Massive intrasplenic arterial thrombosis in a patient with chronic ITP during the development of an Evans syndrome.

Long-term safety and efficacy of eltrombopag in adults with persitent/chronic primary immune thrombocytopenia (ITP) evaluated in EXTEND study, showed a high response rate (80%) but, in the clinical safety study, it was observed that 6% of the patients presented venous and arterial thrombotic events. In addition, in the course of the disease, autoimmune hemolytic anemia (Evans syndrome, ES) may occur and could increase the risk of thrombosis. We report an interesting case of splenic rupture due to massive intrasplenic arterial thrombosis in the course of ES in a patient with chronic ITP treated with eltrombopag. The purpose of this case report is to highlight the potential increase in thrombotic risk that may involve the use of eltrombopag in hemolysis situations in patients with ITP.

Integrating genomic alterations in diffuse large B-cell lymphoma identifies new relevant pathways and potential therapeutic targets.

Genome studies of diffuse large B-cell lymphoma (DLBCL) have revealed a large number of somatic mutations and structural alterations. However, the clinical significance of these alterations is still not well defined. In this study, we have integrated the analysis of targeted next-generation sequencing of 106 genes and genomic copy number alterations (CNA) in 150 DLBCL. The clinically significant findings were validated in an independent cohort of 111 patients. Germinal center B-cell and activated B-cell DLBCL had a differential profile of mutations, altered pathogenic pathways and CNA. Mutations in genes of the NOTCH pathway and tumor suppressor genes (TP53/CDKN2A), but not individual genes, conferred an unfavorable prognosis, confirmed in the independent validation cohort. A gene expression profiling analysis showed that tumors with NOTCH pathway mutations had a significant modulation of downstream target genes, emphasizing the relevance of this pathway in DLBCL. An in silico drug discovery analysis recognized 69 (46%) cases carrying at least one genomic alteration considered a potential target of drug response according to early clinical trials or preclinical assays in DLBCL or other lymphomas. In conclusion, this study identifies relevant pathways and mutated genes in DLBCL and recognizes potential targets for new intervention strategies.

Comparison of four prognostic scores in peripheral T-cell lymphoma.

BACKGROUND: To compare the usefulness of four prognostic scores in patients with peripheral T-cell lymphoma (PTCL) from a single institution. PATIENTS AND METHODS: One hundred twenty-one patients (77 male/36 female, median age 53 years) with PTCL [anaplastic large-cell lymphoma (ALCL) 21, PTCL not otherwise specified 56 and other 44)]. Complete response (CR) rate and 5-year overall survival (OS) were 41% and 31%, respectively. International Prognostic Index (IPI), Prognostic Index for T-cell lymphoma (PIT), International peripheral T-cell lymphoma Project score (IPTCLP) and modified Prognostic Index for T-cell lymphoma (mPIT) were calculated as in the original references. mPIT was only assembled to 41 patients in whom Ki-67 immunostaining was available. ALCL patients were analyzed separately. RESULTS: Concordance among IPI, PIT and IPTCLP was 52% for low-risk group, 27% for low/intermediate-risk group, 20% for high/intermediate-risk group and 14% for high-risk group. IPI, PIT and IPTCLP predicted CR, with IPI being the best score in logistic regression. Neither Ki-67 immunostaining nor mPIT predicted CR. Five-year OS (low-risk versus intermediate- or high-risk categories) according to IPI, PIT, IPTCLP and mPIT were 52% versus 45%, 75% versus 49%, 58% versus 20% and 39% versus 0%, respectively. IPTCLP was the best score for OS in multivariate analysis. CONCLUSION: All the scores demonstrated their usefulness to assess the outcome of patients with PTCL, with IPTCLP being the most significant to predict OS.

Endoscopic ultrasound-guided fine-needle aspiration and trucut biopsy in the diagnosis of gastric stromal tumors: a randomized crossover study.

BACKGROUND AND AIM: The diagnosis of gastrointestinal stromal tumors (GISTs) has important prognostic and therapeutic implications. The specific diagnosis of GIST has to be based on immunocytochemistry. This study aimed to prospectively compare in a crossover manner the accuracy of endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNA) and EUS-guided trucut biopsy (EUS-TCB) in the specific diagnosis of gastric GISTs. We hypothesized that EUS-TCB is superior to EUS-FNA in this respect. PATIENTS AND METHODS: Forty patients with gastric subepithelial tumors suspected on the basis of EUS of being a GIST underwent both EUS-FNA and EUS-TCB. The sequence in which the techniques were employed was randomly assigned to avoid bias. RESULTS: Forty tumors were sampled (mean number of passes: 2.1 +/- 0.9 with EUS-TNB and 1.9 +/- 0.8 with EUS-FNA; P = not significant, NS). Final diagnoses were: GIST (n = 27), carcinoma (n = 2), leiomyoma (n = 1), schwannoma (n = 1), and no diagnosis possible (n = 9). Device failure occurred in 6 patients with EUS-TCB. A cytohistological diagnosis of mesenchymal tumor (n = 29) and carcinoma (n = 2) was made in 70 % of cases by EUS-FNA and in 60 % of cases by EUS-TCB ( P = NS). Among the samples that were adequate, immunohistochemistry could be performed in 74 % of EUS-FNA samples and in 91 % of EUS-TCB samples ( P = 0.025). When inadequate samples were included, the overall diagnostic accuracy of EUS-FNA was 52 % and that of EUS-TCB was 55 % ( P = NS). There were no complications. CONCLUSIONS: EUS-TCB is not superior to EUS-FNA in GISTs because of the high rate of technical failure of trucut. However, when an adequate sample is obtained with EUS-TCB, immunohistochemical phenotyping is almost always possible. EUS-TCB can be safely performed in this set of patients.

Endometrial stromal sarcoma. Is there a place for radiotherapy?

OBJECTIVES: The optimal approach in the management of endometrial stromal sarcoma (ESS) remains unclear. The aim of the present study was to retrospectively report the outcome of patients treated for ESS in our hospital over a 27-year period in order to evaluate the treatment results and the role of radiotherapy. PATIENTS AND METHODS: From 1979 to 2006, 13 patients with ESS were treated at the Hospital Clínic of Barcelona. Patients underwent abdominal hysterectomy and bilateral salpingo-oophorectomy. The 1989 FIGO classification for endometrial carcinoma was used in this retrospective study. Seven patients presented stage I (6 IB and 1 IC), 1 stage II, 3 stage III and 2 stage IV. Nine patients had high-grade tumours with an infiltration of the outer 50% of the myometrium. Postoperative radiotherapy was administered in 10 patients. RESULTS: The mean follow-up of the patients was 54.6 months (range between 3 and 190). Patients with stage IB had a better outcome in comparison to more advanced stages. Five of the six patients with stage IB received adjuvant radiotherapy and none developed local recurrence, while one patient who received no treatment with radiotherapy had a relapse. Seven of the 13 patients had stages over IB: 5 who had received radiotherapy after surgery had locoregional control and 2 who did not receive radiotherapy had local relapse. Nine patients had high-grade tumours, 6 received radiotherapy after surgery and only one had local relapse. Of the three who did not receive radiotherapy, 2 relapsed locally. Local control rate of the patients who received adjuvant radiotherapy was higher than in the patients who did not (88.9% vs. 50%). CONCLUSIONS: Our data reveal that deep myometrial invasion and stage over IB are significantly associated with poor overall survival and this finding is similar to those of studies in patients with endometrial cancer. The present study showed that the local control was higher in patients receiving radiotherapy (AU)

No disponible

Primary neuroendocrine small cell undifferentiated carcinoma of the parotid gland.

Neuroendocrine small cell carcinoma is a malignant neoplasm that most frequently arises in the lung. Salivary gland involvement is rare, and the parotid is the main gland affected. We describe the fine-needle aspiration (FNA) cytology findings, the immunophenotypical study and the differential diagnosis of a small cell carcinoma that presented in the parotid of a 91-year-old man. The tumour was treated only with radiotherapy and presented a complete response, with no evidence of the disease after three years of follow-up. This is the first case reported in the literature with good outcome after exclusive irradiation.

Primary neuroendocrine small cell undifferentiated carcinoma of the parotid gland

Neuroendocrine small cell carcinoma is a malignant neoplasm that most frequently arises in the lung. Salivary gland involvement is rare, and the parotid is the main gland affected. We describe the fine-needle aspiration (FNA) cytology findings, the immunophenotypical study and the differential diagnosis of a small cell carcinoma that presented in the parotid of a 91-year-old man. The tumour was treated only with radiotherapy and presented a complete response, with no evidence of the disease after three years of follow-up. This is the first case reported in the literature with good outcome after exclusive irradiation (AU)

No disponible

Intensive chemotherapy (high-dose CHOP/ESHAP regimen) followed by autologous stem-cell transplantation in previously untreated patients with peripheral T-cell lymphoma.

AIM: To analyze toxicity, response and outcome of a phase II trial with intensive chemotherapy plus autologous stem-cell transplantation (ASCT) for young patients with peripheral T-cell lymphoma (PTCL). PATIENTS AND METHODS: Forty-one patients [30 males and 11 females, median age 47 years] consecutively diagnosed with PTCL received three courses of high-dose cyclophosphamide 2000 mg/m(2)/day, adriamycin 90 mg/m(2)/day, vincristine and prednisone alternating with three courses of etoposide, cisplatin, cytarabine and prednisone. Responders were submitted to ASCT. RESULTS: Sixty-eight percent of patients received the planned treatment. After chemotherapy, 20 patients reached complete response (CR), 4 partial response and 17 failed. ASCT was carried out in 17 of 24 candidates due to lack of mobilization (three cases), toxicity (two), early relapse and patient decision (one each). CR rate after treatment was 51%. With a median follow-up of 3.2 years, 5 of 21 CR patients relapsed and 2 died in CR due to secondary neoplasms. Four-year progression-free survival was 30%. Twenty-two patients have died, with a 4-year overall survival of 39%. International Prognostic Index was the main variable predicting survival. No differences were seen among the 24 candidates according to whether or not they underwent ASCT. CONCLUSION: This intensive regimen resulted in moderate CR rate, with manageable toxicity in PTCL. The contribution of ASCT in preventing relapse is debatable. Novel strategies to increase CR warrant investigation.

Un caso de cáncer ovárico de célula pequeña hipercalcémico / No disponible

El carcinoma ovárico de célula pequeña hipercalcémicoes un tumor raro y agresivo con mayor incidenciaen mujeres jóvenes.La hipercalcemia es una de sus características clínicas.El tratamiento multidisciplinar parece incrementarla supervivencia en un número pequeño de casos.Presentamos el caso de una mujer diagnosticadade este tipo de tumor, su evolución clínica y el tratamientoque recibió

The hypercalcemic ovarian small cell carcinomais a very rare aggressive tumor affecting young women.Hypercalcemia is among its clinical features.Prognosis is poor despite aggressive treatment,but combined treatment seems to increase survivalin a small subset of patients.We report a case of a woman diagnosed of hypercalcemicovary small cell cancer, her clinical evolution and the treatment she received (AU)

Eosinophilic ulcer of the oral mucosa: another histological simulator of CD30+ lymphoproliferative disorders.

Eosinophilic ulcer of the oral mucosa (EUOM), also known as traumatic ulcerative granuloma with stromal eosinophilia or Riga-Fede disease, is an uncommon benign self-limited lesion poorly described in the dermatological literature. It probably includes a spectrum of related disorders presenting as an ulcer with elevated indurated borders affecting the tongue, oral mucosa or lip. Histopathological findings are characteristic and consist of eosinophil-rich mixed infiltrates accompanied by a population of large mononuclear cells whose origins have been a matter of debate. Immunohistochemical studies of these cells have suggested a myofibroblastic or histiocytic origin. We present a 93-year-old woman with two episodes of self-healing ulcers on the upper lip and on the lingual mucosa, respectively. Histopathological findings on both biopsies were consistent with EUOM and showed the presence of large atypical CD30+ lymphocytes. Some recent reports have also shown positivity for the CD30 antigen, raising the possibility that a subset of EUOM could be included within the spectrum of CD30+ lymphoproliferative disorders. This finding most likely suggests that EUOM can represent another histological simulator of CD30+ lymphoproliferative disorders.

The Follicular Lymphoma International Prognostic Index (FLIPI) and the histological subtype are the most important factors to predict histological transformation in follicular lymphoma.

BACKGROUND: Histological transformation (HT) is a well-known event in patients with follicular lymphoma (FL) conferring an unfavorable prognosis. The aim of the study was to analyze incidence and risk factors for HT in a large series of FL patients. PATIENTS AND METHODS: 276 patients (median age: 54 years; M139/F137) diagnosed with FL (42% grade 1, 51% 2, 7% 3) in a single institution were studied. Initial treatment consisted of combined chemotherapy in most cases. Median survival was 11.3 years. Main clinic and biological variables were assessed for HT and survival. RESULTS: 30 of 276 patients (11%) presented HT after a median follow-up of 6.5 years, with a risk of 15% and 22% at 10 and at 15 years, respectively. All HT corresponded to diffuse large B-cell lymphoma (DLBCL). Grade 3 histology, nodal areas >4, increased LDH and beta(2)-microglobulin, and high-risk IPI and FLIPI were associated with HT. In multivariate analysis, grade 3 histology and FLIPI retained prognostic significance. Only FLIPI predicted HT in grade 1-2 patients. 28 patients received salvage treatment for HT, with a CR rate of 52%. Median survival from transformation was 1.2 years, with 6/13 CR patients being alive >5 years after HT. CONCLUSION: FLIPI and histology were the most important variables predicting HT. Upon HT, only patients achieving CR reached prolonged survival, thus emphasizing the need for effective therapies once this event occurs.

Serial topoisomerase II expression in primary breast cancer and response to neoadjuvant anthracycline-based chemotherapy.

OBJECTIVE: We analyzed the value of topoisomerase IIalpha (Topo II) in predicting the clinical response to anthracycline-based neoadjuvant chemotherapy in breast cancers and the potential changes in Topo II after chemotherapy. In parallel, HER2, which is commonly coexpressed with Topo II, and p53, a modulator of chemotherapy activity, were also analyzed. METHODS: Forty-one patients with primary breast cancer and treated with neoadjuvant anthracycline-based chemotherapy (FAC or FEC) were included for the present study. Topo II, HER2 and p53 expression were measured by immunohistochemistry in pre and post chemotherapy (at the time of surgery), tumor specimens and the results were correlated with the clinical response. RESULTS: Topo II was overexpressed in 16 of 41 (31%) tumors before treatment, and this overexpression was significantly associated with clinical response (p = 0.03). HER2 and p53 were unrelated to response. Notably, Topo II overexpression, but not HER2 or p53, was lost in specimens after chemotherapy (p = 0.01). CONCLUSION: The observed link between Topo II and the clinical response to neoadjuvant anthracycline-based chemotherapy, together with its loss after chemotherapy, implies that Topo II deserves further testing in a prospective setting as a predictive marker.

Successful treatment of isolated cutaneous relapse of follicular lymphoma with rituximab.

Patients with follicular lymphoma (FL) usually present with advanced disease, with lymph nodes and bone marrow involvement. Extranodal infiltration is infrequent. In FL isolated cutaneous relapse is a very rare event that, to the best of our knowledge, has not been previously reported. We report on a 55-year-old woman with FL who presented with an isolated skin relapse 5 years after the diagnosis. The patient, who had relapsed after three lines of chemotherapy, was treated with the chimeric anti-CD20 antibody, rituximab, achieving a complete response, which has now persisted for more than 24 months.

Prognostic features and outcome in patients with diffuse large B-cell lymphoma who do not achieve a complete response to first-line regimens.

BACKGROUND: The current study was conducted to analyze the outcome and prognostic factors of patients with diffuse large B-cell lymphoma (DLCL) who did not achieve a complete response (CR) to first-line treatment. METHODS: The current study was comprised of 83 patients (43 males and 40 females with a median age of 62 years) who did not achieve a CR (58 of whom had primary refractory disease and 25 of whom achieved a partial response) with initial treatment (doxorubicin-containing regimens in 87% of cases) from a series of 239 patients consecutively diagnosed with DLCL at a single institution. Initial variables, response to therapy, and salvage treatment were analyzed to predict survival. RESULTS: Compared with patients who achieved a CR, nonresponders or partial responders more frequently were of advanced age and had a poor performance status (PS), B-symptoms, advanced stage of disease, bone marrow infiltration, increased serum lactate dehydrogenase, and a high-risk International Prognostic Index. Among the 58 patients with primary refractory disease, 18 died during initial treatment due to toxicity (14 patients) or disease progression (4 patients). The main variables predicting early death were a poor PS, age > 60 years, and an immunoblastic DLCL subtype. Twenty-five of these 58 patients were able to receive salvage regimens, with only 1 of them achieving a CR. The median survival for this group of patients was 10 months. With regard to those patients achieving a partial response, 18 of the 25 patients received further therapy with 28% of them achieving a CR. The median survival was 23 months. The degree of the response was found to be the only significant variable with which to predict survival, with 2-year survival rates of 4% and 40%, respectively, for patients with primary refractory disease and patients who achieved a partial response. CONCLUSIONS: The prognosis of patients with primarily refractory DLCL is extremely unfavorable, whereas that of patients who achieve a partial response is slightly better. The inclusion of these patients in experimental trials is limited due to their tendency to be of an older age and to have a poor general status.

Rescreening of atypical cervicovaginal smears using PAPNET.

BACKGROUND: Atypical squamous cells of undetermined significance (ASCUS) is a cytopathologic term used to describe cases without specific pathologic substratum. Between 10-60% of ASCUS cases correspond to squamous intraepithelial lesions (SIL). METHODS: The objectives of this study were: 1) to detect the pathologic significance of ASCUS in study patients, 2) to determine whether PAPNET identifies these cases, and 3) to compare the results of PAPNET with those of a second conventional screening. One hundred and sixty-three consecutive patients with the cytologic diagnosis of ASCUS and adequate follow-up were selected. Of these, 111 patients had colposcopic lesions and biopsies were performed; in the remaining 52 cases colposcopy was negative, as were 3 consecutive annual Papanicolaou smears. In a blind review, all 163 cases were rescreened using PAPNET. A second manual screening was performed for comparison. RESULTS: One hundred and twenty-six of the 163 cases (77.3%) showed no SIL on biopsy or follow-up. Of the 37 pathologic cases, the diagnosis was koilocytosis (flat condyloma) in 13 cases (8%), cervical intraepithelial neoplasia (CIN) type I in 11 cases (6.8%) low grade SIL [LSIL] in a total of 24 cases [14.8%]), and CIN II-III or high grade SIL (HSIL) in 11 cases (6.8%). In the review using PAPNET, 57 previous ASCUS cases were classified correctly as negative, and 7 of 13 koilocytosis cases (54%), 9 of 11 CIN I cases (82%), and 7 of 11 CIN II-III cases (64%) were diagnosed correctly. In the second conventional screening, 74 cases were negative and 77 cases were ASCUS; only 3 of 13 koilocytosis cases (23%), 4 of 11 CIN I cases (36.4%) and 5 of 11 CIN II-III cases (45.5%) were reclassified correctly. CONCLUSIONS: Among 163 patients with ASCUS, 77.3% had no precancerous squamous lesions. Concordance with definitive diagnosis was more accurate in our study using PAPNET analysis (Kappa index [K] = 0.7158) than by second conventional screening (K = 0.4537). Furthermore, we reclassified 35% of smears as negative and 15% as SIL.

Expression of the p53 protein in sun-damaged skin.

The expression of the p53 protein in photodamaged skin from the face, forearm and neck of 18 subjects was compared to non-exposed skin taken at autopsy from the abdomens of 9 subjects of the same age. Paraffin sections and the polyclonal antibody CM1 were used with the ABC technique. The p53 protein was expressed in the nuclei of keratinocytes in 7 of the 18 samples obtained from sun-exposed skin and in 1 of 9 samples from non-exposed skin. The expression in sun-exposed skin can be due either to its overexpression due to DNA damage or to the appearance of mutant forms.

[3 new cases of Enterobacter taylorae infection]. / Tres nuevos casos de infección por Enterobacter taylorae.

BACKGROUND: Enterobacter taylorae is a recently identified microorganism pertaining to the enterobacterian family. To date few infections by this organism have been reported with their clinical significance being unknown. Three patients with Enterobacter taylorae infection are described with the possible pathogenic capacity of this microorganism in concurrence with opportune epidemiologic features being commented upon in addition to the different sources of infection. METHODS: Biochemical identification of the microorganisms was performed by the automatized MicroScan system (Baxter). The sensitivity to the different antimicrobians was determined by automatized reading (Baxter) of the seried microdilution to the last point. RESULTS: The two first patients presented infection of an open wound with E. taylorae being isolated from the culture of the exudate of the wound and from a culture of the drainage point, respectively. The third patient developed nosocomial bacteremia following prolonged hospital stay with growth of E. taylorae being found in two different blood culture series. Different biotypes of the E. taylorae species were isolated in the three patients. Specific treatment was administered to the three patients according to the antibiogram with improvement in the clinical manifestations being observed. CONCLUSIONS: The three clinical cases herewith described suggest that E. taylorae is a potentially pathogenic microorganism which, in determined circumstances (empiric antibiotic treatment, open wounds, diagnostic or therapeutic instruments) may produce clinical pictures similar to those described for other Enterobacter species.

Diseño y evaluación de un modelo para la radioinmunolocalización e inmunoterapia del cáncer / Design and evolution of a model for the radioimmunotargetting and immunotherapy of cancer

El anticuerpo mionoclonal B2C114 producido contra el antígeno carcinoembrionario reconoce un carbohidrato del antígeno A de grupo sanguineo humano. La expresión de este determinante antigénico se investigó en estirpes celulares del adenocarcinoma mamario espontáneo M3 y su derivada experimental MM3 de mayor capacidad metastatizante. La reactividad específica in vitro de B2C114 marcado con I a la 125 permitió determinar el número de epitopes antigénicos por celula M3 y la constante de asociación. La biodistribución del anticuerpo monoclonal mostró que I a la 125-B2C114 discriminó, con alta sensibilidad, entre el tumor M3, la variante MM3 y tejidos normales, confirmado por la obtención de imágenes positivas de M3 en cámara gamma. Estos estudios han permitido la obtención de un modelo que facilita el desarrollo de diferentes tecnologías aplicadas al diagnóstico y a la terapéutica del cáncer

Diseño y evaluación de un modelo para la radioinmunolocalización e inmunoterapia del cáncer / Design and evolution of a model for the radioimmunotargetting and immunotherapy of cancer

El anticuerpo mionoclonal B2C114 producido contra el antígeno carcinoembrionario reconoce un carbohidrato del antígeno A de grupo sanguineo humano. La expresión de este determinante antigénico se investigó en estirpes celulares del adenocarcinoma mamario espontáneo M3 y su derivada experimental MM3 de mayor capacidad metastatizante. La reactividad específica in vitro de B2C114 marcado con I a la 125 permitió determinar el número de epitopes antigénicos por celula M3 y la constante de asociación. La biodistribución del anticuerpo monoclonal mostró que I a la 125-B2C114 discriminó, con alta sensibilidad, entre el tumor M3, la variante MM3 y tejidos normales, confirmado por la obtención de imágenes positivas de M3 en cámara gamma. Estos estudios han permitido la obtención de un modelo que facilita el desarrollo de diferentes tecnologías aplicadas al diagnóstico y a la terapéutica del cáncer (AU)