Rare Aggressive Tumor Research Articles

A single-center experience with undifferentiated embryonal sarcoma of the liver.

Undifferentiated embryonal sarcoma of the liver (UESL) is a rare aggressive mesenchymal pediatric tumor. Previously, reported outcomes have been very poor. Here, we report a single-center experience of five patients with UESL treated with upfront gross total resection and adjuvant chemotherapy. We have a median follow-up of 8 years with a range from 5 to 19 years with 100% event-free survival.

Abstract 643: Establishment and mutation analysis of a novel malignant peritoneal mesothelioma cell line, TU-MM-1

Abstract Malignant peritoneal mesothelioma (MPM) is a rare aggressive neoplasm of the peritoneum, and its molecular biological characteristics and mechanisms of development are poorly understood. We, therefore, established a new cell line of human MPM, TU-MM-1, to elucidate its biological properties and to develop novel therapeutic strategies. The cells showed polygonal morphology, grew in monolayers without contact inhibition and were arranged like a jigsaw puzzle. The chromosome numbers ranged from 41 to 44. A low rate of proliferation was observed and the doubling time was 67.9 h. Genomic DNA sequencing revealed that TU-MM-1 cells harbored missense mutations in APC, LATS2, BRCA1/2, and TP53, and mutation of a splice donor site in BAP1 and loss of CDKN2A gene. We observed the absence of BAP1 and p16INK4a proteins, underexpression of LATS2 protein, and overexpression of p53 protein in TU-MM-1 cells in western blot analysis. Heterotransplantation to nude mice produced tumors that had the characteristics of the original tumor. This cell line may be useful for studying biological properties and contribute to novel treatment strategies. Citation Format: Seiya Sato, Nao Oumi, Hiroaki Itamochi, Tetsuro Oishi, Tasuku Harada, Toru Sugiyama. Establishment and mutation analysis of a novel malignant peritoneal mesothelioma cell line, TU-MM-1. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 643.

Low-Dose Histone Deacetylase Inhibitor Treatment Leads to Tumor Growth Arrest and Multi-Lineage Differentiation of Malignant Rhabdoid Tumors.

Malignant rhabdoid tumor (MRT) and atypical teratoid rhabdoid tumors (ATRT) are rare aggressive undifferentiated tumors primarily affecting the kidney and CNS of infants and young children. MRT are almost exclusively characterized by homozygous deletion or inactivation of the chromatin remodeling gene SMARCB1 SMARCB1 protein loss leads to direct impairment of chromatin remodeling and we have previously reported a role for this protein in histone acetylation. This provided the rationale for investigating the therapeutic potential of histone deactylase inhibitors (HDACi) in MRT. Whereas previously HDACis have been used at doses and schedules that induce cytotoxicity, in the current studies we have tested the hypothesis, both in vitro and in vivo, that sustained treatment of human MRT with low-dose HDACi can lead to sustained cell growth arrest and differentiation. Sustained low-dose panobinostat (LBH589) treatment led to changes in cellular morphology associated with a marked increase in the induction of neural, renal, and osteoblast differentiation pathways. Genome-wide transcriptional profiling highlighted differential gene expression supporting multilineage differentiation. Using mouse xenograft models, sustained low-dose LBH589 treatment caused tumor growth arrest associated with tumor calcification detectable by X-ray imaging. Histological analysis of LBH589-treated tumors revealed significant regions of ossification, confirmed by Alizarin Red staining. Immunohistochemical analysis showed increased TUJ1 and PAX2 staining suggestive of neuronal and renal differentiation, respectively. Low-dose HDACi treatment can terminally differentiate MRT tumor cells and reduce their ability to self-renew. The use of low-dose HDACi as a novel therapeutic approach warrants further investigation. Clin Cancer Res; 22(14); 3560-70. ©2016 AACR.

Hilar/endobronchial NUT midline carcinoma: A case report

Nuclear protein of the testis (NUT) midline carcinoma (NMC) is a rare aggressive tumor described in the midline in the chest and head and neck. Initially reported in younger individuals, it has subsequently been shown to have a wider age distribution. The defining feature of these tumors is its association with BRD-NUT rearrangements. Occasionally NMC has been observed in a non-midline location. This case report describes an unusual rapidly progressing non-midline hilar/endobronchial location of an NMC in a 34-year-old man. The clinical and histologic features were that of an undifferentiated neoplasm concerning for a small cell carcinoma or a lymphoma. A broad panel of immunohistochemical markers for carcinoma, lymphoma and melanoma were negative which led us to suspect a diagnosis of NMC. A positive immunostaining with p63 and NUT protein antigen confirmed the diagnosis. The p63 positivity and cytokeratin negativity suggest a primitive/precursor squamous cell derivation.

Adrenal cortical carcinoma with tumor thrombus extension into the right atrium: A case report.

Adrenal cortical carcinoma (ACC) is a rare aggressive malignant tumor associated with a poor prognosis. Patients with ACC usually present with abnormal hormone secretion, tumor growth or encroachment on the surrounding viscera. An early diagnosis of ACC is considered challenging. The present study reports a case of ACC with tumor thrombus extension into the inferior vena cava and right atrium. A 33-year-old male patient exhibited symptoms of gynecomastia and abdominal distention, which were due to the abnormal hormone secretion levels and to the presence of a large mass in the right adrenal gland. An en bloc resection of the tumor was the selected treatment option. Extirpation of the tumor thrombus was performed by means of extracorporeal circulation. No signs of metastasis or recurrence were identified at the 1-month follow-up.

Identical TP53 mutations in pelvic carcinosarcomas and associated serous tubal intraepithelial carcinomas provide evidence of their clonal relationship.

Pelvic carcinosarcomas (PCSs) are rare aggressive biphasic tumors that localize in the ovary, fallopian tube, or peritoneum and present frequently as bilateral disease. We undertook a morphological, p53 immunohistochemical and TP53 gene mutational analysis study in a single institution cohort of 16 PCSs in order to investigate the nature of bilateral tumors and to shed light on their origin and pathogenesis. Of the 16 patients, 10 presented with bilateral disease, 6 with a carcinosarcoma in both adnexa, and the remaining cases with a carcinosarcoma in one adnexum and a carcinoma in the opposite. The carcinoma component showed high-grade serous features in 13/16 of cases (81%). In 10 patients (63%), a serous tubal intraepithelial carcinoma (STIC) was found, in one case bilateral, making a total of 11 STICs. STIC was found only in cases with a carcinoma component with high-grade serous features. All 10 bilateral tumors and all 11 PCS-associated STICs showed a similar p53 immunostaining pattern. At mutation analysis of the TP53 gene, all five bilateral PCS contained an identical mutation in both localizations. Furthermore, a TP53 mutation was found in 8 of 10 STICs, with an identical mutation in the associated PCS. The finding of similar p53 immunostaining in all bilateral cases and identical TP53 mutations in most PCS-associated STIC provides evidence for a clonal relation between these neoplastic lesions, supporting a metastatic nature of bilateral PCS and suggesting that they have an extraovarian origin in a STIC.

Blastic plasmacytoid dendritic cell neoplasm frequently shows occult central nervous system involvement at diagnosis and benefits from intrathecal therapy.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive myeloid neoplasm which shows a high rate of central nervous system (CNS) recurrence and overall survival (OS) of <1 year. Despite this, screening for CNS involvement is not routinely performed at diagnosis and intrathecal (IT) prophylaxis is not regularly administered in BPDCN. Here, we prospectively evaluated 13 consecutive BPDCN patients for the presence of CNS involvement by flow cytometry. Despite none of the patients presented with neurological symptoms, occult CNS involvement was detected in 6/10 cases evaluated at diagnosis and 3/3 studied at relapse/progression. BPDCN patients evaluated at diagnosis received IT treatment -either CNS prophylaxis (n = 4) or active therapy (n = 6)- and all but one remain alive (median follow-up of 20 months). In contrast, all three patients assessed at relapse/progression died. The potential benefit of IT treatment administered early at diagnosis on OS and CNS recurrence-free survival of BPDCN was further confirmed in a retrospective cohort of another 23 BPDCN patients. Our results show that BPDCN patients studied at diagnosis frequently display occult CNS involvement; moreover, they also indicate that treatment of occult CNS disease might lead to a dramatically improved outcome of BPDCN.

Lymphoblastic lymphoma: an updated review on biology, diagnosis, and treatment.

Lymphoblastic lymphoma is a rare aggressive neoplasm of T-/B-precursors resembling acute lymphoblastic leukemia, with no or limited bone marrow involvement (<25%), that develops more frequently in children and young adults and is typically characterized by a grossly enlarged mediastinum, and whose diagnostic hallmark is the expression of a T-/B-precursor cell immunophenotype, the T-cell subset accounting for 90% of all cases. The adoption of pediatric-derived, intensive lymphoblastic leukemia-like protocols led to significantly improved results, with survival rates of about 70% and 90% in adults and children, respectively. Adequate central nervous system prophylaxis and mediastinal irradiation contributed to the therapeutic success; however, the role of radiation therapy is debated due to toxicity concerns and the excellent results obtained with radiation-free programs especially in pediatric patients. With these modern schedules, localized radiotherapy and/or hematopoietic stem cell transplants could be generally omitted, and considered only for high-risk patients identified through postinduction computed tomography/positron-emission tomography scans, minimal residual disease analysis, and new genetics and genomics. New clinical studies will have to confirm the value of these assays for risk-oriented therapy, while further therapeutic progress is expected from the introduction of new drugs and targeting agents.

Gastrointestinal (GI) leiomyosarcoma (LMS) case series and review on diagnosis, management, and prognosis.

This review of 76 gastrointestinal (GI) leiomyosarcoma (LMS) cases that include 11 cases from the American University of Beirut Medical Center represents, to our knowledge, the largest number of combined GI LMS cases reported. The age range of GI LMS is variable, and the presentation is non-specific, making pathological diagnosis essential. LMSs usually lack CD117 and CD 34 mutations and are usually positive for smooth muscle cell markers. The review highlights surgery as the mainstay of treatment with negative margins attained most of the times. Adjuvant chemotherapy is used in around 7-27% of the cases mainly for small intestinal and colorectal LMS. The relatively small number of patients is a limitation on outcome analysis. However, LMS has a risk of recurrence reaching 39-80% and secondary metastasis reaching 55-71% in small intestinal and colorectal cases. In light of the high frequency of recurrence and metastasis, enrolling patients in clinical randomized trials to investigate the role of chemotherapy, radiation therapy, and targeted therapy is required for better control of this rare aggressive GI tumor.

Malignant rhabdoid tumour of kidney - a rare aggressive tumour

Malignant rhabdoid tumour of kidney is a rare highly aggressive neoplasm of childhood. We present the case of a 18- months old girl presenting with decreased appetite, abdominal distention of 20 days duration and 3 episodes of haematuria. The patient underwent left radical nephrectomy and histopathological examination of the excised specimen confirmed the diagnosis of malignant rhabdoid tumour of the kidney. This case highlights the need to consider malignant rhabdoid tumour of the kidney of possibility young children in presenting with a renal mass.

Sebaceous cell carcinoma of axilla: A rare case report

Introduction: sebaceous carcinoma is an uncommon and aggressive malignant cutaneous tumor. this neoplasm is thought to arise from sebaceous glandsin the skin and, therefore, may originate anywhere in the body where these glands are found. this region is a common site of origin because the periocular region is rich in this type of gland. However, axilla has rich sebaceous gland as well which may give rise to carcinoma. case report: We hereby present a case of a 55-year-old female with sebaceous cell carcinoma of the axilla. conclusion: though extra ocular sebaceous cell carcinoma is rare aggressive tumor.

Genomic/Epigenomic Alterations in Ovarian Carcinoma: Translational Insight into Clinical Practice.

Ovarian carcinoma is the most lethal gynecological malignancy worldwide. Recent advance in genomic/epigenomic researches will impact on our prevention, detection and intervention on ovarian carcinoma. Detection of germline mutations in BRCA1/BRCA2, mismatch repair genes, and other genes in the homologous recombination/DNA repair pathway propelled the genetic surveillance of most hereditary ovarian carcinomas. Germline or somatic mutations in SMARCA4 in familial and sporadic small cell carcinoma of the ovary, hypercalcemia type, lead to our recognition on this rare aggressive tumor as a new entity of the atypical teratoma/rhaboid tumor family. Genome-wide association studies have identified many genetic variants that will contribute to the evaluation of ovarian carcinoma risk and prognostic prediction. Whole exome sequencing and whole genome sequencing discovered rare mutations in other drive mutations except p53, but demonstrated the presence of high genomic heterogeneity and adaptability in the genetic evolution of high grade ovarian serous carcinomas that occurs in cancer progression and chemotherapy. Gene mutations, copy number aberrations and DNA methylations provided promising biomarkers for the detection, diagnosis, prognosis, therapy response and targets of ovarian cancer. These findings underscore the necessity to translate these potential biomarkers into clinical practice.

Collecting duct carcinoma of kidney in a teenage boy

Carcinoma of the collecting ducts of Bellini are rare aggressive neoplasms of distal nephron origin; it accounts for 2% of all renal cell carcinomas. Clinically, collecting duct carcinoma (CDC) is characterized by an extremely aggressive phenotype, accompanying metastatic diseases at presentation in most reported cases. Most cases of CDC have been reported with median age above 50 years. To our knowledge, this is the only second case report of CDC in a young teenager patient below 19 years with metastasis to lungs and bones at presentation.

Two Autopsy Cases of Advanced Adrenocortical Carcinoma: The Utility of Immunohistochemical Panel for Pathological Diagnosis

Adrenocortical carcinomas are extremely rare aggressive tumors arising from the adrenal cortex. Histopathologically, differential diagnosis between adrenocortical carcinoma and pheochromocytoma is often difficult. We report two autopsy cases of adrenocortical carcinoma. The first case was a 20-year old man. He had abdominal discomfort and increasing swelling of the lower legs. Computer tomography (CT) detected a tumor of 16 cm in diameter at the right retroperitoneum space and multiple liver nodules. Although he was treated with chemotherapy, he died of the cardiovascular failure accompanying inferior vena cava tumor embolism after 4 days of initial chemotherapy. The second case was a 57-year old woman. She felt easy fatigability. Abdominal ultrasonography and CT detected a tumor of 20 cm in diameter at the left retroperitoneum space and multiple liver nodules. She was also treated with chemotherapy and mitotane. However, she died 13 months after the initial diagnosis. Autopsies were conducted in both cases. Histologically, both tumors were composed of polygonal shaped cells with marked atypia. Immunohistochemically, both showed positive for synaptophysin, carletinin, inhibin, melan A and steroidogenic factor 1 and negative for chromogranin, suggesting that both tumors were adrenal cortex origin. Moreover, both cases were categorized into malignancy according to Weiss criteria. Thus, we diagnosed both cases were aderenocortical carcinoma. We report here two autopsy cases of aggressive advanced adrenocortical carcinoma, emphasizing the utility of the immunohistochemical panel.

Management and Outcomes of Plasmablastic Lymphoma: A Single-Center Experience

Background: Plasmablastic lymphoma (PBL) is a rare aggressive B-cell neoplasm characteristically occurring in patients with HIV infection. Given their rarity, most of the existing literature is from case reports or heterogenous pooled data. Optimal therapy is not clearly defined and outcomes are traditionally poor with median survival in the order of months. We describe the epidemiology, management and outcomes of this rare malignancy at a single center.Methods: We identified patients with PBL diagnosed between 2000-2015 at Parkland Memorial Hospital. Patients were followed till June 2015. Structured forms were used to interview patients and to abstract relevant (demographics, diagnostics, pathology, therapy and outcomes) clinical data. Logistic regression was used to assess variables for association with the odds of treatment failure. Log-rank test was used to assess differences in survival by treatment regimen. Statistical analysis was performed using SAS software version 9.0 (SAS Institute).Results: Twenty-nine patients with PBL were diagnosed in the study period. Median age at presentation was 42 years; 24 (83%) were male. Twenty-sex (90%) occurred in patients with HIV infection; median CD4+ count at diagnosis was 93/mm3; median viral load was 97,823 copies/mL. Only 5 patients (17%) were actively taking antiretroviral therapy at the time of diagnosis. Three patients were immunocompetent. The most common primary site of disease was the gastrointestinal tract (13 patients) followed by oral/maxillofacial sites (10 patients). Twenty patients (69%) presented with adanced stage disease (stage III or IV disease). EBV was detected in all 26 cases where it was tested; HHV-8 was negative in all patients. CD20 positivity was seen in only 4 patients (14%). MYC rearrangements were described in 70% patients. EPOCH (etoposide, prednisolone, vincristine, cyclophosphamide and hydroxydaunorubicin), was the most common treatment regimen used in 16 patients (56%). Radiation therapy was administered in 28% of patients. Overall survival across the cohort was 9.9 months. Twenty patients (69%) died during the follow-up period; their median survival was 2.6 months. Nine patients were alive after a median follow-up of 47.8 months. Those who were treated with EPOCH demonstrated a better median overall survival compared to those who were not (26.3 months vs 1.2 months, p value 0.01).Conclusions: PBL is a rare AIDS-related lymphoma most commonly affecting the oral cavity and gastrointestinal tract. It mostly occurs in HIV patients not on HAART. Patients usually present with advanced stage disease. OS continues to be poor but EPOCH regimens can improve survival compared to non-EPOCH regimens, and should be further explored in this setting. DisclosuresNo relevant conflicts of interest to declare.

A Case of Primary Malignant Melanoma of the Esophagus

Primary malignant melanoma of the esophagus is a rare disease and aggressive tumor of the esophagus. Primary malignant melanoma represents 0.1% to 0.2% of all primary esophageal cancers. Hematogenous and lymphatic metastasis are common. The prognosis is quiet poor, so early dectection and accurate diagnosis should be made. We encountered a patient with a black esophageal lesion, which was histopathologically confirmed to be primary malignant melanoma of the esophagus. A 65-year-old men was admitted for evaluation of a black pigmentation at lower esophagus which was found at regular general physical exam. He had no symptoms, no history of any illness and no family history of cancer. Physical examination found no abnormal pigmentations of the skin or mucosa. Endoscopy revealed multiple scattered 0.4cm sized black pigmented ulcerative lesion at 37cm from the incisors (Figure 1). Pathological findings from endoscopy show melanin pigment deposition and melanophage infiltration (Figure 2). Immunohistochemical staining was positive for HMB45, Ki-67, S100 and melan-A. Computed tomography of chest and abdomen showed no evidence of discernible lesion in the stomach, lung and regional lymphadenopathy. Positron emission tomography demonstrated no regional or distant metastasis. He received esophagectomy and gastroesphagostomy. Muscularis mucosa was involved, but the surgical margin of the esophagus was free from tumors. And all regional lymph nodes were found free of tumor.Figure 1Figure 2

Extra-Ocular Sebaceous Carcinoma of the Skin: A Report of Five Cases and a Review of the Literature

Background: Extra ocular sebaceous carcinoma is a rare aggressive adnexal tumour. The diagnosis of this tumour is difficult due to the variety of its clinical and histopathological features. The prognosis is actually considered as aggressive as the ocular counterpart. Methods and results: We propose to discuss the clinical features, histopathological findings and aggressive potential of extra ocular sebaceous carcinoma. Therefore, five extra ocular sebaceous carcinoma cases, diagnosed at the Dermatology and Pathology departments of Farhat Hached Hospital, from January 1998 to December 2007, were reviewed. The diagnosis was based on a histopathological examination. Three of them developed locoregional and/or distant metastases. One patient died from metastatic disease. Surgery was the mainstay of treatment without any cutaneous recurrence after a mean follow-up of two years. Conclusions: Extra ocular sebaceous carcinoma has an unpredictable prognosis. It can be highly aggressive and cause death. Surgery remains the mainstay of treatment.

Recurrent Oral Melanoma: A Case Report and Challenges in Management in Poor Resource Economy

Oral melanoma is a rare aggressive neoplasm which accounts for only 0.2-8% of all reported malignant melanomas. The common sites of its occurrence are the palate and gingiva with the maxillary arch being affected 80% of the time. Because of their presence at relatively obscure areas in the oral cavity, most of the malignant melanomas of the oral cavity are diagnosed at a late stage. We report a case of oral melanoma in a 55-year-old post-menopausal woman who had surgical excision followed by chemo-radiation but suffered recurrence. The challenges of management and the poor prognosis of the case are emphasized in this case report.

Preoperative cytological diagnosis of malignant mesothelioma of tunica vaginalis.

Malignant mesothelioma of tunica vaginalis testis is a rare aggressive neoplasm with ∼200 cases reported so far. A correct preoperative diagnosis of this rare tumor is difficult. Fine-needle aspiration cytology (FNAC) is a rapid and inexpensive diagnostic tool that may prove helpful in such cases. Very few cases have been diagnosed on cytology so far, and the descriptions of the cytological features have rarely been described in the literature. In this report we present the cytological features of malignant mesothelioma of tunica vaginalis testis which was diagnosed by FNAC and subsequently confirmed by histopatholoy and immunohistochemical (IHC) studies.

Primary Splenic Angiosarcoma: Clinical and Imaging Manifestations of This Rare Aggressive Neoplasm

Primary splenic angiosarcoma is a rare and fatal neoplasm arising from vascular endothelial cells within the spleen. With an incidence of 2 cases per 10 million people worldwide, the diagnosis and treatment of this rare entity is unfamiliar and challenging. We describe the case of a previously healthy 45-year-old woman who presented with vague upper-abdominal pain and was found to have a splenic mass on computed tomography. The patient underwent laparoscopic splenectomy and was found to have splenic angiosarcoma on microscopic evaluation. Although specific radiologic diagnosis is not possible, bringing the possibility of primary splenic angiosarcoma to the ordering clinician's attention has the potential to hasten treatment and improve patient outcomes. This case highlights the importance for radiologists to be aware of this rare neoplasm and to consider it in the differential when encountering a heterogeneously enhancing splenic mass.