Clinical and therapeutic considerations of GIST.

Gastrointestinal stromal tumors (GIST) are rare tumors of the digestive tract, with an incidence of about 1.5 per 100,000/year. Clinical features may vary depending on location, size and aggressiveness. The diagnosis is confirmed by immunohistochemistry tests that identify CD 117 or DOG1 (typical receptors/markers for most GISTs) at the level of biopsy specimen. The treatment of localized GIST is based primarily on the surgery, while for metastatic GIST the targeted therapy with tyrosine kinase inhibitors represents the current standard. The neoadjuvant and adjuvant therapy indications guided and depending on genetic analysis included in the diagnostic and treatment algorithm as well as the strategy for cases surveillance are listed in the journal. All these data obtained from the literature have been integrated in a practical experience of 19 cases of GIST, operated in the clinic in the last 10 years for which we have proposed an adapted diagnostic algorithm.

Prognostic significance of KRAS gene mutations in colorectal cancer--preliminary study.

OBJECTIVE: The prognostic significance of KRAS gene mutations, evaluated by using two methods in patients with colorectal cancer (CRC). MATERIAL AND METHODS: Retrospective study involving 58 patients diagnosed with CRC and treated between 2003 and 2010 in the General and Esophageal Surgery Clinic of "Sf. Maria" Hospital, Bucharest. The macroscopic and microscopic examination of the resected specimens was also processed for genetic analysis in NIRDPBS, where KRAS status was determined by using two methods: PCR-RFLP and pyrosequencing. RESULTS: The clinical and biological parameters of the patients were assessed for 72 months in average. A relapse in 21 patients and a 5-year survival rate of 79.3% was discovered. The genetic analyses of KRAS gene found mutations in 22 cases (45.3%): 17 cases had mutations in codon 12, 5 cases in codon 13. The survival rate analyses of patients with wild KRAS gene compared with the patients carrying the mutation on codon 12 /13 revealed a superposition of the survival curve. The statistical analysis based on the TNM stage revealed different survival curves in stage I and II, shorter survival period in patients with KRAS mutation on codon 13 than in those with wild type gene (stage I--p_value=0.015; stage II--p_value=0.000). CONCLUSIONS: It was not found that KRAS gene status had any prognostic significance. Nevertheless, for stage I and II patients, the mutation found on codon 13 determined a statistic significant shorter survival rate than for those with wild type. The results obtained by using the pyrosequencing method for the determination of KRAS gene status proved that it represented a reliable and reproducible method.

Clinical diagnosis of cardiac involvement in HIV infection.

HIV infection is continuously raising, and different treatments did not manage to extend the patient's life. Clinical and morphopathological features of respiratory, gastrointestinal, hematological and nervous system are well characterized in HIV infection, but cardiac involvement is not so well known. Cardiac involvement is extremely rare in HIV disease, but demonstrated by echocardiography and anatomo-pathologic methods, it is more frequently met than the clinical features are supposed to be, and it can be demonstrated by positive serologic tests.The main reason of this research is the necessity to obtain data from HIV infection concerning heart involvement.

[Synchronous gastrointestinal stromal tumor (GIST) and multiple digestive neoplasms, benign and malignant]. / Tumora gastro-intestinala stromala (GIST) asociata sincron cu multiple neoplazii digestive benigne, precursoare si maligne.

Gastrointestinal stromal tumors (GIST) are a broad category of mesenchymal, non-epithelial primary tumors of the digestive tract, located in the wall of hollow viscera, from the esophagus to the anus and often in adjacent mesentery and omentum. They are clinically unpredictable (may be discovered incidentally during an imagistic investigation or during surgery for other pathological entity, or at necropsy) and also have an unpredictable behavior (GISTs with very low risk, with low or moderate malignancy, which have benign histopathologic features but can recurr or can metastasize). The case we present here represents a rare association between a synchronous gastrointestinal stromal tumor (GIST) and multiple gastric benign and malignant tumors.

IL-17 in cutaneous lupus erythematosus.

BACKGROUND: Lupus erythematosus (LE) is a heterogeneous disease with broad clinical spectrum from cutaneous to visceral and systemic inflammation. IL-17 isoforms (IL-17A and IL-17F) are proinflammatory cytokines with unclear implications in lupus erythematosus pathogenesis. In this study we focused upon IL-17 in normal and modified lupus skin with a correlative study between local and serological expression. MATERIAL AND METHODS: 89 subjects were recruited and divided in 5 groups-10 patients with psoriasis (disease control group), 13 healthy controls, 26 with discoid chronic lupus (DLE), 23 with systemic lupus erythematosus (SLE) and 17 with subacute lupus erythematosus (SCLE). Blood samples and skin punched-biopsy specimens were performed. Serum IL-17A, IL-17F, and IL-23 concentrations were determined by ELISA. Skin IL-17A and CD4 expression were evaluated by immunohistochemistry. RESULTS: Immunohistochemical expression of IL-17A was higher in DLE, SCLE and SLE patients than in negative control subjects (all p<0.05). Serum IL-17A concentrations were higher in DLE and SLE patients than in negative controls (p<0.05). Serum IL-17A levels were similar in SCLE and negative controls (p>0.05). Serum IL-17F concentrations were higher in DLE, SCLE and SLE patients than in healthy controls (all p<0.05). In DLE, SCLE, SLE patients and healthy controls we observed comparable levels of IL-23 (p>0.05). Serum anti Ro antibodies correlate with IL-17A+ lymphocytes from SCLE lesion and SLE normal skin (all p<0.05). CONCLUSION: IL-17 isoforms (IL-17A and IL-17F) are implicated in SLE but also in DLE and SCLE immunopathogenesis.

Angiocentric glioma: presentation of two cases with dissimilar histology.

OBJECTIVE AND IMPORTANCE: Angiocentric glioma (AG) is a recently described tumor of the brain which was included as a distinct entity in the 2007 WHO classification. To date only 26 cases have been reported in the literature. We describe two additional cases of this possibly confusing lesion of the brain. Emphasis is put on variations in the histopathological picture. CLINICAL PRESENTATION: The patients (20- and 55-year-old males) presented with seizures and headaches, respectively. Imaging examination showed a small cortical-subcortical tumor in each case. Both tumors were totally removed. MATERIAL AND METHODS: Paraffin blocks from the two cases were examined with classical histopathology stainings and immunohistochemistry for GFAP, vimentin, EMA, neurofilament protein, synaptophysin, S100 protein, CD31, CD34, FVIII, smooth muscle actin and Ki67. RESULTS: The tumor proliferation was restricted around small intraparenchymal vessels. Immunohistochemistry demonstrated positivity for glial and negativity for vascular or neuronal markers. The cell shape and arrangement was different in the two cases. CONCLUSIONS: AG is a peculiar tumor of uncertain histogenesis but with certain glial reactivity. Histopathology is variable but restricted, for unknown reasons, to perivascular areas. Apparently, a better prognosis than for other gliomas is distinctive. Further studies are needed in order to expand the information regarding the clinical behavior and therapeutic approach of this tumor type.

Meningeal melanocytosis in a young patient--an autopsy diagnosis.

Primary diffuse leptomeningeal melanocytosis is a very rare form of brain tumor. We report on a rapidly fatal case in an 18-year-old man presenting with symptoms and imaging features suggestive for subarachnoid hemorrhage or meningitis. The laboratory findings and imaging examination were still confusing and the diagnosis remained unclear during the patient's life. Autopsy was the cornerstone in disclosing the lesion, confirming its usefulness in the assessment of such unusual cases. The complete profile of the tumor was obtained only by histology and immunohistochemistry. Clinicians and pathologists must be aware of diagnosis difficulties in this rare disease which can represent a serious challenge in clinical practice.

[Gastric stromal tumors--Clinical and histopathological analysis of four cases]. / Tumori gastrice stromale--analiza clinica si histopatologica a patru cazuri.

BACKGROUND: The aim of this study is to present our experience concerning a rare form of gastric tumor--gastrointestinal stromal tumor (GIST). METHODOLOGY: We reviewed data of four patients with gastric stromal tumors, which have been admitted in our department from 1998-2002. RESULTS: There were two females and two males with age of 75, 70, 65 and 63 years old. The average duration of symptoms until hospital admission was 7 days. During surgery we discovered proximal gastric tumors with 4, 5, 10 and 20 cm in largest diameter. We performed excision of the whole tumor with a security limit of 2 cm or gastric resection (one case), without limphadenectomy. One patient developed an anastomotic fistula with a good evolution under conservative treatment. All patients left the hospital in a good condition. Histopathological and immunohistochemical study diagnosed gastric stromal tumors by identifying the CD 117 maker. Postoperatively neither one of our patients received chemotherapy or radiotherapy. One female and one male patient died of peritoneal metastasis at nine months and respectively two years after operation. The other two patients are in a good condition up to date, without metastasis, one and respectively three years after surgical treatment. CONCLUSIOUS: Correct diagnosis, complete tumor resection and surveillance are essential steps in management of gastric stromal tumors.

[Merkel cell carcinoma]. / Carcinomul cu celule Merkel.

Merkel Cell Carcinoma (MCC) is a rare and aggressive neuroendocrine dermal neoplasm. This study is a retrospective outcomes analysis of two cases of MCC with data regarding clinical, histopathological, immunohistochemistry and also surgical, chimio and radiological treatment. MCC is a rare dermal tumors, this tumors are most predictable found on sunexposed sites. Diagnosis is best accomplished by a thorough clinical evaluation coupled with light microscopy and defined panel of immunohistochemical studies which are necessary for the definitive diagnosis of Merkel cell carcinoma (cytokeratins, neuron specific enoiase and chromogranin). A lot of other disease must be included in the differential diagnosis. MCC is an aggressive tumor with local or locoregionale extension and distant spread by hematogen or lymphatic way. Surgical excision of tumor and regional lymphadenectomy is the first step of treatment completed with radiotherapy and chemotherapy bat in advanced studies the rate of local or distant recidives is high.

Cellular immune response in atypical tuberculosis diagnosed by PCR in paraffin embedded material.

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.

Morpho-functional aspects of the influence of procaine and diethylaminoethanol treatment on the immune system of rabbits.

Research was conducted in 24 male rabbits divided into three equal groups: 1) Controls; 2) Given daily i.m. injections with 15 mg/kg body weight of procaine for 30 days; 3) Given daily i.m. injections with 15 mg/kg body weight of diethylaminoethanol (DEAE) for 35 days. Blood samples were taken from the auricular vein to perform haematological investigations: before treatment, during treatment and for another 7 weeks after termination of treatment. At the end of the experiment, the animals were sacrificed in order to collect: 1) leukocytes, macrophages and lymphocytes from their spleen, for the purpose of immunological investigations, and 2) fragments of bone marrow (femur), thymus and spleen, for histopathological investigations. The result of haematological investigations indicated a statistically significant increase of circulating lymphocytes had occurred in rabbits treated with DEAE. There was an increase of percentage as well as of number of circulating lymphocytes. The increase occurred gradually in the course of treatment and continued after treatment was terminated. There were higher values than the initial ones by 44.4% and 66.4%, respectively, during the second and the fourth week after termination of treatment. Afterwards, the values started decreasing, so that by the end of the experiment (week 7 after termination), the values came close to those before treatment. Immunological findings indicated that T lymphocytes collected from rabbits treated with procaine or DEAE did not synthesize migration inhibition factors. Procaine and DEAE were found, in vitro, not to have a polyclonal stimulating effect over T lymphocytes. A study of blastic differentiation showed lymphocytes from treated rabbits to incorporate a larger amount of tritiated thymidine, by 52.6% in the procaine group and by 90% in the DEAE group, than those from non-treated rabbits. Histopathological examination indicated signs of a more intense activity in tissue formations involved in cell proliferation in the lymphoid organs collected from DEAE treated rabbits.

Histopathological aspects of pulmonary carcinoid tumors.

Pulmonary carcinoid tumors are considered low grade malignant tumors, arising from neuroendocrine cells from bronchial mucosa. The small cell proliferation is arranged in small nests or trabeculae, the nuclei are round to oval with finely dispersed chromatin, indistinct nucleoli, small amount of cytoplasm, indistinct borders. Problems of differential diagnosis could appear in distinction with others malignancies like adenocarcinomas, squamous cell carcinomas, lymphomas and others neuroendocrine tumors, especially in the different prognosis and therapeutic approach. We described 15 cases of pulmonary carcinoid tumors diagnosticated by morphologic and immunohistochemical methods.

Morphological and immunohistochemical features of tumor infiltrating lymphocytes (TIL) in carcinomas. Note I.

Some malignant tumours like testicular seminomas and ovarian dysgerminomas or medullar carcinoma of the breast, present an unusually lympho-histiocytic (TIL) rich stroma. Many reports have concluded that the prognosis for these patients is correlated with the intensity of TIL. Recently, some analyses consider that tumour-host interactions have a significant prognostic role in many other neoplasms. The presence of TIL may be a sign of less aggressive behaviour of some epithelial neoplasm like gastro-intestinal, pulmonary, mammary, urinary or cutaneous carcinomas (Wilson et al.). The aim of this study is a morphological and immunohistochemical (IHC) characterisation of the lympho-histiocytic populations of TIL in some gastro-intestinal and mammary carcinomas. The two localisation were chosen for their different contact with the exogene antigens and their possible different type of host's immune response.

Histopathologic and immunohistochemic correlations in virus B chronic hepatitis.

Complete diagnosis of chronic hepatitis relies on exploring the liver by bipsic punction, performing the classic histopathologic and immunohistochemic exams. We worked out viral antigens hepatocytes by using avidin-biotin-peroxidase complex technique as following: Ag HBs placed in cytoplasm or at the level of the cell membrane. Ag HBc preferably placed in nucleus and, a small part of it, in cytoplasm. Ag HD present especially in nucleus. A correlation between tissular antigen expression and hepatic histopathologic aspect was established. Two main types of viral expression were remarked: a regressive type reflected by cytoplasmatic Ag HBs in the absence of generalised nuclear Ag HBc--situations linked to persistent chronic hepatitis: an aggressive type characterised by the presence of the focal nuclear Ag HBc, cytoplasmatic Ag HBc or antigen HD--situations linked to active chronic hepatitis with various degrees of severity.

Calcifying odontogenic cyst: report of two cases and review of literature.

The "Histological Typing of Odontogenic Tumours" (W.H.O., 1992) classified the Calcifying Odontogenic Cyst (C.O.C.) into two variants: the non-neoplastic cystic C.O.C. and the odontogenic ghost cell tumour, which is predominantly solid. We reported two cases of C.O.C.: a case with intraosseous development and another with extraosseous localisation, in the soft tissue of the alveolar area. The first case represents a cyst delimited by a squamous, non-keratinized epithelium, thickened in some areas through the accumulation of ghost cells (big pale-staining cells with a non-staining nuclear area). The connective tissue wall contains small ameloblastoma like islands. Dysplastic dentine islands, adjacente to the basal layer of the epithelium or in the connective tissue wall were also observed. The second case was a well-delimitated tumour consisting of ameloblastoma-like islands with numerous ghost cells inside. Islands of dysplastic dentine with psammomathous calcifications also exist. In certain histological sections microcystic aspects surrounded by ghost cells, dentinoid and ameloblastoma-like structures were noticed. The histochemical reaction for keratin and the immunohistochemical reaction for epithelial membrane antigen and for citokeratin were positive for ghost cells, suggesting their epithelial origin. Through this article we try to render pathologists sensitive with a particular and rare maxillary tumour.

Occurrence and significance of vascular invasion in multinodular adenomatous goiter.

Solitary follicular neoplasms of the thyroid gland are usually classified as adenomas or carcinomas according to two main criteria: vascular invasion and capsular penetration. No information is available on the occurrence of vascular invasion in multinodular goiter lesions, except for the case of a follicular carcinoma within a goiter. One thousand consecutive cases of multinodular adenomatous goiter were reviewed. After screening all H&E-stained slides, 5 patients with histological features typical of adenomatous goiter but displaying foci of vascular invasion at the periphery of the nodes were selected. A single vessel (2 patients) and 2-4 vessels (3 patients) at the periphery of different nodules were involved, with clusters of follicular cells lined by endothelium and partly filling the lumen. Clinical information was obtained from all patients: No recurrences or progressive disease were reported 14 to 16 years after operation. These findings indicate that presence of minimal vascular invasion, although a valuable criterion of differentiation in solitary follicular lesions of the thyroid, has little diagnostic importance in the setting of multinodular adenomatous goiter. It does not appear to justify a diagnosis of malignancy and does not indicate a need for further therapy.

Tumoral infiltrate after local treatment with interferon in squamous cell carcinoma.

Using monoclonal antibodies UCHL-1 (T lymphocytes), MT-1 (pan T) and L-26 (B lymphocytes) in the study of the tumoral infiltrate after local treatment with alpha interferon (Roferon) in patients with squamous cell carcinoma of the lower lip, it was observed that: the proportion of UCHL-1 positive cells was between 30% and 80%, the proportion of MT-1 positive cells was of 85% and that of the L-26 positive cells was of 30% of all the cells in the infiltrate. In the area in which after treatment with interferon the tumoral structures had disappeared, the proportion of T lymphocytes was smaller than in the areas in which the tumoral structures were still present. The therapeutic effect of interferon is due both to the direct effects on the tumoral cell and also to the indirect effects, namely the activation of the cytotoxic T lymphocytes and of other cells in the tumoral infiltrate.