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BACKGROUND Three driver mutations have been identified in patients with essential thrombocythemia - JAK2 V617F, CALR, and MPL. Out of these, JAK2 V617F is mostly common. These mutations are thought to be mutually exclusive; therefore, the initial workup may not include the identification of all mutations separately. CASE REPORT We present a case of a 55-year-old woman who was referred to the hematology clinic for an elevated platelet count noted when she was hospitalized for a renal stone. The patient was asymptomatic. A workup was initiated for essential thrombocythemia, and she was tested for JAK2 V617F mutation using an allele-specific polymerase chain reaction (AS-PCR) test in peripheral blood, which came back positive. The variant allele frequency was 2%. She underwent a bone marrow biopsy, and next-generation sequencing (NGS) showed a CALR mutation. A 52 bp deletion-type mutation was detected in the CALR gene on exon 9, with a variant allele frequency of 7%. The NGS did not detect JAK2 mutation due to its low sensitivity. She was started on aspirin alone as she was less than 60 years old and had no history of thrombotic events. The patient has been following up with the hematology clinic for the last 2 years and has not had any thrombotic events. CONCLUSIONS We propose that in patients with a low JAK2 V617 allele variant, testing for other driver mutations should be performed. In our patient, JAK2 mutation could be clonal hematopoiesis of indeterminate potential; therefore, the dominant mutation (CALR) would determine the disease phenotype.
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Trombocitemia Esencial , Trombosis , Femenino , Humanos , Persona de Mediana Edad , Trombocitemia Esencial/diagnóstico , Trombocitemia Esencial/genética , Mutación , Exones , Reacción en Cadena de la Polimerasa , Janus Quinasa 2/genéticaRESUMEN
BACKGROUND Histiocytic disorders, a group of disorders with heterogeneous pathogenesis, morphology, and clinical presentation, include Rosai-Dorfman disease, Langerhans cell histiocytosis, and Erdheim-Chester disease. They can mimic primary or metastatic tumors, both clinically and radiologically, when involving the brain. Therefore, it is crucial to present and discuss cases of histiocytic disorder involving the central nervous system (CNS) to provide new information on disease presentation and diagnosis more. In this paper, we present 2 cases of histiocytic lesions involving the brain and mimicking primary brain tumors. CASE REPORT Case 1: A 65-year-old man presented with increasing memory loss, confusion, and depression. CT scans showed an isolated 2.9×2.0×0.6 cm intracranial hypothalamic lesion. Case 2: A 61-year-old woman presented with dizziness and confusion for 3 weeks and headaches for 1 day. MRI showed a single 5.0×4.0×3.3 cm extra-axial, dural-based, avidly enhancing, well-defined lesion along the left parietal convexity causing mass effect upon the underlying brain parenchyma, left atrial effacement, and minimal vasogenic edema. CONCLUSIONS Histiocytic disorders are relatively rare in the CNS compared with other locations and mimic more common entities in the brain, such as glioma or metastatic tumors. Despite its rarity, one should remain aware of the condition and consider it in the differential diagnosis. This article provides a brief review and adds pivotal data to the literature.
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Neoplasias Encefálicas , Histiocitosis Sinusal , Anciano , Neoplasias Encefálicas/diagnóstico por imagen , Diagnóstico Diferencial , Femenino , Histiocitosis Sinusal/diagnóstico , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
Significance StatementUnilateral Eagle Syndrome is relatively rare and highlights important concepts in anatomy and pathophysiology. Bilateral Eagle Syndrome is exponentially more rare and has only been mentioned several times in the literature. Understanding the impact this can have on the human body and the severity of symptoms and sequelae is valuable for several types of specialists that treat this disorder.
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Osificación Heterotópica , Hueso Temporal , Humanos , Hueso Temporal/diagnóstico por imagen , Osificación Heterotópica/diagnóstico por imagenRESUMEN
BACKGROUND: Testicular cancer constitutes 1.0% of male cancer and typically carries a good prognosis. As far as we are aware, the role for hydrogen sulfide in testicular cancer and the level of hydrogen sulfide-synthesizing enzyme have never been addressed. Here we examined cystathionine gamma-lyase (CSE) expression in several germ-cell testicular tumors. MATERIALS AND METHODS: Tissue microarrays were employed to examine CSE expression in 32 benign testicular samples, 88 testicular seminomas, 34 embryonal carcinomas, 4 mature teratomas, and 16 yolk sac tumors, and CSE expression was compared to that seen in benign testicular tissue. RESULTS: Compared to benign testicular tissue, CSE expression was increased in all three types of testicular neoplasm but not in mature teratomas. Highest CSE expression was identified in embryonal carcinomas, which often show a relatively aggressive clinical course. CONCLUSION: For the first time, we show that CSE is increased in several common testicular germ-cell tumor types.
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Carcinoma Embrionario/metabolismo , Cistationina gamma-Liasa/metabolismo , Tumor del Seno Endodérmico/metabolismo , Neoplasias Testiculares/metabolismo , Regulación hacia Arriba , Estudios de Casos y Controles , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Seminoma , Análisis de Matrices TisularesRESUMEN
Non-Hodgkin's lymphoma (NHL) is a common malignancy of childhood; however, a lung primary presentation is an uncommon finding, as is finding an association with the Epstein-Barr virus (EBV). We report the case of a 23-month-old female who developed EBV-associated diffuse large B-cell lymphoma (DLBCL) that was initially thought to be pneumonia. Extensive tissue necrosis, focal angioinvasion, and angiodestruction were observed. She was refractory to various therapy regimens, subsequently developed DLBCL in the central nervous system, and eventually expired. Although EBV+ DLBCL was initially considered to occur predominantly in elderly patients over 50 years of age, it is now increasingly recognized to occur in younger patients with primarily nodal involvement who have overall better prognoses. To our knowledge, this case is the first reported EBV+ DLBCL occurring in a patient below two years of age with lung involvement as the initial clinical presentation.
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Gamma delta (γδ) T-cell antigen receptor (TCR) expression and its related T-cell differentiation are not commonly reported in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL). Here we report two pediatric T-ALL cases and present their clinical features, histology, immunophenotypes, cytogenetics, and molecular diagnostic findings. The first patient is a two-year-old girl with leukocytosis, circulating lymphoblasts, and a cryptic insertion of a short-arm segment at 10p12 into the long-arm segment of 11q23 resulting in an MLL and AF10 fusion transcript, which may be the first reported in γδ T-ALL. She responded to the chemotherapy protocol poorly and had persistent diseases. Following an allogeneic bone marrow transplant, she went into remission. The second patient is an eleven-year-old boy with a normal white cell count, circulating blasts, and a normal karyotype, but without any immature cellular markers by flow cytometric analysis. He responded to the chemotherapy well and achieved a complete remission. These cases demonstrate the diverse phenotypic, cytogenetic, and molecular aspects of γδ T-ALL. Early T-precursor- (ETP-) ALL and their differential diagnosis from other mature γδ T-cell leukemia/lymphomas are also discussed.
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BACKGROUND: T-cell lymphomas with anaplastic morphology typically comprise of anaplastic lymphoma kinase positive, anaplastic large cell lymphoma (ALK+ ALCL), ALK-negative ALCL (ALK- ALCL), and primary cutaneous ALCL (PC-ALCL). However, other entities such as diffuse large B-cell lymphoma, peripheral T-cell lymphoma, Hodgkin lymphoma, and undifferentiated carcinoma can also show similar anaplastic features. AIMS: To study the clinical features and histological spectrum of ALCL and emphasize the role of immunohistochemistry (IHC) in their diagnosis and categorization. SETTING AND DESIGN: Eight cases of ALCL diagnosed over a period of 4 years were selected for the study. MATERIALS AND METHODS: Histopathological review and IHC was performed on all cases. Two ALK+ ALCL cases were tested by fluorescent in situ hybridization (FISH) for t(2;5)(p23;q35). RESULTS: There were four cases of ALK+ ALCL and two each of ALK- ALCL and PC-ALCL. Histologically, all the subtypes showed pleomorphic and "hallmark" cells with strong CD30 expression and variable loss of T-cell antigens. One case of PC-ALCL was leukocyte common antigen (LCA) negative. Epithelial membrane antigen was positive in all the six systemic ALCL cases. Two cases tested for t(2;5)(p23;q35) by FISH were positive. CONCLUSIONS: Diagnosis of ALCL is based on recognizing the key morphological features, especially the presence of "hallmark" cells. IHC is essential for confirmation of diagnosis and excluding other malignancies with anaplastic morphology. The inclusion of CD30 in the initial IHC panel will help identify LCA negative cases and avoid misdiagnosis.
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Histiocytic sarcoma (HS) is an extremely rare non-Langerhans cell disorder with an aggressive course and limited treatment options. Recent advances in molecular/genetic sequencing have suggested a common clonal origin between various hematolymphoid disorders and cases of secondary HS. Deriving conclusions from previously reported cases of HS arising secondarily to certain hematolymphoid disorders, here we have tried to provide insight into the mechanisms influencing this evolution. We also discuss a clinical case of a 72-year-old man with a diagnosis of chronic myeloid leukemia (CML), presenting subsequently with a heterogeneous liver mass positive with a diagnosis of HS. The liver mass showed a retained BCR-ABL1 translocation suggesting clonality between the CML and HS. As seen in our case and other reported cases of HS derived secondarily, the concurrent expression of immunoglobulin heavy (IGH)-/light-chain rearrangements or cytogenetic markers common to the primary malignancy suggests an evolutionary mechanism involving lineage switching that could potentially be influenced by genetic or epigenetic cues which may occur at the level of a progenitor or the malignant cell itself.
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Sarcoma Histiocítico/diagnóstico , Sarcoma Histiocítico/etiología , Sarcoma Histiocítico/terapia , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Primarias Secundarias/etiología , Neoplasias Primarias Secundarias/terapia , Anciano , Biopsia , Médula Ósea/patología , Reprogramación Celular , Diagnóstico Diferencial , Epigénesis Genética , Secuenciación de Nucleótidos de Alto Rendimiento , Sarcoma Histiocítico/epidemiología , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Masculino , Mutación , Neoplasias Primarias Secundarias/epidemiologíaRESUMEN
BACKGROUND: The overall prognosis of multiple myeloma has improved significantly over the last 15 years. We wondered whether the overall improvement would also be seen in unselected patients in an academic center in Northwest Louisiana with a high proportion of minority patients, and if second malignant neoplasms are relevant for our patients. MATERIALS AND METHODS: Between 1998 and 2009, 215 patients were treated for multiple myeloma at our center and had complete follow-up until May 2013. RESULTS: The mean survival of patients with multiple myeloma increased from 3.25 to 5.34 years, which is comparable to patients treated at larger centers. No prognostic difference was observed in the subgroups of myeloma patients. Among 215 patients followed for the development of secondary cancers, 16 already had a preexisting or concomitant malignancy (7.4%) and 10 developed secondary cancers. Our data indicate a significant background of histologically unrelated cancers and a cumulative incidence of new cancers of about 20% after 10 years of follow-up. Based on SEER data, preexisting or secondary cancers were not statistically increased in our population. CONCLUSIONS: The use of autologous transplantation and the introduction of new agents resulted in a significant improvement in the prognosis of multiple myeloma. Other cancers are not statistically increased before or after multiple myeloma is diagnosed and are not prognostically relevant.
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Mieloma Múltiple/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Louisiana/epidemiología , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Estadificación de Neoplasias , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/etiología , Pronóstico , Factores de Riesgo , Trasplante de Células Madre , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
Secondary leukemia is a common late complication after exposure to cancer therapies such as chemotherapy and radiotherapy. With the increase in the overall survival of cancer patients over the past 3 decades, treatment-related malignant neoplasms have increased in incidence. Secondary leukemias due to breast cancer and Hodgkin lymphoma have been studied in detail, but to our knowledge only a few case studies have reported secondary leukemias with previous lung cancer.¹â»4 Lung cancer is the leading cause of cancer death in the United States.5 Since the overall survival (OS) as well as the progression-free survival (PFS) of lung cancer has improved, secondary malignancies, which are usually aggressive and have a poor prognosis, have become a common occurrence among survivors. The use of concurrent chemo-radiotherapy could increase the risk for secondary cancers. Here we report the case of a patient who developed treatment-related acute myelogenous leukemia (t-AML) with a likely prior myelodysplasia (t-MDS) after receiving combined chemo-radiotherapy for lung cancer.
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Among the plasma cell dyscrasias, non-secretory myeloma is one of the rarest. This diagnosis is based on the absence of monoclonal proteins in the serum and urine. When serum free light chains are trace and the kappa: lambda ratio normal, clonality may however be established by PCR. We present a case of an oligosecretory myeloma confirmed by PCR, which would have hitherto been classified as non-secretory.
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Mieloma Múltiple/complicaciones , Mieloma Múltiple/metabolismo , Proteínas de Mieloma/metabolismo , Paraproteinemias/etiología , Adulto , Biopsia , ADN de Neoplasias/análisis , Diagnóstico Diferencial , Humanos , Masculino , Mieloma Múltiple/diagnóstico , Proteínas de Mieloma/genética , Paraproteinemias/sangre , Reacción en Cadena de la PolimerasaAsunto(s)
Anemia/etiología , Exantema/etiología , Hepatomegalia/etiología , Histiocitosis de Células de Langerhans/complicaciones , Histiocitosis de Células de Langerhans/diagnóstico , Esplenomegalia/etiología , Histiocitosis de Células de Langerhans/patología , Humanos , Lactante , Masculino , RecurrenciaRESUMEN
Karyopyknotic cytoplasmic inclusions in neutrophils (KPCI) have been previously called "Howell-Jolly" like inclusions and identified in immunosuppressed patients with human immunodeficiency virus (HIV) and in patients with various malignancies who have undergone chemotherapy. Attempts to characterize these inclusions have included the Grocott's methenamine silver (GMS), periodic acid Schiff (PAS), Gram, and Feulgen stains. Previous authors have concluded that these inclusions are of deoxyribonucleic acid (DNA) origin. We present a case describing an additional method to confirm this observation and to document previously undescribed curvilinear forms.
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Inclusiones Eritrocíticas/patología , Linfoma de Células del Manto/patología , Neutrófilos/patología , Histocitoquímica , Humanos , Leucocitos/patología , Masculino , Persona de Mediana EdadRESUMEN
Primary tracheal non-Hodgkin's lymphoma (NHL) is rare, with fewer than 30 cases reported to date. We review the clinical presentation, evaluation, and treatment of 2 cases of tracheal NHL mimicking granulation tissue. The first patient was a 67-year-old man with myelodysplastic syndrome and Crohn's disease who had a recurring lesion of the proximal trachea causing significant airway obstruction. The second patient was a 47-year-old man with a history of multiple intubations who presented with dyspnea and stridor due to circumferential tracheal stenosis. In both cases, bronchoscopy revealed abundant granulation tissue, and the initial biopsy results indicated benign disease. However, after requests from the diagnostic team to rule out lymphoma, additional immunohistochemical stains and polymerase chain reaction testing confirmed NHL. Radiotherapy was initiated. The first patient responded well and remains disease-free after 4 years. The second patient died of airway obstruction due to severe distal tracheal stenosis. Recurrent granulation tissue should raise the suspicion of malignancy and prompt further tissue evaluation for evidence of lymphoma. Steroids for airway compromise may cause progression to mature stenosis as prednisone is used in the treatment of lymphoma. Localized disease involving the central airways may be treated successfully with limited chemotherapy and radiotherapy.
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Tejido de Granulación/patología , Linfoma no Hodgkin/diagnóstico , Neoplasias de la Tráquea/diagnóstico , Anciano , Broncoscopía , Resultado Fatal , Humanos , Linfoma no Hodgkin/patología , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Neoplasias de la Tráquea/patología , Estenosis Traqueal/diagnóstico por imagen , Estenosis Traqueal/patologíaRESUMEN
OBJECTIVE: To compare autoimmune lymphoproliferative syndrome (ALPS) and Stevens-Johnson syndrome (SJS) with respect to the defects in Fas- and Fas ligand (FasL)-mediated apoptosis. DATA SOURCES: Selected reviews, case reports, and original studies were searched in PubMed and MEDLINE for the keywords ALPS, SJS, Fas, FasL, and apoptosis. STUDY SELECTION: Case reports of ALPS and SJS were selected as examples of Fas- and FasL-mediated diseases. In addition, we selected articles that examined the pathophysiology of apoptosis in the context of Fas-FasL interaction. RESULTS: Failure to initiate apoptosis of abnormal T lymphocytes occurs in such diseases as ALPS, leading to the accumulation of double negative T cells with an increase in autoimmunity. In contrast to apoptotic failure, SJS is associated with a pathological increase in programmed keratinocyte cell death. CONCLUSION: The consequences of dysregulated Fas- and FasL-mediated apoptosis leads to self-reactivity, malignant transformation, and immune dysfunction. An understanding of underlying mechanisms and qualitative assessment of Fas and FasL may have clinical benefits when control of these homeostatic mechanisms is in question.
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Síndrome Linfoproliferativo Autoinmune/fisiopatología , Proteína Ligando Fas/metabolismo , Síndrome de Stevens-Johnson/fisiopatología , Receptor fas/metabolismo , Adulto , Apoptosis/fisiología , Síndrome Linfoproliferativo Autoinmune/tratamiento farmacológico , Síndrome Linfoproliferativo Autoinmune/inmunología , Síndrome Linfoproliferativo Autoinmune/patología , Proteína Ligando Fas/genética , Femenino , Humanos , Lactante , Síndrome de Stevens-Johnson/tratamiento farmacológico , Síndrome de Stevens-Johnson/patología , Receptor fas/genéticaRESUMEN
BACKGROUND: Fine-needle aspiration (FNA) has been used in the evaluation of lymphadenopathy for a long time and is highly reliable in the identification of metastatic malignancies. However, the role of FNA in the assessment of new lymphoproliferative disorders continues to be a subject of debate. The objective of the current study was to evaluate the role of molecular cytogenetic studies in FNA diagnoses of lymphoproliferative disorders. METHODS: A retrospective, computer-based search for lymph node FNAs from 2006 to 2007 was performed. Cases with either fluorescence in situ hybridization (FISH) and/or polymerase chain reaction (PCR) studies were subjected to further analysis. RESULTS: In total, 243 lymph node FNAs were performed during the period, including 104 that were positive/suspicious for metastatic malignancies, 16 that were positive/suspicious for lymphomas, 15 that demonstrated atypical lymphoid proliferation, 73 that were reactive, 14 that were deemed granulomas, and 21 that were determined to be nondiagnostic. Molecular analysis included combined FISH/PCR in 4 cases, FISH only in 7 cases, and PCR only in 4 cases. By using multiplex PCR, 6 cases with atypical/negative flow cytometry results were diagnosed as 4 B-cell lymphomas, 1 T-cell lymphoma, and 1 reactive lymph node; and 4 cases that had atypical T cells determined by flow cytometry were diagnosed as reactive. One CD10-negative follicular lymphoma and 2 cases with suspicious flow cytometry results were positive for t(14;18)(q32;q21) by FISH. Forty-five cases had follow-up histology with 3 false-negative findings and no false-positive results. CONCLUSIONS: In this study, multiplex PCR studies for immunoglobulin heavy-chain or T-cell receptor gene rearrangements were useful for demonstrating clonality, and FISH studies were able to detect translocations or gene rearrangements that allowed for the subclassification of B-cell non-Hodgkin lymphomas.
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Biopsia con Aguja Fina , Hibridación Fluorescente in Situ , Ganglios Linfáticos/patología , Trastornos Linfoproliferativos/diagnóstico , Técnicas de Diagnóstico Molecular , Reacción en Cadena de la Polimerasa , Aberraciones Cromosómicas , Humanos , Linfoma/diagnóstico , Linfoma/genética , Trastornos Linfoproliferativos/genéticaRESUMEN
Warthin's tumor is rarely associated with malignant lymphoma. Only 18 cases were reported in the literature so far. In most cases the latter is a low grade process, including Marginal zone/Mucosa associated lymphoid tissue (MALT) type lymphoma, follicular lymphoma, and rarely diffuse large cell lymphoma which may arise de novo or secondary to low grade lymphoma. This study was conducted to determine the prevalence of occult B cell monoclones and genetic alterations in Warthin's tumor. Fourteen cases of Warthin's tumor were stained with antibodies to CD3, CD20, kappa and lambda light chains. On six cases of randomly selected Warthin's tumor, polymerase chain reaction (PCR) of IgH gene rearrangement (IgH-GR) was performed on genomic DNA extracted from formalin-fixed paraffin embedded tissue. One case of primary salivary gland indolent B-cell lymphoma and 3 cases of sialadenitis were analyzed by the same methods for comparison. In all Warthin's tumor and sialadenitis cases most of lymphoid stroma was B cell phenotype and concentrated in germinal centers. T cells were mostly located between germinal centers. No light chain restriction was demonstrable by kappa and lambda immunostains. Molecular genetic studies failed to show IgH-GR by FISH and showed polyclonal by IgH PCR. In contrast, the lymphoma case showed a diffuse proliferation of small B cells with light chain restriction and a minor component of reactive T cells. FISH showed IgH-GR and bcl-2 gene translocation with monoclonality by IgH PCR. Our study concludes that the lymphoid stroma of Warthin's tumor is reactive.
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OBJECTIVE: To report the 12th case of a patient with a plasma cell granuloma of the thyroid, a rare cause of goiter and hypothyroidism. METHODS: We present a case report of a woman with a plasma cell granuloma of the thyroid. The clinical and pathologic features of the lesion are described, the differential diagnosis is discussed, and the relevant literature is reviewed. RESULTS: Plasma cell granulomas are uncommon benign lesions most typically located in the lung and only rarely identified in other organs. Only 11 cases of plasma cell granuloma of the thyroid gland have been reported previously. We describe the case of a 55-year-old woman with a long history of hypothyroidism and compressive symptoms from an enlarging neck mass. A thyroidectomy was performed. On gross examination, the thyroid had been replaced by firm, white, fibrotic tissue with a multinodular appearance. On microscopy, the infiltrate consisted predominantly of plasma cells that were polyclonal with the expression of both kappa and lambda light chains. A minor component of CD5- and CD20-positive (T and B) lymphocytes was observed. These features were important for establishing the diagnosis of a plasma cell granuloma and distinguishing the lesion from a plasmacytoma. CONCLUSION: This is the 12th reported case of plasma cell granuloma of the thyroid gland, a very rare cause of either a diffuse or a nodular goiter and hypothyroidism. The presence of a polyclonal plasma cell population with the expression of both kappa and lambda light chains helps to distinguish a plasma cell granuloma from a malignant plasmacytoma of the thyroid gland.
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Granuloma de Células Plasmáticas/diagnóstico , Enfermedades de la Tiroides/diagnóstico , Femenino , Granuloma de Células Plasmáticas/inmunología , Granuloma de Células Plasmáticas/cirugía , Humanos , Inmunofenotipificación , Persona de Mediana Edad , Enfermedades de la Tiroides/inmunología , Enfermedades de la Tiroides/cirugía , TiroidectomíaRESUMEN
BACKGROUND: For Philadelphia chromosome positive (Ph+) leukemias (chronic myelogenous leukemia [CML], acute lymphoblastic leukemia [ALL], and rare other leukemias), both allogeneic transplantation and treatment with tyrosine kinase inhibitors offer chances of molecular remission (the molecular marker being consistently undetectable). Molecular remission is defined as a reduction in the quantification of BCR-ABL transcripts to an undetectable level by molecular diagnostic methods, and is considered as a surrogate marker for cure or long-term disease control. The molecular diagnostic methods including fluorescence in situ hybridization (FISH) and quantitative reverse transcription-polymerase chain reaction (QRT-PCR) are more sensitive than classical cytogenetic analysis for the detection of BCR-ABL positive cells. QRT-PCR, due to its superior sensitivity, is considered the gold standard for the follow-up of Ph+ leukemias treated with imatinib. AIM: The objective of our study was to compare the diagnostic and clinical usefulness of FISH and QRT-PCR at different timepoints for Ph+ leukemias. PATIENTS AND METHODS: We investigated 23 unselected patients with Ph+ CML (n = 21) or Ph+ ALL (n = 2) at 77 different timepoints in a comparative study with both FISH and QRT-PCR using commercially available reagents in a routine laboratory. RESULTS: Our study demonstrated a good correlation of QRT-PCR with FISH in detecting the BCR-ABL fusion gene among patients with CML or ALL (coefficient of correlation = 0.77493, p < 0.0001, using Spearman's correlation procedure). All newly diagnosed or untreated cases were positive with both methods. Lower coefficients of correlation were found when FISH and QRT-PCR were correlated with the white blood cell count (WBC). An overall concordance of FISH and QRT-PCR (being either negative or positive in both tests) was found in 65 cases (84.4%) and a discrepancy identified in 12 cases (15.6%). CONCLUSIONS: We confirm that QRT-PCR allows precise measurement of low levels of BCR-ABL transcripts and can serve as a sensitive indicator for minimal residual disease. In addition, we demonstrate in most cases a good correlation of QRT-PCR with FISH in detecting the BCR-ABL fusion gene among patients with CML or Ph+ ALL. FISH is not suitable for monitoring minimal residual disease.
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Proteínas de Fusión bcr-abl/metabolismo , Hibridación Fluorescente in Situ/métodos , Leucemia/diagnóstico , Leucemia/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Adulto , Anciano , Recuento de Células Sanguíneas , Femenino , Estudios de Seguimiento , Humanos , Leucemia/sangre , Leucocitos , Masculino , Persona de Mediana EdadRESUMEN
The pathologic diagnosis of multiple myeloma and other plasma cell dyscrasias includes histopathologic examination of a bone marrow aspirate and biopsy and clinical laboratory tests to assess end organ damage and other prognostic information. Plasma cell dyscrasias are characteristically classified and staged based on the results of these pathologic studies in conjunction with other clinical and radiologic parameters. New staging systems such as the International Staging System (ISS) use readily available laboratory tests to stratify prognostic subgroups. The continued introduction of new laboratory assays will help improve our understanding of plasma cell dyscrasias and the therapeutic management of these patients.