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Paraneoplastic neurological syndromes (PNS) are remote effects of cancer. They are much less common, but are nevertheless important because they cause severe neurological morbidity and mortality. The present cases were studied to characterize the clinical features of patients of suspected PNS and to study their association with different types of tumors. In this study conducted from a super speciality teaching institute from South India, forty five (incidence-0.25%) patients were diagnosed with PNS based on the clinical data. They were subdivided into two groups patients with central nervous system (CNS) manifestations and those with neuromuscular manifestations. Immunological markers were assessed in a subset of patients. Majority of them (75.6%) were above 40 years. There was no sex predilection and a chronic presentation was common (42.2%). While more than half had involvement of peripheral nervous system (64.4%), CNS manifestations were present in 16 (35.6%) cases. Immunological markers were present in 10 out of 14 (58.8%) patients. Classic PNS was seen 22 cases (48.9%), while 23 (51.1%) were non classical. Most common tumor was lung cancer followed by myeloma and breast carcinoma. Present study construed that, in patients with neurological syndromes of unknown cause, search should be focused for occult malignancy based on the phenotype and onconeural antibodies, targeting the lung and breast in particular.
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Síndromes Paraneoplásicas do Sistema Nervoso/epidemiologia , Adolescente , Adulto , Idoso , Anticorpos/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Condução Nervosa/fisiologia , Neuroimagem , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Síndromes Paraneoplásicas do Sistema Nervoso/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso/patologia , Nervos Periféricos/patologia , Nervos Periféricos/fisiopatologia , Estudos Retrospectivos , Adulto JovemRESUMO
AIMS AND OBJECTIVES: To study the histopathological features with particular emphasis on perineural invasion in invasive rhinocerebral mucormycosis. MATERIALS AND METHODS: Tissue sections from 30 patients with invasive rhinocerebral mucormycosis were included in the study. Demographic features, predisposing conditions, and clinical features were obtained from medical records. Tissue sections were reviewed with hematoxylin and eosin (H and E), Gomori's methenamine silver (GMS), and periodic acid Schiff (PAS) stains for (i) the presence and type of inflammation (suppurative/granulomatous; sparse/absent), (ii) invasion into soft tissues, and (iii) type of spread (angio/perineural) and presence of infarction/necrosis and fungal morphology. RESULTS: The study material included 20 males and 10 females with age ranging from 15-84 years. The clinical syndromes included rhino-orbital in 15, rhinocerebral in 6, and rhino-orbito-cerebral in 9 patients. On histopathological examination, inflammation was suppurative with predominance of neutrophils in 25 biopsies. Suppurating granuloma with neutrophils, lymphocytes, and foreign body giant cells was seen in 3 biopsies. Invasion into soft tissues, muscles, and adipose tissues was seen in 20 biopsies. Angioinvasion was noted in 25 and soft tissue invasion in 20 biopsies. Peripheral nerves were identified in 19 and perineural spread was identified in 15 biopsies. In all, biopsies with perineural invasion, angioinvasion, and soft tissue invasion were seen. CONCLUSIONS: Perineural invasion is one of the important histological features of invasive rhinocerebral mucormycosis and it indicates advanced the extent of invasion.
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Encefalopatias/patologia , Mucormicose/patologia , Doenças Nasais/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Encefalopatias/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucorales/isolamento & purificação , Mucormicose/microbiologia , Doenças Nasais/microbiologia , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: The two main oesophageal cancer subtypes namely adenocarcinoma and squamous cell carcinoma exhibit interesting clinical, pathological and geographical variations with the former being more common in the West and the latter in Asia. MATERIALS AND METHODS: We evaluated status of p53, EGFR, Wnt and HPV in addition to microsatellite instability and loss of heterozygosity of several chromosomal loci in the two oesophageal cancer subtypes from India. The comparative analysis was extended to two oesophageal adenosquamous mixed cancer samples. RESULTS: Our results reveal a high frequency of EGFR overexpression in ESCC as against EAC, while Wnt activation was a significantly more common event in EAC as against ESCC. Frequencies of p53 perturbations were not significantly different in the two subtypes. Interestingly, the EGFR and Wnt status in adenocarcinoma and squamous components of the two oesophageal adenosquamous cancer samples were identical to primary tumours. In addition, no common molecular aberration (including instability and loss of heterozygosity) in several microsatellites was detected in DNA isolated from the two components in both adenosquamous cancer samples. CONCLUSIONS: Our results reveal the presence of distinct aberrations in oesophageal adenocarcinoma and squamous cell carcinoma which are replicated in the respective components of adenosquamous cancers. The study therefore suggests perhaps an independent origin of the two components of oesophageal adenosquamous mixed cancer.
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Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Alphapapillomavirus/genética , DNA de Neoplasias/genética , DNA Viral/genética , Evolução Fatal , Feminino , Genes erbB-1/genética , Genes p53/genética , Testes de DNA para Papilomavírus Humano , Humanos , Perda de Heterozigosidade , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Proteínas Wnt/genéticaRESUMO
BACKGROUND: Congenital myopathies (CMs) are rare and they are clinically and genetically heterogeneous. Muscle biopsy is characterized by structural abnormality that is diagnostic. There are few studies from India. MATERIALS AND METHODS: This is a retrospective study of 12 years. The demographic data, clinical features and laboratory data of patients diagnosed as CMs on muscle biopsy were retrieved from medical records. The slides were reviewed for morphological and structural abnormalities using the following stains hematoxylin and eosin, modified Gomori trichrome, masson trichrome, periodic acid schiff, adenosine triphosphatase preincubated at pH 9.4, 4.6 and 4.3, nicotinamide adenine dinucleotide tetrazolium reductase, succinic dehydrogenase and cytochrome c oxidase. Immunohistochemistry was performed with dystrophin, sarcoglycans and desmin wherever necessary. RESULTS: There were 50 patients with CMs: Centronuclear myopathy (23), myotubular myopathy (3) and central core disease (CCD) (8), nemaline myopathy (5), congenital fiber type proportion (10) and desmin related myopathy with arrythmogenic right ventricular cardiomyopathy (ARVD) (1). Of the 50 patients, 30 (60%) presented in the first decade of life. Proximal muscle weakness and hypotonia were the common presenting features. Type 1 atrophy and predominance were seen in most cases on muscle biopsy. CCD had one patient with high creatine phosphokinase levels, biopsy in one patient showed both rods and cores, in the other limb girdle muscular dystrophy like picture and one biopsy showed uniform type 1 fibers. There was one desmin related myopathy with ARVD, who had cardiac transplantation and both skeletal and cardiac muscle showed characteristic rimmed vacuoles and inclusions positive for desmin. CONCLUSION: CMs are rare and the diagnosis can only be established on muscle biopsy. Defining the specific CMs helps the clinician in counseling the patient and family.
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Fibras Musculares Esqueléticas/patologia , Miopatias Congênitas Estruturais/patologia , Adolescente , Adulto , Biópsia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Miopatias da Nemalina/patologia , Miopatias Congênitas Estruturais/classificação , Miopatia da Parte Central/patologia , Músculo Quadríceps/patologia , Estudos Retrospectivos , Adulto JovemAssuntos
Colágeno Tipo VI/genética , Sequenciamento de Nucleotídeos em Larga Escala , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofias Musculares/congênito , Mutação/genética , Pré-Escolar , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Distrofias Musculares/diagnóstico , Distrofia Muscular do Cíngulo dos Membros/diagnósticoRESUMO
Surgical resection is a generally accepted treatment for residual masses after chemotherapy for metastatic testicular germ cell tumour (GCT). About half the patients have necrosis in post-chemotherapy residual masses, whereas rest have viable tumour and teratoma. The likelihood of leaving behind teratoma with its subsequent complications such as growing teratoma syndrome necessitates resection outweighing its surgical complications. Ours is a retrospective observational study and aims at assessing post-chemotherapy residual masses in testicular GCTs and to predict importance of teratomatous and non-seminomatous components. A total of 62 cases of testicular GCTs resected after chemotherapy between January 2012 and June 2019 were included. Demographic, clinical, biochemical and imageological findings were noted and categorised according to WHO classification (2016). They were divided into two groups - those who underwent retroperitoneal lymph node dissection (RPLND) post-high inguinal orchidectomy (HIO) and chemotherapy (CT) as group 1 (n = 40) and those who underwent HIO and/or RPLND post-chemotherapy as group 2 (n = 22). The gross and microscopic examination was carried out to assess response to chemotherapy in terms of residual viable tumour, necrosis and teratoma. Viable tumour, necrosis and teratoma were 10%, 62.5% and 35% respectively in group 1 and in group 2, the same were 15%, 70% and 25% respectively in HIO specimen and 7%, 50% and 21% respectively in RPLND specimen. All the cases with viable tumour were proven to be yolk sac tumours (YST) based on morphology and immunohistochemistry (IHC).Twenty cases had teratoma in the post-CT residual masses out of which 11 cases had teratoma despite reduction in size. At a median follow-up of 47.85 months, 5 cases in group 1 and 2 cases in group 2 showed relapse and it was observed that group 1 had a prolonged relapse-free survival over group 2. Our study re-emphasises the importance of performing resection of residual mass post-CT irrespective of the size, imageological or biochemical evidence of tumour regression. There does not appear to be reliable predictors of post-chemotherapy histology of residual masses indicating the continued need for surgical resection in specialised centres.
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CONTEXT: Immunohistochemistry (IHC) to differentiate germ cell tumors. AIMS: The aim of the study is to differentiate seminomatous and nonseminomatous germ cell tumors (GCTs) with morphological overlap using a minimal and affordable panel of IHC markers. SETTINGS AND DESIGN: This is a retrospective observational study. SUBJECTS AND METHODS: All testicular GCTs (TGCT) which were diagnosed on biopsies and/or resection specimens (prechemotherapy) between January 2014 and June 2019. The demographic, clinical, and imaging findings were noted from the medical records. Hematoxylin and eosin (H and E)-stained sections were reviewed for morphology. The IHC markers constituted Octamer-binding transcription factor (OCT) 3/4, glypican 3 (GPC3), CD117, CD30, placental-like alkaline phosphatase, Sal-like protein 4, and ß-human chorionic gonadotropin (HCG). IHC markers were performed in various combinations depending on the morphology, and a panel constituting OCT 3/4, CD117, GPC3, and CD30 was performed on cases with diagnostic dilemma and morphological overlaps. STATISTICAL ANALYSIS USED: Sensitivity, specificity, positive (PPV), and negative predictive value (NPV) were calculated for suggested panel of IHC OCT 3/4, CD117, GPC3, and CD30. RESULTS: The study included 36 patients with TGCT with a mean age of 27 (15-58) years. Nonseminomatous tumors were the most common (86%). The concise panel was performed in 20/36 (56%) tumors to resolve the diagnosis. The sensitivity, specificity, PPV, and NPV for OCT3/4 were 80%, 55%, 31%, and 92% in seminomas and 65%, 100%, 100%, and 46% in embryonal carcinomas (EC), for CD117 was 89%, 82%, 73%, and 93% in seminomas and 60%, 77%, 60%, and 77% in yolk sac tumors (YST), for GPC3 was 95%, 90%, 95%, and 90% in YST, CD30 96%, 100%, 100%, and 91% in ECs, respectively. CONCLUSIONS: Designing a novel concise and affordable IHC panel constituting OCT 3/4, CD117, GPC3, and CD30 has good sensitivity and specificity in differentiating seminomas, YST, and EC, respectively. Additional markers, namely ß-HCG, can be used in identifying the choriocarcinoma component.
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CONTEXT: The diagnosis of prostatic adenocarcinoma on histopathology depends on architectural and cytomorphological features supported by immunohistochemistry (IHC). Though all the prostate markers show excellent specificity, the sensitivity and percentage positivity vary. AIMS: In this study, we aim to study the expression of prostein in normal, benign, and malignant (primary and metastatic) lesions with particular emphasis on its utility in the differential diagnosis of poorly differentiated and metastatic prostatic adenocarcinoma along with a standard panel of IHC markers. SETTINGS AND DESIGN: This was both a prospective and retrospective as well as descriptive and observational study. SUBJECTS AND METHODS: All samples from patients with clinically suspected carcinoma prostate from both primary and metastatic sites from June 2015 to May 2016 were included in the study. Samples with difficulty in diagnosis on hematoxylin and eosin staining were subjected to a panel of IHC markers along with prostein. STATISTICAL ANALYSIS USED: Receiver operating curve analysis and Chi-square test. RESULTS: Prostein showed a 100% sensitivity and specificity to identify normal prostatic epithelium, benign and premalignant lesions, and prostatic adenocarcinoma. Prostein showed a specificity of 100% in differentiating prostatic carcinoma from poorly differentiated urothelial carcinoma and in differentiating metastatic prostatic carcinoma from adenocarcinoma of nonprostatic origin. CONCLUSIONS: Prostein is a new and promising prostate-specific marker that showed slightly more sensitivity and specificity than prostate-specific antigen. Thus, adding prostein to the IHC panel will greatly improve the detection of poorly differentiated primary and metastatic lesions of the prostate.
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Adenocarcinoma/diagnóstico , Imuno-Histoquímica , Proteínas de Membrana/análise , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/secundário , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pesquisa Qualitativa , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
CONTEXT: Morphological cocktails in renal cell carcinoma (RCC). AIMS: Minimal immunohistochemistry (IHC) panel to resolve the diagnosis of renal cell cacinoma (RCC) with morphological overlaps. SETTINGS AND DESIGN: RCC is the most common malignancy in kidney accounting for 90% of all kidney cancers. Clear cell RCC is the most common histological type followed by papillary RCC. However, many of the RCCs show morphological cocktails which may pose diagnostic difficulties in small biopsies and even in the resection specimens. Accurate diagnosis has both prognostic and therapeutic implications; hence, correct differentiation is necessary. SUBJECTS AND METHODS: This retrospective study includes all renal cell tumors diagnosed on core biopsies, radical and partial nephrectomies between January 2015 and September 2017 were studied. The demographic, clinical, and gross findings were noted. The cases that had morphological overlap among the subtypes were subjected to a panel of IHC markers, including CD10, CK7, alpha-methyl acyl-coenzymeA racemase (AMACR), and CD117. RESULTS: There were 128 RCC in the study period, and morphological overlap was seen in 36 (27.9%) specimens including 13 core biopsies, 16 radical, and 7 partial nephrectomies. IHC resolved 35/36 (97.2%) cases rendering a diagnosis of clear cell (11), papillary (15), chromophobe (4), and oncocytoma (5). However, in one case where the provisional diagnosis was oncocytic tumor, all IHC markers were negative rendering IHC noncontributory. CONCLUSIONS: Difficulty in diagnosis was encountered in many core biopsies, resection specimens which when subjected to IHC panel of CD10, CK7, AMACR, and CD117 helped in resolving the diagnosis of subtypes of RCC.
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BACKGROUND: Pulmonary alveolar proteinosis (PAP) poses a risk of opportunistic infections with a variety of organisms with Nocardia being the most common pathogen followed by mycobacteria and fungi. CASE PRESENTATION: A 7-year-old female child, presented with headache and multiple episodes of vomiting. There was no fever or altered sensorium. On examination, there were no focal deficits or cranial nerve palsies. An MRI brain showed a small T2 hyperintense lesion in the left superior parietal lobe suggestive of an abscess. She was diagnosed as PAP based on CT chest and bronchioloalveolar lavage 7 months earlier and treated with corticosteroids. A left parieto-occipital craniotomy was done with drainage of abscess and abscess wall excision. Histopathology revealed a suppurative lesion with slender septate acute angle branching hyphae which were positive on fungal stains. Culture done on the pus was positive for Aspergillus fumigatus. The patient was treated with voriconazole and stable at 1 year follow-up. CONCLUSION: Opportunistic infections are common in patients diagnosed with PAP. High index of clinical suspicion and early diagnosis are important for favorable outcome.
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We have studied differentially regulated nuclear proteome of the clinical tissue specimens of glioblastoma (GBM, WHO Grade IV) and lower grades of gliomas (Grade II and III) using high resolution mass spectrometry- based quantitative proteomics approach. The results showed altered expression of many regulatory proteins from the nucleus such as DNA binding proteins, transcription and post transcriptional processing factors and also included enrichment of nuclear proteins that are targets of granzyme signaling - an immune surveillance pathway. Protein - protein interaction network analysis using integrated proteomics and transcriptomics data of transcription factors and proteins for cell invasion process (drawn from another GBM dataset) revealed YBX1, a ubiquitous RNA and DNA-binding protein and a transcription factor, as a key interactor of major cell invasion-associated proteins from GBM. To verify the regulatory link between them, the co-expression of YBX1 and six of the interacting proteins (EGFR, MAPK1, CD44, SOX2, TNC and MMP13) involved in cell invasion network was examined by immunohistochemistry on tissue micro arrays. Our analysis suggests YBX1 as a potential regulator of these key molecules involved in tumor invasion and thus as a promising target for development of new therapeutic strategies for GBM.
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Neoplasias Encefálicas/genética , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Invasividade Neoplásica/genética , Proteína 1 de Ligação a Y-Box/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Redes Reguladoras de Genes , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Invasividade Neoplásica/patologia , Mapas de Interação de Proteínas , Ativação Transcricional , Proteína 1 de Ligação a Y-Box/metabolismoRESUMO
BACKGROUND: Meningeal hemangiopericytoma (HPC) is a rare neoplasm. It is closely related to hemangiopericytomas in systemic tissues, with a tendency to recur and metastasize outside the CNS. Only a few case reports describe the cytomorphologic appearance of these metastasizing lesions, most having primary tumor in deep soft tissues. We report a case of recurrent meningeal HPC metastasizing to lungs. CASE: A 48-year-old woman presented with a history of headache. She underwent primary surgery 10 years previously for left parietal tumor. Histopathologic diagnosis was HPC. Radiotherapy was given postoperatively. Brain magnetic resonance imaging (MRI) at admission suggested local recurrence. She also complained of dry cough and shortness of breath. On evaluation, computed tomography (CT) scan lung showed multiple, bilateral, small nodules. Fine needle aspiration cytology (FNAC) of a larger nodule revealed spindle-shaped cells arranged around blood vessels. Immunohistochemistry with CD34 on cell block confirmed metastatic HPC. CONCLUSION: FNAC is an easy, accurate, relatively noninvasive procedure for diagnosing metastases, especially in patients with a history of recurrent intracranial HPC. Immunohistochemistry on cell block material collected at the time of FNAC may aid in distinguishing HPC from other tumors that are close mimics cytologically.
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Biópsia por Agulha Fina , Citodiagnóstico , Hemangiopericitoma/diagnóstico , Neoplasias Pulmonares/secundário , Neoplasias Meníngeas/diagnóstico , Antígenos CD34/metabolismo , Feminino , Hemangiopericitoma/metabolismo , Hemangiopericitoma/patologia , Humanos , Imuno-Histoquímica , Neoplasias Meníngeas/metabolismo , Neoplasias Meníngeas/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , RecidivaRESUMO
OBJECTIVE: To study the distribution, prevalence and cytomorphologic features of mediastinal lesions and assess the utility of fine needle aspiration cytology (FNAC) in such lesions by correlating with clinical, laboratory and imageologic parameters. STUDY DESIGN: A retrospective study was performed of mediastinal lesions that were referred for ultrasonographic/computed tomography-guided FNAC during the years 2001-2006. Correlation was done wherever possible using the following parameters: histology, bone marrow, imageology, tumor markers, cytology, immunohistochemistry, antecedent history and regression after therapy. RESULTS: A total of 161 patients underwent 182 aspirates. Diagnosis was possible in 130 (80.7%) patients, and, in 31 cases (19.3%), aspirates were unsatisfactory. In 71 (54.6%) correlation was done, and in 70 (98.5%) positive correlation was found. CONCLUSION: FNAC in correlation with clinical, imageologic and hematologic features proved to be an excellent diagnostic tool in diagnosing as well as classifying mediastinal lesions and can be used as a substitute to core biopsy.
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Biópsia por Agulha Fina/estatística & dados numéricos , Neoplasias do Mediastino/patologia , Adolescente , Adulto , Biópsia por Agulha Fina/métodos , Carcinoma/patologia , Diagnóstico Diferencial , Endossonografia , Feminino , Humanos , Linfoma/patologia , Masculino , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias de Tecido Nervoso/patologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Sarcoma/patologia , Timoma/patologia , Neoplasias do Timo/patologia , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: The objective of this study is to retrospectively evaluate follicular variant of papillary thyroid carcinoma (FVPTC) and reclassify encapsulated FVPTC as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) according to the criteria proposed by The Endocrine Pathology Society working group in 2015 to correlate with outcome. MATERIALS AND METHODS: Retrospective review of case records of all patients diagnosed as carcinoma of thyroid between 2015 and 2016 was done for the histologic subtype. Gross and microscopic features on resected specimens of FVPTC were reviewed and subtyped as invasive and encapsulated based on capsular/vascular invasion; the encapsulated forms were further studied for size, number, follicular architecture, nuclear features, presence of psammoma bodies, stromal fibrosis, necrosis, mitoses, and lymph node status. RESULTS: Out of the 383 patients with thyroid carcinomas in the study period, 349 were PTC which included 106 FVPTC. Thirty-three patients fulfilled the criteria to be labeled as NIFTP. Total thyroidectomy was performed in 8 patients and hemithyroidectomy in 25 patients. Lymph node dissection along with total thyroidectomy was done in 3 and completion thyroidectomy following hemithyroidectomy was done in 9. There were 29 single and 4 multiple lesions with size varying from 0.2 to 7 cm including 5 lesions measuring <1 cm. The involvement was confined to one lobe in 31 and both lobes in 2 specimens. Patients are on follow-up with no recurrence till date. CONCLUSION: Thyroid carcinomas currently diagnosed as FVPTC should be evaluated for criteria of NIFTP to avoid overtreatment as they have an indolent behavior.
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Carcinoma Papilar/patologia , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/classificação , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Folicular/patologia , Adenocarcinoma Folicular/ultraestrutura , Adolescente , Adulto , Idoso , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/ultraestrutura , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estudos Retrospectivos , Glândula Tireoide/citologia , Glândula Tireoide/cirurgia , Glândula Tireoide/ultraestrutura , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/ultraestrutura , Tireoidectomia , Adulto JovemAssuntos
Cistos do Sistema Nervoso Central/complicações , Ossificação Heterotópica/etiologia , Matriz Óssea/patologia , Cistos do Sistema Nervoso Central/diagnóstico , Epitélio/metabolismo , Epitélio/patologia , Feminino , Humanos , Queratinas/metabolismo , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Ossificação Heterotópica/patologiaRESUMO
Isolated angitis of the central nervous system (IACNS)/primary angitis of central nervous system vasculitis (PACNS) is an uncommon vascular disease, sparingly presenting as an isolated inflammatory lesion on magnetic resonance imaging (MRI). The disease usually manifests as a long-drawn and progressive ischemic event. Delay in diagnosis due to focal nature of the lesion also contributes to the poor prognosis as the dismal natural history and immunosuppressive therapy. To date, only a few cases with tumor-like isolated angitis of CNS have been reported with clear and definitive diagnostic workup.
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Purpose: Leber's hereditary optic neuropathy (LHON; OMIM 535000) is one of the most common maternally inherited mitochondrial disorders. Three mitochondrial DNA point mutations-m.3460G>A (MT-ND1), m.11778G>A (MT-ND4), and m.14484T>C (MT-ND6)-account for the majority of reported LHON cases. Only approximately 50% of males and approximately 10% of females carrying these mutations develop optic neuropathy and blindness. Additional factors, such as mtDNA/nuclear genetic background and environmental modifiers, are likely to contribute toward the observed incomplete penetrance and gender bias. We aimed to investigate whether mtDNA haplogroup influences LHON clinical expression in Indian patients harboring the m.11778G>A mutation. Methods: Detailed clinical assessment and complete mitochondrial genome sequencing was undertaken in 64 LHON families harboring the m.11778G>A mutation. Mitochondrial haplogroup was assigned based on evolutionarily conserved mtDNA variations. Results: A total of 543 individuals (295 male, 248 female) from 64 unrelated families harboring the m.11778G>A mutation were recruited to the study. The overall disease penetrance was 27.07% (146 of 543) and higher in males (37.9%; 112 of 295) than females (13.7%; 34 of 248). The mtDNA haplogroup analysis revealed that all affected probands belonged to different mtDNA haplogroups. No association between the m.11778G>A mutation and the background mtDNA haplogroup was detected. Conclusions: The first detailed study of Indian LHON patients confirm that the m.11778G>A-related LHON in India coexists with multiple different mtDNA haplogroups, unlike the preferential association of west Eurasian haplogroup J and the reported increased clinical penetrance with the J2 subhaplogroup. However, we observed variable penetrance of LHON in different Indian mtDNA haplogroup backgrounds, indicating their possible influence on clinical expression. These data suggest that a similar heterogeneity, resulting from the mtDNA haplogroup, might also exist in other mitochondrial diseases among Indian populations.
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Povo Asiático/genética , DNA Mitocondrial/genética , NADH Desidrogenase/genética , Atrofia Óptica Hereditária de Leber/genética , Mutação Puntual , Adulto , Análise Mutacional de DNA , Família , Feminino , Haplótipos/genética , Humanos , Índia/epidemiologia , Masculino , Mitocôndrias/genética , Atrofia Óptica Hereditária de Leber/epidemiologia , Atrofia Óptica Hereditária de Leber/patologia , Linhagem , Adulto JovemRESUMO
Leigh syndrome (LS) is a heterogeneous familial or sporadic neurodegenerative disorder. It is typically seen in infancy or childhood, although rare cases of adult onset have been described. The authors describe a 37-year-old woman who presented with protracted gastrointestinal symptoms followed by acute brain stem syndrome with severe metabolic acidosis and who subsequently showed dramatic clinical and neuroradiological improvement.
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Chronic progressive external ophthalmoplegia (CPEO) is caused by defects in both mitochondrial and nuclear genes, however, the causal genetic factors in large number of patients remains undetermined. Therefore, our aim was to screen 12 unrelated patients with CPEO for mutation/multiple deletions in mtDNA and mutations in the coding regions of C10orf2, which is essential for mtDNA replication. Histopathological study of muscle biopsy revealed cytochrome c oxidase-deficient fibers and ragged blue fibers in all the patients. Long-range PCR of DNA from skeletal muscle revealed multiple mtDNA deletions in all the 12 patients. Further, sequencing coding regions of C10orf2 revealed three variants in three different patients, of which two were novel (c.1964G>A/p.G655D; c.204G>A/p.G68G) variants and one was reported (c.1052A>G/p. N351S). Sequencing of other nuclear genes that are associated with CPEO and multiple mtDNA deletions, such as; POLG1, POLG2, TK2, ANT1, DGUOK, MPV17 and RRM2B did not reveal any pathogenic mutation in patients with C10orf2 mutation. Since in silico analyses revealed p.G655D could be a potentially pathogenic and it was absent in 200 healthy controls, p.G655D could be the causative factor for CPEO. Therefore, we suggest that C10orf2 gene should be screened in CPEO individuals with multiple mtDNA deletions, which might help in prognosis of this disease and appropriate genetic counseling.