RESUMO
Therapy-related myeloid neoplasms (t-MNs) are a complication of treatment with cytotoxic chemotherapy and/or radiation therapy. The majority of t-MNs show chromosomal abnormalities associated with myelodysplastic syndrome (MDS) or KMT2A rearrangements and are characterized by poor clinical outcomes. A small but substantial subset of patients have normal karyotype (NK) and their clinical characteristics and mutational profiles are not well studied. We retrospectively studied patients diagnosed with t-MN at three institutions and compared the mutational profile and survival data between t-MNs with NK and t-MNs with abnormal karyotype (AK). A total of 204 patients with t-MN were identified including 158 with AK and 46 with NK. NK t-MNs, compared to AK, were enriched for mutations in TET2 (p < 0.0001), NPM1 (p < 0.0001), ASXL1 (p = 0.0003), SRSF2 (p < 0.0001), RUNX1 (p = 0.0336) and STAG2 (p = 0.0099) and showed a significantly lower frequency of TP53 mutations (p < 0.0001). Overall survival (OS) was significantly lower in AK t-MNs as compared to NK cases (p = 0.0094). In our study, NK t-MNs showed a significantly better OS, a higher prevalence of MN-associated mutations and a lower frequency of TP53 mutations compared to their AK counterparts. The distinct clinical and mutational profile of NK t-MNs merits a separate classification.
Assuntos
Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Segunda Neoplasia Primária , Cariótipo Anormal , Genômica , Humanos , Cariótipo , Leucemia Mieloide Aguda/genética , Mutação , Síndromes Mielodisplásicas/genética , Prognóstico , Estudos RetrospectivosRESUMO
Nodal follicular helper T-cell-derived lymphoproliferations (specifically the less common peripheral T-cell lymphomas of follicular type) exhibit a spectrum of histologic features that may mimic reactive hyperplasia or Hodgkin lymphoma. Even though angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma of follicular type share a common biologic origin from follicular helper T-cells and their morphology has been well characterized, flow cytometry of peripheral T-cell lymphomas of follicular type has not been widely discussed as a tool for identifying this reactive hyperplasia/Hodgkin lymphoma mimic. We identified 10 peripheral T-cell lymphomas of follicular type with available flow cytometry data from five different institutions, including two cases with peripheral blood evaluation. For comparison, we examined flow cytometry data for 8 classical Hodgkin lymphomas (including 1 lymphocyte-rich classical Hodgkin lymphoma), 15 nodular lymphocyte predominant Hodgkin lymphomas, 15 angioimmunoblastic T-cell lymphomas, and 26 reactive nodes. Lymph node histology and flow cytometry data were reviewed, specifically for the presence of a CD3(-/dim)CD4(+) aberrant T-cell population (described in angioimmunoblastic T-cell lymphomas), besides other T-cell aberrancies. Nine of 10 (90%) peripheral T-cell lymphomas of follicular type showed a CD3(-/dim)CD4(+) T-cell population constituting 29.3% (range 7.9-62%) of all lymphocytes. Five of 10 (50%) had nodular lymphocyte predominant Hodgkin lymphoma or lymphocyte-rich classical Hodgkin lymphoma-like morphology with scattered Hodgkin-like cells that expressed CD20, CD30, CD15, and MUM1. Three cases had a nodular growth pattern and three others exhibited a perifollicular growth pattern without Hodgkin-like cells. Epstein-Barr virus was positive in 1 of 10 cases (10%). PCR analysis showed clonal T-cell receptor gamma gene rearrangement in all 10 peripheral T-cell lymphomas of follicular type. By flow cytometry, 11 of 15 (73.3%) angioimmunoblastic T-cell lymphomas showed the CD3(-/dim)CD4(+) population (mean: 19.5%, range: 3-71.8%). Using a threshold of 3% for CD3(-/dim)CD4(+) T cells, all 15 nodular lymphocyte predominant Hodgkin lymphoma controls and 8 classical Hodgkin lymphomas were negative (Mann-Whitney P=0.01, F-PTCL vs Hodgkin lymphomas), as were 25 of 26 reactive lymph nodes. The high frequency of CD3(-/dim)CD4(+) aberrant T cells is similar in angioimmunoblastic T-cell lymphomas and peripheral T-cell lymphomas of follicular type, and is a useful feature in distinguishing peripheral T-cell lymphomas of follicular type from morphologic mimics such as reactive hyperplasia or Hodgkin lymphoma.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Doença de Hodgkin/diagnóstico , Linfoma de Células T Periférico/diagnóstico , Subpopulações de Linfócitos T/imunologia , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Citometria de Fluxo , Doença de Hodgkin/imunologia , Humanos , Linfoma de Células T Periférico/imunologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
PURPOSE OF REVIEW: Bacteria are frequently implicated in acute exacerbations of chronic obstructive pulmonary disease (COPD), but their influence on airway inflammation remains unclear. This review will focus on nontypeable Haemophilus influenzae (NTHi), its impact on host immune responses, and the potential for vaccination strategies in COPD. RECENT FINDINGS: NTHi is associated with impaired immune function in patients with COPD. Features of the bacterium itself potentiate its ability to colonize the lower airways. An imbalance between bacterial load and host immunity may lend itself to the development of exacerbations. Oral immunotherapy may be a method of augmenting the host immune response and could provide protection from exacerbations. SUMMARY: A causal link between NTHi and COPD exacerbations has not been clearly established. However, colonization of the lower airways by NTHi likely plays a significant role in the inflammatory state of COPD.
Assuntos
Infecções por Haemophilus/imunologia , Haemophilus influenzae/patogenicidade , Doença Pulmonar Obstrutiva Crônica/imunologia , Infecções Respiratórias/imunologia , Imunidade Adaptativa , Aderência Bacteriana/imunologia , Progressão da Doença , Infecções por Haemophilus/microbiologia , Infecções por Haemophilus/fisiopatologia , Haemophilus influenzae/isolamento & purificação , Humanos , Imunoterapia/métodos , Imunoterapia/tendências , Inflamação/imunologia , Inflamação/microbiologia , Doença Pulmonar Obstrutiva Crônica/microbiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Mucosa Respiratória/imunologia , Infecções Respiratórias/microbiologia , Infecções Respiratórias/fisiopatologia , Vacinação/tendênciasRESUMO
Kaposiform hemangioendothelioma (KHE), a rare form of vascular neoplasm, is typically seen in children. In this paper, we report a unique case of KHE replacing bone marrow tissue mimicking myeloproliferative neoplasm with additional involvement in the lung, liver, and brain in a 60-year-old Caucasian woman. The patient was initially seen in the hematology department for the chief complaint of epigastric pain and anemia. Abdominal magnetic resonance imaging (MRI) revealed mild splenomegaly with iron deposition secondary to extramedullary hematopoiesis. Additional workup was inconclusive. Subsequent bone marrow and lung biopsies eventually revealed bone marrow with extensive grade 3 fibrosis and multiple foci of low-grade vasoformative neoplasm in the lung suggestive of KHE. Although rare, KHE can present as an aggressive disease with indolent behavior in adults and can be distinguished from other vascular malignancies based on histopathology and imaging findings.
RESUMO
A whole exome sequencing (WES)-driven approach to uncover the etiology of unexplained inflammatory gastritides has been underutilized by surgical pathologists. Here, we discovered the pathobiology of an unusual chronic atrophic gastritis in two unrelated patients using this approach. The gastric biopsies were notable for an unusual pattern of gastritis with persistent dense inflammation, loss of both parietal and neuroendocrine cells in the oxyntic mucosa, and sparing of the antral mucosa. The patients were found to harbor pathogenic variants in telomeropathic genes (POT1 and DCLRE1B). Clonality testing for one of the patients showed evidence of evolving clonality of TCR-gene rearrangement. Both patients showed significantly decreased numbers of stem/progenitor cells by immunohistochemistry, which appears to be responsible for the development of mucosal atrophy. No such cases of unusual chronic atrophic gastritis in the setting of telomeropathy have been previously reported. The loss of stem/progenitor cells suggests that stem/progenitor cell exhaustion in the setting of telomere dysfunction is the likely mechanism for development of this unusual chronic atrophic gastritis. The results underscore the need for close monitoring of these gastric lesions, with special regard to their neoplastic potential. This combined WES-driven approach has promise to identify the cause and mechanism of other uncharacterized gastrointestinal inflammatory disorders.
Assuntos
Gastrite Atrófica , Gastrite , Humanos , Gastrite Atrófica/genética , Gastrite Atrófica/patologia , Sequenciamento do Exoma , Gastrite/genética , Gastrite/patologia , Biópsia , Biologia , ExodesoxirribonucleasesRESUMO
Background: Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) is a rare T-cell neoplasm, accounting for approximately 3% of adult non-Hodgkin lymphomas. Although NPM1 is the most common fusion partner with ALK, many others have been described, necessitating break-apart FISH studies for confirmation of the diagnosis. TNF receptor-associated factor 1 (TRAF1) is a rare ALK partner that is thought to confer a worse prognosis in patients. We describe the utility of next-generation sequencing (NGS) RNA analysis in detection of this uncommon ALK partner. Case Description: A 42-year-old male with cervical lymphadenopathy presented for excisional biopsy. Following a tissue diagnosis of ALCL, ALK+, RNA from the biopsy was extracted from Formalin-fixed paraffin-embedded (FFPE) tissue and prepared for Anchored Multiplex PCR using the Archer® FusionPlex® v2 assay, which employs unidirectional gene-specific primers using NGS to detect novel or unknown gene partners. Results: Histologic evaluation of the excised lymph node showed atypical cells, including "horseshoe/kidney"-shaped nuclei. Neoplastic cells were immunoreactive against CD30, ALK (diffuse, cytoplasmic), CD2, CD4, granzyme B, and TIA-1. A diagnosis of ALCL, ALK+ was made. The pattern of ALK immunostaining suggested a non-NPM1-associated ALK translocation pattern, prompting further investigation. NGS fusion analysis showed a translocation involving exon 7 of TRAF1 and exon 20 of ALK. Conclusion: ALK positivity suggests an overall favorable prognosis of ALCL as compared to ALK-negative cases. However, in the rare published cases of TRAF1-ALK, an aggressive clinical course has been observed, which may reflect the aggressive propensity of this particular fusion, as these cases appear to be refractory to standard chemotherapy and also to the first generation ALK inhibitors. This study highlights the advantage of using NGS in RNA-based fusion assays to detect rare translocations, which can be of some clinical importance in detecting rare but aggressive fusion partners of ALK. As these technologies become more available, there is potential to identify such changes and effectively stratify the prognosis of ALCL patients.
RESUMO
OBJECTIVE: Evidence shows that the switch/sucrose nonfermenting chromatin remodeling complex plays a critical role in DNA repair, cancer progression and dedifferentiation. BRG1 is one of its key catalytic subunits. While the loss of BRG1 expression by immunocytochemistry has been identified in a subset of malignancies arising in various sites with undifferentiated/rhabdoid morphology and poor prognosis, the underlying basis for its loss is unclear. METHODS: A retrospective search was conducted in our cytopathology archive for undifferentiated malignant tumors with rhabdoid phenotype and BRG1 loss. Clinical information was obtained from electronic medical records. Next-generation sequencing was performed following macro-dissection of paraffin-embedded cellblock tissue. RESULTS: Three cases were identified; all presented with widely metastatic disease with no previously diagnosed primary malignancy, and subsequently died within 6 months of initial presentation. Cytologically, the aspirates showed dyshesive and undifferentiated cells with rhabdoid features. Extensive immunocytochemical workup demonstrated immunoreactivity with vimentin only and could not establish a specific lineage. BRG1 expression was absent, while INI1 expression was retained. Two cases harbored deleterious mutations in BRG1/SMARCA4. Pathogenic mutations in TP53 were identified in all tumors. CONCLUSIONS: BRG1 deficiency reflects underlying mutation in SMARCA4 gene in some but not all cases, suggesting that additional mechanisms may be causing BRG1 silencing. Pathogenic mutations in TP53 in all tumors are consistent with their highly aggressive nature. Recognizing the cytomorphology of this group of neoplasms and confirming their BRG1-deficient status by immunocytochemistry not only has prognostic implications, but may also impart potentially therapeutic value in the near future.
Assuntos
Biomarcadores Tumorais/genética , Diferenciação Celular , DNA Helicases/genética , Neoplasias Pulmonares/genética , Mutação , Proteínas Nucleares/genética , Tumor Rabdoide/genética , Neoplasias da Glândula Submandibular/genética , Fatores de Transcrição/genética , Idoso , Biomarcadores Tumorais/deficiência , Biópsia por Agulha Fina , DNA Helicases/deficiência , Análise Mutacional de DNA , Evolução Fatal , Feminino , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/deficiência , Fenótipo , Valor Preditivo dos Testes , Estudos Retrospectivos , Tumor Rabdoide/enzimologia , Tumor Rabdoide/patologia , Tumor Rabdoide/terapia , Neoplasias da Glândula Submandibular/enzimologia , Neoplasias da Glândula Submandibular/patologia , Neoplasias da Glândula Submandibular/terapia , Fatores de Transcrição/deficiência , Resultado do Tratamento , Proteína Supressora de Tumor p53/genéticaRESUMO
Renal cell carcinoma (RCC) with leiomyomatous stroma is a provisional category of RCC in the 2016 World Health Organization Classification of Tumors of the Urinary System. Microscopic examination of hematoxylin and eosin-stained sections reveals this entity to be well-circumscribed with tubulopapillary growth of cells with clear cytoplasm in a background of leiomyomatous stroma. Herein we describe the genetic features of 15 University of Chicago Medical Center archived cases with hematoxylin and eosin histology matching the provisional diagnosis. Immunohistochemical (IHC) stains revealed 1/15 of these tumors to be clear cell renal cell carcinoma (ccRCC) and 6/15 to be clear cell papillary renal cell carcinoma (ccpRCC), demonstrating the morphologic overlap with these discrete known entities. Interestingly 3/6 of the ccpRCCs had chromosome 18 gain suggesting there may be novel specific genetic changes in ccpRCC with leiomyomatous stroma. Of the remaining 8 tumors with IHC staining patterns that do not fit either ccRCC or ccpRCC only 3 of these had mutations in the recently described TCEB1 gene with concurrent monosomy of chromosome 8. These 3 cases had a somewhat unique IHC pattern that possibly could separate them from the 5 other non-ccRCC/non-ccpRCC cases. This descriptive study, although small, demonstrates the difficulty in applying the current World Health Organization provisional criteria at a single institution with suggestion of an immunohistochemcial panel that may assist in the diagnosis of TCEB1-mutated RCC with leiomyomatous stroma.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Leiomioma/genética , Células Estromais/patologia , Adulto , Idoso , Biomarcadores Tumorais/análise , Carcinoma de Células Renais/química , Carcinoma de Células Renais/patologia , Chicago , Feminino , Predisposição Genética para Doença , Humanos , Neoplasias Renais/química , Neoplasias Renais/patologia , Leiomioma/química , Leiomioma/patologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Células Estromais/químicaRESUMO
BACKGROUND: Pulmonary medicine specialists find themselves responsible for the diagnosis and management of patients with sleep disorders. Despite the increasing prevalence of many of these conditions, many sleep medicine fellowship training slots go unfilled, leading to a growing gap between the volume of patients seeking care for sleep abnormalities and the number of physicians formally trained to manage them. To address this need, we convened a multisociety panel to develop a list of curricular recommendations related to sleep medicine for pulmonary fellowship training programs. METHODS: Surveys of pulmonary and pulmonary/critical care fellowship program directors and recent graduates of these programs were performed to assess the current state of sleep medicine education in pulmonary training, as well as the current scope of practice of pulmonary specialists. These data were used to inform a modified Delphi process focused on developing curricular recommendations relevant to sleep medicine. RESULTS: Surveys confirmed that pulmonary medicine specialists are often responsible for the diagnosis and treatment of a number of sleep conditions, including several that are not traditionally considered related to respiratory medicine. Through five rounds of voting, the panel crafted a list of 52 curricular competencies relevant to sleep medicine for recommended inclusion in pulmonary training programs. CONCLUSIONS: Practicing pulmonary specialists require a broad knowledge of sleep medicine to provide appropriate care to patients they will be expected to manage. Training program directors may use the list of competencies as a framework to ensure adequate mastery of important content by graduating fellows.
Assuntos
Educação , Pneumologia , Medicina do Sono , Currículo/normas , Técnica Delphi , Educação/métodos , Educação/normas , Bolsas de Estudo/métodos , Bolsas de Estudo/organização & administração , Humanos , Comunicação Interdisciplinar , Pneumologia/educação , Pneumologia/métodos , Melhoria de Qualidade , Medicina do Sono/educação , Medicina do Sono/métodos , Medicina do Sono/normasRESUMO
Despite the relatively high prevalence of thyroid cancer, the occurrence of multiple synchronous, distinct subtypes of primary thyroid carcinoma is uncommon. The incidental finding of papillary thyroid microcarcinoma in a gland with a biologically relevant follicular or medullary carcinoma is more frequent than the synchronous occurrence of multiple clinically significant carcinomas. We report a case of synchronous papillary and follicular thyroid carcinomas metastatic to lymph node and bone, respectively. Next generation sequencing showed BRAF V600E mutation in the primary papillary carcinoma and NRAS Q61R mutation in the primary follicular carcinoma and bony metastasis. To our knowledge, this is the first reported case of synchronous and metastatic primary papillary and follicular carcinomas, and the first report of synchronous BRAF V600E mutated papillary and NRAS mutated follicular carcinoma.
Assuntos
Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/patologia , Carcinoma Papilar/genética , Carcinoma Papilar/patologia , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Feminino , GTP Fosfo-Hidrolases/genética , Humanos , Metástase Linfática/genética , Metástase Linfática/patologia , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas B-raf/genéticaRESUMO
The BTK inhibitor ibrutinib has demonstrated a remarkable therapeutic effect in mantle cell lymphoma (MCL). However, approximately one-third of patients do not respond to the drug initially. To identify the mechanisms underlying primary ibrutinib resistance in MCL, we analyzed the transcriptome changes in ibrutinib-sensitive and ibrutinib-resistant cell lines on ibrutinib treatment. We found that MYC gene signature was suppressed by ibrutinib in sensitive but not resistant cell lines. We demonstrated that MYC gene was structurally abnormal and MYC protein was overexpressed in MCL cells. Further, MYC knockdown with RNA interference inhibited cell growth in ibrutinib-sensitive as well as ibrutinib-resistant cells. We explored the possibility of inhibiting MYC through HSP90 inhibition. The chaperon protein is overexpressed in both cell lines and primary MCL cells from the patients. We demonstrated that MYC is a bona fide client of HSP90 in the context of MCL by both immunoprecipitation and chemical precipitation. Furthermore, inhibition of HSP90 using PU-H71 induced apoptosis and caused cell cycle arrest. PU-H71 also demonstrates strong and relatively specific inhibition of the MYC transcriptional program compared with other oncogenic pathways. In a MCL patient-derived xenograft model, the HSP90 inhibitor retards tumor growth and prolongs survival. Last, we showed that PU-H71 induced apoptosis and downregulated MYC protein in MCL cells derived from patients who were clinically resistant to ibrutinib. In conclusion, MYC activity underlies intrinsic resistance to ibrutinib in MCL. As a client protein of HSP90, MYC can be inhibited via PU-H71 to overcome primary ibrutinib resistance.
Assuntos
Resistencia a Medicamentos Antineoplásicos , Proteínas de Choque Térmico HSP90/metabolismo , Linfoma de Célula do Manto/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Pirazóis/farmacologia , Pirimidinas/farmacologia , Adenina/análogos & derivados , Animais , Benzodioxóis/farmacologia , Linhagem Celular Tumoral , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/genética , Humanos , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/patologia , Masculino , Camundongos , Piperidinas , Proteínas Proto-Oncogênicas c-myc/genética , Purinas/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A 36-year-old male was found to have a 7.0 cm left upper pole renal mass on renal ultrasound. Following nephrectomy, the mass was grossly ill-demarcated, friable and red-brown, invading renal parenchyma, hilar fat and the renal vein. Microscopically, the tumor had a nested and papillary architecture. The cells demonstrated abundant clear and eosinophilic cytoplasm and focal intracytoplasmic melanin pigment. Nucleoli were prominent. By immunohistochemistry, the tumor was positive for TFE3; HMB-45 stained approximately 5% of tumor cells corresponding to the histologic melanin pigment, which was confirmed with Fontana-Masson stain with bleach. Immunostains for PAX8, CD10, MiTF, and CAIX were negative; keratins Cam 5.2 and AE1/AE3 were focally positive. Targeted next-generation sequencing revealed an ARID1B-TFE3 gene fusion. Melanotic Xp11 renal cell carcinoma is a rare, pigment containing translocation variant demonstrating overlapping features with melanoma and is usually associated with an SFPQ-TFE3 gene fusion. The patient is alive and without evidence of disease 7 years after his diagnosis. The combination of high grade histopathology, the presence of melanin, absent PAX8, keratin positivity, and relatively indolent clinical behavior with a unique translocation may warrant recognition as a distinct renal cell carcinoma translocation subtype.
Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Biomarcadores Tumorais , Carcinoma de Células Renais/genética , Cromossomos Humanos X , Proteínas de Ligação a DNA/genética , Fusão Gênica , Neoplasias Renais/genética , Melaninas/análise , Fatores de Transcrição/genética , Translocação Genética , Adulto , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/análise , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia , Carcinoma de Células Renais/química , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Queratinas/análise , Neoplasias Renais/química , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Gradação de Tumores , Nefrectomia , Fator de Transcrição PAX8/análise , Fenótipo , Análise de Sequência de DNARESUMO
Epithelioid sarcoma (ES) is a malignant mesenchymal neoplasm with some morphologic or immunophenotypic evidence of epithelial differentiation. The "classic" subtype occurs in younger patients, often in distal extremities as compared with the "proximal" type. Tumors of the proximal type primarily arising in solid organs are rare with only few case reports in the literature. We report 2 cases of primary ES in the kidney of a 27-year-old woman and the adrenal gland of a 73-year-old man. Clinical examination and imaging, including computed tomography and positron-emission tomography, did not reveal tumor elsewhere in both cases. Histologic features were those of ES, proximal type with epithelioid/rhabdoid phenotype. Immunohistochemical study in both cases showed strong, diffuse expression of epithelial markers, CD34, and CD31. Nuclear expression of SMARCB1 protein was lost, but fluorescence in situ hybridization analysis was negative for SMARCB1 deletion. We believe that these are the first reports of primary kidney and adrenal gland ES.
Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Biomarcadores Tumorais , Células Epitelioides , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Renais/diagnóstico , Sarcoma/diagnóstico , Neoplasias das Glândulas Suprarrenais/química , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/terapia , Adulto , Idoso , Antígenos CD34/análise , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia , Células Epitelioides/química , Células Epitelioides/patologia , Evolução Fatal , Feminino , Deleção de Genes , Humanos , Neoplasias Renais/química , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Masculino , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Valor Preditivo dos Testes , Proteína SMARCB1/análise , Proteína SMARCB1/genética , Sarcoma/química , Sarcoma/genética , Sarcoma/patologia , Sarcoma/terapia , Resultado do TratamentoRESUMO
Perivascular epithelioid cell neoplasms (PEComas) are a family of mesenchymal tumors with features of both smooth muscle and melanocytic differentiation, with or without true melanin pigment. The highly variable morphology of PEComas results in a broad differential diagnosis that is also dependent on anatomic site. A subset demonstrates rearrangements involving the TFE3 (Xp11) locus, which can be used in diagnostically difficult cases. Here we describe a case of a melanotic PEComa with NONO-TFE3 fusion occurring in the sinonasal mucosa, as demonstrated by both next-generation sequencing and molecular cytogenetic studies. This case is the first of its kind in the literature and only the second documented PEComa harboring a NONO-TFE3 rearrangement. In light of unequivocal molecular ancillary studies, this case illustrates that PEComa must enter the differential for pigmented lesions of the sinonasal mucosa, where malignant melanoma would be much more likely to occur.
Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Fusão Gênica , Melaninas/análise , Melanoma/genética , Mucosa Nasal/química , Neoplasias Nasais/genética , Proteínas Associadas à Matriz Nuclear/genética , Fatores de Transcrição de Octâmero/genética , Neoplasias de Células Epitelioides Perivasculares/genética , Proteínas de Ligação a RNA/genética , Biópsia , Proteínas de Ligação a DNA , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Melanoma/química , Melanoma/patologia , Pessoa de Meia-Idade , Mucosa Nasal/patologia , Neoplasias Nasais/química , Neoplasias Nasais/patologia , Neoplasias de Células Epitelioides Perivasculares/química , Neoplasias de Células Epitelioides Perivasculares/patologia , Valor Preditivo dos Testes , Análise de Sequência de DNARESUMO
Burkitt lymphoma patients with bulky disease often have bone marrow involvement. However, leukemic presentation of Burkitt lymphoma in the absence of a mass (pure Burkitt leukemia; PBL) is uncommon. Both PBL and Burkitt lymphoma/leukemia, presenting with a tumor mass and marrow involvement (BLL), are considered stage IV disease, which is associated with a poor prognosis. However, there is limited information on the prognosis in adults with PBL because they have typically been included in cohorts of patients with BLL. This study identified 23 patients, which included 10 PBL and 13 BLL cases. Complex karyotypes (100%) were seen in all BLL cases compared to the PBL group (40%; p = 0.061). Patients with PBL had a significantly better 5-year overall survival of 87.5% vs only 24.3% in the BLL group (p = 0.005). The 5-year overall survival of patients with PBL treated with intensive chemotherapy is superior to those with BLL who are similarly treated.
Assuntos
Medula Óssea/patologia , Linfoma de Burkitt/mortalidade , Linfoma de Burkitt/patologia , Adulto , Idoso , Linfoma de Burkitt/terapia , Terapia Combinada , Feminino , Humanos , Cariótipo , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Although patients with medullary thyroid cancer are known to present with paraneoplastic hormone production, this is much less common with papillary thyroid cancer. METHODS: We present a patient with the cribriform morular variant of papillary thyroid cancer in association with familial adenomatous polyposis who developed a positive pregnancy test in the absence of known pregnancy. The patient had developed vaginal bleeding, and her laboratory testing was characterized by elevated serum human chorionic gonadotropin (ß-hCG) concentrations, but negative qualitative urine results. After a thorough gynecological evaluation to exclude unexpected normal, ectopic, or molar pregnancy, we pursued an evaluation for other sources of ß-hCG production. RESULTS: We showed that the elevated serum ß-hCG concentrations were not the result of heterophile antibody interferences, and ultimately we proved that her recurrent tumor produced the ectopic ß-hCG. This is the first report of ß-hCG production by papillary thyroid cancer. Thus, the possibility of ectopic production of ß-hCG by papillary thyroid cancer needs to be included in the differential diagnosis of elevated hCG concentration in the absence of pregnancy. CONCLUSIONS: This study of an unusual paraneoplastic syndrome highlights the importance of investigating discrepancies in the clinical laboratory.
Assuntos
Polipose Adenomatosa do Colo/diagnóstico , Biomarcadores/análise , Carcinoma Papilar/diagnóstico , Gonadotropina Coriônica/sangue , Gonadotropina Coriônica/urina , Recidiva Local de Neoplasia/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Polipose Adenomatosa do Colo/sangue , Polipose Adenomatosa do Colo/complicações , Polipose Adenomatosa do Colo/urina , Adulto , Carcinoma Papilar/sangue , Carcinoma Papilar/complicações , Carcinoma Papilar/urina , Diagnóstico Diferencial , Feminino , Humanos , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/complicações , Recidiva Local de Neoplasia/urina , Gravidez , Prognóstico , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/urinaRESUMO
Transient myeloproliferative disorder (TMD) is a unique form of acute megakaryocytic leukemia (AMKL) that spontaneously regresses and is found in 3% to 10% of neonates with Down syndrome (DS). We report the case of a neonate with DS who presented with a widespread vesiculopustular eruption as an initial sign of TMD. Complete blood count was normal but peripheral smear revealed circulating megakaryoblasts. The severity of skin lesions correlated with the blast count. By age 2 months the TMD resolved and the patient remains disease-free after 18 months of follow-up. Several important features of TMD are highlighted: skin findings may provide an important clinical clue to TMD diagnosis; manual review of the peripheral smear is necessary when TMD is suspected; and patients with a history of TMD have a very high (â¼30%) risk of recurrence with a persistent AMKL within the first 3 years of life.
Assuntos
Síndrome de Down/diagnóstico , Reação Leucemoide/diagnóstico , Dermatopatias Vesiculobolhosas/diagnóstico , Síndrome de Down/complicações , Humanos , Recém-Nascido , MasculinoRESUMO
A 68-year-old man was referred to the pulmonary clinic for evaluation of cough and a 5-cm right upper lobe mass. He was in his usual state of health until 1 year prior when he developed intermittent cough, wheezing, and sinus congestion. He denied any sputum production or hemoptysis. He also denied any fevers, chills, or weight loss. He had received various treatments within the prior 6 months, including short courses of oral prednisone, levofloxacin, and bronchodilators, without any relief of his symptoms.