Relación entre volumen de la glándula prostática y algunos marcadores histológicos de malignidad / Relation Between Prostate Gland Volume and Some Histological Markers of Malignancy

Objetivos: La relación entre el volumen total de la glándula prostática, o el peso de la misma tras prostatectomía radical, y los marcadores histológicos de malignidad en casos de cáncer de próstata, es motivo de controversia. Hemos analizado 100 muestras consecutivas de prostatectomía radical para determinar la relación entre el volumen o el peso de la glándula prostática y la agresividad biológica del proceso tumoral expresado por diferentes marcadores histológicos. Material y métodos: Se han revisado las piezas de prostatectomía radical de 100 pacientes consecutivos, que no recibieron tratamiento hormonal preoperatorio. Estas muestras quirúrgicas fueron procesadas siguiendo un protocolo común. En la ulterior valoración se investigó con mayor precisión: el grado de Gleason, volumen tumoral, multifocalidad, invasión vascular o neural, estadio pT y presencia de focos de PIN. Los hallazgos fueron comparados con el peso de la glándula utilizando el paquete estadístico de WINDOWS SPSS 13.0 con valor estadístico significativo de p<0,05. Según el peso de la glándula se formaron tres grupos:<40g (33%), entre 40-90g (61%) y >90g (6%). Resultados: Se encontró una asociación estadísticamente significativa (p=0,001) entre el peso de la glándula y el volumen del tumor, ya que 15 de 33 glándulas de peso inferior a 40g mostraron más del 50% de la glándula afectada por tumor, comparado con ninguno de los 6 pacientes con peso total mayor de 90g. También se encontró relación significativa entre la multifocalidad y el peso (p=0,03), de forma que 24 de 33 glándulas menores de 40g tenían multifocalidad bilateral en comparación con solo una de 6 glándulas mayores de 90g. La invasión neural, el número de focos de PIN y un grado combinado de Gleason más alto fueron más frecuentes en las próstatas pequeñas, pero la diferencia no alcanzó significación estadística. Conclusiones: Nuestro estudio indica que las glándulas prostáticas de gran volumen albergan tumores de menor malignidad (volumen tumoral, bilateralidad). El hallazgo justifica la conveniencia de contar con el volumen total de la glándula prostática para decisiones diagnósticas (indicación de biopsia prostática y repetición de las mismas) y determinación pronóstica (AU)

Objectives: The relationship between the total volume of the prostate gland or its weight after radical prostatectomy and the histological markers of malignancy in cases of prostate cancer is a controversial subject. We have analyzed 100 consecutive radical prostatectomy specimens in order to determine the relationship between volume or weight of the prostate gland and the biological aggressiveness of the tumor process by different histological markers. Material and methods: One hundred consecutive radical prostatectomy specimens in patients who had not received pre-operative hormone treatment were retrospectively reviewed. These surgical samples were processed according to a standardized protocol. In a subsequent evaluation, the following were studied with greater detail: Gleason grade, tumor volume, multimodality, neural or vascular invasion, put stage, and presence of PIN foci. The histological findings were compared with the prostate gland weight using Windows SPAS, 13.0 statistical package with a significance value of p<0.05. According to the prostate gland weight, three groups were established: <40g (33%), 40 - 90g (61%), and >90g (6%). Results: A statistically significant association (p=0.001) was found between the prostate gland weight and tumor volume since 15 of the 33 glands with weight under 40g accounted for more than 50% of the glands affected by tumor compared to none of the 6 patients with total weight over 90g. A significant relationship was also found between the multimodality and weight. (P=0.03), so that 24 of the 33 glands under 40g had bilateral multimodality compared to only 1 out of the 6 glands over 90g. The neural invasion, number of PIN foci and the highest combined Gleason grade were frequent in low volume prostates, but the difference did not reach statistical significance. Conclusions: Our study indicates that large volume prostate glands have tumors with lower malignancy (tumor volume, bilateralism). This finding justifies the adequacy of using total volume of the prostate gland for diagnostic decision (indication of prostatic biopsy and their repetition) and the prognostic determination (AU)

[Relation between prostate gland volume and some histological markers of malignancy]. / Relación entre volumen de la glándula prostática y algunos marcadores histológicos de malignidad.

OBJECTIVES: The relationship between the total volume of the prostate gland or its weight after radical prostatectomy and the histological markers of malignancy in cases of prostate cancer is a controversial subject. We have analyzed 100 consecutive radical prostatectomy specimens in order to determine the relationship between volume or weight of the prostate gland and the biological aggressiveness of the tumor process by different histological markers. MATERIAL AND METHODS: One hundred consecutive radical prostatectomy specimens in patients who had not received pre-operative hormone treatment were retrospectively reviewed. These surgical samples were processed according to a standardized protocol. In a subsequent evaluation, the following were studied with greater detail: Gleason grade, tumor volume, multimodality, neural or vascular invasion, put stage, and presence of PIN foci. The histological findings were compared with the prostate gland weight using Windows SPAS, 13.0 statistical package with a significance value of p<0.05. According to the prostate gland weight, three groups were established: <40 g (33%), 40 - 90 g (61%), and >90 g (6%). RESULTS: A statistically significant association (p=0.001) was found between the prostate gland weight and tumor volume since 15 of the 33 glands with weight under 40 g accounted for more than 50% of the glands affected by tumor compared to none of the 6 patients with total weight over 90 g. A significant relationship was also found between the multimodality and weight. (P=0.03), so that 24 of the 33 glands under 40 g had bilateral multimodality compared to only 1 out of the 6 glands over 90 g. The neural invasion, number of PIN foci and the highest combined Gleason grade were frequent in low volume prostates, but the difference did not reach statistical significance. CONCLUSIONS: Our study indicates that large volume prostate glands have tumors with lower malignancy (tumor volume, bilateralism). This finding justifies the adequacy of using total volume of the prostate gland for diagnostic decision (indication of prostatic biopsy and their repetition) and the prognostic determination.

Scleredema diabeticorum in a patient with type 2 diabetes mellitus.

Background. Scleredema adultorum, a connective tissue disorder of unknown aetiology, is characterized by a thickening of the reticular dermis in the upper back of the body that may decrease the mobility of the affected tissues. It has been reported in diabetic patients with poor metabolic control. Therapeutic options are limited with generally poor results. Case Report. 53-year-old white male with type 2 diabetes mellitus was referred to our department for evaluation of incipient nephropathy and retinopathy. On examination, he presented erythematous, indurated, painless and ill-defined plaque on the skin of the upper back with limited movement of shoulders. A biopsy was done revealing scleredema. PUVA treatment and physiotherapy were started with the amelioration of mobility and acquiring some elasticity of the upper back. Discussion. The development of scleredema in diabetic patients has been related to prolonged exposure to chronic hyperglycaemia. Our patient has had diabetes for 20 years with an acceptable glucose control, however he developed the scleredema 10 years ago. Conclusions. Scleredema is a rare connective disorder that seems to appear most frequently in diabetic subjects. Good metabolic control seems not to preclude its development. PUVA treatment and physiotherapy are therapeutic options that seem to be of some help.

Immunohistochemistry for the differential diagnosis of renal tumors with oncocytic features.

OBJECTIVE: Histologic analysis of renal tumors usually enables accurate diagnosis, but some tumors may show overlapping histopathologic features, which makes classification difficult. Diagnosis can be extremely challenging in tumors showing oncocytic change, mainly for oncocytomas, chromophobe carcinoma, papillary carcinomas with eosinophilic cells (type 2), and conventional renal cell carcinomas with eosinophilic oncocytic-like cells. The purpose of the present study is to analyze whether the patterns of immunohistochemical expression can help differential diagnosis of these tumors. MATERIAL AND METHODS: A thorough review of the files of the Department of Surgical Pathology, Fundación Jiménez Díaz, Madrid, Spain has retrieved 308 records of renal cell carcinomas in the last 12 years, with 15 renal oncocytomas (RO), 28 papillary carcinomas (PRCC), and 13 chromophobe carcinomas (CHRCC). We have performed immunohistochemistry on representative paraffin blocks from 9 oncocytomas, 11 chromophobe carcinomas, 10 papillary carcinomas, and 11 conventional cell carcinomas with oncocytic cells, from which we had suitable material. The immunohistochemical panel included CD117, α-methylacyl-coenzyme A racemase, CD10, p53, progesterone receptors, and cytokeratins 7 and 20. RESULTS: Our results show a considerable overlap between immunohistochemical expression in these tumors. Although immunohistochemistry can be helpful in some difficult cases, no markers allow a clear-cut distinction between these tumors, and diagnosis must still rely on morphologic features and histochemical techniques, as well as on molecular techniques when available.

[Early histopathological aspects of benign prostatic hyperplasia: myxoid-inflammatory nodules]. / Aspectos histopatológicos iniciales de la hiperplasia benigna de próstata: nódulos mixo-inflamatorios.

OBJECTIVES: Infiltration of benign prostatic hyperplasia (BPH), nodular prostatic hyperplasia (NPH) or prostatic adenoma by mononuclear cells, predominantly lymphocytes, is a common finding in surgical specimens. The biological significance of this infiltration, very similar to chronic inflammation, is unknown, but it is suspected as being related to the pathogenesis and progression of the BPH. The identity and number of the infiltrating cells is not well known. The objectives of the present study were: 1) to describe in more detail the histologic pattern of early lesions BPH, that is myxoid nodules. 2) to count and locate these myxoid nodules and to analyse the possible influence of age 3) and describe the patterns of mononuclear cell infiltration in BPH. MATERIALS AND METHODS: One hundred and seventy-three specimens of BPH tissue were reviewed. These samples were processed routinely for histological examination and immunohistochemical examination was performed in selected cases in order to further define the cellular composition of the described lesions. The immunohistochemical stains were performed automatically. Vimentin, specific smooth muscle actin an desmin were use to show the stromal cells and CD3, CD20 and CD68 monoclonal antibodies were used to quantify the populations of T-lymphocytes, B-lymphocytes and macrophages, respectively. The number of myxoid nodules identified in each patient was counted and the maximum and minimum diameter measured. These data have been compared in two groups of patients, those younger than 57 years and those over 80. Statistical analysis has been performed with SPSS 13.0. Student s t test was used for bivariate analysis and Pearson s r for correlation. RESULTS: Interstitial infiltration involving T and B lymphocytes with less macrophages was a constant finding of the early nodules of BPH. The bivariate analysis with Student s t has shown a statistically significant difference between the mean number of myxoid nodules (p

Aspectos histopatológicos iniciales de la hiperplasia benigna de próstata: nódulos mixo-inflamatorios / Early histopathological aspects of benign prostatic hyperplasia: myxoid—inflammatory nodules

Objetivos: La infiltración de la hiperplasia benigna de próstata (HBP; hiperplasia nodular de próstata, adenoma prostático) por células mononucleares, con predominio de linfocitos, es un hallazgo frecuente en piezas quirúrgicas. Se desconoce la importancia biológica de esta infiltración, pero se sospecha que guarda relación con la patogenia y la progresión de la HBP. No se conocen demasiado bien la identidad ni el número de células infiltrantes. Los objetivos del presente estudio fueron: 1) describir con más detalle el patrón histológico de las lesiones iniciales de HBP, es decir, los nódulos «mixoides»; 2) contar y localizar estos nódulos mixoides y analizar la posible influencia de la edad, y 3) describir los patrones de infiltración por células mononucleares en la HBP. Materiales y métodos: Se examinaron 173 muestras de tejido de HBP. Estas muestras se procesaron sistemáticamente para su examen histológico y se realizó un examen inmunohistoquímico en casos seleccionados para definir mejor la composición celular de las lesiones descritas. Se realizaron tinciones inmunohistoquímicas de forma automatizada. Se utilizaron anticuerpos contra vimentina, actina específica del músculo liso y desmina para poner de manifiesto las células del estroma y los anticuerpos monoclonales CD3, CD20 y CD68 para evaluar las poblaciones de linfocitos T, linfocitos B y macrófagos, respectivamente. Se contó el número de nódulos mixoideos identificados en cada paciente y se midió el diámetro máximo y mínimo. Estos datos se compararon en dos grupos de pacientes, menores de 57 y mayores de 80 años. El análisis estadístico se realizó con el programa informático SPSS 13.0. Se empleó la prueba de la t de Student en el análisis bifactorial y la prueba de la r de Pearson en el análisis de correlación. Resultados: La infiltración intersticial por parte de linfocitos T y B, con acompañamiento minoritario de macrófagos fue un hallazgo constante en los nódulos iniciales de HBP. El análisis bifactorial con la prueba de la t de Student reveló una diferencia estadísticamente significativa entre el número medio de nódulos mixoides (p=0,02), significativamente más bajo en los pacientes más jóvenes. Aunque se constataron diferencias entre los diámetros medios de los nódulos de menor y mayor tamaño en ambos grupos, estas diferencias no alcanzaron significación estadística. No se identificaron correlaciones significativas entre el número de nódulos y la edad del paciente (p=0,11) con la prueba de la r de Pearson. Conclusión: Los nódulos mixoides con células inflamatorias crónicas de distribución intersticial son un hallazgo constante en las piezas quirúrgicas de HBP. El número medio de nódulos mixoideos es significativamente menor en los pacientes más jóvenes. Los linfocitos B y T son las células inflamatorias más abundantes en los nódulos mixoides iniciales (AU)

Objectives: Infiltration of benign prostatic hyperplasia (BPH), nodular prostatic hyperplasia (NPH) or prostatic adenoma by mononuclear cells, predominantly lymphocytes, is a common finding in surgical specimens. The biological significance of this infiltration, very similar to chronic inflammation, is unknown, but it is suspected as being related to the pathogenesis and progression of the BPH. The identity and number of the infiltrating cells is not well known. The objectives of the present study were: 1) to describe in more detail the histologic pattern of early lesions BPH, that is “myxoid” nodules. 2) to count and locate these myxoid nodules and to analyse the possible influence of age 3) and describe the patterns of mononuclear cell infiltration in BPH. Materials and methods: One hundred and seventy-three specimens of BPH tissue were reviewed. These samples were processed routinely for histological examination and immunohistochemical examination was performed in selected cases in order to further define the cellular composition of the described lesions. The immunohistochemical stains were performed automatically. Vimentin, specific smooth muscle actin an desmin were use to show the stromal cells and CD3, CD20 and CD68 monoclonal antibodies were used to quantify the populations of T-lymphocytes, B-lymphocytes and macrophages, respectively. Conclusion: Inflammatory cells and myxoid nodules are a constant finding in BPH surgical samples. The mean number of myxoid nodules is significantly lower in younger patients. Interstitial distribution is the most common pattern of mononuclear cell infiltration. B and T-cell lymphocytes are the most frequently found inflammatory cells in early myxoid nodules (AU)

Double immunostaining with CD1A and CD68 in the phenotypic characterization of indeterminate cell histiocytosis.

Indeterminate cell histiocytosis (ICH) is a rare disorder in which histiocytic cells proliferate, expressing markers of both X- and non-X histiocytosis. Nevertheless, it is not totally clear if both types of markers are co-expressed by the same cell in this disorder, or on the contrary, the histiocytosis is made of two phenotypically different types of cells. Some recent reports seem to indicate this latter option, since there is a non-homogeneous distribution of the cells in the dermis. The ones in the most superficial part of the biopsy would lose some of their markers when moving towards the bottom part of the dermis. In order to check if there is co-expression of CD1a and CD68 by the same cell, we performed an immunohistochemical study with double staining, in a case of ICH of a 74-year-old male, who presented multiple yellowish papules in chest, back and both arms. Their sizes varied between 1 and 3 mm. One of the biopsies from one lesion of the back showed a dermal histiocytic infiltrate, which expressed S-100, CD1a, Factor XIIIa and CD68 in the common immunohistochemical study. Birbeck granules were not found in the ultrastructural study. Our results with the double stain for CD1a and CD68 demonstrated that most of the histiocytes expressed either one marker or the other. Nevertheless, some of the histiocytes of the infiltrate co-expressed both markers. In all the cases, the cells with this combined phenotype were mononuclear. Although CD1a was mainly expressed by the cells at the top of the dermis, some cells of the deep dermis kept expressing this marker. The cells expressing both markers were mostly found in the top part of the dermis. The multinucleate cells expressed only CD68, but not CD1a.

Nephrotic syndrome complicating chronic visceral leishmaniasis: re-emergence in patients with AIDS.

Leishmania infection may be associated with immunecomplex-mediated glomerular injury. Contrary to immune-competent individuals, leishmaniasis in HIV patients is a chronic, relapsing disease. Despite the increasing frequency of the Leishmania/ HIV co-infection, there is a paucity of information on the effects of such co-infection in the kidney. We present a patient with AIDS and refractory, relapsing visceral leishmaniasis who developed nephrotic syndrome associated with renal involvement by Leishmania in the absence of immunecomplex glomerular deposition. For the first time, the relapsing nature of renal injury in this context is documented.

BPH and inflammation: pharmacological effects of Permixon on histological and molecular inflammatory markers. Results of a double blind pilot clinical assay.

INTRODUCTION: The role of infiltrating cells (I.C.), commonly observed in the adenoma interstitial tissue, is unknown. We tested the hypothesis that I.C. are related with BPH progression by: phenotypically characterising these cells; quantifying the expression of lymphokines and growth factors; investigating the response to Permixon (P) in a clinical study. Permixon is a lipido sterolic extract of Serenoa repens possessing pharmacological activities and widely used in the treatment of men with BPH. MATERIAL AND METHODS: A multicenter open pilot study of two parallel groups on BPH patients was carried out. They were randomized to receive either oral Permixon (P) 160 mg bid for three months or to be followed for 3 weeks without any treatment before surgery (control group C). Strict inclusion and exclusion criteria were applied to conform homogeneous groups, avoiding interferences of inflammatory drugs or others. Baseline clinical profile was almost identical in both groups in terms of age (65.7+/-5.1 vs. 67.1+/-5.8 years), IPSS (19.8+/-6.1 vs. 19.0+/-5.8), prostate volume (64.8+/-18.9 vs. 71.5+/-29.3cc), Q(max) (9.6+/-3.2 vs. 10.6+/-2.6 ml/s), and Q(L) (4.0+/-1.1 vs. 3.5+/-0.7). Surgery was ultimately performed on 29 patients (17C, 12P) by TURP or retropubic adenomectomy. Adenoma samples were routinely stained with HE and later prepared for immunohistochemical studies using CD3, CD20 and CD68 antibodies. Counting of positives cells, lymphoid aggregates and foci were done using EnVision technique and the Tech Mate processor. Cytokines, growth factors and eicosanoids were determined by Elisa kits following the manufactured recommendation. RESULTS: HISTOLOGICAL: A difference was observed in the number of lymphocytes B between C (91.4+/-44.1) and P treated (58.2+/-53.7) groups (p=0.097). BIOLOGICAL MARKERS: TNFalpha and IL-1beta were dramatically lower in the Permixon treated group. Other parameters did not show significant changes. CLINICAL: IPSS in the Permixon treated group was significantly reduced (p<0.006) from 20.0+5.9 to 14.9+3.8 after three months of treatment. COMMENTS: The BPH inflammatory hypothesis was tested in humans. Our pilot study shows a significant reduction of some inflammatory parameters in prostatic tissues of patients treated with Permixon. These biological findings justify a pharmacological effect of this drug on the inflammatory status of the adenoma. A correlation with clinical improvement was observed.