Immunohistochemical staining with CD117 and PGP9.5 of excised vestibular tissue from patients with neuroproliferative vestibulodynia.

BACKGROUND: Neuroproliferative vestibulodynia (NPV), a provoked genital pain characterized by severe allodynia and hyperalgesia, is confirmed in excised vestibular tissue by immunohistochemical staining (>8 CD117-positive immunostained cells/100× microscopic field) rather than by hematoxylin and eosin staining. AIM: In this study we sought to assess immunostaining of tissue samples obtained during vestibulectomy surgery and to correlate results with patient outcomes. METHODS: Patients (n = 65) meeting criteria for NPV who underwent vestibulectomy during the period from June 2019 through December 2022 formed the study cohort. We performed assessment of pathology of vestibular tissues by use of immunohistochemical staining, including quantitation of mast cells by CD117 (mast cell marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments. OUTCOMES: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement. RESULTS: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments. OUTCOMES: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement. RESULTS: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the median area of CD117 immunostaining was similar in both regions (0.69% and 0.73%). The median area of PGP9.5 immunostaining was 0.47% and 0.31% in these same regions. Pain scores determined with cotton-tipped swab testing were nominally higher in lifelong vs acquired NPV patients, reaching statistical significance in the 1:00-11:00 o'clock region (P < .001). The median score for the McGill Pain Questionnaire affective subscale dimension was also significantly higher in lifelong vs acquired NPV patients (P = .011). No correlations were observed between hematoxylin and eosin results and density of mast cells or neuronal markers. Of note, 63% of the patient cohort reported having additional conditions associated with aberrant mast cell activity. CLINICAL IMPLICATIONS: The pathology of NPV is primarily localized to the vestibular epithelial basement membrane and subepithelial stroma with no visible vulvoscopic findings, making clinical diagnosis challenging. STRENGTHS AND LIMITATIONS: Strengths of this study include the large number of tissues examined with what is to our knowledge the first-ever assessment of the 12:00 vestibule. Major limitations are specimens from a single timepoint within the disease state and lack of control tissues. CONCLUSIONS: Performing immunohistochemical staining of excised vestibular tissue with CD117 and PGP9.5 led to histometric confirmation of NPV, indications that NPV is a field disease involving all vestibular regions, validation for patients whose pain had been ignored and who had experienced negative psychosocial impact, and appreciation that such staining can advance knowledge.

Morphological and immunohistochemical characteristics of diffuse seminoma in horses: A case report.

The present study describes the morphological and immunohistochemical characteristics of a case of diffuse seminoma in a 16-year-old male mixed-breed horse. According to the owner, the animal's left testicle had been gradually increasing in size over a period of 2 months. On palpation, the testicle had a firm consistency, with no sensitivity to digital pressure, was adhered to the scrotum and measuring 16 cm × 8 cm. In the ultrasound examination, it presented a heterogeneous texture and areas of hypoechogenic echogenicity without visualization of the mediastinum. Therefore, the bilateral orchiectomy was performed. After the surgical procedure, it was found that the affected testicle presented a firm mass measuring 9 cm × 7 cm × 3.5 cm. Histologically, a multilobulated, non-encapsulated and invasive tumour mass was found, which replaced the seminiferous tubules, consisting of polygonal cells arranged in a mantle that varied from cohesive to loosely cohesive, supported by a scarce fibrous stroma. In the immunohistochemical examination, the neoplastic cells showed positive immunolabelling for OCT4 and C-KIT. In this report, the physical examination combined with the ultrasonographic examination were fundamental to the therapeutic management of the case, and the final diagnosis was made after histopathological and immunohistochemical tests.

BRAFV600E and KIT immunoexpression in early-stage melanoma

Abstract: Melanoma is widely known as the most lethal skin cancer. Specific tumor-related mortality can be significantly reduced if diagnosis and treatment are properly performed during initial phases of the disease. The current search for biomarkers in early-stage melanomas is a high-priority challenge for physicians and researchers. We aimed to assess the immunoexpression of BRAFV600E and KIT in a case series consisting of 44 early-stage melanomas. Formalin-fixed paraffin-embedded samples were systematically evaluated using a semi-quantitative method based on scores of percentage and intensity for immunostained tumor cells. We observed significant concordance between BRAFV600E and KIT immunoexpression in thin invasive melanomas. Our findings corroborate previous evidence showing abnormal expression of proteins associated with MAPK intracellular signaling pathway in early-stage melanomas.

Gastrointestinal stromal tumours: an actualized overview

The gastrointestinal stromal tumour (GISTs), the most common mesenchymal neoplasm in the gastrointestinal tract, has been the subject of great interest in recent years in terms of prognosis, diagnosis and treatment. Its etiology is linked to the mutation of c-KIT and PDGFRA genes, although between 5 and 15% show no signs of such mutations. It is still diagnosed using immunohistochemical staining. The first line of treatment continues to be surgery, although advances in the molecular biology of GISTs are facilitating the development of new treatment strategies. Those that act by regulating tyrosine kinase activity are of particular interest. Drugs such as imatinib and sunitinib have improved the prognosis of these patients, although the development of resistance constitutes one of the main limitations of the treatment. The aim of this review is to present an up-to-date overview of the main etiopathogenic, diagnostic and therapeutic aspects of these tumours

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Evaluation of the relationship between c-Kit expression and mean platelet volume in classic Kaposi's sarcoma

Abstract: Background: c-Kit is a proto-oncogene that encodes tyrosine kinase receptor (CD117). Mean platelet volume (MPV) is a useful marker, providing information on platelet function and diameter. Objective: To investigate c-Kit expression and intensity in patients with Kaposi's sarcoma (KS) and to investigate the relation between Ki-67 proliferation and MPV. Methods: A total of 32 patients, diagnosed with classic cutaneous KS, were included in this study. We reevaluated the histopathological reports with the preparations, confirmed the diagnosis and then determined the patients' histopathological stages. c-Kit expression and Ki-67 proliferation were investigated immunohistochemically in KS cases, while MPV in all cases was checked. Results: Although c-Kit expression was detected in 22 cases (68.8%), it was not expressed in 10 cases (31.2%). We detected 8 cases with + (25%), 6 with ++ (18.8%) and 8 with +++ (25%). Ki-67 expression was 5.0% (min-max 1.0-20.0). Relapse was observed in 5 cases (15.6%) out of 32. There was positive correlation between c-Kit expression and MPV (rs=0.598, p<0.001), and between c-Kit intensity and MPV (rs=0.588, p<0.001). Conclusion: c-Kit is highly positive in KS. c-Kit positivity indicates a high risk of tumor growth, invasion and relapse. Furthermore, c-Kit expression stimulates megakaryocytes to release young and large thrombocytes into the periphery. Thus, high MPV, c-Kit expression and immunostaining intensity indicate high invasion and relapse in KS subjects.

C -kit en tumores estromales gastrointestinales y neoplasias asociadas: estudio en población con aislamiento genético / C-KIT in gastrointestinal stromal tumors and associated malignancies: A Study in a population with genetic isolation

INTRODUCCIÓN: Los tumores estromales gastrointestinales (GIST) son los tumores mesenquimales más frecuentes del tracto gastrointestinal. Han surgido numerosas publicaciones de GIST asociados con otras neoplasias. OBJETIVOS: El objetivo de este estudio fue investigar esta posible asociación en una población aislada genéticamente. MÉTODOS: Se realizó un estudio retrospectivo de pacientes con GIST en nuestro centro entre los años 2002-2009. Se compararon datos epidemiológicos, patológicos y familiares de pacientes con GIST sin neoplasias asociadas (grupo A) frente a pacientes con GIST y neoplasias asociadas (grupo B). Se investigó un posible mecanismo genético común entre GIST y las neoplasias asociadas mediante la detección, en todos los tumores, por el marcador inmunohistoquímico CD117. RESULTADOS: Se hallaron 22 pacientes con GIST, 10 del grupo A (45%) y 12 del grupo B (55%). En el grupo B, el tumor asociado fue maligno en 6 pacientes (50%) y benigno en otros 6 (50%). De 22 pacientes con GIST, 8 (36%) presentaron antecedentes familiares de neoplasia maligna. De estos 8 pacientes, 7 eran (87,5%) del grupo B (p = 0,03) y en 3 (37,5%) coincidieron el tipo anatomopatológico de neoplasia padecida por el paciente y su familiar. No hubo GIST en ningún familiar. Todos los GIST mostraron positividad para el CD117, mientras que las neoplasias asociadas fueron negativas para este marcador. CONCLUSIONES: No se ha demostrado positividad inmunohistoquímica para CD117 en las neoplasias asociadas. Dadas las especiales características de la población a estudio, la relación entre GIST y las neoplasias asociadas posiblemente sea casual

INTRODUCTION: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Numerous studies have reported the association between GIST and other neoplasms. OBJECTIVES: The aim of this study was to investigate the possible association between GIST and other tumors in a genetically isolated population. METHODS: A retrospective study was conducted of patients with GIST between 2002 and 2009 at our center. Epidemiological, pathological and family data in patients with GIST alone (group A) were compared with those in patients with GIST associated with other neoplasms (group B). A possible common genetic mechanism was investigated between GIST and associated malignancies by testing the detection of the immunohistochemical marker, CD117, in all tumors. RESULTS: Twenty-two patients with GIST were identified, 10 in group A (45%) and 12 in group B (55%). In group B, the associated tumor was malignant in 6 patients (50%) and benign in another 6 (50%). Of the 22 patients with GIST, 8 (36%) had a family history of malignancies. Of these 8 patients, 7 (87.5%) were in group B (p = 0.03) and 3 (37.5%) showed the same pathological type of neoplasm as their relatives. All GIST were positive for CD117 whereas associated malignancies were negative for this marker. CONCLUSION: We did not find immunohistochemical positivity for CD117 in malignancies associated with GIST. Given the special characteristics of the study population, the association between GIST and associated malignancies may be incidental

Tumores del estroma gastrointestinal (GIST): serie del Hospital Central de la Defensa Gómez Ulla / Gastrointestinal stromal tumors (GIST): series of the Defense Central Hospital «Gómez Ulla»

Objetivo: Los tumores del estroma gastrointestinal (GIST) se han diferenciado hace poco más de una década de los tumores de músculo liso y de origen neural gracias a métodos de identificación inmunohistoquímica (CD117). Al mismo tiempo, la introducción del Mesylato de Imatinib, fármaco empleado en el tratamiento de la leucemia mieloide crónica (LMC), ha mejorado la expectativa de vida, no sólo en GIST irresecables o metastáticos, sino también para aquéllos de intermedio o alto grado de malignidad como terapia adyuvante e incluso se plantea como tratamiento neoadyuvante. El objetivo de esta comunicación es estudiar los GIST diagnosticados e intervenidos quirúrgicamente en el Servicio de Cirugía General y del Aparato Digestivo del Hospital Central de la Defensa «Gómez Ulla» (Madrid) en un periodo de 9 años y realizar una revisión de la literatura enfocada fundamentalmente a los avances en el tratamiento. Material y métodos: Estudio retrospectivo observacional de los pacientes diagnosticados de GIST e intervenidos quirúrgicamente en nuestro Servicio de 2003 a 2012. Se estudia el motivo de consulta inicial, la localización, el grado histológico y el tipo de intervención quirúrgica realizado. Resultados: Se encontraron 11 pacientes entre Noviembre de 2003 y Abril de 2012, todos hombres. La edad media fue de 65’17 años (rango, 53-84). Hay que destacar que en 8 casos (72’7 %) el hallazgo fue incidental, sin ninguna sintomatología previa. La localización más frecuente fue el estómago en 6 casos (54’5%), y en el intestino delgado en 5 (45’5%). En cuanto al riesgo de malignidad, 5 casos (45’5%) fueron de bajo grado, 4 (36’4%) de grado intermedio, 1 (9%) de muy bajo grado y 1 (9’1%) de alto grado de malignidad. La técnica quirúrgica empleada fue la gastrectomía parcial en 6 casos (54’5%) seguida de la resección intestinal segmentaria en 5 casos (45’5%). Conclusiones: La incidencia anual de tumores GIST intervenidos en nuestro servicio es de 1 nuevo caso/año. Las localizaciones han sido el estómago y el intestino delgado. Todos los tumores de grado bajo se han beneficiado de cirugía, con tasas de supervivencia excelentes sin tratamiento adicional. Hasta conocer los resultados de los estudios en curso sobre la terapia neoadyuvante con Imatinib, parece que en tumores GIST operables se debería realizar primero cirugía y valorar, según los hallazgos intraoperatorios, la adyuvancia y, en casos de tumores solo parcialmente resecables o metastásicos, la neoadyuvancia (AU)

Introduction: Since a little more than a decade the gastrointestinal stromal tumors (GIST) have been differentiated from the tumors of smooth muscle and of neural origin by immunohistochemical methods (CD117). Simultaneously the introduction of imatinib mesylate, utilized in the treatment of chronic myeloid leukemia (CML), has improved the life expectancy, not only in unresectable or metastatic GIST, but also in those of high or intermediate degree of malignancy as adjuvant therapy or even as neoadjuvant therapy. Objective: To study the GIST diagnosed and operated in the Department of General and Digestive Surgery of the Defense Central Hospital in 9 years and to review the literature mainly focused on therapeutic advances. Material and Methods: Retrospective observational study of the GIST patients diagnosed and operated in our Department from 2003 to 2012. The reason for the initial consultation, localization, histologic grade and type of surgery performed are analyzed. Results: Eleven patients, all male, were diagnosed between November 2003 and April 2012. Average age was 65.17 (range 53-84). It must be emphasized that in 8 cases (72.7 %) the finding was incidental, without any previous symptoms. The most frequent localization was the stomach in 6 cases (54.5%) and the small intestine in 5 (45.5%). As far as the malignancy risk is concerned 5 cases (45.5%) were low grade, 4 cases (36.4%) intermediate grade, 1 case (9%) very low grade and 1 case (9.1%) high malignancy grade. The surgical technique utilized was partial gastrectomy in 6 cases (54.5%) followed by segmental intestinal resection in 5 cases (45.5%). Conclusions: The annual incidence of GIST tumors operated in our Department is 1 new case / year. The localizations were in the stomach and small intestine. All low grade tumors have benefited from surgery with excellent survival rates without additional treatment. Until the results of the ongoing studies about neoadjuvant therapy with imatinib are known, it seems that operable GIST tumors should first undergo surgery and assess, in accordance with intraoperative findings, the adjuvancy and for only partially resectable o metastatic tumors, the neoadjuvancy (AU)

Gastrointestinal stromal tumors (GISTs): SEAP-SEOM consensus on pathologic and molecular diagnosis

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract, with an incidence of 1.1 cases/100,000 inhabitants/year. A group of experts from the Spanish Society of Pathology and the Spanish Society of Oncology met to discuss a brief update on GISTs and agree on aspects relating to the pathological and molecular diagnosis of these tumors. GISTs are generally solitary, well-circumscribed lesions of variable size (< 10 mm-35 cm) that may present with intra- or extra-luminal parietal growth or a mixed-type (hourglass) growth pattern. Histologically, they are unencapsulated neoplasms displaying expansive growth and spindle-shaped (70%), epithelioid (20%), or mixed cellularity (10%). Mitotic activity is generally moderate or low and should be evaluated only in areas with high cellularity or higher mitotic frequency. The great majority of GISTs harbour mutually exclusive activating mutations in genes coding for the type III receptor tyrosine kinases KIT and PDGFRA; less commonly, GISTs have also been reported to display mutations elsewhere, including BRAF and NF1 and SDH-complex genes. The method most widely used to detect KIT and PDGFRA mutations is amplification of the exons involved by polymerase chain reaction followed by direct sequencing (Sanger method) of these amplification products. Molecular analyses should always specify the type of analysis performed, the region or mutations evaluated, and the sensitivity of the detection method employed (AU)

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Schwannoma gástrico: descripción de un caso con presencia de células gigantes multinucleadas tipo osteoclásticas / Gastric schwannoma containing osteoclastic-type multinucleated giant cells: a case report

Describimos el caso de un schwannoma gástrico en un paciente de 64 años que clínica y radiológicamente simulaba un tumor del estroma gastrointestinal. Se realizó una gastrectomía parcial y se encontró un tumor de 4cm de diámetro en la pared muscular, con mucosa íntegra. Microscópicamente, presentó un patrón de crecimiento fusocelular con notable presencia de acúmulos linfoides en la periferia e intralesionales. Se observaron escasas formaciones similares a cuerpos de Verocay abortivas. Además, se observaron células gigantes multinucleadas tipo osteoclástico dispersas aleatoriamente. Las células fusiformes mostraron atipia leve focal. No se identificaron figuras de mitosis. Inmunohistoquímicamente, las células fusiformes se tiñeron intensa y difusamente con S-100 y GFAP, mientras que las tinciones de CD34, CD117 y DOG1 fueron negativas. Las células multinucleadas fueron CD68 positivas. Describimos brevemente su diagnóstico diferencial (AU)

We describe a gastric schwannoma in a 64 year-old man which clinical and radiologically simulated a gastrointestinal stromal tumor. A partial gastrectomy was performed showing an intramuscular wall tumour measuring 4cm in diameter with unaffected mucosa. Microscopically the tumour presented a spindle cell pattern showing cuffing of lymphoid aggregates in the periphery and interstitium. Scattered abortive Verocay-like formations were present. In addition, some multinucleated osteoclastic-type cells were evenly dispersed. The spindle cells showed focal nuclear atypia. No mitotic figures were recorded. Immunohistochemically, the fusiform cells were strongly and diffusely positive for S-100 and GFAP, whereas stains for CD34, CD117 and DOG1 were negative. Multinucleated cells were CD68 positive. We briefly discuss the differential diagnosis (AU)

Tumor del estroma gastrointestinal (TEGI): un estudio de su frecuencia y perfil de inmunohistoquímica / Gastrointestinal stromal tumors: analysis of 51 cases, immunohistochemical expression

Background: Gastrointestinal Stromal Tumors (GIST) have a mesenchymal origin and correspond to 1 percent of all gastrointestinal tumors. They have a benign behavior in approximately 75 percent of cases. They express CD117, CD34, smooth muscle actin, S-100 and desmin, markers that are useful in the differential diagnosis of smooth muscle tumors and those of neurogenic origin. Aim: To report our experience with GIST. Material and Methods: A retrospective, observational study. The pathology reports of GIST in the period 2004-2008 were reviewed. Immunohistochemical expression, pathological grade, mitotic index and histological patterns were reviewed. The medical records of patients were reviewed to obtain age and gender, location, size and presence of metastases. Results: A total of 51 GIST were identified, coming from 21 males and 30 females. Nineteen tumors were located in the small bowel, 18 in the stomach, four in the rectum, two in the colon and in five, the location was not specified. In 28 cases, the pathological pattern was spindle cell, in 12 mixed, in six epithelioid, in three pleomorphic, in one signet ring cell and giant cell in one. Forty nine percent of tumors were of high grade. Metastases were found in the liver in two cases, in the omentum in two and in the spleen, kidney, retroperitoneum and pancreas, in one case each. Two had lymph node involvement. Conclusions: GIST tumor corresponded to a 0.12 percent of all pathology reports during the study period. Most tumors in this series were of high grade.

Introducción: Los Tumores del Estroma Gastrointestinal (TEGI) son de origen mesenquimal comprendiendo el 1 por ciento de todos los tumores GI. Son benignos del 70 a 80 por ciento. Expresan CD117, CD34, actina de músculo liso, S-100 y desmina, marcadores útiles en el diagnóstico diferencial de tumores de músculo liso y tumores de origen neurogénico. Material y Método: Es un estudio retrospectivo y descriptivo. Se revisaron los reportes en el período 2004-2008 registrados como TEGI, valorando la expresión Inmunohistoquímica, grado histológico, índice mitótico, y patrones histológicos. Del reporte histológico se obtuvo la edad y sexo del paciente, localización, tamaño y metástasis. Resultados: Se recolectaron 51 casos corroborados como TEGI. Encontrando una prevalencia del sexo femenino (30) y una edad media de 52 años. Las localizaciones fueron: Intestino delgado (19), estómago (18), no especificado (5), recto (4), colon (2), retroperitoneo (2), no encontramos en esófago. Los patrones encontrados fueron el fusocelular (28), mixto (12), epitelioide (6), pleomórfico (3), células en anillo de sello (1), células gigantes (1). La mayoría (49 por ciento) fue de alto grado, presentando metástasis a hígado (2), ganglios (2), epiplón (2), bazo (1), riñón (1), retroperitoneo (1) y páncreas (1). Discusión: Se realizaron un total de 41.035 estudios histopatológicos, de los cuales 51 casos corresponden a LEGI, esto equivale al 0,12 por ciento. Encontramos tumores en los que su morfología, tamaño e índice mitótico fueron de bajo grado y presentaron metástasis y recidivas al momento del diagnóstico. Veinticinco casos fueron de alto grado (49 por ciento), lo cual es mayor a lo reportado por la literatura 20-30 por ciento, probablemente porque este es un hospital de concentración y generalmente los pacientes acuden a atención médica en una etapa avanzada de la enfermedad.

Recomendaciones para la determinación de biomarcadores en el melanoma metastásico. Consenso Nacional de la Sociedad Española de Anatomía Patológica y de la Sociedad Española de Oncología Médica / Guidelines for biomarker testing in metastatic melanoma. A National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology

Este documento de consenso nace como una iniciativa conjunta de la Sociedad Española de Anatomía Patológica (SEAP) y de la Sociedad Española de Oncología Médica (SEOM) y propone recomendaciones diagnósticas y terapéuticas para el manejo del paciente con melanoma avanzado o metastásico basadas en la evidencia científica que existe en la actualidad sobre el uso de biomarcadores. Por tanto, este documento supone una oportunidad para mejorar la eficiencia de la actividad asistencial y la utilización de recursos, lo que redundará en un beneficio para estos pacientes. Con los datos disponibles hasta el momento, este grupo de expertos recomienda que en los pacientes con melanoma metastásico se analice de forma rutinaria el estado mutacional de BRAF, ya que su resultado condiciona el manejo terapéutico posterior de estos pacientes. El análisis de alteraciones genéticas de KIT puede ser razonable en pacientes con tumores primarios de localización acral, en mucosas o en piel crónicamente expuesta al sol, en situación avanzada, pero no en pacientes con otro tipo de melanomas. Este panel no considera actualmente indicado como práctica clínica habitual el estudio de otras alteraciones genéticas, como pueden ser el estado mutacional de NRAS en pacientes no portadores de mutaciones de BRAF, el análisis mutacional de GNAQ/GNA11 o las alteraciones genéticas de PTEN, ya que hoy por hoy sus resultados no influyen en la planificación del tratamiento de estos pacientes. Otros aspectos importantes que se desarrollan en este documento son los requisitos organizativos y los controles de calidad necesarios para la determinación adecuada de estos biomarcadores, y las implicaciones legales que se deben tener en cuenta (AU)

This consensus statement is a joint initiative of the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM). Based on current scientific evidence of biomarker use, it makes diagnostic and therapeutic recommendations for the management of patients with advanced or metastatic melanoma. Its aim is to improve both healthcare efficiency and the use of resources in benefit of the patients. Based on the most recent available data, the group of experts recommends testing patients with metastatic melanoma routinely for BRAF mutation status, as the result affects their subsequent therapeutic management. Analysis of genetic alterations in KIT may be practical in patients with primary tumours in acral or mucosal sites or on skin subjected to chronic sun exposure, in an advanced condition; however, this does not apply to patients with other types of melanomas. This expert panel believes that testing for other genetic alterations, such as NRAS mutation status in patients not carrying BRAF mutations, GNAQ/GNA11 mutational analysis or genetic alterations in PTEN, is not currently indicated as a routine clinical practice because, at the present time, the results do not influence treatment. The organizational requirements and quality controls needed for the correct testing of biomarkers as well as the legal implications involved are also considered (AU)

Is the positive c-kit immunostaining associated with the presence of cells analogous to the intersticial cells of Cajal in the ciliary muscle? / A imunomarcação positiva para c-kit está associada com a presença de células análogas às intersticiais de Cajal no músculo ciliar?

PURPOSE: Interstitial cells of Cajal were identified in the gastrointestinal tract of several species, with close relation to the enteric nervous system. Since it was recognized that interstitial cells of Cajal express the gene product of c-kit, we performed immunohistochemistry for c-kit protein in ciliary muscle specimens of monkeys' eyes. METHODS: Eight eyes from four adult male new world monkeys (Cebus apella) were studied. After blocking endogenous peroxidase activity and nonspecific protein binding, 1:100 dilution of mouse monoclonal antibody against c-kit human oncoprotein was applied to tissues. Antigen-antibody reaction was visualized using the avidin-biotinylated horseradish peroxidase complex in each slide. RESULTS: We observed some groups of fusiform c-kit expressing cells located amongst muscle bundles of the ciliary muscle. Other pigment cells and mast cells were also observed. CONCLUSION: C-kit expressing cells observed in the ciliary muscle of Cebus apella, showed no similarity to melanocytes or mast cells and they could be associated with their gastrointestinal interstitial cells of Cajal counterpart.

OBJETIVO: As células intersticiais de Cajal estão presentes no trato gastrintestinal de diversas espécies animais, em íntima relação com o sistema nervoso entérico. Uma vez que as células intersticiais de Cajal expressam o produto do gene c-kit, realizou-se um ensaio imuno-histoquímico a fim de se verificar a marcação da proteína c-kit no músculo ciliar de amostras de olhos de macacos. MÉTODOS: Oito olhos de quatro macacos do novo mundo (Cebus apella) foram estudados. Após bloqueio da peroxidase endógena e de ligação protéica não específica, os tecidos receberam aplicação de anticorpos de camundongos antioncoproteína c-kit humana (1:100). A reação antígeno-anticorpo foi verificada através da aplicação do complexo avidina-biotinilada-peroxidase em cada lâmina. RESULTADOS: Foram observados grupos de células que expressam c-kit, localizadas entre as fibras do músculo ciliar. Mastócitos e outras células pigmentadas também foram observadas. CONCLUSÃO: Algumas células que expressam c-kit, observadas no músculo ciliar de Cebus apella, não mostraram similaridade com mastócitos ou melanócitos e podem ser classificadas como análogas das células intersticiais de Cajal gastrintestinais.

Adenocarcinoma gástrico primario concomitante con tumor estromal gastrointestinal: Reporte de un caso y revisión de literatura / Concomitant presence of a gastric adenocarcinoma and gastrointestinal stromal tumor: Report of one case

The concomitant presence of a primary gastric adenocarcinoma and a gastrointestinal stromal tumor in the stomach is uncommon. We report a 68-year-old male with an advanced gastric adenocarcinoma. During gastrectomy, a nodular intramural lesion was found. The pathological study, revealed a gastrointestinal stromal tumor, positive form CD117. After six months of follow up, there is no evidence of recurrence of either tumor.

CD34-positive cells and their subpopulations characterized by flow cytometry analyses on the bone marrow of healthy allogenic donors / Células CD34-positivas e suas subpopulações caracterizadas por análise de citometria de fluxo em doadores para transplante alogênico de medula óssea

CONTEXT AND OBJECTIVE: Counting and separating hematopoietic stem cells from different sources has importance for research and clinical assays. Our aims here were to characterize and quantify hematopoietic cell populations in marrow donors and to evaluate CD34 expression and relate this to engraftment. DESIGN AND SETTING: Cross-sectional study on hematopoietic stem cell assays, using flow cytometry on donor bone marrow samples, for allogenic transplantation patients at two hospitals in São Paulo. METHODS: Immunophenotyping of marrow cells was performed in accordance with positive findings of CD34FITC, CD117PE, CD38PE, CD7FITC, CD33PE, CD10FITC, CD19PE, CD14FITC, CD13PE, CD11cPE, CD15FITIC, CD22PE, CD61FITC and CD56PE monoclonal antibodies in CD45PerCP+ cells, searching for differentiation and maturation regions. CD34+ sorting cells were analyzed for CD38 and CD117. Rh-123 retention was done before and after sorting. Antigen expression and CD34+ cells were correlated with engraftment. RESULTS: In region R1, 0.1 percent to 2.8 percent of cells were CD34+/CD45+ and 1.1 percent, CD34+/CD45-. The main coexpressions of CD45+ cells were CD38, CD22, CD19 and CD56 in R2 and CD33, CD11c, CD14, CD15 and CD61 in R3 and R4. After sorting, 2.2x10(6) CD34+ cells were equivalent to 4.9 percent of total cells. Coexpression of CD34+/CD38+ and CD34+/CD117+ occurred in 94.9 percent and 82 percent of events, respectively. There was a positive relationship between CD34+ cells and engraftment. More than 80 percent of marrow cells expressed high Rh-123. CD34+ cell sorting showed that cells in regions of more differentiated lineages retained Rh-123 more intensively than in primitive lineage regions. CONCLUSION: We advocate that true stem cells are CD34+/CD45-/CD38-/low-Rh-123 accumulations.

CONTEXTO E OBJETIVO: A contagem e separação de células-tronco hematopoéticas de diferentes fontes tem importância para ensaios clínicos e pesquisa basica. Nosso objetivo foi caracterizar e quantificar as populacões de células hematopoéticas, bem como avaliar a expressão do antígeno CD34 em populações mais primitivas e correlacioná-las com a enxertia nos doadores de medula óssea para transplante alogênico. TIPO DE ESTUDO E LOCAL: Estudo transversal no qual a diferenciação e a seleção de células-tronco hematopoéticas foram realizadas em amostras de medula óssea de doadores de pacientes submetidos a transplante alogênico nos Hospitais São Paulo e Santa Marcelina, São Paulo, Brasil. MÉTODOS: Imunofenotipagem de células mononucleares de medula óssea foi feita na população de células CD45PerCP+ com os seguintes anticorpos: CD34FITC, CD117PE, CD38PE, CD7FITC, CD33PE, CD10FITC, CD19PE, CD14FITC, CD13PE, CD11cPE, CD15FITC, CD22PE, CD61FITC e CD56PE. Após a definição de regiões de células positivas ao CD34, estas células foram selecionadas e analisadas para a co-expressão do CD38 e CD117. Células mononucleares totais de medula óssea e aquelas obtidas após a seleção foram testadas para a retenção de Rh-123. O teste de Friedman e o coeficiente de Sperman foram utilizados para comparar as expressões e correlacionar a contagem de células CD34+ com a enxertia. RESULTADOS: Na região R1, 0,1 por cento a 2,8 por cento das células foram CD34+/CD45+, porém apenas 1,1 por cento das células foram CD34+/CD45-. As principais co-expressões de células CD45+ foram CD38, CD22, CD19 e CD56 na região R2 e CD33, CD11c, CD14, CD15 e CD61 nas regiões R3 e R4. Após a seleção, a mediana de 2,2x106 células CD34+ foi equivalente a 4,9 por cento do total mediano de células da medula óssea. Co-expressões de células CD34+/CD38+ e CD34+/CD117+ ocorreram em 94,95 e 82 por cento, respectivamente. Houve relação positiva entre o número de células CD34+ infundidas e o dia da enxertia. ...

Histological and functional organization in human testicle: expression of receptors c-kit and androgens / Organización histológica y funcional en el testículo humano: expresión de los receptores c-kit y andrógenos

The objective of this work was identify the presence of interstitial cells of Cajal, muscle cells, nerves and androgen receptor positive cells in adult human testicle, using immunohistochemical detection for c-kit/CD-117, actin smooth muscle specific (ASMS), neurofilament (N) and androgen receptor (AR), respectively. The samples were obtained from patients (n= 10) with diagnosis of prostate cancer, with surgery of orchiectomy. Subsequently were processed by histology and for immunohistochemistry using specific antibodies. It showed the presence of cells c-kit/CD-117, with diverse degrees of positivity, distributed mainly in the interstitial peritubular area of the human testicle. The peritubular myoides cells were positive to the presence of the actin smooth muscle and androgen receptor. The neurofilaments elements (+) only were observed in the vascular tunic. The specific immunohistochemistry describe the presence of the interstitial cells of Cajal in human testicular interstitium, opening a new perspective for the functional interpretation of the testicular cellularity and tubular motility. Possibly associated functionally to peribubulars cells of smooth muscle to regulate the mobility of the seminiferous tabules, whose integration and function would be androgen dependent. The cells that express the c-kit receptor, were found exclusively in the interstitial compartment. This cellular type in addition of the muscular cells of peritubules and the absence of nervous fibers to the interior of the testicle, could be responsible for the regulation of tubular mobility, as it happens in the gastrointestinal apparatus.

El objetivo de este trabajo fue identificar la presencia de células interticiales de Cajal, células musculares lisas, células nerviosas y células que expresan receptores de andrógeno en el testículo de humano adulto, usando inmunohistoquímica específica para: c-kit/CD-117, músculo liso actina específico (ASMS), neurofilamentos (N) y para receptores de andrógenos (AR). Las muestras fueron obtenidas de pacientes (n=10) con diagnóstico de cáncer prostático sometidos a cirugía de orquiectomía. Las biopsias se procesaron para histología e inmunohistoquímica usando anticuerpos específicos. Se muestra la presencia de células c-kit/CD-117, con diversos grados de positividad y distribuidas en el compartimento interticial del testículo. Las células peritubulares mioides fueron positivas para la presencia de músculo liso actina específico y para receptor de andrógenos. La marcación de neurofilamentos positivos, sólo fueron observados en la túnica vascular. Conclusiones: La inmunohistoquímica específica describe la presencia de células interticiales de Cajal en los interticios testiculares humanos, abriendo una nueva visión en la interpretación funcional de la celularidad testicular y la motilidad tubular. Lo anterior asociado a la funcionalidad de las células peritubulares (músculo liso) regularían la motilidad de los túbulos seminíferos. Este proceso posiblemente es andrógeno dependiente. Las células que expresan receptores c-kit se encuentran exclusivamente en los compartimentos interticiales, estas células en conjunto con las células musculares peritubulares agregado a la ausencia de fibras nerviosas al interior del testículo, podrían ser los responsables de la regulación de la motilidad tubular, similar a como se informa para el tracto gastrointestinal.

Acute GI bleeding by multiple jejunal gastrointestinal autonomic nerve tumour associated with neurofibromatosis type I / No disponible

Se describe una urgencia quirúrgica por sangrado intestinal debidoa tumor gastrointestinal de nervios autónomos (GANT) asociadoa enfermedad de von Recklinghausen.Una mujer de 72 años con neurofibromatosis fue ingresadacon signos de melena. La endoscopia digestiva alta y baja fue negativa.Se indicó TAC con contraste que advirtió tumores yeyunalescomo causa del sangrado. Se realizó laparotomía y resecciónde un segmento de 20 cm de yeyuno que incluía varios tumores.La causa del sangrado activo fue lesión en mucosa intestinalpor erosión tumoral. El análisis por inmunohistoquímica de la piezamostró diferenciación neuronal, con células fusiformes con tinciónpositiva para el C-Kit (CD 117), CD 34.Esta nota clínica pone de manifiesto la asociación entre la neurofibromatosisy los tumores estromales y debe alertar a gastroenterólogosy cirujanos sobre las posibles manifestaciones intestinalesen pacientes con enfermedad de von Recklinghausen

We describe a surgical emergency due to GI-bleeding causedby gastrointestinal autonomic nerve tumours (GANT’s) in a patientwith von Recklinghausen’s disease.A 72 year old female patient with von Recklinghausen’s diseasewas admitted with maelena. Endoscopy showed no activebleeding in the stomach and the colon. Therefore an angio-CTscanwas performed which revealed masses of the proximal jejunumas source of bleeding. Laparotomy was indicated and a 20cm segment of jejunum which carried multiple extraluminal tumourswas resected.The source of the bleeding was a 2 cm tumour which haderoded the mucosal surface. Immunohistologically, evidence ofneuronal differentiation could be shown in the spindle-formedcells with positive staining for C-Kit (CD 117), CD 34, and a locallypositive staining for synaptophysine and S100.This case report illustrates the association between neurofibromatosisand stromal tumours and should alert surgeons and gastroenterologistabout gastrointestinal manifestations in patientswith von Recklinghausen’s disease

Tumores de la estroma gastrointestinal (GIST): aspectos clínicos / Gastrointestinal stromal tumors (GISTs): Clinical aspects

Introducción: los tumores GIST son los tumores mesenquimales más frecuentes del tubo digestivo. Se caracterizan por la expresión del receptor c-KIT/CD 117. Objetivos y métodos: pretendemos describir las manifestaciones clínicas, las exploraciones que llevan al diagnóstico, los aspectos histológicos e inmunohistoquímicos, la evolución y factores predictores de esta a partir de una serie de pacientes. Resultados: se han diagnosticado 17 casos de GIST entre diciembre de 1999 y abril de 2005. La edad media de los pacientes fue 64,5 años (± 11,9). El 47% eran mujeres. La localización de los tumores por paciente fue: yeyuno-íleon en el 52,9%, gástrica en el 29,4%, duodenal en el 11,7% y mesentérica en el 5,8%. Los tumores medían 6,0 cm (± 5,0). El 47% eran tumores asintomáticos, menos frecuentemente produjeron dolor abdominal o hemorragia digestiva. El 94,1% de los tumores expresaba CD 117. Se diagnosticaron principalmente durante una laparotomía o con ecografía. Se extirparon el 94,1% de los tumores. En el 35,2% (6/17) de los pacientes había criterios de alto riesgo de malignidad según el consenso establecido. A lo largo de 25,6 meses (± 22,5) las metástasis o la recidiva tumoral se dieron en el 23,5% (4/17) de los pacientes y en estos fueron más frecuentes: los criterios de alto riesgo, los tumores sintomáticos, los de mayor tamaño y los que no expresan CD 117. Los tres pacientes con recidiva recibieron imatinib mesilato. Tres pacientes fallecieron por causa del tumor. Otros 4 pacientes fallecieron por otras causas no relacionadas con el GIST. Conclusiones: se diagnosticaron aproximadamente 12 casos por millón de habitantes y año. Su diagnóstico con frecuencia es casual. Son malignos en cerca de la cuarta parte de los casos. Existe la posibilidad de predecir la evolución en función de diferentes aspectos

Introduction: gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract. One of their features is the expression of the c-KIT / CD117 receptor. Aims and methods: we will focus on describing the symptoms, clinical studies prior to diagnosis, histologic and immunohistochemical characteristics, as well as the progression of disease in a group of patients. Results: seventeen cases were diagnosed between December 1999 and April 2005. Mean age of patients was 64.5 (± 11.9); 47% were women. Tumor location was as follows: 52.9% in the jejunum or ileum, 29.4% were gastric, 11.7% were in the duodenum, and 5.8% were located in the mesentery. Tumor size was 6.0 cm on average (± 5.0); 47% were asymptomatic, and to a lesser degree caused abdominal pain or digestive bleeding; 94.1% of tumors expressed CD117. Most of them were discovered while performing a laparotomy or ultrasound scan; 94.1% of tumors were removed; 35.2% (6 out of 17) of patients suffering from GIST met consensus criteria for aggressive behavior. Over 25.6 months (± 22.5) metastasis or tumor relapse occurred in 23.5% (4 out of 17) of patients – those with more frequent high-risk criteria, symptomatic and bigger tumors, and tumors not expressing CD117. The three patients with tumor relapse were prescribed imatinib mesylate. Three patients died because of the tumor, and four from other causes unrelated to GIST. Conclusions: GIST was diagnosed in around 12 cases per million a year. Its diagnosis was usually an incidental finding during a medical evaluation, and tumors were malignant in nearly one fourth of cases. We can predict its outcome depending on different aspects

Tumores gastrointestinales estromales (GIST): Experiencia del Servicio de Cirugía del Hospital Clínico de la Universidad de Chile entre 1999 y 2005 / Gastrointestinal stromal tumors: Review of 15 patients

Background: Gastrointestinal stromal tumors (GIST) are the most common mesenchymatous tumors of the digestive tract. The pathological diagnosis is based on microscopy and immunohistochemistiy. Aim: To review the experience of our surgical unit in patients with GIST Material and methods: Review of medical records of 15 patients (aged 66+13 years, 11 women), with a pathological diagnosis of GIST, treated between 1999 and 2005. Results: The main presenting symptoms were melena in 40 percent, hematemesis in 20 percent, abdominal pain in 60 percent and anemia in 13 percent. In only one patient, the tumor appeared as an incidentaloma. All patients underwent upper gastrointestinal endoscopy A CAT scan was done in 87 percent, a barium swallow in 60 percent and a digestive endosonography in 20 percent. Thirteen tumors were located in the stomach and two in the small bowel. Mean tumor diameter was 5.3+1.7 cm. Surgical management was a tumor resection in 40 percent, a partial gastrectomy in 27 percent, a total gastrectomy in 20 percent and an intestinal excision in the rest. Mean hospital stay was 6.9+4.2 days. No postoperative complications were recorded. Conclusions: The main clinical presentation of GIST in this retrospective series was an upper gastrointestinal bleeding. Surgical treatment was devoid of complication.

Guía de práctica clínica en los tumores estromales gastrointestinales (GIST): actualización 2010 / No disponible

No disponible