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2.
Medicine (Baltimore) ; 99(5): e19072, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000457

RESUMO

RATIONALE: Epithelial-myoepithelial carcinoma is an extremely rare, malignant neoplasm that occurs most frequently in the major salivary glands and accounts for approximately 1% of all salivary gland neoplasms. Few reports have described the presence of epithelial-myoepithelial carcinoma in the sinonasal region; hence, the treatment guideline and prognosis remain unclear. PATIENT CONCERNS: We reported a case of a 75-year-old woman with complaint of nasal obstruction and frequent epistaxis for 3 years. During the nasal endoscopic examination, a mass in the left nasal cavity originating from the left nasal septum that caused bleeding on touch was observed. DIAGNOSES: A diagnosis of epithelial-myoepithelial carcinoma was made based on the features of histopathology and immunohistochemistry of the surgical specimens. The patient was treated by surgical removal of the septal mass using the endonasal endoscopic approach. OUTCOMES: In the serial follow-up paranasal sinus imaging and endoscopic inspection, evidence of recurrence was absent for 18 months after surgery. LESSONS: This report highlights a case of epithelial-myoepithelial carcinoma originating from a minor salivary gland in the nasal septum, one of the most unusual locations. Diagnosis of epithelial-myoepithelial carcinoma should be made based on the findings of immunohistochemistry of the operative specimen. Clinicians should consider complete surgical resection as the effective treatment of choice.


Assuntos
Carcinoma/patologia , Mioepitelioma/patologia , Septo Nasal/patologia , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares Menores/patologia , Idoso , Carcinoma/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Mioepitelioma/cirurgia , Septo Nasal/cirurgia , Neoplasias das Glândulas Salivares/cirurgia , Glândulas Salivares Menores/cirurgia
3.
Zhongguo Fei Ai Za Zhi ; 23(2): 127-132, 2020 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-32093457

RESUMO

BACKGROUND: Pulmonary epithelial-myoepithelial carcinoma is a very rare type of salivary gland lung tumor. No standard treatment plan yet. This article intends to analyze the clinical characteristics of pulmonary epithelial-myoepithelial carcinoma and discuss the diagnosis and treatment of pulmonary epithelial-myoepithelial carcinoma. METHODS: The clinical data of a patient with pulmonary epithelial-myoepithelial carcinoma were analyzed and other relevant clinical literatures were reviewed. RESULTS: Epithelial cells immunohistochemically expressed cytokeratin and myoepithelial cells immunohistochemically expressed SMA and S-100. The next-generation sequencing was mainly HRAS gene mutation and the express of PD-L1 protein was negative. CONCLUSIONS: Most of the patients with Pulmonary epithelial-myoepithelial carcinoma have a good prognosis. Diagnosis mainly depends on microscopic examination and immunohistochemistry. The treatment of pulmonary epithelial-myoepithelial carcinoma is mainly surgical resection. The effect of radiotherapy and chemotherapy is not clear.


Assuntos
Neoplasias Pulmonares/diagnóstico , Mioepitelioma/diagnóstico , Antígeno B7-H1/genética , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Mutação , Mioepitelioma/diagnóstico por imagem , Mioepitelioma/genética , Mioepitelioma/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética
4.
Niger J Clin Pract ; 23(2): 266-269, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32031104

RESUMO

Epithelial myoepithelial carcinoma (EMC), a very rarely seen, low-grade, malignant, salivary gland tumor is most commonly located in the parotid gland followed by the submandibular gland. It is more often observed in females and in the 6th decade of life. Although primary treatment of the tumor is surgical resection, adjuvant radiotherapy may be applied to the adjacent area or close follow-up can be done if the surgical margin is closed. Patients must be followed up closely for recurrence and metastasis. Physical and radiological examinations (USG and MRI) should be performed to see for any recurrence in the operated area during the first year for every 2-3 months. This study presents the clinical, radiological, and pathological characteristics of a 59-year-old female patient with low-grade, oncocytic variant of EMC located in the left parotid gland.


Assuntos
Carcinoma/patologia , Mioepitelioma/patologia , Glândula Parótida/diagnóstico por imagem , Neoplasias Parotídeas/patologia , Neoplasias das Glândulas Salivares/patologia , Carcinoma/diagnóstico por imagem , Carcinoma/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Mioepitelioma/diagnóstico por imagem , Mioepitelioma/cirurgia , Paratireoidectomia , Neoplasias Parotídeas/diagnóstico por imagem , Neoplasias Parotídeas/cirurgia , Neoplasias das Glândulas Salivares/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
5.
Diagn Pathol ; 15(1): 3, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915021

RESUMO

BACKGROUND: Myoepithelioma-like tumor of the vulvar region (MELTVR) is a recently described mesenchymal neoplasm which typically arising in vulvar regions of adult women. CASE PRESENTATION: Here we report a case of a 65-year-old woman who presented with a 6-year history of subcutaneous mass in the vulvar region. The mass had recently increased in size continuously. Histologically, the tumor cells had an epithelioid to spindled shape. Epithelioid tumor cells proliferated singly or in a loosely cohesive manner with myxoid areas, while spindled tumor cells grew in diffuse sheets or storiform arrangements mainly in nonmyxoid areas. Immunohistochemically, the tumor cells were positive for vimentin, epithelial membrane antigen, calponin, and were partially mild to moderate positive for estrogen receptor, but completely negative for S100 protein, glial fibrillary acidic protein, CD34, desmin, SMA and cytokeratin. INI1/SMARCB1 expression was deficient. EWSR1 and FUS genes were intact tested by fluorescence in situ hybridization analysis. Based on these findings, we diagnose this case as MELTVR. The patient remained relapse-free after the lesion was widely excised during 8 months follow-up. CONCLUSIONS: This disease should be included in the differential diagnostic list of vulvar tumors with epithelioid to spindled morphology. Recognition of its histopathological features and immunohistochemical reactivity will help to understand the tumor better.


Assuntos
Biomarcadores Tumorais/análise , Mioepitelioma/diagnóstico , Neoplasias Vulvares/diagnóstico , Idoso , China , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Mioepitelioma/patologia , Proteína SMARCB1/genética , Proteína SMARCB1/metabolismo , Neoplasias Vulvares/patologia
6.
Am J Case Rep ; 21: e920702, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31983728

RESUMO

BACKGROUND Myoepithelioma is a rare neoplasm that differentiates toward myoepithelial cells. This condition mainly occurs in the salivary gland and rarely in the  soft tissue or internal organs. Long-term survival with repeated multiple rounds of resection for recurrence is rarely reported. CASE REPORT A 69-year-old man was diagnosed with metachronous pancreatic and thyroid metastases from myoepithelioma, which initially originated from a resected soft-tissue lesion in the left clavicular region in 2007. In addition, a locally recurrent lesion was resected and the patient received brachytherapy in 2015. Moreover, a metachronous metastatic lesion in the right lung was resected in 2017. Histopathological examination confirmed that all lesions were myoepithelioma. In the present case, pancreatoduodenectomy and right hemithyroidectomy for both metastatic lesions were successfully performed. Histopathology revealed small round-to-spindle-shaped tumor cells with atypia, proliferating in reticular formation, accompanied by myxoid stroma with chondromyxoid and hyalinized stroma, and the histology was similar to that observed in the previous specimen. Immunohistochemistry revealed positivity for cytokeratin (AE1/AE3), glial fibrillary acidic protein, vimentin, and S-100, and confirmed the diagnosis of myoepithelioma. To the best of our knowledge, this is the first study presenting a long-term survivor of soft-tissue myoepithelioma who underwent repeated multiple rounds of resection for recurrence in various organs. CONCLUSIONS We reported the case of a long-term survivor of soft-tissue myoepithelioma requiring multiple rounds of surgical resection for local recurrence and metachronous metastases in the lung, pancreas, and thyroid. When managed appropriately, some patients might benefit in terms of survival from repeated resection of recurrent lesions.


Assuntos
Neoplasias Pulmonares/cirurgia , Mioepitelioma/cirurgia , Neoplasias Pancreáticas/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Idoso , Clavícula , Humanos , Neoplasias Pulmonares/secundário , Masculino , Mioepitelioma/patologia , Neoplasias Pancreáticas/secundário , Neoplasias de Tecidos Moles/patologia , Neoplasias da Glândula Tireoide/secundário
7.
Clin Imaging ; 61: 90-94, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32000118

RESUMO

The spectrum of myoepithelial tumors usually occur in the salivary glands, and occasionally in the skin, breast, upper aero-digestive tract, and soft tissues. The myoepithelial tumors have no sex predominance and usually present within a wide range of age of distribution around the third and fifth decades. We describe a 12 year old male patient with primary malignant myoepithelial tumor in the foot plantar soft tissues. Including this tumor with unusual location, and age of presentation is essential in the differential diagnosis for soft tissue tumors in the pediatric population.


Assuntos
Mioepitelioma/diagnóstico por imagem , Neoplasias de Tecidos Moles/diagnóstico por imagem , Biomarcadores Tumorais , Criança , Diagnóstico Diferencial , Humanos , Masculino , Mioepitelioma/patologia , Placa Plantar/diagnóstico por imagem , Sarcoma/diagnóstico , Neoplasias de Tecidos Moles/patologia
8.
Am J Surg Pathol ; 44(1): 140-147, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31567188

RESUMO

Pneumocytic adenomyoepithelioma (PAM) was first described in 2007 and was included in the 2015 World Health Organization Classification of lung tumors as a variant of epithelial-myoepithelial tumor. This rare pulmonary neoplasm was reported to show both myoepithelial and duct-like components, with the latter exhibiting pneumocytic differentiation with TTF-1 expression. We present an index case and 6 additional retrospectively identified cases of pulmonary tumors with prototypical features of PAM. However, with additional clinicoradiologic, histologic, immunohistochemical and cytogenetic data, we were able to reclassify them as myoepithelial neoplasms-both primary and metastatic-with entrapped exuberantly hyperplastic alveolar structures lined by TTF-1 pneumocytes. We reviewed the available literature related to PAM and myoepithelial tumors. Our cases suggest that the entity referred to as PAM represents interstitial growth of myoepithelial neoplasms enticing marked proliferation of entrapped pneumocytes rather than a distinct biphasic neoplasm with pneumocytic differentiation.


Assuntos
Adenomioepitelioma/classificação , Adenomioepitelioma/patologia , Células Epiteliais Alveolares/patologia , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/patologia , Mioepitelioma/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
9.
Diagn Cytopathol ; 48(1): 61-65, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31433568

RESUMO

Epithelial-myoepithelial carcinoma (EMCa) is a rare neoplasm that most frequently afflicts the parotid gland. Histologically, a dual layer of inner, luminal epithelial cells and outer myoepithelial cells with associated background hyalinization characterize these tumors. Several variants of EMCa have been described, including the more recent description of the apocrine variant. We present here a case of a 71-year-old male with a parotid mass diagnosed on FNA as an apocrine epithelial-myoepithelial carcinoma. To our knowledge, this is the first case report describing the cytomorphologic features of apocrine EMCa on FNA smears.


Assuntos
Carcinoma/diagnóstico , Mioepitelioma/diagnóstico , Glândula Parótida/patologia , Neoplasias Parotídeas/patologia , Idoso , Biópsia por Agulha Fina , Carcinoma/patologia , Células Epiteliais/patologia , Humanos , Masculino , Mioepitelioma/patologia
10.
Med Oncol ; 37(2): 13, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31879796

RESUMO

Soft tissue myoepithelial carcinomas are a rare, malignant subgroup of myoepithelial tumours mostly arising in the extremities with equal predilection for women and men. The mainstay of management of localised disease is complete surgical resection. Despite optimal treatment, 40-45% of tumours recur. Data regarding the efficacy of systemic therapy for advanced and metastatic disease are lacking. The primary aim of this study was to evaluate the outcome of all patients with soft tissue myoepithelial carcinoma treated at a single referral centre. The secondary aim was to establish the efficacy of systemic therapies in patients with advanced disease. A retrospective review of the prospectively maintained Royal Marsden Sarcoma Unit database was performed to identify soft tissue myoepithelial carcinoma patients treated between 1996 and 2019. Patient baseline characteristics and treatment history were recorded. Response to systemic therapy was evaluated using RECIST 1.1. We identified 24 patients treated at our institution between 1996 and 2019,12 males and 12 females. Median age at presentation was 49.6 years [interquartile range (IQR) 40.5-63.3 years]. Twenty-two out of 24 patients (91.7%) underwent primary surgical resection. Nine patients (37.5%) received systemic treatment. A partial response was documented in one patient treated with doxorubicin. The median progression-free survival for first-line chemotherapy was 9.3 months. Myoepithelial carcinoma frequently recurs after complete surgical resection. Conventional chemotherapy demonstrated some activity in myoepithelial carcinoma, however, more effective systemic therapies are required and enrolment in clinical trial should be encouraged.


Assuntos
Doxorrubicina/uso terapêutico , Mioepitelioma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Inibidores da Topoisomerase II/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mioepitelioma/patologia , Estadiamento de Neoplasias , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias de Tecidos Moles/patologia , Taxa de Sobrevida , Resultado do Tratamento
11.
Neurol India ; 67(5): 1347-1351, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31744974

RESUMO

Intracranial myoepithelial tumors are extremely rare with <10 cases reported outside the sellar region. The authors describe a case of a 43-year-old male patient who presented with headache, numbness in the face, and a dumbbell-shaped lesion in the Meckel's cave clinically and radiologically suggestive of a Schwannoma. The histopathological and immunohistochemical evaluation led to a diagnosis of myoepithelioma. A review of literature reveals that this is only the ninth case of intracranial myoepithelial tumor reported, fifth benign case, and the first to be reported in the Meckel's cave region.


Assuntos
Neoplasias Encefálicas/patologia , Mioepitelioma/patologia , Adulto , Humanos , Masculino
12.
Medicine (Baltimore) ; 98(39): e17245, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574838

RESUMO

RATIONALE: Over the past decade, although several new entities of renal tumors have emerged, a form of renal cell carcinoma (RCC) that morphologically resembles epithelial-myoepithelial carcinoma has not been reported thus far. Herein, we describe a case of an unusual renal tumor that remained unclassified under a current RCC subtype, and briefly present its morphologic, immunophenotypic, and genetic features. PATIENT CONCERNS: The patient was an 85-year-old man who presented with hematuria and flank pain. Imaging studies revealed a left renal mass without enlarged lymph nodes. There were no abnormal masses or nodules in other organs. DIAGNOSES: The patient underwent no other treatment except the left radical nephrectomy under a clinical diagnosis of invasive urothelial carcinoma and was discharged on the thirteenth day. Histologically, the renal tumor showed biphasic proliferation of epithelial (strongly cytokeratin-positive; P63, P40, and vimentin-negative) and myoepithelial (strongly vimentin-positive; focal P63 and P40-positive; and weakly cytokeratin-positive) cells arranged in a perivascular pseudorosette-like pattern. No mutations were detected in multiple gene tests. According to the pathological structure, the patient was diagnosed as primary epithelial myoepithelial carcinoma-like renal tumor. INTERVENTIONS: To the best of our knowledge, the present tumor has not been previously described, and thus, this variant has not been integrated into a known form of PCC. Therefore, we cannot diagnose this type of tumor with other types of kidney tumors. OUTCOMES: Three years after primary diagnosis, the patient died of multiple organ failure result from multiple distant metastases. LESSONS: We present the first case of carcinoma of the kidney with EMC-like features and a perivascular pseudorosette-like growth pattern. Clinicians should be aware of the features of this uncommon variant of RCC to avoid diagnostic delays or misdiagnosis and prevent unnecessary or inappropriate treatment.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Mioepitelioma/patologia , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/genética , Evolução Fatal , Humanos , Imunofenotipagem , Rim/patologia , Neoplasias Renais/genética , Masculino , Mioepitelioma/genética , Formação de Roseta
13.
Artigo em Inglês | MEDLINE | ID: mdl-31400990

RESUMO

OBJECTIVES: Plasmacytoid cells (PLCs) in salivary pleomorphic adenoma (SPA) are regarded as modified neoplastic myoepithelia and define plasmacytoid myoepithelioma (pMYO). However, histochemically, immunohistochemically and ultrastructurally, PLCs fail to demonstrate frank myogenous properties. Epithelial-mesenchymal transition (EMT) may explain the phenotypes in SPA. Our aim was to evaluate (1) PLCs with accepted or purported myoepithelial and EMT-related markers; and (2) pMYOs for PLAG1 aberrations by using fluorescence in situ hybridization. STUDY DESIGN: Eight SPAs with or without PLC-predominance and 3 pMYOs were immunohistochemically studied. RESULTS: PLCs in SPA and pMYO exhibited strong, scattered to diffuse positivity for K7, rare K14 positivity and were mostly negative for α-smooth muscle actin, h-caldesmon, and p63/p40. S100 staining was strong and diffuse, whereas calponin was variable. DOG1 was negative. PLCs in pMYO and PLC-rich SPA exhibited selective or diffuse WT1 and D2-40 immunoreactivity. EMT markers SNAIL/SLUG exhibited strong and variable immunoreactivity in PLCs in contrast to weak or absent E-cadherin expression. SOX10 was diffusely and strongly positive. PLAG1 rearrangement was present in 1 pMYO. CONCLUSIONS: PLCs mostly fail to express myoepithelial markers; PLCs are neoplastic cells adapting to microenvironmental changes and capable of EMT; and tumors composed solely of PLCs are apparently SPAs depleted of a ductal component.


Assuntos
Adenoma Pleomorfo , Mioepitelioma , Neoplasias das Glândulas Salivares , Adenoma Pleomorfo/diagnóstico , Adenoma Pleomorfo/patologia , Biomarcadores Tumorais , Transição Epitelial-Mesenquimal , Humanos , Hibridização in Situ Fluorescente , Mioepitelioma/diagnóstico , Mioepitelioma/patologia , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/patologia
14.
J Cutan Pathol ; 46(12): 949-953, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31278765

RESUMO

Isolated cases of basal cell carcinoma (BCC) with partial myoepithelial component have been described. However, myoepithelial differentiation has not been described in sarcomatoid basal cell carcinomas, which usually show features resembling osteosarcoma, chondrosarcoma, or leiomyosarcoma. We report a case of an 87-year-old man with a forehead lesion that histologically showed a minor component of conventional nodular BCC in transition with a major biphasic sarcomatoid growth composed of invasive spindle-cell and epithelial-like components, the latter with a reticular pattern and scattered ductal structures. Both components showed cytological atypia and high mitotic rate (26/10HPF), with atypical mitotic figures. BER-EP4 immunostaining was exclusively found in the nodular BCC component whereas the sarcomatoid component revealed immunostaining for α-smooth muscle actin (SMA), muscle-specific actin (MSA), calponin, and p63 in both epithelial-like and spindle-cell populations. Focal immunoreactivity was observed in the epithelial component for S100 and glial fibrillary acidic protein (GFAP). Furthermore, EWSR1-PBX1 gene fusion was also detected. This is to our knowledge, the first fully documented case of biphasic sarcomatoid BCC with myoepithelial carcinoma differentiation.


Assuntos
Carcinoma Basocelular/patologia , Mioepitelioma/patologia , Sarcoma/patologia , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Basocelular/genética , Carcinoma Basocelular/ultraestrutura , Diferenciação Celular , Curetagem/métodos , Testa/patologia , Fusão Gênica/genética , Humanos , Masculino , Mioepitelioma/complicações , Mioepitelioma/genética , Mioepitelioma/ultraestrutura , Fator de Transcrição 1 de Leucemia de Células Pré-B/genética , Proteína EWS de Ligação a RNA/genética , Sarcoma/genética , Sarcoma/ultraestrutura , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/ultraestrutura
15.
Vet Pathol ; 56(6): 889-894, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31170892

RESUMO

An 11-year-old female miniature Dachshund dog presented with a solid, soft, gray mass on the hepatic lateral left lobe. Histologically, the mass consisted of neoplastic proliferation of cells with round nuclei and eosinophilic and vacuolated cytoplasm arranged in alveolar, trabecular, and solid patterns. Immunohistochemically, the neoplastic cells were positive for pancytokeratin (CK AE1/AE3), CK5, CK14, vimentin, Sox9, and myoepithelial markers (α-smooth muscle actin, p63, and calponin). The morphological and immunohistochemical findings indicated a diagnosis of myoepithelial carcinoma. We conducted immunohistochemical studies on other representative canine hepatic tumors. Although the myoepithelial phenotype was not observed in the hepatocellular carcinoma, some tumor cells in cholangiocarcinoma showed immunohistochemical features of myoepithelium, suggesting that some neoplastic cells in cholangiocarcinoma may have the potential to differentiate into myoepithelial cells. To our knowledge, this is the first report in veterinary medicine of a hepatic carcinoma with a myoepithelial phenotype.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/veterinária , Doenças do Cão/diagnóstico , Neoplasias Hepáticas/veterinária , Mioepitelioma/veterinária , Animais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Diferenciação Celular , Proliferação de Células , Doenças do Cão/patologia , Cães , Células Epiteliais/patologia , Feminino , Imuno-Histoquímica/veterinária , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Mioepitelioma/diagnóstico , Mioepitelioma/patologia , Fenótipo
16.
Am J Surg Pathol ; 43(10): 1349-1354, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31135487

RESUMO

Cutaneous syncytial myoepithelioma (CSM) is a rare but distinctive benign variant in the family of myoepithelial neoplasms of skin and soft tissue. CSM has unique morphologic and immunohistochemical features, characterized by intradermal syncytial growth of spindled, ovoid, and histiocytoid cells and consistent staining for S-100 protein and EMA, and differs from other myoepithelial tumors by showing only infrequent keratin staining. Rearrangement of the EWSR1 gene is now known to occur in up to half of all skin and soft tissue myoepithelial tumors, with a wide family of documented fusion partners. In 2013, we reported frequent (80%) EWSR1 rearrangements in CSM, but were unable to identify the fusion partner using available studies at that time. After recent identification of an index case of CSM harboring an EWSR1-PBX3 fusion, we used a combination of targeted RNA sequencing and fluorescence in situ hybridization (FISH) studies to investigate the genetic features of a cohort of CSM. An EWSR1-PBX3 fusion was identified in all 13 cases successfully tested. RNA sequencing was successful in 8/13 cases, all of which were found to have identical breakpoints fusing exon 8 of EWSR1 to exon 5 of PBX3. FISH confirmed both EWSR1 and PBX3 rearrangements in 9/9 cases tested, which included 4 confirmed to have EWSR1-PBX3 fusion by RNA-Seq, 3 cases that failed RNA-Seq, and 2 cases examined by FISH alone. Two cases failed RNA sequencing but had no additional tissue remaining for FISH studies. Our findings demonstrate that EWSR1-PBX3 fusions occur in most (and possibly all) cases of CSM.


Assuntos
Biomarcadores Tumorais/genética , Fusão Gênica , Rearranjo Gênico , Proteínas de Homeodomínio/genética , Mioepitelioma/genética , Proteínas Proto-Oncogênicas/genética , Proteína EWS de Ligação a RNA/genética , Neoplasias Cutâneas/genética , Adolescente , Adulto , Idoso , Feminino , Predisposição Genética para Doença , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Mioepitelioma/patologia , Análise de Sequência de RNA , Neoplasias Cutâneas/patologia , Adulto Jovem
17.
Am J Surg Pathol ; 43(7): 1005-1013, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31094929

RESUMO

Adenomyoepitheliomas (AME) of the breast and epithelial-myoepithelial carcinomas (EMCs) of salivary gland are morphologically similar tumors defined by the presence of a biphasic population of ductal epithelial elements mixed with myoepithelial cells. We sought to explore the molecular profile of AMEs and determine whether they might also share the PLAG1, HMGA2, and HRAS alterations seen in EMCs. Tumor tissue from 19 AMEs was sequenced and analyzed using Ion AmpliSeq Cancer Hotspot Panel v2 covering ∼2800 COSMIC mutations across 50 cancer-related genes. Cases were additionally screened by FISH for PLAG1 and HMGA2 rearrangements. Of 19 AMEs (12 benign; 7 malignant), 2 cases failed the DNA extraction. Of the remaining 17 cases, 14 had at least one nonsynonymous mutation identified. The most common mutations were in PIK3CA (6/17) and AKT1 (5/17), which were mutually exclusive. Two tumors demonstrated mutations in APC, while 1 demonstrated an STK11 mutation. Mutations in ATM, EGFR, FGFR3 or GNAS were identified in 4 cases with concurrent AKT1 mutations. HRAS mutation co-occurring with PIK3CA mutation was noted in 1 case of ER-negative malignant AME. While 2 cases harbored alterations in HMGA2, none was positive for PLAG1 rearrangement. Our findings confirm that breast AMEs are genetically heterogeneous exhibiting recurrent mutually exclusive mutations of PIK3CA and AKT1 in a majority of cases. HRAS mutations co-occur with PIK3CA mutations in ER-negative AMEs and may possibly be linked to clinically aggressive behavior. We identified hotspot mutations in additional genes (APC, STK11, ATM, EGFR, FGFR3, and GNAS). We report the presence of HMGA2 alterations in 2/16 AMEs, supporting their relationship with EMC of salivary glands in at least a subset of cases. PIK3CA, AKT1 and HRAS may serve as potential actionable therapeutic targets in clinically aggressive AMEs.


Assuntos
Adenomioepitelioma/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Mutação , Mioepitelioma/genética , Neoplasias Epiteliais e Glandulares/genética , Proteínas Proto-Oncogênicas c-akt/genética , Neoplasias das Glândulas Salivares/genética , Adenomioepitelioma/enzimologia , Adenomioepitelioma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Análise Mutacional de DNA , Proteínas de Ligação a DNA/genética , Feminino , Predisposição Genética para Doença , Proteína HMGA2/genética , Humanos , Pessoa de Meia-Idade , Mioepitelioma/enzimologia , Mioepitelioma/patologia , Neoplasias Epiteliais e Glandulares/enzimologia , Neoplasias Epiteliais e Glandulares/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/enzimologia , Neoplasias das Glândulas Salivares/patologia
18.
Am J Surg Pathol ; 43(7): 984-994, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30994537

RESUMO

Epithelial-myoepithelial carcinoma (EMC) is a rare salivary gland tumor that is histologically characterized by biphasic tubular structures composed of inner ductal and outer clear myoepithelial cells. Because of its histologic variety, it is sometimes challenging to make an accurate diagnosis, and useful ancillary tests are essential for this purpose. We investigated 87 cases of EMC arising in the major and minor salivary glands and seromucinous glands in the nasal cavity or bronchus to describe the histologic features and mutation status of selected key oncogenes. Classic EMC accounted for 40.2% of all cases. Other cases showed various growth patterns and cytologic features in addition to the typical histology; cribriform patterns, a basaloid appearance, and sebaceous differentiation were relatively common (17.2% to 18.4%), whereas oncocytic/apocrine, papillary-cystic, double-clear, squamous, psammomatous, Verocay-like, and high-grade transformation were rare. HRAS mutations were found in 82.7% of EMCs and were concentrated in codon 61. There was no significant correlation between the HRAS mutation status and the histology. No EMC ex pleomorphic adenoma cases had HRAS mutations. PIK3CA and/or AKT1 mutations were the second most frequent mutations (20.7%, 6.5%, respectively) and almost always cooccurred with HRAS mutations. It is noteworthy that the HRAS mutation was not identified in any salivary gland tumor entities manifesting EMC-like features, including adenoid cystic carcinoma, pleomorphic adenoma, basal cell adenoma/adenocarcinoma, and myoepithelial carcinoma. We conclude that HRAS mutations are a frequent tumorigenic gene alteration in EMC, despite its histologic diversity. This study provides further insight into strategies for diagnosing EMC and discriminating it from its mimics.


Assuntos
Biomarcadores Tumorais/genética , Mutação , Mioepitelioma/genética , Neoplasias Epiteliais e Glandulares/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias das Glândulas Salivares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA , Diagnóstico Diferencial , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Mioepitelioma/patologia , Neoplasias Epiteliais e Glandulares/patologia , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/patologia
20.
J Cutan Pathol ; 46(6): 421-424, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30834570

RESUMO

Cutaneous syncytial myoepithelioma (CSM) is a recently recognized, histopathological variant of myoepithelial (ME) tumors of the skin. It is characterized by a syncytial arrangement of spindled, ovoid, and/or epithelioid cells forming a well-circumscribed, unencapsulated dermal nodule. There is a paucity of intervening stroma, and absent duct or gland formation. Strong immunohistochemical staining for S100 and epithelial membrane antigen (EMA) has been described, while cytokeratin expression has been uncommon. The majority of CSMs harbor a rearrangement involving the EWSR1 gene. Although various fusion partner genes have been discovered in ME tumors at other anatomic sites, none has yet been described in CSM. We present a case of CSM represented clinically by a papule on the mid-upper back of a healthy 44-year-old female. It exhibited morphological and immunohistochemical features of a CSM with strong, diffuse S100 and alpha-actin expression, and focal positivity for EMA and cytokeratin AE1/AE3. Fluorescence in-situ hybridization showed an EWSR1 gene rearrangement. Massively parallel next-generation RNA sequencing revealed PBX3 as the fusion partner. The EWSR1-PBX3 gene fusion has been previously identified in three cases of ME tumors of bone and soft tissue, and in a case of retroperitoneal leiomyoma. This is the first report of an EWSR1-PBX3 fusion in CSM.


Assuntos
Biomarcadores Tumorais , Proteínas de Homeodomínio , Mioepitelioma , Proteínas de Fusão Oncogênica , Proteínas Proto-Oncogênicas , Proteína EWS de Ligação a RNA , Neoplasias Cutâneas , Adulto , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Feminino , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Queratinas/genética , Queratinas/metabolismo , Mioepitelioma/genética , Mioepitelioma/metabolismo , Mioepitelioma/patologia , Fusão Oncogênica , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteína EWS de Ligação a RNA/genética , Proteína EWS de Ligação a RNA/metabolismo , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia
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