Carcinoma análogo secretor de mama: revisión de diagnóstico y tratamiento a propósito de 2 casos / Mammary analogue secretory carcinoma: presentation of 2 cases and a review of its diagnosis and treatment

Introducción. El carcinoma análogo secretor de mama (MASC: mammary analogue secretory carcinoma) es una entidad neoplásica de las glándulas salivares caracterizada por presentar importantes similitudes histológicas e inmunohistoquímicas con el carcinoma secretor de mama. Hasta su descripción en 2010, el MASC era frecuentemente clasificado como carcinoma de células acinares por su solapamiento morfológico. Ante la falta de evidencia científica en la literatura respecto al tratamiento óptimo de estos tumores, el objetivo de este artículo es presentar 2casos tratados recientemente en nuestro servicio y revisar la literatura descrita acerca de su diagnóstico y tratamiento. Material y métodos. Se trata de un paciente varón de 41 años con diagnóstico de MASC de glándula salivar menor en paladar duro y de una paciente de 56 años con el mismo diagnóstico en la glándula submaxilar. Resultados. En ambos casos se realizó resección quirúrgica con márgenes de la lesión. En uno de ellos, al presentar bordes libres, se decidió control clínico, mientras que en el otro se decidió tratamiento adyuvante con radioterapia al presentar un borde cercano a la lesión. Ambos pacientes tras 2años están libres de enfermedad y mantienen seguimiento clínico. Discusión. En la literatura se había descrito la existencia de un tumor de glándulas salivares con unas características morfológicas comunes entre el carcinoma de células acinares y el carcinoma secretor de mama, caracterizado inmunohistoquímicamente por ser positivo a vimentina y a la proteína S-100, pero no fue conocido como MASC hasta su descripción en 2010. La alteración genética asociada al MASC es la presencia de la translocación t(12;15)(p13;q25) en el oncogén ETV6-NTRK3, lo que lo convierte en un marcador prácticamente patognomónico de este tumor. Respecto al tratamiento, existe consenso en el tratamiento quirúrgico de la lesión primario, y no existe consenso respecto a la disección cervical. El valor de la RT postoperatoria es difícilmente valorable por los escasos casos en la literatura. Conclusiones. El MASC es una enfermedad neoplásica de glándula salivar que precisa un diagnóstico correcto previo a la elección de su tratamiento. Debido a su comportamiento como una neoplasia maligna de bajo grado, consideramos que su tratamiento debe ser el quirúrgico, con unos márgenes de seguridad a la lesión, pero en algunos casos su comportamiento puede ser agresivo (AU)

Introduction. Mammary analogue secretory carcinoma (MASC) is a neoplastic tumour of the salivary glands, characterised by having important histological and immuno-histochemical similarities with secretory breast carcinoma. Until its description in 2010, MASC was often diagnosed as carcinoma of acinar cells due to their morphological overlapping. As there is a lack of evidence in the scientific literature concerning the optimal treatment of these tumours, the aim of this article is to present 2recently treated cases, and review the described literature about their diagnosis and treatment. Material and methods. The first case concerns a 41 year-old male with MASC of the minor salivary gland of the hard palate, and the other a 56 year-old patient with the same diagnosis at the level of the submandibular gland. Results. Surgical resection with lesion-free margins was performed in both cases. Clinical surveillance was decided for one case with free margins, while in the other one, it was decided to give adjuvant therapy with radiotherapy due to the narrow lesion free margin. Both patients are disease free and continue on clinical follow-up. Discussion. The literature describes the existence of a salivary glands tumour with common morphological characteristics between acinar cell carcinoma and breast carcinoma, and immunohistochemically characterised by being positive to vimentin and S-100 protein, but it was not known as MASC until its description in 2010. The genetic alteration associated with MASC is the presence of a translocation t(12;15) (q25; Q13) in ETV6-NTRK3, making it a pathognomonic tumour marker. There is consensus in the surgical treatment of primary lesions, but there is no agreement as regards neck dissection. The value of post-surgical radiotherapy is difficult to assess by the few cases in the literature. Conclusions. MASC is a recently described salivary gland tumour characterised by ETV6 translocation. Due to its behaviour as a low grade malignant neoplasm, it is recommended that its treatment should be excision with surgical margins, but in some cases its behaviour can be aggressive (AU)

Correction: Neuronal Hyperactivity Disturbs ATP Microgradients, Impairs Microglial Motility, and Reduces Phagocytic Receptor Expression Triggering Apoptosis/Microglial Phagocytosis Uncoupling.

[This corrects the article DOI: 10.1371/journal.pbio.1002466.].

Correction: Neuronal Hyperactivity Disturbs ATP Microgradients, Impairs Microglial Motility, and Reduces Phagocytic Receptor Expression Triggering Apoptosis/Microglial Phagocytosis Uncoupling.

[This corrects the article DOI: 10.1371/journal.pbio.1002466.].

Neuronal Hyperactivity Disturbs ATP Microgradients, Impairs Microglial Motility, and Reduces Phagocytic Receptor Expression Triggering Apoptosis/Microglial Phagocytosis Uncoupling.

Phagocytosis is essential to maintain tissue homeostasis in a large number of inflammatory and autoimmune diseases, but its role in the diseased brain is poorly explored. Recent findings suggest that in the adult hippocampal neurogenic niche, where the excess of newborn cells undergo apoptosis in physiological conditions, phagocytosis is efficiently executed by surveillant, ramified microglia. To test whether microglia are efficient phagocytes in the diseased brain as well, we confronted them with a series of apoptotic challenges and discovered a generalized response. When challenged with excitotoxicity in vitro (via the glutamate agonist NMDA) or inflammation in vivo (via systemic administration of bacterial lipopolysaccharides or by omega 3 fatty acid deficient diets), microglia resorted to different strategies to boost their phagocytic efficiency and compensate for the increased number of apoptotic cells, thus maintaining phagocytosis and apoptosis tightly coupled. Unexpectedly, this coupling was chronically lost in a mouse model of mesial temporal lobe epilepsy (MTLE) as well as in hippocampal tissue resected from individuals with MTLE, a major neurological disorder characterized by seizures, excitotoxicity, and inflammation. Importantly, the loss of phagocytosis/apoptosis coupling correlated with the expression of microglial proinflammatory, epileptogenic cytokines, suggesting its contribution to the pathophysiology of epilepsy. The phagocytic blockade resulted from reduced microglial surveillance and apoptotic cell recognition receptor expression and was not directly mediated by signaling through microglial glutamate receptors. Instead, it was related to the disruption of local ATP microgradients caused by the hyperactivity of the hippocampal network, at least in the acute phase of epilepsy. Finally, the uncoupling led to an accumulation of apoptotic newborn cells in the neurogenic niche that was due not to decreased survival but to delayed cell clearance after seizures. These results demonstrate that the efficiency of microglial phagocytosis critically affects the dynamics of apoptosis and urge to routinely assess the microglial phagocytic efficiency in neurodegenerative disorders.

From the Cajal alumni Achúcarro and Río-Hortega to the rediscovery of never-resting microglia.

Under the guidance of Ramón y Cajal, a plethora of students flourished and began to apply his silver impregnation methods to study brain cells other than neurons: the neuroglia. In the first decades of the twentieth century, Nicolás Achúcarro was one of the first researchers to visualize the brain cells with phagocytic capacity that we know today as microglia. Later, his pupil Pío del Río-Hortega developed modifications of Achúcarro's methods and was able to specifically observe the fine morphological intricacies of microglia. These findings contradicted Cajal's own views on cells that he thought belonged to the same class as oligodendroglia (the so called "third element" of the nervous system), leading to a long-standing discussion. It was only in 1924 that Río-Hortega's observations prevailed worldwide, thus recognizing microglia as a unique cell type. This late landing in the Neuroscience arena still has repercussions in the twenty first century, as microglia remain one of the least understood cell populations of the healthy brain. For decades, microglia in normal, physiological conditions in the adult brain were considered to be merely "resting," and their contribution as "activated" cells to the neuroinflammatory response in pathological conditions mostly detrimental. It was not until microglia were imaged in real time in the intact brain using two-photon in vivo imaging that the extreme motility of their fine processes was revealed. These findings led to a conceptual revolution in the field: "resting" microglia are constantly surveying the brain parenchyma in normal physiological conditions. Today, following Cajal's school of thought, structural and functional investigations of microglial morphology, dynamics, and relationships with neurons and other glial cells are experiencing a renaissance and we stand at the brink of discovering new roles for these unique immune cells in the healthy brain, an essential step to understand their causal relationship to diseases.