Hand2 Immunohistochemistry in the Diagnosis of Paragangliomas and Other Neuroendocrine Neoplasms.

Hand2 is a core transcription factor responsible for chromaffin cell differentiation. However, its potential utility in surgical pathology has not been studied. Thus, we aimed to investigate its expression in paragangliomas, other neuroendocrine neoplasms (NENs), and additional non-neuroendocrine tumors. We calibrated Hand2 immunohistochemistry on adrenal medulla cells and analyzed H-scores in 46 paragangliomas (PGs), 9 metastatic PGs, 21 cauda equina neuroendocrine tumors (CENETs), 48 neuroendocrine carcinomas (NECs), 8 olfactory neuroblastomas (ONBs), 110 well-differentiated NETs (WDNETs), 10 adrenal cortical carcinomas, 29 adrenal cortical adenomas, 8 melanomas, 41 different carcinomas, and 10 gastrointestinal stromal tumors (GISTs). Both tissue microarrays (TMAs) and whole sections (WSs) were studied. In 171 NENs, previously published data on Phox2B and GATA3 were correlated with Hand2. Hand2 was positive in 98.1% (54/55) PGs, but only rarely in WDNETs (9.6%, 10/104), CENETs (9.5%, 2/21), NECs (4.2%, 2/48), or ONBs (12.5%, 1/8). Any Hand2 positivity was 98.1% sensitive and 91.7% specific for the diagnosis of PG. The Hand2 H-score was significantly higher in primary PGs compared to Hand2-positive WDNETs (median 166.3 vs. 7.5; p < 0.0001). Metastatic PGs were positive in 88.9% (8/9). No Hand2 positivity was observed in any adrenal cortical neoplasm or other non-neuroendocrine tumors, with exception of 8/10 GISTs. Parasympathetic PGs showed a higher Hand2 H-score compared to sympathetic PGs (median H-scores 280 vs. 104, p < 0.0001). Hand2 positivity in NENs serves as a reliable marker of primary and metastatic PG, since other NENs only rarely exhibit limited Hand2 positivity.

Cardiovascular Complications in Pheochromocytoma and Paraganglioma: Does Phenotype Matter?

BACKGROUND: Adrenaline-producing tumors are mostly characterized by a sudden release of catecholamines with episodic symptoms. Noradrenergic ones are usually less symptomatic and characterized by a continuous overproduction of catecholamines that are released into the bloodstream. Their effects on the cardiovascular system can thus be different. The aim of this study was to determine the prevalence of cardiovascular complications by catecholamine phenotype. METHODS: We retrospectively analyzed data on the prevalence of cardiovascular events in 341 consecutive patients with pheochromocytoma and paraganglioma treated from 1995 to 2023. Biochemical catecholamine phenotype was determined based on plasma or urinary catecholamines and metanephrines. RESULTS: According to the phenotype, 153 patients had noradrenergic pheochromocytoma and paraganglioma and 188 had adrenergic pheochromocytoma and paraganglioma. In the whole sample, the incidence of serious cardiovascular complications was 28% (95 patients), with no difference between the phenotypes or sexes. The noradrenergic phenotype had significantly more atherosclerotic complications (composite end point of type 1 myocardial infarction and symptomatic peripheral artery disease; odds ratio, 3.58 [95% CI, 1.59-8.83]; P=0.003), while the adrenergic phenotype more often had type 2 myocardial infarction and takotsubo-like cardiomyopathy (OR, 0.24 [95% CI, 0.09-0.57]; P=0.002). These changes remained even after adjustment for conventional risk factors of atherosclerosis. CONCLUSIONS: We found a 28% incidence of cardiovascular complications in a consecutive group of patients with pheochromocytoma and paraganglioma. Patients presenting with a noradrenergic phenotype have a higher incidence of atherosclerotic complications, while the adrenergic phenotype is associated with a higher incidence of acute myocardial damage due to takotsubo-like cardiomyopathy.

Clinical and molecular genetic analysis of cytologically uncertain thyroid nodules in patients with thyroid disease.

BACKGROUND: The current requirement is to establish the preoperative diagnosis accurately as possible and to achieve an adequate extent of surgery. The aim of this study was to define the preoperative clinical and molecular genetic risks of malignancy in indeterminate thyroid nodules (Bethesda III and IV) and to determine their impact on the surgical strategy. METHODS: Prospectively retrospective analysis of 287 patients provided the basis of preoperative laboratory examination, sonographic stratification of malignancy risks and cytological findings. Molecular tests focused on pathogenic variants of genes associated with thyroid oncogenesis in cytologically indeterminate nodules (Bethesda III and IV). The evaluation included clinical risk factors: positive family history, radiation exposure and growth in size and/or number of nodules. RESULTS: Preoperative FNAB detected 52 cytologically indeterminate nodules (28.7%) out of 181 patients. Postoperative histopathological examination revealed malignancy in 12 cases (23.7%) and there was no significant difference between Bethesda III and IV categories (P=0.517). Clinical risk factors for malignancy were found in 32 patients (61.5%) and the presence of at least one of them resulted in a clearly higher incidence of malignancy than their absence (31.3% vs. 10.0%, respectively). Pathogenic variants of genes were detected in 12/49 patients in Bethesda III and IV, and in 4 cases (33.3%) thyroid carcinoma was revealed. The rate of malignancies was substantially higher in patients with pathogenic variants than in those without (33.3% vs. 16.2%, respectively). CONCLUSIONS: Our experience implies that molecular genetic testing is one of several decision factors. We will continue to monitor and enlarge our patient cohort to obtain long-term follow-up data.

Total thyroidectomy can still remain the method of choice in some Bethesda III cases.

BACKGROUND: The latest WHO classification of tumours of endocrine organs defines new units of borderline thyroid tumours (BTT). The aim of our study was to evaluate ultrasonographic and cytological features, mutation profile and surgery treatment in rare thyroid tumours. METHODS: An analysis of 8 BTT out of 487 patients, who underwent thyroid surgery between June 2016 and June 2020. The definitive diagnosis was made postoperatively by extensive histopathological examination. Molecular genetic analysis of genes associated with thyroid oncology (BRAF, HRAS, KRAS, NRAS, TERT, TP53, fused genes) were performed from one FNAB, and 7 formalin-fixed paraffin-embedded (FFPE) samples. RESULTS: BTT were found in a total of 8 patients (1.6%), with a predominance of men with respect to other operated patients. FNAB samples were classified in the Bethesda system as Bethesda I, Bethesda II and Bethesda III in one, four and three cases, respectively. Hemithyroidectomy and total thyroidectomy were performed equally in four patients. The histopathological diagnosis revealed non-invasive encapsulated follicular neoplasm with papillary-like nuclear features (NIFTP) in three patients, follicular tumour of uncertain malignant potential (FT-UMP) in three patients, well differentiated tumour of uncertain malignant potential (WDT-UMP) in one patient, and hyalinizing trabecular tumour (HTT) in one case. In NIFTP cases mutation in HRAS gene in one patient together with probable pathogenic variant in TP53 gene and in NRAS gene in two patients were detected. In HTT patient PAX8/GLIS3 fusion gene was detected. CONCLUSION: The surgical treatment of BTT is necessarily individual influenced by preoperative clinical, ultrasonographic, cytological and molecular genetic findings, and the presence of other comorbidities.

The importance of lung biopsy in a patient with idiopathic pulmonary fibrosis: a case report.

Idiopathic pulmonary fibrosis (IPF) is a severe progressive fibrotic disease of the lung. Its etiology is not yet completely clear. The affected population is exclusively older than 40 years with maximum incidence in the age categories of 60 to 70 years. Its worldwide prevalence varies from 2 to 29/100 000 people (in the Czech Republic 5-6/100 000). Annual incidence is constantly rising, mainly thanks to the ever-improving diagnostic possibilities. Untreated IPF disease causes rapid structural and functional devastation of the lungs with development of respiratory insufficiency and death of the patient within 2 to 3 years after diagnosis, prognosis with IPF is therefore fully (without any exaggeration) comparable to untreated bronchogenic carcinoma. In recent years, the prognosis and quality of life of patients have significantly improved thanks to available specific antifibrotic treatment, which can substantially slow down the disease progression and thus prolong survival. However, a necessary condition for the timely treatment initiation is a quick and accurate diagnosis. The following case report describes a protracted journey to the correct diagnosis in a patient with atypical radiological findings, so that the definitive diagnosis was established only as a result of a surgical lung biopsy.

Postoperative adrenal insufficiency in Conn's syndrome-does it occur frequently?

Primary aldosteronism (PA) is the most frequent form of endocrine hypertension. Recently, frequent clinically significant adrenal insufficiency after adrenalectomy in subjects with PA has been reported, which may make the early postsurgical management difficult. We retrospectively searched for possible adrenal insufficiency in subjects who underwent adrenalectomy for PA and have measured cortisol in the early postoperative course. We included subjects with confirmed diagnosis of PA who underwent either posture testing (blood draw at 06:00 and 08:00) and/or adrenal venous sampling (AVS) (blood draw between 08:00 and 09:00) and have also measured cortisol after surgery (cortisol measured approximately at 07:00). Cortisol was measured by immunoassay. In this study, we identified 150 subjects (age 48.5 ± 10.3 years) with available cortisol values in the early postoperative course (median [25th percentile, 75th percentile]) 6 [5,6] days. Postoperative cortisol values (551 ± 148 nmol/l) were normal and significantly higher, compared to preoperative standing cortisol values (404 ± 150 nmol/l; (P < 0.001) and AVS cortisol values (493 ± 198 nmol/l; P = 0.009), and did not significantly differ from preoperative supine cortisol values. Postsurgical cortisol values were not different among subjects with or without abnormal dexamethasone suppression test or elevated urinary free cortisol pre-surgery, and were significantly higher in subjects with abnormal diurnal cortisol variability compared with subjects with normal diurnal variability. No patient presented with adrenocortical crisis in the later follow-up. In conclusion, postoperative cortisol values did not indicate any suspicion of possible adrenal insufficiency. To exclude possible adrenal insufficiency, it may be sufficient to measure morning cortisol in the early postoperative course.

Cytological examination of cerebrospinal fluid.

Cytological examination of cerebrospinal fluid (CSF) has some specifics. In the pre-analytical phase, due to collection into a tube without fixation and hypooncotic nature with rapid cell degradation, processing is required within 2-3 hours. In the subsequent analytical phase it is necessary to take into account the quantitative limit of the sample due to regular parallel cytological processing and non-morphological methods. A regular entry step of cytological examination is the quantification of cellularity. Even oligocellular samples may exhibit severe cytological findings. In the category of inflammatory processes, the cytological diagnosis of purulent meningitis within a few hours has a fundamental influence on prognosis of the disease. Non-purulent inflammations with a broad differential diagnosis are specified not only by cytological images, but also by parallel non-morphological examinations aimed at detecting an infectious agent or autoimmune nature of inflammation. Neoplastic processes in the intermeningeal space generally require immunocytochemical verification. The minimum amount of CSF for immunocytochemical examinations is 3-5 ml. The requirement for these examinations resulting from the baseline assessment may indicate the need for another sample. If the appropriate procedures and interpretations are followed in the context of parallel non-morphological examinations, the cytological examination of MM can contribute significantly to the diagnosis of pathological conditions in CSF spaces.

Current issues in fine needle aspiration biopsy of thyroid gland.

Fine-needle aspiration biopsy (FNAB) has become an established procedure for the basic examination of thyroid nodules, which remain common in our population. The widely used Bethesda system for reporting thyroid cytopathology has undoubtedly contributed to the understanding among clinicians and cytopathologists. Since its publication in 2010, the systems overall applicability has been tested by many studies and reclassification of follicular thyroid tumours has occurred. The consensus embedded in the latest version of the WHO classification was the impetus for a revision of the very successful Bethesda 2010 system in 2017. We present a brief overview of the changes in the persistent categories of the original classification to the newly established format along with practical recommendations for routine FNAB diagnostics of thyroid lesions.

Chromogranin A in the Laboratory Diagnosis of Pheochromocytoma and Paraganglioma.

This work discusses the clinical performance of chromogranin A (CGA), a commonly measured marker in neuroendocrine neoplasms, for the diagnosis of pheochromocytoma/paraganglioma (PPGL). Plasma CGA (cut-off value 150 µg/L) was determined by an immunoradiometric assay. Free metanephrine (cut-off value 100 ng/L) and normetanephrine (cut-off value 170 ng/L) were determined by radioimmunoassay. Blood samples were collected from PPGL patients preoperatively, one week, six months, one year and two years after adrenal gland surgery. The control patients not diagnosed with PPGL suffered from adrenal problems or from MEN2 and thyroid carcinoma. The clinical sensitivity in the PPGL group of patients (n = 71) based on CGA is 90% and is below the clinical sensitivity determined by metanephrines (97%). The clinical specificity based on all plasma CGA values after surgery (n = 98) is 99% and is the same for metanephrines assays. The clinical specificity of CGA in the control group (n = 85) was 92% or 99% using metanephrines tests. We can conclude that plasma CGA can serve as an appropriate complement to metanephrines assays in laboratory diagnosis of PPGL patients. CGA is elevated in PPGLs, as well as in other neuroendocrine or non-neuroendocrine neoplasia and under clinical conditions increasing adrenergic activity.

Cytology of effusions in the coelom cavities.

oelom cavities (pleura, pericardium, peritoneum, tunica vaginalis testis) lined with mesothelial lining derived from the mesoderm, represent a frequent place of propagation of pathological processes both from the neighbourhood and primary. These are most often manifested by effusion, whose cytological examination contributes significantly to the diagnosis. Each larger amount of fluid in the coelom spaces is pathological. The primary task is, as a rule, the identification of tumour cells, more often of metastatic origin (with decreasing frequency (adenocarcinomas, melanoma, sarcomas) than primary (mesothelioma, primary lymphomas of coelom cavities). The differentiation of carcinoma or other tumour populations from mesothelial cells often requires, following careful morphological evaluation, the indication of complementary methods of staining, immunocytochemistry (in haematological malignancies, preferably in combination with flow cytometry) or methods of molecular pathology. Standardization is not yet advanced in this diagnostic area, however there is a consensus for a panel to distinguish between carcinoma and mesothelioma. Diagnosis is always generated via a summation of features. A good outcome requires adequate control of all three phases of the diagnostic process and a clear and unambiguous diagnosis, or differential diagnosis, formulation. Keywords: cytology of effusions - body cavity fluids - coelom cavities - carcinoma - reactive mesothelial cells - mesothelioma.

In vivo study on biodegradable magnesium alloys: Bone healing around WE43 screws.

Introduction A standard osteosynthetic material for maxillofacial skeleton is titanium and its alloys. The convenience of degradable material is avoiding of second surgery in cases, where removal of the material is necessary. Magnesium biodegradable alloys have similar mechanic properties as cortical bone - reasonable corrosion and sufficient biologic properties. They might be used in facial skeleton fixation. Materials and methods The study included a total of 16 rabbits, and they were randomly divided into two groups. Each group received two screws (WE4 and titanium as a standard material) in artificially drilled defect into right tibia. Animals were euthanized at four-week intervals. Bone samples with implants underwent microfocus CT scans and were histologically examined. Results WE43 alloys showed fragmentation of the material on the 16th week - statistically significant volume loss was found between weeks 12 and 16. Bone healing around the WE43 screws was of similar quality as around titanium screws, and no adverse effect was noticed. Conclusion The study showed good quality of bone healing around WE43 implants. From this point of view, the WE43 alloy meets the requirements of osteosynthetic material for maxillofacial skeleton.

Assisting the neurologist in diagnosis of CNS malignancies - Current Possibilities and Limits of Cerebrospinal Fluid Cytology and Immunocytochemistry.

OBJECTIVES: In tumorous impairment of CNS, cytological identification of the neoplastic cells in CSF frequently requires the use of ancillary techniques. Our methods are focused on identifying algorithms that increase the probability of identifying CSF malignant cells. MATERIALS AND METHODS: A total of 1.272 CSF samples from patients with tumorous infiltration of CNS of nonhematologic origin along with 721 samples from patients with hematologic malignancies were analyzed in a complex setting including cytological and immunocytochemical investigations. RESULTS AND DISCUSSION: In CSF diagnostics we are aware of the limited amount of sample combined frequently with neoplastic oligocytosis. Provided atypical, potentially malignant cells in CSF are found, further investigation(s) should maximize the probability of their identification-an appropriate cytological staining and immunocytochemical panel is to be applied. (i) In cases of known recent malignancy: immunoprofile of the recent neoplasm has been considered in immunocytochemical panel. (ii) In patients with a history of malignancy: The propensity to develop a new different malignancy must be taken into account. (iii) Atypical cells found in the CSF of a patient with a negative history of malignancy: Considering the most frequent clinically silent malignancies, stepwise immunocytochemistry is employed. Three milliliter of initial CSF sample represents the absolute minimum to start with. CONCLUSIONS: The steps of the laboratory activity targeted on malignancy in the CSF detection can be expected as follows: (i) The sample will be divided for both nonmorphology and cytopathology investigations. (ii) Basic stainings will triage the samples into those with no suspicion of malignancy and the remaining ones. (iii) Special stainings and stepwise immunocytochemistry will be performed in parallel with the nonmorphology investigations.

Contribution of Hormonal Cytology in Girls and Adolescents to Reproductive Health: A Traditional Technique Monitoring Recent Problems.

OBJECTIVE: To study the contribution of hormonal cytology in contemporary disturbances of fertility. DESIGN: Over a 10-year period (2006-2015), 6,688 vaginal fornix cytologies of 2,350 patients were investigated. For a more detailed analysis, a 3-year period from 2013 to 2015 was chosen. Four hundred and fifty-two patients were investigated, many of them several times and for a period longer than the 3 years analyzed. RESULTS: The main disorders examined and treated via a gentle hormonal medication support and life style corrections by a pediatric gynecologist were: pubertas praecox - thelarche praecox and early menarche; dysfunctional juvenile metrorrhagia; central and peripheral endocrine disorders; eating disorders - anorexia mentalis and bulimia; obesity; excessive sport activities; autoimmune disorders, and others. Normalization of the menstrual cycle was achieved while monitoring progress with a series of hormonal cytologies in a majority of patients. CONCLUSIONS: Hormonal cytology is a non-invasive and economical method, illustrating the direct effect of steroid on target cells. It contributes to reproductive health support by: (a) indicating the possible need and type of steroid therapy; (b) monitoring the normalization of cycle disturbances; (c) ruling out or indicating the need for more detailed steroid metabolism investigation. Thus, it represents a basic but valuable means of examination in child and adolescent gynecology.

Solitary Metastasis of Clear Renal Cell Carcinoma to Thyroid Gland: Three reported cases with review of the literature.

Metastasis to the head and neck and more specifically to the thyroid gland from distant primary tumors is less common in comparison to the local regional metastasis of squamous cell carcinomas of the upper aero-digestive tract. Preoperative diagnosis of these cases can be difficult. The authors present three cases with distant solitary metastases of clear renal cell carcinoma to the thyroid gland with ambiguous mechanism of tumor spread to the thyroid. Solitary metastases of clear renal cell carcinomas are an uncommon variant of metastasis of this tumor and may imitate thyroid well differentiated carcinoma which most commonly affects the thyroid gland. Therefore, thorough endocrinological investigation of the thyroid gland is necessary. The recommended therapy of renal cell carcinoma metastasis includes surgical removal of all cancerous tissues - i.e. of the gland with the possibly infiltrated adjacent tissues, as well as removal of the affected lymph nodes - selective radical neck dissection. In our study, we discuss the clinical picture, pathology, diagnosis, differential diagnosis and prognosis together with literature review.

Performance indicators in a newly established organized cervical screening programme: registry-based analysis in the Czech Republic.

In 2008, the organized Czech National Cervical Cancer Screening Programme (CNCCSP) was initiated by transformation of the existing opportunistic efforts. The aim of our study was to examine recent cervical cancer burden trends and to assess the quality of the Czech National Cervical Cancer Screening Programme using a set of standard performance indicators. Our study utilized data from the national Cervical Cancer Screening Registry and the Czech National Cancer Registry. We computed internationally accepted indicators and assessed time trends and variability among screening centres. Between 1995 and 2011, the incidence of age-standardized cervical cancer decreased by 21% (1023 cases in 2011), and the mortality decreased by 35% (399 deaths in 2011). The annual coverage of the target population by cervical screening increased to 56% in 2013 (as compared with 35% in 2001). If we consider a 2-year interval (2012-2013), the estimated coverage was 77%. Over two million women underwent screening in 2013; 96% of them had a negative result. About 0.2% of smears showed cytological signs of a high-grade intraepithelial lesion or a malignancy, and the estimated positive predictive value for advanced intraepithelial neoplasia (cervical intraepithelial neoplasia grade 2+) was 79.6%. However, performance indicators show considerable heterogeneity between screening centres. The reported values of performance indicators are in line with the results of programmes that have previously been shown to be successful in terms of decreasing the cervical cancer burden, and are promising with respect to an even more pronounced decrease in cervical cancer mortality in the near future, provided that continuous quality improvement can be maintained. Linkage studies between screening, cancer and cause-of-death registers can provide further information on screening effectiveness and validity issues.

[Changes in pathology since the times of Purkinje]. / Promeny patologie od dob Purkynových.

The discipline of pathology was founded in the Purkinje era on the principles of building scientific knowledge of diseases through co-operation among clinical specialists. During the 20th century the focus of pathologists work has progressed from autopsies to biopsy diagnostics. The discipline of histopathological and cytopathological biopsy took form and continuously incorporates new methodologies and new standards. Its future course compels us to reflect on the changing requirements of clinical medicine. Current undergraduate education programs are directed toward forming a basis of expertise for both clinicians and non-medical healthcare professionals. At the postgraduate level and in research we are seeing an ever-closer interdisciplinary link, especially within the fields of genetics. This approach brings pathological processes to a new level, but also demands new levels of knowledge. Through comprehensive diagnostic experience, both prognostic and predictive, a pathologist is an indispensable member of the diagnostic and therapeutic team.

Secondary or second primary malignancy in the thyroid? metastatic tumors suggested clinically: a differential diagnostic task.

OBJECTIVE: To describe the algorithms employed to explore the suggestion or consideration of metastatic malignancy in the thyroid. STUDY DESIGN: Thirty-seven cases with a history of malignancy (n = 21) and/or uncommon fine-needle aspiration biopsy (FNAB) findings (n = 37) were reviewed and reclassified according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). RESULTS: The group was heterogeneous in terms of the final histopathology results: the suggested metastasis was confirmed in only half of the cases (11/21; 52.4%). Primary thyroid malignancies were mostly nondifferentiated, medullary, or rare. However, 3 papillary carcinomas (the less common variants) were also found. Finally, 5 out of 37 cases were surprisingly benign upon histopathological investigation (uncommon repair and fibrotizing Hashimoto thyroiditis). CONCLUSIONS: The metastatic nature of thyroid gland nodule(s) must be considered in cases of generalization of malignancy and/or uncommon FNAB findings. We must be as open-minded as possible from the outset. Additional techniques are helpful if available - cytoblock and immunocytochemistry can contribute substantially. Morphological comparisons with the previous malignancy are recommended whenever possible. To avoid overtreatment, cases without precise typing should not be classified as TBSRTC diagnostic category VI - malignant, but should remain in TBSRTC diagnostic category V - suspicious for malignancy. Repeated FNAB to enable additional techniques may be suggested.

[Cytopathology 2012: screening - education - diagnostics highlights of 37th European cytology congress, dubrovník - cavtat, croatia 30.9. -3.10.2012]. / Cytopatologie 2012: screening - vzdelávání - diagnostika Hlavní témata 37. evropského cytologického kongresu: Dubrovník - Cavtat, Chorvatsko 30. 9. - 3. 10. 2012.

In Dubrovnik - Cavtat, Croatia more than 550 cytopathologists, representing 50 countries, met in the 37th European Cytology Congress. Three main topics dominated the programme: The cervical screening programmes focused on the optimal combination of HPV tests and screening cytology aimed at cost-effective and safe prolongation of the screening interval while still covering the target population. Regarding the mammary screening, the best organized "one day" diagnostic systems (French, Italian, Scandinavian) utilized sonography-guided fine needle diagnostics followed (only if needed) with a core biopsy.Great emphasis was placed on standardized European programmes of training and certification of cytotechnologists and pathologists. The role of cytotechnologists having a general education is increasing. The participation of clinical specialists will be limited to taking cytopathology samples.The strengthening role of cytodiagnostics was evident. Diagnostics is becoming a complex and multidisciplinary predictive process. Pathology lesions are regularly and routinely diagnosed with combined materials (smears, liquid based cytology, cytoblocks). ROSE (rapid on the spot evaluation) is performed - at minimum by a cytotechnician, but preferably by a pathologist with the rapid diagnosis made if possible. Cytotechnicians/cytopathologists are also responsible for optimal handling of these materials for molecular biology methods. The cooperation of the representatives of the Czech Society of Pathologists within working groups of EFCS (screening, education) represents an opportunity to improve the system of cytodiagnostics in the Czech Republic.

Metastatic pheochromocytoma: does the size and age matter?

BACKGROUND: Pheochromocytomas are tumours arising from chromaffin tissue located in the adrenal medulla associated with typical symptoms and signs which may occasionally develop metastases, which are defined as the presence of tumour cells at sites where these cells are not found. This retrospective analysis was focused on clinical, genetic and histopathologic characteristics of primary metastatic versus primary benign pheochromocytomas. MATERIALS AND METHODS: We identified 41 subjects with metastatic pheochromocytoma and 108 subjects with apparently benign pheochromocytoma. We assessed dimension and biochemical profile of the primary tumour, age at presentation and time to develop metastases. RESULTS: Subjects with metastatic pheochromocytoma presented at a significantly younger age (41·4 ± 14·7 vs. 50·2 ± 13·7 years; P < 0·001) with larger primary tumours (8·38 ± 3·27 vs. 6·18 ± 2·75 cm; P < 0·001) and secreted more frequently norepinephrine (95·1% vs. 83·3%; P = 0·046) compared to subjects with apparently benign pheochromocytomas. No significant differences were found in the incidence of genetic mutations in both groups of subjects (25·7% in the metastatic group and 14·7% in the benign group; P = 0·13). From available histopathologic markers of potential malignancy, only necrosis occurred more frequently in subjects with metastatic pheochromocytoma (27·6% vs. 0%; P < 0·001). The median time to develop metastases was 3·6 years with the longest interval 24 years. CONCLUSIONS: In conclusion, regardless of a genetic background, the size of a primary pheochromocytoma and age of its first presentation are two independent risk factors associated with the development of metastatic disease.

Papillary thyroid carcinoma: an easy fine needle aspiration biopsy diagnosis?

OBJECTIVE: To analyze reasons for unclear or missed diagnoses in fine needle aspiration biopsy (FNAB) of papillary thyroid carcinoma (PTC). STUDY DESIGN: Among 35,000 thyroid FNAB diagnoses made during 1989-2009, 135 PTC FNAB diagnoses were divided into 3 categories by expressed probability. A group of 10 cases with histologic PTC diagnosis not mentioned in our previous FNAB sample was also analyzed. RESULTS: Of the 75 PTC FNAB diagnoses, 71 were confirmed; the remaining 4 were hyperplastic goiters. In the group of 45 cases with PTC, in which FNAB diagnosis was the next most probable differential diagnosis, 23 were confirmed. In the group of 15 cases, in which the PTC FNAB diagnosis was considered the less probable differential diagnosis, 3 PTCs were found. The other cases in both groups were usually histologically diagnosed as lymphocytic thyroiditis. In the group of 10 cases with histologic PTC diagnosis, 6 were evaluated as suspicious for (other) malignancy, 3 were diagnosed as hyperplasia with oncocytes and 1 as low cellularity; sample reaspiration was recommended. CONCLUSION: FNAB diagnosis of PTC is not always possible, with success rate influenced by lesion type and size, accompanying diagnoses, representativeness of cytology sample and experience of the cytopathologist.