Epithelioid Leiomyosarcoma Research Articles

Expanding the Spectrum of NR4A3 Fusion–Positive Gynecologic Leiomyosarcomas

Recurrent gene fusions have been observed in epithelioid and myxoid variants of uterine leiomyosarcoma. PGR::NR4A3 fusions were recently described in a subset of epithelioid leiomyosarcomas exhibiting rhabdoid morphology. In this study, we sought to expand the clinical, morphologic, immunohistochemical, and genetic features of gynecologic leiomyosarcomas harboring NR4A3 rearrangements with PGR and novel fusion partners. We identified 9 gynecologic leiomyosarcomas harboring PGR::NR4A3, CARMN::NR4A3, ACTB::NR4A3, and possible SLCO5A1::NR4A3 fusions by targeted RNA sequencing. Tumors frequently affected premenopausal women, involving the uterine corpus, uterine cervix, or pelvis. All were similarly characterized by lobules of monomorphic epithelioid and/or spindled cells arranged in sheets, cords, trabeculae, and micro- and macrocysts associated with abundant myxoid matrix and hemorrhage, creating labyrinth-like or pulmonary edema–like architecture. Myogenic differentiation with frequent estrogen receptor and progesterone receptor staining and no CD10 expression characterized all tumors. All cases showed high NR4A3 RNA expression levels and NOR1 (NR4A3) nuclear staining similar to salivary gland acinic cell carcinomas and a subset of extraskeletal myxoid chondrosarcomas harboring NR4A3 rearrangements. NOR1 (NR4A3) immunohistochemistry may serve as a useful diagnostic marker of NR4A3 fusion–positive gynecologic leiomyosarcomas.

PLAG1 Rearranged Soft Tissue Tumor in an Adult

Abstract Introduction/Objective PLAG1 rearranged soft tissue tumor is a recently described entity in the pediatric population. Less than 10 cases have been reported identifying PLAG1 gene fusions with various gene partners. This tumor is characterized by spindled cells with low cellularity in fibromyxoid stroma, expressing CD34 and desmin. PLAG1 gene fusions have been identified in various other tumors, including lipoblastoma, salivary gland pleomorphic adenoma, myoepithelial tumors, uterine epithelioid and myxoid leiomyosarcomas, and chondroid syringoma. To our knowledge, we report the first case of a PLAG1 rearranged soft tissue tumor in an adult. Methods/Case Report A 32-year-old female with no significant medical history presented with a left thigh mass. MRI showed a 9.8 cm mass involving subcutaneous fat and causing marked sartorius muscle displacement. Resection showed a well-circumscribed, spindle cell tumor of low cellularity in a myxo-collagenous stroma. Bland, elongated, and ovoid-shaped spindled cells with occasional punctate nucleoli were seen. No mitoses or necrosis were identified. The tumor cells expressed CD34 and androgen receptors, partially expressed desmin and estrogen receptors, and focally expressed S100. MUC4 and beta-catenin were negative. Next-generation sequencing performed at Mayo Clinic Labs identified UBC::PLAG1 gene rearrangement. Results (if a Case Study enter NA) NA Conclusion To our knowledge, we describe the first case of PLAG1 rearranged soft tissue tumor in an adult. This case is also unique as the fusion partner gene, UBC, was not previously identified. All other cases reported occurred in those four years of age or younger, with one report in a 15-year-old female. Our patient has had less than six months of follow-up with no recurrence. With few cases reported, and relatively short follow-up periods thus far, the behavior of these tumors remains undetermined.

Uterine Epithelioid Leiomyosarcoma Arising Within Leiomyoma in A Postmenopausal Woman: A Case Report

Uterine leiomyosarcoma is a malignant smooth muscle tumour of the uterus. It is rare and accounting for less than 2% of cases in malignant gynaepathology. To date, only a few reported cases of leiomyosarcoma arising from leiomyoma documented in the literature. We shared an uncommon occurrence of leiomyosarcoma arising from leiomyoma. Presented herein is a case of a ‘rare epithelioid subtype’ of leiomyosarcoma arising from a leiomyoma in a postmenopausal woman. We highlighted the importance of recognizing the possibilities of this event to allow for a timely diagnosis of leiomyosarcoma and to provide insights on management of patients presented with clinically presumed fibroid.

Diagnostic des sarcomes utérins et tumeurs mésenchymateuses utérines rares à potentiel de malignité. Référentiels du Groupe Sarcome Français et des Tumeurs Rares Gynécologiques

The landscape of uterine sarcomas is becoming more complex with the description of new entities associated with recurrent driver molecular alterations. Uterine sarcomas, in analogy with soft tissue sarcomas, are distinguished into complex genomic and simple genomic sarcomas. Leiomyosarcomas and undifferentiated uterine sarcomas belong to complex genomic sarcomas group. Low-grade and high-grade endometrial stromal sarcomas, other rare tumors associated with fusion transcripts (such as NTRK, PDGFB, ALK, RET ROS1) and SMARCA4-deficient uterine sarcoma are considered simple genomic sarcomas. The most common uterine sarcoma are first leiomyosarcoma and secondly endometrial stromal sarcomas. Three different histological subtypes of leiomyosarcoma (fusiform, myxoid, epithelioid) are identified, myxoid and epithelioid leiomyosarcoma being more aggressive than fusiform leiomyosarcoma. The distinction between low-grade and high-grade endometrial stromal sarcoma is primarily morphological and immunohistochemical and the detection of fusion transcripts can help the diagnosis. Uterine PEComa is a rare tumor, which is distinguished into borderline and malignant, according to a risk assessment algorithm. Embryonal rhabdomyosarcoma of the uterine cervix is more common in children but can also occur in adult women. Embryonal rhabdomyosarcoma of the uterine cervix is almost always DICER1 mutated, unlike that of the vagina which is wild-type DICER1, and adenosarcoma which can be DICER1 mutated but with less frequency. Among the emerging entities, sarcomas associated with fusion transcripts involving the NTRK, ALK, PDGFB genes benefit from targeted therapy. The integration of molecular data with histology and clinical data allows better identification of uterine sarcomas in order to better treat them.

Clinically Aggressive Uterine Epithelioid Leiomyosarcoma with Rhabdomyoblastic Differentiation and High Proliferation Rate: A Case Report.

BACKGROUND Leiomyosarcoma is the most common uterine sarcoma. Leiomyosarcoma is classified into conventional leiomyosarcoma, epithelioid leiomyosarcoma, and myxoid leiomyosarcoma. Leiomyosarcomas with rhabdoid features have been rarely reported. Herein, we report a case of uterine leiomyosarcoma with rhabdoid features. CASE REPORT A 58-year-old Korean woman presented with acute abdominal pain. Computed tomography and magnetic resonance imaging of the pelvis revealed a large solid mass in the posterior wall of the uterus that extended to the uterine cervix. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy and tumorectomy. Microscopic and immunohistochemical examination of the tumor revealed leiomyosarcoma with rhabdoid features and high proliferation rate. Next-generation sequencing showed PI3K amplification and ERBB2 amplification. Postoperative abdominal and pelvic computed tomography performed 3 weeks after the operation showed a mass at the vaginal stump that was attached to the urinary bladder and rectum. The patient underwent pelvic exenteration of remnant vaginal stump, rectum, and urinary bladder with loop ileostomy, and was diagnosed with recurrent leiomyosarcoma. One month later, after the second operation, a 13-cm recurrent mass was noted on the computed tomography. Chemotherapy was not done and the patient died during supportive treatment 7 months after diagnosis. CONCLUSIONS This case, which is a uterine leiomyosarcoma with rhabdoid features and high proliferation rate, recurred very fast, within 1 month, and showed an aggressive clinical course. The molecular classification and postoperative therapy are not well established in uterine leiomyosarcomas. Further studies are required to clarify the clinical and pathological characteristics of leiomyosarcomas.

Distinct oncogenic signatures in malignant PEComa and leiomyosarcoma identified by integrative RNA-seq and H3K27ac ChIP-seq analysis.

11552 Background: Malignant perivascular epithelioid cell tumor (PEComa) and leiomyosarcoma (LMS) are two sarcomas with overlapping morphologic and immunophenotypic features which can make their diagnostic distinction challenging. We aimed to characterize the transcriptional and epigenetic landscape of PEComa and LMS to identify distinguishing features. Methods: We performed whole transcriptome RNA-sequencing on 19 PEComas and compared their gene expression profile to 259 sarcomas from The Cancer Genome Atlas (TCGA) including 104 LMS. ChIP-sequencing for H3K27ac, a histone modification associated with activation of nearby genes/open chromatin, was conducted on 9 malignant PEComas and 12 LMS and were compared with publicly available data from 4 other sarcoma subtypes (chordoma; osteosarcoma; undifferentiated pleomorphic sarcoma; rhabdomyosarcoma; n = 29 tumors). Results: Genome-wide epigenetic and transcriptional analyses revealed overlapping patterns between PEComa and LMS, which were distinct from other sarcomas. However, we also identified a set of highly expressed and epigenetically distinct transcripts which may represent diagnostic?biomarkers: e.g., DAPL1, MLANA, SULT1C2, GPR143, and CHI3L1 for PEComa; and MYOCD, WDFC2, DES, MYH11, and CNN1 for LMS; each of which showed >17x fold higher expression for each tumor entity by DESeq2 (FDR<0.0001). Gene Set Enrichment Analyses (GSEA) demonstrated enrichment in the KEGG Lysosome pathway for PEComa (FDR=0.11), whereas myogenesis and smooth muscle contraction pathways were enriched in LMS (FDR=0.09). Integrative transcriptomic and epigenetic analyses revealed a unique set of master core transcription factors for each tumor type including among others MYOCD for LMS; MITF for PEComa, which require further functional investigation. Twelve selected genes including new as well as known and standard diagnostic markers (e.g., DAPL1, MLANA, GPR143, PNL2, CHI3L1, DES, MYH11, ER, CD68, PU.1, pS6 and CNN1) were validated by immunohistochemistry (IHC) in multiple sections from PEComa and LMS (n = 26). The combination of three melanocytic markers (HMB45, MLANA, PNL2) and pS6 can distinguish LMS from PEComas (**** p<0.0001). IHC for CD68 and PU.1 macrophage markers did not show any difference regarding the degree of immune infiltration in PEComa vs. LMS. Conclusions: Our studies revealed novel epigenetic signatures translating into lysosomal and melanocytic proteins for PEComa and myogenic proteins for LMS, which may serve as useful diagnostic biomarkers in the distinction of these two sarcoma subtypes.

Coincidence of Undifferentiated Pleomorphic Sarcoma and Epithelioid Leiomyosarcoma in a Patient; A Case Report

Introduction: Soft tissue sarcoma (STS) is a rare tumor with mesodermal origin. There are more than 100 different types of histology in sarcoma, which present different clinical behaviors. Liposarcoma, leiomyosarcoma, and undifferentiated pleomorphic sarcoma are among the most common pathologies Case Presentation: The patient was a 46-year-old man with 2 masses. The pathology of chest-wall mass (250 × 187 mm) was compatible with undifferentiated pleomorphic sarcoma (UPS). Arm mass (42 × 29 mm) pathology was suggestive of low-grade epithelioid leiomyosarcoma with smooth muscle differentiation. He received two cycles of mesna and doxorubicin and ifosfamide (MAI) regimen chemotherapy due to large and multiple masses, but the tumor size did not change. After consultation with an orthopedic oncosurgeon, wide masses resection was done. Adjuvant chemotherapy with an MAI regimen was continued for a total of 6 courses and radiation with a 60 Gy total dose to the posterior aspect of the chest wall. No recurrence or complications was observed after 4 months of follow-up. Conclusions: Multiple STS is rare; nevertheless, its probability, either synchronous or metachronous, should be considered during patient examine and follow-up. In the case of a secondary lesion, different histology is probable, and the patient should be biopsied and imaged.

A Case of Transverse Colon Epithelioid Leiomyosarcoma Treated with Laparoscopic Surgery

A Case of Transverse Colon Epithelioid Leiomyosarcoma Treated with Laparoscopic Surgery

Epithelioid Leiomyosarcoma of the Uterus: Modern Outcome-based Appraisal of Diagnostic Criteria in a Large Institutional Series.

Epithelioid leiomyosarcoma of the uterus is rare and poorly understood. Herein, we characterize a large institutional series of epithelioid leiomyosarcomas aiming to define outcome-determinant diagnostic pathologic features. We also retrieved epithelioid smooth muscle tumors of unknown malignant potential and evaluated a consecutive cohort of leiomyomas for epithelioid subtypes. Of a total of 1177 uterine leiomyosarcomas, 81 (7%) were categorized as epithelioid after review. Epithelioid leiomyosarcoma was strictly defined as having round to polygonal cells with visible pink cytoplasm and round to ovoid nuclei in ≥50% of the tumor volume. Average age was 55 years (range: 26 to 81 y). Median tumor size was 11 cm; tumor was >5 cm in 93% of subjects; 47% were stage 1 at presentation. An infiltrative tumor border was observed, grossly and/or microscopically, in 89% of cases; necrosis was noted in 80%, and vascular invasion in 47%. Mitotic count in 2.4 mm2 (totalling 10 high-power fields, each field 0.55 mm in diameter) ranged from 3 to 100 (median: 26). All cases had moderate, severe or highly pleomorphic atypia. All cases had 2 or 3 of the following: necrosis, at least moderate atypia and ≥4 mitoses in 2.4 mm2. Immunohistochemistry revealed frequent expression of smooth muscle markers including SMA (96%), desmin (95%), and caldesmon (81%). HMB45 and Melan-A were negative in 92% and 100% of cases, respectively. Estrogen and progesterone receptors were expressed by 65% and 54% of tumors, respectively. Follow-up information was available in 68 subjects (median: 23 mo, range: 1 to 254); cancer-related death occurred in 63%, and an additional 15% had recurrent or metastatic disease at last follow-up. Disease-specific survival was shorter in epithelioid leiomyosarcoma patients (median: 44 mo; 35% at 5-y) than in a matched cohort of nonepithelioid leiomyosarcoma (median: 55 mo; 46% at 5-y) (P=0.03). Three epithelioid smooth muscle tumors of unknown malignant potential were evaluated, all <5 cm in size and with atypia and/or irregular borders but mitotic count below the threshold for malignancy. Two of these had follow-up available, which was uneventful. Of 142 consecutive leiomyomas assessed, none had epithelioid morphology as defined. Epithelioid leiomyosarcoma is an aggressive neoplasm, sometimes with a remarkably low mitotic count. In the setting of an epithelioid smooth muscle tumor of the uterus, we postulate that the diagnosis of malignancy is made in the presence of ≥2 of the following: moderate or severe atypia, ≥4 mitoses/2.4 mm2 and tumor cell necrosis. In their absence, the finding of tumor size ≥5 cm, vascular invasion, infiltrative edges or atypical mitoses should be treated with caution, and designation as of at least uncertain malignant potential is warranted.

Analysis of Extended Resection of Limb Soft Tissue Leiomyosarcoma.

Leiomyosarcoma is an uncommon soft tissue sarcoma that composed of malignant mesenchymal cells with distinct features of the smooth muscle lineage. Typically affects the uterus and gastrointestinal tract, it can rarely be seen in large blood vessels, lymphatic and glandular duts, the mesentery, the omentum, retroperitoneum, and limbs. Occurrence is particularly rare in the limb region. Retrospective study based on patient records and postoperative pathological histological features. Four patients with limb leiomyosarcoma that were operated between 2016 and 2020 were included, three of them arising in the subcutis of the thigh region and one in cubitus. Extend resection with satisfactory outcomes is reported. Pathological examination showed that masses were composed of a fascicular arrangement of hyperchromatic spindle-shaped cells, characterized by the proliferation of epithelioid cells with eosinophilic cytoplasm for epithelioid leiomyosarcoma. Leiomyosarcomas that arise in the soft tissue, although rare, should be differentiated from other lesions, such as neurilemoma, neurofibroma, liomyoma,lipomyoma, synoviosarcoma, rhabdomyosarcoma, malignant fibrous histiotoma, and malignant neurinoma.

Leiomyosarcoma: A Rare Cause of Colocolic Intussusception

Intussusception is an infrequent presentation in adult patients and accounts for less than 1% of all cases of adult bowel obstruction. Colon is most commonly involved site and in 56% cases, the underlying cause is a malignant neoplasm. Leiomyosarcoma of colon is an extremely rare tumour. A 30-year-old male patient presented to the Surgery Department with chief complaints of dull, diffuse and colicky abdominal pain associated with abdominal distension and vomiting for 15 days. On abdominal examination, abdomen was distended with generalised tenderness and rigidity. X-ray abdomen showed features suggestive of bowel obstruction. Contrast Enhanced Computed Tomography (CECT) revealed bowel within bowel appearance of a segment of descending colon suggestive of colocolic intussusception. Exploratory laparotomy revealed colocolic intussusception with a large obstructing growth in the descending colon acting as a lead point. Left hemicolectomy with colocolic anastomosis was done. Final histopathological report confirmed epithelioid leiomyosarcoma. Adjuvant chemotherapy was administered and the patient is disease free at one year of follow-up. Present case report was a rare case of colonic leiomyosarcoma presenting with intussusception. The rarity of this disease and the rare presentation makes this an interesting case. Surgical management remains the mainstay of treatment of these cases.

Malignant Epithelioid Soft Tissue Tumours- A Pathologist's Perspective With Review of Literature.

BackgroundSoft tissue tumours with epithelioid morphology have many differential diagnoses, which include epithelioid sarcoma, malignant extrarenal rhabdoid tumour, epithelioid malignant peripheral nerve sheath tumour, epithelioid leiomyosarcoma, epithelioid angiosarcoma and sclerosing epithelioid fibrosarcoma. There are other rare entities also. They often express characteristic patterns of immunohistochemical markers that can be used to identify these tumours.Materials and methodsThis retrospective study comprises 22 cases of malignant soft tissue tumours with epithelioid differentiation diagnosed over a period of four years. Findings regarding clinical presentation, cytological findings, histopathological findings and immunohistochemical profile of the tumours were noted and analyzed.ResultsA total of 22 cases were included in the study including five cases of epithelioid sarcoma (conventional and proximal), three cases of epithelioid angiosarcoma and epithelioid myxofibrosarcoma, two cases of epithelioid malignant peripheral nerve sheath tumour, epithelioid gastrointestinal stromal tumour and clear cell sarcoma each, one case of epithelioid leiomyosarcoma, sclerosing epithelioid fibrosarcoma, malignant extrarenal rhabdoid tumour, monophasic synovial sarcoma and malignant and malignant perivascular epithelioid cell tumour each.ConclusionPathologists should be aware of the various differential diagnoses of soft tissue tumours with epithelioid morphology. Over and above the clinical findings and morphological features, ancillary methods like immunohistochemistry help to arrive at a definitive diagnosis in most cases.

Recent advances in smooth muscle tumors with PGR and PLAG1 gene fusions and myofibroblastic uterine neoplasms.

Uterine epithelioid and myxoid leiomyosarcomas and inflammatory myofibroblastic tumors are rare mesenchymal neoplasms. Next-generation sequencing recently detected novel PGR fusions in uterine epithelioid leiomyosarcomas that demonstrate characteristic rhabdoid and spindled morphology. PLAG1 gene fusions have also been identified in a subset of myxoid leiomyosarcomas and are associated with PLAG1 overexpression. ALK rearrangements underpin the vast majority of uterine inflammatory myofibroblastic tumors, which demonstrate morphologic, and immunohistochemical features similar to those of inflammatory myofibroblastic tumors elsewhere. This review summarizes the morphologic, immunophenotypic, and molecular genetic features of PGR fusion-positive epithelioid leiomyosarcoma, PLAG1 fusion-positive myxoid leiomyosarcoma, and inflammatory myofibroblastic tumors of the uterus.

Tumeur des cellules épithélioïdes périvasculaires (PECome) maligne de l’utérus : deux observations

Tumors of the perivascular epithelioid cells (PEComa) of the uterus are rare mesenchymal tumors that are characterized by the expression of both melanocyte and smooth muscle markers. It is often difficult to distinguish PEComas from other uterine tumors: endometrial stromal sarcoma, smooth muscle tumors including epithelioid tumors, melanoma and clear cell sarcoma. We report two cases of malignant PEComas of the uterus, treated in two different hospitals, found in women over 60, presenting a clinical picture of metrorrhagia in a context of myomatous uterus. In the first case, the histological examination of the hysterectomy specimen found a diffuse proliferation of epithelioid cells expressing HMB45. In the second case, the question of the differential diagnosis of the PEComa with a uterine epithelioid leiomyosarcoma arose, in front of the weak or even absent expression of the melanocytic immunohistochemical markers (melanA negative and focal HMB 45). The opinion requested from a network of experts (RRePS) had made it possible to validate the diagnosis of PEComa, notably by carrying out a complement of immunohistochemistry (expression of cathepsin K) by the tumor cells. In spite of its rarity, the diagnosis of PEComa should be considered before this type of epithelioid or clear cell uterine tumor because of the possibility of treatment by targeted therapies such as the mTOR (mammalian target of rapamycin) inhibitors.

Uterine mesenchymal tumours: recent advances.

Almost all uterine mesenchymal tumours have been historically classified as either smooth muscle or endometrial stromal neoplasms. Recent application of molecular techniques has identified numerous lesions with distinctive genetic abnormalities and clinicopathological characteristics. Newly discovered uterine sarcoma subtypes include high-grade endometrial stromal sarcomas with BCOR genetic abnormalities, fibrosarcoma-like uterine sarcomas with NTRK rearrangements and COL1A-PDGFRB fusions, as well as undifferentiated uterine sarcomas with SMARCA4 mutations. Novel PLAG1 and PGR fusions have been identified in subsets of myxoid and epithelioid leiomyosarcomas. Some uterine tumours resembling ovarian sex-cord tumour harbour GREB1 and ESR1 rearrangements. Histological and immunophenotypical features as well as underlying genetic abnormalities defining these lesions are discussed.

Characteristics of mismatch repair deficiency in sarcomas

Due to the efficacy of immune checkpoint inhibitor therapy in tumors with deficient mismatch repair, there has been a surge in demand for mismatch repair deficiency testing in various tumor types. Mismatch repair deficiency is not known to play a significant role in the pathogenesis of sarcomas, and the utility of testing these tumor types is not established. This study aimed to determine the frequency, pattern, and clinicopathologic correlates of mismatch repair deficiency in sarcomas. Three hundred and four sarcomas were profiled using a genomic platform that employs massively parallel sequencing to interrogate 447 cancer-associated genes. Mismatch repair status was evaluated by determining the number of small insertion/deletion events occurring in homopolymer regions per megabase of exonic sequence data across all genes. Molecular characteristics of mismatch repair-deficient sarcomas were compared to mismatch repair-deficient carcinomas (n = 70) also identified using the sequencing panel. Seven sarcomas (2.3%) were classified as mismatch repair-deficient: four unclassified sarcomas, and one each of pleomorphic rhabdomyosarcoma, epithelioid leiomyosarcoma and malignant PEComa. One patient had an established diagnosis of Lynch syndrome. In the remaining patients, the mismatch repair gene mutation was confirmed or suspected to be somatic. Mismatch repair immunohistochemistry confirmed the mismatch repair-deficiency status of all cases with alterations in the tested proteins. As expected, mismatch repair-deficient sarcomas showed a significantly elevated tumor mutation burden relative to mismatch repair-proficient sarcomas (median 16 versus 4.6, p < 0.001). However, in comparison to mismatch repair-deficient carcinomas, mismatch repair-deficient sarcomas showed a lower tumor mutation burden (median 28 versus 16, p = 0.006) and a significantly greater degree of chromosomal instability. Among mismatch repair-deficient sarcomas, PD-L1 was variably expressed on tumor-associated macrophages but not on tumor cells. Three patients received pembrolizumab: two progressed and one has stable disease with five months follow-up. Mismatch repair deficiency in histologically classifiable sarcomas is rare (1%) and is more common in unclassified sarcomas (10%). Additional study is required to determine the predictive role of mismatch repair-deficiency in sarcomas for immunotherapy.

PGR Gene Fusions Identify a Molecular Subset of Uterine Epithelioid Leiomyosarcoma With Rhabdoid Features.

Genetic aberrations among uterine epithelioid leiomyosarcomas are unknown. Following identification of an index case with NR4A3-PGR fusion demonstrating monomorphic morphologic features, we interrogated additional uterine tumors demonstrating similar histology and sought to describe the morphologic and immunohistochemical characteristics of PGR-rearranged sarcomas. Targeted next-generation RNA sequencing was performed on RNA extracted from formalin-fixed paraffin-embedded tissue of the index case. Fluorescence in situ hybridization using custom probes flanking PGR and NR4A3 genes was applied to 17 epithelioid leiomyosarcomas, 6 endometrial stromal tumors, and 3 perivascular epithelioid cell tumors. NR4A3-PGR fusion (n=4) and PGR rearrangement (n=2) were detected in 6 (35%) epithelioid leiomyosarcomas. Median patient age was 45 years, and all presented with FIGO stage I or II tumors, 2 being alive with disease at 75 and 180 months. All tumors were centered in the cervical stroma or myometrium and consisted of cells with abundant eosinophilic cytoplasm (epithelioid), including many displaying dense intracytoplasmic inclusions (rhabdoid). Myxoid matrix and hydropic change imparted a microcystic growth pattern in 4 tumors. Five also showed a minor spindle cell component which was low-grade in 3, consisting of bland spindle cells with low mitotic activity. High-grade spindle cell morphology was seen in 2 tumors, exhibiting a storiform pattern of atypical spindle cells associated with brisk mitotic activity. Desmin, estrogen receptor, and progesterone receptor were positive in all 6 tumors, while CD10 and HMB45 were negative. PGR rearrangements define a genetic subset of epithelioid leiomyosarcomas with often biphasic morphology consisting of epithelioid and rhabdoid as well as spindle cell components.

Misdiagnosis of Leiomyosarcoma after Radiofrequency Ablation of Uterine Myomas

Minimally invasive therapies to treat symptoms of uterine myomas can be effective alternatives to major surgery. Such modalities include pharmacologic agents, uterine artery embolization, magnetic resonance-guided focused ultrasound, and laparoscopic radiofrequency ablation, known as the Acessa procedure. Acessa is used to treat women with symptomatic myomas and was approved by the US Food and Drug Administration in 2012. This case describes a patient who underwent Acessa and subsequently required hysterectomy for refractory symptoms. Pathology of her tumor was initially classified as epithelioid leiomyosarcoma but on subsequent review was classified as benign. This report highlights the challenges of accurate histologic diagnosis in the setting of using new therapeutic modalities. Clinicians should report such interventions to pathologists at the time of surgery to allow for accurate diagnosis.

Primary epithelioid leiomyosarcoma of left atrium: Pathologist clinches it all

Primary cardiac neoplasms are rare with an estimated prevalence of 0.001%–0.2%. Cardiac tumors are mostly benign and myxomas are the commonest. Malignant tumors are rare in which metastasis and infiltration from the adjacent malignant tumor is more common than the primary ones. Amongst the primary malignant tumors sarcomas are the commonest. Primary epithelioid leiomyosarcoma of the heart is extremely rare. Here, we present a case of a 67-year-old female patient who was admitted with acute onset of pulmonary edema; on investigation, the patient was found to have left atrial mass. A provisional diagnosis of large left atrial myxoma with left ventricular inflow obstruction was made. Biopsy taken showed features of leiomyosarcoma which was confirmed by immunohistochemistry. Most of the patients with cardiac sarcoma have a high-grade tumor at the time of diagnosis with distant metastasis in the lungs (35.7%), lymph node (14.2%) followed by liver (7.14%) and they potent a poor prognosis. At present, only a few hundred primary cardiac sarcomas have been reported, most of which are based on autopsy series. Primary cardiac epithelioid leiomyosarcoma is a rare entity that can pose a diagnostic dilemma. However, atypical presentation of “atrial myxoma” being the common differential diagnosis. Histopathological evaluation is confirmatory to diagnose such a lesion. The pathologist should be aware of such an entity which can be attended by morphological evaluation including immunohistochemistry.

Ileal epithelioid leiomyosarcoma with omental and peritoneal seeding

Ileal epithelioid leiomyosarcoma with omental and peritoneal seeding