BACKGROUND: Primary pulmonary myxoid sarcoma (PPMS) is a rare, low-grade malignant tumor, constituting approximately 0.2% of all lung tumors. Despite its rarity, PPMS possesses distinctive histological features and molecular alterations, notably the presence of EWSR1-CREB1 gene fusion. However, its precise tissue origin remains elusive, posing challenges in clinical diagnosis.
UNASSIGNED: A 20-year-old male patient underwent a routine physical examination 6 months prior, revealing a pulmonary mass. Following surgical excision, microscopic evaluation unveiled predominantly short spindle-shaped tumor cells organized in a fascicular, beam-like, or reticular pattern. The stromal matrix exhibited abundant mucin, accompanied by lymphocytic and plasma cell infiltration, with Russell bodies evident in focal areas. Immunophenotypic profiling revealed positive expression of vimentin and epithelial membrane antigen in tumor cells, whereas smooth muscle actin and S-100, among others, were negative. Ki-67 proliferation index was approximately 5%. Subsequent second-generation sequencing identified the characteristic EWSR1-CREB1 gene fusion. The definitive pathological diagnosis established PPMS. The patient underwent no adjuvant chemotherapy or radiotherapy and remained recurrence-free during a 30-month follow-up period.
CONCLUSIONS: We report a rare case of PPMS located within the left lung lobe interlobar fissure, featuring Russell body formation within the tumor stroma, a novel finding in PPMS. Furthermore, the histomorphological characteristics of this case highlight the diagnostic challenge it poses, as it may mimic inflammatory myofibroblastic tumor, extraskeletal myxoid chondrosarcoma, or hemangiopericytoma-like fibrous histiocytoma. Therefore, accurate diagnosis necessitates an integrated approach involving morphological, immunohistochemical, and molecular analyses.

Mesenchymal tumors of the lungs are rare, mostly aggressive, with a high metastatic rate, representing only 0.013-1.1% of all pulmonary malignancies. Primary pulmonary myxoid sarcoma is an extremely rare type of lung sarcoma and stands as a separate entity in the 2015 WHO classification, characterized by EWSR1-CREB fusion gene. So far, 37 myxoid sarcoma cases have been reported. We offer an overview of the most important characteristics of pulmonary myxoid sarcoma and differential diagnosis, while reviewing the reported cases. We present the case of a 47-year-old patient with pulmonary myxoid sarcoma, who was diagnosed with a right central pulmonary mass, showing rapid endobronchial progression, complicated by empyema. EWSR1 gene translocation could not be detected. During chemotherapy, tumor progression occurred. Molecular genetic examinations revealed MET gene exon 14 skipping mutation, based on which tyrosine-kinase inhibitor treatment was administered. Pulmonary myxoid sarcoma can be classified as a nonvascular, spindle cell entity of mesenchymal tumors, with the characteristic EWSR1-CREB1 gene translocation. The male-female ratio is similar, with a slightly higher incidence in middle-aged women (1.5 : 1). Patients\' average age is 44 years; with predilection in the right upper lobe (62%), or endobronchially (85%). Without specific symptoms, diagnosis is often cumbersome. Immunohistochemical methods, typical hystological image and molecular genetic tests confirm the diagnosis. Pulmonary myxoid sarcoma is a rare entity, without specific symptoms. In our case, myxoid sarcoma was complicated by empyema, which was drained. Because of advanced stage, surgical resection was not an option. Radical surgery offers the best results, in inoperable cases therapeutic recommendations for sarcomas are the guiding principles. Our case belongs to the rare group of myxoid sarcomas, where MET activating mutation was detected, making it eligible for targeted treatment. Orv Hetil. 2023; 164(27): 1077-1083.
A tüdőből kiinduló rosszindulatú mesenchymalis daganatok ritkák, többnyire agresszív, áttétet képző tumorok, melyek az összes rosszindulatú tüdődaganatnak csak a 0,013–1,1%-át teszik ki. Az Egészségügyi Világszervezet 2015. évi beosztásában külön entitásként szereplő primer myxoid tüdősarcoma egy még ritkábban előforduló tüdősarcoma-típus: a legtöbb esetben ismétlődő kiegyensúlyozott kromoszomális transzlokáció jellemzi, amely az EWSR1–CREB1 fúziós génhez vezet. Eddig 37, myxoid tüdősarcomás esetet közöltek az irodalomban. Esetünk kapcsán áttekintjük a primer myxoid tüdősarcoma fontosabb jellemzőit és differenciáldiagnosztikáját, valamint áttekintést adunk az irodalomban eddig talált myxoid tüdősarcomás betegekről. Egy 47 éves, primer myxoid tüdősarcomás beteg esetét mutatjuk be, akinél rapid endobronchialis progressziót mutató, jobb oldali centrális tüdőtumor igazolódott, mely empyemával szövődött. Az EWSR1-gén transzlokációját betegünknél nem lehetett kimutatni. A kemoterápiás kezelés mellett, átmeneti egyensúlyi állapotot követően, tumorprogresszió alakult ki. A molekuláris genetikai vizsgálat során a MET-gén 14. exonjának ’skipping’ mutációját igazoltuk, amelyre célzott tirozin-kináz-gátló kezelés indult. A primer myxoid tüdősarcoma a mesenchymalis tumorok nonvascularis, orsósejtes tumorai közé sorolható, a jellegzetes EWSR1–CREB1 fúziós gén transzlokációjával. A férfi-nő arány közel egyező, középkorú nők körében némileg gyakoribb előfordulású (1,5 : 1). Az átlagéletkor 44 (23–80) év. Általában jobb felső lebenyi (62%), illetve endobronchialis (85%) elhelyezkedésű. Specifikus tünettan hiányában a diagnózis nem könnyű. Immunhisztokémiai módszerek, a jellegzetes szöveti kép, illetve a molekuláris genetikai vizsgálat erősítheti meg a diagnózist. A primer myxoid tüdősarcoma ritka entitás, specifikus tünetek nélkül. Betegünknél a myxoid tüdősarcoma empyemával szövődött, mely miatt mellűri drenázs történt. Az előrehaladott stádium miatt reszekcióra nem került sor. Pulmonalis sarcomákban a legjobb eredményeket radikális műtéti eltávolítással lehet elérni, inoperábilis esetekben a sarcomákra vonatkozó terápiás ajánlások irányadóak. Esetünk a myxoid tüdősarcomák azon ritka csoportjába tartozik, amelynél célzott kezelésre alkalmas MET-aktiváló mutációt lehetett kimutatni. Orv Hetil. 2023; 164(27): 1077–1083.

Primary pulmonary myxoid sarcoma (PPMS) is an extremely rare malignant mesenchymal tumor of the lung, with only less than 40 cases reported. We described a case of a 64-years-old man with a mass on the medial and lower lobe of the right lung confirmed as a primary pulmonary myxoid sarcoma on biopsy. Diagnosis of this tumor remains challenging because of its nonspecific clinical and imaging characteristics. This study emphasizes CT finding to improve the understanding of PPMS.

Primary pulmonary myxoid sarcoma is a rare lung sarcoma, mostly involving the central lung and harboring the EWSR1::CREB1 fusion. We report an exceptional case of primary pulmonary myxoid sarcoma arising in the peripheral lung and harboring an EWSR1::ATF1 gene fusion. A 67-year-old man presented with a solid nodule in the right lower lobe, and wedge resection was performed. Microscopically, the tumor consisted of reticular proliferation of uniform mildly atypical spindle cells within abundant myxoid stroma. Immunohistochemically, smooth muscle actin was positive but desmin was negative. Fluorescence in situ hybridization confirmed EWSR1 and ATF1 gene rearrangements. No recurrence was seen for 12 months. Pathological findings and gene rearrangements are important for the diagnosis of primary pulmonary myxoid sarcoma. Complete resection and careful observation are required.

BACKGROUND: Primary pulmonary sarcoma is extremely rare and mostly metastatic, and primary pulmonary myxoid sarcoma PPMS is a rare low-grade malignant sarcoma. The clinical manifestations of PPMS patients are relatively non-specific, sometimes found by physical examination. We report a case designed to explore the clinicopathologic features, diagnosis, and differential diagnosis of primary pulmonary myxoid sarcoma (PPMS). A 44-year-old man was found to have a primary myxoid sarcoma in the upper right lung on physical examination. The patient did not have any symptoms of discomfort. Histologically, the tumors had well-defined borders, and with grayish-white or grayish red cut surfaces. Under the microscope, the tumor cells were composed of oval and spindle cells arranged in a network or strips in a mucus-like stroma. Immunohistochemically, neoplastic cells showed diffuse and strong vimentin expression and focal weak EMA, and Bcl-6 staining. The expression of AE1/AE3, ALK, CD34, CD68, SMA, and CD99 were all negative. The Ki-67 index was low.
CONCLUSIONS: PPMS is a rare low-grade malignant primary pulmonary sarcoma without characteristic clinical symptoms and difficult to diagnose. It is mainly diagnosed by immunohistochemistry and genetic testing.

Primary pulmonary mesenchymal tumors are rare, yet they compromise a variety of entities. A novel low-grade malignant neoplasm coined primary pulmonary myxoid sarcoma (PPMS) has been introduced in the WHO classification of lung tumors. Molecular analysis in PPMS revealed recurrent gene fusions between EWSR1 and CREB1, a member of the cAMP response element binding protein (CREB) family. However, only 23 PPMS have been reported in the literature reflecting their exceedingly low incidence. Here, we describe the case of a 41-year-old female patient with a lung tumor obstructing the right main bronchus. Histologically, the tumor was composed of spindle-shaped and epithelioid cells exhibiting a reticular growth pattern within a prominent myxoid matrix. Solid areas were also observed. Molecular analysis by next-generation sequencing identified a fusion transcript with an unusual gene fusion involving exon 7 of EWSR1 and exon 5 of CREB1. Together, the diagnosis PPMS was established.

Primary pulmonary myxoid sarcoma (PPMS) is a recently defined rare neoplasm with histological and molecular similarity to extraskeletal myxoid chondrosarcoma. To date, 20 cases have been reported. A 48-year-old man presented with a huge mass filling the right hemithorax and extending into the tracheobronchial system. Histological findings were consistent with PPMS. Immunohistochemistry was positive for vimentin, CD10, and EMA, but other lineage-specific markers were negative. SMARCB1 (INI1) expression was lost in the tumour cells. FISH analysis (EWSR1, FUS, NR4A3, and SMARCB1) revealed no abnormalities. This case suggests SMARCB1 loss as a possible alternative molecular event driving EWSR1-negative PPMS.

Primary pulmonary myxoid sarcoma (PPMS) is a recently described, exceedingly rare low-grade lung sarcoma that tends to present in young females as an endobronchial mass and shows evidence of an EWSR1- CREB1 fusion. Herein, we present a case of PPMS with fluorescence in situ hybridization (FISH) analysis for EWSR1 and CREB1 rearrangements. An 80-year-old woman presented with an endobronchial, multinodular tumor exhibiting spindle, ovoid and epithelioid cells arranged in reticular/lattice-like and alveolar-like patterns in a myxoid background. The tumor showed focal epithelial membrane antigen immunoreactivity as well as an Alcian blue-positive stroma that was sensitive to digestion with hyaluronidase. EWSR1 and CREB1 rearrangements were detected by break-apart FISH probes. The patient showed persistence of disease 36 months after diagnosis and was discharged to hospice care. We contribute with a report of an additional case of this very unusual entity and perform a brief review of the literature published so far on the subject.