Role of fine needle aspiration cytology in the diagnosis of soft tissue tumours

Fine needle aspiration cytology (FNAC) is a widely accepted safe, simple and rapid diagnostic procedure used in the examination of neoplastic and non‐neoplastic lesions of various locations. Since its introduction, FNAC has developed into an effective diagnostic tool practiced in a large majority of medical centres evaluating and treating oncological patients. The role of FNAC has been limited in the examination of primary soft tissue lesions, however, as many physicians working in this area recommended against using FNAC. An increasing use of minimally invasive diagnostic procedures in the last decade has resulted in a better acceptance of FNAC as a first‐line approach or as a complementary tool to core needle biopsy in the diagnosis of musculoskeletal lesions. This review discusses the role and value of FNAC in the evaluation and treatment of soft tissue tumours based on the experience gathered over the course of 48 years at the Sarcoma Center in Lund, Sweden. FNAC reports most often provide diagnostic information allowing the initiation of treatment or, when definitive diagnosis cannot be rendered from a cytological examination, guiding the continued diagnostic investigation. The main advantages of soft tissue FNAC are good sensitivity and specificity, low morbidity, speed of diagnosis, and low cost/benefit ratio. The most important disadvantages stem from limited experience in cytological diagnosis of soft tissue tumours and a lack of standardised and uniform reporting system for soft tissue FNAC.     

Advances in the management of paediatric Cushing's disease

Cushing's disease (CD) is rare in the paediatric age range, but may present a difficult therapeutic challenge. Most paediatric endocrinologists have limited experience managing children or adolescents with CD and thus benefit from close consultation with adult colleagues. Prior to definitive treatment, a diagnostic protocol for investigation is required which broadly follows the model for adult patients. Treatment strategies for CD are described and critically appraised. The management of paediatric CD patients after cure also presents challenges for optimizing growth, bone health, reproduction and body composition from childhood into and during adult life.     

Fine needle aspiration cytology: a survey of current European practice

Fine needle aspiration cytology (FNAC) is practised widely throughout Europe. The majority of countries have dedicated cytopathologists as well as histopathologists practicing cytology. Despite this, FNAC is performed mostly by clinicians and radiologists except in the larger centres with dedicated staff with a special interest in cytopathology. The advent of One-Stop diagnostic services and image-guided procedures are prompting further development of FNAC clinics where cytopathologists take their own samples, issue reports in the same clinical session and take extra material for ancillary tests to complete the diagnosis. The volume of FNAC work varies accordingly; in dedicated centres FNAC represents up to 80% of the workload whilst, in the majority of countries, it represents one quarter or less. Hence, the rate of inadequate FNAC varies widely, depending on the local sampling policies and the organ, but does not exceed 25% in any of the countries. The most sampled organs are breast and thyroid, followed by lymph nodes. Most countries have dedicated training in cytopathology for pathology trainees, the duration varying between 6 months and 2 years of the total training time. This discussion, focusing on European practices, highlights the heterogeneity of FNAC activity but also its success in many centres where it is practiced to a high standard, particularly in breast, thyroid and lymph node pathology. The relatively high rate of inadequate material in some centres reflects local policies and calls for greater uniformity of FNAC practice, particularly specimen sampling. To achieve this, the future direction should concentrate on specialist training, to include performing as well as interpreting FNAC, as part of the curriculum. Current emphasis on web-based training may not provide first hand experience of the FNAC procedure and should be supplemented by attending FNAC clinics and developing the technique to its full potential.     

Pancreatobiliary cytology in the multidisciplinary setting

This review article discusses the role of endoscopic ultrasound‐guided fine needle aspiration (EUS FNA) cytology in the clinical management of patients with pancreatic tumours in the setting of a multidisciplinary team (MDT). The commonest diagnosis encountered is pancreatic adenocarcinoma, which is seldom diagnosed early enough for surgical resection. Thus, cytology is likely to be the only form of diagnosis in the majority of cases. Nevertheless, about half the lesions discussed at the MDT meeting are lesions other than primary adenocarcinoma and a wide differential diagnosis must be considered in order to identify tumours, including neuroendocrine tumours, that are amenable to surgical resection. Cytology is not always definitive and the diagnosis may be helped by categorizing results according to whether they are malignant, suspicious, atypical/indeterminate, benign or inadequate. Discussion at MDT meetings and correlation with clinical and imaging findings along with review of cytology slides may allow equivocal results to be clarified before treatment is decided. Inadequate cytology results are avoided by rapid on‐site evaluation of slides; although this is cost‐effective in terms of overall patient care, attendance of cytopathologists on‐site may not be feasible. At Imperial College NHS Trust, specially trained biomedical scientists successfully carry out rapid on‐site evaluation.     

Cytologic characterization of postiodization residual goiter in schoolchildren by fine needle biopsy

OBJECTIVE: To determine the relevance and utility of fine needle biopsy (FNB) for providing a tissue-level diagnosis during a community-based survey of postiodization residual goiter in schoolchildren in India. STUDY DESIGN: A total of 14,762 schoolchildren (56.0% girls and 44.0% boys), aged 6-18 years, with a countrywide representation, were clinically screened for the presence of goiter. FNB was performed under field conditions by means of a nonaspiration technique from both lobes of goitrous glands. The cytologic diagnosis and findings were correlated with age, sex, goiter grade and biochemical parameters of serum T4, TSH, thyroid microsomal (TMA) and thyroglobulin (TGA) antibodies. RESULTS: The overall prevalence of goiter was 23.0%, with a greater frequency in girls (27.1%) than boys (17.8%). FNB was successful in 75.6% of subjects without any significant complications. The cytologic diagnoses in 1,312 successful cases were colloid goiter (92.8%), Hashimoto's thyroiditis (4.6%), focal lymphocytic thyroiditis (1.7%) and hyperplastic goiter (0.9%). Autoimmune thyroiditis (AIT), which accounted for only 6.3% cases, showed a strikingly different age-specific prevalence between girls and boys. Serologic markers of TMA and TGA at various titers were observed to lack requisite sensitivity and specificity for establishing an accurate diagnosis of AIT. CONCLUSION: The nonaspiration technique of FNB is capable of yielding valuable diagnostic information during an epidemiologic survey of goiter. The technique can be easily performed under field conditions on children without significant complications. FNB is preferable to serologic markers for accurate diagnosis of AIT. A relatively low frequency of AIT, as observed in the present study, raises the possibility of a significant role of environmental goitrogens as the underlying pathogenetic factor in postiodization residual goiter in Indian schoolchildren.     

Management of cytologic material,preanalytic procedures and biobanking in lymph node cytopathology

The range of pathologies that lymph node (LN) fine needle cytology (FNC) may encounter is extremely wide and ancillary techniques, in addition to traditional smears, are generally required to reach reliable cytologic diagnoses. Storing part of the cytologic material may be useful or necessary for molecular testing. The main difficulties concern the generally small size of the sample and the different methods of acquisition of LN‐FNC. Therefore, the preanalytic phase is extremely important for LN‐FNC. This article outlines the management of LN‐FNC material, vials, technical devices (e.g.: additional smears, cytospin slides, LBC slides, cards, resins, etc.) and main ancillary techniques to assess their optimal application, taking into account the different diagnostic needs and cell storage.     

Identification of novel biomarker candidates for immunohistochemical diagnosis to distinguish low‐grade chondrosarcoma from enchondroma

Chondrosarcoma is the third most common primary bone cancer, requiring surgical resection. However, differentiation of low‐grade chondrosarcoma (grade 1) from enchondroma that is benign and only requires regular follow‐up is one of the most frequent diagnostic dilemmas facing orthopedic oncologists in clinical management. Although multiple techniques are applied to make the distinction, immunohistochemistry is an important ancillary technique, especially when a histopathological stain of specimen must be obtained in order to guarantee an accurate confirmation. Currently, no adequate immunohistochemical diagnostic protein biomarkers are available to distinguish low‐grade chondrosarcoma from enchondroma. To discover novel protein biomarker candidates, an LC‐MS/MS approach was applied to directly compare formalin‐fixed, paraffin‐embedded low‐grade chondrosarcoma with enchondroma tissue samples. The proteomics analysis revealed 17 protein biomarker candidates. A principle was developed to prioritize the candidates using category and ranking. An algorithm, prioritization index of biomarker candidates for immunohistochemistry on tissue specimens, was developed to rank the candidates inside each category. Using the proteomics data and bioinformatics results, the prioritization index of biomarker candidates for immunohistochemistry on tissue revealed periostin as a top candidate. Immunohistochemical staining of periostin in 23 low‐grade chondrosarcoma and 31 enchondroma tissue specimens disclosed 87% specificity and 70% sensitivity.     

Multimodal analgesia protocol for pain management after total knee arthroplasty: comparison of three different regional analgesic techniques

Objectives:To evaluate three different analgesic techniques, continuous epidural analgesia (EA), continuous intra-articular (IA) infusion analgesia and continuous femoral nerve block (FNB) in postoperative pain management, length of hospital stay (LOS), and time of patient mobilization after total knee arthroplasty (TKA).Methods:Seventy-two patients undergoing TKA were randomly allocated into three groups according to the analgesic technique used for postoperative pain management. Group EA patients received epidural analgesia (control group), group IA received intra-articular infusion and group FNB received femoral nerve block.Results:Upon analyzing the Numerical Rating Scale (NRS) scores at rest, at passive and active movement, up to 3 days postoperatively, we observed no statistically significant differences at any time point among the three groups. Similarly, no association among these analgesic techniques (EA, IA, FNB) was revealed regarding LOS. However, significant differences emerged concerning the time of mobilization. Patients who received IA achieved earlier mobilization compared to FNB and EA.Conclusions:Both IA and FNB generate similar analgesic effect with EA for postoperative pain management after TKA. However, IA appears to be significantly more effective in early mobilization compared to EA and FNB. Finally, no clinically important differences could be detected regarding LOS among the techniques studied.     

Role of ancillary techniques in diagnosing and subclassifying non-Hodgkin''s lymphomas on fine needle aspiration cytology

Non-Hodgkin's lymphomas (NHL) are tumours of the lymphoid cells. During the process of development of lymphoid cells, neoplasia may evolve at any point. Neoplastic cells usually carry the imprint of cell of origin at the stage of origin. Various types of NHL may have similar morphology with wide variation in origin, immunophenotype and other biological features. Different ancillary laboratory techniques may help to overcome the limitations of morphology in this aspect. The commonly used ancillary techniques in lymphomas are immunocytochemistry (IC), flow cytometry, Southern blot (SB) technique, polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH). In addition, laser scanning cytometry (LSC) and DNA microarray technologies are in the research phase. Various laboratory techniques are used for immunophenotyping, demonstration of monoclonality, identification of chromosomal translocation, assessment of cell kinetics and expression of mRNA in the tumour cells. Flow cytometry helps in rapid immunophenotying of NHL and it has an added advantage over IC in recognizing the co-expression of CD markers. Fine needle aspiration cytology (FNAC) combined with flow immunophenotyping may help us to diagnose and subclassify certain NHLs, such as follicular lymphoma and mantle cell lymphoma, which were previously recognized as pure morphological entities. Loss of morphology is one of the important limitations of flow cytometry. LSC can overcome this limitation by studying morphology along with the immunophenotyping pattern of individual cells. Chromosomal changes in NHL can be identified by SB, PCR and FISH. Molecular diagnosis of NHL helps in diagnosis, subclassification, prognostic assessment and even in planning of therapy. DNA microarray is a relatively newer and promising technology. It gives information about the expression of several thousands of genes in a tumour in a single experiment. In the near future, FNAC combined with ancillary techniques may play a major role in diagnosis, subclassification and management of lymphomas.     

Role of β-catenin expression in paediatric mesenchymal lesions: a tissue microarray-based immunohistochemical study

Beta-catenin is a major protein in the Wnt signalling pathway. Although it has been studied in various types of carcinoma, little is known about its expression in mesenchymal tumours. In this study 41 specimens of a variety of mesenchymal childhood tumours were compared to 24 samples of the corresponding adult tumours to assess the diagnostic value of nuclear β-catenin expression using tissue microarray-based immunohistochemistry. Similar to adult sarcoma and fibromatosis, β-catenin was not expressed in the majority of childhood sarcomas, and its nuclear translocation was detected in paediatric fibromatosis; non-negligible levels of nuclear staining in other tumour types demonstrate Wnt pathway activation in mesenchymal neoplasms of childhood and adolescence.Key words: beta-catenin, Wnt pathway, immunohistochemistry, paediatric mesenchymal tumours.     

Temporal trends in incidence of childhood cancer in Switzerland, 1985–2014

BackgroundIncidence of childhood cancer increased in most countries worldwide, but reasons are unclear. This study investigates trends of childhood cancer incidence in Switzerland from 1985 to 2014.MethodsWe extracted data on all childhood cancer cases diagnosed at ages 0–14 years in Switzerland from the Swiss Childhood Cancer Registry. We included ICCC-3 main groups I-XII and calculated age-standardised, cumulative, and age-specific incidence for different diagnostic groups. We analysed trends of annual age-standardised incidence using JoinPoint regression models.ResultsOver the study period from 1985 to 2014, 5104 of 5486 cancer diagnoses (93%) were microscopically verified. The proportion of children treated in paediatric cancer centres increased from 84% during 1985–1994 to 93% in 1995–2004 and 98% in 2005–2014 (p < 0.001). Using the World standard population, age-standardised incidence was 143 in 1985–1994, 154 in 1995–2004, and 162 per million in 2005–2014. Incidence increased by 0.7% (95% confidence interval (CI) 0.5; 1.0) per year for all cancers from 1985 to 2014, 0.8% (95% CI 0.2%–1.4%) for leukaemias over the same period, 3.0% (95% CI 0.2%–1.4%) for CNS tumours during 1985–2002, and 3.8% (95% CI 1.7%–6.0%) for epithelial neoplasms and melanomas over the period 1985–2014.ConclusionTrends in incidence were driven mostly by increases among leukaemias and CNS tumours. For CNS tumours, observed trends may be explained at least partially by diagnostic changes and improved registration. For leukaemias, rising incidence may be real and due to risk factors that experience similar increases in trends.     

The role of fine needle aspiration cytology (FNAC) in the investigation of superficial lymphadenopathy; uses and limitations of the technique

Aspirates (n = 163) from 157 patients with enlarged superficial lymph nodes were obtained over a 5-year period in a combined surgical/FNAC clinic. A definitive diagnosis was achieved in over 77% of the cases: benign 52.7%, malignant 25.1%. The diagnostic accuracy was 94.4%, sensitivity 85.4%, and specificity 100%. The false-negative rate was 12.5% but decreased to 3.5% when lymphoma cases were excluded. There were 36 cases of metastatic disease, the majority of which were from a primary breast carcinoma. The main diagnostic difficulty was in distinguishing low-grade lymphoma from reactive hyperplasia. An added advantage was that aspirated material could be used in ancillary tests to help with the differential diagnosis. FNAC has a well-defined role in the investigation of superficial lymphadenopathy. Used in the proper setting it will provide a definitive diagnosis in the majority of cases, especially relating to recurrent malignancy or metastatic disease. Patients with a reactive cytological picture and no clinically suspicious symptoms could be spared unnecessary surgery and reviewed through follow up. This technique is cost-effective, of high diagnostic accuracy, and results in considerable resource savings.     

The geriatric institution as a therapeutic modality.

Geriatric centres complete with day-hospital facilities are essential for good care of the elderly. Institutions for the ill elderly should be upgraded to provide these people with the full range of services required as their diseases wax and wane. Within this community the resident could move as his needs altered, from minimal support in lodge-style accomodation, to continual "heavy" nursing in a hospital setting providing long-term care. Such a concept accepts that, in the elderly, as they age, new diseases develop that are often difficult to diagnose, and that they require diagnostic and therapeutic services of much greater range than is presently considered adequate in most institutions providing long-term care.     

Diagnostic potentials of computed tomography in tumors of the thymus

115 patients with different morphological thymus lesions, including 67 with thymoma have been examined on a computer tomograph "Somatom DR-2" ("Siemens", FRG). Characteristic features of hyperplasia and thymus cysts, as well as benign and malignant thymus tumours have been revealed by computer tomography (CT). Diagnostic value of CT in conditions of pneumomediastinum and CT employing an "amplification" technique in dynamic CT-scanning (angio-CT) in combination with puncture tumour biopsy under CT control are discussed. CT was found to have certain advantages over other diagnostic techniques: simplicity, safety, the value of the information obtained, possible shortening of the diagnostic period.     

Maximizing the use of the abdominoplasty incision

Candidates for abdominoplasty often request multiple procedures at the time of consultation. Some of these patients have the potential opportunity to have ancillary procedures performed through the abdominoplasty incision, such as breast augmentation or suction-assisted lipectomy. Access via the abdominoplasty incision can also limit the need for distant donor sites, for instance, when autologous fillers or rib graft are necessary. The techniques described are straightforward and are based on standard principles that should be considered when ancillary procedures are performed in conjunction with abdominal contouring procedures. In a review of 70 consecutive patients undergoing abdominoplasty, 91 ancillary procedures were performed in conjunction with the abdominoplasty. Of the total number of patients undergoing abdominoplasty, 29 patients underwent 30 procedures facilitated through their abdominoplasty incision, including 23 suction-assisted lipectomies of the flanks, six breast augmentations, and one rib cartilage harvesting for rhinoplasty. A review of the author's experience and discussion for potential options afforded by this exposure are presented.     

Implementation of the 2015 European Society of Cardiology guidelines for the management of infective endocarditis in the Netherlands

Because the occurrence of infective endocarditis (IE) continues to be associated with high mortality, a working group was created by the Dutch Society of Cardiology to examine how the most recent European Society of Cardiology (ESC) guidelines for IE management could be implemented most effectively in the Netherlands. In order to investigate current Dutch IE practices, the working group conducted a country-wide survey. Based on the results obtained, it was concluded that most ESC recommendations could be endorsed, albeit with some adjustments. For instance, the suggested pre-operative screening and treatment of nasal carriers of Staphylococcus aureus as formulated in the ESC guideline was found to be dissimilar to current Dutch practice, and was therefore made less restrictive. The recently adapted ESC diagnostic criteria for IE were endorsed, while the practical employment of the relevant diagnostic techniques was simplified in an adapted flowchart. In addition, the presence of a multidisciplinary, so-called ‘endocarditis team’ in tertiary centres was proposed as a quality indicator. An adapted flowchart specifically tailored to Dutch practice for microbiological diagnostic purposes was constructed. Lastly, the working group recommended the Stichting Werkgroep Antibioticabeleid (SWAB; Dutch Working Party on Antibiotic Policy) guidelines for IE treatment instead of the antibiotic regimens proposed by the ESC.

     

Management of cytological material,pre‐analytical procedures and bio‐banking in effusion cytopathology

Serous effusion fluid is one of the most commonly encountered specimens in routine cytopathology practice. It provides invaluable information about the patient and the clinical status; but to get the most of it, specimen handling and processing must be carried out properly. Cytomorphology is the basis of a successful analysis which should complemented by ancillary tests when needed. A wide spectrum of ancillary techniques ‐ ranging from immunocytochemistry and flow cytometry to different assays of molecular pathology ‐ can be applied to serous effusions. This article describes the acquisition and management of serous effusion fluids, methods for preservation and transportation, different techniques of cytopreparation, application of immunocytochemistry, flow cytometry, and fluorescence in‐situ hybridization (FISH), as well as DNA extraction for polymerase chain reaction (PCR) and next generation sequencing (NGS). Principles of bio‐banking of effusion samples are also discussed which is getting more important in correlation with the developments in personalized medicine.     

The 3-dimensional organization of the nucleoli of benign and malignant tumor cells from different human organs]

The method of ultrathin serial sections was used to perform a comparative ultrastructural and 3-dimensional analysis of nucleoli for the following variants of human tumours: benign (fibroadenoma) and malignant (infiltrating ductal carcinoma) tumours of one organ (mammary gland); malignant tumours of epidermal genesis in different organs (squamous cell carcinomas of skin, larynx, lung, gullet, uterus); two forms of malignant tumours (squamous cell and small cell carcinomas) of one organ (lung). The spatial models of nucleoli in these tumour cells are given. The specific signs in architecture of tumour nucleoli was found. Nucleoli of fibroadenomas have well pronounced 1-4 fibrillar centres forming a united system with a lacunar component and intranucleolar chromatin. Unlike benign tumour cells, nucleoli of infiltrating ductal carcinomas are characterized by large, prominent nucleoli containing giant, multiform fibrillar centres with a complicated surface, a well developed granular component and an unusually organized lacunar system. In squamous cell carcinomas of various localization, active, hypertrophied nucleoli with pseudonucleolonemal organization were found. The small cell carcinoma of lung differs from the squamous cell cancer of the same organ by dense, fibrillar nucleoli with a small amount of granular component located on the periphery of the nucleolar body. Nucleolar type reflecting the functional state of malignization process may serve as an additional diagnostic criterion for tumour identification.     

Expression of the gene for the alpha-subunit of inhibin in human adrenocortical tumours

BACKGROUND: To determine whether the pathogenesis of human adrenocortical tumours is associated with variations of inhibin expression, we assayed the mRNA of the alpha-subunit of inhibin in 5 normal adrenals and 48 adrenocortical tumours, including 10 paediatric tumours. RESULTS: mRNA of alpha-subunit of inhibin was detected in all adrenocortical tissues. It was similarly abundant in the three pathological groups of adult tumours (benign, suspect and malignant) and in normal adrenal tissues, irrespective of the hormonal pattern. However, in paediatric tumours, the levels of the mRNA for the alpha-subunit of inhibin were significantly higher than those in adult tumours (p < 0.01). CONCLUSION: Inhibin is more abundant in the foetal than in the adult adrenal cortex and therefore these data suggest that the paediatric tumours may have a foetal pattern.     

Clinical proteomics of breast cancer

Despite the lifetimes that increased in breast cancers due to the the early screening programs and new therapeutic strategies, many cases still are being lost due to the metastatic relapses. For this reason, new approaches such as the proteomic techniques have currently become the prime objectives of breast cancer researches. Various omic-based techniques have been applied with increasing success to the molecular characterisation of breast tumours, which have resulted in a more detailed classification scheme and have produced clinical diagnostic tests that have been applied to both the prognosis and the prediction of outcome to the treatment. Implementation of the proteomics-based techniques is also seen as crucial if we are to develop a systems biology approach in the discovery of biomarkers of the early diagnosis, prognosis and prediction of the outcome of the breast cancer therapies. In this review, we discuss the studies that have been conducted thus far, for the discovery of diagnostic, prognostic and predictive biomarkers, and evaluate the potential of the discriminating proteins identified in this research for clinical use as breast cancer biomarkers.