecular subset among an emerging group of mesenchymal neoplasms with kinase gene (NTRK, BRAF, RET and others) alterations. Both tumors were congenital, occurred in female patients and presented as huge masses on the trunk and thigh, measuring 18 and 20 cm in the largest dimension. Both cases showed identical areas with a distinctive triphasic morphology resembling fibrous hamartoma of infancy (FHI), consisting of haphazardly arranged ovoid to spindled cells traversed by variably cellular and hyalinized fascicles admixed with (most likely non-neoplastic) adipose tissue. In other areas, a high-grade infantile fibrosarcoma/malignant peripheral nerve sheath tumor-like (IFS/MPNST-like) morphology was present in both cases. While the first case co-expressed CD34 and S100 protein, the other case did not. When combined with the three previously reported MET-rearranged cases (of which two harbored TFG::MET fusion), 3/5 and 3/4 of MET-rearranged and TFG::MET fusion-associated tumors, respectively exhibited similar triphasic FHI-like low-grade morphology. This points toward the existence of a relatively distinct morphological subset among kinase-fusion-associated tumors which seems to be strongly associated with MET fusions. It seems some of these low-grade cases may transform into a high-grade variant with IFS/MPNST-like morphology as has been observed in other tumors with kinase gene fusions. While most cases seem to follow an indolent clinical course, the recognition of these tumors is clinically relevant as MET tyrosine kinase inhibitors might represent an effective treatment option for clinically aggressive or unresectable cases.

• MeSH
• Fibrosarcoma * genetics   MeSH
• Gene Fusion MeSH
• Humans MeSH
• Biomarkers, Tumor genetics   MeSH
• Skin Neoplasms * MeSH
• Soft Tissue Neoplasms * genetics   pathology   MeSH
• Neoplasms, Connective and Soft Tissue * MeSH
• Neurofibrosarcoma * MeSH
• Proteins genetics   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• Publication type
• Meeting Abstract MeSH

The knowledge of clinical features and, particularly, histopathological spectrum of EWSR1-PATZ1-rearranged spindle and round cell sarcomas (EPS) remains limited. For this reason, we report the largest clinicopathological study of EPS to date. Nine cases were collected, consisting of four males and five females ranging in age from 10 to 81 years (average: 49 years). Five tumors occurred in abdominal wall soft tissues, three in the thorax, and one in the back of the neck. Tumor sizes ranged from 2.5 to 18 cm (average 6.6 cm). Five patients had follow-up with an average of 38 months (range: 18-60 months). Two patients had no recurrence or metastasis 19 months after diagnosis. Four patients developed multifocal pleural or pulmonary metastasis and were treated variably by surgery, radiotherapy, and chemotherapy. The latter seemed to have little to no clinical benefit. One of the four patients was free of disease 60 months after diagnosis, two patients were alive with disease at 18 and 60 months, respectively. Morphologically, low, intermediate, and high-grade sarcomas composed of a variable mixture of spindled, ovoid, epithelioid, and round cells were seen. The architectural and stromal features also varied, resulting in a broad morphologic spectrum. Immunohistochemically, the following markers were most consistently expressed: S100-protein (7/9 cases), GFAP (7/8), MyoD1 (8/9), Pax-7 (4/5), desmin (7/9), and AE1/3 (4/9). By next-generation sequencing, all cases revealed EWSR1-PATZ1 gene fusion. In addition, 3/6 cases tested harbored CDKN2A deletion, while CDKN2B deletion and TP53 mutation were detected in one case each. Our findings confirm that EPS is a clinicopathologic entity, albeit with a broad morphologic spectrum. The uneventful outcome in some of our cases indicates that a subset of EPS might follow a more indolent clinical course than previously appreciated. Additional studies are needed to validate whether any morphological and/or molecular attributes have a prognostic impact.

• MeSH
• Child MeSH
• Adult MeSH
• Phenotype MeSH
• Gene Fusion MeSH
• Genetic Predisposition to Disease MeSH
• Middle Aged MeSH
• Humans MeSH
• Biomarkers, Tumor analysis   genetics   MeSH
• Soft Tissue Neoplasms chemistry   genetics   pathology   surgery   MeSH
• RNA-Binding Protein EWS genetics   MeSH
• Repressor Proteins genetics   MeSH
• Sarcoma chemistry   genetics   pathology   surgery   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Kruppel-Like Transcription Factors genetics   MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe MeSH
• United States MeSH

Neexistuje žádný univerzální imunohistochemický panel, který by byl v diagnostice nádorů měkkých tkání užitečný za každé situace. Přesto je možné doporučit základní sadu markerů, které jsou vhodné pro použití zejména u nepříliš charakteristických vřetenobuněčných lézí, kdy na základě morfologie nelze jednoznačně určit nejen konkrétní diagnózu, ale často ani směr diferenciace. V tomto přehledovém článku budou shrnuty poznatky o hlavních a letitou praxí osvědčených imunohistochemických markerech pro diagnostiku jednotlivých nádorových skupin v této části patologie se vyskytující: CD34, desmin, epiteliální membránový antigen, širokospektré cytokeratiny, S100 protein a hladkosvalový aktin. Dále bude diskutována problematika spojená jak s využitím imunohistochemického barvení s protilátkou MDM2, tak s metodou fluorescenční in situ hybridizace pro detekci amplifikace genu MDM2 v lipomatózních tumorech.

There is no universal immunohistochemical panel which would be useful for the diagnosis of soft tissue tumors in all circumstances. Nevertheless, especially when faced with an uncharacteristic spindle cell neoplasm, a basic immunohistochemical panel can be recommended consisting of CD34, desmin, epithelial membrane antigen, broad-spectrum cytokeratins, S100 protein and smooth muscle actin. This review will address the utility and pitfalls of this panel. The use of MDM2 immunohistochemistry and fluorescence in situ hybridization in the diagnosis of lipomatous tumors will be discussed as well.

• MeSH
• Immunohistochemistry methods   MeSH
• Humans MeSH
• Soft Tissue Neoplasms * diagnosis   MeSH
• Proto-Oncogene Proteins c-mdm2 MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Nebývalé prohloubení poznatků o molekulárně genetickém pozadí mezenchymálních tumorů v posledních letech přineslo i výrazné rozšíření palety dostupných molekulárních markerů pro rutinní diagnostickou praxi. Spolu s těmito pokroky a často právě díky nim, došlo také ke značnému rozvoji na poli imunohistochemie. Byly objeveny a následně praxí ověřeny nové protilátky jak pro detekci různých směrů diferenciace, tak i protilátky vyvinuté přímo k diagnostice konkrétních nádorových typů. V tomto textu budou shrnuty imunohistochemické a molekulárně genetických markery užitečné v diagnostice vaskulárních tumorů, maligních tumorů z pochev periferních nervů, low-grade fibromyxoidních sarkomů/sklerozujících epiteloidních fibrosarkomů, solitárních fibrózních tumorů, epiteloidních sarkomů, rhabdomyosarkomů a dalších lézí exprimujících markery diferenciace do příčně pruhované svaloviny. Přehledový článek se rovněž zabývá imunohistochemickými a molekulárně genetickými znaky pro diagnostiku některých nověji popsaných a klinicky obzvlášť významných lézí.

Recent years have brought an immense increase of knowledge regarding the molecular genetic background of mesenchymal tumors which in turn has significantly expanded the repertoire of molecular markers available for the routine diagnostic practice. This progress has also been followed by a rising number of available immunohistochemical markers useful for the diagnosis of soft tissue neoplasia. Both lineage specific and tumor-specific immunohistochemical antibodies have been discovered and subsequently tested in the surgical pathology practice. This article will review some of the immunohistochemical and molecular genetic markers useful in the diagnosis of vascular tumors, malignant peripheral nerve sheath tumors, low-grade fibromyxoid sarcomas/sclerosing epithelioid fibrosarcomas, solitary fibrous tumors, epithelioid sarcomas, rhabdomyosarcomas and other lesions showing skeletal muscle differentiation. The immunohistochemical and molecular genetic features of some recently characterized and clinically particularly important entities will be discussed as well.

• Keywords
• mezenchymální nádory,
• MeSH
• Immunohistochemistry methods   MeSH
• Humans MeSH
• Molecular Biology methods   MeSH
• Soft Tissue Neoplasms * diagnosis   genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Inflammatory leiomyosarcoma (ILMS) is a very rare soft tissue tumor that usually follows an indolent clinical course, but long-term follow-up studies are lacking. Recent publications primarily focused on its genetic profile characterized by a near haploid genome. One study also showed these tumors to have upregulation of genes known to be crucial for skeletal muscle differentiation. Nevertheless, immunohistochemical expression of skeletal muscle markers, as well as markers that would help to distinguish ILMS from a long list of relevant differential diagnostic entities, has not been extensively studied. Nine cases of ILMS were collected and stained by a broad IHC panel which, besides others, contained MyoD1, myogenin, and PAX-7. A subset of cases was also analyzed by 2 different NGS assays and by MDM2 fluorescence in situ hybridization. Five male and 4 female patients ranged in age from 25 to 54 years (mean, 36 years). The tumors showed a predilection for intramuscular sites of the lower limbs (n = 4) and back (n = 2), whereas the remaining 3 cases affected an unspecified skeletal muscle, lung, and omentum. Follow-up with an average length of 10.6 years (range 0.5-22) was available for 8 patients. The omental tumor spread locally within the abdominal cavity, but the patient has been free of disease 7 years after treatment. None of the 5 patients with somatic soft tissue tumors (and follow-up longer than 1.5 years) had either recurrence or metastasis. Immunohistochemical studies revealed a substantial expression of skeletal muscle markers in almost all cases. This phenotype coupled with a highly characteristic genotype and significantly more indolent clinical behavior as compared with conventional leiomyosarcoma of deep soft tissue offers a strong rationale to change the current nomenclature. Based on the clinicopathological features and gene expression profile, we propose the name low-grade inflammatory myogenic tumor.

• MeSH
• Diagnosis, Differential MeSH
• Adult MeSH
• Phenotype MeSH
• Immunoenzyme Techniques methods   MeSH
• Muscle, Skeletal metabolism   pathology   MeSH
• Leiomyosarcoma metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Recurrence, Local pathology   MeSH
• Biomarkers, Tumor metabolism   MeSH
• Soft Tissue Neoplasms pathology   MeSH
• Inflammation metabolism   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH