Estudio inmunohistoquímico de los factores de trancripción de desarrollo neural (TTF1, ASCL1 y BRN2) en los tumores neuroendocrinos de próstata / Immunohistochemical study of the neural development transcription factors (TTF1, ASCL1 and BRN2) in neuroendocrine prostate tumours

Objetivo: El carcinoma neuroendocrino de célula pequeña de próstata es una neoplasia infrecuente que supone el 0,5-1% de todas las neoplasias prostáticas. La mediana de supervivencia cáncer-específica de los pacientes con carcinoma neuroendocrino de célula pequeña de próstata es de 19 meses, y el 60,5% de los pacientes presentan enfermedad metastásica. Los factores de transcripción de desarrollo neural son moléculas implicadas en la organogénesis del sistema nervioso central y de precursores neuroendocrinos de diversos tejidos, que incluyen la glándula suprarrenal, el tiroides, el pulmón y la próstata, entre otros órganos. Material y métodos: Presentamos 3 casos de esta infrecuente entidad, aplicando los nuevos criterios de la OMS. Realizamos estudios mediante tinción de H-E y analizamos la expresión de los factores de transcripción de desarrollo neurales Achaete-scute homolog like 1, Thyroid transcription factor 1 y los factores de transcripción clase iii/iv POU, como nueva línea de investigación en la carcinogénesis de los tumores neuroendocrinos de próstata. Resultados: En el caso 1 no se observó inmunoexpresión para TTF1. Los casos 2 y 3 presentaron inmunotinción positiva para ASCL1, e inmunotinción negativa en el caso 1. La inmunotinción para BRN2 fue negativa en el caso 1 y positiva en los casos 2 y 3. Conclusión: Actualmente, la OMS no reconoce ningún marcador molecular ni genético con valor pronóstico. ASCL-1 está relacionado con las vías de señalización NOTCH y WNT. ASCL-1, TTF1 y BRN2 podrían usarse para el diagnóstico precoz y como factor pronóstico y diana terapéutica

Objective: Prostatic small-cell neuroendocrine carcinoma is an uncommon malignancy that constitutes 0.5-1% of all prostate malignancies. The median cancer-specific survival of patients with prostatic small-cell neuroendocrine carcinoma is 19 months, and 60.5% of the patients have metastatic disease. Neural development transcription factors are molecules involved in the organogenesis of the central nervous system and of neuroendocrine precursors of various tissues, including the suprarenal gland, thyroid glands, lungs and prostate. Material and methods: We present 3 cases of this uncommon condition, applying the new World Health Organisation criteria. We conducted studies through haematoxylin and eosin staining and analysed the expression of the neural development transcription factors achaete-scute homolog like 1, thyroid transcription factor 1 and the class III/IV POU transcription factors, as a new research line in the carcinogenesis of prostatic neuroendocrine tumours. Results: In case 1, there was no TTF1 immunoexpression. Cases 2 and 3 had positive immunostaining for ASCL1, and Case 1 had negative immunostaining. BRN2 immunostaining was negative in case 1 and positive in cases 2 and 3. Conclusion: The World Health Organisation does not recognise any molecular or genetic marker with prognostic value. ASCL-1 is related to the NOTCH and WNT signalling pathways. ASCL-1, TTF1 and BRN2 could be used for early diagnosis and as prognostic factors and therapeutic targets

Carcinoma mucinoso tubular y de células fusiformes. Una neoplasia renal infrecuente de buen pronóstico / Mucinous tubular and spindle cell carcinoma. An uncommon renal neoplasm with favorable prognosis

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Immunohistochemical study of the neural development transcription factors (TTF1, ASCL1 and BRN2) in neuroendocrine prostate tumours. / Estudio inmunohistoquímico de los factores de trancripción de desarrollo neural (TTF1, ASCL1 y BRN2) en los tumores neuroendocrinos de próstata.

OBJECTIVE: Prostatic small-cell neuroendocrine carcinoma is an uncommon malignancy that constitutes 0.5-1% of all prostate malignancies. The median cancer-specific survival of patients with prostatic small-cell neuroendocrine carcinoma is 19 months, and 60.5% of the patients have metastatic disease. Neural development transcription factors are molecules involved in the organogenesis of the central nervous system and of neuroendocrine precursors of various tissues, including the suprarenal gland, thyroid glands, lungs and prostate. MATERIAL AND METHODS: We present 3 cases of this uncommon condition, applying the new World Health Organisation criteria. We conducted studies through haematoxylin and eosin staining and analysed the expression of the neural development transcription factors achaete-scute homolog like 1, thyroid transcription factor 1 and the class III/IV POU transcription factors, as a new research line in the carcinogenesis of prostatic neuroendocrine tumours. RESULTS: In case 1, there was no TTF1 immunoexpression. Cases 2 and 3 had positive immunostaining for ASCL1, and Case 1 had negative immunostaining. BRN2 immunostaining was negative in case 1 and positive in cases 2 and 3. CONCLUSION: The World Health Organisation does not recognise any molecular or genetic marker with prognostic value. ASCL-1 is related to the NOTCH and WNT signalling pathways. ASCL-1, TTF1 and BRN2 could be used for early diagnosis and as prognostic factors and therapeutic targets.

Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study.

BACKGROUND: Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). METHODS: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (ß-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. RESULTS: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with ß-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. CONCLUSION: In patients with PCa and bone metastases treated with ZA, ß-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important.

Gastrointestinal stromal tumors (GISTs): CD117, DOG-1 and PKCθ expression. Is there any advantage in using several markers?

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. Expression of CD117, DOG1 and PKCθ was investigated immunohistochemically in a series of 99 paraffin-embedded GISTs in order to determine the sensitivity and diagnostic value of these markers. KIT exons 9, 11, 13 and 17 and PDGFRA exons 12 and 18 were amplified by PCR and sequenced. A total of 94/99 (94%) GISTs stained positive for CD117, 81/99 (82%) for PKCθ and 90/99 (91%) for DOG-1. A significant correlation was noted between CD117 and DOG-1 expression (p=0.0001). All three markers were expressed in 74% (73/99) of GISTs. Of the five CD117-negative cases, two were PKCθ-negative/DOG1-negative and had mutations in KIT exon 11. Two were PKCθ-positive/DOG1-positive and had mutations in PDGFRA (one each in exons 12 and 18), and one was DOG1-negative/PKCθ-positive, with a PDGFRA exon 18 mutation. The most sensitive marker was CD117, followed by DOG-1 and PKCθ. Although PKCθ was less sensitive, and its staining is more challenging and difficult to interpret, the use of this marker is highly recommended, particularly in CD117-negative/DOG-1-negative GISTs.

The cadherin-catenin complex in laryngeal squamous cell carcinoma.

Abnormal Wnt signaling and impaired cell-cell adhesion due to abnormal E-cadherin and ß-catenin function have been implicated in many cancers, but have not been fully explored in laryngeal squamous cell carcinoma. In this study, ß-catenin cellular location and E-cadherin expression levels were analyzed in 16 laryngeal squamous cell carcinomas (LSCCs) (9 glottic and 7 supraglottic) and 11 samples of non-tumoral inflammatory larynx tissue, using immunohistochemical methods. All non-tumoral tissues showed equally strong membranous expression of ß-catenin, while cytoplasmic expression was found in only 3 of the 11 samples. By contrast, whereas 8/9 glottic LSCCs exhibited only membranous expression of ß-catenin, 6/7 supraglottic LSCCs displayed both membranous and cytoplasmic expression (p = 0.003). Strong E-cadherin staining was observed in 9/11 non-tumoral tissues and 7/9 glottic LSCCs, whereas 4/7 supraglottic LSCCs exhibited weak expression. Reduced membrane expression of E-cadherin and cytoplasmic retention of ß-catenin in supraglottic LSCC seems to be related with more aggressive biological behavior which has been described in clinical studies. Further research is required to clarify the involvement of ß-catenin in the mechanism associated with malignant transformation in laryngeal tissues.

[Cervical myositis ossificans. A case report]. / Miositis osificante cervical. A propósito de un caso clínico.

This is the case of a middle-aged male with a slow growing lateral cervcal painful tumour, and without previous history of local trauma. Radiological testing reveals an ossifying soft tissue lesion without any osseous compromise. The lesion is completely resected, and the histological result is of ossifying myositis. It is an osseous tumour non neoplastic that originates within muscle and in particular the flexors of the inferior extremities and thigs or in the soft tissues. The incidence within the head and neck region is low (20%). There is an hereditary progressive form, Munchmeyer's disease, and another circumscribed, which can be subdivided in traumatic or atraumatic.

Miositis osificante cervical. A propósito de un caso clínico / Cervical myositis ossificans. A case report

Se presenta el caso clínico de un paciente varón de mediana edad con una tumoración laterocervical dolorosa y de crecimiento lento, y sin antecedentes de traumatismos sobre la zona. Las pruebas de imagen constatan que se trata de una lesión de partes blandas osificada, descartándose afectación ósea. Se practica la exéresis quirúrgica completa y el resultado histológico es de miositis osificante (MO). Se trata de una neoformación ósea no neoplásica que se origina en los músculos y en particular los flexores de los miembros superiores y muslos o en el tejido celular subcutáneo. La incidencia en la región de la cabeza y cuello es baja (20%). Existe una forma progresiva y hereditaria, la enfermedad de Munchmeyer, y otra circunscrita, que se subclasifica en traumática o atraumática

This is the case of a middle-aged male with a slow growing lateral cervcal painful tumour, and without previous history of local trauma. Radiological testing reveals an ossifying soft tissue lesion without any osseous compromise. The lesion is completely resected, and the histological result is of ossifying myositis. It is an osseous tumour non neoplastic that originates within muscle and in particular the flexors of the inferior extremities and thigs or in the soft tissues. The incidence within the head and neck region is low (20%). There is an hereditary progressive form, Munchmeyer's disease, and another circumscribed, which can be subdivided in traumatic or atraumatic

[High grade transitional cell carcinoma with signet ring cell pattern. Case report]. / Carcinoma urotelial de alto grado vesical con patrón de células "en anillo de sello". A propósito de un caso.

OBJECTIVE: The presence of signet ring cells within a transitional cell carcinoma is a factor of poor prognosis. METHODS: We report the case of a 69-year-old male patient with the diagnosis of high grade transitional cell carcinoma with signet ring cell pattern, the presence of which could have been foreseen in serial cytological tests performed after the clinical debut. RESULTS: To achieve such a diagnosis, it is necessary to rule out the possibility of metastasis or infiltration of a neoplasia from other organ. CONCLUSION: Both the presence of an in situ neoplasia or the coexistence of infiltrative transitional cell tumor can help to determine primary origin of these neoplasias.

Diagnóstico inicial de leishmaniasis en una biopsia endoscópica digestiva. A propósito de 2 casos / Initial diagnosis of leishmaniasis in endoscopic gastrointestinal biopsy. Apropos of 2 cases

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Carcinoma urotelial de alto grado vesical con patrón de células "en anillo de sello". A propósito de un caso / No disponible

OBJETIVO: La presencia de células "en anillo de sello" constituye un factor de mal pronóstico en aquellas neoplasias uroteliales, generalmente de alto grado, que las presentan. MÉTODO: Presentamos el caso de un varón de 69 años diagnosticado de carcinoma urotelial de alto grado con patrón de células “en anillo de sello” cuyo diagnóstico pudo ser intuido en los estudios citológicos seriados que se realizaron tras el debut clínico. RESULTADOS: Para la realización de tal diagnóstico es preciso descartar la posibilidad de que estemos ante la metástasis o infiltración de una neoplasia de otra localización. CONCLUSIONES: La presencia de neoplasia "in situ" o bien la coexistencia de un componente urotelial infiltrante ayudan a determinar el origen primario de tales neoplasias (AU)

OBJECTIVE: The presence of signet ring cells within a transitional cell carcinoma is a factor of poor prognosis. METHODS: We report the case of a 69-year-old male patient with the diagnosis of high grade transitional cell carcinoma with signet ring cell pattern, the presence of which could have been foreseen in serial cytological tests performed after the clinical debut. RESULTS: To achieve such a diagnosis, it is necessary to rule out the possibility of metastasis or infiltration of a neoplasia from other organ. CONCLUSION: Both the presence of an in situ neoplasia or the coexistence of infiltrative transitional cell tumor can help to determine primary origin of these neoplasias (AU)

[Multifocal motor neuropathy with conduction blocks and prurigo nodularis. A paraneoplastic syndrome in a patient with non-Hodgkin B-cell lymphoma?]. / Neuropatía multifocal motora con bloqueos de conducción y prurigo nodular. ¿Un síndrome paraneoplásico en un paciente con un linfoma no Hodgkin de tipo B?

Multifocal motor neuropathy with conduction blocks (MMNCB) is a peripheral demyelinating neuropathy. The etiology of this disease is unknown, but an autoimmune origin is postulated. Prurigo nodularis (PN), a chronic dermatosis also having an unknown etiology and many peripheral neuropathies of different nature are associated to hematological tumors. We have found no cases in the literature in which MMNCB was presented as a paraneoplastic syndrome of a non-Hodgkin B-cell type lymphoma (NHL-B). We present the case of a 67 year old man who simultaneously developed PN and MMNCB in upper limbs and who was diagnosed of a NHL-B 19 months later. We raise the hypothesis that both prurigo and neuropathy are a paraneoplastic syndrome for lymphoma with a possible common autoimmune pathogenic mechanism.

Cutaneous pseudolymphoma in association with molluscum contagiosum in an elderly patient.

BACKGROUND: Molluscum contagiosum (MC) is a common cutaneous infection, which has been reported in association with cutaneous pseudolymphoma in few cases. METHODS: A 72-year-old woman with a nodule arising on the external canthus was reviewed. The lesion was surgically removed, and the histopathological study demonstrated an epidermal invagination filled by molluscum bodies and a diffuse infiltrate comprising atypical lymphocytes. RESULTS: Immunohistochemical stains disclosed predominance of T cells with positive CD30 labeling. Polymerase chain reaction failed to demonstrate clonal rearrangement of the T-cell receptor. CONCLUSION: After ruling out systemic involvement, the patient was followed up for 2 years with no evidence of recurrence. We report this case to the best of our knowledge and discuss the literature about atypical clinical and histological presentations of MC.

Prognostic value of DNA flow cytometry in sympathoadrenal paragangliomas.

OBJECTIVE: To determine whether ploidy patterns are related to prognosis in sympathoadrenal paragangliomas (SAP) using flow cytometry. STUDY DESIGN: DNA flow cytometric analysis of formalin-fixed, paraffin-embedded tumor samples from 36 patients with SAP was performed. Eight cases fulfilled at least one of the following malignancy criteria: (1) extensive invasion of adjacent structures (5 cases), (2) local recurrence (3 cases), or (3) metastases (4 cases). RESULTS: Of the 36 tumors, 22 (61%) showed nondiploid patterns (12 aneuploid, 10 tetraploid). All diploid tumors were benign, while all malignant cases showed nondiploid patterns (P = .0131). The differences between diploid and aneuploid tumors and between diploid and tetraploid tumors, with regard to the malignancy of the disease, were statistically significant (P = .03311 and .01976, respectively). Only one malignant tumor had a DNA index < 1.75 (P = .00259). CONCLUSION: Anomalous DNA ploidy patterns are frequent in SAP, without necessarily implying malignancy. However, diploid DNA content may be a marker of a good prognosis. The likelihood of malignancy is greater in the tetraploid and peritetraploid range.

Extramuscular soft tissue myxoma of the lateral neck.

Myxomas are rare benign connective tissue tumours of unclear histogenesis. In this case a lateral neck tumour initially behaved, both clinically and radiographically as a lipoma, and was therefore managed conservatively. Subsequently the lesion caused pressure symptoms and therefore a surgical approach was taken with subsequent histology confirming a myxoma. Only five cases of soft tissue myxoma of the lateral neck have been reported in the English literature of which two were extramuscular. This is the largest reported myxoma of the head and neck region and was treated with simple enucleation. There has been no evidence of recurrence five years after surgery.