Ika Kardum-Skelin

The role of breast FNAC in diagnosis and clinical management: a survey of current practice.

Most participating countries have now adopted a triple assessment approach, i.e. clinical,imaging and pathology, to breast diagnosis, with FNAC as the first‐line pathological investigation in both screening and symptomatic populations, with the exception of microcalcifications. Pathologists specialized in cytopathology are best qualified to collect and interpret FNAC samples, but this is not always possible or practical. Radiologists involved in breast imaging should ensure that they have the necessary skills to carry out FNAC under all forms of image guidance. Best results are achieved by a combination of both techniques, as shown in the image‐guided FNAC in the presence of the cytopathologist. The majority of European countries use similar reporting systems for breast FNAC (C1–C5), in keeping with European Guidelines for Quality Assurance in Breast Cancer Screening and Diagnosis, although some still prefer descriptive reporting only. When triple assessment is concordant, final treatment may proceed on the basis of FNAC, without a tissue biopsy. ER and PR assessment can be done safely on FNAC material. However, not all institutions may have expertise in doing this. HER‐2 protein expression on direct cytological preparations is insufficiently reliable for clinical use, although its use for FISH is possible, if expertise is available. The majority of participants practise a degree of one‐stop diagnosis with a cytopathologist present in the out‐patient clinic. Formal recognition of the importance of the time spent outside the laboratory, both for cytopathologist and cytotechnologist, is necessary in order to ensure appropriate resourcing. The use of core biopsy (CB) has increased, although not always for evidence‐based reasons. CB and FNAC are not mutually exclusive. FNAC should be used in diagnosis of benign, symptomatic lesions and CB in microcalcifications, suspicious FNAC findings and malignancies where radiology cannot guarantee stromal invasion.

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.

Survey of medical training in cytopathology carried out by the journal Cytopathology

Anshu, A. Herbert, B. Cochand‐Priollet, P. Cross, M. Desai, R. Dina, J. Duskova, A. Evered, A. Farnsworth, W. Gray, S. S. Gupta, K. Kapila, I. Kardum‐Skelin, V. Kloboves‐Prevodnik, T. K. Kobayashi, H. Koutselini, W. Olszewski, B. Onal, M. B. Pitman, Ž. Marinšek, T. Sauer, U. Schenck, F. Schmitt, I. Shabalova, J. H. F. Smith, E. Tani, L. Vass, P. Vielh and H. Wiener
Survey of medical training in cytopathology carried out by the journal Cytopathology

Training and practice of cytotechnologists: a discussion forum focused on Europe

To discuss the role and training of cytotechnologists (CTs) in Europe, to identify areas of good practice and to provide an informed opinion to those providing guidelines for training and practice in Europe.

Pre-B-cell acute lymphoblastic leukemia with bulk extramedullary disease and chromosome 22 (EWSR1) rearrangement masquerading as Ewing sarcoma

We report a 2‐year‐old female with a subcutaneous tumor who was initially misdiagnosed as suffering from Ewing sarcoma with a positive EWSR1 rearrangement and EWS/FLI1 transcript. After finding lymphoblasts in peripheral blood, the diagnosis of acute lymphoblastic leukemia was established. This necessitated further analysis of the subcutaneous tumor. The tissue was positive for immature B‐cell markers and an immunoglobulin heavy chain gene rearrangement, which confirmed the final diagnosis of common type acute lymphoblastic leukemia with bulk extramedullary disease. The patient was treated with chemotherapy and was in remission 30 months after the diagnosis. Pediatr Blood Cancer 2010;54:606–609.

Multinational study of oestrogen and progesterone receptor immunocytochemistry on breast carcinoma fine needle aspirates

Ž. P. Marinšek, N. Nolde, I. Kardum‐Skelin, R. Nizzoli, B. Önal, T. Rezanko, E. Tani, K. T. Ostović, P. Vielh, F. Schmitt and G. Kocjan 
Multinational study of oestrogen and progesterone receptor immunocytochemistry on breast carcinoma fine needle aspirates

Metachronous Gastrointestinal Stromal Tumor and Acute Leukemia after Liver Transplantation for Cholangiocellular Carcinoma: Is There a Link?

The synchronous or metachronous coexistence of gastrointestinal stromal tumors (GISTs) with solid and hematologic neoplasms has been addressed in a non-transplant population. However, the association with primary hepatic neoplasms and leukemias is uncommon. Scarce data exist considering association of GISTs and other neoplasms in a transplant population where long-term immunosuppression carries the additional burden of de novo malignancy. We present a case of posttransplant metachronous GIST and acute biphenotypic leukemia in a patient transplanted for intrahepatic cholangiocellular carcinoma, emphasizing the possible link between mechanisms of carcinogenesis and influence of other factors upon their development.

Parotid gland tumors: Correlation between routine cytology and cytomorphometry by digital image analysis using conventional and newly introduced cytomorphometric parameters

The objective of this study was to compare qualitative cytomorphology and morphometric characteristics of parotid gland tumor cells, with the aid of a computer‐assisted system of image analysis. Routine qualitative cytologic and quantitative morphometric results from 64 parotid gland tumors were compared. Ultrasound (US)‐guided fine‐needle aspiration (FNA) specimens were taken from 54 patients. Eleven conventionally used morphometric parameters were studied: area, perimeter, convex area, convexity, maximal and minimal radius, length, breadth, form factor (FF), elongation factor, and nuclear‐ cytoplasmatic (N/C) ratio. Two newly introduced nuclear form factors were also measured: area symmetry factor and perimeter symmetry factor. The following nuclear morphometric parameters were significantly different between malignant and benign tumors: area, perimeter, convex area, convexity, maximal and minimal radius, length, breadth, FF, elongation factor, area symmetry factor, and perimeter symmetry factor. Comparing the cutoff values and receiver operating characteristic (ROC) curves the following nuclear morphometric parameters were found most useful in separating benign from malignant tumors: area, perimeter, convex area, maximal radius, length, and FF. The following whole cell morphometric parameters were significantly different between malignant and benign tumors: minimal and maximal radius, convexity, breadth, FF, and elongation factor. N/C ratio was significantly higher in malignant tumors. The quantitative morphometric analysis is a useful tool in the cytological differentiation between benign and malignant parotid gland tumors. Computerized image analysis may add to morphological evaluation by turning qualitative data into quantitative values. Diagn. Cytopathol. 2013;41:776–784.

Acute leukemia in patients with untreated chronic lymphocytic leukemia: A report of two cases with remarkably similar time cluster

The association of chronic lymphocytic leukemia (CLL) and acute leukemia (AL) is rare [1]. In most cases, AL develops after treatment of CLL; thus, previous chemotherapy or radiotherapy is usually considered to be a leukemogenic event [2]. We report two cases of acute leukemia occurring in patients with untreated chronic lymphocytic leukemia with remarkably similar time cluster. These two ALs had the same morphological but distinct immunophenotypic features. The first patient was a 55-year-old woman. A diagnosis of CLL was made in 1998 when hematologic work-up was consistent with B-cell CLL, Rai stage 1 [3], and a low tumor burden by total tumour mass classification [4]. The clinical course was stable, and the patient was observed without therapy. She was admitted to University Hospital ‘Merkur’ in June 2002 for evaluation of a newly developed leukocytosis. Laboratory studies revealed a white blood cell (WBC) count of 1276 10/l (myeloblasts 49%, promyelocytes 19%, lymphocytes 18%, monocytes 9%, promonocytes 5%), hemoglobin of 77 g/l, platelet count of 866 10/l, and lactate dehydrogenase of 1013 U/l. A cytological bone marrow smear revealed approximately 10% atypical blasts type I and approximately 80% blasts type II and III, with numerous granules, some basophile-like, and some Auer rods (Figure 1A). Two cell populations were found by flow cytometric analysis; one with phenotypic characteristics of B-cell CLL [CD5/CD19þ, CD5/CD23þ, monoclonal CD19/kappaþ (with a weak expression of light chains)] and a blasts population (MPOþ, CD2þ, CD13þ, CD33þ, CD117þ, HLA D/DR – /þ, CD 34 – ). The results were consistent with a mixed cell population within the lymphocyte gate (Table I). Approximately 20% of cells in the lymphocyte ‘window’ had the immunophenotypic characteristics of B-cell CLL (18.67% CD19/kappaþ versus 0.67% CD19/ lambdaþ, showing imbalance and supporting clonality) whereas approximately 80% of the cells in that gate had characteristics of blasts (MPOþ), and most likely corresponded to a subpopulation of smaller blasts which fitted the window. By contrast, all the cells in the blasts ‘window’ had the immunophenotypic characteristics of acute leukemia blasts whereas the B-cell CLL clone was not present (Table I). The cytogenetic analysis from the bone marrow sample did not show any chromosomal abnormalities, and the karyotype was 46,XX [10]. The second patient was a 59-year-old woman. A previous diagnosis of B-CLL was also made in 1998 with a stable clinical course, and was observed without therapy. She referred to University Hospital ‘Merkur’ in May 2002 for evaluation of a progressive leukocytosis. WBC count was 104.56 10/l (atypical blasts 45%, promyelocytes 9%, band neutrophiles 1%, lymphocytes 41%, prolymphocytes 3%, plasma cells 1%), hemoglobin 50.6 g/l, platelet count 246 10/l. A cytological smear of bone marrow

Chromosomal abnormalities and DNA image cytometry of haematological neoplasms in fine needle aspirates of lymph nodes

The current diagnostics of haematological neoplasms along with morphological analysis, immunophenotyping and molecular analysis inevitably includes cytogenetic analysis. In this work the possibility of cytomorphological subclassification of haematological neoplasms from lymph node fine needle aspirates was examined without depending upon the referential histological diagnosis and cytogenetic analysis. In addition, the feasibility of cytogenetic analysis of the material obtained by lymph node fine needle aspiration (FNA) was examined. By analysing the findings of cytogenetic analysis and DNA image cytometry, it was decided to examine the possibility of comparing the findings and supplementing diagnostic possibilities of these methods. In 15 cases cytological diagnoses and cytogenetic analysis of haematological neoplasms were performed on the material obtained by lymph node FNA. In 12 of 15 cases histological diagnosis was made separately. A good cytohistological correlation was available in 9 of 12 cases (75%). Cytomorphological diagnoses in 10 of 15 cases (76%) were confirmed by the finding of a specific chromosomal translocation. In two cases cytological diagnosis did not correlate with the histological diagnosis and was confirmed only with specific chromosomal translocations. The lymphocytes obtained by lymph node FNA were adequate material for cytogenetic analysis – in 15 of 18 (83%) cases mitoses in cell cultures were obtained. In 13 of 15 (87%) cases clonal chromosomal abnormalities were detected, whereas in 2 of 15 (13%) cases a normal karyotype was found. DNA image cytometry was performed on nine samples, whereas in six samples the material was not sufficient. Although a small number of samples was analysed in the cases with identical cytomorphological diagnoses, the analysed histograms regarding the DNA index values showed heterogeneity. In conclusion, a cell culture sampled by FNA of lymph nodes is an adequate method for the chromosomal analysis. The specific cytogenetic abnormality associated with cytological diagnosis provides an opportunity to make a definitive diagnosis and provides a powerful approach when reference diagnosis on biopsy material cannot be obtained.