First insights for targeted therapies in odontogenic myxoma.

OBJECTIVE: Odontogenic myxoma (OM) occasionally responds poorly to surgical treatment. The MAPK pathway is constitutively activated in several neoplasms and we aimed to test if the MAPK pathway is activated in OM, in order to pave the way for an alternative therapy for aggressive and recurrent cases. MATERIALS AND METHODS: The immunoexpression of phosphorylated ERK1/2 (pERK1/2) was assessed in OM. We established a 3D organotypic culture model for the in vitro study and patient-derived xenografts (PDX) in mice for the in vivo study. The MEK inhibitor U0126 was used to inhibit phosphorylation of ERK1/2 in the in vitro and in vivo models. RESULTS: All OM showed strong pERK1/2 immunoexpression, consistent with MAPK pathway activation. Treatment of the 3D culture with U0126 resulted in a reduced pERK1/2/ERK1/2 ratio. Consistent with the in vitro results, all PDX of animals treated with U0126 showed a decreased volume fold change compared with controls. CONCLUSIONS: The MAPK pathway is activated in OM and its inhibition leads to tumor shrinkage in PDX and cell culture models. CLINICAL RELEVANCE: Our results offer a pre-clinical frame for OM-targeted therapy. Further work is needed to determine if this initial finding holds clinical promise.

Novel HMGA2-YAP1 fusion gene in aggressive angiomyxoma.

We describe a case of a 44-year-old woman with locally advanced aggressive angiomyxoma with a novel translocation high-mobility group AT-hook 2-yes-associated protein 1 (HMGA2-YAP1) fusion, implying a t(11;12)(q22.1;q14.3) translocation. She was started on gonadotropin-releasing hormone agonist injection and an aromatase inhibitor for persistent disease, which responded to treatment; she was subsequently treated with radiation before a more definitive operation was conducted. This case report indicates that HGMA2-YAP1-translocated aggressive angiomyxoma is responsive to oestrogen antagonism and hopefully will allow for the development of diagnostics useful for this rare but often morbid neoplasm. This case also highlights the importance of appropriate workup of a soft tissue mass.

Treatment Outcomes and Sensitivity to Hormone Therapy of Aggressive Angiomyxoma: A Multicenter, International, Retrospective Study.

BACKGROUND: Aggressive angiomyxoma (AA) is a rare, locally aggressive tumor usually arising from pelvis or perineum, with a high local-recurrence rate after complete surgery. Anecdotal responses to hormone therapy have been reported. In the present study we aimed at studying surgical treatment outcomes and sensitivity to hormone therapy of AA. MATERIALS AND METHODS: We conducted a multicenter, international retrospective effort including patients with AA treated at three European referral centers (Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy and the Italian Rare Cancer Network; Centre Léon Bérard, Lyon, France; and Hospital Universitario Virgen del Rocio, Seville, Spain). RESULTS: A total of 36 patients were included. Median follow-up was 51.3 months. Thirty-three patients (92%) underwent complete (R0 + R1) surgery, with a local relapse rate of 50% and a median relapse-free survival of 39 months (95% confidence interval [CI], 27-68.1). Thirteen patients received a first-line systemic treatment with hormone therapy for locally advanced disease, with an overall response rate of 62% and a median progression-free survival of 24.6 months (95% CI, 11.0-39.7). In two patients, adding an aromatase inhibitor (AI) on progression to first-line GnRH agonist (GnRHa) resulted in a new tumor response. CONCLUSION: Our findings confirm that in AA, surgical local control may be challenging, with a significant rate of local relapse despite complete surgery. Hormone therapy is an active treatment option, with a potential of disease control and of being combined with surgery. The addition of an AI to first-line GnRHa could be an effective second-line systemic therapy in premenopausal female patients with AA. IMPLICATIONS FOR PRACTICE: In this retrospective effort including 36 patients with aggressive angiomyxoma, local relapse rate after complete surgery was 50%, with a median relapse-free survival of 39 months, confirming that local control is challenging. Overall response rate to first-line hormone therapy was 62%, with a median progression-free survival of 24.6 months. Thus, hormone therapy has a potential of disease control and of being combined with surgery.

Huge abdominal and perineal aggressive angiomyxoma: A misdiagnosed case report and literature review.

Aggressive angiomyxoma (AA) is a distinctive soft tissue tumor with a high risk of local recurrence. Clinicians must be aware of this rare tumor pre-operatively. Excision is the preferred method of AA treatment. The case report presents a case of a 36-year-old woman who was difficulty in walking due to a non-painful tumor in the abdomen and perineum. She was misdiagnosed as abdomen neurofibroma for more than 10 years, and an operation was performed in 1997. However, the tumor was incompletely resected because its huge volume accompanies with extensive infiltration and bleeding. The tumors in her abdomen and perineum were growing gradually, and the latter became a large lump which impeded her daily life. In 2008, the perineal tumor was incompletely resected, which weighed 10725 g. The severe hemorrhage had been ceased by Gonadotropin-Releasing Hormone treatment. She is alive till now. Details of the history and operative procedures are presented. An AA diagnosis was made by microscopy immunohistochemically. Long-time misdiagnosis and improper treatment are the important reasons for making it impossible to be radically resected. Pathological and immunohistochemical examination are important for avoiding misdiagnosis. For this case, there is a remaining tumor in her abdomen. A special project including further follow-up and treatment will be taken out.

Aggressive Angiomyxoma of the Vulva and Bladder.

BACKGROUND: Aggressive angiomyxoma is a rare, locally infiltrative tumor, frequently occurring in female patients. Although wide local excision is considered standard therapy, radical surgery may be needed. CASE: A 49-year-old woman presented with an aggressive angiomyxoma involving the vulva and bladder. Given the hormone receptor status and size of the tumor, the patient was initially treated with fulvestrant and goserelin acetate in an attempt to reduce the size of the mass. She was followed up at 1- to 3-month intervals; after 6 months of treatment, owing to increasing size of the mass and worsening symptoms, the decision was made to proceed with radical surgery. CONCLUSION: Although a less radical surgical approach is preferred, radical surgery is possible for treatment of aggressive angiomyxoma when needed.

Hormonal therapy for aggressive angiomyxoma: a case report and proposed management algorithm.

OBJECTIVE: This study aimed to report the results of hormonal therapy in the management of a patient with recurrent aggressive angiomyxoma (AAM) and to propose a management strategy for AAM based on (1) the estrogen receptor (ER) and progestin receptor contents of the tumor (2) the extent of disease based on magnetic resonance imaging findings and (3) the patient's menopausal status. MATERIALS AND METHODS: The chart of a patient with multiple pelvic recurrences of AAM managed surgically during a 16-year period followed by hormonal therapy was reviewed, and a literature search of pelvic, vaginal, and vulva AAM was performed. RESULTS: The patient presented in this report experienced 7 recurrences of AAM managed surgically during a 16-year period. She then was placed on leuprolide acetate for 3 monthly cycles, but the tumor recurred 6 months after the leuprolide acetate was discontinued. The patient was placed back on monthly leuprolide acetate for 5 years and has remained free of disease for more than 2 years after discontinuing the leuprolide acetate. A literature review suggest a role for hormonal therapy in the management of AAM based on the presence of ER/progestin receptor, the extent of the disease, and the menopausal status of the patient. Gonadotropin-releasing hormone analogs have been successfully used in premenopausal women as neoadjuvant therapy before surgery for previously untreated or recurrent disease, as adjuvant therapy after the initial surgical resection or after the resection of recurrent disease, and as the definitive treatment of AAM. Aromatase inhibitors may play a role in the treatment of ER-positive AAM occurring in postmenopausal women. CONCLUSIONS: Aggressive angiomyxoma can be an extremely hormonally sensitive tumor. Hormonal therapy may have a significant role in the treatment of patients with extensive or recurrent AAM that is ER positive. The selection of hormonal agents used for treating AAM can be based on the patient's menopausal status.

Insuficiencia mitral severa posresección de mixoma auricular gigante: presentación de un caso y revisión de la literatura / Severe mitral regurgitation following resection of a giant atrial myxoma: case report and literature review

La evaluación de la competencia de la válvula mitral puede ser imposible en el escenario de un mixoma auricular gigante. Presentamos el caso de una paciente de 50 años, que sufrió insuficiencia mitral severa en el período posderivación cardiopulmonar, tras resección de un mixoma auricular izquierdo, que precisó recambio valvular. La ausencia de insuficiencia mitral en el examen ecocardiográfico preoperatorio no debe ser tomada como un predictor fiable de una función valvular adecuada. Discutimos el papel del ecocardiograma intraoperatorio, los mecanismos fisiopatológicos y el tratamiento propuesto de la insuficiencia mitral severa, después de la resección del mixoma(AU)

Evaluation of the competence of a mitral valve can often be impossible in the clinical setting of a giant atrial myxoma. A 50-year-old woman with severe mitral regurgitation in the post-bypass period following a myxoma resection was managed with a mitral valve replacement. The absence of mitral insufficiency in the preoperative examination should not be taken as a reliable predictor of normal valve function. So herein, we discuss the role of the intraoperative echocardiographic examination, the underlying mechanisms, and the proposed management of severe mitral regurgitation following the resection of an atrial myxoma(AU)

[Case report. Aggressive angiomyxoma of vagina. A rare tumor diagnosed]. / Angiomixoma agresivo de vagina: un tumor poco diagnosticado.

The case of a female patient of 35 years of age, with a pedunculated tumor dependent of the vagina, of approximately 25 x 12 x 8 cm, who had a wide resection. The report was consistent with myxoid aggressive angiomyxoma. This is a myxoid mesenchymal neoplasm of slow growth, which mainly appears in deep soft tissues of the pelvic, genital or perineal areas of adult women. It is usually diagnosed after surgical resection by histopathologic examination. Routine evaluation includes: complete physical examination, imaging and pathology report of diagnostic confirmation.

Inhibitory effect of atorvastatin on the cell growth of cardiac myxomas via the PTEN and PHLPP2 phosphatase signaling pathway.

Insulin-like growth factor 1 (IGF-1) is a molecule with strong proliferative effects, and statins have been reported to exhibit antitumor effects based on clinical and experimental studies. However, their effects on cardiac myxoma (CM) cells and the underlying signaling mechanism(s) are largely unknown. Therefore, we investigated whether the protein/lipid phosphatases and tensin homolog deleted on chromosome ten (PTEN) and pleckstrin homology domain leucine-rich repeat phosphatase 1 and 2 (PHLPP1 and 2) are involved in the proliferative effect of IGF-1 on CM cells and the pharmacological impact of atorvastatin. The activity of PTEN and PHLPPs was determined using specific substrate diC16PIP3 and pNPP. We found that IGF-1 enhanced CM cell proliferation and inhibited both PTEN and PHLPP2 activity in a concentration- and time-dependent manner. Atorvastatin acted counter to IGF-1 and reversed the above effects mediated by IGF-1. Both IGF-1 and atorvastatin did not affect the activity of PHLPP1 and the protein expression of the three phosphatases. The results suggest that IGF-1 may exert its proliferative effects by negatively regulating the PTEN/PHLPP2 signaling pathway in CM cells, and atorvastatin may be a potential drug for the treatment of CM by enhancing the activity of PTEN and PHLPP2.

Aggressive angiomyxoma of the vulva treated by using a gonadotropin-releasing hormone agonist: a case report.

A rare case of a 38-year-old woman with progesterone receptor-positive aggressive angiomyxoma is presented. She underwent local excision and was treated with a gonadotropin-releasing hormone agonist as adjuvant therapy, and is free of disease 20 months after.

Cavitating atrial myxoma mimicking hydatid cyst on echocardiography: utility of cardiac magnetic resonance imaging and computed tomography for diagnosis and preoperative evaluation.

A cavitating cardiac mass may represent various etiologies, the most common being hydatid cyst, myxoma, and thrombus. Diagnosis is crucial as treatment strategies are very different. Although echocardiography is the initial imaging modality for a suspected cardiac mass, it does not allow for accurate tissue characterization. Cardiac magnetic resonance imaging helps to confirm the diagnosis as it incorporates a variety of pulse sequences and assesses the perfusion and delayed enhanced characteristics of the mass and myocardium. Multidetector computed tomography angiography is useful for preoperative demonstration of coronary arteries and tumor vascularity. This report describes a case of cavitating atrial myxoma suspected to be a hydatid cyst on echocardiography. Magnetic resonance imaging and multidetector computed tomography helped in the complete diagnostic workup.

Molecular features, markers, drug targets, and prospective targeted therapeutics in cardiac myxoma.

Treatment of sporadic cardiac myxoma (CM) has always been a challenging task. Currently, surgical excision remains the only option; however, targeted drug discovery schemes are in progress in order to improve treatment strategies and efficacy. The molecular mechanisms behind CM pathogenesis are still not totally unveiled thus drug target identification is still at early steps, trying to compile structured data on the pathophysiology of CM, targets and targeting moieties. Five critical disease pathways involving molecules of seven functional groups have been recently shown by us to be associated with the pathogenesis of CM. In addition, 15 to 20 drug targets and their targeting molecules have also mapped on pathways in an effort to start decoding the molecular profiles based on which early efforts for CM patient stratification into targeted therapeutic regimes. The present review describes the current data and discusses critical issues in the field of targeted and personalized medicine of CM.

Angiomixoma agresivo penoescrotal / Penoscrotal agressive angiomyxoma

Angiomixoma agresivo designa una neoplasia mesenquimatosa extremadamente rara. Afecta casi exclusivamente estructuras genitales, pélvicas o perineales de pacientes de sexo femenino, siendo muy raros los casos que envuelven el sexo masculino. Se trata de neo formaciones bien caracterizadas desde el punto de vista histológico y de comportamiento benigno. Los autores presentan un caso clínico de un tumor de este tipo en un adulto joven de sexo masculino con envolvimiento penoescrotalde grandes dimensiones implicando exéresis y reconstrucción compleja, con recurso a colgajos e injertos cutáneos. Es igualmente realizada una revisión bibliográfica exhaustiva sobre el tema englobando aspectos etiopatogénicos, clínicos, de imagen, anatomo-patológicos y de diagnóstico diferencial, así como terapéuticos y de pronóstico (AU)

Aggressive angiomyxoma denotes an extremely infrequent mesenchymal tumour. In virtually every case it involves genital, pelvic or perineal female structures. Cases involving male patients are extremely rare. It is a distinctive tumour with a characteristic clinical course and specific and well characterized microscopic features. The authors report an additional clinical case in a young male patient with massive scrotal and penile involvement, necessitating exeresis followed by complex reconstructive procedure implying flap and graft use. A review of the available literature concerning etiopathogenic, clinical, imagiologic, histological and differential diagnosis, therapeutic and prognostic aspects is also presented (AU)