Myoepithelial carcinoma (MC) arises from the myoepithelial cells. It is a rare tumor with a predilection for salivary glands. MC in soft tissue is uncommon. Soft tissue MC exhibits dual epithelial and smooth muscle phenotype. The extremities and limb girdles are commonly affected. We present cytological findings of retroperitoneal MC with an accurate diagnosis being rendered with the aid of immunocytochemistry on the cell block and demonstration of EWSR1 rearrangements by fluorescence in situ hybridization on cytology smear. The smears were cellular, showing loose clusters and sheets of tumor cells embedded in dense eosinophilic to myxoid matrix material. The cells were oval to polygonal, with focal areas showing moderate nuclear pleomorphism, vesicular to coarse chromatin, and vacuolated cytoplasm with clearing. On immunocytochemistry, tumor cells were positive for epithelial membrane antigen, pan-cytokeratin, calponin, smooth muscle actin, and S-100. A literature review shows only a handful of cases of soft tissue MC. The current report emphasizes the need for cytomorphological awareness with the employment of ancillary testing for accurately diagnosing this rare tumor at an uncommon location. We also discuss the diagnostic challenges and troubleshooting.

Myoepithelial tumors of the soft tissue and bone occurring in patients 21 years of age and younger are rare, and their clinicopathologic features remain incompletely understood. We studied a well-characterized series of 40 such tumors. Cases were retrieved from our archives for the period 2009-2022 and re-reviewed. Available immunohistochemical and molecular genetic data was collected. Clinical information including available follow-up was obtained. The tumors occurred in 18 males and 22 females, ranging from 3 months to 21 years of age (median 11.5 years), and involved a wide variety of soft tissue (n = 36) and bone (n = 4) locations. Histologically benign myoepithelial tumors tended to occur in adolescents (median age 14.5 years; range 5-21 years), whereas myoepithelial carcinomas occurred in younger patients (median age 8.5 years; range 3 months-20 years). Microscopically, the tumors showed a complex admixture of epithelioid, plasmacytoid and spindled cells in a variably hyalinized, myxoid, chondroid or chondromyxoid background. Small subsets of histologically malignant tumors had rhabdoid or \"round cell\" features. Immunohistochemistry showed 35/40 (88%) cases to be positive with at least one keratin antibody. The 5 keratin-negative tumors were uniformly positive for S100 protein and/or SOX10 and expressed EMA (4 cases) and/or p63 (3 cases). EMA, SMA and GFAP were positive in 21/25 (84%), 13/21 (62%), and 8/21 (38%) tumors, respectively. SMARCB1 and SMARCA4 expression was retained in 29/31 (94%) and 22/22 (100%) of cases, respectively. FISH for EWSR1 gene rearrangement was positive in 6/18 (33%) tested cases. Two EWSR1-negative tumors were also FUS-negative. NGS identified EWSR1::POU5F1, FUS::KLF17, and BRD4::CITED1 gene fusions in 3 tested cases. Clinical follow-up (22 patients; median 23 months; range 1-119 months) showed 3 patients with local recurrences and 5 with distant metastases (lymph nodes, lung, and brain). Three patients died of disease, 3 were alive with recurrent or unresectable disease, and 16 were disease-free. Adverse clinical outcomes were seen only in patients with malignant tumors. We conclude that myoepithelial neoplasms of soft tissue and bone are over-repesented in patients ≤21 years of age, more often histologically malignant, and potentially lethal. Histologic evaluation appears to reliably predict the behavior of these rare tumors.

The EWSR1::PBX3 fusion gene, commonly associated with cutaneous syncytial myoepitheliomas, is also found in myoepithelial tumors (METs) of bone and soft tissue. These tumors typically demonstrate benign histology and favorable outcomes. This study examines 6 previously unreported intraosseous METs harboring the EWSR1::PBX3 fusion, focusing on their histopathologic characteristics, immunophenotype, clinical and radiographic profiles, and patient outcomes. The cohort comprised 5 men and 1 woman, aged 25 to 65 years (median age: 31 years), with tumors located in the proximal tibia (3 cases), distal radius (2 cases), and ilium (1 case) and sizes between 3.2 and 12.2 cm (median size: 3.9 cm). Imaging showed osteolytic lesions with varying degrees of cortical involvement and soft tissue extension in 3 cases. Histologically, 4 tumors showed mainly uniform oval-to-spindled cells in syncytial or fascicular arrangements within a collagenous matrix, displaying either bland nuclear features or mild atypia, and low to slightly elevated mitotic activity (≤1 per 10 high-power fields in 3 cases and 6 per 10 high-power fields in 1), classifying them as benign or atypical METs. In contrast, 2 tumors exhibited pronounced nuclear atypia with ovoid, spindled, epithelioid and round cells, hyperchromatic nuclei, inconspicuous nucleoli, increased N/C ratios, high mitotic rates (17 and 19 per 10 high-power fields), and extensive necrosis. Both tumors behaved aggressively-one patient underwent amputation after neoadjuvant chemotherapy and radiation, and the other died within 7 months with the disease still present. Immunohistochemically, the tumors consistently expressed epithelial membrane antigen and S100 but lacked keratin (AE1/AE3) expression. Our study demonstrated that bone METs with EWSR1::PBX3 fusions encompass a histologic continuum from benign to malignant, with benign/atypical METs mirroring their cutaneous analogs in morphology, and malignant variants distinguished by heterogeneous cytologic and architectural features, pronounced nuclear atypia, and high mitotic rates.

OBJECTIVE: To depict histological and imaging features of myoepithelial carcinoma of the bone and soft tissue.
METHODS: We retrospectively examined histological features in 22 patients with myoepithelial carcinoma of the bone (4 patients) and soft tissue (18 patients) at a single institution. Imaging analysis of 15 patients (bone, 3 patients; soft tissue, 12 patients;) with preoperative images involved classifying lytic bone lesions via the modified Lodwick-Madewell classification; the growth patterns of soft tissue lesions were classified as well-defined, focally invasive, or diffusely invasive.
RESULTS: Local recurrence occurred in eight out of 22 patients (36.3%). Four of 22 patients (18.2%) had metastasis at presentation, whereas 11 of 22 patients (50.0%) had distant metastasis during follow-up. Severe cytological pleomorphism was observed in 14 of 22 patients (63.6%), and 10 of 22 tumors (45.5%) showed ≥ 10 mitoses/10 high-power fields. Vascular invasion was observed in 10 of 22 patients (45.5%). Extracapsular/extraskeletal infiltration into the surrounding tissues was assessed in 20 patients, with 14 of them (70%) showing infiltration beyond the tumor border. Regarding imaging of bone lesions, two patients had Ludwick type IIIB, whereas one patient had type II. The growth pattern of soft tissue lesions was well-defined in two patients (16.7%), focally invasive in seven patients (58.3%), and diffusely invasive in three (25.0%) out of 12 patients.
CONCLUSIONS: Myoepithelial carcinoma of the bone and soft tissue presents high risk of local recurrence and distant metastasis. Histological and imaging features might be important to understand the aggressive behavior of the tumor.

OBJECTIVE: Epidemiological evidence on myoepithelial carcinoma is rare. This study aimed to investigate the effect of tumor primary site and treatment modality on survival in patients with head and neck myoepithelial carcinoma.
METHODS: Data on adult patients diagnosed with head and neck myoepithelial carcinoma between 2000 and 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Uni- and multivariable Cox proportional hazard models were utilized to evaluate the effects of different tumor primary sites and treatment modalities on overall survival (OS) and cancer-specific survival (CSS), and expressed as hazard ratio (HR) and 95% confidence interval (CI).
RESULTS: A total of 415 patients were enrolled. No significant differences in OS and CSS were found between different tumor primary sites (P > 0.05). Compared with partial excision, patients with total excision (HR = 1.65, 95%CI: 1.12-2.42) (partial or total removal of the organ in which the tumor is located and complete removal of the tumor) or no surgery (HR = 3.52, 95%CI: 2.05-6.03) had worse OS. Compared with surgery only, patients with radiotherapy only had poorer OS (HR = 4.69, 95%CI: 2.32-9.46) and CSS (HR = 6.72, 95%CI: 2.59-17.46), while no significant differences in OS (P = 0.120) and CSS (P = 0.847) were found among patients who received surgery combined with radiotherapy. In patients with AJCC III/IV, patients with radiotherapy only (HR = 4.51, 95%CI: 1.61-12.62) had poorer OS compared to those with surgery only, whereas patients who received surgery combined with radiotherapy had better OS (HR = 0.50, 95%CI: 0.29-0.89).
CONCLUSIONS: The tumor primary site may not affect the prognosis of patients with myoepithelial carcinoma, while the effect of treatment modality on prognosis is related to the primary site and stage of the tumor.

UNASSIGNED: Salivary gland tumours are rare neoplasms. Pleomorphic adenoma (PA) is the most frequent benign lesion. Myoepithelial carcinoma (MECA) is rarely recognized malignancy, but the prognosis is unfavourable. The aim of this study was to identify genetic rearrangements that might be responsible for dynamic MECA progression in patients with primary radical PA excision.
UNASSIGNED: Next-generation sequencing (NGS) of 1500 gene coding sequences was performed in primary and recurrent tumour tissue collected from 2 patients, in whom PA was initially diagnosed and within one year multifocal MECA was detected. Formalin-fixed paraffin-embedded blocks with tumour tissues were subject to NGS analysis, involving small-scale mutations, as well as focal and chromosomal arm-level copy number changes.
UNASSIGNED: This study showed mutations in the FGFR2 gene in PA and MECA tissues, obtained from both patients. One of them, pathogenic mutation p.Pro253Arg, was associated with sensitivity to registered drug inhibitors. Additionally, FGFR1, EGFR, and CDK4/CDK6 amplification, as well as CDKN2A/B deletion, were detected in one case. Furthermore, mutations in suppressor gene APC2 and PIK3C2A were detected, but only in MECA tissue. The analysis also identified the following chromosomal copy alterations: 4q12-q13.3, 9p21.3, 5q23.1-q34, del8p23.3-p12, and del13q21.31-q31.1.
UNASSIGNED: Rearrangement of the FGFR2 gene, identified in primary PA and MECA ex PA samples of both our patients, may be responsible for the malignant transformation and the disease progression. Further studies are encouraged to confirm the relevance of the findings. The therapy option with FGFR2 inhibitors may be considered in advanced or metastatic MECA ex PA with confirmed FGFR2 mutations.

Myoepithelial carcinoma occurs mainly in salivary glands but rarely can also occur in soft tissues or bone. In this paper, we evaluated the role of surgical margins, radiotherapy, and chemotherapy in myoepithelial carcinoma of soft tissue and bone (MC-SB) treated at our Institute.
Medical records of 33 patients presenting with MC-SB between 1998 and 2015 at our institution were retrospectively analysed, and diagnosis and treatment were studied.
The median follow-up was 58.5 months. Twenty patients had tumours originating in soft tissues and 13 in bone. Eight patients (24.2%) had metastases at diagnosis, the remaining 25 had localised disease. Thirty-two underwent resection of the primary lesion. In 29 surgical margins were evaluated: wide in 28 with 10/28 who recurred (35.7%) and marginal resection in 1 who also recurred. Six patients received adjuvant radiotherapy. Metastases developed in 15/25 patients (60%) with localised disease at onset. Chemotherapy was administered in patients with metastatic advanced disease. Cisplatin+doxorubicin was administered in six patients as first-line chemotherapy with an objective response in 5/6 patients with a median 4-month duration. Five-year overall survival rate was 62.6% in patients with localised tumours and 12.5% in those metastatic at diagnosis.
MC-SB showed a high incidence of local recurrences and metastases. Despite different chemotherapy regimens, the outcome remains poor in patients with metastatic disease. Due to the absence of a standard protocol, we encourage treatment by multidisciplinary teams in referral centres with renowned expertise.

OBJECTIVE: Recently, HMGA2::WIF1 fusion has been reported in pleomorphic adenoma (PAs) originating from the parotid gland with a characteristic canalicular adenoma (CAA)-like pattern. However, it is unclear whether HMGA2::WIF1 fusion may occur in salivary gland carcinoma or tumours originating from the minor salivary glands. We herein conducted a detailed clinicopathological review of eight salivary gland tumours harbouring HMGA2::WIF1 fusions.
RESULTS: The reviewed diagnoses of salivary gland neoplasms with HMGA2::WIF1 fusion were PA (n = four), myoepithelioma (n = one), myoepithelial carcinoma ex PA (n = two) and high-grade carcinoma with basaloid features (n = one). Two tumours originated from the minor salivary glands. Six tumours (80%) contained areas reminiscent of CAA characterised by interconnected trabeculae/canaliculi of monotonous oncocytic or cuboidal tumour cells associated with a hypocellular, hyalinised to myxoid stroma. Areas typical of PA were seen in four (50%) cases. All tumours showed diffuse S100 and CK7 immunopositivity. Adverse events were detected in two cases, including local recurrence in a patient with PA, and local and distant recurrences and disease-related death in a patient with a high-grade carcinoma of the minor salivary gland of the buccal space, showing tumour necrosis and perineural invasion.
CONCLUSIONS: Salivary gland neoplasms with HMGA2::WIF1 fusion are predominantly characterised by CAA/striated duct adenoma-like histology and a S100+/CK7+ immunoprofile. These tumours are not always benign, as among all reported cases approximately 20% showed malignancy (six of 28) and adverse outcome (three of 15), including recurrence, distant metastasis and disease-specific mortality.

Primary renal myoepithelial carcinoma is an exceedingly rare neoplasm with an aggressive phenotype and Ewing sarcoma breakpoint region 1 (EWSR1) rearrangement in a small fraction of cases. In addition to its rarity, the diagnosis can be challenging for the pathologist due to morphologic heterogeneity, particularly on the biopsy specimen. At times, immunohistochemistry may be indecisive; therefore, molecular studies should be undertaken for clinching the diagnosis. We aim to illustrate a case of primary myoepithelial carcinoma of the kidney with EWSR1-rearrangement in a 67-year-old male patient who presented with right supraclavicular mass, which was clinically diagnosed as carcinoma of an unknown primary. An elaborate immunohistochemical work-up aided by fluorescent in-situ hybridization allowed us to reach a conclusive diagnosis. This unusual case report advocates that one should be aware of the histological mimickers and begin with broad differential diagnoses alongside sporadic ones and then narrow them down with appropriate ancillary studies.

Myoepithelioma, also known as malignant myoepithelioma, is a rare malignant tumor originating from myoepithelial cell. This article reports a patient with a huge tumor in the neck and left elbow who underwent fine needle aspiration under local anesthesia. The pathological diagnosis was a myoepithelioma. Under general anesthesia, giant tumors in the lower neck, posterior cranial fossa, neck, and left elbow were removed, and postoperative pathology showed that they were all myoepithelial tumors. Immunohistochemistry showed AE1/AE3 (+), P63 (+), CK7 (+), CK5 (+), and CD138 (+). The clinical characteristics and diagnosis and treatment process of this case are reported and relevant literature is reviewed.
摘要: 肌上皮肿瘤，又称恶性肌上皮瘤，是一种罕见的起源于肌上皮细胞的恶性肿瘤。本文报道1例伴巨大项部肿物、左肘部肿物的患者，在局部麻醉下行超声引导项部及肘部肿物穿刺，病理诊断为肌上皮肿瘤。在全身麻醉下，切除下颈部、后颅窝、颈部和左肘的巨大肿瘤，术后病理显示均为肌上皮肿瘤。免疫组织化学显示AE1/AE3（+）、P63（+）、CK7（+）、CK5（+），CD138（+）。现对本病例的临床特征和诊治经过进行报告及相关文献复习。.