Pleomorphic Tumor Research Articles

PO12 Salivary gland type carcinoma arising from recurrent pleomorphic adenoma-like tumour of the breast

PO12 Salivary gland type carcinoma arising from recurrent pleomorphic adenoma-like tumour of the breast

Unresectable hepatic PEComa: a rare malignancy treated with stereotactic body radiation therapy (SBRT) followed by complete resection

BackgroundPerivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors occurring in various anatomic regions. Although diagnostic criteria and treatment management are not established, current treatment options consist of surgery and chemotherapy including mTOR inhibitors.Stereotactic body radiation therapy (SBRT) is a non-invasive ablative treatment which has shown excellent control rates for more common types of unresectable liver tumors and metastases. In this report we present a rare case of PEComa of the liver that was treated by stereotactic radiotherapy followed by resection. Staging and evaluation of treatment response was done by FDG-PET/CT. This case highlights the potential of SBRT as a neoadjuvant treatment even for rare liver malignancies. It is the first case of liver PEComa treated by SBRT and resection.Case presentationA 52-year-old woman presented at an external hospital with abdominal pressure and pain in the right upper abdominal quadrant. A CT scan showed a 700 cm3 liver lesion in segment IV. In repeated biopsy in July 2015 histopathological workup showed a pleomorphic epitheloid tumor with small to medium sized cells expressing vimentin and melan-A while being negative for cytokeratin establishing the diagnosis of PEComa of the liver.To achieve high, ablative doses a stereotactic body radiotherapy (SBRT) technique was chosen consisting of 60Gy (biologically effective dose 105Gy) in 8 fractions of 7.5Gy. Radiotherapy planning was based on MRI resulting in a planning target volume (PTV) of 1944 cm3. Treatment toxicity was limited to a slight elevation of transaminases (grade 1 and 3). A complete resection was performed 21 weeks after radiotherapy confirmed by negative surgical margins.At last follow-up 21 months after therapy, MRI showed neither local nor distant tumor recurrence. The patient was in stable condition (ECOG 1) and without late radiation toxicity.ConclusionsThis is the first documented case of liver PEComa treated by SBRT and resection. A favorable post-treatment course demonstrates that SBRT is a potential neoadjuvant treatment that is capable of reducing an inoperable rare liver tumor to a resectable lesion.

Primary splenic angiosarcoma with liver metastasis: A rare neoplasm diagnosed on fine-needle aspiration cytology and cell block immunocytochemistry

Primary splenic angiosarcoma is a rare malignant vascular neoplasm of mesenchymal origin. The tumor is highly aggressive and has a high metastatic potential. It is usually diagnosed on histopathological examination of splenectomy specimen. Only few cases of angiosarcoma diagnosed by fine-needle aspiration (FNA) cytology alone have been reported in the literature. The cytologic features of angiosarcoma are heterogeneous, however, diagnosis can be suggested by FNA when vasoformative features are present. A 55-year-old female presented with abdominal pain and hepatosplenomegaly. Computed tomography scan revealed a heterogeneous splenic lesion with liver metastases. FNA from the splenic and liver lesions showed moderately pleomorphic tumor cells closely associated with anastomosing vascular channels. Cell block immunocytochemistry (ICC) showed tumor cells positive for CD31, CD34, CD68 as well as for CD99. FNA supplemented by cell block ICC can render a definite diagnosis of primary splenic angiosarcoma with liver metastasis.

Calvarium mass as the first presentation of glioblastoma multiforme: A very rare manifestation of high-grade glioma

Glioblastoma multiforme (GBM) is a high grade glial tumor, primarily located in cerebral hemispheres. The most common clinical presentations are slowly progressive neurological deficit such as motor weakness, seizure, and headaches that last less than three months. Calvarium and extra-axial invasion are very rare and generally occur after a brain biopsy or surgery, or secondary to radiotherapy of primary intra-axial glial tumors. We report a case of GBM with calvarium involvement in a 60-year-old man who presented with a frontal bump and left-sided clumsiness. Imaging studies revealed a tumoral lesion that destroyed the frontal bone with white matter involvement of the frontal lobe and extension into the corpus callosum. Histopathological examination of intra-axial and extra-axial lesions revealed pleomorphic high-grade tumor with large areas of necrosis and hemorrhage. Immunohistochemical (IHC) studies confirmed GBM that spread directly into the dura, galea, and calvarium (positive reaction for GFAP, S-100, CD68, OLIG2, and p53). The patient was treated with radiotherapy (60Gy/30 fractions) and concomitant temozolomide. Unfortunately, the patient died seven months after the initial diagnosis.

"Atypical" Pleomorphic Lipomatous Tumor: A Clinicopathologic, Immunohistochemical and Molecular Study of 21 Cases, Emphasizing its Relationship to Atypical Spindle Cell Lipomatous Tumor and Suggesting a Morphologic Spectrum (Atypical Spindle Cell/Pleomorphic Lipomatous Tumor).

The classification of the until recently poorly explored group of atypical adipocytic neoplasms with spindle cell features, for which recently the term atypical spindle cell lipomatous tumor (ASLT) has been proposed, remains challenging. Recent studies have proposed ASLT as a unique entity with (in at least a significant subset of cases) a specific genetic background, namely deletions/losses of 13q14, including RB1 and its flanking genes RCBTB2, DLEU1, and ITM2B. Similar genetic aberrations have been reported in pleomorphic liposarcomas (PLSs). This prompted us to investigate a series of 21 low-grade adipocytic neoplasms with a pleomorphic lipoma-like appearance, but with atypical morphologic features (including atypical spindle cells, pleomorphic [multinucleated] cells, pleomorphic lipoblasts and poor circumscription), for which we propose the term "atypical" pleomorphic lipomatous tumor (APLT). Five cases of PLS were also included in this study. We used multiplex ligation-dependent probe amplification to evaluate genetic changes of 13q14. In addition, array-based comparative genomic hybridization was performed on 4 APLTs and all PLSs. Multiplex ligation-dependent probe amplification showed consistent loss of RB1 and its flanking gene RCBTB2 in all cases of APLT. This genetic alteration was also present in all PLSs, suggesting genetic overlap, in addition to morphologic overlap, with APLTs. However, array-based comparative genomic hybridization demonstrated more complex genetic alterations with more losses and gains in PLSs compared with APLTs. APLTs arose in the subcutis (67%) more frequently than in the deep (subfascial) soft tissues (33%). With a median follow-up of 42 months, recurrences were documented in 2 of 12 APLTs for which a long follow-up was available. Herein, we also demonstrate that APLTs share obvious overlapping morphologic, immunohistochemical, genetic and clinical characteristics with the recently defined ASLT, suggesting that they are related lesions that form a spectrum (atypical spindle cell/pleomorphic lipomatous tumor).

Solitary Pancreatic Metastasis From Breast Matrix-Producing Carcinoma: A First Case Report

Introduction: Breast matrix-producing carcinoma (MPC) is a rare histologic type. Pancreatic metastases from breast cancers are also rare. We report the first case of solitary pancreatic metastasis from breast MPC, treated with distal pancreatectomy. Case presentation: A 56-year-old woman presented with a 56-mm mass in her right breast and a swollen right axillary lymph node. Both lesions had characteristic early ring enhancement on dynamic magnetic resonance imaging (MRI). Tumor biopsy revealed MPC. She underwent total mastectomy and axillary clearance. On histopathologic examination, the tumor was composed of extracellular matrix with areas of osseous and chondroid differentiation without spindle cells or osteoclasts, surrounded by a dense population of glandular epithelial tumor cells. On immunohistochemical analysis, the tumor cells were positive for AE1/AE3 and cytokeratin 5/6. The final diagnosis was breast MPC with axillary metastasis. Two years later, dynamic MRI displayed a mass in the pancreatic body with early ring enhancement, suspicious for solitary breast MPC metastasis. Distal pancreatectomy was performed. Histopathologic examination revealed bone and cartilaginous matrix with necrosis, surrounded by pleomorphic sarcomatous tumor cells. Tumor cells showed less cytokeratin positivity than the primary breast lesion. These findings were compatible with breast MPC metastasis. Conclusion: Solitary pancreatic metastasis from breast MPC has not yet been reported. Surgical resection of malignant pancreatic metastases is controversial; however, considering that breast MPC has limited responsiveness to radiotherapy and chemotherapy, curative resection would be important in this case. The histopathologic features of MPC may reflect enhancement and calcification on radiologic studies.

Pancreatic metastasis from invasive pleomorphic lobular carcinoma of the breast: a rare case report

BackgroundInvasive pleomorphic lobular carcinoma (PLC) is an aggressive subtype of invasive lobular carcinoma of the breast, which has its own histopathological and biological features. The metastatic patterns for PLC are distinct from those of invasive ductal carcinoma. In addition, pancreatic metastasis from PLC is extremely rare.Case presentationWe report a rare case of a 48-year-old woman presenting with clinical gastrointestinal symptoms and pancreatic metastasis of PLC. The pancreatic tumor was composed of pleomorphic tumor cells arranged in the form of solid sheets and nests and as single files, with frequent mitotic figures, nucleolar prominence, high nuclear to cytoplasmic ratio and loss of cohesion. The malignant cells were positive for p120 (cytoplasmic) and GATA3 and negative for estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, E-cadherin, gross cystic disease fluid protein 15 and mammaglobin, which indicated a lobular carcinoma phenotype of the breast.ConclusionsTo the best of our knowledge, this is one of the few reported cases in the literature of pancreatic metastasis of invasive lobular carcinoma of the breast, of which the definitive diagnosis was obtained only after surgery. Rare metastasis sites should be considered, particularly, when a patient has a medical history of PLC.

Adrenocortical Carcinoma Arising in an Adrenal Rest: a Case Report and Review of the Literature

Carcinomas arising from embryonic adrenal rests are rare with only a handful of reported cases. We report a case of an adrenocortical carcinoma arising from an adrenal rest located between the bladder and prostate in a 51 year-old man. The patient presented following a year of rectal pain and constipation. Computed tomography (CT) scan revealed a 9 cm pelvic mass that appeared to arise from the soft tissue between the bladder and prostate, with displacement of the organs and narrowing of the rectal lumen, suspected to be a sarcoma. The surgically resected specimen showed a well-circumscribed, partially encapsulated tumor measuring 10.0 cm in greatest dimension. Both adrenal glands were identified intraoperatively. Grossly, the lesion was heterogeneous tan-brown to yellow, hemorrhagic and necrotic. Histology revealed sheets and nests of high-grade pleomorphic tumor cells with abundant clear to vacuolated cytoplasm with areas of necrosis, a high mitotic index (>10 mitoses/10 HPF) and foci suspicious for lymphovascular invasion. Adjacent adrenal cortical-type tissue was identified. Immunohistochemical stains revealed the tumor cells were weakly and focally positive for MiTF, Melan-A, inhibin and synaptophysin, and negative for CKAE1/AE3, HMB-45, calretinin, EMA, SMA, chromogranin, PAX8, MDM2 and CDK4. Based upon the morphologic and immunohistochemical profile, this was diagnosed as an adrenocortical carcinoma, arising in an adrenal rest. To our knowledge, no such tumor has been previously described in this location.

P1.08-023 Analysis of Prognostic Factors and Long-Term Results of Primary Pulmonary Pleomorphic Carcinoma

Pulmonary pleomorphic carcinoma (PPC) is a rare neoplasm and factors affecting survival after pulmonary resection, as well as its clinical and pathologic characteristics, are still unknown. For a better understanding we reviewed our large experience with these patients. Records of patients 134 patients (108 men, median age: 65 years) with diagnosis of PPC operated on between January 1999 and May 2015 were retrospectively analyzed from a prospective database; survival was calculated by using Kaplan-Meier method. 86 patients (64.1%) were smokers. Median tumor size was 4.8 cm (range, 0.6 to 23 cm). Initial histological diagnosis was NSCLC in 88 cases, adenocarcinoma in 21, pleomorphic tumor in 13, and no diagnosis in 12. 62 patients (46.0%) received a platinum based induction chemotherapy. Surgery included lobectomy in 87 patients (65%), pneumonectomy in 27 (20.1%), wedge resection in 12 (8.9%), and segmentectomy in 8 (6%). Four patients (3%) had an incomplete resection. Postoperative staging included 45 stage I (33.6%), 47 stage II (35.1%), and 42 stage III (31.3%). 64 patients (47.7%) received adjuvant treatment. Five-year overall survival and disease-free survival were 36.6% and 35.7%, respectively (median, 28 and 18 months, respectively). Recurrences occurred in 76 patients (56.7%) most of them at distant sites (47/76 [61.8%]). Factors associated with increased survival included no smoke habit (p=.02), no induction therapy (p=.04), right side disease (p=.01); pathological stage I (p=.001), no metastatic lymph nodes (p=.001), and adjuvant treatment (p=.003). At multivariate analysis, pN0, pstage I, and adjuvant treatment were independent prognostic factors (p=.002, 95%CI: 1.54-6.43; p=.003, 95%CI: 1.23-7.32, p=.001, 95%CI: 1.26-4.72, respectively). PPC are aggressive tumors usually presented as a large lesion in males. Preoperative diagnosis remains difficult. Prognosis is poor, and distant recurrence rate is high. Long-term survival can be achieved in early stage disease and by an appropriate adjuvant therapy.

Subependymal Giant Cell Astrocytoma Presenting with Tumoral Bleeding: A Case Report.

We report a rare case of subependymal giant cell astrocytoma (SEGA) associated with tumoral bleeding in a pediatric patient without tuberous sclerosis complex (TSC). A 10-year-old girl presented with a 2-week history of an increasingly aggravating headache. Brain magnetic resonance imaging revealed an approximately 3.6-cm, well-defined, heterogeneously enhancing mass with multistage hemorrhages on the right-sided foramen of Monro. The tumor was completely resected using a transcallosal approach. Intraoperatively, the mass presented as a gray-colored firm tumor associated with acute and subacute hemorrhages. The origin of the mass was identified as the ventricular septum adjacent to the foramen of Monro. A pathological analysis revealed pleomorphic multinucleated eosinophilic tumor cells with abundant cytoplasm. These cells showed positive staining for the glial fibrillary acidic protein and S100 protein. A diagnosis of SEGA was established. The patient recovered without any neurological symptoms. There was no evidence of TSC. The radiological follow-up showed no recurrence for 2 years. This was a case of SEGA with intratumoral hemorrhage, for which a favorable outcome was achieved, without any neurological deficit after tumoral resection.

Amelanotic Signet Ring Cell Melanoma Presenting as Breast Lump- A Diagnostic Conundrum

Amelanotic signet ring cell melanoma is one of the rare variants of malignant melanoma. Here we are presenting a case of a 58-year-old female with chief complaints of swelling in the left sternal region/breast, and right cervical region. Contrast Enhanced CT scan showed the two well circumscribed lobular mass lesions with central necrosis in the left breast. The radiologist opined the lesions as intramammary nodes. Biopsy from the larger breast mass lesion showed a tumour with cells arranged in discohesive pattern less with hetrogenos morphology. These tumour cells had a predominantly signet ring morphology along with markedly pleomorphic tumour cells and giant cells. These tumour cells were negative for pan CK and positive for S100, HMB45. So the case was diagnosed as metastatic amelanotic malignant melanoma with signet ring morphology.

Assessing the clinical value of microRNAs in formalin-fixed paraffin-embedded liposarcoma tissues: Overexpressed miR-155 is an indicator of poor prognosis.

Liposarcoma (LPS) is a malignancy with extreme heterogeneity and thus optimization towards personalizing patient prognosis and treatment is essential. Here, we evaluated miR-155, miR-21, miR-143, miR-145 and miR-451 that are implicated in LPS, as novel FFPE tissue biomarkers.A total of 83 FFPE tissue specimens from primary LPS and lipomas (LPM) were analyzed. A proteinase K incubation-Trizol treatment coupled protocol was used for RNA isolation. After polyadenylation of total RNA and reverse transcription, expression analysis of 9 candidate reference and 5 target miRNAs was performed by qPCR. Genorm and NormFinder were used for finding the most suitable molecules for normalization. Survival analyses were performed in order to evaluate the prognostic potential of miRNAs.MiR-103 and miR-191 are most suitable for normalization of miRNA expression in LPS. MiR-155 and miR-21 are clearly overexpressed (P<0.001) in LPS compared with LPM specimens, whereas miR-145 (P<0.001), miR-143 (P =0.008) and miR-451 (P=0.037) are underexpressed. MiR-155 (P=0.007) and miR-21 (P=0.029) are differentially expressed between well-differentiated, dedifferentiated, myxoid/round cell and pleomorphic LPs tumor subtypes. MiR-155 represents a novel independent indicator of unfavorable prognosis in LPS (HR = 2.97, 95% CI = 1.23–7.17, P = 0.016).

Retraction note: Cutaneous mast cell tumor (Mastocytoma): cyto-histopathological and haematological investigations.

Cutaneous mast cell tumours (MCTs) are the most common skin tumours in dogs. Due to the prevalence of canine MCTs and the variable biologic behavior of this disease, accurate prognostication and a thorough understanding of MCT biology are critical for the treatment of this disease. A cytologic diagnosis of mast cell tumor with evidence of prior hemorrhage was made, and the masses were surgically removed. Cytological evaluation of fine-needle aspirates from the cutaneous mass from the axillary comprised many well-differentiated, highly granulated mast cells with moderate numbers of eosinophils. Nuclei were varied in size and shape with high nuclear’to’cytoplasmic ratio, prominent nucleoli, marked atypical and mitotic figures. Microscopically, mass consisted of sheets of neoplastic round cells that formed nonencapsulated nodules in the dermis and infiltrated into the adjacent dermal collagen, and also there was diffuse subcutis invasion of round to pleomorphic tumor cells. Tumor cells had moderate to abundant cytoplasm, round to ovoid nuclei with scattered chromatin, and mitotic figures. In this tumor, cytoplasmic granules showed atypical metachromasia. In addition, eosinophils were scattered among the mast cells at the periphery of the nodules. The presence of eosinophils and the observation, at high magnification, of cells with cytoplasmic metachromatic granules. Invasion of the deep subcutaneous fat or cutaneous muscles were a common feature of grade III tumour. Finally, a diagnosis of grade III cutaneous mast cell tumor was made. The virtual slide(s) of this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4755249151157024 .

Dendritic and mast cell involvement in the inflammatory response to primary malignant bone tumours.

BackgroundA chronic inflammatory cell infiltrate is commonly seen in response to primary malignant tumours of bone. This is known to contain tumour-associated macrophages (TAMs) and lymphocytes; dendritic cells (DCs) and mast cells (MCs) have also been identified but whether these and other inflammatory cells are seen commonly in specific types of bone sarcoma is uncertain.MethodsIn this study we determined the nature of the inflammatory cell infiltrate in 56 primary bone sarcomas. Immunohistochemistry using monoclonal antibodies was employed to assess semiquantitatively CD45+ leukocyte infiltration and the extent of the DC, MC, TAM and T and B lymphocyte infiltrate.ResultsThe extent of the inflammatory infiltrate in individual sarcomas was very variable. A moderate or heavy leukocyte infiltrate was more commonly seen in conventional high-grade osteosarcoma, undifferentiated pleomorphic sarcoma and giant cell tumour of bone (GCTB) than in Ewing sarcoma, chordoma and chondrosarcoma. CD14+/CD68+ TAMs and CD3+ T lymphocytes were the major components of the inflammatory cell response but (DC-SIGN/CD11c+) DCs were also commonly noted when there was a significant TAM and T lymphocyte infiltrate. MCs were identified mainly at the periphery of sarcomas, including the osteolytic tumour-bone interface.DiscussionOur findings indicate that, although variable, some malignant bone tumours (e.g. osteosarcoma, GCTB) are more commonly associated with a pronounced inflammatory cell infiltrate than others (e.g. chondrosarcoma. Ewing sarcoma); the infiltrate is composed mainly of TAMs but includes a significant DC, T lymphocyte and MC infiltrate.ConclusionTumours that contain a heavy inflammatory cell response, which includes DCs, TAMs and T lymphocytes, may be more amenable to immunomodulatory therapy. MCs are present mainly at the tumour edge and are likely to contribute to osteolysis and tumour invasion.

Needle-based confocal endomicroscopy for evaluation of malignant lymph nodes - a feasibility study.

Current modalities for lymph node staging in cancer can be limited. We sought to evaluate the feasibility of needle-based confocal laser endomicroscopy (nCLE) at the time of endoscopic ultrasound (EUS) and to describe the nCLE features that distinguish between benign, malignant, and inflammatory lymph nodes. We collected data on 28 consecutive patients during EUS staging of malignancy or assessment of enlarged lymph nodes. Patients underwent nCLE at the time of EUS followed by fine needle biopsy. nCLE images were correlated with the patients' final histopathology. All 28 patients successfully underwent nCLE during EUS without adverse events. There were 17 cases of carcinoma, 4 lymphoid malignancies, and 7 benign lymph nodes. We characterized the various nCLE features of the lymph node capsule and cortex. Features of carcinoma, such as clusters of dark pleomorphic tumor cells, were identified and found to correlate well with the final pathology. Lymphoid malignancies often had enlarged follicles, but this was inconsistent. nCLE of lymph nodes at the time of EUS is feasible and appears to be safe. Dark pleomorphic cells were readily identified in all of the malignant lymph nodes and correlated with tumor cells seen on histology.

Application of DTI and ARFI imaging in differential diagnosis of parotid tumours.

To explore the utility of diffusion tensor imaging (DTI) and acoustic radiation force impulse (ARFI) imaging in the diagnosis of parotid tumours. 51 patients with parotid tumours were examined with DTI on 3.0-T MRI and ARFI imaging on an ultrasound scanner before surgery. Values of apparent diffusion coefficient (ADC), fractional anisotropy (FA) and shear-wave velocity (SWV) were calculated and analyzed with independent samples Wilcoxon-Mann-Whitney test. Cut-off values, sensitivity and specificity were calculated with receiver-operating characteristic (ROC) curve analysis. The value of combination was calculated through parallel test for the cut-off value of ADC, FA and SWV (combination = 0 or 1); then, ROC analysis was performed with pathological results as the gold standard to calculate the sensitivity and specificity for the combination of the three parameters distinguishing benign and malignant parotid tumours. Pathological diagnosis for every patient was made post-operatively from the tumour tissue taken during operation. There was a significant difference between benign and malignant tumours in the values of ADC, FA and SWV (p = 0.032, p = 0.011 and p < 0.0001); a significant difference in the values was also found between pleomorphic adenoma and malignant tumour (p = 0.0012, p < 0.0001 and p = 0.0002). The diagnosis cut-off points between benign and malignant tumours for ADC, FA and SWV were 1.02 × 10(-3) mm(2) s(-1), 0.24 and 2.76 m s(-1), respectively; the sensitivity for ADC, FA and SWV was 87.50, 62.50 and 68.75%; the specificity was 45.71, 82.86 and 97.14%. Analysis of the combination of the three parameters increased the sensitivity, specificity, Youden index and area under the ROC curve compared with analysis of each parameter alone for distinguishing benign and malignant tumours. The diagnostic value of the combination of the three parameters for distinguishing benign and malignant parotid tumours is the best; SWV is the preferred indicator. Parameters of DTI and ARFI may reflect the histological characteristics of parotid tumours and predict benignancy and malignancy and could provide quantitative information about the tumour. Combination of DTI with ARFI imaging had obvious advantage for the diagnosis of parotid tumours than each alone.

MP83-16 EMETINE DIHYDROCHLORIDE ENHANCES CISPLATIN/GEMCITABINE-MEDIATED GROWTH INHIBITION OF BLADDER TUMOR CELLS IN VIVO

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology IV1 Apr 2016MP83-16 EMETINE DIHYDROCHLORIDE ENHANCES CISPLATIN/GEMCITABINE-MEDIATED GROWTH INHIBITION OF BLADDER TUMOR CELLS IN VIVO Kimberly Foreman, Alexandra Mitchell, Samuel White, Emil Bielecki, Maria Picken, and Gopal Gupta Kimberly ForemanKimberly Foreman More articles by this author , Alexandra MitchellAlexandra Mitchell More articles by this author , Samuel WhiteSamuel White More articles by this author , Emil BieleckiEmil Bielecki More articles by this author , Maria PickenMaria Picken More articles by this author , and Gopal GuptaGopal Gupta More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2198AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We previously reported that emetine, a natural alkaloid, acts synergistically with cisplatin to inhibit growth of muscle invasive bladder cancer (MIBC) cell lines, but not normal urothelial cells in vitro. These studies were recently extended to show emetine also enhances growth inhibition of tumor cells treated with cisplatin-gemcitabine (CG), a current first-line chemotherapy regime for MIBC patients. Here, we evaluated the efficacy of combined emetine and CG (CG&E) in a xenograft model of MIBC and examined the resulting tumors for evidence of proliferation (Ki67) and apoptosis (activated caspase 3) using immunostaining. METHODS UMUC3, a human MIBC cell line, were injected subcutaneously into nude mice. Established tumors were treated with emetine, CG, CG&E, or left untreated (n=5-6 per group). Tumors were measured every other day, and at various time points, the tumors were excised, formalin fixed, and paraffin embedded. Tissue sections were immunostained for Ki67 and activated caspase 3. Positive and negative cells were counted in 10 high-power fields from each specimen using ImageJ software to quantify the results. RESULTS CG- and CG&E-treated tumors were significantly smaller than untreated and emetine-treated specimens throughout the study. CG&E tumors were significantly smaller compared with CG-treated tumors as early as day 8 post-treatment in animals receiving higher doses of emetine. About day 20 post-treatment, CG-treated tumors began to rapidly grow, while CG&E tumors did not show evidence of growth until day 27. Histologically, untreated and emetine-treated tumors revealed areas of hemorrhage and necrosis among sheets of pleomorphic tumor cells with numerous mitotic figures. In contrast, CG- and CG&E-treated tumors were smaller with nests of tumor cells surrounded by residual matrigel. CG- and CG&E-treated tumors contained significantly fewer Ki67 positive cells than untreated controls (p<0.01), but there was no difference in Ki67 positivity between CG and CG&E-treated tumors. In contrast, activated caspase 3 positivity was significantly higher in CG&E-treated tumors compared to CG-treated tumors (p<0.01) beginning at day 20 post-treatment. CONCLUSIONS The addition of emetine to CG chemotherapy resulted in significantly smaller tumor volumes in a xenograft model of MIBC. While CG effectively reduced proliferation and increased apoptosis, the addition of emetine enhanced this effect, possibly through increased apoptosis. The results suggest addition of emetine to standard of care CG treatment may benefit patients with MIBC. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1087 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Kimberly Foreman More articles by this author Alexandra Mitchell More articles by this author Samuel White More articles by this author Emil Bielecki More articles by this author Maria Picken More articles by this author Gopal Gupta More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Pleomorphic hyalinising angiectatic tumour: A case report

Pleomorphic hyalinising angiectatic tumour: A case report

Spontaneously occurring lymphohematopoietic tumors in three young Sprague Dawley rats

To assess the toxicological and pharmacological effects of chemicals, it is important to know what kinds of neoplasms naturally occur in the early life of laboratory animals. In the present study, we identified three spontaneous hematopoietic tumors in three of 52 young female Sprague-Dawley rats used in a pharmacological study. These cases included two rats (Case 1 and 2) from a sesame oil-treated group and one rat (Case 3) from a chemical-treated group in the same single gavage study. Case 1 rapidly lost body weight at 13 weeks of age without any clinical signs and died. Round lymphoid tumor cells were found in the spleen, liver, bone marrow, and pancreas. The tumor cells were immunohistochemically positive for CD3 and PCNA, which is suggestive of malignant T-cell lymphoma. Cases 2 and 3 had rapid body weight loss at 14 and 16 weeks of age, respectively, exhibited severe anemia, hypolocomotion, and decreased body temperature, and were euthanized due to a poor prognosis based on severe clinical signs. Pleomorphic large tumor cells were found in the spleen, liver, bone marrow, lymph nodes, heart, kidneys, lung, pancreas, adrenal glands, pituitary gland, ovaries, Harderian gland, and/or eyes. The tumor cells were immunoreactive for CD34, lysozyme, and PCNA, which is suggestive of myeloid leukemia. These cases might provide useful historical control information for rat toxicity studies.

A Review on Primary Angiosarcoma of the Prostate Gland: An Update

Primary angiosarcoma of the prostate (PASOP) is a very rare tumour which most clinicians have not encountered and may be unaware of Literature of PASOP was reviewed by obtaining information from various internet data bases including: Google, Google Scholar, Educus, and PUB Med. Less than 20 cases of PASOP have been reported. PASOP may present in a male child or adult with lower urinary tract symptoms, dysuria, haematuria, pain and constipation. There may be in some cases a history of prior radiotherapy for adenocarcinoma of prostate. Diagnosis is based upon histological examination of prostate biopsy specimens which tend to reveal: proliferative vascular channels that are lined by atypical multi-layered or atypical solid endothelial cells, variable pleomorphic tumour cells ranging from spindle cells to large/plump cells; nuclei which are large and pleomorphic and which contain clumped chromatin and prominent nucleoli; mitotic figures of which some may look atypical are frequently seen. PASOPs on immunohistochemical staining tend to stain positively for CD34, Factor 8 (Factor VIII), Vimentin. PASOPs on immunohistochemical staining tend to exhibit negative staining for PSA, Keratin and S-100. Surgical resection with surgical margins that are clear of tumor has been shown to be the treatment associated with a chance of long-term survival but a number of reported cases of PASOP at the time of initial diagnosis had presented with metastatic disease or locally advanced disease and curative surgery