Mufaddal Moonim

Diagnosis and Subtyping of De Novo and Relapsed Mediastinal Lymphomas by Endobronchial Ultrasound Needle Aspiration

RATIONALE The current management of lymphoma requires accurate diagnosis and subtyping of de novo lymphoma and of relapsed or refractory lymphoma in known cases. The role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the clinical management of lymphomas is unclear. OBJECTIVES To investigate the use of EBUS-TBNA in the diagnosis of de novo and relapsed mediastinal lymphomas. METHODS A total of 2,256 consecutive patients who underwent EBUS-TBNA in a tertiary center between February 2008 and April 2013 were prospectively evaluated. The diagnostic accuracy and clinical use of EBUS-TBNA in 100 cases of de novo or suspected relapsed mediastinal lymphoma was investigated by comparing EBUS-TBNA diagnosis with the final diagnosis. MEASUREMENTS AND MAIN RESULTS De novo mediastinal lymphoma was correctly diagnosed by EBUS-TBNA in 45 (88%) of 51 and relapsed lymphoma in 15 (100%) of 15 lymphoma cases. EBUS-TBNA accurately established a diagnosis other than lymphoma in 32 (97%) of 33 patients with suspected lymphoma relapse. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EBUS-TBNA in the diagnosis of mediastinal lymphoma were 89%, 97%, 98%, 83%, and 91%, respectively. Sensitivity of EBUS-TBNA in subtyping lymphomas into high-grade non-Hodgkin lymphoma, low-grade non-Hodgkin lymphoma, and Hodgkin lymphoma was 90%, 100%, and 79%, respectively. EBUS-TBNA diagnosis was adequate for clinical management in 84 (84%) of 100 cases. CONCLUSIONS Multimodality evaluation of EBUS-TBNA can be successful in the diagnosis of de novo mediastinal lymphomas and is ideally suited in distinguishing lymphoma relapse from alternative pathologies; it is least sensitive in subtyping Hodgkin lymphoma.

Current literature and imaging techniques of aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL)

Aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) are a recognized complication of metal-on-metal bearing hip prostheses. There is an impending concern regarding the future investigation and management of patients who have received such implants. The current literature is discussed, and the current guidelines for management of these patients in the UK are reviewed. The various imaging techniques available, such as computed tomography, metal artefact reduction magnetic resonance imaging, and ultrasound are discussed and evaluated with respect to the assessment of patients with suspected ALVAL. The histopathological findings are discussed with images of the tissue changes provided. Images of the radiological findings are also provided for all general radiological methods. ALVAL and its radiological presentation is an important issue that unfortunately may become a significant clinical problem.

Diagnosis and subclassification of thymoma by minimally invasive fine needle aspiration directed by endobronchial ultrasound: a review and discussion of four cases

M.T. Moonim, R. Breen, B. Gill‐Barman and G. Santis

Identifying HIV infection in diagnostic histopathology tissue samples – the role of HIV‐1 p24 immunohistochemistry in identifying clinically unsuspected HIV infection: a 3‐year analysis

Moonim M T, Alarcon L, Freeman J, Mahadeva U, van der Walt J D & Lucas S B
(2010) Histopathology56, 530–541

P24 immunohistochemistry on lymphoid tissue: the histopathologist's role in HIV diagnosis

In an associated original research paper published in this issue of Histopathology we have demonstrated the value of p24 immunohistochemistry on paraffinembedded sections of surgical biopsy specimens of lymphoid tissue in the diagnosis of human immunodeficiency virus (HIV) disease. Most histopathologists in the UK are aware of the existence of this immunostain, but it is rarely used in the diagnostic setting, despite the well-recognized medical and social advantages of early diagnosis of HIV infection. Anecdotal experience suggests that this relates to confusion surrounding the anomalous position of testing for HIV infection in tissue and the question of consent. In this review we address the ethical and political issues relating to immunohistochemical testing for HIV on diagnostic biopsy specimens and advance the case for normalization of the usage of p24 in diagnostic histopathology.

Benign metastasizing mesothelial cells in an axillary lymph node secondary to a chest wall fibromatosis.

A 19-year-old female presented with a mass on the right side of the chest of less than 1 year’s duration. She underwent a right chest wall excision followed by a chest wall reconstruction. Macroscopic examination of the excised tumour showed a 175 · 160 · 125 mm sized dumbbell-shaped mass with a small anterior chest wall component and a larger subpleural component. The tumour on slicing showed a fleshy, creamish pink, glistening cut surface with a few small cystic spaces predominantly in the subpleural component (Figure 1A). Dissection of the lateral aspect of the specimen revealed two lymph nodes, one of which had multiple pale white areas distributed around its periphery. The patient was last seen 6 months post surgery and at that time was well and without evidence of local or systemic disease.

Benign Metastasizing Mesothelial Cells: A Potential Pitfall in Mediastinal Lymph Nodes

Case Report An 18-year-old woman with an unremarkable past medical history presented after experiencing several weeks of constitutional symptoms that included weight loss and night sweats. She also complained of gradually worsening shortness of breath. On hospital admission, she was found to have a microcytic anemia and a chest x-ray showed a large soft tissue opacity obscuring the left heart border resulting in a loss of volume of the left hemithorax and elevation of the hemidiaphragm. A subsequent computed tomography scan confirmed the presence of a 12-cm predominantly solid, partially cystic anterior mediastinal mass as well as an effusion (Fig 1). An ultrasound-guided biopsy was performed initially, but the results were not conclusive. An anterior mediastinotomy was performed to obtain a biopsy of the mass. During the procedure, an enlarged left internal mammary lymph node was also noted and this was excised. Histologic review of the biopsy from the mediastinal mass showed a classical Hodgkin’s lymphoma, nodular sclerosis type 1. Sections from the enlarged internal mammary lymph node showed vascular transformation of the peripheral sinuses and marked widening of the paracortical and medullary sinuses (Fig 2). These were filled with a population composed of sheets, single cells, strips, and papillae of mesothelial cells (Figs 3, 4), which were strongly positive for calretinin (Fig 5), WT-1 (Fig 6), and desmin (Fig 7). The cells were negative for epithelial membrane antigen (EMA). The final report was of benign metastasising mesothelial cells in a lymph node; an incidental finding. The patient is currently on chemotherapy for the Hodgkin’s lymphoma.

Fluorescence in situ hybridisation analysis of bone marrow trephine biopsy specimens; an additional tool in the diagnostic armoury

Fluorescence in situ hybridisation (FISH) analysis is now widely employed in the diagnosis and risk stratification of a wide range of malignant diseases. While this technique is used successfully with formalin-fixed paraffin-embedded (FFPE) sections from numerous tissue types, FISH analysis of FFPE tissue sections from trephine biopsy specimens has been less widely reported, possibly due to technical limitations relating to the decalcification protocols employed. During the last 4 years FISH analysis has been carried out successfully in 42 out of 55 (76%) consecutive trephine biopsy specimens received as part of the standard diagnostic service at our institution. Samples decalcified using EDTA-based protocols were analysed successfully in 31/31 cases (100%), whereas only 11/24 samples (46%) decalcified using formic acid-based protocols were successful. In our experience, FISH analysis of trephine biopsy specimens is a highly reproducible technique and a very useful adjunctive tool in the diagnostic armoury; however, its use in a standard diagnostic setting relies on the use of EDTA-based decalcification protocols.

Carney Stratakis Syndrome in a Patient with SDHD Mutation

Paragangliomas (PGLs) and pheochromocytomas (PCCs) are rare, usually benign tumours that originate from the neuroendocrine tissue along the paravertebral axis. Up to 35 % of these tumours may be hereditary [1]. They may be inherited in an autosomal dominant manner either alone or as a component of a multiple tumour syndrome [2]. Over the last decade, major advances have been made in understanding the molecular genetics of PCC and PGL syndromes [3]. In 1977, Carney et al. reported the Carney Triad (CT). CT is a rare syndrome comprising a group of tumours affecting the stomach, lung and paraganglionic system. The stomach features gastrointestinal stromal tumours (GISTs), the lung chondroma and the paraganglionic system paraganglioma. The tumours can be multiple in each of the organs. It mainly affects young women. It is a chronic, persistent, and generally indolent condition with a long natural history. Its etiology is unknown [4]. In 2002, Carney and Stratakis reported a new familial syndrome distinctive from CT. Carney Stratakis syndrome (CSS) is an inherited condition predisposing affected individuals to GISTs and PGLs. It is probably more frequent than CT [5] and is caused by germline mutations in succinate dehydrogenase (SDH) subunits B, C or D, leading to dysfunction of complex II of the electron transport chain. SDH acts as a tumour suppressor gene, and its defects result in a reduction in enzymatic activity, which is known to be oncogenic. GISTs in this condition are probably caused by SDH deficiency [6]. Germline mutations of the genes encoding SDHB and SDHD also predispose to paraganglioma syndromes type 4 (PGL-4) and type 1 (PGL-1), respectively. SDHD carriers have multifocal paragangliomas more frequently [7]. GISTs, the most common mesenchymal neoplasms of the gastrointestinal tract, usually affect adults in the 6th and 7th decades of life without any proven gender prevalence [8]. Oncogenic mutations in KIT or platelet-derived growth factor receptor-α (PDGFRA) have been identified as central tumour-initiating events in many GISTs. However, 85 % of GIST occurring in children and 15 % of GISTs occurring in adults lack KIT or PDFRA mutations (termed wild type or WT GISTs). The tumour-initiating events in these GISTs are not completely understood [5]. Interestingly, germline SDH mutations are present in 12 % of individuals with WT GIST without a personal or family history of PGL [5]. We present a case of CSS with multiple paragangliomas and an incidentally discovered solitary GIST with an SDH mutation, and we discuss its molecular genetics, pathological diagnosis and clinical implications. For submission to the Proceedings of the 3rd International Symposium on Pheochromocytoma and Paraganglioma C. Tenorio Jiménez : P. V. Carroll : B. M. McGowan Department of Diabetes and Endocrinology, Guy’s and St Thomas’ Foundation Trust, St Thomas’ Hospital, Westminster Bridge Road, London SE1 7EH, UK

Beneficial effects of JAK inhibitor therapy in Systemic Mastocytosis

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