[Pharmacogenomics in neuro-oncology]. / Farmacogenomica en neurooncologia.

INTRODUCTION AND DEVELOPMENT: Chemotherapy protocols for treatment of brain tumors use toxic molecules for killing cancer cells in a similar way that protocols for treating other cancers. Therefore, secondary effects and poor response are the major handicaps. Technological developments based on pharmacogenomics and pharmacoproteomics will predict response and toxicity giving rise to a personalized medicine. However, there are only few studies that correlate chemotherapeutical molecules for brain tumor treatment and prediction of response and toxicity. CONCLUSIONS: The development of new technologies based on high-density microarrays allows the progressive identification of genes whose presence will predict the efficacy of therapeutic protocols. Once identified, specific equipments based on low-density arrays will detect exclusively in an easy and fast way the presence of genes in order to predict patient's response and avoid toxicity. Other more sophisticated techniques at present still at an experimental step based on proteomics as MALDI (Matrix-Assisted Laser Desorption Ionization) and SELDI (Surface-Enhanced Laser Desorption Ionization) will allow the identification of proteins that could predict response and toxicity.

Farmacogenómica en neurooncología / Pharmacogenomics in neuro-oncology

Introducción y desarrollo. Los protocolos de quimioterapiaen el tratamiento de los tumores cerebrales, como en los deotras localizaciones, emplean moléculas tóxicas para matar célulascancerosas. Pero, al igual que sucede con todos los tratamientoscontra el cáncer, la aparición de efectos secundarios y la ausenciade respuesta son los principales problemas para su eficacia.Su predicción va a ser posible gracias a los avances tecnológicosque se apoyan en la farmacogenómica y farmacoproteómica, dandolugar a la medicina personalizada. Sin embargo, todavía sonpocos los estudios que relacionan moléculas activas para el tratamientode tumores cerebrales y la posibilidad de predecir el porcentajede respuesta y de toxicidad. Conclusiones. El desarrollo denuevas tecnologías basadas en los microarrays de alta densidadestá logrando la identificación de genes cuya presencia permitirápredecir el efecto de determinado protocolo terapéutico. Una vezidentificados, equipos de arrays de baja densidad detectarán exclusivamentelos genes que pueden intervenir en la capacidad derespuesta del paciente y la posibilidad de presentar cuadros tóxicos.Otras técnicas sofisticadas en fase más experimental, que sebasan en el estudio de proteínas (proteómica), como las MALDI(Matrix-Assisted Laser Desorption Ionization) y las SELDI (Surface-Enhanced Laser Desorption Ionization), permitirán reconocerproteínas asociadas a la predicción de respuesta y de toxicidad

Introduction and development. Chemotherapy protocols for treatment of brain tumors use toxic molecules forkilling cancer cells in a similar way that protocols for treating other cancers. Therefore, secondary effects and poor responseare the major handicaps. Technological developments based on pharmacogenomics and pharmacoproteomics will predictresponse and toxicity giving rise to a personalized medicine. However, there are only few studies that correlate chemotherapeuticalmolecules for brain tumor treatment and prediction of response and toxicity. Conclusions. The development ofnew technologies based on high-density microarrays allows the progressive identification of genes whose presence will predictthe efficacy of therapeutic protocols. Once identified, specific equipments based on low-density arrays will detect exclusivelyin an easy and fast way the presence of genes in order to predict patient’s response and avoid toxicity. Other moresophisticated techniques at present still at an experimental step based on proteomics as MALDI (Matrix-Assisted LaserDesorption Ionization) and SELDI (Surface-Enhanced Laser Desorption Ionization) will allow the identification of proteinsthat could predict response and toxicity

Síndrome de la úlcera rectal solitaria / Solitary rectal ulcer syndrome

Presentamos el caso de una paciente, quien, tras haber sufrido un cuadro de anorexia, presentaba pérdida importante de peso y deposiciones mucosanguinolentas, de un año de evolución. Los signos clínicos, morfológicos y especialmente histopatológicos son compatibles con el denominado "síndrome de la úlcera rectal solitaria", cuadro que se corresponde con un grupo de enfermedades que con diferentes denominaciones presentan similitud en el complejo clínico y cuyo diagnóstico es anatomopatológico. La buena respuesta al tratamiento quirúrgico, 3 años después de la intervención, nos permite considerarlo una alternativa eficaz al tratamiento conservador cuando con éste no se obtenga la respuesta deseada (AU)

[Congenital bladder diverticulum and Ehlers-Danlos syndrome: an unusual association]. / Divertículo vesical congénito y síndrome de Ehlers-Danlos: una rara asociación.

The existence of a vesical diverticulum in the context of a congenital connective tissue disorder such as Ehlers-Danlos syndrome led us to consider the possibility of a relationship. Four types of diverticula can be found in the literature: congenital, acquired, iatrogenic and syndrome-associated. Within the later, Ehlers-Danlos syndromes type IV and IX, even type V, are associated to the existence of vesical diverticula. The potential spontaneous rupture of the diverticulum is a typical feature, as well as post-surgery relapse. The attitude towards such diverticula should be one of watchful waiting, and simple, plasty-free diverticulectomy on the bladder's neck is indicated when performing a surgical procedure.

[Glandular cystic cystitis]. / Consideraciones sobre la cistitis quística glandular.

Cystic-glandular cystitis is considered as part of the urothelial pre-neoplastic proliferative abnormalities. This group includes atypical hyperplasia. Von Brunn's nidus, and cystitis cystica. They are a consequence of the changes experienced at the urothelium level in response to inflammation, irritation or carcinogens. Diagnosis is mainly based in the pathoanatomical study of the biopsy obtained following endoscopic resection. The signs and symptoms it presents are varied and show a clear relationship to distribution and extension of cysts. Treatment is based in the removal of irritative factors. Cystectomy with urinary by-pass may be necessary if required by clinical evolution.

Divertículo vesical congénito y síndrome de Ehlers-Danlos: una rara asociación / Congenital vesical diverticulum and Ehlers-Danlos syndrome: a rare association

La existencia de un divertículo vesical en el contexto de una alteración congénita del tejido conectivo como es el Síndrome de Ehlers-Danlos, nos hizo plantearnos su posible relación. En la literatura se describen en la actualidad cuatro tipos de divertículos: congénitos, adquiridos, yatrogénicos y asociados a síndromes. Dentro de este último, el síndrome de Ehlers-Danlos en sus tipos IV y IX y ocasionalmente en el tipo V se relaciona con la existencia de divertículos vesicales. Es característica la posible ruptura espontánea del divertículo, así como su recidiva tras cirugía. La actitud ante estos divertículos debe a poder ser expectante y sólo, la diverticulectomía simple sin plastia sobre el cuello vesical está indicada, si fuera necesaria realizar alguna técnica quirúrgica. (AU)

Consideraciones sobre la cistitis quística glandular / Reflections on glandular cystitis cystica

La cistitis quístico-glandular se engloba dentro de las anormalidades proliferativas preneoplásicas uroteliales. En este grupo se engloban la hiperplasia atípica, los nidos de Von Brunn y la cistitis quística.Se caracterizan por ser consecuencia de los cambios experimentados a nivel del urotelio en respuesta a la inflamación, la irritación o los carcinógenos. Su diagnóstico se basa fundamentalmente en el estudio anatomopatológico de la biopsia obtenida tras la resección endoscópica. Su clínica es muy variada, estando en clara relación con la distribución y extensión de los quistes. Su tratamiento se basa en la eliminación de los factores irritativos, pudiendo llegar a requerir la realización de una cistectomía con derivación urinaria si su evolución clínica asi lo requiriese (AU)

[Polymorphic reticulosis of the rhinopharynx]. / Reticulosis polimorfa de rinofaringe.

"Malignant centrofacial granulomatosis" is an unusual but devastating spectrum of lymphoproliferative disorders that is now thought to include several entitites, such as polymorphic reticulosis or peripheral T-cell lymphoma. Characteristically there are destructive centrofacial lesions which often produce difficulties for the diagnostic to the clinician and pathologist. The case of a 71-year-old man diagnosed in our Department as polymorphic reticulosis sitting on the rhinopharynx is reported.

[Epithelial-myoepithelial carcinoma of smaller salivary gland]. / Carcinoma epitelial-mioepitelial de glándula salivar menor.

The epithelial-myoepithelial carcinoma of salivary glands is rarely presented and it's considered as an intermediate grade tumor. Usually are located in the parotid gland, however sometimes occur on minor salivary glands. An epithelial-myoepithelial carcinoma sitting on a palatine minor salivary gland of long course is reported.

[Epithelioid amelanotic melanoma of the nose and paranasal sinuses]. / Melanoma epitelioide amelanótico de fosas y senos paranasales.

Mucous melanomas are rare, representing 1-3% of melanomata and 3% of malignant nasosinusal tumors. The more usual location is the nasal cavity and paranasal sinuses. In early stages occur with a poor and unespecific features, which delays the diagnosis and worsen the prognosis. An amelanotic melanoma case is reported and bibliographic review of these tumors are made.

High-grade carcinoma component in epithelial-myoepithelial carcinoma of salivary glands clinicopathological, immunohistochemical and flow-cytometric study of three cases.

Three cases of epithelial-myoepithelial carcinoma (EMC) with coexisting areas of high grade carcinoma are reported. In two of the cases there was a previous recurrence, and in all three patients there had been a sudden increase in size before final surgery. The typical ductal and myoepithelial components of EMC showed the usual biphasic pattern and the expected immunophenotypes, with expression of wide spectrum cytokeratins, Cam 5.2 and EMA in the ductal part, and muscle-specific actin, smooth muscle actin, S-100 protein, vimentin and cytokeratins in the myoepithelial component. These areas also had a low mitotic count and low proliferation rate as measured by immunohistochemistry and by flow cytometry. Conversely, areas of high-grade tumour had the features of a large cell carcinoma, with focal mucin secretion in two cases. This high-grade component showed an epithelial immunophenotype in two cases, and was negative for all tested markers in the third one. The mitotic counts and the proliferation rates were much higher in these anaplastic areas. One of the patients died 3 months after treatment; another developed lymph node metastases 1 year later and was alive after 6 years of follow-up. The third patient was alive without evidence of disease 7 months after wide surgical resection of the tumour. The possibility of anaplastic transformation in EMC makes thorough sampling mandatory in this type of neoplasm.

Atypical microangiopathy in a patient treated with ticlopidine.

Microangiopathies are rare complications during treatments with ticlopidine. We describe an atypical microangiopathy, affecting almost exclusively myocardium, and thrombocytopenia, shortly after onset of ticlopidine. The patient died a few days after. Autopsy showed no bleedings or large thrombi in most organs, but were compatible with microangiopathy in myocardial small vessels.

Facial nerve palsy produced by plasma cell granuloma.

There are many causes for peripheral facial nerve palsy, such as an isolated phenomenon occurring in a healthy person (Bell's palsy), a manifestation of a systemic illness, or a component of a more widespread neurological disease. Plasma cell granuloma is the proliferation of polyclonal, nonneoplastic plasma cells. Several cases have been reported in the literature in which plasma cell granulomas have affected the brain, lungs, gastrointestinal tract, kidneys, salivary glands, and skin. We report a case of peripheral facial nerve palsy produced by a plasma cell granuloma that was confirmed by histological and immunohistochemical studies.

Integration of the SV40 promoter/enhancer sequences in an anchorage-independent clonal subline of SV40-infected human keratinocytes.

Long-term cultures of SV40-infected human keratinocytes contain integrated, but structurally altered copies of the viral sequences. The presence of these sequences is required for expression of properties associated with the transformed phenotype including immortalization. The integrated viral sequences in an anchorage-independent line of viral-transformed human keratinocytes have been found to be contained on two BamHI fragments of about 6.9 and 5.2 kb. In the larger fragment the viral sequences were present as two tandemly repeated subgenomic fragments containing the viral origin/promoter region with nucleotide alterations that affect enhancer function, the origin of replication and T antigen binding site 1. The viral early gene promoter in one integrant gave rise to an unspliced fusion transcript comprised of a short portion of the viral early gene leader sequence and the flanking human sequences. The smaller fragment consisted of full-length SV40 containing a nine-nucleotide insertion in the C-terminal portion of the SV40 T antigen, a region involved in the regulation of viral host range.

[Kikuchi-Fujimoto necrotizing lymphadenitis associated with brucellosis]. / Linfadenitis necrotizante de Kikuchi-Fujimoto asociada a brucelosis.

A 22 year-old woman was referred to the hospital for treatment after being diagnosed of Hodgkin's disease, established by lymph node biopsy. She complained of fever and sweats, and no lymph node enlargement or visceromegaly could be appreciated. Kikuchi's necrotising lymphadenitis was diagnosed after reviewing the lymph node specimen. The microbiological and serologic tests performed showed the existence of brucellosis. The clinical symptoms easily disappeared after treatment with streptomycin and doxycycline and she has been well, with no other symptoms or lymph node enlargement, after one year of follow-up. Kikuchi's disease is usually associated with different infections, although it had never been reported in association with brucellosis. This picture can easily be mistaken as malignant lymphoma or Hodgkin's disease.