Rare Aggressive Tumor Research Articles

Gene-asbestos interaction in malignant pleural mesothelioma susceptibility.

Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, on average less than 10% of subjects highly exposed to asbestos develop MPM, suggesting the possible involvement of other risk factors. To identify the genetic factors that may modulate the risk of MPM, we conducted a gene-environment interaction analysis including asbestos exposure and 15 single nucleotide polymorphisms (SNPs) previously identified through a genome-wide association study on Italian subjects. In the present study, we assessed gene-asbestos interaction on MPM risk using relative excess risk due to interaction and synergy index for additive interaction and V index for multiplicative interaction. Generalized multifactor dimensionality reduction (GMDR) analyses were also performed. Positive deviation from additivity was found for six SNPs (rs1508805, rs2501618, rs4701085, rs4290865, rs10519201, rs763271), and four of them (rs1508805, rs2501618, rs4701085, rs10519201) deviated also from multiplicative models. However, after Bonferroni correction, deviation from multiplicative model was still significant for rs1508805 and rs4701085 only. GMDR analysis showed a strong MPM risk due to asbestos exposure and suggested a possible synergistic effect between asbestos exposure and rs1508805, rs2501618 and rs5756444. Our results suggested that gene-asbestos interaction may play an additional role on MPM susceptibility, given that asbestos exposure appears as the main risk factor.

Primary hepatic choriocarcinoma in a female patient

Choriocarcinoma is a germ cell tumor belonging to the spectrum of gestational trophoblastic diseases, and occurs most commonly in the gonads. Primary hepatic choriocarcinoma is very rare, especially in females. A 59-year-old woman was referred to our clinic with a history of upper right quadrant pain lasting 1 month. Computed tomography and magnetic resonance imaging revealed a large hypervascular mass in the right liver, characteristic of angiosarcoma. The patient underwent right hemihepatectomy without unexpected events. Histopathology revealed the tumor as a choriocarcinoma, with numerous syncytiotrophoblasts. Immunohistochemistry was positive for β-human chorionic gonadotropin and CK-19, with a Ki-67 labeling index of 90%. The tumor showed focal positivity for CD31 and human placental lactogen. The patient started chemotherapy (vincristine and cyclophosphamide) on postoperative day 16. The patient’s clinical condition improved and she was discharged on postoperative day 17. Primary hepatic choriocarcinoma in female adults is a rare aggressive tumor, and further studies are needed to improve its diagnosis and treatment. Keywords: Hepatic choriocarcinoma, Choriocarcinoma, hepatic

COAGULATION DISORDERS IN CHILDREN WITH VASCULAR ANOMALIES

Background. The term Kasabaha-Merit syndrome is often used as a eponym for general description of the for coagulation disorders in different vascular lesions in both children and adults. However, subsequent studies show that for certain types of vascular tumors and vascular malformations different types of coagulopathy occur. The aim of the study is to determine which vascular anomalies are at risk for coagulopathy. Methods: 64 patients aged from 1 month to 15 years with vascular anomalies were enrolled in prospective investigation. Of the 26 patients with vascular tumors 20 have hemangiomas, including 6 liver hemangiomas, 2 have kaposhiforme hemangioendothelioma, 1 tufted angioma, and 3 PHACE syndrome. Vascular malformations have 38 patients, 15 of them have cystic lymphatic malformations, 8 have primary lymphedema, 11 have venous malformations, 2 have arteriovenous malformation, and two have CLOVES syndrome. Measurement of D-dimer levels, platelet count, and fibrinogen in blood, witсh was drawn from a peripheral vein not involved by the vascular anomalies. Results. None patients with hemangiomas had any coagulation disorders. Very low platelet count so called Kasabach-Merritt phenomenon had two patients younger than one year with rare local aggressive tumor kaposiform hemangioendothelioma. 14 year old patient with huge tufted angioma of extremities had normal platelet count. Among the 11 patients with venous malformations (VM) 6 (54.5%) had elevated D-dimer levels. Patients with multiple gastrointestinal venous malformations had very high D-dimer lever (≥4 µg/ml) associated with low fibrinogen level. Patients with large unifocal truncal VM and VM of perineum and pelvis had D-dimer levels above 1 µg/ml and normal fibrinogen level. In contrast, patients with small localized VM of limbs and children with lymphatic malformations had normal coagulations tests. Conclusions. Children with vascular anomalies have risk of coagulopathy. Very low platelet count is specific for kaposhiform hemangioendothelioma and tufted angioma and is age dependent. Elevated D-dimer level is highly specific for VMs and don’t depends of patients age only of VMs size.

Stage, age, and EBV status impact outcomes of plasmablastic lymphoma patients: a clinicopathologic analysis of 61 patients.

BackgroundPlasmablastic lymphoma (PBL) is a rare aggressive neoplasm with lymphoid and plasmacytic differentiation that is commonly associated with immunodeficiency and an unfavorable prognosis. Clinicopathologic features have been largely derived from cases reports and small series with limited outcome analyses.Patients and methodsThe demographic, clinicopathologic features, and clinical outcomes of a cohort of 61 patients with PBL were reviewed and analyzed.ResultsPatients had a median age of 49 years (range 21–83 years) and most (49/61; 80 %) were men. Human immunodeficiency virus (HIV) status was available for 50 patients: 20 were HIV-positive and 30 HIV-negative. Twenty-three patients were immunocompetent. Abdominal/gastrointestinal complaints were the most common presenting symptoms, reported in 14 of 47 (30 %) of patients. At presentation, 24 of 43 (56 %) patients had stage III or IV disease. Epstein-Barr virus (EBV) was detected in 40 of 57 (70 %) cases. MYC rearrangement was identified in 10/15 (67 %) cases assessed, and MYC overexpression was seen in all cases assessed regardless of MYC rearrangement status. HIV-positive patients were significantly younger than those who were HIV-negative (median 42 vs. 58 years; p = 0.006). HIV-positive patients were also significantly more likely to have EBV-positive disease compared with HIV-negative patients (19/19, 100 % vs. 15/29, 52 %; p = 0.002). Patients who received CHOP chemotherapy tended to have better overall survival (OS) compared with those who received hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) (p = 0.078). HIV status had no impact on OS. Patients with EBV-positive PBL had a better event-free survival (EFS) (p = 0.047) but not OS (p = 0.306). Notably, OS was adversely impacted by age ≥50 years (p = 0.013), stage III or IV disease (p = <0.001), and lymph node involvement (p = 0.008).ConclusionsThe most significant prognostic parameters in patients with PBL are age, stage, and, to a lesser extent, EBV status. In this study, two-thirds of PBL cases assessed were associated with MYC rearrangement and all showed MYC overexpression.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-015-0163-z) contains supplementary material, which is available to authorized users.

Oral Malignant Melanoma of the Maxilla: A Case Report

A case report of oral malignant melanoma (OMM). An 84-year-old male patient presented with enlarged, swollen anterior left upper gingiva with mild pain lasting eight weeks from the lower occluded teeth. Histopathological examination and immunohistochemical studies confirm OMM. OBJECTIVES: OMM, a neoplasm of melanocytes, is a rare aggressive tumor of the oral cavity. This paper aims to explain and discuss the clinical features, histopathology and immunohistochemical studies of OMM. MATERIAL AND METHODS: We report on a case of OMM treated at our institute. An oral examination, differential diagnosis and biopsy were performed for a definitive diagnosis. RESULTS: Histopathological examination showed sheets of atypical melanocytic tumor cells with abundant cytoplasmic pigmentation. The tumor cells were positive for S-100 protein, HMB-45 and MART 1 or Melan A. A final diagnosis of OMM was made. CONCLUSION: OMM is a rare tumor of the oral cavity with a poor prognosis; although an aggressive treatment is available to patients. Early diagnosis and aggressive multimodal treatment are important ways for surgeons to achieve a better outcome for patients with OMM.

Choroid plexus carcinoma in children: The Head Start experience

Choroid plexus carcinoma (CPC) is a rare aggressive intracranial neoplasm with a predilection for young children and a historically poor outcome. Currently, no defined optimal therapeutic strategy exists. The Head Start (HS) regimens have included irradiation-avoiding strategies in young children with malignant brain tumors using high dose chemotherapy to improve survival and minimize neurocognitive sequelae. Three sequential HS studies have been conducted from 1991 to 2009. HS treatment strategy has consisted of maximal surgical resection followed by five cycles of intensive induction followed by consolidation myeloablative chemotherapy with autologous hematopoietic stem cell rescue (AuHCR). Irradiation was given following recovery from consolidation based on the patient's age and evidence of residual disease. Twelve children with CPC (median age of 19.5 months) have been treated with HS regimens. Ten patients had >95% resection. Three patients had disseminated disease at diagnosis. Ten patients completed consolidation of whom five are alive, irradiation and disease free at 29, 43, 61, 66 and 89 months from diagnosis. Seven patients experienced tumor recurrence/progression at a median time of 13 months (range 2-43 months). Five patients received irradiation, one for residual disease and four upon progression or recurrence, of whom one is alive at 61 months. The 3- and 5-year progression-free survivals are 58% and 38% and overall survivals 83% and 62% respectively. Late deaths from disease beyond 5 years were also noted. Head Start strategies may produce long-term remission in young children with newly diagnosed CPC with avoidance of cranial irradiation.

Extrapulmonary Small Cell Carcinoma: Imaging Features with Radiologic-Pathologic Correlation

Extrapulmonary small cell carcinoma (EPSCC) refers to small cell carcinoma arising outside of the lungs. EPSCC extrapulmonary small cell carcinoma is a rare aggressive neoplasm, representing a minority of all small cell carcinomas. Despite its uncommon occurrence, EPSCC extrapulmonary small cell carcinoma has been described in nearly every organ, most commonly in the gastrointestinal and genitourinary systems. As such, it is important for radiologists to be aware of the entity. Although imaging is neither sensitive nor specific for EPSCC extrapulmonary small cell carcinoma , it plays an important role by helping exclude metastases from a primary pulmonary tumor, establish tumor staging, and assess response to therapy. EPSCC extrapulmonary small cell carcinoma is diagnosed by demonstrating pathologic features of small cell carcinoma in an extrapulmonary site. There are two ways to stage EPSCC extrapulmonary small cell carcinoma . One method uses the Veterans Administration Lung Study Group system developed for small cell lung cancer that allocates patients into limited or extensive disease categories. The second approach is the American Joint Committee on Cancer tumor-node-metastasis system applied to other tumor subtypes arising from the same organ. Because of its rare and varied manifestations, the most effective treatment for EPSCC extrapulmonary small cell carcinoma has not been established. Current management recommendations are derived from retrospective studies and single-institution experiences or are extrapolated from small cell lung cancer data. Regardless of therapy, overall survival rates are poor, with 5-year survival rates around 13%. To help radiologists increase their familiarity with EPSCC extrapulmonary small cell carcinoma , this article provides (a) a background for EPSCC extrapulmonary small cell carcinoma based on the literature and (b) a pictorial review of EPSCC extrapulmonary small cell carcinoma in multiple organs, with radiologic-pathologic correlation.

Oral malignant melanoma: A rare malignancy

Primary malignant melanoma of the oral cavity is a rare neoplasm. It is very rare aggressive neoplasm arising from a benign melanocytic lesion or de novo from melanocytes within normal skin or mucosa. It is deadly, biologically unpredictable with worst prognosis. These tumors tend to metastasize or locally invade tissue more readily than other malignant tumors in the oral region. The survival of patients with mucosal melanomas is less than for those with cutaneous melanomas. Tumor size and metastases are related to the prognosis of the disease. Early detection, therefore, is important. The paper presents such a rare case that occurred in a young patient.

Uterine leiomyosarcoma: a review article.

Uterine leiomyosarcomas (LMSs) are rare aggressive tumors, with high recurrence rates, even when confined to the uterine corpus at the time of diagnosis. These tumors are large myometrial masses, which typically spread hematogenously. Patients present with vague symptoms similar to those of patients with leiomyomas. Most patients are diagnosed with LMS postoperatively. In the presence of metastatic disease, complete surgical cytoreduction should be attempted when feasible. Lymphadenectomy should be performed only in patients with nodes suspected of harboring metastatic disease and as part of a cytoreductive effort. There are conflicting data to support adjuvant chemotherapy or radiation therapy for early-stage disease. Patients with advanced-stage disease should receive gemcitabine and docetaxel adjuvant chemotherapy. Patients with recurrent disease are candidates for a wide variety of second-line treatments, of which many are investigational. Although prognosis remains dismal, ongoing studies are investigating the role of advanced imaging, multimodality treatment, prognostic nomograms, and unique biomedical pathways to increase understanding of LMS and improve therapeutic options for patients.

PT-09 * TARGETED THERAPY IN GLIOBLASTOMA MULTIFORME PRESENTING AS GLIOMATOSIS CEREBRI

BACKGROUND: Glioblastoma multiforme (GBM) presenting as gliomatosis cerebri (GC) is a rare aggressive neoplasm of the central nervous system (CNS) with a median survival of less than one year. To-date no well-defined therapeutic strategy exists for these tumors. We report our experience of the likely benefit of using an individualized personalized therapeutic (IPT) approach to profile a new combinatorial treatment regimen in a child with GBM/GC of the CNS. CASE REPORT: An 8-year-old male with a Lansky score of 50 presented with headache, dysarthria and ataxia. MRI of the CNS showed tumor involvement of the thalamus, cerebellum, brain stem and spinal cord. Pathology of the biopsy performed was consistent with GBM. Diffuse positivity of the tumor for epidermal growth factor receptor (EGFR) was noted by immunohistochemistry. He received radiation therapy along with temozolomide followed by adjuvant therapy with temozolomide, irinotecan, and bevacizumab every 28 days. After 2 cycles, he demonstrated disease progression. Based on the diffuse EGFR expression profile of his tumor, Erlotinib (EGFR tyrosine-kinase inhibitor) was started orally daily. Marked response was noted clinically and by neuroimaging. However, following six cycles, MRI of the brain demonstrated a new lesion in the frontal lobe. Temsirolimus (m-TOR inhibitor) was added to Erlotinib. Currently he continues to tolerate this regimen, remains well with a Lansky scale of 80, 16 months post-diagnosis. DISCUSSION: EGFR-AKT-mTOR pathway is known to be up-regulated in GBM justifying targeting multiple oncogenic drivers and report the likely benefit of using erlonitib with temsirolimus. Prospective studies are warranted to standardize an IPT approach for such rare pediatric CNS tumors. Future studies will explore the potential benefit of this regimen targeting key molecules of this signaling pathway driving GBM tumorogenesis and evaluate its therapeutic efficacy in improving overall survival in comparison to historical controls.

Merkel cell carcinoma

Merkel cell carcinoma is a rare aggressive malignant neuroendocrine skin tumor, which can metastasize to lymph nodes early and often shows local recurrence. The prognosis depends on tumor size and disease stage. The majority of recurrences appear during the first 2 years after the primary diagnosis. The 5-year survival rate for primary tumor < 2 cm is 66-75 % and for primary tumors > 2 cm is 50-60 %. With lymph node metastases the 5-year survival rate is 42-52 %, while with distant metastases it drops to 17-12 %. Extensive staging inclusive sentinel lymph node biopsy is essential to assess the risk for distant metastasis and to allow the best recommendations for therapy. After surgical treatment with adequate safety margin, subsequent adjuvant radiation therapy of the tumor region and lymphatic draining basin is recommended to reduce the risk of local recurrence and lymphatic spread.

Pseudomyogenic (Epithelioid sarcoma-like) hemangioendothelioma with bone invasion

AimPseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma is a rare local aggressive vascular tumor. Herein we present a 54-year-old male patient with a tumor on his index finger. CaseThe patient presented with a 1-year history of pain and swelling that progressively exacerbated. Bone invasion was observed on the middle phalanx via direct radiography. Histopathological examination findings were compatible with epithelioid sarcoma-like hemangioendothelioma. ConclusionTo the best of our knowledge is the first case report of epithelioid sarcoma-like hemangioendothelioma with bone invasion.

Rare aggressive natural killer cell leukemia presented with bone marrow fibrosis - a diagnostic challenge.

Aggressive natural killer cell leukemia is an extraordinary rare aggressive malignant neoplasm of natural killer cells. Although its first recognition as a specific entity was approximately 20 years ago, this leukemia has not yet been satisfactorily characterized as fewer than 200 cases have been reported in the literature and up to our knowledge, this is the first case report in Qatar. Reaching a diagnosis of aggressive natural killer leukemia was a challenging experience, because in addition to being a rare entity, the relative scarcity of circulating neoplastic cells, failure to obtain an adequate aspirate sample sufficient to perform flow cytometric analysis, together with the absence of applicable method to prove NK clonality (as it lack specific clonal marker); our case had atypical confusing presentation of striking increase in bone marrow fibrosis that was misleading and complicated the case further. The bone marrow fibrosis encountered may be related to the neoplastic natural killer cells’ chemokine profile and it may raise the awareness for considering aggressive natural killer leukemia within the differential diagnosis of leukemia with heightened marrow fibrosis.

Squamous Cell Carcinoma of the Prostate With Strong FDG Uptake on PET/CT

Primary squamous cell carcinoma (SCC) of the prostate is a rare aggressive neoplasm with a poor prognosis. A 60-year-old man presented with urinary frequency and interrupted urination for 4 months. Serum prostate-specific antigen and SCC antigen were elevated. T2-weighted MR images showed a hyperintense lesion in the central area of the prostate. FDG PET/CT showed strong FDG uptake of the lesion with SUVmax of 15.5. Prostate biopsy revealed moderate differentiated SCC. This case indicates SCC of the prostate should be considered in the differential diagnosis of abnormal prostate FDG accumulation (especially with elevated SCC antigen level).

Cytological features of pure micropapillary carcinoma of various organs: A report of eight cases.

Micropapillary carcinoma (MPC) is a rare aggressive tumor, which generally accompanies the primary carcinoma of the organ of its origin, while the pure form is extremely uncommon. Angiolymphatic involvement is widespread and a considerable proportion of the cases present with metastases. The current study presents eight pure MPC cases arising from the breast (n=3), urinary bladder (n=3), parotid gland (n=1) and lung (n=1, presenting with pericardial effusion), with the cytological findings. The eight patients included three female and five male cases aged between 48 and 74 years. The most common cytological findings were three-dimensional aggregates, cell clusters with angulated or scalloped borders, single cells with a columnar configuration and eccentric nuclei, and high-grade nuclear features. Histopathological sections showed accompanying in situ ductal carcinoma in the cases of MPC arising in the parotid gland and breast (n=3), and one case in the bladder exhibited only in situ MPC. The average follow-up period was 20 months (range, 6–54 months) and, during this period, three patients succumbed to the disease. At present, four patients are alive with disease and one patient is alive and disease-free. In conclusion, cytology is an important tool for the diagnosis and management of MPC.

Association of time to diagnosis of ESFT with tumor origin and location, metastasis, and survival: A single institutional study of 374 cases.

e21502 Background: Ewing’s sarcoma family of tumors (ESFT) is a rare aggressive bone tumor of childhood with poor outcome. In developing countries most of ESFT patients have delayed presentation. W...

Preclinical Evaluation of Engineered Oncolytic Herpes Simplex Virus for the Treatment of Pediatric Solid Tumors

Recently, investigators showed that mice with syngeneic murine gliomas that were treated with a neuroattenuated oncolytic herpes simplex virus-1 (oHSV), M002, had a significant increase in survival. M002 has deletions in both copies of the γ134.5 gene, enabling replication in tumor cells but precluding infection of normal cells. Previous studies have shown antitumor effects of other oHSV against a number of adult tumors including hepatocellular carcinoma and renal cell carcinoma. The purpose of the current study was to investigate the oncolytic potential of M002 against difficult to treat pediatric liver and kidney tumors. We showed that the oHSV, M002, infected, replicated, and decreased cell survival in hepatoblastoma, malignant rhabdoid kidney tumor, and renal sarcoma cell lines. In addition, we showed that in murine xenografts, treatment with M002 significantly increased survival and decreased tumor growth. Finally, these studies showed that the primary entry protein for oHSV, CD111 (nectin-1) was present in human hepatoblastoma and malignant rhabdoid kidney tumor specimens. We concluded that M002 effectively targeted these rare aggressive tumor types and that M002 may have potential for use in children with unresponsive or relapsed pediatric solid tumors.

Malignant peripheral nerve sheath tumors of the head and neck: a case series and literature review.

Background. Malignant peripheral nerve sheath tumors (MPNSTs) of the head and neck are rare aggressive neoplasms with a poor prognosis. This study describes the management and outcomes of 3 of our patients with MPNSTs of the head and neck. Methods. We identified 3 patients presenting with MPNST of the head and neck and treated at the University of North Carolina. We compared our results to the literature from 1963 to 2014. Results. Mean follow-up was 31 months. Average age at diagnosis was 44.7 years of age. All patients received wide-local excision and adjuvant radiotherapy. No patients recurred during the series. Recurrence-free survival time for the patients was 45, 37, and 3 months, respectively. Conclusions. Our data series confirms that a combined-modality approach with complete surgical resection and adjuvant radiotherapy leads to improved outcomes in MPNSTs of the head and neck. Nonetheless, due to historically poor outcomes, continued research into newer therapies needs to be explored.

Case of Malignant Mesothelioma of the Peritoneum and Pleura

Malignant mesothelioma is a rare aggressive tumor and arises from mesothelial cells in the pleural, peritoneal and pericardial cavities. Median survival is -1 year and the incidence is approximately 0.7 per million persons, and is increasing annually in Korea. It is difficult to diagnose malignant mesothelioma because of nonspecific symptoms, signs and laboratory findings. It needs to be confirmed by histological examination and immunohistochemistry. There is no case report of malignant mesothelioma of the peritoneum and pleura in Korea. We report a rare case of malignant mesothelioma with simultaneous involvement of the peritoneum and pleura in a 75-year-old man without evidence of asbestos exposure. (Korean J Med 2014;87:756-760)

Adrenal cortical carcinoma presenting with secondary amyloidosis: A case report

Introduction: Adrenal cortical carcinoma is a rare aggressive tumor with a poor prognosis. Associated systemic amyloidosis is a rare phenomenon with only single case reported in English literature. case report: We report a case of a 50-year-old female harboring a huge adrenal cortical tumor along with systemic amyloidosis who underwent primary curative surgical resection of the tumor. Our patient had a Weiss score of 6 which is indicative of bad prognosis. conclusion: the presence of proteinuria in patients with adrenal cortical carcinoma may be indicative of amyloidosis. Further, the high risk of metastasis in adrenal cortical cancer mandates a close clinical follow-up.