RESUMEN
Spinal muscular atrophy (SMA) is caused by a deletion or mutation of the survival motor neuron 1 (SMN1) gene. Reduced SMN levels lead to motor neuron degeneration and muscular atrophy. SMN protein localizes to the cytoplasm and Cajal bodies. Moreover, in myofibrils from Drosophila and mice, SMN is a sarcomeric protein localized to the Z-disc. Although SMN participates in multiple functions, including the biogenesis of spliceosomal small nuclear ribonucleoproteins, its role in the sarcomere is unclear. Here, we analyzed the sarcomeric organization of SMN in human control and type I SMA skeletal myofibers. In control sarcomeres, we demonstrate that human SMN is localized to the titin-positive M-band and actin-positive I-band, and to SMN-positive granules that flanked the Z-discs. Co-immunoprecipitation assays revealed that SMN interacts with the sarcomeric protein actin, α-actinin, titin, and profilin2. In the type I SMA muscle, SMN levels were reduced, and atrophic (denervated) and hypertrophic (nondenervated) myofibers coexisted. The hypertrophied myofibers, which are potential primary targets of SMN deficiency, exhibited sites of focal or segmental alterations of the actin cytoskeleton, where the SMN immunostaining pattern was altered. Moreover, SMN was relocalized to the Z-disc in overcontracted minisarcomeres from hypertrophic myofibers. We propose that SMN could have an integrating role in the molecular components of the sarcomere. Consequently, low SMN levels might impact the normal sarcomeric architecture, resulting in the disruption of myofibrils found in SMA muscle. This primary effect might be independent of the neurogenic myopathy produced by denervation and contribute to pathophysiology of the SMA myopathy.
Asunto(s)
Músculo Esquelético/metabolismo , Atrofia Muscular Espinal/metabolismo , Miofibrillas/metabolismo , Sarcómeros/metabolismo , HumanosRESUMEN
Myxomas are rare in the vocal cords. A 69-year-old man was admitted with one-year history of progressive dysphonia. Laryngoscopy revealed a polypoid mass on the right vocal cord. The diagnosis was cellular myxoma. A review of the literature including the present case revealed eleven reported cases of myxoma. Ten cases were classic myxoma. To the best of our knowledge, cellular myxoma has not been previously reported in the vocal cord. Hypercellularity does not affect the behavior of cellular myxoma. However, its recognition is important to prevent confusion with the group of low-grade myxoid sarcomas. Cellular myxoma should be considered in the differential diagnosis of any vocal cord mass.
Asunto(s)
Neoplasias Laríngeas/patología , Mixoma/patología , Pliegues Vocales/patología , Anciano , Humanos , Neoplasias Laríngeas/cirugía , Masculino , Mixoma/cirugía , Resultado del Tratamiento , Pliegues Vocales/cirugíaRESUMEN
Type I spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by the loss or mutation of the survival motor neuron 1 (SMN1) gene. The reduction in SMN protein levels in SMA leads to the degeneration of motor neurons and muscular atrophy. In this study, we analyzed the nuclear reorganization in human skeletal myofibers from a type I SMA patient carrying a deletion of exons 7 and 8 in the SMN1 gene and two SMN2 gene copies and showing reduced SMN protein levels in the muscle compared with those in control samples. The morphometric analysis of myofiber size revealed the coexistence of atrophic and hypertrophic myofibers in SMA samples. Compared with controls, both nuclear size and the nuclear shape factor were significantly reduced in SMA myonuclei. Nuclear reorganization in SMA myonuclei was characterized by extensive heterochromatinization, the aggregation of splicing factors in large interchromatin granule clusters, and nucleolar alterations with the accumulation of the granular component and a loss of fibrillar center/dense fibrillar component units. These nuclear alterations reflect a severe perturbation of global pre-mRNA transcription and splicing, as well as nucleolar dysfunction, in SMA myofibers. Moreover, the finding of similar nuclear reorganization in both atrophic and hypetrophic myofibers provides additional support that the SMN deficiency in SMA patients may primarily affect the skeletal myofibers.
Asunto(s)
Núcleo Celular/genética , Músculo Esquelético/patología , ARN/genética , ARN/metabolismo , Atrofias Musculares Espinales de la Infancia/genética , Atrofias Musculares Espinales de la Infancia/patología , Núcleo Celular/metabolismo , Humanos , Recién Nacido , Masculino , Músculo Esquelético/metabolismoRESUMEN
A woman underwent surgical intervention for a carcinoma of the ovary. In the intervention, a submucosal nodule of the ileum was found. Pathological study revealed a spindle cell lipoma (SCL). This case revealed the presence of CD34-positive spindle and stellate cells with dendritic cytoplasmic prolongations, a feature shared with dendritic fibromyxolipoma. Fluorescence in in situ hybridisation analysis showed 13q14 heterozygous deletion. Spindle cell lipoma of the small intestine has not been previously reported. Spindle cell lipoma, although rare, should be included among the benign mesenchymal lesions of the small intestine. This report extends the range of locations in which this tumour is found to arise.
Asunto(s)
Neoplasias del Íleon/patología , Hallazgos Incidentales , Lipoma/patología , Anciano , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Biopsia , Deleción Cromosómica , Cromosomas Humanos Par 13 , Femenino , Humanos , Neoplasias del Íleon/química , Neoplasias del Íleon/genética , Neoplasias del Íleon/cirugía , Inmunohistoquímica , Hibridación Fluorescente in Situ , Lipoma/química , Lipoma/genética , Lipoma/cirugíaRESUMEN
Histiocytoid/oncocytic cardiomyopathy (HCM) is a rare, distinctive arrhythmogenic disorder that presents as arrhythmia or sudden death in infants and children. Ventricular noncompaction (VNC) is a rare cardiomyopathy characterized by a thickened endocardial layer of noncompacted myocardium and a thin epicardial layer of compacted myocardium. Only six cases of the association of both cardiomyopathies have been reported previously in the literature. All these cases were in children. To the best of our knowledge, a case of HCM has not been described in the adult. We report the case of a 45-year-old man with an increased heart weight and involvement of both ventricles by HCM and VNC cardiomyopathy. Besides, multiple foci of myocardial disorganization were detected. He died suddenly while hiking. The association of both processes HCM and VNC was an unexpected finding at autopsy. The death was linked to functional abnormalities of the cardiac histiocytoid cells, and it was favored by a state of abnormal development of the heart.
Asunto(s)
Cardiomiopatías/fisiopatología , Muerte Súbita/etiología , Ventrículos Cardíacos/patología , Miocardio/patología , Cardiomiopatías/diagnóstico , Corazón/fisiopatología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Valvular hemangioma incidence is extremely low. In this report, we describe a 62-year-old man who presented with mild edema of the lower limbs. An echocardiogram revealed an incidental 1.3-cm diameter mass on the anterior mitral valve leaflet for which he underwent surgical resection and mitral valve replacement. Histopathological examination showed a lymphocyte-rich capillary-cavernous hemangioma. The exuberant lymphoid stroma is unusual for hemangioma and represents an undescribed pattern of cardiac hemangioma. Including the present report, only 13 cases of mitral valve hemangioma have been reported to date. Most patients are adult. Mitral hemangioma originates in the atrial aspect of the valve and involves more commonly the anterior leaflet. The average maximum diameter of the lesion is 1.7 (S.D.=0.75) cm. Pure cavernous hemangioma is the predominant type of mitral hemangioma. Most of them are described as pedunculated or polypoid. Surgical excision appears to be curative. Recurrences have not been reported. Lymphocyte-rich cardiac hemangioma represents a peculiar type of hemangioma which should be included in the differential diagnosis of other vascular lesions.
Asunto(s)
Neoplasias Cardíacas/patología , Hemangioma Capilar/patología , Hemangioma Cavernoso/patología , Linfocitos Infiltrantes de Tumor/patología , Válvula Mitral/patología , Biomarcadores de Tumor/análisis , Biopsia , Ecocardiografía , Neoplasias Cardíacas/química , Neoplasias Cardíacas/inmunología , Neoplasias Cardíacas/cirugía , Implantación de Prótesis de Válvulas Cardíacas , Hemangioma Capilar/química , Hemangioma Capilar/inmunología , Hemangioma Capilar/cirugía , Hemangioma Cavernoso/química , Hemangioma Cavernoso/inmunología , Hemangioma Cavernoso/cirugía , Humanos , Inmunohistoquímica , Hallazgos Incidentales , Linfocitos Infiltrantes de Tumor/química , Linfocitos Infiltrantes de Tumor/inmunología , Masculino , Persona de Mediana Edad , Válvula Mitral/química , Válvula Mitral/inmunología , Válvula Mitral/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Benign melanocytic nevi (MN) of the anal canal are exceptional and require adequate differential diagnosis. There are no data on incidence of these lesions. Only a single case report of hemorrhoid with an MN has been reported. The necessity of routine pathologic evaluation of hemorrhoidectomy specimens has been questioned. MATERIAL AND METHODS: The authors undertook a retrospective histologic study of the hemorrhoidal tissue obtained in a series of 1918 consecutive hemorrhoidectomies performed between January 2004 and November 2012. RESULTS: Incidental hemorrhoidal MN were detected in 4 (0.21%) patients. The ratio observed was 1 nevus in 480 specimens. Lesions were intradermal or purely junctional in nature. There were no mitoses or architectural disorder. An intradermal nevus showed localized pagetoid melanocytes. The mean age of the patients was 56.5 years (range 47-73 years). The mean size of nevi was 5.86 mm (range 1.89-13.86 mm). All cases were present in external hemorrhoids. CONCLUSIONS: Although uncommonly, incidental MN can be observed in hemorrhoidal tissue. They may show features of flexural nevi and pagetoid melanocytes. Routine histopathological study of hemorrhoidectomy specimens would help to detect benign or malignant melanocytic tumors of the anal canal as these neoplasms can be easily missed clinically. Furthermore, this practice would allow early diagnosis of significant associated processes.
Asunto(s)
Neoplasias del Ano/complicaciones , Hemorroides/complicaciones , Nevo Pigmentado/complicaciones , Neoplasias Cutáneas/complicaciones , Anciano , Neoplasias del Ano/epidemiología , Femenino , Hemorreoidectomía , Humanos , Hallazgos Incidentales , Masculino , Persona de Mediana Edad , Nevo Pigmentado/epidemiología , Estudios Retrospectivos , Neoplasias Cutáneas/epidemiologíaRESUMEN
La incidencia de tumores malignos extratímicos en pacientes con timoma es significantivamente más alta que en la población general. El linfoma no Hodgkin es la neoplasia más comúnmente asociada. En esta revisión, informamos la concurrencia de un carcinoma epidermoide tímico y un linfoma intravascular de células B grandes diseminado, caracterizado por presentación clínica rápidamente progresiva y fatal, en un hombre de 78 anos. Este caso constituye la primera asociación informada entre ambas neoplasias. Debido a su rareza y a la multiplicidad de presentaciones, es muy difícil diagnosticar este tipo de linfoma antemortem, por lo que debería ser incluido en el diagnóstico diferencial de todo paciente que presente enfermedad sistémica y elevación marcada de la deshidrogenada láctica sérica. En el presente caso pensamos que el linfoma pudiera haberse desarrollado como resultado de un defecto en la vigilancia inmunológica o una alteración de la inmunorregulación causada por el carcinoma tímico. En casos como el actual la autopsia es el único método de diagnostico seguro(AU)
The incidence of extrathymic malignancies in patients with thymoma is significantly higher than in the general population. Non-Hodgkin lymphoma represents the most commonly associated tumor type. We report the concurrence of primary thymic squamous cell carcinoma and disseminated intravascular large B-cell lymphoma (IVL) in a 78-year-old man characterized by a rapidly fatal clinical course. To our knowledge, this is the first time that such an association is reported. Due to its rarity and the multiplicity of presentations, it is very difficult to diagnose this type of extranodal lymphoma antemortem. The intravascular lymphoma should be included in the differential diagnosis when a patient presents signs of a systemic disease and marked elevation of serum LDH. In this case the lymphoma may have been developed as a result of defective immunologic surveillance or impaired immunoregulation caused by the thymic carcinoma. In our case as in some other cases of IVL, diagnosis could only be conclusively confirmed on autopsy(AU)
Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Timoma/diagnóstico , Timoma/patología , Neoplasias del Timo/patología , Linfocitos B/patología , Diagnóstico Diferencial , Neoplasias del Mediastino/complicaciones , Neoplasias del Mediastino/diagnóstico , Neoplasias del Mediastino/patología , Mediastino/patología , MediastinoRESUMEN
We report herein one case of conventional renal cell carcinoma (RCC) producing extensive extracellular mucinous secretion in a 71-year-old man. To the best of our knowledge, the presence of mucinous secretion in this tumor has not been documented. Mucin production, despite its low frequency, can be considered an additional feature of conventional RCC. Therefore, clear cell RCC should be added to the list of parenchymal renal tumors that can show significant mucin secretion; and it should be included in the inventory of morphologic variations of this tumor, which may cause diagnostic difficulties. It is of primary importance to distinguish mucin-secreting clear cell RCC from the metastasis of a mucin-secreting tumor to conventional RCC. Presence of mucin in a clear cell carcinoma does not exclude a renal origin.
Asunto(s)
Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Mucinas/biosíntesis , Anciano , Diabetes Mellitus Tipo 2/epidemiología , Humanos , Hipertensión/epidemiología , Masculino , Tuberculosis Pulmonar/epidemiologíaRESUMEN
Malignant tumors at the site of implantation of a pacemaker generator, although rare, have been reported in the literature. We present a case of an 89-year-old man with atypical fibroxanthoma in a pacemaker pocket. The device had been implanted for more than 4 years. An exophytic tumor had developed in this place and was clinically interpreted as a pyogenic granuloma. An excisional biopsy revealed the nature of the tumor. To our knowledge, the association of atypical fibroxanthoma arising from a pacemaker pocket has not been previously reported. A review of the literature has revealed four malignant soft tissue tumors previously reported at the pacemaker site. Routine examination in all patients with implanted pacemaker generators should be practiced at follow-up visits. This would allow an early diagnosis of a malignant associated neoplasm. Pathologists should become familiar with this type of devices and their potential neoplastic complications.
Asunto(s)
Errores Diagnósticos , Granuloma de Cuerpo Extraño/patología , Granuloma Piogénico/patología , Histiocitoma Fibroso Maligno/patología , Marcapaso Artificial/efectos adversos , Neoplasias Cutáneas/patología , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biopsia , Diseño de Equipo , Granuloma de Cuerpo Extraño/etiología , Granuloma Piogénico/etiología , Histiocitoma Fibroso Maligno/química , Histiocitoma Fibroso Maligno/etiología , Histiocitoma Fibroso Maligno/cirugía , Humanos , Inmunohistoquímica , Masculino , Valor Predictivo de las Pruebas , Neoplasias Cutáneas/química , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/cirugía , Resultado del TratamientoRESUMEN
Cardiac papillary fibroelastomas (PFEs) are uncommon valve tumors. Multiple PFEs at the same or different locations in the heart account for less than 10% of patients with PFE. We herein describe a case of an asymptomatic PFE of both pulmonary and aortic valves which was incidentally diagnosed by echocardiography in a 60-year-old woman. Both PFEs were removed surgically without valve replacement. To our knowledge, this combination of lesions has not been previously reported. Even though PFEs are classified as benign cardiac tumors, they can present serious complications, such as embolic episodes, mechanical obstruction or valvular dysfunction. Valve-sparing shave excision of the lesions can be readily accomplished in most instances with good long-term results. All surgically removed valvular lesions should be histopathologically examined to confirm the echocardiographic diagnosis.
Asunto(s)
Válvula Aórtica/patología , Fibroma/patología , Neoplasias Cardíacas/patología , Válvula Pulmonar/patología , Ecocardiografía , Femenino , Fibroma/cirugía , Neoplasias Cardíacas/cirugía , Humanos , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Type I spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by loss or mutations of the survival motor neuron 1 (SMN1) gene. The reduction in SMN protein levels in SMA leads to degeneration and death of motor neurons. In this study, we have analyzed the nuclear reorganization of Cajal bodies, PML bodies and nucleoli in type I SMA motor neurons with homozygous deletion of exons 7 and 8 of the SMN1 gene. Western blot analysis is is revealed a marked reduction of SMN levels compared to the control sample. Using a neuronal dissociation procedure to perform a careful immunocytochemical and quantitative analysis of nuclear bodies, we demonstrated a severe decrease in the mean number of Cajal bodies per neuron and in the proportion of motor neurons containing these structures in type I SMA. Moreover, most Cajal bodies fail to recruit SMN and spliceosomal snRNPs, but contain the proteasome activator PA28, a molecular marker associated with the cellular stress response. Neuronal stress in SMA motor neurons also increases PML body number. The existence of chromatolysis and eccentric nuclei in SMA motor neurons correlates with Cajal body disruption and nucleolar relocalization of coil in, a Cajal body marker. Our results indicate that the Cajal body is a pathophysiological target in type I SMA motor neurons. They also suggest the Cajal body-dependent dysfunction of snRNP biogenesis and, therefore, pre-mRNA splicing in these neurons seems to be an essential component for SMA pathogenesis.
Asunto(s)
Nucléolo Celular/metabolismo , Cuerpos Enrollados/metabolismo , Neuronas Motoras/metabolismo , Proteínas Nucleares/metabolismo , Atrofias Musculares Espinales de la Infancia/metabolismo , Atrofias Musculares Espinales de la Infancia/patología , Proteína 1 para la Supervivencia de la Neurona Motora/metabolismo , Nucléolo Celular/química , Cuerpos Enrollados/química , Humanos , Atrofias Musculares Espinales de la Infancia/genética , Proteína 1 para la Supervivencia de la Neurona Motora/química , Proteína 1 para la Supervivencia de la Neurona Motora/genéticaRESUMEN
Xanthogranulomatous orchitis (XGO) is a rare chronic inflammatory process characterized by destruction of tissue that is replaced by an outstanding cellular infiltrate of lipid-laden macrophages. To date, 20 cases of this process have been reported previously. We present herein the case of a 55-year-old man who had sustained complete tetraplegia at C-6 level and neuropathic bladder for 21 years. After repeated episodes of urinary tract infection, the patient developed a bilateral XGO and a right xanthogranulomatous epididymitis (XGE) that were treated with bilateral orchiepididymectomy. To our knowledge, a bilateral XGO has not yet been reported. Repeated episodes of high-pressure urinary reflux along the vas deferens during dyssynergic voiding possibly led to retrograde extension from the urinary tract by common urinary pathogens and development of bilateral XGO and right XGE. Since tissue destruction is a feature of this process, curative treatment required antibiotic therapy followed by bilateral excision of testes and epididymes.
Asunto(s)
Granuloma/patología , Orquitis/patología , Cuadriplejía/complicaciones , Xantomatosis/patología , Granuloma/etiología , Humanos , Masculino , Persona de Mediana Edad , Orquitis/etiología , Vejiga Urinaria Neurogénica/complicaciones , Xantomatosis/etiologíaRESUMEN
Oncocytosis (oncocytomatosis) is a rare condition characterized by the presence of innumerable oncocytic nodules in one or both kidneys, usually associated with the presence of a dominant nodule. An incidental detection of a renal tumor in a renal biopsy performed for the diagnosis of a medical disease of the kidney is exceptional. We report herein a case of a 58-year-old woman presenting with idiopathic nephrotic syndrome. Histological examination of the percutaneous renal core biopsy revealed a minimal-change glomerular lesion and oncocytosis. A contrast-enhanced abdominal CT scan showed two solid round masses, one in each kidney, measuring 1.5 and 2 cm. The nephrotic syndrome was responsive first to prednisone and finally to cyclosporine. Pathological study of both renal dominant masses confirmed that they were oncocytomas. As far as we are aware, renal oncocytosis incidentally discovered in a biopsy performed for the diagnosis of a medical disease of the kidney has not been reported.
Asunto(s)
Adenoma Oxifílico/patología , Neoplasias Renales/patología , Riñón/patología , Proteinuria/patología , Adenoma Oxifílico/diagnóstico por imagen , Adenoma Oxifílico/terapia , Enfermedades Asintomáticas , Biopsia , Ciclosporina/uso terapéutico , Diagnóstico Diferencial , Femenino , Humanos , Inmunosupresores/uso terapéutico , Hallazgos Incidentales , Riñón/diagnóstico por imagen , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/terapia , Persona de Mediana Edad , Nefrectomía , Síndrome Nefrótico/tratamiento farmacológico , Síndrome Nefrótico/patología , Prednisona/uso terapéutico , Tomografía Computarizada por Rayos XAsunto(s)
Carcinoma de Células Transicionales/patología , Neoplasias Ureterales/patología , Anciano , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Transicionales/metabolismo , Carcinoma de Células Transicionales/cirugía , Femenino , Humanos , Queratinas/metabolismo , Neoplasias Ureterales/metabolismo , Neoplasias Ureterales/cirugía , Urotelio/metabolismo , Urotelio/patologíaRESUMEN
We report here one case of renal oncocytoma producing focal extracellular mucinous secretion in a 47-year-old woman. To the best of our knowledge, the presence of mucinous secretion in this tumor has not yet been reported. Mucin production, despite its low frequency, can be considered an additional feature of renal oncocytoma. Therefore, oncocytoma should be added to the list of parenchymal renal tumors that can show significant mucin secretion, and it should be included in the inventory of morphologic variations of oncocytoma which may cause diagnostic difficulties.