RESUMO
The tumor microenvironment (TME) is important in the pathogenesis and prognosis of lymphoma. Previous studies have demonstrated that features of the diffuse large B-cell lymphoma (DLBCL) TME can be associated with prognosis, but questions remain about the mechanisms underlying these TME features, and the interplay between tumor cells and the local TME. Therefore, we performed multispectral immunofluorescence (mIF) using two 6-color panels to interrogate the cellular proportions of T-cell subsets, macrophages, and natural killer cells in 57 cases of de novo DLBCL treated with R-CHOP chemotherapy. We found that very low CD3+ T-cell proportion and low CD4+PD1+ and CD8+PD1+ T cells have poor survival compared to those with a high T-cell proportion. Also, cases with concurrently low TIM3 and PD1 have a poor prognosis. This poor prognosis with low T-cell proportion was validated using immune deconvolution of gene expression profiling data from 351 cases of DLBCL and an additional cohort of 53 cases of DLBCL using routine immunohistochemistry. In addition, cases with loss of B2M, HLA I and/or HLA II protein expression on the tumor cells also had a low T-cell proportion, providing evidence that lack of these proteins allows for immune evasion. Overall, our results show that patients with DLBCL with a low T-cell proportion in the TME have a poor survival when treated with R-CHOP and exhibit mechanisms of immune escape.
Assuntos
Linfoma Difuso de Grandes Células B , Microambiente Tumoral , Humanos , Microambiente Tumoral/genética , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Prognóstico , Linfócitos T CD8-Positivos/metabolismo , Subpopulações de Linfócitos T/metabolismoRESUMO
BACKGROUND: Patients negative for the JAK2 p.V617F somatic variant are frequently reflexed to testing for MPL exon 10 variants. Detection of these variants via multiplexed allele-specific PCR followed by fragment analysis has been previously published. The present study builds on this concept by improving the detection of the p.W515A variant, adding a second allele-specific primer to detect the p.W515R variant, and incorporating an improved primer for p.S505N detection. METHODS: The W515 amplification employs 5'-labeled allele-specific forward primers to detect p.W515K, p.W515L, p.W515R, and p.W515A. The p.S505N amplification includes an allele-specific reverse primer with a tail extension. Fragments were subject to capillary electrophoresis on an ABI 3500 Genetic Analyzer and analyzed using GeneMapper 6.0 (Thermo Fisher Scientific). RESULTS: Thirty MPL-negative and 13 MPL-positive samples previously tested by a reference laboratory were tested with the MPL LDT. Results were 100% concordant. The MPL LDT has a limit of detection of at least 5% VAF for the p.W515 variants and 10% VAF for the p.S505N variant. CONCLUSION: Current MPL assays are predominantly focused on p.W515L/K and p.S505N mutations. We have engineered an MPL test for detecting p.W515A/L/K/R and p.S505N variants, thereby increasing the diagnostic yield with little additional expense or technician time.
Assuntos
Transtornos Mieloproliferativos , Neoplasias , Humanos , Neoplasias/genética , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Mutação/genética , Éxons , Códon , Janus Quinase 2/genética , Receptores de Trombopoetina/genéticaRESUMO
Primary CNS diffuse large B-cell lymphoma (PCNS-DLBCL) and systemic DLBCL harbor mutations in MYD88 and CD79B. DNA methyltransferase (MGMT) is methylated in some DLBCL. Our goal was to investigate the frequencies of these events, which have not been previously reported within the same series of patients with PCNS-DLBCL. Fifty-four cases of PCNS-DLBCL from two institutions were analyzed by Sanger sequencing for MYD88 and CD79B, and pyrosequencing for MGMT. MYD88 mutations were identified in 68.8% (35 of 51 cases), with L265P being the most frequent mutation. Mutations other than L265P were identified in 21.6% of cases, of which eight novel MYD88 mutations were identified. Of mutated cases, 17.6% had homozygous/hemizygous MYD88 mutations, which has not been previously reported in PCNS-DLBCL. CD79B mutations were found in six of 19 cases (31.6%), all in the Y196 mutation hotspot. MGMT methylation was observed in 37% (20 of 54 cases). There was no significant difference in median overall survival (OS) between the wild type and mutated MYD88 cases, or between methylated and unmethylated MGMT cases. However, a significant difference (P = 0.028) was noted in median OS between the wild type and mutated CD79B cases.
Assuntos
Antígenos CD79/genética , Neoplasias do Sistema Nervoso Central/genética , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Linfoma Difuso de Grandes Células B/genética , Fator 88 de Diferenciação Mieloide/genética , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Neoplasias do Sistema Nervoso Central/patologia , Metilação de DNA , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , PrognósticoRESUMO
Following the outbreak and subsequent pandemic of coronavirus disease 2019 (COVID-19), clinical diagnostic laboratories worldwide sought accurate and reliable testing methodologies. However, many laboratories were and still are hindered by a number of factors, including an unprecedented demand for testing, reagent and laboratory supply shortages and availability of qualified staff. To respond to these concerns, two separate laboratory-developed tests were validated for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using two different specimen types. In addition, these assays target different genomic regions of SARS-CoV-2, allowing for viral detection and mitigating genetic variation. Lower limit of detection and clinical evaluation studies showed detection of SARS-CoV-2 at 500 cp/mL with nasopharyngeal and saliva samples. These multiplexed RT-qPCR assays, although based on modified CDC, New York State Department of Health, and World Health Organization Emergency Use Authorization tests, allow for higher throughput and rapid turnaround time, benefiting patients, clinicians, and communities as a whole. These cost-effective tests also use readily obtainable reagents, circumventing commercial assay supply chain issues. The laboratory-developed tests described here have improved patient care and are highly adaptable should the need arise at other clinical diagnostic laboratories. Furthermore, the foundation and design of these assays may be modified in the future for detection of COVID-19 variants or other RNA-based viral detection tests.
Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , Genômica , Humanos , RNA Viral/análise , RNA Viral/genética , SARS-CoV-2/genética , Sensibilidade e EspecificidadeRESUMO
MYC rearrangement is a relatively rare genetic abnormality in follicular lymphoma (FL). In this study, we evaluated the relative frequency of MYC rearrangement in 522 cases of FL and studied their clinicopathologic, cytogenetic, and molecular characteristics. Fluorescence in situ hybridization studies for MYC (break-apart probe), MYC/IGH, IGH/BCL2, and BCL6 rearrangements were performed on tissue microarrays. Immunohistochemical stains for CD10, BCL2, BCL6, and MYC were performed and scored on MYC-rearranged cases. On 4 FL cases, a custom targeted panel of 356 genes was used for mutation analysis. Ten cases (1.9%) were positive for MYC rearrangement. Histologically, 6 of 10 cases were grade 1-2, and 4 cases were grade 3A. By immunohistochemistry, 9 of 9 tested cases were CD10+, all cases were BCL6+, and 9/10 cases were BCL2+. MYC protein staining was low in all cases tested. IGH/BCL2 rearrangement was detected in 5 of 9 cases, whereas BCL6 rearrangement was detected in 3 of 7 tested cases and 4 of 10 cases showed MYC/IGH rearrangement. The most commonly detected mutations in the MYC-positive cases included HLA-B, TNFRSF14, and KMT2D. MYC and/or B2M abnormalities were detected in 2 cases. In conclusion, MYC rearrangement is uncommon in FL and these cases do not appear to have specific histologic characteristics. Molecular analysis showed abnormalities in genes associated with transformation, namely MYC and B2M. Larger studies are needed to evaluate if MYC-rearrangement in FL has prognostic significance.
Assuntos
Biomarcadores Tumorais/genética , Rearranjo Gênico , Linfoma Folicular/genética , Proteínas Proto-Oncogênicas c-myc/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Análise Mutacional de DNA , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Linfoma Folicular/química , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/patologia , Masculino , Manitoba , Pessoa de Meia-Idade , Mutação , Prognóstico , Proteínas Proto-Oncogênicas c-myc/análise , Análise Serial de Tecidos , Estados UnidosRESUMO
PURPOSE: We performed detailed genomic analysis on 87 cases of de novo diffuse large B-cell lymphoma of germinal center type (GCB DLBCL) to identify characteristics that are associated with survival in those treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). EXPERIMENTAL DESIGN: The cases were extensively characterized by combining the results of IHC, cell-of-origin gene expression profiling (GEP; NanoString), double-hit GEP (DLBCL90), FISH cytogenetic analysis for double/triple-hit lymphoma, copy-number analysis, and targeted deep sequencing using a custom mutation panel of 334 genes. RESULTS: We identified four distinct biologic subgroups with different survivals, and with similarities to the genomic classifications from two large retrospective studies of DLBCL. Patients with the double-hit signature, but no abnormalities of TP53, and those lacking EZH2 mutation and/or BCL2 translocation, had an excellent prognosis. However, patients with an EZB-like profile had an intermediate prognosis, whereas those with TP53 inactivation combined with the double-hit signature had an extremely poor prognosis. This latter finding was validated using two independent cohorts. CONCLUSIONS: We propose a practical schema to use genomic variables to risk-stratify patients with GCB DLBCL. This schema provides a promising new approach to identify high-risk patients for new and innovative therapies.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Centro Germinativo/patologia , Linfoma Difuso de Grandes Células B/mortalidade , Mutação , Proteína Supressora de Tumor p53/genética , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Perfilação da Expressão Gênica , Centro Germinativo/efeitos dos fármacos , Centro Germinativo/metabolismo , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prognóstico , Estudos Retrospectivos , Rituximab/administração & dosagem , Taxa de Sobrevida , Translocação Genética , Vincristina/administração & dosagemRESUMO
Patients with non-small cell lung cancer (NSCLC) harboring ROS proto-oncogene 1 (ROS1) gene rearrangements show dramatic response to the tyrosine kinase inhibitor (TKI) crizotinib. Current best practice guidelines recommend that all advanced stage non-squamous NSCLC patients be also tested for ROS1 gene rearrangements. Several studies have suggested that ROS1 immunohistochemistry (IHC) using the D4D6 antibody may be used to screen for ROS1 fusion positive lung cancers, with assays showing high sensitivity but moderate to high specificity. A break apart fluorescence in situ hybridization (FISH) test is then used to confirm the presence of ROS1 gene rearrangement. The goal of Canadian ROS1 (CROS) study was to harmonize ROS1 laboratory developed testing (LDT) by using IHC and FISH assays to detect ROS1 rearranged lung cancers across Canadian pathology laboratories. Cell lines expressing different levels of ROS1 (high, low, none) were used to calibrate IHC protocols after which participating laboratories ran the calibrated protocols on a reference set of 24 NSCLC cases (9 ROS1 rearranged tumors and 15 ROS1 non-rearranged tumors as determined by FISH). Results were compared using a centralized readout. The stained slides were evaluated for the cellular localization of staining, intensity of staining, the presence of staining in non-tumor cells, the presence of non-specific staining (e.g. necrosis, extracellular mater, other) and the percent positive cells. H-score was also determined for each tumor. Analytical sensitivity and specificity harmonization was achieved by using low limit of detection (LOD) as either any positivity in the U118 cell line or H-score of 200 with the HCC78 cell line. An overall diagnostic sensitivity and specificity of up to 100% and 99% respectively was achieved for ROS1 IHC testing (relative to FISH) using an adjusted H-score readout on the reference cases. This study confirms that LDT ROS1 IHC assays can be highly sensitive and specific for detection of ROS1 rearrangements in NSCLC. As NSCLC can demonstrate ROS1 IHC positivity in FISH-negative cases, the degree of the specificity of the IHC assay, especially in highly sensitive protocols, is mostly dependent on the readout cut-off threshold. As ROS1 IHC is a screening assay for a rare rearrangements in NSCLC, we recommend adjustment of the readout threshold in order to balance specificity, rather than decreasing the overall analytical and diagnostic sensitivity of the protocols.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Canadá , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Proteínas Tirosina Quinases/genética , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/genética , Proto-Oncogenes , Espécies Reativas de OxigênioRESUMO
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2, created an unprecedented need for comprehensive laboratory testing of populations, in order to meet the needs of medical practice and to guide the management and functioning of our society. With the greater New York metropolitan area as an epicenter of this pandemic beginning in March 2020, a consortium of laboratory leaders from the assembled New York academic medical institutions was formed to help identify and solve the challenges of deploying testing. This report brings forward the experience of this consortium, based on the real-world challenges which we encountered in testing patients and in supporting the recovery effort to reestablish the health care workplace. In coordination with the Greater New York Hospital Association and with the public health laboratory of New York State, this consortium communicated with state leadership to help inform public decision-making addressing the crisis. Through the length of the pandemic, the consortium has been a critical mechanism for sharing experience and best practices in dealing with issues including the following: instrument platforms, sample sources, test performance, pre- and post-analytical issues, supply chain, institutional testing capacity, pooled testing, biospecimen science, and research. The consortium also has been a mechanism for staying abreast of state and municipal policies and initiatives, and their impact on institutional and laboratory operations. The experience of this consortium may be of value to current and future laboratory professionals and policy-makers alike, in dealing with major events that impact regional laboratory services.
RESUMO
The Prolactin Inducible Protein (PIP) is a 15â¯kDa protein secreted by normal apocrine glands, including salivary, lacrimal and sweat glands. PIP levels are normally low in the mammary glands of healthy individuals, but high levels have been observed in pathological conditions of the breast such as benign breast cystic disease and breast cancer. While the function of PIP is not well elucidated, accumulating evidence strongly point to a role in both innate and adaptive immunity. Using PIP deficient mice (Pip-/- mice) our laboratory demonstrated that loss of PIP function led to impaired T helper type 1 response and cell mediated immunity. In the present study we provide additional supporting evidence showing abnormal lymphocytic distribution in primary and secondary lymphoid organs of Pip-/- mice. Significant morphological changes in the Eustachian tube, an immune-protected site where PIP is normally found, were also associated with the absence of PIP. Collectively, these results further support an immuno-regulatory role for PIP and have implications for a spectrum of immune-related illnesses including otitis media and hearing loss as well as breast cancer.
Assuntos
Tuba Auditiva/anormalidades , Linfonodos/anormalidades , Proteínas/imunologia , Baço/anormalidades , Células Th1/imunologia , Timo/anormalidades , Animais , Feminino , Imunidade Celular , Masculino , Camundongos Knockout , Proteínas/genéticaRESUMO
Differentiating malignant melanoma from benign melanocytic lesions can be challenging. We undertook this study to evaluate the use of the immunohistochemical mitosis marker phospho-Histone H3 (pHH3) and the proliferation markers Ki-67 and survivin in separating malignant melanoma from benign nevi. Sixty-six melanocytic lesions (18 malignant melanomas, 8 Spitz nevi, 20 dysplastic nevi, and 20 compound nevi) were stained with antibodies to pHH3, Ki-67, and survivin. No pHH3 expression was detected in the dermis of compound and dysplastic nevi. Rare mitoses were observed in the superficial dermis in 3 of 8 Spitz nevi (37%). Staining for pHH3 was higher in malignant melanomas [average 25 per 10 high-power field (HPF), range 2-75 per 10 HPF] than in Spitz nevi (average 0.5 per 10 HPF, range 0-2 per 10 HPF) and was heterogeneously distributed in the malignant melanomas compared with a superficial dermal location in Spitz nevi. There was no cytoplasmic staining for survivin in any of the 66 melanocytic lesions and no nuclear staining in any of the benign ones. Survivin nuclear staining was present in 12 of 18 cases of malignant melanoma (67%) with an average index of 7% (range 0%-15%). In benign melanocytic lesions, the Ki-67 index was less than 5% (range 0%-4%) and staining was present close to the dermo-epidermal junction compared with an average index of 27% in melanomas (range 5%-50%) and a generally heterogeneous pattern of staining throughout the dermis. pHH3 and Ki-67 can be useful adjuncts to histopathology to separate malignant melanoma from benign nevi. pHH3 is especially useful to highlight mitoses and to rapidly assess the mitotic activity in melanocytic lesions.
Assuntos
Biomarcadores Tumorais/análise , Histonas/análise , Antígeno Ki-67/análise , Melanoma/química , Proteínas Associadas aos Microtúbulos/análise , Proteínas de Neoplasias/análise , Nevo de Células Epitelioides e Fusiformes/química , Nevo Pigmentado/química , Neoplasias Cutâneas/química , Adolescente , Adulto , Idoso , Biópsia por Agulha , Distribuição de Qui-Quadrado , Pré-Escolar , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Lactente , Proteínas Inibidoras de Apoptose , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Nevo de Células Epitelioides e Fusiformes/patologia , Nevo Pigmentado/patologia , Probabilidade , Prognóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias Cutâneas/patologia , SurvivinaRESUMO
OBJECTIVES: To assess bone marrow (BM) sampling in academic medical centers. METHODS: Data from 6,374 BM samples obtained in 32 centers in 2001 and 2011, including core length (CL), were analyzed. RESULTS: BM included a biopsy (BMB; 93%) specimen, aspirate (BMA; 92%) specimen, or both (83%). The median (SD) CL was 12 (8.5) mm, and evaluable marrow was 9 (7.6) mm. Tissue contraction due to processing was 15%. BMB specimens were longer in adults younger than 60 years, men, and bilateral, staging, and baseline samples. Only 4% of BMB and 2% of BMB/BMA samples were deemed inadequate for diagnosis. BM for plasma cell dyscrasias, nonphysician operators, and ancillary studies usage increased, while bilateral sampling decreased over the decade. BM-related quality assurance programs are infrequent. CONCLUSIONS: CL is shorter than recommended and varies with patient age and sex, clinical circumstances, and center experience. While pathologists render diagnoses on most cases irrespective of CL, BMB yield improvement is desirable.
Assuntos
Doenças da Medula Óssea/patologia , Medula Óssea/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia com Agulha de Grande Calibre , Doenças da Medula Óssea/diagnóstico , Exame de Medula Óssea/normas , Canadá , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos , Adulto JovemRESUMO
In anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK) activates (phosphorylates) signal transducer and activator of transcription 3 (STAT3) with subsequent cytoplasmic expression, in some cases, of survivin and tissue inhibitor of metalloprotease 1 (TIMP1). These are inhibitors of apoptosis and negative prognostic factors. CD56 is also a negative prognostic marker in ALCL. We assayed 40 cases of predominantly ALK+ pediatric ALCL for pSTAT3, survivin, TIMP1, and CD56 using immunohistochemical analysis. The patients were derived from a Pediatric Oncology Group treatment protocol that showed 72% event-free survival at 4 years for ALCL. The results show that in advanced-stage pediatric ALCL, although most tumors express ALK and a majority show activated STAT3, cytoplasmic localization of survivin and TIMP1 is not frequent, nor is expression of CD56. This may help, in part, explain the relatively good prognosis of pediatric ALCL.
Assuntos
Linfoma Difuso de Grandes Células B/química , Proteínas Tirosina Quinases/análise , Fator de Transcrição STAT3/análise , Adolescente , Adulto , Quinase do Linfoma Anaplásico , Antígeno CD56/análise , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Proteínas Inibidoras de Apoptose , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Proteínas Associadas aos Microtúbulos/análise , Proteínas de Neoplasias/análise , Receptores Proteína Tirosina Quinases , Survivina , Inibidor Tecidual de Metaloproteinase-1/análiseRESUMO
Human granulocytic anaplasmosis is a rare, tick-borne infectious disease caused by Anaplasma phagocytophilum. Herein, we report a rare case of human granulocytic anaplasmosis associated with cytopenias and clonal expansion of gamma/delta T-cells in the bone marrow. A 77-year old man presented multiple times to the emergency department complaining of muscle weakness. Complete blood count detected cytopenias and peripheral blood smear showed pseudo Pelger-Huet neutrophils. These findings prompted bone marrow evaluation with ancillary studies including flow cytometry, karyotyping and T-cell rearrangement studies. Careful examination of peripheral blood smear revealed very rare neutrophils with intracytoplasmic inclusions, suggestive of ehrlichiosis/anaplasmosis. Bone marrow evaluation showed dyserythropoiesis, dysmegakaryopoiesis and prominence of hemophagocytic histiocytes. Furthermore, an increased number of T-cells was seen in the bone marrow and flow cytometry showed excess of gamma/delta T-cells, while T-cell rearrangement studies detected a T-cell clone. Serologic evaluation confirmed the diagnosis of anaplasmosis. This case nicely illustrates hematologic sequelae of infection with Anaplasma and potential diagnostic pitfalls, such as myelodysplastic syndrome and T-cell lymphoproliferative disorder. To our knowledge, this is the first reported case of clonal expansion of gamma/delta T-cells associated with anaplasmosis. Pathologists should be careful and vigilant when screening peripheral blood smears, as they are often the first to raise the suspicion of anaplasmosis.
Assuntos
Anaplasmose/diagnóstico , Pancitopenia , Receptores de Antígenos de Linfócitos T gama-delta/análise , Idoso , Proliferação de Células , Células Clonais/patologia , Diagnóstico Diferencial , Humanos , Masculino , Linfócitos T/patologiaRESUMO
Composite lymphomas consist of 2 or more distinct lymphomas occurring in a single anatomical site or simultaneously in different sites and can be composed of any combination of B-cell non-Hodgkin lymphoma (NHL), T-cell NHL, or Hodgkin lymphoma (HL). Cases of composite lymphomas with more than 2 lymphomas are extremely rare, with only 4 reports in the literature. We report the case of a 49-year-old man with a triple composite lymphoma in a single lymph node, consisting of small lymphocytic lymphoma, follicular lymphoma, and mantle cell lymphoma in situ. The patient received multiple courses of chemotherapy and an autologous stem cell transplant, which resulted in complete remission. Then, 6 years after the stem cell transplant, he developed classical HL. This unique case is, to our knowledge, the first report of a patient with triple composite lymphoma consisting of 3 small mature B-cell NHLs, who subsequently developed a fourth lymphoma.
Assuntos
Linfoma Composto/patologia , Doença de Hodgkin/patologia , Leucemia Linfocítica Crônica de Células B/patologia , Linfoma Folicular/patologia , Linfoma de Célula do Manto/patologia , Linfoma não Hodgkin/patologia , Segunda Neoplasia Primária/patologia , Linfoma Composto/terapia , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Linfocítica Crônica de Células B/terapia , Linfonodos/patologia , Linfoma Folicular/terapia , Linfoma de Célula do Manto/terapia , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-IdadeRESUMO
The optimal use of transcription factors to determine B-lineage specificity in B-acute lymphoblastic leukemia/lymphoma (B-ALL) has not been fully investigated. We undertook an extensive immunohistochemical study of a panel of B-cell transcription factors in B- and T-ALL and Burkitt lymphoma to evaluate those with the best specificity and sensitivity. Tissue microarrays were constructed from 34 B-ALL, 19 T-ALL, and 30 Burkitt lymphoma samples. All 34 (100%) cases of B-ALL expressed PAX5; 32 (94%), BOB.1; 33 (97%), PU.1; 29 (85%), CD79a; 27 (79%), CD22; 2 (6%), CD20; 9 (26%), OCT-2; and 3 (9%), MUM1. Burkitt lymphoma cases were positive for PAX5 (30/30 [100%]), BOB.1 (27/30 [90%]), PU.1 (23/30 [77%]), CD79a (29/30 [97%]), CD22 (14/30 [47%]), CD20 (30/30 [100%]), OCT-2 (23/30 [77%]), and MUM1 (5/30 [17%]). T-ALLs were only positive for PU.1 (15/19 [79%]) and BOB.1 (12/19 [63%]). PAX5 demonstrated better specificity for B-lineage determination than BOB.1 and PU.1 and better sensitivity than CD79a, CD22, and CD20. These findings suggest that PAX5 has the greatest diagnostic usefulness and lineage determination in B-ALL, especially in cases with an inadequate specimen for flow cytometric analysis.
Assuntos
Biomarcadores Tumorais/metabolismo , Linfoma de Burkitt/metabolismo , Fator de Transcrição PAX5/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Células Precursoras de Linfócitos B/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Células da Medula Óssea , Linfoma de Burkitt/genética , Linfoma de Burkitt/patologia , Linhagem da Célula , Citometria de Fluxo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Imunofenotipagem , Análise de Sequência com Séries de Oligonucleotídeos , Fator de Transcrição PAX5/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Células Precursoras de Linfócitos B/patologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Valor Preditivo dos Testes , Análise Serial de TecidosRESUMO
An association between Hashimoto thyroiditis and papillary thyroid carcinoma has been postulated for decades. We undertook this study to identify potential precursors of papillary thyroid carcinoma in Hashimoto thyroiditis using a combination of morphologic, immunohistochemical, and molecular techniques. For the study, samples from 59 cases of Hashimoto thyroiditis were stained with antibodies to HBME1 and cytokeratin (CK)19. Tiny HBME1+ and CK19+ atypical cell clusters were identified and analyzed for the BRAF mutation by the colorimetric Mutector assay and allele-specific polymerase chain reaction. HBME1+ and CK19+ atypical cell clusters were identified in 12 (20%) of 59 cases. The minute size (<1 mm) of the clusters and the incomplete nuclear changes precluded a diagnosis of papillary microcarcinoma. The atypical cell clusters from all 12 cases were negative for BRAF. The absence of the BRAF mutation in these atypical cell clusters suggests that they may not be preneoplastic. Caution should be exercised in interpreting positive HBME1 or CK19 staining in Hashimoto thyroiditis.
Assuntos
Adenocarcinoma Papilar/genética , Doença de Hashimoto/genética , Mutação , Lesões Pré-Cancerosas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias da Glândula Tireoide/genética , Adenocarcinoma Papilar/metabolismo , Adenocarcinoma Papilar/patologia , Biomarcadores Tumorais/metabolismo , Análise Mutacional de DNA , DNA de Neoplasias/análise , Diagnóstico Diferencial , Doença de Hashimoto/metabolismo , Doença de Hashimoto/patologia , Humanos , Queratina-19/metabolismo , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Proteínas Proto-Oncogênicas B-raf/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologiaRESUMO
Therapeutic plasma exchange is a procedure used to remove pathologic substances from a patient's blood that has proven useful in some cases of drug overdose. Overdose by calcium channel blocker antihypertensive agents has been shown to be a cause of significant morbidity and can often times prove fatal. These agents cause systemic hypotension by inhibiting cell membrane calcium channels, which leads to a slowing of intracardiac electric conduction with consequent impairment of myocardial function and widespread vasodilation. Shock and metabolic acidosis result from the persistent hypotension. In high doses, calcium channel blocking agents cause insulin resistance. We describe the case of a previously healthy young woman who ingested a massive dose of amlodipine and was treated by therapeutic plasma exchange after non-responsiveness to conventional therapy. The case illustrates the need for utilization of therapeutic plasma exchange in the emergency management of certain cases of severe amlodipine overdose.
Assuntos
Anlodipino/intoxicação , Bloqueadores dos Canais de Cálcio/intoxicação , Troca Plasmática , Adulto , Overdose de Drogas/terapia , Feminino , Humanos , Tentativa de Suicídio , Resultado do TratamentoRESUMO
Sarcoidosis is a multisystemic disease that usually involves the lungs and lymph nodes, but almost any organ can be involved. Genitourinary involvement with sarcoidosis is extremely rare. We report the case of a 30-year-old African-American male who presented with a right-sided intrascrotal mass and diffuse lymphadenopathy. On further workup, he was found to have sarcoidosis. Two months of corticosteroid treatment resulted in the disappearance of his intrascrotal mass.
Assuntos
Sarcoidose/diagnóstico , Escroto/patologia , Doenças Testiculares/diagnóstico , Adulto , Glucocorticoides/uso terapêutico , Humanos , Masculino , Prednisona/uso terapêutico , Sarcoidose/tratamento farmacológico , Doenças Testiculares/tratamento farmacológicoRESUMO
Papillary thyroid carcinoma and its variants can be difficult to distinguish from cellular adenomatous nodules. Prior studies have advocated various antibodies to aid in the differential diagnosis, but there is little agreement on their utility. We undertook this study to evaluate immunohistochemical markers in the diagnosis and differential diagnosis of papillary thyroid carcinoma. Ten cases of papillary thyroid carcinoma were initially stained for HBME1, CK19, fibronectin1, Ki-67, Calretinin, p16, SFTPB and CITED1. Additionally, two previously untested antibodies to molecules that have been found to be upregulated in papillary thyroid carcinoma (CST6 and EPS8) were also evaluated. Of these, only HBME1, CK19 and fibronectin1 showed diagnostic utility. These three markers were then further evaluated in 51 papillary thyroid carcinomas and 57 benign thyroids. HBME1 was the most sensitive and specific marker, staining 49/51 papillary thyroid carcinomas and only 4/57 benign thyroids. CK19 was equally sensitive staining all 51 papillary thyroid carcinomas, but it was nonspecific staining 39 of 57 benign thyroids. A negative result, however, was helpful in excluding papillary thyroid carcinoma. Fibronectin1 was positive in 35/51 papillary thyroid carcinomas (69%) and 4/57 (7%) benign thyroids, but its utility was hampered by high background staining. These findings suggest that the combination of HBME1 and CK19 has the greatest diagnostic utility in the differentiation of papillary thyroid carcinoma from its benign mimics.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Papilar, Variante Folicular/diagnóstico , Técnicas Imunoenzimáticas/métodos , Queratina-19/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico , Carcinoma Papilar, Variante Folicular/metabolismo , Carcinoma Papilar, Variante Folicular/cirurgia , Diagnóstico Diferencial , Fibronectinas/metabolismo , Humanos , Doenças da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
The morphological presentation of malignant plasma cells in multiple myeloma (MM) varies from mature to anaplastic plasma cells with only one reported case of signet ring variant. We describe here another case of signet ring-like lambda light chain MM associated with extra-skeletal spread to lymph nodes, spleen and liver. The clinical and pathological presentations were atypical with no evidence of bone-lytic lesions or monoclonal component on protein electrophoresis, leading to a delay of several years in the diagnosis. Recognition of this morphological entity of MM may help in an early diagnosis of this rare variant.