Adenoma pleomorfo con lipometaplasia: inesperada causa de obstrucción traqueal / Unexpected cause of tracheal obstruction: pleomorphic adenoma with lipometaplasia

Resumen El adenoma pleomorfo de tráquea es un tumor benigno, infrecuente, que genera cuadros obstructivos, pudiendo confundirse con asma, lo que retrasa su diagnóstico. Presentamos el caso de una mujer de 40 años con antecedentes de asma y episodios de obstrucción respiratoria de 8 meses de evolución. La fibrobroncoscopía mostró una lesión polipoide, pediculada, en el primer anillo traqueal, con oclusión de 80% de la luz, que se resecó. El diagnóstico histopatológico fue adenoma pleomorfo con lipometaplasia. El tratamiento de estos tumores consiste en la resección completa de la lesión y seguimiento a largo plazo por la baja proba bilidad de recurrencia, malignización y metástasis.

Abstract Pleomorphic adenoma of the trachea is a benign tumor, extremely rare, that generates obstructive symp toms and sometimes is confused with asthma, which delays its diagnosis. We present the case of a 40-year-old woman with history of asthma and airway obstruction, of 8-months duration. Fibrobronchoscopy showed polypoid, pedunculated lesion in first tracheal ring which occluded 80% of the lumen, that was resected. The histopatho logical diagnosis was pleomorphic adenoma with lipometaplasia. Treatment of these tumors consists in complete resection of the lesion and long-term follow-up due to low probability of recurrence, malignancy and metastasis.

[Unexpected cause of tracheal obstruction: pleomorphic adenoma with lipometaplasia]. / Adenoma pleomorfo con lipometaplasia: inesperada causa de obstrucción traqueal.

Pleomorphic adenoma of the trachea is a benign tumor, extremely rare, that generates obstructive symptoms and sometimes is confused with asthma, which delays its diagnosis. We present the case of a 40-year-old woman with history of asthma and airway obstruction, of 8-months duration. Fibrobronchoscopy showed polypoid, pedunculated lesion in first tracheal ring which occluded 80% of the lumen, that was resected. The histopathological diagnosis was pleomorphic adenoma with lipometaplasia. Treatment of these tumors consists in complete resection of the lesion and long-term follow-up due to low probability of recurrence, malignancy and metastasis.

El adenoma pleomorfo de tráquea es un tumor benigno, infrecuente, que genera cuadros obstructivos, pudiendo confundirse con asma, lo que retrasa su diagnóstico. Presentamos el caso de una mujer de 40 años con antecedentes de asma y episodios de obstrucción respiratoria de 8 meses de evolución. La fibrobroncoscopía mostró una lesión polipoide, pediculada, en el primer anillo traqueal, con oclusión de 80% de la luz, que se resecó. El diagnóstico histopatológico fue adenoma pleomorfo con lipometaplasia. El tratamiento de estos tumores consiste en la resección completa de la lesión y seguimiento a largo plazo por la baja probabilidad de recurrencia, malignización y metástasis.

[Disseminated histoplasmosis in a woman with seronegative arthritis]. / Histoplasmosis diseminada en una mujer con artritis seronegativa.

Histoplasma capsulatum is an environmental fungus commonly found in the Ohio and Mississippi River valleys, Central and South America, and Asia. The most affected areas in Argentina are the Paraná and de La Plata river basins. Patients with histoplasmosis can have a wide range of clinical presentations. Most of them are asymptomatic, while those with compromised cellular immunity are at increased risk for the disseminated form. We present the case of a patient undergoing treatment with methotrexate for seronegative arthritis who developed the disseminated form of the disease, and who represented a diagnostic challenge due to the difficulty in identifying the etiologic agent.

Histoplasma capsulatum es un hongo ambiental que se encuentra distribuido comúnmente en los valles de los ríos Ohio y Mississippi, América Central, Sudamérica y Asia. Las zonas más afectadas en Argentina son las cuencas de los ríos Paraná y de La Plata. Los pacientes con histoplasmosis tienen una amplia variedad de manifestaciones clínicas. La mayoría son asintomáticos, mientras que aquellos con compromiso de la inmunidad celular tienen un riesgo aumentado de padecer la forma diseminada. Presentamos el caso de una mujer adulta, en tratamiento con metotrexato por una artritis seronegativa, que desarrolló la forma diseminada de la enfermedad, y que representó un desafío diagnóstico debido a la dificultad para identificar el agente etiológico.

Histoplasmosis diseminada en una mujer con artritis seronegativa / Disseminated histoplasmosis in a woman with seronegative arthritis

Resumen Histoplasma capsulatum es un hongo ambiental que se encuentra distribuido comúnmente en los valles de los ríos Ohio y Mississippi, América Central, Sudamérica y Asia. Las zonas más afectadas en Argentina son las cuencas de los ríos Paraná y de La Plata. Los pacientes con histoplasmosis tienen una amplia variedad de manifestaciones clínicas. La mayoría son asintomáticos, mientras que aquellos con com promiso de la inmunidad celular tienen un riesgo aumentado de padecer la forma diseminada. Presentamos el caso de una mujer adulta, en tratamiento con metotrexato por una artritis seronegativa, que desarrolló la forma diseminada de la enfermedad, y que representó un desafío diagnóstico debido a la dificultad para identificar el agente etiológico.

Abstract Histoplasma capsulatum is an environmental fungus commonly found in the Ohio and Mississippi River valleys, Central and South America, and Asia. The most affected areas in Argentina are the Paraná and de La Plata river basins. Patients with histoplasmosis can have a wide range of clinical presentations. Most of them are asymptomatic, while those with compromised cellular immunity are at increased risk for the disseminated form. We present the case of a patient undergoing treatment with methotrexate for seronegative arthritis who developed the disseminated form of the disease, and who represented a diagnostic challenge due to the difficulty in identifying the etiologic agent.

Dramatic clinical response to dabrafenib plus trametinib in anaplastic thyroid carcinoma and the challenges faced during the COVID-19 pandemic

SUMMARY Anaplastic thyroid carcinoma is the rarest tumor of the thyroid gland, representing less than 2% of clinically recognized thyroid cancers. Typically, it has an extremely rapid onset, fatal outcomes in most cases, and a median overall survival of 3 to 10 months despite aggressive multidisciplinary management. The presence of targetable mutations in anaplastic thyroid carcinoma patients is an opportunity for treatment when conventional therapeutics approaches are not effective, a frequent situation in the majority of patients. We present our experience in the management of a patient with unresectable anaplastic thyroid cancer who had a remarkable and rapid response to treatment with dabrafenib and trametinib during the COVID-19 pandemic. After four weeks of dabrafenib 150 mg twice daily plus trametinib 2 mg daily, he showed a dramatic reduction of the cervical mass around 90%. Nearly eight weeks under treatment with dabrafenib plus trametinib, the patient remains with minimal locoregional disease without distant metastases.

Dramatic clinical response to dabrafenib plus trametinib in anaplastic thyroid carcinoma and the challenges faced during the COVID-19 pandemic.

Anaplastic thyroid carcinoma is the rarest tumor of the thyroid gland, representing less than 2% of clinically recognized thyroid cancers. Typically, it has an extremely rapid onset, fatal outcomes in most cases, and a median overall survival of 3 to 10 months despite aggressive multidisciplinary management. The presence of targetable mutations in anaplastic thyroid carcinoma patients is an opportunity for treatment when conventional therapeutics approaches are not effective, a frequent situation in the majority of patients. We present our experience in the management of a patient with unresectable anaplastic thyroid cancer who had a remarkable and rapid response to treatment with dabrafenib and trametinib during the COVID-19 pandemic. After four weeks of dabrafenib 150 mg twice daily plus trametinib 2 mg daily, he showed a dramatic reduction of the cervical mass around 90%. Nearly eight weeks under treatment with dabrafenib plus trametinib, the patient remains with minimal locoregional disease without distant metastases.

Nefropatía por IgA y microangiopatía trombótica / IgA Nephropathy and Thrombotic Microangiopathy

INTRODUCCIÓN: La asociación de microangiopatía trombótica (MAT) y nefropatía por IgA (N.IgA) resulta un hecho conocido, aunque su prevalencia, patogénesis y evolución aún no se han esclarecido. MATERIAL Y MÉTODOS: Se realizó un estudio descriptivo y retrospectivo de 12 pacientes con N.IgA y MAT (N.IgA-MAT), diagnosticadas por biopsia renal en nuestro hospital, para analizar las características clinicopatológicas. Todas las biopsias renales se procesaron para microscopía óptica e inmunofluorescencia. RESULTADOS: La prevalencia de pacientes con N.IgA-MAT fue del 4.4% (12/274). La edad media fue de 33 años y 58.3% eran hombres, con tensión arterial sistólica y diastólica media al momento del diagnóstico de 171.3±53mmHg y 97.5±19.8mmHg respectivamente. La proteinuria promedio resultó 5.3 ± 3.7g/24hs y en 8 pacientes estuvo en rango nefrótico. Se constató deterioro de la función renal en 11 pacientes, con una creatinina sérica media de 7.2±4.7mg/dl. Ningún paciente presentó hallazgos clínicos o de laboratorio sugestivos de microangiopatía trombótica. La biopsia renal mostró MAT aguda con trombos de fibrina arteriolares en el 75% y lesiones crónicas con hiperplasia intimal concéntrica y aspecto de "catáfilas de cebolla" en 83.3%, que se asociaron con un elevado porcentaje de esclerosis glomerular global (72%), atrofia tubular moderada (38.6%) y/o fibrosis intersticial (31.3%). En 91.7% de los casos, la MAT se asoció con grado histológico V. CONCLUSIÓN: La prevalencia y significado de la asociación de N.IgA-MAT nos plantea si la MAT es causa o consecuencia de estadios avanzados de N.IgA. Distintos estudios clinicopatológicos han demostrado que la MAT juega un rol importante en la progresión de la N.IgA. La relación de MAT con los niveles de creatinina sérica y proteinuria apoya su rol en la progresión de la N.IgA. Mientras que las MAT sistémicas cursan con afección de múltiples órganos, en estos casos el riñón fue el único órgano comprometido. La injuria endotelial y subsecuente trombosis microvascular conducen a la isquemia y disfunción renal. El hallazgo de MAT-N.IgA en pacientes con presión arterial normal al momento de la biopsia sugiere que ni la hipertensión ni las lesiones parenquimatosas avanzadas son prerrequisitos para el desarrollo de MAT. Los mecanismos fisiopatológicos que conducen a la injuria endotelial son aún desconocidos, pero parecerían ser distintos a los de la nefropatía hipertensiva maligna

INTRODUCTION: Although the association between thrombotic microangiopathy (TMA) and IgA nephropathy (IgAN) is a known fact, its prevalence, pathogenesis and progression are not clear yet. METHODS: A descriptive, retrospective study involving 12 patients with IgAN and TMA (IgAN-TMA) was carried out; patients were diagnosed by a renal biopsy performed in our hospital in order to analyze clinicopathologic features. All the biopsy samples were processed for light microscopy and immunofluorescence. RESULTS: The prevalence of patients with IgAN-TMA was 4.4% (12/274). The mean age was 33 and 58.3% of the subjects were men, showing, during diagnosis, mean systolic and diastolic blood pressure values of 171.3±53 mmHg and 97.5±19.8 mmHg, respectively. The average amount of protein in urine was 5.3 ± 3.7g/24 h and 8 patients had nephrotic-range proteinuria. Impairment of renal function was found in 11 patients, with a mean serum creatinine level of 7.2±4.7 mg/dL. No clinical or laboratory findings suggested thrombotic microangiopathy in any of the patients. The renal biopsy showed acute TMA with arteriolar fibrin thrombi in 75% of the subjects and 'onion-skin-like' chronic lesions with concentric intimal hyperplasia in 83.3% of them, which were associated with a high percentage of global glomerulosclerosis (72%), moderate tubular atrophy (38.6%) and/or interstitial fibrosis (31.3%). In 91.7% of the cases, TMA was related to histological grade 5. CONCLUSIONS: The prevalence and significance of the relationship between IgAN and TMA pose the question of whether TMA is the cause or consequence of advanced stage IgAN. Several clinicopathologic studies have proved that TMA plays a major role in IgAN progression. The connection of TMA with creatinine serum and proteinuria levels seems to support this conclusion. While systemic TMA usually affects multiple organs, in these cases, the kidney was the only one compromised. Endothelial injury and the subsequent microvascular thrombosis lead to ischaemia and kidney failure. The TMA-IgAN finding in patients with normal blood pressure at the time of the biopsy suggests that neither hypertension nor advanced parenchymal lesions are a prerequisite for the development of TMA. The physiopathological mechanisms leading to endothelial injury are still unknown, but appear to be different from those of malignant nephrosclerosis

Tabaquismo y glomeruloesclerosis / Smoking and glomerulosclerosis

El tabaquismo es un factor de riesgo para el desarrollo de lesiones vasculares y glomeruloesclerosis. La glomerulopatía nodular relacionada con el tabaquismo es una entidad bien reconocida que simula clínica y patológicamente a la nefropatía nodular diabética. El humo del tabaco altera la hemodinamia intrarrenal por activación simpática y contiene radicales libres que inducen estrés oxidativo, incrementando la matriz extracelular glomerular. Presentamos un caso de esclerosis glomerular focal y segmentaria e hialinosis arteriolar severa en un hombre de 63 años, con proteinuria en rango nefrótico, hipertensión leve y función renal normal, con una historia de tabaquismo de larga data. La ausencia de otros factores de riesgo y los hallazgos clinicopatológicos sugieren en este caso, el posible rol del tabaquismo en la patogenia de la esclerosis glomerular focal y segmentaria

Smoking is a risk factor for the development of vascular lesions and glomerulosclerosis. Nodular glomerulopathy associated with this habit is well known and resembles diabetes nephropathy clinically and pathologically. Tobacco smoke affects intrarenal hemodynamics through sympathetic activation and contains free radicals inducting oxidative stress, which increases glomerular extracellular matrix. We report the case of a 63-year-old man with focal segmental glomerulosclerosis, severe arteriolar hyalinosis, nephrotic-range proteinuria, mild hypertension, normal renal function and a long-term smoking history. The absence of other risk factors and the clinicopathologic findings suggest that in this case smoking may play a role in the pathogenesis of focal segmental glomerulosclerosis

Experimental severe Pseudomonas aeruginosa pneumonia and antibiotic therapy in piglets receiving mechanical ventilation.

BACKGROUND: Little is known about the general and local consequences of severe pneumonia under mechanical ventilation (SPMV) and how these are resolved with antibiotic therapy (ABT). OBJECTIVES: To investigate the physiologic, biological, microbiological, and pathologic changes produced by experimental SPMV in a porcine model, and to evaluate the effect of ABT. METHODS: Pseudomonas aeruginosa was inoculated in 12 large white-Landrace piglets receiving mechanical that were killed after 72 h if death did not occur before. Vital signs, serum and BAL cytokines, serum C-reactive protein (CRP), and graded postmortem lung pathology and cultures (blood and quantitative BAL and lung) were evaluated. Six piglets received inappropriate ABT (no ABT or ceftriaxone), and six piglets received appropriate ABT (ciprofloxacin). MEASUREMENTS AND MAIN RESULTS: Pathologic and microbiological evidence of infection were present in all the animals in both groups. SPMV produced significant oxygenation and lung compliance worsening, increased serum CRP, and reduced BAL fluid tumor necrosis factor (TNF)-alpha. Arterial thrombosis in lung pathology was associated with higher temperature, hypoxemia and low lung compliance, higher initial serum CRP and TNF-alpha concentrations, and increased serum interleukin (IL)-6 and BAL IL-6 and TNF-alpha. Reduced ABT reduced body temperature and culture positivity. CONCLUSIONS: This model resembles VAP and has been used for studying pulmonary infection and inflammation related to mechanical ventilation. ABT reduced fever and bacterial burden in SPMV but had no effect on cytokine or CRP concentrations, oxygenation, or lung mechanics. Pulmonary artery thrombosis was associated with worse response to infection.