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Gastric cancer (GC) remains a significant contributor to cancer-related mortality. Novel high-throughput techniques have enlightened the epigenetic mechanisms governing gene-expression regulation. Epigenetic characteristics contribute to molecular taxonomy and give rise to cancer-specific epigenetic patterns. Helicobacter pylori (Hp) infection has an impact on aberrant DNA methylation either through its pathogenic CagA protein or by inducing chronic inflammation. The hypomethylation of specific repetitive elements generates an epigenetic field effect early in tumorigenesis. Epstein-Barr virus (EBV) infection triggers DNA methylation by dysregulating DNA methyltransferases (DNMT) enzyme activity, while persistent Hp-EBV co-infection leads to aggressive tumor behavior. Distinct histone modifications are also responsible for oncogene upregulation and tumor-suppressor gene silencing in gastric carcinomas. While histone methylation and acetylation processes have been extensively studied, other less prevalent alterations contribute to the development and migration of gastric cancer via a complex network of interactions. Enzymes, such as Nicotinamide N-methyltransferase (NNMT), which is involved in tumor's metabolic reprogramming, interact with methyltransferases and modify gene expression. Non-coding RNA molecules, including long non-coding RNAs, circular RNAs, and miRNAs serve as epigenetic regulators contributing to GC development, metastasis, poor outcomes and therapy resistance. Serum RNA molecules hold the potential to serve as non-invasive biomarkers for diagnostic, prognostic or therapeutic applications. Gastric fluids represent a valuable source to identify potential biomarkers with diagnostic use in terms of liquid biopsy. Ongoing clinical trials are currently evaluating the efficacy of next-generation epigenetic drugs, displaying promising outcomes. Various approaches including multiple miRNA inhibitors or targeted nanoparticles carrying epigenetic drugs are being designed to enhance existing treatment efficacy and overcome treatment resistance.
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Infecções por Vírus Epstein-Barr , MicroRNAs , Neoplasias Gástricas , Humanos , Infecções por Vírus Epstein-Barr/genética , Neoplasias Gástricas/patologia , Herpesvirus Humano 4/genética , Epigênese Genética , Metilação de DNA , MicroRNAs/genética , MicroRNAs/metabolismo , Biomarcadores/metabolismo , Metiltransferases/metabolismoRESUMO
Bladder carcinoma is globally among the most prevalent cancers and is associated with a high mortality rate at advanced stages. Its detection relies on invasive diagnostic methods that are unpleasant for the patient. Non-invasive molecular biomarkers, such as miRNAs, could serve as alternatives for early detection and prognosis of this malignancy. We designed a computational approach that combines transcriptome profiling, survival analyses, and calculation of diagnostic power in order to isolate miRNA signatures with high diagnostic and prognostic utility. Our analysis of TCGA-BLCA data from 429 patients yielded one miRNA signature, consisting of five upregulated and three downregulated miRNAs with cumulative diagnostic power that outperforms current diagnostic methods. The same miRNAs have a strong prognostic significance since their expression is associated with the overall survival of bladder cancer patients. We evaluated the expression of this signature in 19 solid cancer types, supporting its unique diagnostic utility for bladder carcinoma. We provide computational evidence regarding the functional implications of this miRNA signature in cell cycle regulation, demonstrating its abundance in body fluids, including peripheral blood and urine. Our study characterized a novel miRNA signature with the potential to serve as a non-invasive method for bladder cancer diagnosis and prognosis.
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MicroRNAs , Neoplasias da Bexiga Urinária , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Bexiga Urinária/patologia , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão GênicaRESUMO
Linitis Plastica (LP) is a rare and aggressive tumor with a distinctive development pattern, leading to the infiltration of the gastric wall, the thickening of the gastric folds and a "leather bottle appearance". LP is an extremely heterogeneous tumor caused by mutations in oncogenic and tumor suppressive genes, as well as molecular pathways, along with mutations in stromal cells and proteins related to tight junctions. Elucidating the molecular background of tumorigenesis and clarifying the correlation between cancerous cells and stromal cells are crucial steps toward discovering novel diagnostic methods, biomarkers and therapeutic targets/agents. Surgery plays a pivotal role in LP management, serving both as a palliative and curative procedure. In this comprehensive review, we aim to present all recent data on the molecular background of LP and the novel approaches to its management.
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Linite Plástica , Neoplasias Gástricas , Humanos , Linite Plástica/diagnóstico , Linite Plástica/genética , Linite Plástica/terapia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , GenômicaRESUMO
It is well known that various human papillomavirus (HPV) genotypes are present in semen specimens. Also, it has been demonstrated that sperm parameters are negatively affected when HPV infection is present in the sperm sample. Besides all these, the effect of cryopreservation on HPV sensitivity and resistance is not known. The aim of the present study is to evaluate first the prevalence of HPV and secondly to elucidate whether cryopreservation of sperm HPV-positive samples has any effect on the viability of HPV. For this purpose, a cohort of 78 sperm specimens was used from a respective number of patients. After giving informed consent, semen analysis was performed. Each sperm sample was divided into four equal aliquots. The first one (fresh) was evaluated for the prevalence of HPV, while the other three aliquots were cryopreserved by adding an equal quantity of cryoprotectant and plunged into the LN. Each of the three aliquots was thawed 3, 6, and 12 months later, respectively, so as to evaluate whether there is a time-resistance period of HPV prevalence. HPV infection was found to be in eleven sperm samples, demonstrating a 14.1% (11/78) HPV prevalence. Among the HPV-positive samples, six of them were high-risk and the remaining were low-risk genotypes. Moreover, the high-risk fresh samples demonstrated higher motility values than the low-risk samples (60% ± 2.7 vs 45.6% ± 3.7, p < .05), while semen volume in the high-risk samples was significantly lower than the respective volume in the low-risk samples (2.26 ± 0.2ml vs 3.5 ± 0.6ml, p < .05). Interestingly, cryopreservation of the HPV-positive samples resulted in the sustainability and time-resistance of HPV in all high-risk HPV-positive samples, something that was not the case with the low-risk HPV-positive samples. Conclusively, sperm samples infected with high-risk HPV, demonstrate lower sperm parameters and time-resistance activity during cryopreservation.
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Infecções por Papillomavirus , Preservação do Sêmen , Humanos , Masculino , Sêmen , Motilidade dos Espermatozoides , Preservação do Sêmen/métodos , Espermatozoides , Criopreservação/métodosRESUMO
Langerhans cell histiocytosis (LCH) comprises a wide spectrum of clinical presentations in children and adults, ranging from favorable lesions to aggressive disseminated disease. We present 2 cases where cytology introduced the diagnosis of LCH in the appropriate clinicoradioliogical settings. Cytology can serve accurately in LCH interpretation based on the characteristic cytomorphology and selected immunocytochemistry, so unwarranted biopsy can be overruled and treatment can be adjusted largely where histopathology services are unavailable. Diagnosis may be difficult in cases with scant or insufficient cellular material.
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Background: The risk of recurrence after nephrectomy for primary clear cell renal cell carcinoma (ccRCC) is estimated in daily practice solely based on clinical criteria. The aim of this study was to assess the prognostic relevance of common somatic mutations with respect to tumor aggressiveness and outcomes of ccRCC patients after definitive treatment. Methods: Primary tumors from 37 patients with ccRCC who underwent radical nephrectomy were analyzed for presence of somatic mutations using a 15-gene targeted next-generation sequencing (NGS) panel. Associations to histopathologic characteristics and outcomes were investigated in the study cohort (n=37) and validated in The Cancer Genome Atlas (TCGA) ccRCC cohort (n=451). Results: VHL was the most frequently mutated gene (51%), followed by PBRM1 (27%), BAP1 (13%), SETD2 (13%), KDM5C (5%), ATM (5%), MTOR (5%), and PTEN (3%). One-third of patients did not have any somatic mutations within the 15-gene panel. The vast majority of tumors harboring no mutations at all or VHL-only mutations (51%) were more frequently of smaller size (pT1-2) and earlier stage (I/II), whereas presence of any other gene mutations in various combinations with or without VHL was enriched in larger (pT3) and higher stage tumors (III) (p=0.02). No recurrences were noted in patients with unmutated tumors or VHL-only mutations as opposed to three relapses in patients with non- VHL somatic mutations (p=0.06). Presence of somatic mutations in PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR, or PTEN genes in 451 TCGA ccRCC patients was associated with a significantly shorter disease-free survival (DFS) compared to those with unaltered tumors (q=0.01). Conclusions: Preliminary findings from this ongoing study support the prognostic value of non- VHL mutations including PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR, and PTEN in primary ccRCC tumors as surrogates of earlier recurrence and potential selection for adjuvant immune checkpoint inhibition.
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Carcinoma de Células Renais , Inibidores de Checkpoint Imunológico , Neoplasias Renais , Mutação , Recidiva Local de Neoplasia , Ubiquitina Tiolesterase , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/mortalidade , Masculino , Feminino , Neoplasias Renais/genética , Neoplasias Renais/patologia , Pessoa de Meia-Idade , Idoso , Inibidores de Checkpoint Imunológico/uso terapêutico , Ubiquitina Tiolesterase/genética , Recidiva Local de Neoplasia/genética , Proteínas Supressoras de Tumor/genética , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Prognóstico , Histona-Lisina N-Metiltransferase/genética , Adulto , Fatores de Transcrição/genética , Idoso de 80 Anos ou mais , Proteínas Nucleares/genética , Sequenciamento de Nucleotídeos em Larga Escala , Proteínas de Ligação a DNA , Histona DesmetilasesRESUMO
Background: Hypoxia is recognized as a key feature of cancer growth and is involved in various cellular processes, including proliferation, angiogenesis, and immune surveillance. Besides hypoxia-inducible factor 1-alpha (HIF-1α), which is the main mediator of hypoxia effects and can also be activated under normoxic conditions, little is known about its counterpart, HIF-2. This study focused on investigating the clinical and molecular landscape of HIF-2-altered urothelial carcinoma (UC). Methods: Publicly available next-generation sequencing (NGS) data from muscle-invasive UC cell lines and patient tumor samples from the MSK/TCGA 2020 cohort (n = 476) were interrogated for the level of expression (mRNA, protein) and presence of mutations, copy number variations, structural variants in the EPAS1 gene encoding HIF-2, and findings among various clinical (stage, grade, progression-free and overall survival) and molecular (tumor mutational burden, enriched gene expression) parameters were compared between altered and unaltered tumors. Results: 19% (7/37) of UC cell lines and 7% (27/380) of patients with muscle-invasive UC display high EPAS1 mRNA and protein expression or/and EPAS1 alterations. EPAS1-altered tumors are associated with higher stage, grade, and lymph node metastasis as well as with shorter PFS (14 vs. 51 months, q = 0.01) and OS (15 vs. 55 months, q = 0.01). EPAS1 mRNA expression is directly correlated with that of its target-genes, including VEGF, FLT1, KDR, DLL4, CDH5, ANGPT1 (q < 0.001). While there is a slightly higher tumor mutational burden in EPAS1-altered tumors (9.9 vs. 4.9 mut/Mb), they are enriched in and associated with genes promoting immune evasion, including ARID5B, SPINT1, AAK1, CLIC3, SORT1, SASH1, and FGFR3, respectively (q < 0.001). Conclusions: HIF-2-altered UC has an aggressive clinical and a distinct genomic and immunogenomic profile enriched in angiogenesis- and immune evasion-promoting genes.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Carcinoma de Células de Transição/patologia , Variações do Número de Cópias de DNA , Genômica , Hipóxia , Neovascularização Patológica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neoplasias da Bexiga Urinária/genéticaRESUMO
Background: Somatotroph adenomas (SAs) exhibit a variable responsiveness to somatostatin analogue (SS-a) treatment, a process that is not well understood. We investigated established and novel histological markers as predictors of SS-a responsiveness. Methods: We retrospectively investigated pathology samples from 36 acromegalic patients that underwent transsphenoidal surgery. Clinical, hormonal, and imaging data were available in 24/36 patients, before and after SS-a treatment. Specimens were semiquantitatively analyzed with immunocytochemistry for Ki-67, KER, SSTR-2, SSTR-5, ZAC-1, E-cadherin, and AIP. Results: Collectively, 18 (50%) adenomas were each classified as densely/sparsely granulated somatotroph adenomas (DGSAs/SGSAs), respectively. Patients that received preoperative SS-a had lower expression of SSTR-2 compared to those that did not (2.0 (1.0, 3.0) vs. 3.0 (3.0, 3.0), p = 0.042). Compared with DGSAs, SGSAs had higher Ki-67 labeling index (LI) (1.0 (0.5, 1.0) vs. 2.0 (1.0, 3.5), p = 0.013), and a higher proportion of high MR T2 signal (1 (6%) vs. 6 (33%), p = 0.035), and tended to express less ZAC-1 (p = 0.061) and E-cadherin (p = 0.067). In linear regression corrected for baseline growth hormone (GH), ZAC-1 immunostaining was significantly associated with a decrease in GH levels after SS-a treatment (beta (95% confidence interval): -1.53 (-2.80, -0.26), p = 0.021). No markers were associated with changes in circulating insulin-like growth factor-I (IGF-I) after treatment with SS-a. Conclusion: The novel marker ZAC-1 was associated with GH response to medical treatment with SS-a. The SGSA cases were characterized by higher Ki-67 values and MR T2 signals indicative of an inferior response to SS-a. These findings improve our understanding of the mechanisms underlying SA response to medical treatment.
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Head and neck paragangliomas (PGLs) most commonly derive from the carotid body, jugulotympanic, vagal, and laryngeal paraganglia. Thyroid PGLs originate in the inferior laryngeal paraganglion, which may lie inside the thyroid parenchyma. Intrathyroid PGLs are rare with approximately 75 cases reported to date, mostly as solitary lesions. The coexistence of thyroid PGL with medullary thyroid carcinoma (MTC) has not been reported. Here, we report a unique case of intrathyroid PGL concomitant with MTC in the context of multiple endocrine neoplasia type 2B syndrome. Interestingly, the patient showed a prolonged survival with good clinical response to tyrosine kinase inhibitors, despite her advanced metastatic MTC. We discuss the challenges in pathology, differential diagnosis, and genetic background for the development of these thyroid lesions.
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"Small-cell malignancies of thyroid" is an unsolved dilemma. This term represents an umbrella terminology in thyroid, encompassing for a small group of tumors in which some of them are well-recognized tumors like medullary thyroid carcinoma, poorly differentiated thyroid carcinoma, and primary thyroid lymphomas and teratoma, whereas the remaining are less known as primary neuroendocrine carcinoma of thyroid, primary extraskeletal Ewing family tumors, and adamantinoma-like Ewing sarcoma. When the issue comes to evaluate a cytological sample predominantly composed of small-cell morphology, metastatic small-cell carcinomas to thyroid also should be excluded. In this review, our group focused on the main cytomorphological and clinical clues of each entity that help to set up a correct differential diagnosis. The literature discussions were also included for the entities that are not yet recognized by the mother publication WHO. A key point of the issue's simple algorithm based on FNAC with small-cell morphology of thyroid was suggested by the authors.
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Carcinoma Neuroendócrino , Carcinoma de Células Pequenas , Sarcoma de Ewing , Neoplasias da Glândula Tireoide , Carcinoma Neuroendócrino/diagnóstico , Carcinoma de Células Pequenas/diagnóstico , Diagnóstico Diferencial , Humanos , Sarcoma de Ewing/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologiaRESUMO
High-risk pituitary adenomas are aggressive. They show clinical and imaging features similar to those of carcinomas, including infiltration of the surrounding brain structures, but lack cerebrospinal or systemic metastases. In addition, they display distinct behavior, including tendency for fast growth and frequent recurrences, which are difficult to control. The term "high-risk" adenoma was first introduced in the 4th edition of the World Health Organization Classification of Endocrine Tumors in 2017. Five defined adenoma types belong to this category, including sparsely granulated somatotroph, lactotroph in men, Crooke cell, silent corticotroph, and plurihormonal PIT-1 positive adenomas. The morphological and immunohistochemical characteristics of high-risk adenomas are herein described in detail. In addition, the clinical features and the treatment options are presented. This review focuses on predictive markers assessed by immunohistochemistry, which help clinicians to design the appropriate treatment strategies for high-risk adenomas. Somatostatin receptor status predicts effectiveness of postsurgical treatment with somatostatin analogs, and MGMT expression predicts response to treatment with temozolomide. This comprehensive review presents the clinical and pathological features of high-risk pituitary adenomas, underlines the contribution of immunohistochemistry, and emphasizes the leading role of pathology in the design of optimal clinical management.
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Adenoma , Carcinoma , Neoplasias Hipofisárias , Adenoma/diagnóstico , Adenoma/tratamento farmacológico , Humanos , Imuno-Histoquímica , Imunoterapia , Masculino , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/tratamento farmacológicoRESUMO
Telomeres promote genome integrity by protecting chromosome ends from the activation of the DNA damage response and protecting chromosomes from the loss of coding sequences due to the end replication problem. Telomere length (TL) is progressively shortened as age progresses, thus resulting in cellular senescence. Therefore, TL is in strong adverse linear correlation with aging. Mounting evidence supports the notion that telomeres and male/female infertility are in a close relationship, posing the biology of telomeres as a hot topic in the era of human-assisted reproduction. Specifically, the length of sperm telomeres is gradually increasing as men get older, while the telomere length of the oocytes seems not to follow similar patterns with that of sperm. Nonetheless, the telomere length of the embryos during the cleavage stages seems to have a paternal origin, but the telomere length can be further extended by telomerase activity during the blastocyst stage. The latter has been proposed as a new molecular biomarker with strong predictive value regarding male infertility. As far as the role of telomeres in assisted reproduction, the data is limited but the length of telomeres in both gametes seems to be affected mainly by the cause of infertility rather than the assisted reproductive therapy (ART) procedure itself. The present review aims to shed more light into the role of telomeres in human embryological parameters, including gametes and embryos and also presents opinions regarding the association between telomeres and in vitro fertilization (IVF).
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In fine-needle aspirations (FNA) of thyroid, Hürthle cells can be found in a broad spectrum of lesions, ranging from non-neoplastic conditions to aggressive malignant tumors. Recognize them morphologically, frequently represents a challenging for an adequately diagnosis and are associated with a significant interobserver variability. Although the limitations of the morphologic diagnosis still exist, the interpretation of the context where the cells appear and the recent advances in the molecular knowledge of Hürthle cells tumors are contributing for a more precise diagnosis. This review aims to describe the cytology aspects of all Hürthle cells neoplastic and non-neoplastic thyroid lesions, focusing on the differential diagnosis and reporting according to The Bethesda System for Reporting Thyroid Cytology (TBSRTC). New entities according to the latest World Health Organization (WHO) classification are included, as well as an update of the current molecular data.
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Citodiagnóstico/métodos , Células Oxífilas/patologia , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/diagnóstico , Biópsia por Agulha Fina , Diagnóstico Diferencial , HumanosRESUMO
Carcinomas of the breast with neuroendocrine features are rare primary neoplasms positive for neuroendocrine markers. According to the WHO classification of tumours of the breast they are divided into three morphologically distinct categories. They comprise neuroendocrine tumour (NET), neuroendocrine carcinoma (NEC) and carcinoma with neuroendocrine differentiation (NED). The purpose of this study was to investigate for the first time the full spectrum of sstr expression status in breast carcinomas with neuroendocrine features. Fifteen primary breast carcinomas with histological and immunohistochemical neuroendocrine features were studied. Four of them were classified as NETs and two as NECs, and the remaining 9 as carcinomas with NED. All six types of somatostatin receptor (sstr) types (sstr1, sstr 2A, sstr2B, sstr3, sstr4 and sstr5) were investigated by immunohistochemistry. To assess the distribution and intensity of membranous receptor immunoreactivity, a four-scale scoring system was used. Overall predominant receptors were sstr2A, sstr2B, sstr3 and sstr5 showing the highest membranous staining scores 3+ and 2 + . The sstr1 was not detected. Given that carcinomas with neuroendocrine features represent distinct entities, patients with such tumours may benefit from sstr targeting therapies. Immunohistochemistry for sstrs can predict the effectiveness of administration of SST analogues to those patients, thus contributing to achieve the maximum therapeutic outcome, particularly in NETs and NECs with scores 2+ and 3 + .
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Neoplasias da Mama/metabolismo , Carcinoma Neuroendócrino/metabolismo , Tumores Neuroendócrinos/metabolismo , Receptores de Somatostatina/metabolismo , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Masculino , Tumores Neuroendócrinos/patologiaRESUMO
OBJECTIVES: Thyrotroph adenomas are the most infrequent adenohypophysial tumors. Somatostatin (SST) inhibits hormone secretion and suppresses cell proliferation. SST receptors (sstr) belong to a family of 5 types of G-coupled membrane proteins, which show high binding affinity to SST. Currently, SST analogs used to treat pituitary adenomas, have a preferential binding activity to sstr2 and sstr5. The aim of this study was to evaluate the status of all active sstrs on cell membrane of thyrotroph adenomas. PATIENTS: Nine cases of thyrotroph adenomas were studied for all types of sstrs. All patients were clinically associated with hyperthyroidism. The adenomas were initially diagnosed and classified by histology and immunohistochemistry for all pituitary hormones and two of them were examined by electron microscopy. METHODS: For sstr immunohistochemistry, antisera against all sst types (1, 2A, 2B, 3, 4 and 5) were used. To enhance sensitivity, the tyramide amplification technique was applied. This is the first report investigating the full spectrum of sstrs in thyrotroph adenomas by immunohistochemistry. RESULTS: All tumors were immunoreactive for ß-subunit of thyroid-stimulating hormone and for α-subunit of glycoprotein hormones. The sst2A, sst2B and sstr5 were co-expressed in all adenomas. The sstr1 and sstr3 were noted in 8 and sstr4 in 7 adenomas respectively. High scores 2+ and 3+ were prominent in sstr2A, sstr2B, sstr3 and sstr5. High score 3+ for sstr4 was also noted in one tumor, while score 3+ for sstr1 was not observed. CONCLUSIONS: Knowledge of the sstr status may contribute to a better selection of patients, anticipating benefit from treatment with SST analogs. Given that multiligand SST analogs have a broader ability to bind other sstrs, such as sstr1 and sstr3, patients with thyrotroph adenomas expressing these receptors may benefit from novel sstr targeting therapy.
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Adenoma/metabolismo , Neoplasias Hipofisárias/metabolismo , Receptores de Somatostatina/metabolismo , Tireotrofos/metabolismo , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Hemangiossarcoma/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/diagnóstico por imagem , Idoso , Antígenos CD34/genética , Antígenos CD34/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biópsia por Agulha Fina , Diagnóstico Diferencial , Feminino , Hemangiossarcoma/genética , Hemangiossarcoma/patologia , Hemangiossarcoma/cirurgia , Humanos , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Tomografia Computadorizada de Emissão , UltrassonografiaRESUMO
Extranodal Hodgkin lymphoma involving the breast is infrequent. Most cases reported in the literature were diagnosed by histology after lumpectomy. We present a Hodgkin lymphoma mimicking inflammatory breast carcinoma in a 57-year-old woman. The diagnosis was performed by fine-needle aspiration (FNA) of the breast lesion and the axillary lymph nodes with rapid on-site evaluation followed by immunocytochemistry, and it was confirmed by histology. The patient after first-line chemotherapy developed relapse/refractory disease. Salvage chemotherapy regimens were applied with poor results and severe toxicity. Total remission was achieved with monotherapy of brentuximab vedotin, a novel anti-CD30-targeted antibody drug conjugate. This is a unique case of breast HL with misleading clinical presentation initially diagnosed by cytology. FNA as a minimally invasive diagnostic tool was crucial in avoiding unnecessary breast surgery and further delay of chemotherapy. It is also the first report highlighting the importance of this novel immunotherapy in the management of refractory Hodgkin lymphoma with breast involvement.
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Antineoplásicos Alquilantes/uso terapêutico , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Neoplasias Hipofisárias/tratamento farmacológico , Temozolomida/uso terapêutico , Proteínas Supressoras de Tumor/genética , Biomarcadores Tumorais/genética , Humanos , Neoplasias Hipofisárias/genética , PrognósticoRESUMO
INTRODUCTION: Temozolomide (TMZ) is currently considered as a rational therapeutic option for patients with progressively aggressive pituitary adenomas and carcinomas not responding to conventional therapies. Administration of TMZ results in clinical response and improvement in survival of many of these patients depending upon the expression of the DNA repair enzyme O-6 methylguanine DNA transferase (MGMT). Low or negative MGMT immunoreactivity predicts responsiveness to TMZ therapy. Therefore, MGMT serves as a criterion to select candidate patients anticipating response to treatment. MATERIALS AND METHODS: The MGMT expression was investigated in 25 pituitary adenomas with Ki-67 labeling index more that 3% and p53 expression, using various antigen retrieval protocols. After direct application of the antibody, only one adenoma yielded positive for MGMT. However, after pretreatment of tissue sections with antigen retrieval protocols, another 3 adenomas, initially negative turned to positive. CONCLUSIONS: These findings could explain lack of response to TMZ treatment in patients with false negative MGMT immunohistochemistry. Evaluation of tumor samples for MGMT expression should carefully be carried-out using the optimum immunohistochemical protocol to obtain consistent and reliable results that help to identify patients that could respond to TMZ therapy.
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Antineoplásicos Alquilantes/uso terapêutico , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/metabolismo , Temozolomida/uso terapêutico , Proteínas Supressoras de Tumor/metabolismo , Feminino , Humanos , Imuno-Histoquímica , MasculinoRESUMO
Double and multiple adenomas of the pituitary are composed of two or more distinct tumors located in the same gland. They represent uncommon lesions measuring less than 1 cm, reported as having a low incidence in autopsies and occurring even more infrequently in surgical series. The histological diagnosis of double adenomas in surgical material is often extremely difficult, and confirmation requires immunohistochemistry and, occasionally, electron microscopy. Fragmented tissue material submitted for histology after transsphenoidal resection complicates the diagnosis. Difficulties in demonstrating double or multiple adenomas by imaging techniques contribute to diagnostic failure. Magnetic resonance imaging (MRI) techniques may disclose two separate adenomas located in the same pituitary gland. Intraoperative MRI and imaging ultrasonography, together with positron emission computed tomography, more accurately identify sites of residual tumors. These techniques might also detect postoperatively a residual tumor belonging to the second component of double adenoma. Double adenomas may also create extreme clinical diagnostic challenges. It is almost impossible to suspect functioning double adenomas with combined hormone secretion, each one secreting a different hormone, and distinguish them from an isolated plurihormonal adenoma, simultaneously secreting more than one hormone. Double adenomas may underlie surgical failure when one adenoma is removed while the other is left behind. Despite the low frequency of double adenomas, identification and resection of both of them is of major importance for the achievement of biochemical cure.