Imaging features and radiologic-pathologic correlations of inflammatory pseudotumor-like follicular dendritic cell sarcoma.

BACKGROUND: Inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) is a rare tumor. This study aimed to reveal the radiological characteristics of IPT-like FDCS by radiologic-pathologic correlation. RESULTS: We analyzed two cases of IPT-like FDCS in the liver, nine in the spleen, and two in both the liver and spleen concomitantly. IPT-like FDCS presented as well-defined iso- or hypodense masses on unenhanced computed tomography (CT) images in both the liver and spleen. Hyperintensities on T1-weighted images and hypointensities on T2-weighted images with hypointense rings were characteristic features in splenic cases. "Halo signs" were observed in two out of three liver tumors. Hepatic lesions showed significant enhancement, whereas splenic lesions showed only mild enhancement. Delayed annular enhancement was observed in both liver and spleen cases. On ultrasonographic examination, IPT-like FDCS presented as hypoechoic lesions with enhancement similar to that observed on CT. Hyaline fibrous pseudocapsules, which correlated with the hypointensities on T2-weighted images, were microscopically observed at the tumor edge. IPT-like FDCS was characterized by an abundance of small blood vessels and capillaries. Capillaries were also found in the fibrous capsule of some IPT-like FDCSs, which may explain the delayed annular enhancement. CONCLUSIONS: The manifestations of IPT-like FDCS in the liver and spleen showed differences that warrant them to be approached differently during diagnosis. Characteristic radiological findings of IPT-like FDCS included different enhancement patterns between liver and spleen tumors and rim-like hypointensities on T2-weighted images, as well as annular enhancement on CT and magnetic resonance images. These imaging features correlated with tumor pathology.

[ANALYSIS OF COMPLICATIONS POSTOPERATIVE CAUSES AND MORTALITY AFTER RADICAL TREATMENT FOR TUMORS OF THE LEFT ANATOMICAL SEGMENT OF THE PANCREAS].

Radical surgery for tumors of the left anatomical and surgical segment of the pancreas proved for distal resection in various versions, central resection and enucleation of tumors. The causes of early postoperative complications and mortality in 129 patients aged from 14 to 81 years, operated on for neoplastic lesions of the left anatomical segment of the pancreas in the period from 2009 to 2014 were analysed. The influence of various factors of risk of complications and mortality were studied in particular, extended resection, for tumor invasion of adjacent organs, and adjacent vessels.

Hematogenous Splenic Metastases as an Independent Negative Prognosis Factor at the Moment of Primary Cytoreduction in Advanced Stage Epithelial Ovarian Cancer--A Single Center Experience.

Ovarian cancer represents an aggressive gynecological malignancy with a high capacity for dissemination. Once the tumor cells go beyond the pelvic area, upper abdominal involvement, including hepatic, diaphragmatic or even splenic, is frequently seen. The aim of the present study was to determine the impact on survival of parenchymatous versus peritoneal splenic metastases versus splenic hilum lymph node involvement at the time of primary cytoreduction for advanced-stage epithelial ovarian cancer. Sixty-six patients with a mean age of 54.12 years (range=25-80 years) were submitted to splenectomy in the context of primary cytoreduction at the Dan Setlacec Center of Gastrointestinal Disease and Liver Transplantation, Fundeni Clinical Institute, between January 2002 and May 2014. Although complete macroscopic resection was attempted in all cases, an R0 resection was achieved only in 57 out of the 66 cases. Histopathological studies confirmed the presence of serous subtype in 61 cases, while in the other five cases, the mucinous subtype was found. When studying the specimens of splenectomy, capsular invasion was found in 35 cases (53%), parenchymatous involvement was present in 19 (28.7%), and hilar involvement was present in 12 (18.1%). The overall morbidity rate was 30%, while the 30-day postoperative mortality rate was 7%. The median overall survival for cases with peritoneal seeding was 58.4 months, while that for patients with parenchymatous involvement was 24.5 months (p=0.0126); patients diagnosed with hilar involvement had a median overall survival of 40.6 months (p=0.362). In conclusion, the presence of parenchymatous splenic metastases at primary cytoreduction for advanced-stage ovarian cancer is associated with significantly poorer survival when compared to hilar or peritoneal seeding.

Distinctive immunohistochemical staining in littoral cell angioma using ERG and WT-1.

Littoral cell angioma (LCA) is a rare vascular tumor of the spleen. It has an immunohistochemical staining pattern that is somewhat distinctive but can still be occasionally confused with other vascular and stromal proliferations in the spleen. In this study, LCA was evaluated using Ets-related gene (ERG) and Wilms tumor-1 (WT-1), relatively recently described vascular markers. In addition, other vascular lesions including normal spleen, hemangiomas, hamartoma, peliosis, and sclerosing angiomatoid nodular transformation were evaluated using these stains. In LCA, ERG stains the endothelial cells of the tumor as expected. ERG also was uniformly positive in vascular elements of other lesions except peliosis. However, in contrast to most other vascular elements, LCA was negative for WT-1 staining. This staining pattern may prove useful in diagnosing LCA and may provide insight into the derivation of the distinctive tumor.

[FIRST EXPERIENCE OF APPLICATION OF TECHNOLOGY OF A TWO-STREAM LOW-FREQUENCY ULTRASOUND TECHNOLOGY IN ABDOMINAL SURGERY].

Biophysical peculiarities of action on tissues of a two-strem low-frequency ultrasound (TSLFU) technology, elaborated by "Arobella Medical LLC" (USA) firm, were studied. Capacity of ultrasound to separate a pathologically-changed and healthy tissues, to divide the structures in accordance to their bioacoustical parameters constitutes the technology peculiarities. The presence of such a biophysical effect permits to achieve high resectability (R0) in patients with oncological diseases. Antibacterial effect and stimulation of intraorgan microcirculation with ultrasound irradiation were noted. Biophysical peculiarities of TSLFU were successfully applied in surgical treatment of 48 patients, suffering inflammatory and oncological diseases of the abdominal cavity organs.

DNA vaccination against membrane-bound Kit ligand: a new approach to inhibiting tumour growth and angiogenesis.

A functional c-Kit/Kit ligand (KitL) signalling network is required for tumour angiogenesis and growth, and therefore the c-Kit/KitL system might well be a suitable target for the cancer immunotherapy approach. We herein describe a strategy that targets membrane-bound KitL (mbKitL) via DNA vaccination. The vaccination procedure generated antibodies which are able to detect mbKitL on human tumour endothelial cells (TECs) and on the breast cancer cell line: TSA. DNA vaccination, interferes with tumour vessel formation and transplanted tumour growth in vivo. Histological analysis demonstrates that, while tumour cell proliferation and vessel stabilisation are impaired, vessel permeability is increased in mice that produce mbKitL-targeting antibodies. We also demonstrate that vessel stabilisation and tumour growth require Akt activation in endothelial cells but not in pericytes. Moreover, we found that regulatory T cells (Treg) and tumour infiltrating inflammatory cells, involved in tumour growth and angiogenesis, were reduced in number in the tumour microenvironment of mice that generate anti-mbKitL antibodies. These data provide evidence that mbKitL targeted vaccination is an effective means of inhibiting tumour angiogenesis and growth.

[Local level of neoangiogenesis factors in dynamics of experimental metastatic process in liver].

UNLABELLED: The aim--to study the dynamics content of VEGF-A, VEGF-R1, EGF and EGF-R1 in liver and spleen tissues from rats at different stages of liver metastases. MATERIALS AND METHODS: We have designed a model of liver metastases in male rats. The content of growth factors was examined by ELISA at 1, 2 and 5 weeks of carcinogenesis in tissue of liver and tumors of spleen. RESULTS: The content of growth factors increased in liver tissue at different stages of metastasis. The concentration of VEGF-A increased gradually from the 1st to 5th week carcinogenesis. The concentration of VEGF-R1 increased after 2 weeks and decreased slightly after 5 weeks of carcinogenesis. The level of all components of EGF/EGF-R1 increased after 2 weeks of carcinogenesis. CONCLUSION: The following pathogenetic aspects of liver metastasis were defined: change in levels of VEGF-A/VEGF-R1 indicating the progressive development of the process of neoangiogenesis, and increased levels of EGF/EGF-R1 responsible for metastasis processes.

Sclerosing angiomatoid nodular transformation of the spleen related to IgG4-associated disease: report of a case.

Sclerosing angiomatoid nodular transformation (SANT) of the spleen is a rare benign vascular mass, with fewer than 100 cases documented. It is generally recognized as a vascular lesion that develops in the red pulp of the spleen; however, its pathogenesis is not clearly defined. We report a case of SANT of the spleen, which presents evidence to support the hypothesis that this disease entity is associated with IgG4-associated disease. Microscopically, the tumor was composed of multiple vascular structures separated by fibrous connective tissue and immunohistochemical examination revealed positive staining for CD31, CD34, factor VIII, and IgG4. Further research based on large number of cases is warranted to clarify the pathogenesis of this tumor.

Canine splenic haemangiosarcoma: influence of metastases, chemotherapy and growth pattern on post-splenectomy survival and expression of angiogenic factors.

Splenic haemangiosarcomas (HSAs) from 122 dogs were characterized and classified according to their patterns of growth, survival time post splenectomy, metastases and chemotherapy. The most common pattern of growth was a mixture of cavernous, capillary and solid tumour tissue. Survival time post splenectomy was independent of the growth pattern; however, it was influenced by chemotherapy and metastases. Immunohistochemical assessment of the expression of angiogenic factors (fetal liver kinase-1, angiopoietin-2, angiopoietin receptor-2 and vascular endothelial growth factor A) and conventional endothelial markers (CD31, factor VIII-related antigen) revealed variable expression, particularly in undifferentiated HSAs. Therefore, a combination of endothelial markers should be used to confirm the endothelial origin of splenic tumours.

Color and power Doppler ultrasonography for characterization of splenic masses in dogs.

Benign and malignant splenic masses can appear similar on B-mode imaging, making ultrasound sensitive but not specific in their diagnosis. Our goal was to characterize color and/or power Doppler characteristics of vasculature within and adjacent to a splenic mass, which would distinguish benign vs. malignant lesions. The hypothesis was that malignant splenic masses will have altered vascular patterns compared with benign masses. Color and power Doppler cineloops evaluating the vasculature within the mass and normal splenic parenchyma were obtained in sagittal and transverse planes using a standardized protocol. Categories of evaluation included presence of peritoneal effusion, a large aberrant or tortuous vessel within the mass, relative blood flow within the mass compared with normal parenchyma, and path of vessels in the adjacent parenchyma entering into the mass. All patients had histopathologic or definitive cytologic diagnosis. Thirty-one dogs were included. There were 13 malignant masses and 18 were benign. Peritoneal effusion was significantly associated with malignancy (P = 0.0007). Presence of an aberrant or tortuous vessel within the mass was nearly significant (P = 0.059). There was no significant difference in any of the color or power Doppler blood flow evaluations. Ultrasonographic findings of a splenic mass and peritoneal effusion may indicate malignancy. The presence of an aberrant vessel within a splenic mass could suggest malignancy; however more data are needed.

Contrast enhanced sonographic assessment of feeding vessels as a discriminator between malignant vs. benign focal splenic lesions.

Contrast-enhanced sonography was conducted in 17 confirmed focal splenic lesions (five malignant, 12 benign). Relative echogenicity changes were used for subjective interpretation of lesion perfusion. A rapid influx of contrast agent, resulting in an increased relative echogenicity of the lesion, followed by a rapid clearance of contrast agent was referred to as early washin/early washout. There were 6/12 benign, and 3/5 malignant lesions characterized by early washin/early washout. Therefore, sensitivity, specificity, and accuracy for this parameter in differentiating malignant from benign lesions was 60%, 50%, and 53%, respectively. There were 2/12 benign, and 2/5 malignant lesions with persistent hypoperfusion throughout all phases. Therefore, sensitivity, specificity, and accuracy for malignancy using this criterion were 40%, 83%, and 71%, respectively. However, none of the benign and all malignant lesions were characterized by tortuous and persistently visible feeding vessels. This suggests that interpretation of splenic lesions cannot be performed accurately on the basis of echogenicity or persistent hypoperfusion, but that assessment of vascular tortuosity may be helpful in discriminating between a malignant vs. benign focal splenic lesion.

Extremely weak tumor-promoting effect of troglitazone on splenic hemangiosarcomas in rasH2 mice induced by urethane.

To examine the tumor-promoting effect of troglitazone (TRG), a novel thiazolidinedione insulin-sensitizing agent, on splenic hemangiosarcomas in rasH2 mice, histopathological and molecular analyses were performed in the spleen of female rasH2 mice fed a diet containing 6,000 or 0 ppm TRG for 16 weeks after 1,000 or 0 mg/kg urethane (UR) initiation. Histopathologically, splenic hemangiosarcomas were observed in the UR-alone and UR + TRG groups, but there was no significant difference in the incidence of splenic hemangiosarcomas between the UR-alone and UR+TRG groups. There were increasing tendencies in the number of positive cells for anti-PCNA antibody and gene expression in the UR + TRG group, but such a change was not statistically significant as compared to that in the UR-alone group. The gene expressions of VEGF, VEGFR1, VEGFC, VEGFR2 and Tie2 related to angiogenesis; c-fos related to MAPK cascade activation; and cyclin D1 related to cell cycle in the UR-alone and UR + TRG groups were significantly higher than those in the untreated control group. However, only the Tie2 gene in the UR + TRG group was significantly increased as compared to that in the UR-alone group. These results suggest that the vascular tumor-promoting activity of TRG in rasH2 mice is extremely low in the present experimental condition and a part of the gene related to angiogenesis probably contributes to the promotion of splenic hemangiosarcomas in rasH2 mice given TRG.

Color Doppler sonographic findings in focal spleen lesions.

UNLABELLED: Since focal lesions of the spleen are rare (0.2%), there is little data concerning color Doppler images of focal lesions of the spleen. OBJECTIVE: The aim of this study is to describe the color Doppler images of 98 etiologically proved focal spleen lesions. METHODS: In about 110,000 consecutive abdominal ultrasound examinations, which included the spleen, 600 patients with focal lesions of the spleen were identified. In 98 of these patients a color Doppler scan of the lesion was performed and documented. These scans were analysed retrospectively and classified as avascular, hypovascular, isovascular, hypervascular and arterio-venous "high flow", using the surrounding spleen tissue as an in vivo reference. RESULTS: In color Doppler sonography (CDS) 68.4% (n=67) of the focal spleen lesions showed no flow. 15.3% (n=15) appeared hypovascular, 8.2% (n=8) isovascular, 5.1% (n=5) hypervascular, and in 3.1% (n=3) an arterio-venous "high flow"-pattern was found. CONCLUSIONS: In CDS about two thirds (68%) of focal spleen lesions appear to be avascular. Except from diagnosis of intra-splenic pseudo-aneurysm, the practical utility of CDS in diagnosing focal spleen lesions has to be estimated as low.

Intestinal obstruction caused by infarcted splenic hemangioma with renal vein thrombosis in a newborn: a case report.

The spleen in newborns, infants, and children is rarely involved in a variety of pathological processes. These processes may involve an isolated splenic disease or may be a part of a systemic illness. Renal vein thrombosis in infants of diabetic mothers has been reported. We report a case of a newborn with intestinal obstruction caused by an infarcted splenic hemangioma and renal vein thrombosis. To the best of our knowledge, this is the youngest case with both above-mentioned diagnoses and causes of intestinal obstruction in the English medical literature.

Littoral cell angioma associated with portal hypertension and resected colon cancer.

Littoral cell angioma (LCA) is a rare vascular tumor of the spleen with an unknown etiology and unclear natural history. An association with synchronous malignancy has been described. We report the case of a 54-year-old woman who had progressive splenomegaly over 3 years following resection of a colon adenocarcinoma. The splenomegaly was associated with portal hypertension and severe thrombocytopenia. Splenectomy was performed, and the histologic and immunocytochemical features of the spleen specimen were consistent with LCA. The relationship between LCA and malignancy is reviewed.

Effect of all-trans retinoic acid on growth of xenograft tumor and its metastasis in nude mice.

OBJECTIVE: To study the effect of all-trans retinoic acid on growth of xenograft tumor and its metastasis in nude mice. METHODS: Human gastric cancer BGC-823 and MKN-45 cells were inoculated into spleen subcapsule of nude mice, respectively. The nude mice were subsequently administered with all-trans retinoic acid every other day. Food consuming and body weight of nude mice were measured weekly. Six weeks later, the nude mice were killed. Xenograft tumors in spleen and metastatic tumors in liver were pathologically examined. Microvessel density in the tumors was detected immunohistochemically, and serum carcinoembryonic antigen was measured by radioimmunoassay. RESULTS: After the nude mice were fed with all-trans retinoic acid, the growth of splenic tumor and its liver metastasis were inhibited and the metastatic rates decreased by 50% (BGC-823) and 33.3% (MKN-45), respectively. The microvessel density in splenic and hepatic tumors reduced by 28.58% and 35.47% (BGC-823), 19.45% and 14.52% (MKN-45), respectively. The concentration of carcinoembryonic antigen decreased by 50.24% (BGC-823) and 48.10% (MKN-45). CONCLUSION: All-trans retinoic acid may effectively inhibit the growth of xenograft tumor in spleen and its metastasis to liver in nude mice, which can be corroborated by the decrease of carcinoembryonic antigen and microvessel density.

Hemangioendothelioma of the spleen: imaging findings at color Doppler, US, and CT.

The ultrasonographic, color Doppler, and computed tomography findings of an unusual vascular primary tumor of the spleen are reported. A brief clinical and histopathological analysis of this entity is discussed and the differential diagnosis of other primary lesions of the spleen is attempted.

Hereditary melanoblastoma in miniature pigs and its successful therapy by devitalization technique.

Applying selective breeding for 10 years we established the MeLiM (Melanoblastoma-bearing Libechov Minipigs) strain. Melanoblastoma (MB) in this strain shows a hereditary occurrence. Cutaneous tumours are usually nodular, multiple and distributed on various parts of body. They appear in darkly pigmented animals already at the birth or during two months thereafter (57% of all animals). Numerous organ metastases mainly into the spleen, lymph nodes and lungs are regularly ascertained in animals with cutaneous MB. Tumour cells were surprisingly found also in the inner organs of phenotypically healthy minipigs in which no cutaneous MBs were observed visually (27% of all animals). About 34% of all affected piglets die during the first 2 months of age. These features document a malignancy of this tumour in the MeLiM strain. Original surgical technique was applied in more than 40 affected minipigs at 1-2 months of age. It consists in a devitalization (ischemization) of one of cutaneous tumours by the mattress sutures conducted around the tumour base without any excision of tumour tissue. This simple procedure causes a total destruction of MB cells in all cutaneous tumours as well as in all organ metastases during 4-6 months. Animals treated by this technique were fully healed of tumour cells and no relapses were observed. This technique could bring similar positive results also in therapy of human MB.

Immunohistopathological characterizatin of spontaneous metastases in a human lung mucoepidermoid adenocarcinoma (HLMC) xenograft.

The most common clinical form of lung cancer is a disseminated disease with distant metastases; several years of cancer progression precede presentation, and this ultimately limits the efficacy of curative therapy. In this immunohistochemical study, we examined a mucinous adenocarcinoma cell line, maintained by xenogeneic transplantation, and a spontaneous metastatic variant which produces distant tumors (in liver, spleen and kidney). The aim was to investigate possible parameters which characterize the metastatic process. Histopathological comparison between the two subcutaneous transplanted tumor lines showed that both lines presented a similar cellular morphology, a different pattern of cellular growth and an increased vascularization in the metastatic line with respect to its parent. All the tumor sections expressed differential immune reactivity with monoclonal antibodies against Lewis y (MAb C14), sialyl-Lewis x (MAb SNH3) and Lewis x (MAb FH2) determinants. Neither expressed MUC 1 mucins detectable with monoclonal antibodies reactive with the mucin protein core (MAbs C595 and SM3) nor was carcinoembryonic antigen (MAb C365) expressed. Neoplastic cells were reactive with an anti-pan cytokeratin monoclonal antibody confirming their epithelial histogenesis. Our findings have been evaluated with respect to defining metastatic phenotypes in lung cancer by examination of distinct histopathological and immunological parameters.