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1.
BMJ Case Rep ; 15(11)2022 Nov 04.
Article in English | MEDLINE | ID: mdl-36332932

ABSTRACT

Spindle cell carcinoma is a subtype of sarcomatoid carcinoma, which has previously been described in various anatomical locations, though rarely in the trachea.We present the case of a woman in her 70s who presented with a sore throat and stridor. Fibreoptic nasendoscopy demonstrated a tracheal mass occupying 80% of the airway from the cricoid cartilage to the third tracheal ring, infiltrating the thyroid gland. Subsequent CT demonstrated pulmonary emboli and vertebral metastasis. Biopsy of the infiltrated thyroid confirmed the diagnosis of spindle cell carcinoma. The length of the tumour and metastasis at presentation made this surgically unresectable, and she was referred for a palliative stent but died after an acute deterioration.This pathology has been reported only five times previously in the literature, with management strategies varying greatly between patients. Primary tracheal tumours are difficult to manage as, due to their rarity, there are no clear guidelines.


Subject(s)
Carcinoma , Sarcoma , Soft Tissue Neoplasms , Thyroid Neoplasms , Tracheal Neoplasms , Female , Humans , Trachea/diagnostic imaging , Trachea/pathology , Tracheal Neoplasms/diagnostic imaging , Tracheal Neoplasms/surgery , Sarcoma/diagnostic imaging , Sarcoma/surgery , Carcinoma/pathology , Soft Tissue Neoplasms/pathology , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/surgery , Thyroid Neoplasms/pathology
2.
Cell Rep ; 40(7): 111230, 2022 08 16.
Article in English | MEDLINE | ID: mdl-35977489

ABSTRACT

A defining pathological feature of human lung fibrosis is localized tissue heterogeneity, which challenges the interpretation of transcriptomic studies that typically lose spatial information. Here we investigate spatial gene expression in diagnostic tissue using digital profiling technology. We identify distinct, region-specific gene expression signatures as well as shared gene signatures. By integration with single-cell data, we spatially map the cellular composition within and distant from the fibrotic niche, demonstrating discrete changes in homeostatic and pathologic cell populations even in morphologically preserved lung, while through ligand-receptor analysis, we investigate cellular cross-talk within the fibrotic niche. We confirm findings through bioinformatic, tissue, and in vitro analyses, identifying that loss of NFKB inhibitor zeta in alveolar epithelial cells dysregulates the TGFß/IL-6 signaling axis, which may impair homeostatic responses to environmental stress. Thus, spatially resolved deconvolution advances understanding of cell composition and microenvironment in human lung fibrogenesis.


Subject(s)
Pulmonary Fibrosis , Alveolar Epithelial Cells/metabolism , Fibrosis , Humans , Lung/pathology , Pulmonary Fibrosis/metabolism , Signal Transduction
3.
Neuropathol Appl Neurobiol ; 48(2): e12755, 2022 02.
Article in English | MEDLINE | ID: mdl-34309064

ABSTRACT

We report a rapidly progressive and fatal CD8 T-cell-mediated cerebellitis after ipilimumab (cytotoxic T-lymphocyte-associated protein 4 inhibitor) for small cell lung cancer. Clinical features and histopathology were consistent with an accelerated form of paraneoplastic cerebellar degeneration. A patchy CD8 T-cell infiltrate spatially corresponded to areas of Purkinje cell loss, with occasional CD8 polarisation towards Purkinje cells. CD20-positive B cells were sparse. CD8 T-cell-mediated cerebellitis after immune checkpoint inhibitor treatment may recapitulate the early stages of paraneoplastic cerebellar degeneration.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Immune Checkpoint Inhibitors/adverse effects , Ipilimumab/adverse effects , Lung Neoplasms/drug therapy , Paraneoplastic Cerebellar Degeneration/chemically induced , Purkinje Cells/immunology , Small Cell Lung Carcinoma/drug therapy , Humans , Immune Checkpoint Inhibitors/administration & dosage , Immune Checkpoint Inhibitors/therapeutic use , Ipilimumab/administration & dosage , Ipilimumab/therapeutic use , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Male , Middle Aged , Paraneoplastic Cerebellar Degeneration/immunology , Purkinje Cells/drug effects , Small Cell Lung Carcinoma/immunology , Small Cell Lung Carcinoma/pathology
4.
J Clin Invest ; 131(15)2021 08 02.
Article in English | MEDLINE | ID: mdl-34128839

ABSTRACT

Tuberculosis (TB) is a persistent global pandemic, and standard treatment for it has not changed for 30 years. Mycobacterium tuberculosis (Mtb) has undergone prolonged coevolution with humans, and patients can control Mtb even after extensive infection, demonstrating the fine balance between protective and pathological host responses within infected granulomas. We hypothesized that whole transcriptome analysis of human TB granulomas isolated by laser capture microdissection could identify therapeutic targets, and that comparison with a noninfectious granulomatous disease, sarcoidosis, would identify disease-specific pathological mechanisms. Bioinformatic analysis of RNAseq data identified numerous shared pathways between TB and sarcoidosis lymph nodes, and also specific clusters demonstrating TB results from a dysregulated inflammatory immune response. To translate these insights, we compared 3 primary human cell culture models at the whole transcriptome level and demonstrated that the 3D collagen granuloma model most closely reflected human TB disease. We investigated shared signaling pathways with human disease and identified 12 intracellular enzymes as potential therapeutic targets. Sphingosine kinase 1 inhibition controlled Mtb growth, concurrently reducing intracellular pH in infected monocytes and suppressing inflammatory mediator secretion. Immunohistochemical staining confirmed that sphingosine kinase 1 is expressed in human lung TB granulomas, and therefore represents a host therapeutic target to improve TB outcomes.


Subject(s)
Granuloma, Respiratory Tract/metabolism , Lung/metabolism , Models, Biological , Mycobacterium tuberculosis/metabolism , RNA-Seq , Tuberculosis, Pulmonary/metabolism , Adult , Aged , Female , Granuloma, Respiratory Tract/genetics , Granuloma, Respiratory Tract/microbiology , Granuloma, Respiratory Tract/pathology , Humans , Lung/microbiology , Lung/pathology , Male , Middle Aged , Tuberculosis, Pulmonary/genetics , Tuberculosis, Pulmonary/pathology
5.
Elife ; 92020 02 24.
Article in English | MEDLINE | ID: mdl-32091388

ABSTRACT

Previously, we developed a 3-dimensional cell culture model of human tuberculosis (TB) and demonstrated its potential to interrogate the host-pathogen interaction (Tezera et al., 2017a). Here, we use the model to investigate mechanisms whereby immune checkpoint therapy for cancer paradoxically activates TB infection. In patients, PD-1 is expressed in Mycobacterium tuberculosis (Mtb)-infected lung tissue but is absent in areas of immunopathology. In the microsphere model, PD-1 ligands are up-regulated by infection, and the PD-1/PD-L1 axis is further induced by hypoxia. Inhibition of PD-1 signalling increases Mtb growth, and augments cytokine secretion. TNF-α is responsible for accelerated Mtb growth, and TNF-α neutralisation reverses augmented Mtb growth caused by anti-PD-1 treatment. In human TB, pulmonary TNF-α immunoreactivity is increased and circulating PD-1 expression negatively correlates with sputum TNF-α concentrations. Together, our findings demonstrate that PD-1 regulates the immune response in TB, and inhibition of PD-1 accelerates Mtb growth via excessive TNF-α secretion.


Subject(s)
Immunotherapy/methods , Latent Tuberculosis/pathology , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Tumor Necrosis Factor-alpha/metabolism , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cell Hypoxia , Granuloma/metabolism , Humans , Latent Tuberculosis/immunology , Microspheres , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/growth & development , Mycobacterium tuberculosis/metabolism , Programmed Cell Death 1 Receptor/metabolism , Tumor Necrosis Factor-alpha/pharmacology , Up-Regulation
6.
J Surg Case Rep ; 2019(4): rjz092, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30967930

ABSTRACT

Mucoepidermoid variant of thyroid carcinoma is a rare and complex disease. Securing a diagnosis and formulating an evidence-based treatment plan is challenging. A case report of a patient with the dual pathology of a composite mucoepidermoid carcinoma of the thyroid and a follicular variant of papillary thyroid carcinoma with malignant metastasis is presented in this article. We discuss the challenges in diagnosis, prognostic factors and management of this rare presentation by reviewing current literature.

7.
Elife ; 72018 07 03.
Article in English | MEDLINE | ID: mdl-29966587

ABSTRACT

Matrix stiffening with downstream activation of mechanosensitive pathways is strongly implicated in progressive fibrosis; however, pathologic changes in extracellular matrix (ECM) that initiate mechano-homeostasis dysregulation are not defined in human disease. By integrated multiscale biomechanical and biological analyses of idiopathic pulmonary fibrosis lung tissue, we identify that increased tissue stiffness is a function of dysregulated post-translational collagen cross-linking rather than any collagen concentration increase whilst at the nanometre-scale collagen fibrils are structurally and functionally abnormal with increased stiffness, reduced swelling ratio, and reduced diameter. In ex vivo and animal models of lung fibrosis, dual inhibition of lysyl oxidase-like (LOXL) 2 and LOXL3 was sufficient to normalise collagen fibrillogenesis, reduce tissue stiffness, and improve lung function in vivo. Thus, in human fibrosis, altered collagen architecture is a key determinant of abnormal ECM structure-function, and inhibition of pyridinoline cross-linking can maintain mechano-homeostasis to limit the self-sustaining effects of ECM on progressive fibrosis.


Subject(s)
Amino Acid Oxidoreductases/antagonists & inhibitors , Collagen/chemistry , Enzyme Inhibitors/pharmacology , Extracellular Matrix/chemistry , Pulmonary Fibrosis/drug therapy , Reticulin/chemistry , Amino Acid Oxidoreductases/genetics , Amino Acid Oxidoreductases/metabolism , Amino Acids/chemistry , Animals , Biomechanical Phenomena , Case-Control Studies , Collagen/metabolism , Collagen/ultrastructure , Cross-Linking Reagents/chemistry , Disease Models, Animal , Extracellular Matrix/metabolism , Extracellular Matrix/ultrastructure , Female , Fibroblasts/cytology , Fibroblasts/drug effects , Fibroblasts/metabolism , Gene Expression , Homeostasis/genetics , Humans , Lung/metabolism , Lung/pathology , Mechanotransduction, Cellular , Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/antagonists & inhibitors , Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/genetics , Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/metabolism , Protein-Lysine 6-Oxidase , Pulmonary Fibrosis/genetics , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/pathology , Rats , Rats, Sprague-Dawley , Reticulin/metabolism , Reticulin/ultrastructure , Structure-Activity Relationship , Transforming Growth Factor beta1/antagonists & inhibitors , Transforming Growth Factor beta1/pharmacology
8.
PLoS Pathog ; 13(6): e1006367, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28570642

ABSTRACT

Tuberculosis remains a global pandemic and drives lung matrix destruction to transmit. Whilst pathways driving inflammatory responses in macrophages have been relatively well described, negative regulatory pathways are less well defined. We hypothesised that Mycobacterium tuberculosis (Mtb) specifically targets negative regulatory pathways to augment immunopathology. Inhibition of signalling through the PI3K/AKT/mTORC1 pathway increased matrix metalloproteinase-1 (MMP-1) gene expression and secretion, a collagenase central to TB pathogenesis, and multiple pro-inflammatory cytokines. In patients with confirmed pulmonary TB, PI3Kδ expression was absent within granulomas. Furthermore, Mtb infection suppressed PI3Kδ gene expression in macrophages. Interestingly, inhibition of the MNK pathway, downstream of pro-inflammatory p38 and ERK MAPKs, also increased MMP-1 secretion, whilst suppressing secretion of TH1 cytokines. Cross-talk between the PI3K and MNK pathways was demonstrated at the level of eIF4E phosphorylation. Mtb globally suppressed the MMP-inhibitory pathways in macrophages, reducing levels of mRNAs encoding PI3Kδ, mTORC-1 and MNK-1 via upregulation of miRNAs. Therefore, Mtb disrupts negative regulatory pathways at multiple levels in macrophages to drive a tissue-destructive phenotype that facilitates transmission.


Subject(s)
Macrophages/immunology , Mycobacterium tuberculosis/immunology , Tuberculosis, Pulmonary/immunology , Animals , Humans , Macrophages/microbiology , Matrix Metalloproteinase 1/genetics , Matrix Metalloproteinase 1/immunology , Mechanistic Target of Rapamycin Complex 1 , Mice , Multiprotein Complexes/genetics , Multiprotein Complexes/immunology , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/physiology , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/immunology , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/immunology , Tuberculosis, Pulmonary/genetics , Tuberculosis, Pulmonary/microbiology , Tuberculosis, Pulmonary/pathology
9.
Elife ; 62017 01 07.
Article in English | MEDLINE | ID: mdl-28063256

ABSTRACT

Cell biology differs between traditional cell culture and 3-dimensional (3-D) systems, and is modulated by the extracellular matrix. Experimentation in 3-D presents challenges, especially with virulent pathogens. Mycobacterium tuberculosis (Mtb) kills more humans than any other infection and is characterised by a spatially organised immune response and extracellular matrix remodelling. We developed a 3-D system incorporating virulent mycobacteria, primary human blood mononuclear cells and collagen-alginate matrix to dissect the host-pathogen interaction. Infection in 3-D led to greater cellular survival and permitted longitudinal analysis over 21 days. Key features of human tuberculosis develop, and extracellular matrix integrity favours the host over the pathogen. We optimised multiparameter readouts to study emerging therapeutic interventions: cytokine supplementation, host-directed therapy and immunoaugmentation. Each intervention modulates the host-pathogen interaction, but has both beneficial and harmful effects. This methodology has wide applicability to investigate infectious, inflammatory and neoplastic diseases and develop novel drug regimes and vaccination approaches.


Subject(s)
Host-Pathogen Interactions/drug effects , Leukocytes, Mononuclear/drug effects , Models, Biological , Mycobacterium tuberculosis/pathogenicity , Spheroids, Cellular/drug effects , Alginates/chemistry , Antigens, Bacterial/pharmacology , Bacterial Proteins/pharmacology , Chemokine CCL2/biosynthesis , Chemokine CCL2/metabolism , Chemokine CXCL10/biosynthesis , Chemokine CXCL10/metabolism , Coculture Techniques , Collagen/chemistry , Dinoprostone/pharmacology , Extracellular Matrix/chemistry , Extracellular Matrix/drug effects , Extracellular Matrix/immunology , Gene Expression Regulation , Glucuronic Acid/chemistry , Granulocyte-Macrophage Colony-Stimulating Factor/biosynthesis , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Hexuronic Acids/chemistry , Host-Pathogen Interactions/immunology , Humans , Interleukin-12/biosynthesis , Interleukin-12/metabolism , Interleukin-1beta/biosynthesis , Interleukin-1beta/metabolism , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/microbiology , Microspheres , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/physiology , Spheroids, Cellular/immunology , Spheroids, Cellular/microbiology , Virulence
10.
J Surg Case Rep ; 2017(10): rjx205, 2017 Oct.
Article in English | MEDLINE | ID: mdl-29423146

ABSTRACT

Development of distant metastases from renal cell carcinoma (RCC) is a frequent occurrence and, in nearly 95% of the cases, secondary lesions present within 5 years following nephrectomy. We performed a left pneumonectomy for a peri-hilar lung mass in an 81-year-old man with history of kidney cancer, resected 37 years earlier. Histopathological examination revealed a solitary lung metastasis from RCC, relapsed after an extraordinary 37-year time interval. To the best of our knowledge, this remarkable case represents the longest time interval between radical nephrectomy for RCC and the occurrence of a pulmonary metastasis. After an uneventful post-operative recovery, there are no signs of disease recurrence at a 3-year follow-up. The possibility of a lung metastasis should be taken into account in patients with history of RCC who present with pulmonary nodules, even decades after treatment of the primary neoplasm.

11.
JCI Insight ; 1(5)2016 Apr 21.
Article in English | MEDLINE | ID: mdl-27275013

ABSTRACT

In idiopathic pulmonary fibrosis (IPF), the fibroblast focus is a key histological feature representing active fibroproliferation. On standard 2D pathologic examination, fibroblast foci are considered small, distinct lesions, although they have been proposed to form a highly interconnected reticulum as the leading edge of a "wave" of fibrosis. Here, we characterized fibroblast focus morphology and interrelationships in 3D using an integrated micro-CT and histological methodology. In 3D, fibroblast foci were morphologically complex structures, with large variations in shape and volume (range, 1.3 × 104 to 9.9 × 107 µm3). Within each tissue sample numerous multiform foci were present, ranging from a minimum of 0.9 per mm3 of lung tissue to a maximum of 11.1 per mm3 of lung tissue. Each focus was an independent structure, and no interconnections were observed. Together, our data indicate that in 3D fibroblast foci form a constellation of heterogeneous structures with large variations in shape and volume, suggesting previously unrecognized plasticity. No evidence of interconnectivity was identified, consistent with the concept that foci represent discrete sites of lung injury and repair.

13.
Histopathology ; 67(4): 557-61, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25620085

ABSTRACT

AIMS: Immunoglobulin (Ig)G4-related disease (IgG4-RD) is an increasingly recognized fibroinflammatory condition that commonly exhibits multisystem involvement, with localized (e.g. inflammatory pseudotumours that can mimic malignancy) or diffuse (leading to organ dysfunction) patterns of tissue involvement. The 2012 Boston criteria have standardized the histopathological approach to the diagnosis of IgG4-RD and require one or more of the cardinal morphological features with prominence of IgG4(+) plasma cells and an IgG4(+) /IgG(+) plasma cell ratio of at least 40%. The relative prevalence of the morphological criteria varies between anatomical sites, but granulomas are rarely found and, indeed, their presence would usually deter a pathologist from making this diagnosis. The aim was to characterize two cases of IgG4-RD in which granulomas were present and to highlight this as an unusual feature of the condition. METHODS AND RESULTS: We describe two cases in which the features of IgG4-RD were present within lymph nodes, together with granulomas. This is a recognized but rare morphological pattern of IgG4-RD. CONCLUSIONS: While an unusual finding, the presence of granulomas should not preclude a diagnosis of IgG4-RD in the appropriate clinicopathological context.


Subject(s)
Granuloma/pathology , Immune System Diseases/pathology , Immunoglobulin G/immunology , Lymph Nodes/pathology , Plasma Cells/pathology , Aged , Biomarkers/analysis , Humans , Immunohistochemistry , Male , Middle Aged
14.
J Thorac Dis ; 6(Suppl 5): S537-46, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25349704

ABSTRACT

Advances in our understanding of the pathology, radiology and clinical behaviour of peripheral lung adenocarcinomas facilitated a more robust terminology and classification of these lesions. The International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification introduced new terminology to better reflect this heterogeneous group of adenocarcinomas formerly known as bronchoalveolar cell carcinoma (BAC). There is now a clear distinction between pre-invasive, minimally invasive and frankly invasive lesions. The radiographic appearance of these ranges from pure ground glass nodules to solid mass lesions. Radiologists must be aware of the new classification in order to work alongside multidisciplinary colleagues to allow accurate staging and treatment. This article reviews the new classification of lung adenocarcinomas. Management options of these lesions with particular focus on radiological implications of the new classification will be reviewed.

15.
Eur J Cardiothorac Surg ; 40(6): 1474-81, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21497109

ABSTRACT

OBJECTIVES: The aim of this study is to investigate the role of routine systematic mediastinal nodal dissection (SND) performed during video-assisted thoracic surgery (VATS) major pulmonary resections (VMPRs) as a staging strategy for non-small-cell lung cancer (NSCLC), compared with preoperative staging by conventional positron emission tomography (PET) and computed tomography (CT) imaging. METHODS: All patients suspected of having early lung cancer (T1-2, N0-1 and M0) were staged preoperatively by CT/PET. During VMPR, all lymph nodes on the right side at stations 2-4, 7, 8, 9, 10 and 11 and on the left stations 4-6, 7, 8, 9, 10, 11 and 3 when indicated were dissected en bloc. Histology was provided on the paraffin-embedded nodes, and patients staged accordingly. Preoperative and postoperative stagings were compared. Stage migration and impact on clinical pathway were noted. Stage IIa and higher were referred for adjuvant chemotherapy. RESULTS: Between April 2007 and January 2011, 106 consecutive patients with suspected primary NSCLC proceeded to VMPR+SND. Histology confirmed NSCLC in 96 patients. Forty-five were men and 51 women. Median age was 68.6 (range 42.8-84.7) years. As many as 91 (94.8%) patients underwent lobectomy, three (3.1%) bilobectomy and two (2.1%) pneumonectomy. PET accurately correlated with SND histological diagnosis in 42 (43.8%) patients. The unexpected N2 disease in cN0-1 was 9/86 (10.5%). SND resulted in 25 stage migrations, upstaged 16 (16.6%) and down-staged nine (9.4%) patients. All upstagings were adenocarcinoma. Four (4.2%) PET-negative patients had multi-station N2 disease. SND resulted in changing the clinical pathway for 19 (20%) patients. Fourteen (14.6%) patients upstaged to qualify for chemotherapy, and 5/9 (5.2%) down-staged patients were saved the chemotherapy. There was no morbidity or mortality attributable to this added procedure. CONCLUSIONS: SND during VMPR is safe and should be routinely performed even when nodal metastases is considered unlikely. VATS-SND is more accurate than PET in staging the mediastinum for NSCLC. PET sensitivity is significantly reduced in adenocarcinoma and might result in stage migration. Adjuvant multidisciplinary treatment should be based on SND staging.


Subject(s)
Carcinoma, Non-Small-Cell Lung/secondary , Lung Neoplasms/pathology , Lymph Node Excision/methods , Thoracic Surgery, Video-Assisted/methods , Adult , Aged , Aged, 80 and over , Blood Loss, Surgical , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Critical Pathways , Feasibility Studies , Female , Humans , Length of Stay/statistics & numerical data , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/surgery , Lymphatic Metastasis , Male , Mediastinoscopy , Mediastinum , Middle Aged , Multimodal Imaging , Neoplasm Staging , Pneumonectomy/methods , Positron-Emission Tomography , Tomography, X-Ray Computed
17.
Acta Cytol ; 50(6): 656-62, 2006.
Article in English | MEDLINE | ID: mdl-17152278

ABSTRACT

OBJECTIVE: To assess the diagnostic accuracy offine needle aspiration cytology (FNAC) in the diagnosis of Hodgkin's lymphoma (HL). STUDY DESIGN: We selected all the cases in which a cytologic diagnosis of HL, suggestive of or suspicious for HL, or HL as the prime differential diagnosis was offered on FNAC. These cases were correlated with histopathologic follow-up. Cases of primary HL diagnosed on cytology but without histopathology were excluded from the study. RESULTS: Histopathologic follow-up was available in 46 cases. Of these, 42 were correctly diagnosed as HL, and there was a discorrelation in 4 cases, comprising 3 cases of non-HL (T-cell-rich B-cell lymphoma [TCRBCL]-2, anaplastic large cell lymphoma-1) and 1 case of metastatic carcinoma. Overall accuracy was 91.3%. In 14 cases, the cytologic features were diagnostic ofrecurrence; hence, no histopathologic examination was done. No follow-up was available for the remaining 19 cases, which were excluded from the study. CONCLUSION: FNAC is very useful for rapid and accurate approach to the diagnosis of recurrent and most cases of primary HL. Because of morphologic similarities, it is difficult to differentiate HL from anaplastic large cell lymphoma and TCRBCL on FNAC. It is advisable to request a histopathologic examination in all cases of primary HL.


Subject(s)
Hodgkin Disease/pathology , Adolescent , Adult , Aged , Biomarkers, Tumor/metabolism , Biopsy, Fine-Needle , Cancer Care Facilities , Child , Child, Preschool , Diagnosis, Differential , Diagnostic Errors , Female , Follow-Up Studies , Hodgkin Disease/metabolism , Humans , Immunohistochemistry , Kuwait , Lymphoma, B-Cell/pathology , Lymphoma, Large-Cell, Anaplastic/pathology , Male , Middle Aged , Reproducibility of Results , T-Lymphocytes/pathology
18.
Cytojournal ; 3: 24, 2006 Oct 27.
Article in English | MEDLINE | ID: mdl-17069647

ABSTRACT

AIMS AND OBJECTIVES: In this present study we have evaluated the feasibility of sub-classification of non-Hodgkin's lymphoma (NHL) cases according to World Health Organization's (WHO) classification on fine needle aspiration cytology (FNAC) material along with flow cytometric immunotyping (FCI) as an adjunct. MATERIALS AND METHODS: In this five years study, only cases suggested or confirmed as NHL by FNAC were selected and FCI was performed with a complete panel of antibodies (CD3, CD2, CD 4, CD5, CD8, CD7, CD10, CD19, CD20, CD23, CD45, kappa and lambda) by dual color flow cytometry. Both cytologic findings and FCI data were interpreted together to diagnose and sub-classify NHL according to WHO classification. Wherever possible the diagnoses were compared with cytology. RESULTS: There were total 48 cases included in this study. The cases were classified on FNAC as predominant small cells (12), mixed small and large cells (5) and large cells (26). In five cases a suggestion of NHL was offered on FNAC material and these cases were labeled as NHL not otherwise specified (NHL-NOS). Flow cytometry could be performed in 45 cases (93.8%) and in rest of the three cases the material was inadequate because of scanty blood mixed aspirate. Light chain restriction was demonstrated in 30 cases out of 40 cases of B-NHL (75%). There were 15 cases each of kappa and lambda light chain restriction in these 30 cases. With the help of combined FCI and FNAC, it was possible to sub-classify 38 cases of NHL (79%) according to WHO classification. Combined FNAC and FCI data helped to diagnose 9 cases of small lymphocytic lymphoma (SLL), 2 cases of mantle cell lymphoma (MCL), 4 cases of follicular lymphoma (FL), 17 cases of diffuse large B lymphoma (DLBL) and 6 cases of lymphoblastic lymphoma. Histopathology diagnosis was available in 31 cases of NHL out of which there were 14 recurrent and 17 cases of primary NHL. Out of 15 DLBL cases diagnosed on FCI and FNAC, histology confirmed 14 cases and one of these cases was diagnosed as Burkitt's lymphoma on histology. Cases of FL (4), SLL (3) and MCL (2) were well correlated with histopathology. Out of the five cases suggestive of NHL on cytology, histopathology was available in four cases. Histology diagnosis was given as DLBL (1), SLL (1), anaplastic large cell lymphoma (1) and FL transformed into large cell NHL (1). Considering histopathology as gold standard, diagnostic specificity of combined FNAC and FCI was 100% (31/31) and sensitivity in sub-classification was 83.8% (26/31). CONCLUSION: FNAC combined with FCI may be helpful in accurately sub-classifying NHL according to WHO classification. Many of the subtypes of NHL such as FL and MCL which were previously recognized as a pure morphologic entity can be diagnosed by combined use of FNAC and FCI. Other ancillary investigations such as chromosomal changes, cell proliferation markers etc. may be helpful in this aspect.

19.
Acta Cytol ; 50(5): 507-12, 2006.
Article in English | MEDLINE | ID: mdl-17017435

ABSTRACT

OBJECTIVE: To assess the efficacy of fine needle aspiration cytology (FNAC) in the diagnosis of nodular sclerosis variant of Hodgkin's lymphoma (NSHL) and to analyze cytologic features that could help in subtyping a case of Hodgkin's lymphoma into this variant. STUDY DESIGN: FNAC smears of 18 histopathologically proven cases of NSHL were analyzed for a variety of features. RESULTS: On initial cytologic assessment, 14 of 18 cases were diagnosed as Hodgkin's lymphoma. No further subtyping was performed. In this retrospective analysis it was possible to revise the diagnosis in the remaining 4 cases. Of the various cytologic features analyzed, presence of numerous lacunar-type cells along with fibroblasts and collagenous material were useful pointers toward a diagnosis of nodular sclerosis variant. Fibroblasts were seen in 83.33%, collagenous material in 27.77% and numerous lacunar cells in 77.77%. CONCLUSION: Subtyping of NSHL based on cytologic features alone has been a matter of debate for a long time. Of the various subtypes, nodular sclerosis poses the greatest diagnostic difficulty. Though certain cytologic features may help in suggesting a diagnosis of nodular sclerosis variant, the primary role of fine needle aspiration is to diagnose a case of Hodgkin's lymphoma as such and advise histopathologic examination for further categorization.


Subject(s)
Biopsy, Fine-Needle/statistics & numerical data , Carcinoma/diagnosis , Hodgkin Disease/diagnosis , Lymph Nodes/pathology , Lymphocytes/pathology , Adolescent , Adult , Biopsy, Fine-Needle/standards , Carcinoma/secondary , Child , Child, Preschool , Diagnosis, Differential , Diagnostic Errors/prevention & control , Female , Fibroblasts/pathology , Histiocytosis, Langerhans-Cell/diagnosis , Humans , Male , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies , Sclerosis
20.
Med Princ Pract ; 15(2): 163-5, 2006.
Article in English | MEDLINE | ID: mdl-16484848

ABSTRACT

OBJECTIVE: To report a case of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) in an extranodal site with unusual presentation. CASE PRESENTATION: A 19-year-old girl presented with bilateral upper eyelid swellings of 2 years duration due to tumor. The masses were excised and sent for histopathological examination. Microscopic examination revealed similar features in both masses in the form of a collection of large histiocytic cells showing emperipolesis (lymphocytophagocytosis). The histiocytic cells stained positively with S-100 protein and CD68. The background comprised small lymphocytes and plasma cells. Based on the overall features a diagnosis of sinus histiocytosis with massive lymphadenopathy or Rosai-Dorfman disease was made. CONCLUSION: The present case highlights one of the forms in which extranodal Rosai-Dorfman disease can manifest itself. It is important to keep this differential diagnosis in mind whenever such histopathological features are encountered.


Subject(s)
Eyelid Diseases/diagnosis , Histiocytosis, Sinus/diagnosis , Lymphatic Diseases/diagnosis , Adult , Diagnosis, Differential , Eyelid Diseases/pathology , Female , Histiocytosis, Sinus/pathology , Humans , Lymphatic Diseases/pathology , Syndrome
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