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Bone marrow edema (BME) is defined as an excess of fluids that builds up in the bone marrow (BM), commonly found because of osteoporosis, trauma, infections, ischemia or neoplasia. Histologically, BME is characterized by accumulation of extracellular eosinophilic fluid. Magnetic Resonance Imaging (MRI) is the only method that highlights the presence of BME caused by various diseases, including the one associated with hematological malignancies. The classic MRI protocol for the study of BM and BME includes T1- and T2-weighted sequences, the STIR sequence, and in some cases, the administration of intravenous contrast agents in T1-weighted sequences. Fifty-four patients were investigated; there were identified 30 patients with MRI features of BME. Out of the 30 patients with BME, 24 were known to have a malignant hematological disease (multiple myeloma, leukemia, lymphoma); for the remaining subjects, imagistic findings and other laboratory investigations led to multiple myeloma diagnosis. Of the 30 patients, six showed characteristic lesions of the underlying disease as well as BME; four patients had only BME. BM is a structure that is commonly investigated using MRI scans, regardless of the examined bone segment. T1-weighted images and T2-weighted with fat suppression are essential for BME evaluation. Moreover, MRI allows monitoring disease progression and treatment response in patients with malignant hemopathies.

Chronic myeloid leukemia is a clonal expansion of hematopoietic progenitor cells characterized by exaggerated proliferation of granulocytic lineage, with chronic phase, accelerated phase and blast crisis. Accelerated phase and blast crisis may be associated with extramedulary disease. Extramedullary transformation of CML can be determined both in nodal and extranodal sites. Non-Hodgkin lymphoma is rare in chronic myeloid leukemia and may be misdiagnosed as an extramedullary lymphoid blast transformation; the majorities are T-cell lymphomas with an immature thymic phenotype, while peripheral B-cell lymphomas are rarer. We report the case of a 79-year-old woman carrier Ph+ chronic myeloid leukemia who developed at eight months of diagnosis an accelerated phase of CML associated simultaneous with a tumor of soft palate, which was initial considering an extramedullary disease. The patient was treated with specific chemotherapy for accelerated phase of CML (Cytosinarabinoside) + Anagrelide, and reversed to secondary chronic phase of CML, but soft palate tumor persists. The immunohistochemical findings of bone marrow trephine biopsy examination showed chronic phase of CML (negativity for immature cells such as CD34, Tdt) and the biopsy of soft palate tumor and immunohistochemical findings revealed a primitive non-Hodgkin lymphoma (NHL) with medium B-cells (CD20, CD79a positive) and excluding an extramedullary blast crisis (CD34 negative, Tdt negative). Cytogenetic analysis in tumor revealed absence of Philadelphia chromosome. The patient was treated with local radiotherapy for NHL, with a favorable evolution and Hydroxyurea 1 g/day for CML with hematological remission. A localized lymphoid neoplasm may be an extramedullary localized blast crisis of CML or a distinct malignancy, with distinguished therapy and prognosis. A correct diagnosis based on a complex investigation: immunohistochemistry, conventional cytogenetic analysis and fluorescence in situ hybridization (FISH), molecular analysis (Southern blot and RT-PCR) is necessary. Further studies are required to clarify the pathogenetic relationship between chronic myeloid leukemia and non-Hodgkin lymphomas.

Littoral cell angioma is a rare tumor of the spleen, usually being considered benign and typically discovered incidentally. There are three different modalities of presentation: tumoral splenomegaly, long-standing iron deficient anemia or thrombocytopenia due to hypersplenism. However, some of its manifestations could generate the suspicion of a lymphoma or other more serious condition. We present the case of a 46-year-old man with splenomegaly and iron deficiency anemia. The tumor affected the whole spleen, which was surgically removed. The histopathological examination, together with immunophenotyping, established the diagnosis. Six months after the procedure, the patient is in very good condition. Several differential diagnoses were discussed, as well as the prognostic factors. The case illustrates a rare cause of anemia and the importance of pathology in uncovering such unusual causes for this.

Tumor infiltrating lymphocytes (TIL), as a microenvironment component were studied in various epithelial tumors, with contradictory results. Recent data about regulatory T-cells (Treg) revealed new explanations for pro- and anti-tumor implications of TIL. Tregs immunoprofile was recently completed with Foxp3 expression. A T-cell fraction (Th) is producing cytokine IL17 and is now considered acting in tumor progression. Our study aimed to analyze immunohistochemically (IHC) Foxp3+ and IL17 expression in resected lung adenocarcinomas, since they could become possible targets in the antitumor immunotherapy. The studied material was represented by paraffin-embedded tumor fragments from 59 patients with TIL identified on HE staining. The antibodies used were Foxp3 and IL17. The statistical analysis used logistical regression on SPSS19 software (Chicago, IL, USA). TIL was usually mild or scarce. A positive statistic correlation resulted between the amounts of TIL in peritumoral and intratumoral location but without correlation to histopathological grading. Foxp3 and IL17 were present in TIL lymphocytes, tumor cells and fibroblasts; IL17 was expressed also in periendothelial cells (PEC). Foxp3 positivity was significantly correlated for lymphocytes÷tumor cells, lymphocytes÷fibroblasts and tumor cells÷fibroblasts, suggesting their concerted action. Tumor cells and lymphocytes Foxp3 expression was inversely correlated with the amount of TIL. Between lymphocytic Foxp3 and PEC IL17, we found a weak negative correlation. The TIL had a quite positive correlation with PEC IL17. In these conditions, Foxp3 could be a mediator of the tumor cells inhibitory aggression upon the immune system and could be used as a molecular target for biological antitumor therapy.

In the WHO classification, there is a provisional entity called Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable (MDS/MPN, U). Refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T) was included in this category. Recently published studies report a small percentage of patients with RARS-T. Sixty percent of these have JAK2 V617F mutation, which can suggest the coexistence of two pathological conditions (MDS and MPN). In this paper, we analyzed three patients diagnosed with RARS-T in the Department of Hematology, "Fundeni" Clinical Institute, Bucharest, Romania, during the period 2005-2011. The patients were investigated with cytogenetic exam and molecular biology. In these three cases were identified morphological features of multilineage dysplasia (two-lineage dysplasia in two cases and three-lineage dysplasia in one case). In two cases, thrombocytosis was under 1000×10(3)/μL and clinical evolution was similar to the myelodysplastic syndrome (transfusion dependent anemia with response to administration of erythropoietin). In the third case, the platelets were over 1000×10(3)/μL and with response to the treatment with Hydrea, which improved anemia. JAK2 V617F mutation was not identified in any case. RARS-T remains a provisional entity and requires a complex investigation of patients for the correct diagnosis of these patients. Therapeutic options should be personalized to each case in part because there is not yet a standardized treatment of these patients.

Unlabelled: Primary spinal involvement in hematological diseases is rare., Purpose: The purpose of this article is studying diagnostic and treatment strategies in patients with spinal cord primary hematologic tumors causing spinal cord compression syndrome., Patients and Methods: We report two cases with spinal cord primary hematologic tumors causing spinal cord compression syndrome. One patient had a diffuse large B-cell non-Hodgkin's lymphoma located in the thoracic spine and the second patient had a plasmocytic plasmacytoma located in the thoraco-lumbar spine., Results: Both patients underwent surgery, with resection of the intracanalar tumor and spinal cord decompression and adjuvant systemic and intrathecal chemotherapy. Neurological outcome was favorable with partial remission of spinal cord compression syndrome. Finally, patients developed secondary dissemination and succumbed due to progression of the hematological disease., Conclusions: Clinical onset and radiographic evaluation is uncharacteristic in early stages. Spinal MRI is mandatory in cases with rebel pain, unresponsive to conservative treatment. Surgery is indicated in all patients with spinal cord compression syndrome. Early diagnosis is associated with better prognosis. Recommended treatment is surgical resection and systemic and intrathecal chemotherapy adapted to histological form of each tumor. In selected cases, if indicated radiotherapy can also be associated.

Mastocytosis comprises a spectrum of disorders characterized by abnormal growth of mast cells (MS). Four entities are recognizable according to WHO classification. Association of systemic mastocytosis (SM) with a chronic myeloproliferative neoplasia (SM-AHNMD) is the second frequently category. Published descriptions of the clinicopathologic features of SM-AHNMD are largely limited to individual case reports. We present the case of a 41-year-old woman with thrombocytosis and mild splenomegaly. Clinical suspicion was of chronic myeloproliferative neoplasia (CMN). Bone marrow trephine biopsy examination (histology and immunohistochemistry for CD117 and CD25) revealed a SM associated with CMN, essential thrombocythemia (ET) type. The JAK2 V617F (for CMN) was detected but KIT/Asp816Val (reported in ~80% of SM) was absent. We discussed the particularity of the cases correlated with a review of the literature.

Unlabelled: Acute pancreatitis is a common complication, which occurs with patients suffering from vesicular biliary lithiasis or chronic alcoholism. Hypercalcemia may determine acute pancreatitis, its causes being multiple: primary or secondary hyperparathyroidism, metabolic diseases of the bone, metastatic bone neoplasm, as well as lymphoproliferative syndromes caused by the HTLV-1 virus-adult T-cell leukemia/lymphoma (ATLL). ATLL is a malignant and aggressive lymphoproliferation with the T-cell, associated with the infection caused by the HTLV-1 retrovirus. Organomegaly, cutaneous conditions, and hypercalcemia represent the main characteristics of the disease. From a hematologic point of view, we can notice the atypical lymphocytes (also known as flower cells, due to the shape of their nucleus), with a distinct CD4+ CD25+ phenotype. There have been reported few cases of patients who showed acute pancreatitis in the onset of the disease. We will describe the case of a patient whose diagnosis has not been an easy one, as it showed multiple complications from a very early stage., Conclusions: The atypical onset of ATLL with acute pancreatitis is rarely reported. Its etiology seems to be hypercalcemia but pancreatic infiltration with ATLL cells cannot be ruled out. An attentive investigation of the peripheral blood sample and flow-cytometric tests of peripheral and medullar blood smear are very important for diagnosis. The patient showed from the very beginning severe neurological manifestations which developed to a coma. Causes could have been metabolic as well as CNS infiltration (as shown by the CT examination).

Mantle cell lymphoma (MCL) is a very rare non-Hodgkin B-cell lymphoma, with an aggressive clinical course and poor response to conventional therapy. Few cases of "in situ" MCL were reported in the last years. We present the case of a 31-year-old woman with a unique cervical lymphadenopathy. The morphologic findings are of hyaline-vascular Castleman disease (HV-CD). Immunohistochemical stain for cyclin D1 detects scattered cyclin D1+ cells within the mantle zones of few reactive-appearing lymphoid follicles, corresponding to the definition of "in situ" MCL. We also performed cyclin D1 in other 27 cases of CD (13 HV-CD and 14 plasma-cell CD) but the reported case was the only who associated "in situ" MCL. An adequate immunohistochemical panel, including a marker for cyclin D1, is required to differentiate this neoplasm from follicular hyperplasia. From our knowledge, this is the first reported case of "in situ" MCL associated with HV-CD.

Background: The t(14;18) translocation, which leads to an overproduction of the bcl-2 protein, supposedly occurs in almost all follicular lymphomas (FL) and can be detected by FISH methods or by PCR. Its detection is useful in monitoring the response to therapy and in assessing minimal residual disease in bone marrow. Recently it was observed that the translocation could become negative after treatment. The prognostic and predictive significance of this fluctuation is not entirely understood., Aim: We intended to find significant correlations among morphological features, histological grades, immunohistochemical findings, and cytogenetical aberrations in malignant follicular lymphomas, in order to identify the prognostic and predictive value of the bcl-2/IgH translocation in these malignancies., Material and Methods: We conducted a study on 79 patients with follicular lymphomas. The study was carried out on tissue samples selected from the "Victor Babes" National Institute of Pathology files. These samples were tested by immunohistochemistry and FISH., Results: Most of the cases (65.2%) were low-grade FL (grade 1-2). Approximately 58.8% of cases in the FISH study group presented t(14;18). In 66.6% of the cases with t(14;18), the immunohistochemical reaction for bcl-2 protein was positive. A significant positive correlation was found between the IHC positivity for bcl-2 and t(14;18) detected by FISH (p=0.04)., Conclusions: Bcl-2 t(14;18) plays an important role in the pathogenesis of follicular lymphoma. FISH is an important tool in the diagnosis, treatment and follow up of these malignancies, since the immunohistochemical testing is negative in a significant proportion of cases.

The composite lymphoma (CL) is defined by the presence in the same tissue or organ of two distinct histological aspects of non-Hodgkin's lymphoma (NHL), or NHL and Hodgkin's lymphoma (HL). The definition of the CL has evolved, requesting the identification of the immunophenotypic pattern and clonal distinct aspects for the two-lymphoproliferative lesions. We present a case of a 73-year-old farmer who presented with B-symptoms and multiple adenomegaly. The biopsy of a left cervical lymph node reveal a CL: a histological and immunophenotypic aspect of HL-mixed cellularity (CD15+, CD30+, CD20-) and a diffuse small cell infiltrate which meet the criteria for B-CLL (CD20+, CD23+, and CD5+). The lymphocytes in peripheral blood over 15 000/mm(3) and marrow infiltrate with small lymphocytes also sustain the B-CLL diagnosis. The relationship between the two lymphoproliferations is discussed reported to the case above, but also considering the literature data. In most of the cases the two proliferative processes are clonal related which means they have a commune lymphoid progenitor, pre-GC or early-GC with individual detachment and transit through GC (also, the afferent related processes). It is also possible that the two proliferations, which form the composite lesion to have different cellular origins, possibility sustained by the analysis of the IgH rearrangements and of the somatic mutations identified in the two clones. The EBV-role in HL-pathogeny is related to the way of salvage or/and initiation of a clonal process in a GC-cell which has major deletions in the variable part of IgH.

Visceral leishmaniasis is produced by a protozoan parasite that belongs to the genus Leishmania. Transmission is made through sting, the vector being represented by a species of the genus Phlebotomus. The first case of visceral leishmaniasis in Romania was reported by Manicatide (1912). In 1934, it was described a focus of visceral leishmaniasis in Oltenia region (24 cases).The symptoms of disease are unspecific: fatigue, feverishness, cephalalgia, anorexia, nausea, obnubilation status. The fever is irregular, with high oscillations. Clinical, a sallow pallor of the skin, enlarge lymph nodes, hepatomegaly, splenomegaly, weight loss have been observed. Laboratory exams showed frequently severe anemic syndromes or other cytopenias, erythrocytes sedimentation rate was increased, hypergammaglobulin-emia with monoclonal peak has been found. Immunolectrophoresis showed hyper-IgG and hyper-IgM. Bone marrow biopsy showed lympho-plasmocyte infiltration, histiocytes, Leishman-Donovan bodies intracellular or extracellular. The prognosis of the disease is unfavorable in the absence of specific treatment with antimony. In case of resistance, it is used immunotherapy, amphotericin or miltefosine.

A small percentage of ovarian neoplasms are transitional cell tumors, which proves to be a distinct group with various histological and immunohistochemical patterns. In this study, 13 archived formalin-fixed paraffin-embedded samples of transitional cell tumors of the ovary have been assessed using standard HE stain and the indirect tristadial ABC peroxidase IHC method for 11 antibodies (CA125, CK7, CEA, EMA, MNF116, CK20, Vim, ER, PgR, PCNA, Ki-67). More than 50% were malignant Brenner tumors. CA125 was positive in all malignant tumors (of Brenner type and transitional cell carcinomas), but not in benign and borderline tumors, while CK7 was positive in approximately 70% of all cases. These two antibodies have shown a high sensitivity and low specificity, but do not correlate to each other. PCNA was positive in the study batch with a mean value of 40% and Ki-67 with a mean value under 25%. A direct correlation statistically significant has been noted between the aforementioned proliferation factors and the tumor grade (r = 0.4, p = 0.05). The other markers were unspecific, with low sensitivity and independently of the histopathological type.

Aim: To quantify the apoptotic phenomenon on endometrial biopsies in postmenopausal patients under hormonal replacement therapy (HRT)., Material and Methods: The study lot consisted of 30 endometrial biopsies on which we studied the apoptotic phenomenon through morphological and molecular biology techniques (TUNEL reaction). Examination of endometrial biopsies before and post-therapeutically has been made., Results and Discussions: From morphological point of view, pre-therapeutically, endometrial biopsies presented apoptotic changes in about 1-3% of cells and under TSH there have been observed apoptotic changes in about 1-2% of cells. In female reproductive system, we found out a raised rate of cellular proliferation and concurrently a raised rate of apoptosis. Apoptotic phenomenon can be observed in endometrium at every menstrual cycle. In proliferative endometrium apoptosis rate is low, but in endometrial carcinoma apoptosis rate grow up. Bcl2 and Bax are expressing in normal and hyperplastic endometrium, but in endometrial carcinoma Bcl2/Bax ratio decline., Conclusions: Quantification of apoptosis, using morphological and TUNEL reaction methods, on endometrial biopsies in postmenopausal patients before and after therapy indicate a low rate of apoptotic phenomenon.

The objective of the paper was to observe the ultrastructural aspects of the endometrial biopsies taken from female patients at post-menopause with substitutive hormonal therapy (TSH). Material and methods. A number of three endometrial biopsies were taken from female patients at post-menopause with TSH. The ultrastructural analysis was carried out with the help of the electronic microscope Philips ME 301 using classical electronic microscopy methods. Results and discussions. The ultrastructural analysis has highlighted the presence of cuboidal and columnar epithelial cells, with basally situated nuclei, well represented cellular organelles, some cells having at the apical pole microvilli. At the electronic microscope, three types of epithelial cells are described, at the level of the endometrial mucosa of the woman who is in a fertile period: secretory cells (cells with an average electronic density with microvilli on the luminal surface), ciliated cells and clear cells (cells with a low electronic density). These cells have certain ultrastructural characteristics and of receptivity towards the steroid hormones. The stroma is axial with elongated cells with oval nuclei, with nucleoli and with smooth or undulated membrane. Conclusions. The ultrastructural aspects suggest the presence at endometrial level of epithelial active glandular cells, secretory cells and stromal active cells at female patients at post-menopause with TSH.

Unlabelled: Primary testicular lymphomas are rare entities representing 1-2% of non-Hodgkin lymphoma (NHML) and 1-7% of malignant testicular tumors and they are the most common testicular tumors in men older than 50 years of age. This study included 8 cases of inpatients diagnosed by echography and NMR with testicular tumors. The age of patients was between 46 and 81 (with a mean of 52). The tumors were unilateral, with disease limited to testicle and accompanied by pain except 1 case with bone involvement. Orchectomy was performed as first therapeutic and diagnostic purpose. All patients were clinically staged according to the Ann Arbor criteria in IE and IIID stage and received a doxorubicin based chemotherapy regimen (CHOP, MTX, CVP, and Leukeran). A standard chemotherapy protocol has not been used because of reduced number of patients. Tumor fragments were fixed in 10% formallin, paraffin embedded, sectioned and standard H.E. stained. Immunohistochemistry for L26, Alphafetoprotein, NK1, CD30, and CLA was performed. Microscopy revealed in all cases a stromal proliferation with medium size cells, monomorphic shape and prominent nucleoli. Alphafetoprotein was positive in seminal tubes and negative in tumor, NK1 in small lymphocyte and negative in tumor and L26 diffuse positive in tumor. CLA diffuse positive in tumor. We were able to follow up only four patients., Conclusions: The diagnosis was of NHML in 6 cases and for 2 secondary involvement of hematopoietic malignancy (myeloid sarcoma and leukemia). Lymphoma cases were typed using REAL classification as small and large B-cell lymphoma. Unfavorable evolution with 6 months relapse and one death prove a more aggressive evolution of primitive testicular lymphoma.

The aim was to evaluate the cellular immune response in atypical tuberculosis and granulomatous inflammation consistent with tuberculosis (TBC), negative histochemically for acid-fast bacilli and analysed by PCR for Mycobacterium tuberculosis (MT) detection in paraffin-embedded tissue. Thirty six samples of differently localized atypical tuberculous lesions and granulomatous tuberculoid lesions negative for acid fast bacilli and 4 positive cases on Ziehl-Nielsen stain were analysed by PCR for MT detection and were tested immunohistochemically (IHC) for the cellular immune response in the granulomas and perigranulomatous tissue. The samples selected were: 7 pulmonary and 33 extrapulmonary specimens, especially lymph nodes. Histologically, the atypical tuberculous lesions contained supurative necrosis, defective granulomas and cellular polymorphism. The epithelioid cells showed frequent mitoses. The immunoprofile of cells was polymorphous. L26 positive small lymphocytes were found in nodular lymphoid aggregates surrounding granulomas. A significantly increased number of positive UCHL1 cells were found in 33 out of the 40 analysed cases, with a larger percentage of CD4 positive T cells (81.8% of cases). CD44 was positive in multinucleated giant cells (17.5% of cases), epithelioid cells (60% of cases) and lymphocytes (30% of cases). CD68 was localized in multinucleated giant cells and epithelioid cells, in a 4%, respectively 62.5% of cases. The PCR was performed in all 40 cases; the tissue samples were heterogeneous (lung, lymph nodes, lever, nasopharynx, etc.) and needed a good quality extraction of DNA. Performing a control PCR for Beta Globin tested the extraction; a good result was obtained in 31 cases (77.5%); from these, 19 cases had amplification for IS 6110. The cellular immune response in the atypical tuberculous lesions was similar in cases with and without acid-fast bacilli, but positive for PCR. In the most cases with negative PCR reaction, it was due to a deficient fixation of the material. The T lymphocytes were numerous in all types of tuberculous granulomas, with the prominence of CD4 positive subtype. The immunoprofile of the epithelioid cells, positive for CD44 and CD68, presenting frequently mitoses suggests an activate state in a possible relationship to the T-cell-mediated immune response in tuberculosis.