Analysis of Primary Chronic Lymphocytic Leukemia Cells' Signaling Pathways.

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder characterized by a specific expansion of mature B-cell clones. We hypothesized that the disease has a heterogeneous clinical outcome that depends on the genes and signaling pathways active in the malignant clone of the individual patient. It was found that several signaling pathways are active in CLL, namely, NOTCH1, the Ikaros family genes, BCL2, and NF-κB, all of which contribute to cell survival and the proliferation of the leukemic clone. Therefore, we analyzed primary CLL cells for the gene and protein expression of NOTCH1, DELTEX1, HES1, and AIOLOS in both peripheral blood lymphocytes (PBLs) and the bone marrow (BM) of patients, as well as the expression of BCL2 and miRNAs to see if they correlate with any of these genes. BCL2 and AIOLOS were highly expressed in all CLL samples as previously described, but we show here for the first time that AIOLOS expression was higher in the PBLs than in the BM. On the other hand, NOTCH1 activation was higher in the BM. In addition, miR-15a, miR-181, and miR-146 were decreased and miR-155 had increased expression in most samples. The activation of the NOTCH pathway in vitro increases the susceptibility of primary CLL cells to apoptosis despite high BCL2 expression.

Guidelines for Diagnosis and Treatment of Chronic Lymphocytic Leukemia. Krohem B-Cll 2017.

Recent developments in the diagnosis and treatment of chronic lymphocytic leukemia (B-CLL) have led to change of approach in clinical practice. New treatments have been approved based on the results of randomized multicenter trials for first line and for salvage therapy, and the results of numerous ongoing clinical trials are permanently providing new answers and further refining of therapeutic strategies. This is paralleled by substantial increase in understanding the disease genetics due to major advances in the next generation sequencing (NGS) technology. We define current position of the Croatian Cooperative Group for Hematologic Disease on diagnosis and treatment of CLL in the transition from chemo-immunotherapy paradigm into a new one that is based on new diagnostic stratification and unprecedented therapeutic results of B-cell receptor inhibitors (BRI) and Bcl-2 antagonists. This is a rapidly evolving field as a great number of ongoing clinical trials con-stantly accumulate and provide new knowledge. We believe that novel therapy research including genomic diagnosis is likely to offer new options that will eventually lead to time limited therapies without chemotherapy and more effective clinical care for B-CLL based on individualized precision medicine.

Fine-needle aspiration cytology yield as a basis for morphological, molecular, and cytogenetic diagnosis in alk-positive anaplastic large cell lymphoma with atypical clinical presentation.

ALK positive anaplastic large cell lymphoma is a T-cell lymphoma usually occurring in children and young adults. It frequently involves lymph nodes and extranodal sites and is associated with favorable prognosis. A 20-year old man was admitted for painful mass in the left axilla with overlying skin redness. Clinical presentation and US findings were highly suspicious for sarcoma. Definitive diagnosis was established cytolologically and using ancillary technologies from cytological samples. Fine needle aspiration cytology of tumor mass (lymph node conglomerate and surrounding tissue) show predominance of large, pleomorphic, atypical cells with large nuclei and vacuolised cytoplasm. Atypical cells immunocytochemically were positive for LCA, CD30, CD3, EMA, and ALK; negative for CD15 and CD56. NPM-ALK transcript was detected by reverse transcriptase-polymerase chain reaction (RT-PCT). Molecular analysis of TCRß and TCRγ genes demonstrated clonal TCR genes rearrangement. Complex karyotype with multiple numerical and structural changes was found on conventional cytogenetics. These findings excluded sarcoma and corroborated the diagnosis of ALK positive ALCL. Cutaneous involvement in ALCL can clinically mimic sarcoma, especially in cases with localized disease without B symptoms. In those cases, immunostaining, PCR, and conventional cytogenetics are helpful to exclude sarcoma. Diagn. Cytopathol. 2017;45:51-54. © 2016 Wiley Periodicals, Inc.

Notch affects the prodifferentiating effect of retinoic acid and PMA on leukemic cells.

Notch proteins determine cell fate decisions in the development of diverse tissues. Notch has been initially found in T-ALL but its role has been also studied in myelopoiesis and myeloid leukemias. Studies in different model systems have led to a widespread controversy as to whether Notch promotes or blocks myeloid differentiation. In this work, we evaluated the influence of Notch activation on leukemic cell differentiation along the monocytic and myelocytic pathway induced by phorbol 12-myristate 13-acetate (PMA) or all-trans retinoic acid (ATRA). We observed that differentiation of the human myeloblastic cell line HL-60 can be retarded or blocked by Delta/Notch interaction. ATRA induces complete remission in patients with acute promyelocytic leukemia, but it cannot completely eliminate the leukemic clone and to be effective it should be combined with chemotherapy. Our findings suggest that Notch signaling may contribute to the incomplete elimination of the leukemic cells after PMA or ATRA treatment and the blockage of Notch pathway may be beneficial in the treatment of myeloid leukemia. © 2014 International Society for Advancement of Cytometry.

Hydronephrotic Kidney Previously Treated for Tuberculosis: Rare Primary Squamous Cell Carcinoma of Renal Pelvis Diagnosed by Fine-needle Aspiration Cytology.

Primary squamous cell carcinoma (SCC) of the renal pelvis is a very rare tumor often associated with renal calculi and chronic infections. There are only a few articles in literature which report renal pelvis SCC in kidneys treated for renal tuberculosis, diagnosed after nephrectomy. We report the case of SCC in a hydronephrotic kidney previously treated for tuberculosis, diagnosed by ultrasound (US)-guided fine-needle aspiration cytology (FNAC), prior to core biopsy and nephrectomy. Our report highlights the utility of FNAC and the need for a careful search for renal collecting system tumors, in patients previously treated for renal tuberculosis.

Atypical blast morphology of primary plasma cell leukemia with renal involvement and plasmablasts in urine.

Primary plasma cell leukemia (PCL) is a rare and aggressive variant of plasma cell (PC) myeloma characterized by high levels of circulating PCs. Clinical presentation is like other acute leukemia, with extramedullary infiltration of various tissues and organs being a frequent complication. The disease has a fulminant course and poor prognosis. Morphology of PCs in PCL includes a spectrum of maturity, with most cases having lymphoplasmacytoid or plasmablastic morphology. Presentation as more primitive cells that do not resemble PCs is even rarer and requires additional morphological and immunophenotypic studies. We present a case of 79-year-old woman who presented with severe pancytopenia and lobar pneumonia. Laboratory and clinical evaluation revealed primary, nonsecretory PCL with atypical, immature blast morphology, extramedullary renal involvement, and plasmablasts in urine. Despite therapeutic efforts the patient succumbed to the disease. Detection of PCs in the urine indicates extramedullary spread of disease, especially without accompanying hematuria, and may contribute to impairment of renal function, what is already a frequent complication in these patients.

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.

[Croatian Society for Clinical Cytology guidelines for thyroid cytology]. / Smjernice u citoloskoj dijagnostici stitnjace Hrvatskoga drustva za klinicku citologiju.

The main purpose of thyroid FNA (fine needle aspiration) is to separate malignant and possibly malignant nodules from benign thyroid lesions. Every patient with thyroid nodule is a candidate for FNA. Before a decision to perform an FNA, a complete history, a physical examination directed to the thyroid and cervical lymph nodes, a serum thyrotropin level, and thyroid ultrasound should be obtained. Thyroid lesion with a maximum diameter greater than 1.5 cm or nodule of any size with sonographically suspicious features is an indication for FNA. Ultrasound-guided FNA of the thyroid is recommended. The requisition form that accompanies FNA should contain the identifying data, location and size of the nodule, and relevant laboratory and clinical data. FNA diagnosis of thyroid disease is a clinicocytologic diagnosis, and correlation with clinical findings is mandatory for success. Thyroid FNA classification scheme consists of a four diagnostic categories according to the risk of malignancy: benign lesions, indeterminate lesions according to malignancy, malignant tumors, and non-diagnostic. Ancillary studies (immunocytochemistry, RT-PCR, flow cytometry) are usually helpful in borderline cases.

[Clinical guidelines for diagnosis, treatment and monitoring of patients with non-invasive breast cancer]. / Klinicke smjernice za dijagnostiku, lijecenje i pracenje bolesnika s neinvazivnim rakom dojke.

Breast cancer is the most common malignancy in women. Early diagnosis and more effective treatment of invasive breast cancer resulted in significant mortality reduction, improvement of survival and the quality of life of the patients. The management od non-invasive breast cancer, on the contrary, is still controversial and the problem of overdiagnosis and overtreatment of patients come to evidence. In the following text a multidisciplinary team of experts brings the first consensus guidelines aimed to standardize and optimize the criteria and management in diagnosis, treatment and monitoring of non-invasive breast cancer patients in the Republic of Croatia.

[Why is cytology a profession (branch), not a method? Ten rules for success of the cytology profession]. / Zasto je citologija struka, a ne metoda? Deset pravila za uspjesnost citoloske struke.

Clinical cytology is an interdisciplinary medical diagnostic profession that integrates clinical, laboratory and analytical fields along with final cytologist's expert opinion. Cytology involves nonaggressive, minimally invasive and simple for use procedures that are fully acceptable for the patient. Cytology offers rapid orientation, while in combination with additional technologies on cytologic smear analysis (cytochemistry, immunocytochemistry for cell marker analysis, computer image analysis) or sophisticated methods on cytologic samples (flow cytometry, molecular and cytogenetic analysis) it plays a major role in the diagnosis, subtyping and prognosis of malignant tumors. Ten rules for successful performance in cytology are as follows: 1) due knowledge of overall cytology (general cytologist); 2) inclusion in all stages of cytologic sample manipulation from sampling through reporting; 3) due knowledge of additional technologies to provide appropriate interpretation and/or rational advice in dubious cases; 4) to preserve dignity of the profession because every profession has its advantages, shortcomings and limitations; 5) to insist on quality control of the performance, individual cytologists and cytology team; 6) knowledge transfer to young professionals; 7) assisting fellow professionals in dubious cases irrespective of the time needed and fee because it implies helping the patient and the profession itself; 8) experience exchange with other related professionals to upgrade mutual understanding; 9) to prefer the interest of the profession over one's own interest; and 10) to love cytology.

[Post-transplant lymphoproliferative disease in liver transplant recipients--Merkur University Hospital single center experience]. / Post-transplantacijska limfoproliferativna bolest u bolesnika s transplantacijom jetre - iskustvo KB Merkur.

Post-transplant lymphoproliferative disorder (PTLD) is an increasingly recognized condition as the number of solid organ and bone marrow transplant recipients increases. It can be a life threatening fulminant disorder and affects approximately 8% of solid organ transplant recipients. Epstein-Barr virus (EBV) is closely involved in the pathogenesis of PTLD and the majority of PTLD cases arise in response to primary infection with EBV or to re-activation of previously acquired EBV. The principal risk factors underlying the development of PTLD are the degree of overall immunosuppression and EBV serostatus of the recipient. The most commonly used pathologic classification of PTLD is the World Health Organization classification, which divides PTLD into three categories: early lesions, polymorphic PTLD, and monomorphic PTLD. Early lesions are characterized by reactive plasmacytic hyperplasia. Polymorphic PTLD may be either polyclonal or monoclonal and is characterized by destruction of the underlying lymphoid architecture, necrosis, and nuclear atypia. In monomorphic PTLD, the majority of cases (>80%) arise from B cells, similar to non-Hodgkin's lymphoma in immunocompetent hosts. The most common subtype is diffuse large B-cell lymphoma, but Burkitt's/Burkitt's-like lymphoma and plasma cell myeloma are also seen. Rarely T-cell variants occur, which include peripheral T-cell lymphomas and, rarely, other uncommon types, including gamma/delta T-cell lymphoma and T-natural killer (NK) cell varieties. Hodgkin's disease-like lymphoma is very unusual. An accurate diagnosis of PTLD requires a high index of suspicion, since the disorder may present subtly and/or extranodally. Radiologic evidence of a mass or the presence of elevated serum markers (such as increased LDH levels) are suggestive of PTLD, with positive finding on ultrasonography, computed tomography, magnetic resonance and/or positron emission tomography scanning (possibly indicating metabolically active areas) also favoring the diagnosis. The management of PTLD poses a major therapeutic challenge and although there is reasonable agreement about the overall principles of treatment, there is still considerable controversy about the optimal treatment of individual patients. EBV-related PTLDs are a significant cause of mortality in patients undergoing orthotopic liver transplantation with the observed mortality rate of up to 50%. This paper presents the experience acquired at Merkur University Hospital in the diagnosis and treatment of patients with liver transplantation and PTLD.

[Diagnostic and prognostic significance of CD45 cell surface antigen expression in hematologic malignancies with main focus on acute leukemias]. / Dijagnosticko i prognosticko znacenje izrazaja biljega CD45 u hematoloskim zlocudnim bolestima s posebnim osvrtom na akutne leukemije.

CD45 cell surface antigen is a transmembrane protein with tyrosine phosphatase activity, expressed by all nucleated cells of hematopoietic origin, except erythrocytes and platelets. Monoclonal antibodies directed against CD45 represent irreplaceable tool in differential diagnosis of hematologic and other, non-hematologic low differentiated malignancies, primarily in cases of: extranodal lymphomas, non-hematologic malignancies with nodal or bone marrow localization or their metastases in mentioned sites. As cell surface immunophenotype marker, CD45 is of great value in differentiation of lymphoproliferative diseases subtypes. By flow cytometry, based on CD45 expression, the malignant cell population is being identified and that fact is used in, not only diagnosis, but also in detection of minimal residual disease, especially in cases of CD45 negative acute leukemias. Incidence of childhood CD45 negative acute lymphoblastic leukemias (ALL) is about 10%. Children diagnosed with low CD45 expression ALL generally have better prognosis than those with high CD45 expression, especially when cut-off value for CD45 expression is set on 90%. We have analyzed CD45 expression by flow cytometry in 28 consecutive patients diagnosed with ALL in our institution during a 5-year period. Among these patients 7.1% were CD45 negative. A positive correlation between CD45 and CD20 expression was found, and a negative correlation between CD45 and CD34. In our group of patients, CD45 expression did not have any influence on survival.

[Association of CD34 cell surface antigen expression with cytomorphological characteristics of acute promyelocytic leukemia blasts and clinical characteristics of patients: one center experience]. / Povezanost izrazaja biljega CD34 s morfoloskim znacajkama blasta u akutnoj promijelocitnoj leukemiji i klinickim znacajkama oboljelih: iskustvo jednog centra.

The aims of the study were to investigate the association between cytomorphology and immunophenotypic expression of CD34 cell surface antigen of blasts and their relationship with clinical and laboratory characteristics of patients with acute promyelocytic leukemia (APL). Sixteen consecutive patients (male 69% and female 31%) diagnosed with APL at Department of Hematology, Merkur University Hospital between August 1998 and December 2010 were included in the study. The mean age of patients was 43.9 (range: 18-78, SD 14.9). The patients' clinical and laboratory features, cytomorphological characteristics of APL-blasts and their immunophenotype determined by flow cytometry were analyzed. Patients were divided into two groups, CD34- and CD34+, and were then compared according to clinical and laboratory characteristics. There was no difference according to age, sex or white blood cell count between two groups. The mean value of hypogranular/agranular APL-blasts was markedly higher in CD34+ group than CD34- group (34%, range 9-60, SD 24.4 vs. 11.5%, range 0-38, SD 13.7), with borderline statistical significance (P=0.055). CD34- patients had significantly better overall survival than CD34+ ones (P=0.02). Patients without Auer rods detected in APL-blasts had higher CD34 expression (69.4% +/- 33.8) compared to patients with detected Auer rods (7.3% +/- 24.8), but statistical significance was not reached (p=0.053). Our results are consistent with the results of other published studies and point to the fact that higher CD34 expression and lower cytoplasmic granularity of APL-blasts are factors that seem to define a specific subgroup of APL patients. Together with other diagnostic tools currently available, they could be of value in planning treatment of APL patients.

[Fine needle aspirate of lymph node as the analytical sample for immunophenotyping]. / Punktat limfnog cvora kao analiticki uzorak za fenotipizaciju stanica.

In modern clinical laboratory routine, cell analysis by flow cytometry means help in setting up the diagnosis by determination of B-lymphocyte clonality and thus separation of benign and malignant lymphoproliferative diseases. The aim of this study was to assess the value of cytologic diagnosis and adequacy of the material obtained by fine needle aspiration (FNA) of lymph nodes for flow cytometry analysis in cases of benign lesions and primary malignant lesions of lymph nodes. In addition, the aim was to determine B-lymphocyte clonality in different groups of benign and malignant lymph node lesions. The study was based on medical documentation, cytologic smears of FNA lymph node samples and results of flow cytometry immunophenotyping. A total of 239 patients were included over a one-year period. Patients were classified according to cytologic findings in the groups of non-Hodgkin's lymphoma of B cell origin (55%), benign lymphoproliferative disease (22%), undefined group of monomorphic population of lymphatic cells (16%), and the rest in the group of non-Hodgkin's non B cell origin. Study results showed FNA to be an appropriate method for obtaining sufficient numbers of cells for analysis by flow cytometry because there was no inadequate samples in our study group. In some cases of monomorphic lymphoid cell population, cytologic diagnosis was limited to small cell lymphomas, so determining the clonality by flow cytometry is crucial in separating malignant from benign lymphoproliferative disease. It is concluded that FNA associated with the flow cytometry method is a simple and safe method in the diagnosis of lymphoproliferative disease.

[Education of cytotechnologists--are we satisfied with what we had, what we have, and what we want?]. / Edukacija citotehnologa--jesmo li zadovoljni s onim sto smo imali, sto imamo, a sto bismo zeljeli?

Our aim is to present training of cytotechnologists in Croatia as it looked in the past, as it appears at present, and our desires, needs, and upcoming changes necessary in future education of cytotechnologists. Education in cytotechnology begins at the School of Health Technicians, where the first organized training of cytotechnologists was held in 1968/1969, thanks to the efforts invested by Professor Inga Crepinko. After a period of training in a six-month course, during the 1981-1992 period training took place in the form of a one-year program evaluated as education level V. Since then, efforts to establish education at all academic institutions in Croatia have failed. At Medical College, one-year training was introduced in 1993, however, for only one generation. Under the auspices of the Ministry of Health and Social Welfare and the Croatian Society of Clinical Cytology of the Croatian Medical Association, 5 one-year courses with 630 hours of theoretical classes with practical work and 200 hours of practical training in cytologic activities have been held since 2000. Now, we ask ourselves was there any reason for us to be satisfied in the past and is it there now. In Croatia, there is the need of optimized and standardized training of cytotechnologists at the university level, with a valid certificate in European countries and a curriculum that will meet the needs of new technologies (molecular techniques, LBC, HPV testing, etc.).

[Erythrocyte morphology in urine determined by light microscopy in patients with bladder cancer]. / Podrijetlo eritrocita u urinu odredivano svjetlosnim mikroskopom kod bolesnika s karcinomom mokracnog mjehura.

A finding of 80% or more of dysmorphic erythrocytes is assumed to point to kidney glomeruli, and of 80% or more of isomorphic erythrocytes to lower urinary tract as the origin of bleeding. In urine samples without significant origin of bleeding, there were 20%-80% of mixed results with both dysmorphic and isomorphic erythrocytes. The aim of the study was to show the origin of erythrocytes in malignant urine samples. Samples were fresh native urine sediment contrast stained with 0.1% safranin solution and analyzed under light microscope (X40). Out of 72 patients with malignant cells detected in urine, the origin of erythrocytes was identified in 25 patients (nine female and 16 male) through 90 samples (approximately 3-4 samples per patient); 26 (28.9%) samples did not have enough erythrocytes to define their origin, a mixed origin of erythrocytes was identified in 33 (36.7%) samples, dysmorphic erythrocytes were found in 25 (27.9%) samples, and isomorphic erythrocytes in 6 (6.3%) samples. In conclusion, there was no specific connection between malignant cell findings in urine and origin of erythrocytes. However, the high presence of mixed erythrocyte origin in malignant samples may suggest that the existence of a malignant process and renal disease should be taken in consideration.

[Acute plastic bronchitis--case report]. / Akutni odljevni bronhitis--prikaz bolesnika.

Plastic bronchitis is a rare disorder characterized by formation and sometimes dramatic expectoration of bronchial casts. It may occur at any age, but most published cases refer to pediatric population. We report a case of an 81-year-old man hospitalized at intensive care unit, who presented with the appearance of plastic bronchitis type I. He had profuse expectoration of several pieces, a few cm long and up to 1 cm wide, of wormlike reddish-brownish "tissue". Histologically, it was a slimy purulent secretion with abundant fibrin and blood and with cytopathic effect of herpes virus. The pathogenesis of plastic bronchitis is not clear.

[Isolated myeloid sarcoma involving the mediastinum]. / Izolirani mijeloidni sarkom medijastinuma.

Myeloid sarcoma is a rare extramedullary solid tumor consisting of immature myeloid cells and most commonly involving the bone, skin, lymph nodes, soft tissue, gastrointestinal tract and testis. Mediastinal myeloid sarcoma is very rare. There are two major types of myeloid sarcoma: granulocytic sarcoma and monoblastic sarcoma, according to immature cell type. Myeloid sarcoma is found in 2%-8% of patients with acute myeloid leukemia (AML). Myeloid sarcoma may develop before or concurrently with AML, or may be the initial manifestation of AML relapse in previously treated patients. Blast transformation of some form of myeloproliferative neoplasm or myelodysplastic syndrome may also manifest as myeloid sarcoma. A major differential diagnostic problem is isolated primary myeloid sarcoma without bone marrow and peripheral blood involvement, which may precede leukemic stage for months or years, and which is frequently misdiagnosed, mostly as malignant lymphoma. A case is presented of a 56-year-old female patient complaining of weakness, vertigo, dry cough and breathing difficulties. Clinical examination revealed enhanced vascular pattern on the right chest and right arm edema. Computed tomography (CT) of the thorax showed an expansive growth measuring 11 cm craniocaudally in the anterior mediastinum. Fine needle aspiration cytology of tumor mass yielded a scarcely cellular sample with individual atypical immature cells, fine chromatin structure and scarce cytoplasm with occasional granules and Auer rods. Considering the morphological, cytochemical and immunocytochemical characteristics of immature cells, the diagnosis of myeloid sarcoma was made and verified by histopathology of tumor biopsy sample. Immature cells were not found by analysis of bone marrow puncture sample, immunophenotyping of bone marrow cells and bone biopsy analysis. As immature cell proliferation was not detected in bone marrow and peripheral blood, while spread of the disease beyond the mediastinum was ruled out by imaging methods (CT, ultrasonography), it was decided to be a primary non-leukemic form of mediastinal myeloid sarcoma. Myeloid sarcoma should be taken in consideration on differential diagnosis of solid tumors because making an accurate diagnosis is necessary for timely initiation of appropriate therapy. Weakly expressed or lacking clear signs of myeloid differentiation may hamper morphological diagnosis. As isolated myeloid sarcoma is a very rare entity frequently resembling lymphoma in clinical presentation, it poses a major diagnostic challenge for both morphologists and clinicians.