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1.
Cytopathology ; 35(4): 510-514, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38712698

RESUMO

We offer a comprehensive depiction of the cytomorphological characteristics of lobular endocervical glandular hyperplasia (LEGH) as observed in SurePath™ liquid-based cytology (LBC), subsequently confirmed on cone biopsy. Lobular endocervical glandular hyperplasia (LEGH), a precursor to gastric-type adenocarcinoma (GAE) of the endocervix, is rare and reports of it in cervical cytology are scarce. We provide a thorough description of the cytomorphological features of LEGH observed in SurePath™ liquid-based cytology (LBC), later confirmed by cone biopsy. To the best of our knowledge, this is the first report documenting cytology of LEGH in LBC of a Pap sample.


Assuntos
Colo do Útero , Hiperplasia , Teste de Papanicolaou , Neoplasias do Colo do Útero , Esfregaço Vaginal , Humanos , Feminino , Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal/métodos , Teste de Papanicolaou/métodos , Hiperplasia/patologia , Hiperplasia/diagnóstico , Citodiagnóstico/métodos , Adenocarcinoma/patologia , Adenocarcinoma/diagnóstico , Adulto , Citologia
2.
Cytopathology ; 35(4): 526-529, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38494675

RESUMO

Sertoli-Leydig cell tumours (SLCTs) are rare, mixed sex-cord stromal tumours composed of varying proportions of both Sertoli and Leydig cells, which account for <0.5% of all ovarian tumours. The cytomorphologic features of SLCTs are not well described in literature. Herein, we describe the cytomorphologic features of an SLCT at an uncommon metastatic site in a young female. Sertoli-Leydig cell tumours (SLCTs) are rare, mixed sex-cord stromal tumours composed of varying proportions of both Sertoli and Leydig cells, which account for <0.5% of all ovarian tumours. The cytomorphologic features of SLCTs are not well described in literature. Herein, we describe the cytomorphologic features of an SLCT at an uncommon metastatic site in a young female.


Assuntos
Neoplasias Ovarianas , Tumor de Células de Sertoli-Leydig , Humanos , Feminino , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/diagnóstico , Tumor de Células de Sertoli-Leydig/patologia , Tumor de Células de Sertoli-Leydig/diagnóstico , Adulto
3.
Cytogenet Genome Res ; 2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-38071955

RESUMO

Introduction-Whole genome sequencing of diffuse large B-cell lymphoma [DLBCL] has identified recurrent mutations involved in pathogenesis and potentially affecting response to therapy. In this pilot study, a targeted gene panel was created to identify mutations associated with relapse/refractoriness. Material and methods- A 14-gene targeted panel was designed to sequence thirteen patients who were in remission and nine eight cases that had relapsed/refractory to treatment. A paired diagnostic biopsy and a relapse biopsy were sequenced to find genes repeatedly altered in relapse. Results- A total of 751 nonsynonymous and truncating mutations were identified. Truncated mutations in NOTCH1, TNFAIP3, and CD58 were associated with poor treatment outcomes. In cases that did not respond to treatment, a high number of mutations were found in the EZH2 gene, followed by the DNA-binding domain of TP53 and MYD88. Termination mutations in the intracellular domain of NOTCH were found in 75% of non-responsive cases. Co-occurrence of loss of function mutations of TNFAIP3 and missense mutations in MYD88 was associated with a non-responsive cohort. Discussion-The study highlights mutations associated with chemotherapeutic response in DLBCL with implications for initial diagnostic biopsy response prediction.

4.
Cytopathology ; 34(3): 275-278, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36648323

RESUMO

In this case of phaeohyphomycosis, fine needle aspiration cytology enabled a rapid diagnosis and prompt treatment. This infection is quite prevalent in immunocompromised individuals; however, the Medicopsis romeroi species is a rare causative agent. These cases are associated with inadequate response to standard antifungal therapy and require discussion.


Assuntos
Ascomicetos , Mucormicose , Feoifomicose , Humanos , Antifúngicos/uso terapêutico , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Feoifomicose/diagnóstico , Feoifomicose/tratamento farmacológico , Feminino , Pessoa de Meia-Idade
5.
Cytopathology ; 34(3): 239-249, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36790346

RESUMO

BACKGROUND: Metastasis to the thyroid gland from non-thyroid sites is relatively rare and often poses a diagnostic difficulty on fine-needle aspiration cytology, as it often mimics primary thyroid neoplasms. METHODS: All cases of fine needle aspiration cytology (FNAC) of metastasis to the thyroid gland (2014-2022) were selected from the pathology database. The detailed cytopathological features and histopathology of the cases were studied. RESULTS: There was a total of 18 cases of secondary tumours of the thyroid. All cases had confirmed histopathological data. The most common primary tumours in our study were squamous cell carcinoma of the oesophagus (nine cases) followed by infiltrating ductal carcinoma of the breast (four cases), and one case each of renal cell carcinoma, neuroendocrine carcinoma of the lung, adenocarcinoma stomach and malignant melanoma and squamous cell carcinoma from vallecula. CONCLUSION: Metastasis to thyroid carcinoma is relatively uncommon. A history of malignancy, the presence of malignant cells amid benign thyroid follicular cells, unusual malignancy in a FNAC smear and immunocytochemistry are helpful in diagnosing such cases.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Renais , Neoplasias da Glândula Tireoide , Humanos , Biópsia por Agulha Fina , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia
6.
Cytopathology ; 34(1): 55-60, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36067006

RESUMO

BACKGROUND AND AIM: To describe the cytomorphological findings of all cerebrospinal fluid (CSF) cytology samples showing infiltration by chronic myeloid leukaemia (CML) and their correlation with haematological findings. MATERIALS AND METHODS: A retrospective analysis of all CSF samples reported as showing infiltration by CML on cytology from January 2014 to December 2021 was performed. RESULTS: A total of 10 cases with positive CSF cytology were evaluated. The mean age of the patients was 34.1 years (range 17-70 years). There were more males than females. All cases were pre-diagnosed cases of CML on haematological investigations. On cytology, the smears showed atypical/immature blast-like cells, with a high nucleo-cytoplasmic ratio, opened-up chromatin, 1-2 conspicuous nucleoli and a scant to moderate amount of agranular to fine granular cytoplasm along with occasional granulocytic precursors. The shortest time interval for CSF positivity in a known case of CML was 5 months, and the longest interval was 11 years. CONCLUSION: It is extremely uncommon to encounter CML infiltration in CSF. Timely analysis of CSF cytology samples can allow quick diagnosis and alter the patient management protocol.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Masculino , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico
7.
Pediatr Blood Cancer ; 69(11): e29880, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35841309

RESUMO

BACKGROUND: Distinct prognostic factors for Wilms tumor (WT) in low- and middle-income countries need identification. METHODS: Retrospective study of patients with WT managed by the International Society of Pediatric Oncology (SIOP) approach for over 11 years (2005-2016) at a single center in Chandigarh, India. RESULTS: The study included 200 patients (median age: 33.5 months). The tumor stage (SIOP) distribution included stage I (30%), II (36%), III (14%), IV (17%), and V (3%). The histology-risk groups were low (8%), intermediate (84%), and high risk (9%). At diagnosis, 68 out of 190 (36%) patients were underweight. The median tumor volume at diagnosis was 481 ml (interquartile ratio [IQR]: 306.9, 686.8, n = 146). Following neoadjuvant chemotherapy, it reduced to 110 ml (IQR: 151.2, 222, n = 77). Treatment was abandoned in 20.5% of the patients. Treatment-related mortality occurred in 13 of 179 (7.2%) patients. Relapse occurred in 26 of 158 (16.5%) patients. The 3-year overall survival (OS) and event-free survival (EFS) of patients who completed therapy were 78.3 and 72%, respectively. The stage (p = .013) and histology (p = .023) influenced OS. A lower OS in stage II (75.4%) versus stage III disease (83.7%) suggested understaging. Patients with a higher tumor volume at diagnosis (p = .005; odds ratio [OR]: 0.99; 95% confidence interval [CI]: 0.99-1.00) or a lower weight-for-age z-score (p = .002; OR: 1.68; 95% CI: 1.21-2.33) had an increased risk of death or relapse. CONCLUSIONS: The 3-year OS and EFS of children who completed therapy were 78.3 and 72%, respectively. A higher tumor volume and lower weight-for-age z-score at diagnosis were identified as distinct adverse prognostic factors. A likely suboptimal lymph node assessment (intraoperative and histopathology) contributed to the understaging of stage III to II disease and reduced survival.


Assuntos
Neoplasias Renais , Desnutrição , Tumor de Wilms , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Humanos , Lactente , Neoplasias Renais/patologia , Desnutrição/diagnóstico , Desnutrição/etiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Carga Tumoral , Tumor de Wilms/patologia
8.
Int J Gynecol Pathol ; 41(Suppl 1): S119-S142, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36305537

RESUMO

The move toward consistent and comprehensive surgical pathology reports for cancer resection specimens has been a key development in supporting evidence-based patient management and consistent cancer staging. The International Collaboration on Cancer Reporting (ICCR) previously developed a data set for reporting of the ovarian, fallopian tube and primary peritoneal carcinomas which was published in 2015. In this paper, we provide an update on this data set, as a second edition, that reflects changes in the 2020 World Health Organization (WHO) Classification of Female Genital Tumours as well as some other minor modifications. The data set has been developed by a panel of internationally recognized expert pathologists and a clinician and consists of "core" and "noncore" elements to be included in surgical pathology reports, with detailed commentary to guide users, including references. This data set replaces the widely used first edition, and will facilitate consistent and accurate case reporting, data collection for quality assurance and research, and allow for comparison of epidemiological and pathologic parameters between different populations.


Assuntos
Carcinoma , Patologia Clínica , Feminino , Humanos , Tubas Uterinas/patologia , Patologistas , Carcinoma/patologia , Estadiamento de Neoplasias
9.
Indian J Med Res ; 156(3): 516-523, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36751747

RESUMO

Background & objectives: Accurate and early diagnosis is imperial in the management of endometriosis, endometrioid carcinoma of ovary (ECO) and endometrioid endometrial cancer (EC), yet there are no definitive diagnostic methods available for these diseases. Therefore, the present study was aimed to evaluate the diagnostic potential of differentially expressed miRNAs in serum samples of women with endometriosis, ECO and EC to establish them as diagnostic biomarkers. Methods: Blood samples (5 ml) were obtained from 40 patients (n=10/study group) undergoing laparoscopy/laparotomy/hysterectomy. miRNA-rich RNA was extracted from the serum samples, and quantitative real-time (qRT)-PCR was performed to check the expression levels of miR-16, miR-99b, miR-20a, miR-145, miR-143 and miR-125a in all the samples. Receiver operating characteristic (ROC) curve analysis was done to check the diagnostic potential. Results: In endometriosis, miR-16 was downregulated (P<0.05) whereas miR-99b, miR-125a, miR-143 and miR-145 were upregulated (P<0.05). In ECO group, downregulated expression of miR-16 and miR-125a (P<0.05) was observed, whereas miR-99b, miR-143 and miR-145 were upregulated (P<0.05). In endometrioid EC, miR-16, miR-99b, miR-125 and miR-145 were downregulated (P<0.05), whereas miR-143 was upregulated (P<0.05). ROC curve analysis showed that, for endometriosis, miR-99b, miR-125a, miR-143 and miR-145 served as diagnostic markers. miR-145 showed diagnostic power for ECO, and for endometrioid EC, miR-16, miR-99b, miR-125a and miR-145 showed diagnostic potential. Interpretation & conclusions: The present findings suggested that certain circulating miRNAs (miB99b, miR-16, miR-125a, miR-145) might act as indicators and discriminators of endometriosis and endometrioid subtypes of EC and ovarian cancer and might serve as potential biomarkers for early diagnosis and management of these debilitating diseases.


Assuntos
Carcinoma Endometrioide , Carcinoma Epitelial do Ovário , Endometriose , MicroRNAs , Neoplasias Ovarianas , Feminino , Humanos , Biomarcadores , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/patologia , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Endometriose/genética , Endometriose/patologia , MicroRNAs/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia
10.
Cytopathology ; 33(5): 650-653, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35665550

RESUMO

Neuroendocrine neoplasms (NENs) are a rare heterogeneous group of breast epithelial tumours showing predominant NE differentiation. NENs of the breast account for less than 1% of all NENs. The index case calls for recognition of these tumours using morphology adjunct with ancillary techniques such as immunohistochemistry on FNA cell blocks.


Assuntos
Neoplasias da Mama , Tumores Neuroendócrinos , Biópsia por Agulha Fina , Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Citodiagnóstico , Feminino , Humanos , Tumores Neuroendócrinos/patologia , Corantes de Rosanilina
11.
Cytopathology ; 33(6): 688-695, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35778919

RESUMO

BACKGROUND: Solitary fibrous tumour (SFT) is a tumour of mesenchymal origin. Its diagnosis on cytology is challenging, owing to variation in cellularity, sparsely distributed cellular and stromal components. Cytomorphological findings for this type of tumour have rarely been described in the literature-only a few case reports and the occasional case series have been presented thus far. We present the cytomorphological features of SFT with special emphasis on immunochemical findings. MATERIALS AND METHODS: We present cytological data from eight cases of histopathologically proven SFTs. The cytomorphological features, immunochemical markers and differential diagnostic entities on fine needle aspiration cytology are discussed. RESULTS: Fine needle aspiration was performed at various anatomical sites. Cytology smears showed variable cellularity, with tumour cells arranged in loose clusters and as singly scattered cells. Interlacing fascicles with palisading of cells was noted. The cells were predominantly spindle to elongated, having moderate cytoplasm with elongated wavy nuclei. These nuclei had fine to coarse chromatin, with inconspicuous to prominent nucleoli. There was prominent, metachromatically staining, amorphous to fibrillary, collagenous to myxoid matrix material associated with the tumour cells. Other findings included intranuclear pseudo-inclusions, multinucleated giant cells and atypical mitoses. Cytological diagnoses offered varied from 'spindle cell neoplasm' to 'spindle cell sarcoma' or 'suggestive of sarcoma'. Immunocytochemistry (ICC) performed on cell block sections showed positivity for STAT6, CD34 and Bcl-2. CONCLUSION: Cytological diagnosis of SFT can be challenging. A careful search for characteristic cytomorphological features is diagnostically helpful. The cytomorphology should be interpreted with caution, with an appropriate ICC panel, including STAT6 and CD34.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Tumores Fibrosos Solitários , Antígenos CD34 , Biomarcadores Tumorais , Cromatina , Humanos , Proteínas Proto-Oncogênicas c-bcl-2 , Tumores Fibrosos Solitários/diagnóstico , Tumores Fibrosos Solitários/patologia
12.
Cytopathology ; 33(6): 678-687, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35749049

RESUMO

INTRODUCTION: Malignant effusions are commonly encountered in day-to-day cytology practice. Determining the primary site of malignancy in carcinomatous effusions is a Herculean task. Cytology coupled with immunocytochemistry (ICC) is often found to be helpful in this context. MATERIALS AND METHODS: This study was conducted to evaluate the diagnostic utility of ICC on sections from cell blocks (CBs) in the detection of the primary site of origin in cases of metastatic carcinomatous effusions. To determine the origin of the primary tumour, TTF1 (lung), PAX-8 (ovary), CDX2 (colorectal), GATA3 (breast), and CK19 (pancreaticobiliary) were employed, depending on the clinical and radiological findings, and serum tumour markers. RESULTS: A total of 13,459 serous effusion samples were received for cytological evaluation from January 2017 to December 2021, of which 2708 (20.1%) were carcinomatous effusions. Out of these, 1044 (38.5%), 1611 (59.5%), and 53 (2.0%) were from pleural, peritoneal and pericardial cavities, respectively. Of these, the majority were adenocarcinoma. ICC was performed in 309 (11.4%) cases. The ovary was the most common primary site in 179 cases (57.9%), followed by the lung (75, 24.3%), pancreaticobiliary system (12, 3.9%), colon/rectum (8, 2.6%), breast (6, 1.9%), prostate (2, 0.6%) and kidney (1, 0.3). The lung was the most common primary site in pleural (67/113, 59.3%) and pericardial (6/8, 75%) effusions. The ovary (168/188, 89.4%) was the most common primary site for carcinomatous effusions in the peritoneal cavity. However, in 17 (5.5%) cases, the exact primary site could not be established. CONCLUSIONS: Judicious and methodical use of ICC on CBs helps to identify the primary site of the tumour in most carcinomatous effusions. This is of immense help to the treating clinician in directing appropriate therapy.


Assuntos
Adenocarcinoma , Derrame Pleural Maligno , Adenocarcinoma/patologia , Líquido Ascítico/patologia , Biomarcadores Tumorais , Citodiagnóstico , Feminino , Humanos , Imuno-Histoquímica , Masculino , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/patologia
13.
Cytopathology ; 33(4): 493-498, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35347771

RESUMO

BACKGROUND: Germ cell tumours infrequently metastasise to body cavities, where early detection on fluid samples is possible and can spearhead early treatment and survival. MATERIALS AND METHODS: A total of seven cases of metastatic germ cell tumours were retrieved out of 7500 effusion samples received for cytopathological examination from 2015 to 2021. Detailed cytological features of metastatic germ cell tumours in effusion samples were studied, along with a correlation between clinical, radiological, and histopathological features. RESULTS: A total of seven cases of metastatic germ cell tumours were analysed in effusion samples which included dysgerminoma (2), immature teratoma (2), yolk sac tumour (1), embryonal carcinoma (1), and mixed germ cell tumour (1). The smears showed predominantly discrete or loose clusters of cells. The cells with round nuclei and prominent nucleoli were helpful in detecting dysgerminoma and yolk sac tumours. Immature teratoma showed tiny groups of small cells and mature squamous cells. Serum tumour markers were raised in the majority of cases. CONCLUSION: Metastatic germ cell tumours in effusion are uncommon, but detailed clinical history, including serum markers and characteristic cytological features, are helpful in their diagnosis.


Assuntos
Disgerminoma , Neoplasias Embrionárias de Células Germinativas , Segunda Neoplasia Primária , Neoplasias Ovarianas , Teratoma , Neoplasias Testiculares , Disgerminoma/patologia , Feminino , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Ovarianas/patologia , Teratoma/diagnóstico , Teratoma/patologia , Neoplasias Testiculares/patologia
14.
Cytopathology ; 33(6): 732-737, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35867808

RESUMO

BACKGROUND: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) resistance may be acquired via genotypic and/or phenotypic transformations. Herein, we report an extremely uncommon case with sequential small cell transformation and EGFR T790M mutation, in an elderly female with EGFR exon 21 L858R-mutant lung adenocarcinoma, following treatment with a first-generation EGFR-TKI. CASE: A 67-year-old female never-smoker presented with a cough and dyspnoea of 2 months' duration. Computerised tomography revealed a 39 mm lesion in the upper lobe of the right lung with pleural effusion. Pleural fluid cytology revealed metastatic lung adenocarcinoma, and EGFR testing revealed exon 21 L858R mutation. She was started on gefitinib. After a progression-free survival of 31 months, she presented with disease progression and multiple extra-thoracic metastases. Fine needle aspiration cytology of a chest wall lesion revealed metastatic small cell carcinoma. EGFR testing on this aspirate revealed persistent L858R mutation only. In view of small cell transformation, chemotherapy (etoposide and carboplatin) was administered. After 4 months, ascitic fluid cytology revealed metastatic adenocarcinoma with persistent L858R mutation and an acquired T790M mutation (both detected on liquid biopsy as well) indicating amplification of the adenocarcinoma clone and regression of the small cell carcinoma clone. She was then initiated on osimertinib. CONCLUSIONS: The index case highlights the significance of serial EGFR genotyping along with repeated tissue and/or blood sampling in the prompt detection of genetic and phenotypic resistance mechanisms to EGFR-TKIs. Furthermore, it lends evidence in support of the upfront treatment approaches targeting the heterogeneity of acquired EGFR-TKI resistance mechanisms.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Carcinoma de Células Pequenas , Neoplasias Pulmonares , Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Idoso , Carboplatina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Fator de Crescimento Epidérmico/genética , Fator de Crescimento Epidérmico/uso terapêutico , Receptores ErbB/genética , Etoposídeo/uso terapêutico , Feminino , Gefitinibe/uso terapêutico , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação/genética , Inibidores de Proteínas Quinases/uso terapêutico
15.
Pediatr Hematol Oncol ; 39(7): 587-599, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35271413

RESUMO

ABVD regimen for Hodgkin lymphoma (HL) is frequently used in children and young adults in low-middle income countries (LMIC). The feasibility and safety data for 'non-ABVD' protocols from LMIC is limited. The retrospective study was conducted in a single center in India. The Euronet PHL-C1 based protocol was administered during 2010-19. A PET-CT was performed at diagnosis and following two OEPA cycles. Radiotherapy was administered for inadequate PET response. During the 10-year period, 143 patients with HL were treated. The mean age was 7.8 ± 2.5 years. Bulky disease was observed in 82 (59%). Treatment abandonment was recorded in 13 (9.1%). The median follow-up duration was 46.4 months. An inadequate PET response was observed in 41/119 (34.4%), of which 56.1% received radiotherapy. Twelve (29.3%) patients who were supposed to receive radiotherapy received 2-cycles of COPDAC instead. Sixty-nine episodes of febrile neutropenia were observed in 54 patients. Treatment-related mortality (TRM) was observed in 7 (5.3%). The majority of episodes of febrile neutropenia (61%) and TRM (86%) occurred in the first cycle of OEPA. The 4-year event-free survival (EFS) and overall survival (OS) were 86.2 ± 3.4% and 93.5 ± 2.2%, respectively. Nine (6.3%) patients relapsed. Bulky disease lacked association with inadequate PET response (p = .800) or relapse (p = 1.000). OEPA/COPDAC regimen and response assessment by PET-CT permitted therapy reduction, including radiotherapy. Febrile neutropenia and resultant TRM (5.3%) are concerning and occurred frequently in the first cycle of OEPA. The support system for managing febrile neutropenia should be optimized for administering OEPA in LMIC.


Assuntos
Neutropenia Febril , Doença de Hodgkin , Linfoma , Protocolos de Quimioterapia Combinada Antineoplásica , Criança , Pré-Escolar , Países em Desenvolvimento , Doxorrubicina/uso terapêutico , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/radioterapia , Humanos , Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Retrospectivos , Resultado do Tratamento , Vimblastina , Adulto Jovem
16.
Pediatr Hematol Oncol ; 39(5): 391-405, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34978257

RESUMO

The literature on B-non-Hodgkin lymphoma (NHL) in India is restricted to individual hospital data. The study aimed to evaluate the epidemiology and outcome of B-NHL in our country. One hundred and ninety-one patients of B-NHL from 10 centers diagnosed between 2013 and 2016 were analyzed retrospectively. B/T lymphoblastic lymphoma and patients with inadequate data were excluded. The median age was 88 months (IQR: 56, 144) with an M:F ratio of 5.6:1. Undernourishment and stunting were seen in 36.5% and 22%. Primary site was abdomen in 66.5%. Hypoalbuminemia was noted in 82/170 (48.2%). Histological subtypes: Burkitt lymphoma (BL): 69.6%, Burkitt-like: 10.4%, and diffuse large B cell lymphoma (DLBCL): 13.6%, unclassified and others (6.4%). Stage distribution: I/II, 33 (17.3%), III, 114 (59.7%), and IV, 44 (23%). One-eighty-six patients took treatment. Protocols used were LMB and BFM in 160/186 (86%). At a median follow-up of 21.34 (IQR: 4.34, 36.57) months, the disease-free-survival (DFS) was 74.4% and event-free-survival (EFS) was 60.7%. Treatment-related mortality (TRM), relapse/progression and abandonment were 14.3%, 14.5%, and 8.4%, respectively. Bone marrow positivity, stage IV disease, and lactate dehydrogenase (LDH) > 2,000 U/l predicted inferior EFS. Stage IV disease, LDH > 2,000 U/l, bone marrow positivity, tumor lysis syndrome and low albumin predicted TRM; LDH retained significance on multivariate analysis for EFS and TRM [OR: 4.54, 95% CI: 1.14-20, p 0.03; OR 20, 95%CI: 1.69-250, p 0.017]. BL was the main histological subtype. High TRM and relapse/progression are hampering survival. An LDH > 2,000 U/l was adversely prognostic. These data demonstrate a need to develop a national protocol that balances toxicity and potential for cure.


Assuntos
Linfoma de Burkitt , Linfoma Difuso de Grandes Células B , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Criança , Intervalo Livre de Doença , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Prognóstico , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
17.
Biochem Cell Biol ; 99(5): 587-595, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33677985

RESUMO

Cervical cancer is one of the leading causes of mortality amongst women in developing countries, and resistance to therapy is the main reason for treatment failure. Recent advances suggest that cancer stem cells (CSCs) are critically involved in regulating the chemo-resistant behavior of cervical cancer cells. In our study, cells with the CSC phenotype were isolated, and we examined the expression levels of stem cell markers and genes associated with epithelial-mesenchymal transition (EMT) using different assays. However, the cells with the CSC phenotype could not be cultured for further cytotoxicity studies, so we established a model of CSC in cervical cancer cells. We performed siRNA-mediated knockdown of E-cadherin in these cells, and studied them for EMT-associated stem-cell-like properties. We also performed dose-dependent cell viability assays using clinically relevant drugs such as cisplatin, cyclopamine, and GANT58 to analyze the drug resistant behavior of these cancer cells. We found that knockdown of E-cadherin induces EMT in cervical cancer cells, imparting stem-cell like characteristics along with enhanced tumorsphere formation, cell migration, invasiveness, and drug resistance. This is the first study to establish a CSC model in cervical cancer cells by knockdown of E-cadherin, which can be used to develop anti-cancer therapies.


Assuntos
Caderinas/metabolismo , Células-Tronco Neoplásicas/metabolismo , Neoplasias do Colo do Útero/metabolismo , Antineoplásicos/farmacologia , Caderinas/antagonistas & inibidores , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Ensaios de Seleção de Medicamentos Antitumorais , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Células-Tronco Neoplásicas/efeitos dos fármacos , Fenótipo , Piridinas/farmacologia , RNA Interferente Pequeno/farmacologia , Tiofenos/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Alcaloides de Veratrum/farmacologia
18.
Am J Hum Genet ; 103(5): 740-751, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30388401

RESUMO

Androgenetic complete hydatidiform moles are human pregnancies with no embryos and affect 1 in every 1,400 pregnancies. They have mostly androgenetic monospermic genomes with all the chromosomes originating from a haploid sperm and no maternal chromosomes. Androgenetic complete hydatidiform moles were described in 1977, but how they occur has remained an open question. We identified bi-allelic deleterious mutations in MEI1, TOP6BL/C11orf80, and REC114, with roles in meiotic double-strand breaks formation in women with recurrent androgenetic complete hydatidiform moles. We investigated the occurrence of androgenesis in Mei1-deficient female mice and discovered that 8% of their oocytes lose all their chromosomes by extruding them with the spindles into the first polar body. We demonstrate that Mei1-/- oocytes are capable of fertilization and 5% produce androgenetic zygotes. Thus, we uncover a meiotic abnormality in mammals and a mechanism for the genesis of androgenetic zygotes that is the extrusion of all maternal chromosomes and their spindles into the first polar body.


Assuntos
Androgênios/genética , Mola Hidatiforme/genética , Mutação/genética , Alelos , Animais , Cromossomos/genética , Feminino , Humanos , Masculino , Mamíferos/genética , Camundongos , Camundongos Endogâmicos C57BL , Oócitos/patologia , Gravidez , Zigoto/patologia
19.
Pediatr Blood Cancer ; 68(7): e28996, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33745231

RESUMO

OBJECTIVE: Paediatric malignant renal neoplasms are subjected to neoadjuvant chemotherapy as per Societe Internationale d'Oncologie Pediatrique; International Society of Pediatric Oncology (SIOP) protocol. An accurate tissue diagnosis is required prior to institution of chemotherapy, and hence the aim of this study was to evaluate the diagnostic accuracy of fine needle aspiration biopsy cytology (FNABC) along with cell block histology. MATERIALS AND METHODS: A retrospective audit of all paediatric renal neoplasms diagnosed by FNABC between 2015 and 2019 was performed. Histopathology correlation was done wherever available. WT cases were subjected to detailed cytomorphological evaluation. RESULTS: A total of 121 cases of paediatric renal neoplasms including 109 WT, four clear cell sarcoma, one malignant rhabdoid tumour and three mesoblastic nephroma were evaluated. The age range was 4 weeks to 8 years. FNABC samples were adequate for diagnosis in 120 of 121 cases (99.18%) and a definitive cytological diagnosis was achieved in 117 cases (96.7%). The specificity and sensitivity for a cytopathological diagnosis of WT were 98.7% and 97.4%, respectively. On detailed cytomorphological analysis of 68 histopathology-proven WT, 40 (58.8%) cases were triphasic, 23 (35.3%) were biphasic and four were composed of blastema only. The corresponding cell blocks provided additional information over the conventional smears in 23 (33.8%) cases, with epithelial or mesenchymal elements recognised and evidence of rhabdomyoblastic differentiation. CONCLUSION: FNABC along with cell block histology is highly accurate for diagnosis of WT and other malignant paediatric renal neoplasms and is recommended as the technique of choice in centres with cytopathology expertise for establishing a cellular diagnosis prior to commencement of neoadjuvant chemotherapy.


Assuntos
Neoplasias Renais , Tumor de Wilms , Biópsia por Agulha Fina , Criança , Humanos , Lactente , Recém-Nascido , Nefroma Mesoblástico , Estudos Retrospectivos , Tumor de Wilms/tratamento farmacológico
20.
Indian J Med Res ; 154(2): 367-374, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35295009

RESUMO

Background & objectives: Chemoradiation is the standard therapy for locally advanced invasive cervical cancer and response to treatment determines the outcome. Cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) play a role in response to treatment and hence the aim of this study was to evaluate if their levels in pre-treatment biopsies by immunohistochemistry (IHC) could predict response to treatment and outcome. Methods: The study comprised 60 patients with FIGO Stage IIB/III invasive cervical carcinoma treated by chemoradiation. They were divided into two groups based on their clinical outcome: group 1, 30 patients who had no evidence of disease at 48 month follow up and group 2, 30 patients who had disease relapse within 6-12 months of treatment completion. IHC was performed for CSC markers (ALDH1, CD133, Nanog and Oct-4), EMT markers (E-cadherin and vimentin) and squamocolumnar junction (KRT7) markers and H-scores determined. Intergroup comparison was performed. The expression of these markers was also evaluated in histological sections of cervical pre-cancer (CIN1 and CIN3) in comparison to normal cervix. Results: Cervical Intraepithelial Neoplasia grade 3 (CIN3) showed high expression of ALDH1 and KRT7 as compared to normal cervical epithelium. Aldehyde dehydrogenase 1 (ALDH1) and CD133 were overexpressed in 70 and 24 per cent cervical carcinoma cases whereas E-cadherin showed reduced expression in invasive carcinoma as compared to normal controls. ALDH1 overexpression was significantly associated with disease relapse in invasive cervical carcinoma treated by chemoradiation (P<0.01). Interpretation & Conclusions: Determination of ALDH1 levels in pre-treatment cervical biopsies of invasive cervical carcinoma may be useful for prediction of response to chemoradiation, with high levels predicting for a poor response.


Assuntos
Quimiorradioterapia , Neoplasias do Colo do Útero , Família Aldeído Desidrogenase 1 , Biomarcadores Tumorais/metabolismo , Caderinas , Feminino , Humanos , Isoenzimas/metabolismo , Recidiva , Retinal Desidrogenase/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia
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