Clinical and pathological characteristics of peripheral T-cell lymphomas in a Spanish population: a retrospective study.

We investigated the clinicopathological features and prognostic factors of patients with peripheral T-cell lymphoma (PTCL) in 13 sites across Spain. Relevant clinical antecedents, CD30 expression and staining pattern, prognostic indices using the International Prognostic Index and the Intergruppo Italiano Linfomi system, treatments, and clinical outcomes were examined. A sizeable proportion of 175 patients had a history of immune-related disorders (autoimmune 16%, viral infections 17%, chemo/radiotherapy-treated carcinomas 19%). The median progression-free survival (PFS) and overall survival (OS) were 7·9 and 15·8 months, respectively. Prognostic indices influenced PFS and OS, with a higher number of adverse factors resulting in shorter survival (P < 0·001). Complete response (CR) to treatment was associated with better PFS (62·6 vs. 4 months; P < 0·001) and longer OS (67·0 vs. 7·3 months; P < 0·001) compared to no CR. CD30 was expressed across all subtypes; >15% of cells were positive in anaplastic lymphoma kinase-positive and -negative anaplastic large-cell lymphoma and extranodal natural killer PTCL groups. We observed PTCL distribution across subtypes based on haematopathological re-evaluation. Poor prognosis, effect of specific prognostic indices, relevance of histopathological sub-classification, and response level to first-line treatment on outcomes were confirmed. Immune disorders amongst patients require further examination involving genetic studies and identification of associated immunosuppressive factors.

C4d como herramienta diagnóstica en la nefropatía membranosa / C4d as a diagnostic tool in membranous nephropathy

Introducción: La nefropatía membranosa (NM) es la causa más frecuente de síndrome nefrótico en adultos. El diagnóstico se basa en los hallazgos típicos observados con el microscopio electrónico (ME) y el estudio de inmunofluorescencia (IF). En algunas ocasiones, sólo se dispone de tejido para estudio de microscopio óptico (MO); en estos casos puede ser complicado diferenciar entre una NM y una enfermedad por cambios mínimos (ECM). Recientemente se está extendiendo el estudio con C4d por inmunohistoquímica. Existe muy poca información sobre el depósito de C4d en la NM. Nuestro estudio consistió en analizar si el depósito de C4d realizado en la muestra en parafina podría ser útil en el diagnóstico de NM. Material y métodos: Estudio retrospectivo que incluyó a todos los pacientes diagnosticados de NM mediante biopsia renal en nuestra unidad entre enero de 2001 y octubre de 2008. Se incluyeron sólo adultos con un diagnóstico certero de NM y ECM idiopática que dispusieran de estudios con MO, IF y ME. En octubre de 2008, secciones de 3 µm de tejido renal fijado en formaldehído fueron deparafinadas y rehidratadas. Después se tiñeron mediante inmunohistoquímica con C4d usando un anticuerpo policlonal antihumano obtenido de conejo. Resultados: Se incluyeron finalmente 19 pacientes con ECM y 21 con NM. Ningún depósito de C4d fue observado en ninguno de los glomérulos de los pacientes con ECM y el 100% de estos pacientes fueron clasificados como negativos. Sin embargo, el depósito de C4d se detectó en el 100% de los pacientes con NM y en todos los glomérulos con una distribución uniforme y granular dibujando todas las asas capilares. Conclusiones: El depósito de C4d mediante inmunohistoquímica es una herramienta muy útil en el diagnóstico de NM (AU)

Introduction: membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. The diagnosis is based on typical findings observed using electron microscope (EM) and immunofluorescence (IF) studies. On some occasions, tissues are only available for analysis using an optical microscope (OM); in these cases, it can be difficult to differentiate between MN and minimal change disease (MCD). Recently, the use of C4d immunohistochemical staining has spread. Very little information is available regarding C4d deposits in MN. Our study consisted of analysing whether C4d staining of samples embedded in paraffin could be useful for diagnosing MN. Material and Method: Ours was a retrospective study including all patients diagnosed with MN by renal biopsy in our unit between January 2001 and October 2008. We only included adult patients with a definitive diagnosis of MN or idiopathic MCD by OM, IF, and ME studies. In October 2008, 3µm sections of renal tissue fixed in formaldehyde were removed from paraffin and rehydrated. The samples were then stained for C4d immunohistochemical analysis using anti-human polyclonal antibodies obtained from rabbits. Results: Our study included a final sample of 19 patients with MCD and 21 with MN. No C4d deposits were observed in any of the glomeruli in patients with MCD, and 100% of these patients were classified as negative. However, C4d deposits were detected in 100% of patients with MN, and were observable in all glomeruli with a uniform granular distribution, demarcating all capillary loops. Conclusions: C4d immunohistochemical staining is a very useful tool for diagnosing MN (AU)

C4d as a diagnostic tool in membranous nephropathy.

INTRODUCTION: membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. The diagnosis is based on typical findings observed using electron microscope (EM) and immunofluorescence (IF) studies. On some occasions, tissues are only available for analysis using an optical microscope (OM); in these cases, it can be difficult to differentiate between MN and minimal change disease (MCD). Recently, the use of C4d immunohistochemical staining has spread. Very little information is available regarding C4d deposits in MN. Our study consisted of analysing whether C4d staining of samples embedded in paraffin could be useful for diagnosing MN. MATERIAL AND METHOD: Ours was a retrospective study including all patients diagnosed with MN by renal biopsy in our unit between January 2001 and October 2008. We only included adult patients with a definitive diagnosis of MN or idiopathic MCD by OM, IF, and ME studies. In October 2008, 3µm sections of renal tissue fixed in formaldehyde were removed from paraffin and rehydrated. The samples were then stained for C4d immunohistochemical analysis using anti-human polyclonal antibodies obtained from rabbits. RESULTS: Our study included a final sample of 19 patients with MCD and 21 with MN. No C4d deposits were observed in any of the glomeruli in patients with MCD, and 100% of these patients were classified as negative. However, C4d deposits were detected in 100% of patients with MN, and were observable in all glomeruli with a uniform granular distribution, demarcating all capillary loops. CONCLUSIONS: C4d immunohistochemical staining is a very useful tool for diagnosing MN.

Tumor necrosis factor-α-secreting CD16+ antigen presenting cells are effectively removed by granulocytapheresis in ulcerative colitis patients.

BACKGROUND AND AIM: In human blood, two main subsets of antigen-presenting-cells (APCs) have been described: plasmocytoid dendritic cells (pDC) and myeloid dendritic cells (mDC) which are further subdivided in CD11c-mDC and CD16-mDC DC. In ulcerative colitis patients (UC) peripheral blood APCs express significant levels of the activation and lack immature-tolerogeneic APCs. Adacolumn selective granulocytapheresis (GCAP) has been associated with clinical efficacy in patients with UC. In the present study we sought the effect of sequential GCAP procedures in peripheral blood APCs in patients with UC and the effect on soluble cytokines. METHODS: We used multiparametric flow cytometry to quantify peripheral blood APCs and serum cytokines in 210 samples obtained from seven patients with steroid-dependent or steroid resistant UC undergoing GCAP treatment. Samples were drawn before, after 30 and 60 min of each session. RESULTS: Each GCAP session resulted in a dramatic tenfold reduction of peripheral blood CD16-mDC (P < 0.01), pDC decreased twofold (P = 0.05) but CD11c-mDC remained unchanged. This depletion was reached after 30 min and maintained at 60 min. The depletion of CD16-mDC and monocytes was associated with a reduction of serum tumor necrosis factor levels and a raise in interleukin-10 levels, although no statistical difference was reached. CONCLUSION: The effect of GCAP in peripheral blood APC consisted mainly on a significant depletion of tumor necrosis factor-α secreting CD16-mDC. This finding could suggest a potential mechanism of GCAP beneficial effect that must be confirmed in larger series.

Darbepoetin-α treatment enhances glomerular regenerative process in the Thy-1 glomerulonephritis model.

Recent studies have demonstrated that erythropoietin (EPO) and its analogs induce cytoprotective effects on many nonerythroid cells. In this study, we examined whether darbepoetin-α might prevent glomerular lesions in the Thy-1.1 model of glomerulonephritis (Thy-1-GN). GN was induced in Wistar rats by a single injection of monoclonal anti-Thy-1.1 antibody. Rats were killed at 24 h, 72 h, 7 days, 10 days, or 15 days after antibody injection. Kidneys were removed for histological analysis, and proteinuria was measured. Because at day 7 the maximal degree of renal damage and proteinuria was found, the effect of darbepoetin-α was tested at day 7 and two different protocols of administration were used; After anti-Thy-1.1 injection, rats received two doses of darbepoetin-α or vehicle at days 0 and 4 or at days 4 and 6. At day 7, proteinuria, plasma creatinine concentration, and renal morphology analysis were performed. Also, α-actin, desmin, caspase-3, and Ki67 protein expression were evaluated by immunohistochemistry. Our results showed that in both protocols of administration, darbepoetin-α treatment decreased proteinuria in Thy-1-GN rats and this effect correlated with the improvement in renal morphology. Glomerular lesions, α-actin, and caspase-3 protein expression, observed in most glomeruli of Thy-1-GN rats, were significantly reduced in darbepoetin-α-treated rats, while cell proliferation was significantly enhanced. The results indicate that darbepoetin-α treatment promotes glomerular recovery.

Peripheral T-cell lymphoma with follicular T-cell markers.

INTRODUCTION: Peripheral T-cell lymphomas (PTCLs) in western countries are uncommon tumors with unfavorable prognosis. They may be subclassified as anaplastic large-cell lymphomas (ALCLs), angioimmunoblastic-T-cell lymphomas (AITLs), or unspecified peripheral T-cell lymphomas (PTCLs-U). It has recently been demonstrated that AITLs originate from germinal center follicular helper T cells (TFH), whereas the normal counterparts of other PTCLs remain essentially unknown. The aim of this study was to establish whether other PTCL subgroups also express TFH cell markers. MATERIALS AND METHODS: One hundred forty-six PTCLs were analyzed for programmed death-1 (PD-1) expression in tissue microarrays using a new monoclonal antibody called NAT-105. PD-1-positive cases, which did not fulfill all the criteria for AITL, were further evaluated in whole-tissue sections for another 12 immunohistochemical markers, including the TFH cell markers CXCL13, CD10, and BCL6. Clonal Ig and T-cell receptor rearrangements and Epstein-Barr virus-encoded RNA expression were also evaluated. Morphologic, clinical, and follow-up data were reviewed. RESULTS: Twenty-five out of 87 non-AITL cases (28.75%) showed PD-1 immunostaining. CXCL13, BCL6, and CD10 expression was found in 24/25 (96%), 16/25 (64%), and 6/25 (24%) cases, respectively. All cases expressed at least 2 TFH cell markers. Moreover, 5 cases were positive for all 4 markers. Most cases (17/25, 68%) displayed some AITL-like features. Of the remainder, 1 was considered to be early AITL, 1 was diagnosed as ALCL-anaplastic lymphoma kinase-negative, and 4 of the other 6 PTCLs-U had morphology consistent with lymphoepithelioid (Lennert's) lymphoma. Three AITL-like cases showed IgH clonal rearrangement, 2 of which were associated with Epstein-Barr virus expression. Our series of patients did not differ significantly in their clinical presentation from most reported PTCL cases in the literature: 55% of them were alive and 35% were in complete remission after a median follow-up of 15 months after cyclophosphamide, dexorubicin, vincristine, and prednisone-based chemotherapy. CONCLUSIONS: TFH cell markers, especially PD-1, were expressed in a subset of PTCLs not classified as AITL, although most of them shared some morphologic features with AITL. This suggests that the spectrum of AITL may be wider than previously thought, possibly including cases of lymphoepithelioid (Lennert's) lymphoma. Additionally, the results suggest that a subgroup of PTCLs-U, distinct from AITL and including some cases denominated as ALCL, may also be derived from TFH cells, although they develop along a distinct pathogenic pathway.

Aberrant Bcl6 protein expression in mantle cell lymphoma.

Mantle cell lymphoma is routinely considered as a Bcl6-negative B-cell lymphoma carrying the translocation t(11;14). Here we describe a series of five Bcl6-positive mantle cell lymphoma cases, including three classic and two blastoid variants. The proliferative index of these cases, measured with the Ki-67 antibody, was slightly higher than in Bcl6-negative mantle cell lymphoma cases (32.2 vs. 23.7%) Bcl6 expression was associated with translocations involving 3q27 in four of the five cases and an extra copy of the BCL6 gene in the fifth. A mutational study of the major mutational cluster in the BCL6 gene revealed no increased mutation rate, except in one case. One of the three cases displayed a high mutational index in the IgVH gene, suggesting exposure to a germinal center microenvironment. Chromosomal alterations involving 3q27 seem to be responsible for this increased Bcl6 expression, which needs to be considered when Bcl6 is used in lymphoma diagnosis.

Sclerosing adenosis of the prostate. Histologic features in needle biopsy specimens.

Sclerosing adenosis of the prostate is a pseudoneoplastic lesion that can mimic prostate cancer. Because the lesion is more common in the transition zone, which is only rarely sampled in needle biopsy, it is uncommon to see examples of this lesion in biopsy specimens. Because sampling of the transition zone of the prostate is likely to become more frequent, practicing surgical pathologists must be aware of the morphologic features of sclerosing adenosis of the prostate in needle biopsy specimens, in order to avoid misinterpretation of sclerosing adenosis of the prostate, a benign lesion, as prostate adenocarcinoma. We report the morphologic findings of sclerosing adenosis of the prostate in 3 needle biopsy specimens from 2 patients diagnosed as having sclerosing adenosis. We found a combination of histologic (mainly a cellular myxoid stroma and a double-cell population of acinar cells) and immunohistochemical features demonstrating a continuous basal cell layer with myoepithelial differentiation to be diagnostic.

Correlación radiopatológica de microcalcificaciones en el carcinoma intraductal de mama / Radiologic-pathologic correlation of microcalcifications in intraductal breast carcinomas

Objetivos: Aportar nuestra experiencia en el estudio del carcinoma ductal in situ de la mama (CDis), correlacionando radiopatologicamente las calcificaciones vistas en la mamografía con su localización histológica dentro del tumor.Material y método: Se revisan retrospectivamente 20 casos de CDis, diagnosticados por calcificaciones en la mamografía, que representan un 81 por ciento (20/24) del total de CDis. Se analizan características radiológicas de las calcificaciones como forma de agrupación, numero, distribución, tamaño, forma y densidad. Anatomopatológicamente se clasifican en tres subtipos y se estudia la localización del calcio dentro del tumor, Se correlacionan los datos histológicos con los manifestados en la mamografía.Resultados: En el análisis mamográfico la forma de agrupación más frecuente fue la 'focal no segmentaria' con un 65 por ciento (13/20) y el número de microcalcificaciones de 5 a 10 con un 45 por ciento (9/20). Predominó la heterogeneidad de tamaño y forma (80 por ciento / 75 por ciento), y la morfología más frecuente fue la redondeada (65 por ciento). Histológicamente el 95 por ciento de las microcalcificaciones se identificaron dentro del tumor, correspondiendo en los tipos III a calcio en componente necrótico, y en los tipos I y II a calcio en las cribas o micropapilas del tumor. Se detectó multifocalidad y microinfiltración en los tres subtipos histológicos.Conclusiones: Existe una buena correlación radiopatológica de las microcalcificaciones en los CDis En los grados I y II las calcificaciones en la mamografía son predominantemente redondas y pequeñas, e histológicamente se corresponden con depósitos cálcicos laminados o psamomatosos en las cribas o micropapilas del tumor. En el grado III las calcificaciones son redondas o alargadas (moldeadas) y se corresponden con calcificación amorfa de material necrótico intraductal (AU)