Lymphadenopathy is a common clinical finding, affecting patients of all ages. The majority of lymphadenopathies are reactive processes of lymph nodes in response to a variety of exogenous and endogenous stimulants. They are non-neoplastic conditions that can mimic lymphoma and other malignant tumors. Therefore their recognition and differential diagnosis is of great importance in order to rule-out the neoplastic disease. Signs of malignant etiology include lymph nodes >1,5cm in diameter, supraclavicular localization and generalized lymphadenopathy. A metastatic carcinoma is always in the differential diagnosis of localized lympadenophaty in older individuals. In case of generalized lymphadenopathy lymphomas, metastatic solid tumors and various benign etiologies need to be considered. The reactive lymphadenopathies are grouped into four major categories according to their predominant architectural histologic pattern: follicular-nodular, sinus, interfollicular or mixed, and diffuse. As reactive conditions of the lymph nodes are dynamic processes the predominant pattern may differ depending on when during the course of the disease the biopsy is performed. The most common reactive lymphadenopaties are follicular hyperplasia and toxoplasmic lymphadenitis. Nowdays some lymphadenopathies with foreign-body reaction are side effects of silicone prostheses (silicone lymphadenopathy) and various contrast media (lipid lymphadenopathy). A specific diagnosis and differentiation from neoplastic disease often requires correlation among the morphologic features, the clinical history, serologic studies, immunohistochemistry and molecular genetic analysis.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma worldwide, and represents a clinically, pathologically and biologicaly very heterogeneous group of tumours. Recent studies have subdivided diffuse large B cell lymphomas into morphological variants, molecular and immunophenotypical subgroups and distinct entities. An immunophenotypical subdivision of DLBCL, into germinal centre-like (GCB) and non-germinal centre-like (non-GCB) subgroups, using a combination of antibodies to CD10, BCL6 and MUM1, does not correlate exactly with gene expresion profile of GCB and activated peripheral B-cells (ABC). Some studies reported that combination of CD10, BCL6 and MUM1 expression could subdivide DLBCL patients into long- and short-time survivors.The WHO classification of 2008. recognizes a group of aggressive B-cell lymphomas that are not readily classified as either Burkitt lymphoma (BL) or DLBCL, and provisional category of B-cell neoplasms with features intermidiate between DLBCL and classical Hodgkin lymphoma. Furthermore, the new classification recognizes the patient age, site-specific categories, and clinical factors in defining variants of DLBCL.The WHO classification of 2008. is the result of successful international collaboration among pathologists, biologists and clinicians, but heterogeneous group of DLBCL will be the subject of further investigation.

Pathological diagnosis of lymphoproliferative processes has been associated with a high error rate of 17- 35%, compared to a low diagnostic error incidence of 1-3% in general histopathology. In lymphoma diagnosis, one half of the diagnostic errors result in significant clinical consequences such as delayed or inappropriate therapy, unnecessary treatment, avoidable morbidity and compromised survival.1 Inherent pathological ambiguity of lymphoproliferative processes, interpretational subjectivity, unfamiliarity with diagnostic criteria and novel entities, lack of expert opinion, inappropriate laboratory support and poor clinico-pathological correlation are the main reasons behind most pitfalls in this subspecialty.

Hodgkin lymphoma (HL) accounts for approximately 15% to 30% of all malignant lymphomas. According to current diagnostic criteria, approximately 90% to 95% of HLs fall into the Classical Hodgkin lymphoma (CHL) category; the remaining cases are nodular lymphocyte-predominant subtype of Hodgkin’s lymphoma (NLPHL) which is recognized as a separate entity in the World Health Organization (WHO) classification1. WHO classification is based on the fact that there are clear and consistent histologic, epidemiologic, immunologic, and genetic differences between NLPHL and CHL. NLPHL is an indolent germinal center (GC) B-cell malignancy, that represents a nodular proliferation comprised of a minority of large neoplastic centroblasts with multilobated nuclei, the so-called popcorn or lymphocyte-predominant (LP) cells. Immunohistochemically LP cells are CD20+, PAX5+, BCL6+, EBV-LMP1-, CD30- and CD15-. Background inflammatory infiltrate represent mixture of small B and T lymphocytes1. This type of tumour is characterised clinically by a relatively indolent course and a very good response to standard therapy in cases with low stage disease. Unfortunately, the prognosis is unfavourable for advanced stages2. CHL is also a clonal, malignant lymphoproliferation originating from germinal center B cells3. CHL has a bimodal age curve in western countries, showing a peak at 15-35 years of age and a second peak later in life at 45-60 years1. A histopathologic diagnosis of CHL is based on the identification of diagnostic Reed-Sternberg (RS) cells in an appropriate inflammatory background of mixed infiltrate by histiocytes, small lymphocytes, eosinophils, neutrophils, plasma cells, fibroblasts and colagen. Based on characteristics of the reactive infiltrate and the specific features of neoplastic cells, cases may be subclassified into one of four subtypes: nodular sclerosis (NSCHL), lymphocyte-rich (LRCHL), mixed cellularity (MCCHL) and lymphocyte-depleted classical Hodgkin lymphoma (LDCHL)1,4. Although most cases can be diagnosed on the basis of morphology alone, diagnostic criteria include the characteristic immunophenotype of the neoplastic population. RS cells and variants express the CD30 and CD15 antigens in the majority of cases and lack the common leukocyte antigen CD455,6. The LMP-1 protein of EBV is expressed in approximately 25% to 50% of CHLs depending on the histologic subtype and patient age7. The staining is membranous and cytoplasmic, and usually most neoplastic cells are positive. Etiology of CHL is still questionable, but due to the unique epidemiologic and clinical features of the disease, an infectious cause has long been suspected. Currently, immunohistochemistry for the EBV latent membrane protein-1 (LMP-1) and nonradioactive in situ hybridization for EBV-encoded early RNAs (EBERs) are the methods of choice for the detection of EBV in routinely fixed, paraffin-embedded tissues8. Recent data suggest that the EBV status of tumour cells in classical HL could have prognostic significance for patients with this heterogenous disease9.

Plasma cells (PC) are the terminally differentiated effector cells of the B-cell lineage. The aim of this review is to integrate relevant data on the phenotype of plasma cells, including reactive and malignant PC. The current World Health Organisation classification of lymphoid neoplasm is based on correlation of their morphologic, histologic, immunophenotypic, genetic and clinical features. The extensive application of imunohistochemistry is necessary in diagnosis of plasma cell neoplasm, but also in determining prognosis as well as in evaluating residual/ relapsing disease. This review focuses on immunohistochemical analysis non-neoplastic and neoplastic plasma cell proliferation in facilitating the diagnosis and highlights the recent advances that have been made with regard to their stratifying.

Koža vulve se razlikuje od koze drugih regija po različitoj bakterijskoj flori I uslovima trenja. Dermatološke bolesti vulvarne kože i mukoze se dele u dve grupe. Prvu grupu čine dermatoze slične ekstravulvarnim dermatozama, a drugu čine dermatoze koje zahvataju predominantno vulvarnu regiju. Spečificne dermatoze vulve su kontaktni dermatitis, lichen planus, lichen sclerosus. Infektivne bolesti vulve se mogu preneti direktnim kontaktom. Prepoznavanje tipičnih mikroskopskih karakteristika pomaze u dijagnostici scabiesa, herpes virusne infekcije i molluscum contagiosuma. Humani papilloma virusi (HPV) su epiteliotropni virusi i mogu uzrokovati premalgnu i malignu transformatciju epitelnih ćelija. Sledeći kriterijumi kao što su virusne promene, klinički parametri i mikroskopski nalaz upućuju na postojanje dva puta u karcinogenezi skvamoznog karcinoma vulve i to HPV-zavisni put udružen sa Vulvarnom intraepitelialnom neoplazijom/VIN/ klasičnog tipa i ne -HPV sa VIN diferentovanog (simlex) tipa često udruženim sa lichen sclerosusom i/ili vulvarnom hiperplazijom.Invazivni planocelularni karcinom je najčešći karcinom vulve. Procena prognostičkih faktora je neophodna komponenta patohistoloskog izveštaja. Visoki gradus tumora, vaskularna invazija, veće dimenzije tumora i dubina invazije zaslužuju imunohistohemijsku analizu limfnih čvorova radi nalazenja metastaskih ćelija karcinoma. Extramamarna Pagetova bolest je retka. Može biti primarnog kožnog porekla ili udružena sa nekožnim tumorima gastrointestinalnog ili porekla mokraćne bešike. Imunohistohemijskla analiza je važna za odredjivanje primarnog porekla tumora.

The latest version of uterine tumors classification was done in 2003. According to WHO classification, endometrial cancers are divided into two groups, so called Type I and Type II. Endometrioid adenocarcinoma has a higher frequency and belongs to Type I. Serous and clear-cell adenocarcinoma, are forming Type II and by definition, they are high grade cancers with poor prognosis and no clearly defined precursors and predisposing risk factors. In Type I, there is a PTEN mutation and in Type II overexpression of p53. These two biomarkers are used in their differential diagnosis.WHO has defined a three-step system in determining the grade of endometrioid adenocarcinoma in which squamous component has no significance. There are other, two-step, grading systems which are not generally accepted.2009 FIGO classification is still in use for tumor staging and according to that tumors confined to the uterus body are divided into stages IA and IB. In the group of mesenchyme tumors, undifferentiated sarcoma was separated, due to different morphology and immunohistochemical profile compared to leiomyoma and endometrial stromal sarcoma. New terms, like UTROSCT, are accepted as well as new theory about the origin of carcinosarcoma. Common believe is that these tumors have epithelial origin and therefore sarcoma component showed positivity on epithelial and mesenchymal markers too. Large number of new antibodies was discovered which in the diagnosis and differential diagnosis of uterine tumors are only meaningful when used in correlation with the clinical picture and morphological data (endometrial carcinoma vs. ovarian carcinoma, adenosarcoma vs. adenofibroma).

There is no doubt that obstetrics carries high medical liability risk. In many countries, gynecologists-obstetricians who attend childbirths and perform complex obstetric procedures are faced with increasing malpractice insurance premiums and litigation risk. The American College of Obstetricians and Gynecologists (ACOG) publishes its Survey of Professional Liability since 1983, with the objective to analyze the effect that malpractice litigation has had on the practice of obstetrics and gynecology in the United States1. According to the 2003 ACOG survey, 76.3% of the members who answered the questionnaire have been involved in a lawsuit at least once in their professional career; gynecologists/obstetricians have been sued a total of 2.64 times per individual over the course of their careers1,2. In the 2006 ACOG Survey, 89% of respondents indicated that they had been sued during their careers. The average number of claims per obstetrician was 2.6 (3). The ACOG’s 2009 Survey on Professional Liability showed that nearly 91% of gynecologists/obstetricians had experienced at least one liability claim filed against them during their professional careers, with an average of 2.69 claims per physician. In 2009, 62% percent of the total reported claims were for obstetric care as opposed to gynecology, the same as in the 2006 Survey3,4. In the 2003 ACOG survey, fetal monitoring, neurologically impaired children, neonatal death, shoulder dystocia, uterine rupture, and “decision-to-incision” time were identified as clinical factors frequently present in obstetric malpractice cases1. In both 2006 and 2009 Surveys the reasons for claim were neurologically impaired infant (in 31% of cases in both Surveys), stillbirth/neonatal death (with 16 % of cases in both Surveys), and delay or failure in diagnosis (in 11% of cases in 2009 vs. 14% in 2006)3,4. In all the Surveys, neurological impair is the leading cause of the reasons for liability claim, with the cerebral palsy being the most serious damage. The possible etiologies have been discussed for years, and although the damage to neural tissue is undebatable, there is still no agreement upon the timing of the damage. Some authors think that 90% of the cases of cerebral palsy are not due to intrapartum events, while in the opinion of others most of the devastating events occurred in the perinatal period5,6. It is still impossible to firmly determine in each single case whether the hypoxic insult has developed during delivery, in the first few hours after birth, or was already present before the labor began, as a consequence of long lasting hypoxia during pregnancy. Careful gross and histopathological examination of the placenta in chosen cases can elucidate the events that occurred some time before labor, and help to connect and reconstruct the course of disease7,8.

Gestational trophoblastic disease (GTD) is a term used for a group of pregnancy-related tumours, overwhelmingly affecting women of childbearing age. These tumours are rare, and they appear when trophoblastic cells start to grow out of control. In these conditions production of beta subunit of human chorionic gonadotropin (hCG) is evident. Hydatidiform moles, partial or complete, are in most cases benign featured by villous hydrps, scalloping effect, hyperplastic trophoblastic pseudoinclusions and syncytiotrophoblastic sprouts. Invasive mole is an aggressive trophoblastic lesion with myometrial and/or vascular invasion. Choriocarcinoma, placental site trophoblastic tumor and epitheloid trophoblastic tumor are clearly malignant tumors with proliferation of intermediate trophoblast, with metastatic potential. Tumor-like trophoblastic conditions are placental site nodul and exaggerated placental site wich are proliferative lesions and reactive processes and are not considered as true tumor lesions.In all of these conditions vaginal bleeding is the most common symptom followed by elevation of serum beta hCG. GTD has to be confirmed histologically with extensive sampling of the material. Follow up is necessary in all women with GTD and it is rutinley done by measurment of serum levels of hCG. Since GTDs are proliferative conditions of diferent trophoblastic tisues, pathologists should be well histologicly educated about normal pregnancy stages and its abnormalities in order of adeqate diagnosing these rare conditions.

The major goals of this presentation are to give the updated knowledge of primary heart muscle disease, cardiomyopathies (CMP), their classification, the diagnostic possibilities using endomyocardial biopsy (EMB) and to estimate the value of EMB in the choice of the right therapeutic approach. Despite many controversies, EMB is today a widely accepted method, with low percentage of complications for analysing CMPs, and is considered to be a routine procedure in many cardiological centers. Inspite the fact that we started with the use of EMB in 80’s, it is not performed often today in Belgrade, like many yeras ago (2). It’s difficult to say why ? The CMPs may be subdivided, according to the functional and structural features, into two groups: idiopathic and specific, or primary and secundary. Idipathic group is consisted of 5 subgroups: hypertrophic, dilated, restrictive, arrithmogenic right ventricular CMP and unclassified. Specific CMPs may be subdivided into 8 groups mainly based on etiopathogenetic characteristics: infective, with viral myocarditis as the most common entity, metabolic, including endocrine disorders and infiltration and storage diseases. Deficiency disorders and heart involvement in connective tissue disorders are also included. Granulomas, neoplasms and neuromuscular disorders are also wery often presented with cardiac disfunction and structural abnormalities. Sensitivity and toxic reactions with long list of substances wich may affect the heart are probably the most present today. Finally, the last group represent miscellaneous systemic syndromes with heart affection. EMB has been increasingly used in the diagnosis of CMPs, with special influnce on diagnosis of heart transplant rejection, myocarditis, treatment modalities of different types of myocarditis, with low complication rate, considered effective, usefull and safe procedure.

In this paper we present the experience with 162 consecutive neuromuscular biopsies analyzed in the period from 2009 to 2012. Neuromuscular diseases are a large group of inherited and acquired diseases that are characterized by loss of muscle mass and muscle weakness. Distinguishing myopathies from peripheral neuropathy, diseases of the anterior horn cells of the spinal cord and the diseases of the neuromuscular junction requires careful clinical evaluation, laboratory, neurophysiological and electromyographical examination, radiological tests, muscle biopsy and genetic testing. Muscle biopsy results can solely be interpreted in the context of the above tests. In Serbia, 2009. in Department of Clinical Pathology Clinical Hospital Center Zemun, a decision by the Serbian Ministry of Health, began a routine diagnostic biopsy specimens in the NMB muscles, nerves and skin.

The balance between analytical (low) and clinical (high) sensitivity is crucial for the specificity of a routine HPV test as limited specificity will be harmful due to unnecessary treatment of healthy women. Up to now HPV diagnostics is mainly based on DNA detection for which target and signal amplification methods are available. PCR techniques can be divided into type-specific and consensus PCRs. Due to its high clinical sensitivity and its relatively high specificity the HC2 test is still regarded as the gold standard in routine HPV testing. It hybridizes 13 (near) full-length stabilized RNA probes of high-risk HPV types to denatured target DNA followed by detection via antibodies and chemiluminescence. To avoid costly validation studies for each new HPV test standards for evaluation have been defined. Recently several new HPV detection assays have been commercialized. They all show promising data in first published studies but still await full validation according to the criteria mentioned above. Among them only the cobas HPV test has already been fully validated for use in triage and as adjunct to cytology. HPV 16 and 18 confer a much higher risk for development of a CIN 2+ compared to the other HPV high-risk types. It is therefore appropriate to test for these HPV types independently. Apart from that testing for individual HPV types is of very limited clinical value up to now.HPV RNA testing is a promising option with potentially higher specificity. As a first system, the APTIMA test has now received an FDA approval.