Sandro Casavilca - Academia.edu (original) (raw)
Papers by Sandro Casavilca
Cancer Epidemiology, Biomarkers & Prevention
Background: We have previously identified a genetic variant, rs140068132, which has a strong prot... more Background: We have previously identified a genetic variant, rs140068132, which has a strong protective effect on breast cancer risk. This variant is located near the estrogen receptor 1 gene (ESR1) on chromosome 6q25, a locus which has been repeatedly implicated in breast cancer risk. Women who carry two copies of the protective variant (GG) have 60-70% reduction in risk of developing breast cancer compared to women with none. The G variant has relatively high frequency in Latin American women (up to 23% in the 1000 Genomes Project Peruvians); it is only common in people of Indigenous American ancestry and almost absent in all other populations. We investigated whether the rs140068132-A/G polymorphism is associated with a specific breast cancer subtype among Peruvian women with breast cancer. Methods: Blood samples and clinical data were collected from 441 women with breast cancer at the Instituto Nacional de Enfermedades Neoplasicas in Lima, Peru. Genotypic profiles were generated...
Cancer Research
Around 10% of genetic predisposition for breast cancer is explained by mutations in high/moderate... more Around 10% of genetic predisposition for breast cancer is explained by mutations in high/moderate penetrance genes. The remaining proportion is explained by multiple common variants of relatively small effect. A subset of these variants has been identified mostly in Europeans and Asians; and combined into polygenic risk scores (PRS) to predict breast cancer risk. Our aim is to identify a subset of variants to improve breast cancer risk prediction in Hispanics/Latinas (H/Ls).Breast cancer patients were recruited at the Instituto Nacional de Enfermedades Neoplásicas in Peru, to be part of The Peruvian Genetics and Genomics of Breast Cancer Study (PEGEN). Women without a diagnosis of breast cancer from a pregnancy outcomes study conducted in Peru were included as controls. After quality control filters, genome-wide genotypes were available for 1,809 cases and 3,334 controls. Missing genotypes were imputed using the Michigan Imputation Server using individuals from 1000 Genomes Project ...
Blood, 2020
Background: The human T-cell lymphotropic virus type 1 (HTLV-1) is an oncogenic retrovirus that a... more Background: The human T-cell lymphotropic virus type 1 (HTLV-1) is an oncogenic retrovirus that affects CD4+ T-cell lymphocytes and is the cause for adult T-cell leukemia/lymphoma (ATLL), an aggressive peripheral T-cell neoplasm. Hodgkin-like ATLL subtype is a unique entity usually indistinguishable from Hodgkin lymphoma (HL) in the setting of HTLV-1 infection. HTLV-1 proviral integration and TCR Cb1 gene rearrangement testing are often necessary to differentiate both entities. However, less is known on HTLV-1 carriers diagnosed with HL (HTLV-1+ HL). We aim to compare survival outcomes between HTLV-1+ HL and matched controls treated at the National Cancer Institute in Peru. Methods: We reviewed medical records of patients diagnosed and managed for HL at the National Cancer Institute (Instituto Nacional de Enfermedades Neoplasicas, INEN) in Lima-Peru between 2002 and 2019. All patients should have had serologic evaluation for HTLV-1 infection at the time of diagnosis and should have ...
Clinical and Translational Oncology, 2019
Purpose This study aims to evaluate the association between composition of tumor-infiltrating lym... more Purpose This study aims to evaluate the association between composition of tumor-infiltrating lymphocytes (TIL) and expression of p16 in acral lentiginous melanoma (ALM), and their impact on prognosis. Materials and methods A cohort of 148 surgical pathology specimens of ALM was studied. TIL were evaluated by immunohistochemical detection of CD3 and CD8, along with CD20, CD4, CD68, and CD163 in a subset of 43 cases. p16 protein expression was also investigated in all the cases. Results The median age was 66 years, median Breslow thickness was 6.0 mm, grade III TIL was found in 28.4% and lymph nodes were involved in 54.2%. Breslow thickness (p < 0.001), stage I-II (p < 0.001), negative lymph nodes (p < 0.001) and < 10% p16 (p = 0.01) were associated with longer survival. Grade III of TIL was associated with thinner Breslow thickness (p = 0.008) and lower mitosis (p = 0.047). A higher density of CD3 TIL was associated with male gender (p = 0.008), thinner Breslow thickness (p = 0.047), negative lymph node (p = 0.031), early stage (p = 0.046), and p16 nuclear expression of > 10% (p = 0.045). Higher CD8 TIL was associated with > p16 (p = 0.03). Survival analysis found that longer survival had a trend to be associated with high TIL (p = 0.090). Levels of CD3+ and CD8+ cells were correlated with those of CD4+, CD20+, CD68+ and CD163+ immune cells. Conclusions Higher levels of TIL tend to be associated with better overall survival in ALM. Loss of expression of p16 is associated with lower levels of CD3+ and CD8+ TIL, indicating a probable relationship between p16 and TIL immune response in ALM .
Revista Peruana de Ciencias de la Salud, 2022
Entre las neoplasias malignas más frecuentes del mundo, el carcinoma hepatocelular (CHC) es la se... more Entre las neoplasias malignas más frecuentes del mundo, el carcinoma hepatocelular (CHC) es la segunda causa de muerte relacionada con el cáncer (1). Su incidencia se ha duplicado durante las dos últimas décadas y la mayor carga se produce en los países de ingresos bajos y medianos. Los tumores hepáticos primarios malignos suelen describirse como una patología que afecta principalmente a hombres mayores de 40 años con un hígado cirrótico; rara vez se han registrado en personas más jóvenes y normalmente, en menores de 40, lo más común es el hepatoblastoma.
Epidemiology, 2019
There are few Latin American cohorts with available biospecimens that include women of high Indig... more There are few Latin American cohorts with available biospecimens that include women of high Indigenous American ancestry. The Peruvian population is characterized by a high degree of Native American (NA) ancestry, with this ancestral component varying between 56 to 100% on average, depending on the region. We have collected 1199 Peruvian samples from the Instituto Nacional de Enfermedades Neoplasicas in Lima. This cohort of patients represents a unique opportunity to study the molecular characteristics of breast cancer in the NA genetic and genomic background. Here we present a basic description of the women in the study and a comparison of tumor subtypes distribution and risk factor information of the patients by place of birth and residence. We explored differences in tumor subtype distribution and risk factors in relation to place of birth or residence in the three main geographical region of Peru. To test differences in proportions we used Chi2 or Fisher-exact tests. To test differences in means for continuous variables we used ANOVA or t-tests. Genetic ancestry was estimated using genome wide genotypes and the program ADMIXTURE. Tumor subtypes were defined using the following criteria: ER+/PR+/HER2- as luminal A, ER+/PR+/HER2+ as luminal B, ER-/PR-/HER2+ as HER2+ and ER-/PR-/HER2- as triple negative. Overall, the patients included in the study were relatively young (50 yrs, SD=11.0). The average number of full-term pregnancies was 3 (SD=1.8), the average age at first pregnancy 22 (SD=5.7) and age at menarche was 13 (SD=1.8). The tumor subtype distribution was 31% of Luminal B tumors, 24% luminal A, 12% HER2 and 12% triple negative and did not differ by place of birth or residence. We found that patients from the Coastal region were heavier and taller than those born in the Andean region (p The distribution of tumor subtypes among women in the Peruvian breast cancer cohort did not differ by place of birth or residence. However, we found that for some breast cancer risk factors, exposures differed between women from different regions. Finally, given the relatively low observed values for reproductive and lifestyle related exposures and the high proportion of Indigenous American ancestry of Peruvian women, this cohort is likely to be particularly informative to study genetic predisposition to breast cancer. Citation Format: Valentina Zavala, Tatiana Vidaurre, Katie Marker, Jeannie Vasquez, L Tamayo, Renzo Florez, Sandro Casavilca, M Calderon, J Abugattas, H Gomez, H Fuentes, C Monge-Pimentel, S Song, D Cherry, Laura Fejerman. Tumor and risk factor characteristics among breast cancer patients from different geographic regions in Peru [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4184.
Blood, 2020
Background: Diffuse large B-cell lymphoma (DLBCL) is the most common variant of non-Hodgkin lymph... more Background: Diffuse large B-cell lymphoma (DLBCL) is the most common variant of non-Hodgkin lymphoma (NHL) accounting for approximately 30% of the NHL cases worldwide. Previous reports have associated certain viral infections with the development of DLBCL such as HIV and EBV, both infections related with an aggressive clinical course and worse outcome. The human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus regarded as the pathogenic agent for adult T-cell lymphoma/leukemia. HTLV-1 is endemic in Japan, the Caribbean basin, South America, and parts of Africa. In Peru, up to 3% of the healthy adult population carries HTLV-1. As data on the impact of HTLV-1 infection in DLBCL outcomes is scarce, we aim to describe the clinical features and outcomes of HTLV-1-positive patients with a pathological diagnosis of DLBCL. Methods: We retrospectively reviewed medical records of patients diagnosed and managed for DLBCL at the National Institute of Neoplastic Diseases in Lima-Peru between...
Blood, 2021
Background: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with dismal prognos... more Background: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with dismal prognosis and associated with clonal T-cell expansion driven by Human T-Lymphotropic Virus 1 (HTLV-1) infection. Comprehensive genomic studies in Japan have identified recurrent alterations affecting TCR-NF-kB signaling (i.e. PRKCB, PLCG1, CARD11, VAV1, and IRF4), T-cell trafficking pathways (i.e. CCR4 and CCR7), and the tumor suppressor genes CDKN2A and TP53. HTLV-1 endemic regions include Africa, the Caribbean, and South America in addition to Japan. Retrospective studies from the Western population have reported distinctive features from the Japanese cohort, e.g. younger age, more common lymphomatous presentation, and worse outcomes. Our group sought to evaluate the unique molecular features of ATLL in a large cohort of patients from the Caribbean and South America. Methods: We performed a multimodal genomic study on specimens from 169 patients encountered in the United States (Miami), Peru,...
Blood, 2021
Introduction Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hemato... more Introduction Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological malignancy with multi-organ and frequent skin involvement, and poor clinical outcomes. Based on the limited available data, the estimated incidence is 0.44% of all hematologic malignancies, representing less than 1% of acute leukemias, and 0.7% of cutaneous lymphomas. Due to the rarity of this entity, there have been relatively few studies characterizing the molecular profile of BPDCN. We examined a cohort of 51 patients with BPDCN using OncoScan chromosome microarray, which provides genome-wide copy number abnormality (CNA) analysis. Methods An international cohort of BPDCN cases were collected from centers in Brazil (Laboratorio de Patologia, Botucatu), Swtizerland (University of Zurich), France (Hospital St. Louis, Paris), Peru (Instituto Nacional de Enfermedades Neoplasicas, Lima), Canada (Department of Pathology, University of Montreal), Italy (Derpartment of Pathology, Univ...
European Journal of Cancer, 2018
Glioblastoma multiforme (GBM) is the most common and most aggressive primary brain tumor in
Diffuse large B-cell lymphoma is a rare neoplasm of the central nervous system with aggressive be... more Diffuse large B-cell lymphoma is a rare neoplasm of the central nervous system with aggressive behavior and poor outcome. CD5 expression in nodal or extranodal in this neoplasm is infrequent. These cases tend to be more aggressive than the CD5 negative cases. Herein, we report a case of primary brain CD5-positive diffuse large B-cell lymphoma presenting in an immunocompetent 64-year-old woman. She presented with intensity frontoparietal headache, nausea, vomiting, generalized seizures and confusional symptoms. Nuclear magnetic resonance showed characteristics of malignant lymphoma. The patient received treatment with corticoids with good response. Two years after the initial condition, she presented symptoms again. Brain images studies showed bifrontal neoplasm. No tumors were found in other sites. On the basis of morphology and immunohistochemistry, the diagnosis was CD5-positive diffuse large B-cell lymphoma. The present case confirms in this neoplasm multiple pathways are altered...
Revista Peruana de Medicina Experimental y Salud Pública, 2015
Glioblastoma (GB) is the most common and most lethal primary brain tumor. Epidemiologic informati... more Glioblastoma (GB) is the most common and most lethal primary brain tumor. Epidemiologic information indicate that its incidence is lower in Hispanic race. Surgery is the only curative strategy and has recently introduced new strategies that increase resection rates. The use of concurrent chemotherapy with radiotherapy improves survival of patients but is associated with toxicity. Improved understanding of molecular biology of GB allows the identification of predictive biomarkers of response and prognosis as well as therapeutic targets for the development of new therapeutic strategies. Among biomarkers are currently available 1p /19q codeletion, IDH mutation and O6-methylguanine DNAmethyltransferase promoter methylation. The identification therapeutic targets enables the development of new drugs and their evaluation in clinical trials, but none has been prospectively validated in phase III clinical trials.
Spinal cord oligodendroglioma is an extremely unusual glial neoplasm and only 52 cases have been ... more Spinal cord oligodendroglioma is an extremely unusual glial neoplasm and only 52 cases have been reported at this time. We report the case of a 52 year-old man with paraplegia and an intramedullary tumor of the spinal cord at levels C7 to T4. The final diagnosis was anaplastic oligodendroglioma with an isolated chromosome 1p deletion.
Future microbiology, 2020
Aim: Helicobacter pylori is usually detected based on hematoxylin-eosin (H-E) features, but, immu... more Aim: Helicobacter pylori is usually detected based on hematoxylin-eosin (H-E) features, but, immunohistochemistry (IHC) and real-time PCR (RT-PCR) are more precise in chronic-gastritis. We evaluated the relevance of these tests in Peruvian gastric cancer samples. Materials & methods: We performed and evaluated H-E, IHC staining and RT-PCR in 288 gastric tumors. Slides were independently evaluated by three pathologists. Results: H. pylori was detected in 167/287 through H-E, 140/288 through IHC and 175/288 through RT-PCR, and positive-status were associated (p < 0.001). H. pylori detection by H-E had a good concordance with IHC (kappa index = 0.632) but poor with RT-PCR (kappa index = 0.317). Higher median gene-copies were found in high H. pylori density through H-E or IHC (p < 0.001). Conclusion: H-E evaluation is accurate in gastric cancer, and IHC and RT-PCR can complement its results.
Six cases of amoebic encephalitis admitted to the National Institute of Neoplastic Diseases betwe... more Six cases of amoebic encephalitis admitted to the National Institute of Neoplastic Diseases between the years 1994-2010 in Peru are reported. These cases were admitted for clinical suspicion of malignant primary brain tumor and one orbital-nasal sarcoma. All cases came from coastal regions; three were less than 24 years of age and four were male. The most common symptoms were headache and seizures. Three cases had more than one brain lesion. Stereotactic biopsy was performed in three patients and the differential pathological diagnosis in two cases was glioma of high and low grade. It was possible to confirm the diagnosis using molecular techniques in paraffin-embedded samples in three cases. All patients died within 15 days of admission to the institution. Amoebic encephalitis may be erroneously interpreted as a cerebral neoplasm, causing delay in the management of the infection.
Neuro-Oncology
OBJECTIVE An unexpectedly high incidence of sarcomas of the Central Nervous System (SCNS) was rec... more OBJECTIVE An unexpectedly high incidence of sarcomas of the Central Nervous System (SCNS) was recently observed in Peru. We describe clinical and biological characteristics of the disease. METHODS Seventy pediatric patients with primary SCNS diagnosed between January 2005 and June 2018 were analyzed. DNA methylation profiling and gene panel sequencing was available from 28 and 27 tumors, respectively. RESULTS Median age was 6 years (range 2–17.5), 66/70 patients had supratentorial tumors, 56 patients intratumoral hemorrhage at diagnosis. Three patients fulfilled clinical criteria of NF1; 35 had café-au-lait spots and/or freckling. DNA-methylation profiling classified 28/28 as “intracranial spindle cell sarcoma with rhabdomyosarcoma-like features and DICER1 mutations”. DICER1 mutations were found in 26/27, TP53 mutations in 22/27, and RAS-pathway gene mutations (NF1, KRAS, NRAS) in 19/27 tumors, all of which were somatic (germline control available in n=19 cases). Survival was analyz...
Poster Presentations - Proffered Abstracts
Cancer Epidemiology, Biomarkers & Prevention
Background: We have previously identified a genetic variant, rs140068132, which has a strong prot... more Background: We have previously identified a genetic variant, rs140068132, which has a strong protective effect on breast cancer risk. This variant is located near the estrogen receptor 1 gene (ESR1) on chromosome 6q25, a locus which has been repeatedly implicated in breast cancer risk. Women who carry two copies of the protective variant (GG) have 60-70% reduction in risk of developing breast cancer compared to women with none. The G variant has relatively high frequency in Latin American women (up to 23% in the 1000 Genomes Project Peruvians); it is only common in people of Indigenous American ancestry and almost absent in all other populations. We investigated whether the rs140068132-A/G polymorphism is associated with a specific breast cancer subtype among Peruvian women with breast cancer. Methods: Blood samples and clinical data were collected from 441 women with breast cancer at the Instituto Nacional de Enfermedades Neoplasicas in Lima, Peru. Genotypic profiles were generated...
Cancer Research
Around 10% of genetic predisposition for breast cancer is explained by mutations in high/moderate... more Around 10% of genetic predisposition for breast cancer is explained by mutations in high/moderate penetrance genes. The remaining proportion is explained by multiple common variants of relatively small effect. A subset of these variants has been identified mostly in Europeans and Asians; and combined into polygenic risk scores (PRS) to predict breast cancer risk. Our aim is to identify a subset of variants to improve breast cancer risk prediction in Hispanics/Latinas (H/Ls).Breast cancer patients were recruited at the Instituto Nacional de Enfermedades Neoplásicas in Peru, to be part of The Peruvian Genetics and Genomics of Breast Cancer Study (PEGEN). Women without a diagnosis of breast cancer from a pregnancy outcomes study conducted in Peru were included as controls. After quality control filters, genome-wide genotypes were available for 1,809 cases and 3,334 controls. Missing genotypes were imputed using the Michigan Imputation Server using individuals from 1000 Genomes Project ...
Blood, 2020
Background: The human T-cell lymphotropic virus type 1 (HTLV-1) is an oncogenic retrovirus that a... more Background: The human T-cell lymphotropic virus type 1 (HTLV-1) is an oncogenic retrovirus that affects CD4+ T-cell lymphocytes and is the cause for adult T-cell leukemia/lymphoma (ATLL), an aggressive peripheral T-cell neoplasm. Hodgkin-like ATLL subtype is a unique entity usually indistinguishable from Hodgkin lymphoma (HL) in the setting of HTLV-1 infection. HTLV-1 proviral integration and TCR Cb1 gene rearrangement testing are often necessary to differentiate both entities. However, less is known on HTLV-1 carriers diagnosed with HL (HTLV-1+ HL). We aim to compare survival outcomes between HTLV-1+ HL and matched controls treated at the National Cancer Institute in Peru. Methods: We reviewed medical records of patients diagnosed and managed for HL at the National Cancer Institute (Instituto Nacional de Enfermedades Neoplasicas, INEN) in Lima-Peru between 2002 and 2019. All patients should have had serologic evaluation for HTLV-1 infection at the time of diagnosis and should have ...
Clinical and Translational Oncology, 2019
Purpose This study aims to evaluate the association between composition of tumor-infiltrating lym... more Purpose This study aims to evaluate the association between composition of tumor-infiltrating lymphocytes (TIL) and expression of p16 in acral lentiginous melanoma (ALM), and their impact on prognosis. Materials and methods A cohort of 148 surgical pathology specimens of ALM was studied. TIL were evaluated by immunohistochemical detection of CD3 and CD8, along with CD20, CD4, CD68, and CD163 in a subset of 43 cases. p16 protein expression was also investigated in all the cases. Results The median age was 66 years, median Breslow thickness was 6.0 mm, grade III TIL was found in 28.4% and lymph nodes were involved in 54.2%. Breslow thickness (p < 0.001), stage I-II (p < 0.001), negative lymph nodes (p < 0.001) and < 10% p16 (p = 0.01) were associated with longer survival. Grade III of TIL was associated with thinner Breslow thickness (p = 0.008) and lower mitosis (p = 0.047). A higher density of CD3 TIL was associated with male gender (p = 0.008), thinner Breslow thickness (p = 0.047), negative lymph node (p = 0.031), early stage (p = 0.046), and p16 nuclear expression of > 10% (p = 0.045). Higher CD8 TIL was associated with > p16 (p = 0.03). Survival analysis found that longer survival had a trend to be associated with high TIL (p = 0.090). Levels of CD3+ and CD8+ cells were correlated with those of CD4+, CD20+, CD68+ and CD163+ immune cells. Conclusions Higher levels of TIL tend to be associated with better overall survival in ALM. Loss of expression of p16 is associated with lower levels of CD3+ and CD8+ TIL, indicating a probable relationship between p16 and TIL immune response in ALM .
Revista Peruana de Ciencias de la Salud, 2022
Entre las neoplasias malignas más frecuentes del mundo, el carcinoma hepatocelular (CHC) es la se... more Entre las neoplasias malignas más frecuentes del mundo, el carcinoma hepatocelular (CHC) es la segunda causa de muerte relacionada con el cáncer (1). Su incidencia se ha duplicado durante las dos últimas décadas y la mayor carga se produce en los países de ingresos bajos y medianos. Los tumores hepáticos primarios malignos suelen describirse como una patología que afecta principalmente a hombres mayores de 40 años con un hígado cirrótico; rara vez se han registrado en personas más jóvenes y normalmente, en menores de 40, lo más común es el hepatoblastoma.
Epidemiology, 2019
There are few Latin American cohorts with available biospecimens that include women of high Indig... more There are few Latin American cohorts with available biospecimens that include women of high Indigenous American ancestry. The Peruvian population is characterized by a high degree of Native American (NA) ancestry, with this ancestral component varying between 56 to 100% on average, depending on the region. We have collected 1199 Peruvian samples from the Instituto Nacional de Enfermedades Neoplasicas in Lima. This cohort of patients represents a unique opportunity to study the molecular characteristics of breast cancer in the NA genetic and genomic background. Here we present a basic description of the women in the study and a comparison of tumor subtypes distribution and risk factor information of the patients by place of birth and residence. We explored differences in tumor subtype distribution and risk factors in relation to place of birth or residence in the three main geographical region of Peru. To test differences in proportions we used Chi2 or Fisher-exact tests. To test differences in means for continuous variables we used ANOVA or t-tests. Genetic ancestry was estimated using genome wide genotypes and the program ADMIXTURE. Tumor subtypes were defined using the following criteria: ER+/PR+/HER2- as luminal A, ER+/PR+/HER2+ as luminal B, ER-/PR-/HER2+ as HER2+ and ER-/PR-/HER2- as triple negative. Overall, the patients included in the study were relatively young (50 yrs, SD=11.0). The average number of full-term pregnancies was 3 (SD=1.8), the average age at first pregnancy 22 (SD=5.7) and age at menarche was 13 (SD=1.8). The tumor subtype distribution was 31% of Luminal B tumors, 24% luminal A, 12% HER2 and 12% triple negative and did not differ by place of birth or residence. We found that patients from the Coastal region were heavier and taller than those born in the Andean region (p The distribution of tumor subtypes among women in the Peruvian breast cancer cohort did not differ by place of birth or residence. However, we found that for some breast cancer risk factors, exposures differed between women from different regions. Finally, given the relatively low observed values for reproductive and lifestyle related exposures and the high proportion of Indigenous American ancestry of Peruvian women, this cohort is likely to be particularly informative to study genetic predisposition to breast cancer. Citation Format: Valentina Zavala, Tatiana Vidaurre, Katie Marker, Jeannie Vasquez, L Tamayo, Renzo Florez, Sandro Casavilca, M Calderon, J Abugattas, H Gomez, H Fuentes, C Monge-Pimentel, S Song, D Cherry, Laura Fejerman. Tumor and risk factor characteristics among breast cancer patients from different geographic regions in Peru [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4184.
Blood, 2020
Background: Diffuse large B-cell lymphoma (DLBCL) is the most common variant of non-Hodgkin lymph... more Background: Diffuse large B-cell lymphoma (DLBCL) is the most common variant of non-Hodgkin lymphoma (NHL) accounting for approximately 30% of the NHL cases worldwide. Previous reports have associated certain viral infections with the development of DLBCL such as HIV and EBV, both infections related with an aggressive clinical course and worse outcome. The human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus regarded as the pathogenic agent for adult T-cell lymphoma/leukemia. HTLV-1 is endemic in Japan, the Caribbean basin, South America, and parts of Africa. In Peru, up to 3% of the healthy adult population carries HTLV-1. As data on the impact of HTLV-1 infection in DLBCL outcomes is scarce, we aim to describe the clinical features and outcomes of HTLV-1-positive patients with a pathological diagnosis of DLBCL. Methods: We retrospectively reviewed medical records of patients diagnosed and managed for DLBCL at the National Institute of Neoplastic Diseases in Lima-Peru between...
Blood, 2021
Background: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with dismal prognos... more Background: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with dismal prognosis and associated with clonal T-cell expansion driven by Human T-Lymphotropic Virus 1 (HTLV-1) infection. Comprehensive genomic studies in Japan have identified recurrent alterations affecting TCR-NF-kB signaling (i.e. PRKCB, PLCG1, CARD11, VAV1, and IRF4), T-cell trafficking pathways (i.e. CCR4 and CCR7), and the tumor suppressor genes CDKN2A and TP53. HTLV-1 endemic regions include Africa, the Caribbean, and South America in addition to Japan. Retrospective studies from the Western population have reported distinctive features from the Japanese cohort, e.g. younger age, more common lymphomatous presentation, and worse outcomes. Our group sought to evaluate the unique molecular features of ATLL in a large cohort of patients from the Caribbean and South America. Methods: We performed a multimodal genomic study on specimens from 169 patients encountered in the United States (Miami), Peru,...
Blood, 2021
Introduction Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hemato... more Introduction Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological malignancy with multi-organ and frequent skin involvement, and poor clinical outcomes. Based on the limited available data, the estimated incidence is 0.44% of all hematologic malignancies, representing less than 1% of acute leukemias, and 0.7% of cutaneous lymphomas. Due to the rarity of this entity, there have been relatively few studies characterizing the molecular profile of BPDCN. We examined a cohort of 51 patients with BPDCN using OncoScan chromosome microarray, which provides genome-wide copy number abnormality (CNA) analysis. Methods An international cohort of BPDCN cases were collected from centers in Brazil (Laboratorio de Patologia, Botucatu), Swtizerland (University of Zurich), France (Hospital St. Louis, Paris), Peru (Instituto Nacional de Enfermedades Neoplasicas, Lima), Canada (Department of Pathology, University of Montreal), Italy (Derpartment of Pathology, Univ...
European Journal of Cancer, 2018
Glioblastoma multiforme (GBM) is the most common and most aggressive primary brain tumor in
Diffuse large B-cell lymphoma is a rare neoplasm of the central nervous system with aggressive be... more Diffuse large B-cell lymphoma is a rare neoplasm of the central nervous system with aggressive behavior and poor outcome. CD5 expression in nodal or extranodal in this neoplasm is infrequent. These cases tend to be more aggressive than the CD5 negative cases. Herein, we report a case of primary brain CD5-positive diffuse large B-cell lymphoma presenting in an immunocompetent 64-year-old woman. She presented with intensity frontoparietal headache, nausea, vomiting, generalized seizures and confusional symptoms. Nuclear magnetic resonance showed characteristics of malignant lymphoma. The patient received treatment with corticoids with good response. Two years after the initial condition, she presented symptoms again. Brain images studies showed bifrontal neoplasm. No tumors were found in other sites. On the basis of morphology and immunohistochemistry, the diagnosis was CD5-positive diffuse large B-cell lymphoma. The present case confirms in this neoplasm multiple pathways are altered...
Revista Peruana de Medicina Experimental y Salud Pública, 2015
Glioblastoma (GB) is the most common and most lethal primary brain tumor. Epidemiologic informati... more Glioblastoma (GB) is the most common and most lethal primary brain tumor. Epidemiologic information indicate that its incidence is lower in Hispanic race. Surgery is the only curative strategy and has recently introduced new strategies that increase resection rates. The use of concurrent chemotherapy with radiotherapy improves survival of patients but is associated with toxicity. Improved understanding of molecular biology of GB allows the identification of predictive biomarkers of response and prognosis as well as therapeutic targets for the development of new therapeutic strategies. Among biomarkers are currently available 1p /19q codeletion, IDH mutation and O6-methylguanine DNAmethyltransferase promoter methylation. The identification therapeutic targets enables the development of new drugs and their evaluation in clinical trials, but none has been prospectively validated in phase III clinical trials.
Spinal cord oligodendroglioma is an extremely unusual glial neoplasm and only 52 cases have been ... more Spinal cord oligodendroglioma is an extremely unusual glial neoplasm and only 52 cases have been reported at this time. We report the case of a 52 year-old man with paraplegia and an intramedullary tumor of the spinal cord at levels C7 to T4. The final diagnosis was anaplastic oligodendroglioma with an isolated chromosome 1p deletion.
Future microbiology, 2020
Aim: Helicobacter pylori is usually detected based on hematoxylin-eosin (H-E) features, but, immu... more Aim: Helicobacter pylori is usually detected based on hematoxylin-eosin (H-E) features, but, immunohistochemistry (IHC) and real-time PCR (RT-PCR) are more precise in chronic-gastritis. We evaluated the relevance of these tests in Peruvian gastric cancer samples. Materials & methods: We performed and evaluated H-E, IHC staining and RT-PCR in 288 gastric tumors. Slides were independently evaluated by three pathologists. Results: H. pylori was detected in 167/287 through H-E, 140/288 through IHC and 175/288 through RT-PCR, and positive-status were associated (p < 0.001). H. pylori detection by H-E had a good concordance with IHC (kappa index = 0.632) but poor with RT-PCR (kappa index = 0.317). Higher median gene-copies were found in high H. pylori density through H-E or IHC (p < 0.001). Conclusion: H-E evaluation is accurate in gastric cancer, and IHC and RT-PCR can complement its results.
Six cases of amoebic encephalitis admitted to the National Institute of Neoplastic Diseases betwe... more Six cases of amoebic encephalitis admitted to the National Institute of Neoplastic Diseases between the years 1994-2010 in Peru are reported. These cases were admitted for clinical suspicion of malignant primary brain tumor and one orbital-nasal sarcoma. All cases came from coastal regions; three were less than 24 years of age and four were male. The most common symptoms were headache and seizures. Three cases had more than one brain lesion. Stereotactic biopsy was performed in three patients and the differential pathological diagnosis in two cases was glioma of high and low grade. It was possible to confirm the diagnosis using molecular techniques in paraffin-embedded samples in three cases. All patients died within 15 days of admission to the institution. Amoebic encephalitis may be erroneously interpreted as a cerebral neoplasm, causing delay in the management of the infection.
Neuro-Oncology
OBJECTIVE An unexpectedly high incidence of sarcomas of the Central Nervous System (SCNS) was rec... more OBJECTIVE An unexpectedly high incidence of sarcomas of the Central Nervous System (SCNS) was recently observed in Peru. We describe clinical and biological characteristics of the disease. METHODS Seventy pediatric patients with primary SCNS diagnosed between January 2005 and June 2018 were analyzed. DNA methylation profiling and gene panel sequencing was available from 28 and 27 tumors, respectively. RESULTS Median age was 6 years (range 2–17.5), 66/70 patients had supratentorial tumors, 56 patients intratumoral hemorrhage at diagnosis. Three patients fulfilled clinical criteria of NF1; 35 had café-au-lait spots and/or freckling. DNA-methylation profiling classified 28/28 as “intracranial spindle cell sarcoma with rhabdomyosarcoma-like features and DICER1 mutations”. DICER1 mutations were found in 26/27, TP53 mutations in 22/27, and RAS-pathway gene mutations (NF1, KRAS, NRAS) in 19/27 tumors, all of which were somatic (germline control available in n=19 cases). Survival was analyz...
Poster Presentations - Proffered Abstracts