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Modern Pathology : An Official Journal... Mar 2024Cutaneous mixed tumors exhibit a wide morphologic diversity and are currently classified into apocrine and eccrine types based on their morphologic differentiation. Some...
Cutaneous mixed tumors exhibit a wide morphologic diversity and are currently classified into apocrine and eccrine types based on their morphologic differentiation. Some cases of apocrine-type cutaneous mixed tumors (ACMT), namely, hyaline cell-rich apocrine cutaneous mixed tumors (HCR-ACMT) show a prominent or exclusive plasmacytoid myoepithelial component. Although recurrent fusions of PLAG1 have been observed in ACMT, the oncogenic driver of eccrine-type cutaneous mixed tumors (ECMT) is still unknown. The aim of the study was to provide a comprehensive morphologic, immunohistochemical, and molecular characterization of these tumors. Forty-one cases were included in this study: 28 cases of ACMT/HCR-ACMT and 13 cases of ECMT. After morphologic and immunohistochemical characterization, all specimens were analyzed by RNA sequencing. By immunohistochemistry, all cases showed expression of SOX10, but only ACMT/HCR-ACMT showed expression of PLAG1 and HMGA2. RNA sequencing confirmed the presence of recurrent fusion of PLAG1 or HMGA2 in all cases of ACMT/HCR-ACMT, with a perfect correlation with PLAG1/HMGA2 immunohistochemical status, and revealed internal tandem duplications of SOX10 (SOX10-ITD) in all cases of ECMT. Although TRPS1::PLAG1 was the most frequent fusion, HMGA2::WIF1 and HMGA2::NFIB were detected in ACMT cases. Clustering analysis based on gene expression profiling of 110 tumors, including numerous histotypes, showed that ECMT formed a distinct group compared with all other tumors. ACMT, HCR-ACMT, and salivary gland pleomorphic adenoma clustered together, whereas myoepithelioma with fusions of EWSR1, FUS, PBX1, PBX3, POU5F1, and KLF17 formed another cluster. Follow-up showed no evidence of disease in 23 cases across all 3 tumor types. In conclusion, our study demonstrated for the first time SOX10-ITD in ECMT and HMGA2 fusions in ACMT and further refined the prevalence of PLAG1 fusions in ACMT. Clustering analyses revealed the transcriptomic distance between these different tumors, especially in the heterogenous group of myoepitheliomas.
Topics: Humans; Adenoma, Pleomorphic; DNA-Binding Proteins; Myoepithelioma; Repressor Proteins; Salivary Gland Neoplasms; Skin Neoplasms; SOXE Transcription Factors; Sweat Gland Neoplasms; Transcription Factors
PubMed: 38266920
DOI: 10.1016/j.modpat.2024.100430 -
International Journal of Surgery Case... Jul 2024Tumours of salivary glands are rare and have various histo-pathological subtypes. Myoepitheliomas were first classified by Sheldon et al. and the criterion to classify...
INTRODUCTION
Tumours of salivary glands are rare and have various histo-pathological subtypes. Myoepitheliomas were first classified by Sheldon et al. and the criterion to classify or diagnose it was first defined by Barnes et al. and Sciubba and Brannon. Myoepithelioma accounts for less than 1 % of all salivary gland tumours, 40 % of these tumours occur in the parotid gland while 21 % occur in the minor salivary glands. A case of myoepithelioma of a minor salivary gland of the cheek is described, emphasizing the problems of the differential diagnosis.
PRESENTATION OF THE CASE
A 40-year-old female reported to the department with a complaint of a cheek bite on her right side for a few months. The physical examination showed a presence of lobulated whitish mucosa on the right buccal mucosa at the level of the occlusal plane, on palpation it revealed a non-painful mass approximately 1.5 cm in radius, mobile to bimanual palpation. An excisional biopsy was performed under local anaesthesia. Microscopic and immunohistochemistry confirmed the tumour to be a myoepithelioma of a minor salivary gland with the absence of definitive features of malignancy.
DISCUSSION
Due to their infrequency and multiplicity of histopathology, myoepitheliomas present difficulties in diagnosis. Cellular varieties can be misdiagnosed as malignancies. A key to determining diagnostic criteria for myoepitheliomas is to study cellular morphology, cytoplasmic filament expression, and ultrastructural features of the tumour and apply this information to defining myoepitheliomas.
CONCLUSION
Myoepitheliomas are rare tumours, utilization of immunohistochemical staining and electron microscopy are useful tools for the diagnosis of myoepitheliomas to ensure proper treatment and follow-up.
PubMed: 38875824
DOI: 10.1016/j.ijscr.2024.109849 -
Journal of Cutaneous Pathology Jul 2024While the list of fusion-driven soft tissue neoplasms is expanding rapidly, their importance among cutaneous and superficial mesenchymal and adnexal neoplasms remains...
Fusion-driven cutaneous and superficial mesenchymal and adnexal tumors-A clinicopathologic and molecular study of 15 cases, including a novel case of ACTB::ZMIZ2-rearranged adnexal carcinoma.
BACKGROUND
While the list of fusion-driven soft tissue neoplasms is expanding rapidly, their importance among cutaneous and superficial mesenchymal and adnexal neoplasms remains poorly understood. This challenge is especially evident in cases with ambiguous histopathology that are difficult to classify based on morphology.
AIMS
Our goal was to investigate the benefits of next-generation sequencing in diagnosing complex cutaneous neoplasms.
MATERIALS & METHODS
Departmental archives were searched for fusion-driven cutaneous neoplasms. Slides were retrieved and clinical information including follow-up was obtained.
RESULTS
Fifteen cases occurred in eight female and seven male patients, with a median age of 26 years (range: 1-83) at diagnosis. Tumors involved the extremities (9), scalp (5), and head and neck (1). Predominant features included myoepithelial (5), nested spindled with clear cytoplasm (2), atypical adnexal/squamoid (2), small round blue cell (2), cellular spindled (3), and fibrohistiocytic morphology (1). Most frequently encountered fusions involved EWSR1 (6) fused to ERG (1), FLI1 (1), CREB1 (2), CREM (1), PBX3 (1), followed by PLAG1 (4) with LIFR (2), TRPS1 (1) and CHCHD7. Additional fusions encountered were YAP1::NUTM1, EML4::ALK, SS18::SSX1 (2), and a novel fusion: ACTB::ZMIZ2. Integration of histologic features and molecular findings led to final diagnoses of primary cutaneous Ewing sarcoma (2), soft tissue myoepithelioma (4), cutaneous syncytial myoepithelioma (1), cutaneous adnexal carcinoma (1), porocarcinoma (1), inflammatory myofibroblastic tumor (1), synovial sarcoma (2), clear cell sarcoma (2), and angiomatoid fibrous histiocytoma (1).
DISCUSSION AND CONCLUSION
Our results show that fusion testing can be a helpful diagnostic tool, especially in cases with unusual or uncommon morphology in superficial sites. Furthermore, it can allow for the identification of potential therapeutic targets in some instances.
Topics: Humans; Female; Male; Adult; Skin Neoplasms; Middle Aged; Aged; Child; Adolescent; Aged, 80 and over; Child, Preschool; Infant; Oncogene Proteins, Fusion; High-Throughput Nucleotide Sequencing; Transcription Factors; Neoplasms, Adnexal and Skin Appendage; Young Adult; Gene Rearrangement
PubMed: 38556256
DOI: 10.1111/cup.14610 -
Annales de Pathologie May 2024
Topics: Humans; Biomarkers, Tumor; Carcinoma, Basal Cell; Cell Differentiation; Diagnosis, Differential; Myoepithelioma; Skin Neoplasms
PubMed: 38448266
DOI: 10.1016/j.annpat.2024.02.004 -
Practical Radiation Oncology 2024Salivary gland cancers are rare in general and salivary duct carcinoma and epithelial myoepithelial carcinomas are rare subtypes. This topic discussion will review the... (Review)
Review
Salivary gland cancers are rare in general and salivary duct carcinoma and epithelial myoepithelial carcinomas are rare subtypes. This topic discussion will review the characteristics of these uncommon cancers. Additionally, it will briefly discuss available guidelines for salivary cancers and summarize author opinions on the role of adjuvant radiation therapy for these cases.
Topics: Humans; Salivary Gland Neoplasms; Radiotherapy, Adjuvant; Myoepithelioma; Salivary Ducts
PubMed: 38161001
DOI: 10.1016/j.prro.2023.12.005 -
Human Pathology Jul 2024Myoepithelial tumors of the soft tissue and bone occurring in patients 21 years of age and younger are rare, and their clinicopathologic features remain incompletely...
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.
Topics: Humans; Male; Adolescent; Female; Child; Young Adult; Myoepithelioma; Child, Preschool; Soft Tissue Neoplasms; Bone Neoplasms; Infant; Biomarkers, Tumor; Immunohistochemistry; Gene Rearrangement; Transcription Factors
PubMed: 38782103
DOI: 10.1016/j.humpath.2024.05.007 -
Genes, Chromosomes & Cancer Oct 2023Herein we report a case of an intraosseous myoepithelial carcinoma harboring a EWSR1::PBX3 fusion gene. The patient was a 64-year-old male found to have a 7 cm...
Herein we report a case of an intraosseous myoepithelial carcinoma harboring a EWSR1::PBX3 fusion gene. The patient was a 64-year-old male found to have a 7 cm destructive lesion in the distal ulna with an extraosseous soft tissue component. Microscopic examination of the resected tumor showed a spindle-cell lesion within a sclerotic stroma and intravascular tumor emboli. At higher power the tumor cells showed moderate nuclear atypia with a high mitotic count (20 per mm ). Immunohistochemistry revealed diffuse EMA positivity and focal pancytokeratin (AE1/AE3) and S100 expression, consistent with myoepithelial differentiation. NGS using the Oncomine Childhood Cancer Assay (Thermo Fisher Scientific, Inc.) revealed a EWSR1-PBX3 fusion and ABL amplification. The patient subsequently developed local recurrence as well as distant lymph node, lung and vertebral metastases; he is currently awaiting systemic treatment in the context of a clinical trial. In this report, we present a rare case of a skeletal myoepithelial tumor harboring a EWSR1::PBX3 fusion with demonstrated histological and clinical features of malignancy.
Topics: Humans; Male; Middle Aged; Biomarkers, Tumor; Bone Neoplasms; Carcinoma; Gene Fusion; Myoepithelioma; Neoplasms, Connective and Soft Tissue; RNA-Binding Protein EWS
PubMed: 37129228
DOI: 10.1002/gcc.23148 -
Animals : An Open Access Journal From... May 2024Compared to the number of studies on the neoplasms of laboratory rodents, fewer studies have focused on spontaneous neoplasms in pet rodents. Notably, the mouse mammary...
Compared to the number of studies on the neoplasms of laboratory rodents, fewer studies have focused on spontaneous neoplasms in pet rodents. Notably, the mouse mammary tumor virus (MMTV) is associated with mammary tumors in rodents. In this study, 77 tumors and tumor-like lesions of biopsy samples were collected from 70 pet rodents, including hamsters (n = 47), guinea pigs (n = 16), unknown species (n = 4), rats (n = 2), and a gerbil. Fifty tumors were collected from 47 hamsters, in which the most common tumors were mammary tumors (13/50), followed by fibrosarcoma (9/50), mast cell tumors (4/50), and squamous cell carcinoma (4/50). The collected subtypes of mammary tumors in hamsters included tubular carcinoma (n = 5), tubular adenoma (n = 4), carcinoma and malignant myoepithelioma (n = 1), simple tubular carcinoma (n = 1), adenosquamous carcinoma (n = 1), and tubulopapillary adenoma (n = 1). In addition, twenty tumors were collected from guinea pigs, in which the most common tumor was lipoma (6/20), followed by adenocarcinoma of the mammary gland (4/20), trichofolliculoma (2/20), and collagenous hamartomas (2/20). In guinea pigs, the subtypes of mammary gland tumors were tubular carcinoma (n = 2), tubular and solid carcinoma (n = 1), and tubulopapillary carcinoma (n = 1). In 20 cases of mammary tumors, MMTV was not detected, implicating no evidence of MMTV infection in mammary oncogenesis in pet rodents in Taiwan.
PubMed: 38791685
DOI: 10.3390/ani14101469 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Jul 2023Myoepithelioma, also known as malignant myoepithelioma, is a rare malignant tumor originating from myoepithelial cell. This article reports a patient with a huge tumor... (Review)
Review
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.
Topics: Humans; Myoepithelioma; Immunohistochemistry; Epithelial Cells; Neck; Carcinoma
PubMed: 37549952
DOI: 10.13201/j.issn.2096-7993.2023.07.013 -
Modern Pathology : An Official Journal... May 2024The EWSR1::PBX3 fusion gene, commonly associated with cutaneous syncytial myoepitheliomas, is also found in myoepithelial tumors (METs) of bone and soft tissue. These...
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.
PubMed: 38763423
DOI: 10.1016/j.modpat.2024.100514