Quality of cell blocks prepared from residual pleural effusion and bronchial washing samples for immunocytochemistry.

INTRODUCTION: Cell blocks (CBs) enable the long-term preservation of cytological samples. The aim of this study was to analyse the quality of CBs prepared from leftover fluid from lung adenocarcinoma pleural effusion samples and residual bronchial washing sediment for immunocytochemistry. METHODS: The residual part of 455 lung adenocarcinoma pleural effusion samples and sediment from 384 bronchial washing samples were used to prepare CBs following the agarose method. The quality of CBs was evaluated based on the quantity of malignant cells in haematoxylin and eosin-stained slides and interpreted as optimal or insufficient for immunocytochemistry. Immunocytochemistry on CBs was performed using the Dako EnVision™ FLEX detection visualisation system. The CB results for TTF-1, ALK, and PD-L1 immunocytochemistry were compared with the corresponding cytological smears. RESULTS: Among all CBs, 202 (44.4%) from leftover pleural effusion fluid and 85 (22.1%) from residual bronchial washing sediment had an optimal number of lung adenocarcinoma cells. Eight pleural effusion CBs were stained for TTF-1. Four pleural effusion and two bronchial washing CBs were stained for ALK and PD-L1. All tested pleural effusion CBs were confirmed positive for TTF-1 and negative for ALK. The PD-L1 tumour proportion score (TPS) was ≥ 50% in two pleural effusions. ALK was confirmed negative in bronchial washing CBs. One bronchial washing CB was interpreted as PD-L1-negative while the corresponding smear was positive (TPS ≥1%; 2%). CONCLUSION: The CB results of TTF-1, ALK, and PD-L1 corresponded to the findings for the smears. The inclusion of CBs prepared from leftover fluid from pleural effusion samples and residual bronchial washing sediment in routine cytological practice could provide a source of high-quality material for immunocytochemistry in addition to smears and cytospins.

Infection with human cytomegalovirus, Epstein-Barr virus, and high-risk types 16 and 18 of human papillomavirus in EGFR-mutated lung adenocarcinoma.

AIM: To assess the frequency of human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), and high-risk types of human papillomavirus (HPV16 and HPV18) infections in lung adenocarcinoma samples. METHODS: Lung adenocarcinoma cytological smears and their DNA isolates were obtained from patients hospitalized at the Department for Lung Diseases Jordanovac, Zagreb, in 2016 and 2017. Overall, 67 lung adenocarcinoma samples were examined: 34 with epidermal growth factor receptor gene (EGFR) mutations and 33 without EGFR mutations. The EGFR mutation status and virus presence were assessed with a polymerase chain reaction, and random samples were additionally tested for EBV with Sanger sequencing. HCMV, EBV, HPV16, and HPV18 infections were evaluated in relation to EGFR mutation, smoking status, and sex. A meta-analysis of available data about HPV infection in non-small cell lung cancer was performed. RESULTS: More frequent HCMV, EBV, HPV16, and HPV18 infections were observed in lung adenocarcinoma samples with EGFR mutations than in samples without these mutations. Coinfection of the investigated viruses was observed only in lung adenocarcinoma samples with mutated EGFR. In the group with EGFR mutations, smoking was significantly associated with HPV16 infection. The meta-analysis showed that non-small cell lung cancer patients with EGFR mutations had a higher odds of HPV infection. CONCLUSION: HCMV, EBV, and high-risk HPV infections are more frequent in EGFR-mutated lung adenocarcinomas, which indicates a possible viral impact on the etiology of this lung cancer subtype.

[Combined pulmonary fibrosis and emphysema syndrome]. / Sindrom plucne fibroze udruzene s emfizemom.

CPFE-combined pulmonary fibrosis and emphysema is a new term for a syndrome whose main characteristic is fibrosis in lower pulmonary lobes with simultaneous emphysema in upper pulmonary lobes. CPFE patients have well preserved pulmonary test values for unexpectedly long period, but extremely lowered carbon monoxide diffusion capacity and significant arterial hypertension. All CPFE studies indicate that CPFE occurs predominately in older male population. Smoking is considered main cause in developing CPFE. Reduced survival rate is linked with arterial hypertension extent, and mortality rate is greater than that for patients with isolated pulmonary fibrosis or emphysema. This study is focused on characteristics of twelve CPFE patients. This paper describes cases of 12 patients with the syndrome of pulmonary fibrosis associated with emphysema. All patients were male, mean age of 68 years. At the certain period of life they all were smokers, but most of them were also exposed to air pollution due to their profession. Shortness of breath on exertion was present in all patients. All patients had neat pulmonary function tests with significantly reduced diffusing capacity for carbon mon- oxide (average 39%). Pulmonary arterial hypertension (PAH) averaged 56 mmHg (range 25-75 mmHg) was present in 75% of patients. Four patients died during the period of four months, of which three patients had PAH greater than 70 mmHg. The fourth patient died of lung cancer.

WHOQOL-bREF questionnaire as a measure of quality of life in sarcoidosis.

The aim of this study was to evaluate the usefulness of a short form of the WHOQOL questionnaire, the WHOQOL-BREF, which consists of 24 questions, in evaluating quality of life (QOL) in sarcoidosis patients. A group of 97 sarcoidosis patients and a matched group of 97 healthy controls took part in the study. Their QOL was examined by means of the WHOQOL-BREF, and the respiratory functions were measured in sarcoidosis patients. The WHOQOL-BREF revealed significantly poorer QOL of sarcoidosis patients in the domains of Physical and Psychological Health in comparison to healthy controls. In contrast, sarcoidosis patients perceived their QOL significantly better than healthy controls in the domains of Social Relations and Environment. Differences between sarcoidosis patients and healthy controls were found in several items from the WHOQOL-BREF and some of them were modified by gender. However, the WHOQOL-BREF did not prove to be a sensitive measure of fatigue, which is the most common symptom in sarcoidosis patients.

Influence of deep-freezing and MGG staining on DNA and RNA quality in different types of lung adenocarcinoma cytological smears.

BACKGROUND: Preserving the optimal quality of DNA and RNA is mandatory for molecular testing in lung adenocarcinoma cytological smears (LACSs). METHODS: DNA and RNA were isolated from 90 frozen unstained and 46 May Grünwald Giemsa (MGG) stained LACSs prepared from bronchial washing (BW), bronchial brushing (BB), and pleural effusion (PE) samples during 3 years. Concentrations of nucleic acids in all LACSs were assessed by spectrophotometric analysis. Fragmentation of DNA and RNA was determined by PCR amplification of selected genes. Amplicons of 100, 200, 300, 400, and 600 bp were used for DNA and 108 bp-long HPRT1 transcript fragment for RNA fragmentation analysis. RESULTS: Among 90 frozen LACSs, significantly lower DNA concentrations of BB and RNA concentrations of BW samples frozen for 6-10 months were observed in comparison with samples frozen for longer periods (p < .05). Among 46 paired LACSs, 44 (95.7%) frozen and 15 (32.6%) MGG-stained samples showed 600 bp-long DNA amplicons. Statistically significant difference (p < .05) in the fragmentation of DNA between frozen and MGG-stained LACSs was observed (p < .05), with DNA being less fragmented in frozen LACSs. In addition, 33 (71.7%) frozen and 36 (78.2%) MGG-stained LASCs showed HPRT1 gene amplicon of 108 bp. RNA was less fragmented in 3-year old MGG-stained samples than in LACSs frozen for 3 years. CONCLUSION: DNA and RNA extracted from frozen and MGG-stained LACSs showed different results depending on the time of storage and/or type of samples, but in general all samples had adequate quantity and quality for downstream molecular testing.

Lung lavage cell profiles in diffuse lung disease.

The standard armamentarium of tests that are used by pulmonologist are laboratory tests, pulmonary function tests, different radiological techniques (conventional chest-X rays, HRCT scans, etc) and pathohistological analyses of biopsies. The minimally invasive bronchoalveolar lavage (BAL) procedure, in addition to methods earlier mentioned, is an important diagnostic instrument that can facilitate the diagnosis of various diffuse lung diseases (DLD). BAL fluid white blood cell profiles are analyzed, malignant cells looked for, and in certain circumstances particular stains are performed to detect yet other cell types. Additionally, BAL can play a very important role in the diagnosis of respiratory tract infections. All these analyses are usually readily performed in a moderately equipped cytological laboratory.

Necrotising sarcoid granulomatosis of the spinal cord: case report.

We report a patient who presented with leg weakness and cervical lymphadenopathy. Thoracical magnetic resonance imaging showed an inhomogenously increased signal in the thickened portion of the cord. Multilevel laminectomy and spinal cord biopsy revealed granulomatous infiltrations with necrosis. Review of the histopathological finding established the diagnosis of necrotising sarcoid granulomatosis (NSG) of the spinal medulla, cytological FNA diagnosis of the neck lymph node was granulomatous inflammation with necrosis, but histopathological analysis of the same neck lymph node disclosed granulomatous inflammation without necrosis. On further radiographic chest evaluation mediastinal lymphadenopathy was found. Immunophenotyping of lymphocytes in bronchoalveolar lavage fluid (BALF) was indicative of sarcoidosis. After the administration of corticosteroid therapy the patient's clinical condition improved, and laryngeal and mediastinal lymph nodes subsided with minor changes remaining in the spinal medulla, which, based upon MR assessment, were considered to be irreversible. To our knowledge, this is the first described case with finding of granulomatous inflammation with and without vasculitis in various organs, consistent with the Churg's study who believes NSG to be a histological variant of sarcoidosis.

Clinical cytology and primary health care of children and adults.

Clinical cytology is a diagnostic branch of medicine, best known by the Papa test in gynaecology. But, cytology can be applied in almost all fields of clinical medicine. Its advantages--high accuracy, simplicity, with little or no aggressiveness and low cost--are not used as widely as they could be. Medical practice, as well as medical research, and also medical education, are nowadays often directed at profitable use and not at the real benefit of the patient. Primary practitioners do not have enough chance to get acquainted with clinical cytology as a whole although they need true information, based on the cost-effectiveness and patient-benefit. A panel discussion on this subject was organised at the 4th Croatian Congress of Clinical Cytology, in Split, October 11-14, 2009 by the Croatian Society for Clinical Cytology-Croatian Medical Association, to inform primary practitioners about the possibilities of cytodiagnostics in the health care of children and adults. Indications for cytodiagnostics in infectious diseases (T. Jeren and A. Vince), haematology (I. Kardum-Skelin), pulmonology (S. Smojver-Jezek), thyroid diseases (A. Knezevic-Obad), breast diseases (I. Kardum-Skelin), gastroenterology and urology (G. Kaic) were discussed, as well as technical procedures and the interpretation of the cytological findings. Moderator (Z. Znidarcic) opened the panel with presentation about the role of clinical cytology, particularly in the primary health care. The discussion finally pointed at the necessity of better communication between primary practitioners and cytologists. This review article presents contents of the panel discussion.

Morphometric and DNA image analysis of bronchoalveolar lavage fluid macrophages nuclei in interstitial lung diseases with lymphocytic alveolitis.

Lymphocytic alveolitis is a characteristic of diverse interstitial lung diseases (ILD-s), but macrophages are often more numerous cell population in bronchoalveolar lavage fluid (BALF). Aim of this study is to analyze morphometric characteristics of macrophages nuclei in BALF in patients with ILD-s and to detect possible differences allowing distinguishing sarcoidosis from other lymphocytic alveolitis ILD-s. Thirty-one patient with interstitial lung disease who had lymphocytic alveolitis in BALF cell count (17 sarcoidosis and 14 other ILD-s) and nine controls were included in the study. The following patients data were numbered: age, lymphocyte percentage and CD4/CD8 ratio in BALE Investigated morphometric parameters of macrophages nuclei were: area, outline, maximal radius, minimal radius, length, breadth, form factor (FF), elongation factor (EF) and DNA image cytometry ploidy status determined with Van Velthoven method. Predicted classifications in classification matrix (forward step-wise method in multivariate discriminant function analysis) based on macrophages nuclei length mean, minimum and maximum, breadth SD, FF mean and lymphocyte % were 100% (9/9) correct for control group, 88.235% (15/17) correct for sarcoidosis, and 92.857% (13/14) correct for other lymphocytic alveolitis ILD group. In total, 92.5% (37/40) of the examinees were correctly classified in particular group upon the observed variables.

Detection of human papillomaviruses type 16, 18 and 33 in bronchial aspirates of lung carcinoma patients by polymerase chain reaction: a study of 84 cases in Croatia.

Besides its well-known role in cervical carcinoma, HPV is also suggested to be involved in lung cancer development. A number of authors have been investigating the presence of HPV in histological materials. We used routine bronchial aspirates from 84 patients with lung carcinoma for DNA extraction and then performed polymerase chain reaction for high-risk HPV types 16, 18 and 33. The results were compared to those obtained from buccal and eyelid mucosa. Only three patients were positive for HPV in bronchial aspirates: one for HPV 16 type, one for HPV 18 type, and one for HPV 33. Our data indicated the low prevalence of HPV in patients with lung carcinomas in Croatia, therefore it seems unlikely that HPV contributes to the development of lung carcinomas in this region.

Number of counting cells and cytospins selection influences on bronchoalveolar lavage cell profiles.

Bronchoalveolar lavage (BAL) fluid cells count provides information about presence or absence of interstitial lung diseases. BAL fluid samples were taken from 50 patients hospitalized in University Hospital for Lung Diseases "Jordanovac" in Zagreb, Croatia. The samples of BAL fluid were prepared by cytocentrifuge. From each sample two cytospin were selected (C1 and C2) and after determing adequacy, counted up to 200 and 400 cells. After air drying, samples were stained according to May Grünwald Giemsa (MGG). Cells were counted by light microscope at magnification of 400x. Obtained results were analyzed in Statistics version 6 and Med Calc. Results for bronchial epithelial cells, alveolar macrophages, lymphocytes and neutrophilic granulocytes showed insignificant statistical differences between groups (p > 0.05). Eosinophils percentages showed borderline insignificant statistical difference between groups of these cells (p = 0.052.). As it was exemplificated, the percentages of differentiated cells do not significant differ according to differentiation on 200 and 400 cells and cytospin selection.

Lung cancer biomarker testing: perspective from Europe.

A questionnaire on biomarker testing previously used in central European countries was extended and distributed in Western and Central European countries to the pathologists participating at the Pulmonary Pathology Society meeting 26-28 June 2019 in Dubrovnik, Croatia. Each country was represented by one responder. For recent biomarkers the availability and reimbursement of diagnoses of molecular alterations in non-small cell lung carcinoma varies widely between different, also western European, countries. Reimbursement of such assessments varies widely between unavailability and payments by the health care system or even pharmaceutical companies. The support for testing from alternative sources, such as the pharmaceutical industry, is no doubt partly compensating for the lack of public health system support, but it is not a viable or long-term solution. Ideally, a structured access to testing and reimbursement should be the aim in order to provide patients with appropriate therapeutic options. As biomarker enabled therapies deliver a 50% better probability of outcome success, improved and unbiased reimbursement remains a major challenge for the future.

[The value of transbronchial needle aspiration combined with rapid on-site evaluation]. / Vrijednost transbronhalne iglene aspiracije u kombinaciji s hitnom citoloskom evaluacijom.

UNLABELLED: The samples obtained by transbronchial needle aspiration (TBNA) during fiberoptic bronchoscopy (FOB) are suitable for rapid on-site evaluation (ROSE). Availability of on-site results may increase the effectiveness of FOB. This study prospectively investigated the diagnostic range, yield and practical value of this technique. METHODS AND RESULTS: Consecutive patients with radiologically suitable mediastinal mass lesions or lymph nodes on conventional chest x-rays and lung CT scans were investigated with FOB. TBNA-ROSE was performed during FOB. A cytopathologist prepared unstained slides, stained them and evaluated the aspirates on-site and notified the bronchoscopist about the necessity of further sampling. If adequate diagnostic material was collected with TBNA, the provisional diagnosis was noted and the procedure ended. Fifty patients with mediastinal masses or lymph nodes were included. In 37 (74%) patients, the diagnosis was made on-site: non small cell lung cancer in 16, small cell lung cancer in 4, metastatic cancer in 6, granulomatous disease in 9 and lymphoma in 2 patients. TBNA was not diagnostic in 9 (18%) patients with reactive lymphoid hyperplasia that required additional studies. Overall, ROSE shortened bronchoscopic sampling in 74% of patients. The mean intervention time was 25 minutes. No side effects of TBNA were observed. CONCLUSION: TBNA combined with ROSE is safe and highly effective. ROSE increased the sensitivity of TBNA.

[Thyroid transcription factor-1 in pulmonary cytology]. / TTF-1 u plucnoj citologiji.

UNLABELLED: Currently it is necessary to define in almost each case whether a carcinoma is a small or non-small cell carcinoma, adenocarcinoma, pulmonary or metastatic in origin. Thyroid transcription factor-1 (TTF-1) was positive in more than 80% of primary pulmonary adenocarcinomas and in none from the sites other than the thyroid. Mucinous bronchioloalveolar carcinomas are usually negative. Immunocytochemistry with a panel of cytokeratins (CK) 7 and 20, along with TTF-1, is recommended for identification of the origin of adenocarcinoma in pulmonary cytology. OBJECTIVE: The aim of the study was to assess the value of TTF-1 reactivity in adenocarcinomas determined by immunocytochemistry in different pulmonary cytologic specimens. METHODS AND RESULTS: Cytologic specimens of 83 patients with adenocarcinomas were analyzed. Immunocytochemistry was performed with a panel of antibodies: TTF-1, CK7, CK20 in all cases and CK5/6 if necessary. The study included 17 different bronchoscopic samples (aspirates, brushes, transbronchial FNA), 14 transthoracic FNA, 27 pleural effusions and 25 FNA of peripheral lymph nodes. TTF-1 was positive in 26/83 (31.3%) and negative in 47/83 (68.7%) samples. All TTF-1 positive adenocarcinomas were also CK7 positive, thus being conclusive of pulmonary origin. In TTF-1 negative group, pulmonary origin was proven in 10/57 (17.5%) adenocarcinomas, whereas 18/57 (31.6%) adenocarcinomas were metastatic; in 29/57 (50.9%) adenocarcinomas other diagnostic procedures failed to prove their origin. CK20 positivity with CK7 negativity was conclusive of metastatic gastrointestinal adenocarcinoma. DISCUSSION: Numerous reports support TTF-1 expression in adenocarcinoma as being highly specific for pulmonary origin, if thyroid is excluded. We were able to identify 36/83 (43.4%) adenocarcinomas as pulmonary adenocarcinomas. Among them, only 31.3% were TTF-1 positive. In our study, about 60% of adenocarcinomas with uncertain origin were in the groups of pleural effusions and lymph nodes. In these groups, cytologic diagnosis of adenocarcinoma often provided evidence of the carcinoma expansion, aggressive behavior and poor differentiation, and served as a guideline for patient management. In the studies of mixed pulmonary adenocarcinomas, TTF-1 expression was lower in poorly differentiated segments as well as in the areas with bronchioloalveolar pattern. One explanation for the high percentage of TTF-1 negative adenocarcinomas in our material is morphological selection of adenocarcinomas of presumably non-pulmonary origin before immunocytochemistry. CONCLUSION: TTF-1 in a panel with cytokeratins is specific for differentiation of the origin of adenocarcinomas. TTF-1 negative finding in adenocarcinomas does not exclude pulmonary origin, but only points to other diagnostic procedures for definitive diagnosis.

Epidemiological characteristics of sarcoidosis patients hospitalized in the Uuniversity Hospital for Lung Diseases "Jordanovac" (Zagreb, Croatia) in the 1997-2002 period.

The aim of our study was to explore the characteristics of hospitalized patients with sarcoidosis concerning age, gender, clinical forms and staging, seasonality, geographical distribution, smoking habit and profession, familial clustering and mortality. We included 476 biopsy-proven sarcoidosis patients who were diagnosed at the University Hospital for Lung Diseases "Jordanovac" in the period from 1997-2002. Most of the patients (44%) were in the group of age between 20 and 40 years. The ratio of women to men was 1.4:1. The onset of the disease usually appeared in spring and summer, especially in the patients presenting with erythema nodosum, with majority of patients hospitalized in the period from May to August (51%). More patients came from urban, than from rural areas (1.5:1), and they were mostly nonsmokers (3.3:1). In 2% of sarcoidosis patients we found familial clustering. Although these data are biased regarding the selection of patients they give new insights into characteristics of sarcoidosis patients in Croatia.

Analysis of the frequency of EGFR, KRAS and ALK mutations in patients with lung adenocarcinoma in Croatia.

BACKGROUND: Many studies have been published on the mutational status of patients with lung adenocarcinomas, and great population-based variability in mutation frequencies has been reported. The main objective of the present study was to analyze the EGFR, KRAS and ALK mutation status in a representative cohort of patients in Croatia with lung adenocarcinomas and to correlate the mutational status with clinical data. METHODS: All patients who were newly diagnosed within 6 months with histologically proven primary lung adenocarcinomas were included. Mutational analyses for EGFR and KRAS mutations were performed in a cobas z 480 analyzer. ALK immunohistochemistry was performed using the D5F3 clone on Benchmark XT instrument. Clinical data were obtained from the medical records. RESULTS: Of the 324 patients, 59.9 % were male. At the time of diagnosis, the patients ranged in age range from 35 to 88 years (median 63 years). Most of the patients were current smokers or former smokers (77.2 %). EGFR mutations were found in 15.7 % of the patients, and of these mutations, exon 19 deletion was the most common (45.1 %). KRAS mutations were present in 34.9 % of the patients, while 4.1 % of patients were ALK-positive. The statistical significance of the presence of mutations was detected for both gender and smoking. CONCLUSION: The detected mutation rates demonstrated a slightly higher prevalence of KRAS mutations, but not a higher prevalence of EGFR mutations or ALK gene rearrangement, in comparison with the rates found in other European countries. EGFR and ALK mutational status showed a statistically significant correlation with gender as well as with smoking, while KRAS mutation status showed a statistically significant correlation only with smoking.

Multiple primary intrathoracic neoplasms: case report and a review of the literature.

This is a case report of a patient diagnosed with three distinct primary intrathoracic tumors (mesothelioma, carcinoid and B-cell lymphoma). The patient had previously had mycosis fungoides. The occurrence of multiple neoplasms in a single patient, synchronous or metasynchronous, is not a rare phenomenon; the incidence varies from 1-11% of all neoplasms. They can be hereditary, or connected with some environmental agents or previous therapies. The incidence of multiple neoplasms increases with age. We report an extremely rare case of multiple intrathoracic neoplasms in a 71-year-old man. A left upper lobectomy was performed, followed by 6 courses of chemotherapy and irradiation of the sternum. The patient was stable two years later.

[Bronchoalveolar lavage]. / Bronhoalveolarna lavaza.

Bronchoalveolar lavage (BAL) is a bronchoscopic technique that reveals specific insight in the distal parts of lung parenchyma. During the past twenty years, research of cellular and extracellular bronchoalveolar profiles gave important information on pathogenesis of some pulmonary disorders, promoting this technique as a diagnostic tool in pulmonary infections and interstitial lung diseases. Bronchoalveolar lavage is a safe, well-tolerated and suitable diagnostic procedure in immunocompromised patients. The patients with alveolar proteinosis gain therapeutic benefit of bronchoalveolar lavage. In this article we described technical notes, sampling, storage, cellular and noncellular analyses of bronchoalveolar lavage, including interpretation of results and significance in pulmonary diseases.

PCR-quality DNA isolation from human bronchial aspirates and buccal and eyelid swabs by a simple procedure based on alkaline lysis.

There are only a few systematic reports about DNA extraction from routine diagnostic cytological specimens. An inevitable drawback of such techniques is increased spending of time and funds required for obligatory DNA purification. To implement a simple protocol for human DNA isolation from cytological specimens related to lung cancer, bronchial aspirates together with samples collected by swabbing of the inner cheek and eyelid were used. By combining alkaline and temperature lyses it was possible to isolate DNA solution ready for PCR in less than an hour. Testing the method used for amplification of sex chromatin gene fragments showed that it is highly efficient. The presented protocol preserves high-quality DNA that is suitable for PCR-based assays.

Hypereosinophilic syndrome: diagnosis and treatment.

PURPOSE OF REVIEW: Hypereosinophilic syndrome is increasingly recognized as a heterogeneous group of disorders, in some cases with precisely defined pathogenesis, which has led to changes in diagnostic approaches and therapeutic strategies. An update on causes and modern therapy is presented here. RECENT FINDINGS: Clonal eosinophilias belong to the group of myeloid malignancies. Karyotypically occult FIP1L1- platelet-derived growth factor receptor alpha and beta rearranged eosinophilic disorders respond to imatinib mesylate with almost 100% efficacy. If standard therapies fail, the FIP1L1- platelet-derived growth factor receptor-negative cases of hypereosinophilic syndrome should also be considered for treatment with imatinib. The recognition of acquired resistance to imatinib has aroused interest in developing new tyrosine kinase inhibitors. Other subgroups of clonal eosinophilias have been molecularly defined, but the curative verification of pathogenetic relevance has not been certified. Hypereosinophilic syndrome patients with abnormal T-cell populations have benefited from treatment with anti IL-5 monoclonal antibodies. SUMMARY: The FIP1L1- platelet-derived growth factor receptor alpha and beta-positive patients, and those with abnormal T-cell populations are currently the only clearly defined treatable subgroups of hypereosinophilic syndrome. The FIP1L1- platelet-derived growth factor receptor alpha-negative responders to imatinib pose a question as to the existence of subentities with unrecognized tyrosine kinases-based mutation. The search for such cases and other treatable subgroups of hypereosinophilic syndrome has already begun.