Round Blue Cell Tumors Research Articles

Foxr2 promotes formation of CNS-embryonal tumors in a Trp53-deficient background.

Embryonal tumors in the central nervous system (CNS) are primary, aggressive, and poorly differentiated pediatric brain tumors. We identified forkhead box R2 (Foxr2) as an oncogene for medulloblastoma through a transposon-based insertional mutagenesis screen. Foxr2 translocation has been identified in a subset of human embryonal tumors of the CNS, designated as CNS neuroblastoma with Foxr2 activation (CNS NB-Foxr2); however, the in vivo functions of Foxr2 remain elusive. We analyzed the effect of Foxr2 overexpression in the mouse brain by generating a transgenic strain that expresses Foxr2 in the entire brain under a transformation related protein 53 (Trp53)-deficient background. We performed histological analysis of tumors and characterized tumor-derived sphere-forming cells. We investigated gene expression profiles of tumor-derived cells. Foxr2 and Trp53 loss promoted tumor formation in the olfactory bulb (OB) and brainstem (BS). The tumors showed the common morphological features of small round blue cell tumors, exhibiting divergent, mainly neuronal and glial, patterns of differentiation, which corresponds to the definition of CNS-embryonal tumors. Importantly, all mice developed CNS-embryonal tumors. In the OB, early proliferative lesions consisting of oligodendrocyte transcription factor 2 (Olig2+) cells were observed, indicating that Foxr2 expression expanded Olig2+ cells in the OB. Tumor-derived cells formed spheres in vitro and induced tumors that recapitulated the parental tumor upon transplantation, indicating the presence of tumor-initiating cells. Gene expression profiling revealed that OB and BS tumor cells were enriched for the expression of the genes specific to CNS NB-Foxr2. Our data demonstrate that Foxr2 plays a causative role in the formation of CNS-embryonal tumors.

Rhabdomyosarcoma and Extraosseous Ewing Sarcoma.

Rhabdomyosarcoma (RMS) is a malignant tumor that represents the most common form of pediatric soft tissue sarcoma. It arises from mesenchymal origin and forms part of the group of small round blue cell tumors of childhood. It has a constant annual incidence of 4.5 cases per 1,000,000 children. The known histological diagnosis of the two major subtypes (embryonal and alveolar) has been recently enhanced by tumor biological markers and molecular differentiation diagnostic tools that have improved not only the updated classification based on risk stratification, but also the treatment approach based on the clinical group. Ewing sarcoma (ES) is a round cell tumor, highly malignant and poorly differentiated that is currently the second most common malignant bone tumor in children. In rare instances, it develops from an extraskeletal origin, classified as extraosseous Ewing sarcoma (EES). We provide an updated, evidence-based and comprehensive review of the molecular diagnosis, clinical and diagnostic approach and a multidisciplinary medical and surgical management according to the latest standard of care for the treatment of pediatric RMS and EES.

Diagnostic Utility of Pax8, Pax2, and NGFR Immunohistochemical Expression in Pediatric Renal Tumors.

Pediatric renal tumors (PRT) with small round blue or spindle cell morphology can be diagnostically challenging and only a limited number of immunohistochemical markers have been documented to help in the diagnosis: paired box (Pax) 2 and nerve growth factor receptor (NGFR) positivity have been demonstrated in Wilms tumor (WT) and clear cell sarcoma of the kidney (CCSK), respectively. However, the immunohistochemical expression of these markers in other PRT remains unknown. This study investigated Pax8, Pax2, and NGFR immunophenotype in a large series of PRT. Pax8 and Pax2 showed an identical staining pattern, and were expressed in all (100%) WT while most CCSK were negative. All congenital mesoblastic nephromas, metanephric stromal tumors, primitive neuroectodermal tumors, desmoplastic small round blue cell tumors, most rhabdoid tumors, and synovial sarcomas were negative for Pax8. NGFR was expressed in 96% of CCSK (diffuse expression in 91%). Only a minority of WT stained for NGFR: 16% showed expression in the blastemal and 25% in the mesenchymal components. NGFR expression was noted in synovial sarcomas (67%, with diffuse expression seen in only 1 case, 8%), rhabdoid tumors (19%), cellular congenital mesoblastic nephromas (13%) and metanephric stromal tumors (12.5%). Primitive neuroectodermal tumors and desmoplastic small round blue cell tumors were negative for NGFR. In conclusion, Pax8/Pax2 and NGFR are sensitive markers for the diagnosis of WT and CCSK, respectively. However, their specificity is limited by variable reactivity within a subset of other renal neoplasms.

Melanotic Neuroectodermal Tumor of Infancy.

Melanotic neuroectodermal tumor of infancy, albeit rare and generally regarded as benign, is an important tumor to recognize because of its rapid growth, potential for local recurrence, and small round blue cell morphology, which can lead to misdiagnosis of a malignant neoplasm. To review its clinical presentation and immunomorphologic findings, and discuss common entities in the differential diagnosis. The study involved PubMed searches, including multiple review articles, case studies, retrospective studies, selected book chapters, and University of Michigan cases. Melanotic neuroectodermal tumor of infancy most commonly occurs in the bones of the head and neck region during the first year of life, but it can also present in other locations, including the central nervous system, testes, ovaries, and subcutaneous soft tissues. Histologically, it is composed of a biphasic population of cells, consisting of epithelioid melanin-producing cells and primitive neurogenic cells in a fibrocollagenous stroma. These microscopic findings, especially in small biopsies, can lead to a broad differential diagnosis that includes malignant small round blue cell tumors and malignant melanoma. Melanotic neuroectodermal tumor of infancy commonly has an infiltrative growth pattern, and anatomic constraints often lead to incomplete resection and local recurrence, requiring multiple surgical operations. Because melanotic neuroectodermal tumor of infancy can mimic a more aggressive and aggressively treated malignancy, recognition of this rare tumor is very crucial for pathologists.

Classifying Incomplete Gene-Expression Data: Ensemble Learning with Non-Pre-Imputation Feature Filtering and Best-First Search Technique.

(1) Background: Gene-expression data usually contain missing values (MVs). Numerous methods focused on how to estimate MVs have been proposed in the past few years. Recent studies show that those imputation algorithms made little difference in classification. Thus, some scholars believe that how to select the informative genes for downstream classification is more important than how to impute MVs. However, most feature-selection (FS) algorithms need beforehand imputation, and the impact of beforehand MV imputation on downstream FS performance is seldom considered. (2) Method: A modified chi-square test-based FS is introduced for gene-expression data. To deal with the challenge of a small sample size of gene-expression data, a heuristic method called recursive element aggregation is proposed in this study. Our approach can directly handle incomplete data without any imputation methods or missing-data assumptions. The most informative genes can be selected through a threshold. After that, the best-first search strategy is utilized to find optimal feature subsets for classification. (3) Results: We compare our method with several FS algorithms. Evaluation is performed on twelve original incomplete cancer gene-expression datasets. We demonstrate that MV imputation on an incomplete dataset impacts subsequent FS in terms of classification tasks. Through directly conducting FS on incomplete data, our method can avoid potential disturbances on subsequent FS procedures caused by MV imputation. An experiment on small, round blue cell tumor (SRBCT) dataset showed that our method found additional genes besides many common genes with the two compared existing methods.

Corruption of neuroblastoma patient derived xenografts with human T cell lymphoma

BackgroundPatient derived xenografts (PDXs) provide a unique opportunity for investigators to study tumor cell activity, response to therapeutics, and resistance patterns without exposing the human patient to experimental compounds, and thereby play a crucial role in pre-clinical evaluation of new therapies. It has been reported that PDXs may undergo a transformation to lymphoma, most commonly associated with Epstein Barr virus (EBV). If the character of a xenograft becomes compromised and remains undetected, it could have a detrimental impact on the research community as a whole. Our lab has established a number of pediatric solid tumor PDXs which accurately recapitulate the human tumors following several passages. One particular neuroblastoma PDX was noted to grow quickly and with an unusual phenotype, leading us to hypothesize that this PDX had undergone a transformation. MethodsThe PDX in question was investigated with histology, immunohistochemistry (IHC), EBER in situ hybridization, and PCR to determine its identity. ResultsHistology on the tumor revealed a small, round blue cell tumor similar to the original neuroblastoma from which it was derived. IHC staining showed that the tumor was composed of lymphocytes that were CD3 positive, <5% CD4 positive, and CD20 negative. The cells were Epstein Barr virus negative. PCR demonstrated that the tumor was human and not murine in origin. ConclusionThese findings indicate that a human T Cell lymphoma developed in place of this neuroblastoma PDX. Changes in PDX identity such as this one will significantly impact studies utilizing pediatric PDXs and the mechanism by which this occurred warrants further investigation.

Recurrent Primitive Neuroectodermal Tumor (PNET) of the Pancreas

Ewing's family of tumors (EFT) originate from neuronal crest cells and share morphological, histological and cytogenic features. EFTs include typical (osseous) Ewing's sarcoma, atypical (non-osseous) Ewing's sarcoma, primitive neuroectodermal tumor (PNET), and Askin tumor. Only a few cases of ES/PNETs of the pancreas have been reported and even fewer cases of recurrent pancreatic PNETs are known. Herein we report a case of recurrent pancreatic PNET presenting as abdominal pain ten years following treatment of left scapular Ewing's sarcoma. Four years following partial resection, local radiation and CHOP chemotherapy for left scapular Ewing's sarcoma, a 54-year-old male presented with epigastric abdominal pain. CT scan of the abdomen demonstrated a mass at the head of the pancreas and biopsy confirmed a CD-99 positive round blue cell tumor. FISH showed 15 % ESWR1 locus rearrangement. Together these findings were consistent with pancreatic PNET. The patient was treated with local radiation and CHOP chemotherapy. Treatment response was monitored with serial PET scans. Unfortunately, after six years of sustained response the patient presented with epigastric abdominal pain. Laboratory studies were significant for elevated bilirubin (1.1 mg/dL). A mesenteric vein thrombosis was detected on CT scan as well as a 43 mm by 29 mm mass at the pancreatic head. PET scan confirmed a 19 mm by 22 mm FDG avid area at the head of the pancreas. Biopsy demonstrated a CD-99 positive round blue cell tumor. Overall the findings were consistent with recurrent pancreatic PNET.EFT/PNETs are round blue cell tumors with neuroendocrine differentiation (chromogranin A, synaptophysin or neuron specific enolase) and CD-99 expression. Although, CD-99 is nonspecific. Additionally, many EFTs demonstrate t(11; 12) (q24; q12) chromosomal translocation resulting in the fusion protein EWS-FLI1 which disrupts transcription and drives tumor growth. EFTs commonly arise from long bones and afflict young patients. Although rare, EFT/PNETs can arise from solid organs. Primary PNETs of the lung, urinary bladder, gall bladder, and uterus have been reported. Only 0.3 % of pancreatic masses are diagnosed as EFT/PNET. Our case highlights the importance of correlating clinical, radiographic, and pathological findings in the diagnosis of pancreatic PNET and emphasizes the importance of multimodality treatment of this aggressive disease.

A Rare, yet Aggressive, Intra-Abdominal Malignancy: Ewing Sarcoma of the Pancreas

Introduction: Ewing sarcoma (ES) is a malignant bone tumor of long-bones, which typically occurs in children. Extraskeletal Ewing sarcoma (EES) is a poorly differentiated soft tissue sarcoma within morphologic category of ‘small-round-cell’ tumors and accounts for less than 1% of soft tissue sarcomas. Only 24 cases have been reported in the literature. Herein, we present an interesting case of EES of pancreas. Case Description: 34-year-old male presented to clinic secondary to insidious onset, generalized abdominal pain for past 1-month. Physical exam revealed non-tender, moderately distended abdomen with a palpable mass above the umbilicus. Initial lab workup showed mild elevation of AST 91 (0-50 U/L) and alkaline-phosphatase 337 (38-126 U/L). CT abdomen showed lobulated heterogeneous mass with necrotic transformation in body and tail of pancreas, with multiple liver lesions. Resultantly, a working diagnosis of adenocarcinoma of pancreas with metastasis to liver was made. A CT-guided biopsy of pancreatic and hepatic mass showed small, blue, round cells with scant cytoplasm. Hence, the previous diagnosis of pancreatic adenocarcinoma was disregarded, and other differential diagnoses including EES, neuroblastoma, non-Hodgkin's lymphoma vs desmoplastic small blue round cell tumor were considered. Further testing with immunohistochemistry confirmed the diagnosis of EES. Subsequently, patient was started on chemotherapy with doxorubicin, cyclophosphamide and vincristine. After one round of chemotherapy, patient developed neutropenic fever and died after 1-month from a complicated hospital course. Discussion: This case highlights an extremely rare type of soft tissue sarcoma (EES) at an unusual location. The diagnosis of ESS is confirmed by immunohistochemistry as imaging modalities often remain nonspecific. Histologically, ES and EES are described as small, blue, round cells with hyperchromatic nuclei and scant cytoplasm, with molecular expression of MIC2, CD99 and antibody against FLI1 centered in nucleus. Though 85% of the ES cases are associated with chromosomal translocation t(11;22) and q(24;12), it remains non-specific. EES is an aggressive and malignant tumor with a 5-year survival rate of around 50%. Surgical excision, plus chemotherapy and radiotherapy is the main modality of treatment. Though EES is rare, physicians should be acquainted with and consider it in the differential diagnosis, as early recognition and intervention is very critical.1397_A.tif Figure 1: Necrotic mass (14.8cm x 5.6cm x 6.7cm) again visualized in the pancreas along with multiple hypo-attenuated liver lesions.1397_B.tif Figure 2: Small, blue, round cells with high NC ratio, dark chromatin pattern with scant cytoplasm. Tumor cells positive for vimentin; negative for CD45, CD117, chromogranin, synaptophysin, pan cytokeratin, smooth muscle actin, desmin, HMB-45, S-100 and CD138. Pattern is highly consistent with high grade soft tissue sarcoma- EES.

Array-based DNA-methylation profiling in sarcomas with small blue round cell histology provides valuable diagnostic information

Undifferentiated solid tumors with small blue round cell histology and expression of CD99 mostly resemble Ewing sarcoma. However, they also may include other tumors such as mesenchymal chondrosarcoma, synovial sarcoma, or small cell osteosarcoma. Definitive classification usually requires detection of entity-specific mutations. While this approach identifies the majority of Ewing sarcomas, a subset of lesions remains unclassified and, therefore, has been termed “Ewing-like sarcomas” or small blue round cell tumors not otherwise specified. We developed an approach for further characterization of small blue round cell tumors not otherwise specified using an array-based DNA-methylation profiling approach. Data were analyzed by unsupervised clustering and t-distributed stochastic neighbor embedding analysis and compared with a reference methylation data set of 460 well-characterized prototypical sarcomas encompassing 18 subtypes. Verification was performed by additional FISH analyses, RNA sequencing from formalin-fixed paraffin-embedded material or immunohistochemical marker analyses. In a cohort of more than 1,000 tumors assumed to represent Ewing sarcomas, 30 failed to exhibit the typical EWS translocation. These tumors were subjected to methylation profiling and could be assigned to Ewing sarcoma in 14 (47%), to small blue round cell tumors with CIC alteration in 6 (20%), to small blue round cell tumors with BCOR alteration in 4 (13%), to synovial sarcoma and to malignant rhabdoid tumor in 2 cases each. One single case each was allotted to mesenchymal chondrosarcoma and adamantinoma. 12/14 tumors classified as Ewing sarcoma could be verified by demonstrating either a canonical EWS translocation evading initial testing, by identifying rare breakpoints or fusion partners. The methylation-based assignment of the remaining small blue round cell tumors not otherwise specified also could be verified by entity-specific molecular alterations in 13/16 cases. In conclusion, array-based DNA-methylation analysis of undifferentiated tumors with small blue round cell histology is a powerful tool for precisely classifying this diagnostically challenging tumor group.

Abstract 3181: Class I histone deacetylases (HDAC) critically contribute to Ewing sarcoma pathogenesis

Abstract Introduction: Recent evidence demonstrated that a low mutation rate seems a general feature of pediatric cancers. Ewing sarcoma (EwS) is defined by balanced chromosomal EWS/ETS translocations, which give rise to oncogenic chimeric proteins (EWS-ETS). Previously, we identified the histone methyl-transferase enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), the enzymatic subunit of the polycomb PRC2 complex, to be over-expressed in EwS. RNA interference of EZH2 suppressed tumor development and metastasis in vivo and microarray analysis of EZH2 knock down revealed an EZH2-maintained, undifferentiated, reversible phenotype in EwS. Microarray analysis further revealed that treatment with MS-275 or TSA resulted in the induction of a similar pattern of differentiation genes as was previously observed after EZH2 blockade and seems to be dependent on histone deacetylase (HDAC) activity. Experimental procedures: The role of class I histone deacetylases (HDACs) was determined using different potent inhibitors like Trichostatin A (TSA), Romidepsin (FK228), Entinostat (MS-275) and PCI-34051 as well as a CRISPR/Cas9 approach to knock out class I HDACs. To analyze resulting changes microarray analysis, gene set enrichment analysis (GSEA), qRT-PCR, western blotting, proliferation, apoptosis and invasion assays as well as immunofluorescence experiments were deployed. Results: Interestingly, treatment with enzymatic inhibitors blocking EZH2 activity could not mimic the results observed after EZH2 RNA interference indicating that EZH2-containing PRC2 complexes may serve as a building block of class I HDAC activity in ES. Consequently, in proliferation assays EwS cells were more susceptible to treatment with HDAC inhibitors than other small round blue cell tumors such as neuroblastoma or pediatric cALL cells. Microarray and GSEA analysis demonstrated that treatment with Romidepsin resulted in an inhibition of an EwS specific expression profile while Entinostat suppressed metastasis relevant genes. In addition, EwS cells demonstrated increased susceptibility to treatment with chemotherapeutics such as Doxorubicin and Vincristine in the presence of HDACi. Consequently, CRISPR/Cas9 knock outs of HDAC1 to HDAC3 in EwS cell lines resulted in a reduction of their proliferative ability and greater sensitivity to treatment with chemotherapeutics. Conclusion: Class I HDAC proteins seem to be important mediators of the pathognomonic EWS-ETS-mediated transcription program in EwS and thus interesting new treatment opportunities for this malignant disease. Citation Format: Oxana Schmidt, Nadja Nehls, Kristina von Heyking, Tim Hensel, Stefan Burdach, Günther H. Richter. Class I histone deacetylases (HDAC) critically contribute to Ewing sarcoma pathogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3181.

Abstract 4248: Small round blue cell tumour of childhood. A case of health disparity in Nigeria in the survival of patients

Abstract Introduction Nigeria is Africa's most populous country and the 9th most populous country in the world. The country is the 6th largest producer of petroleum in the world. Health care and general living conditions in Nigeria are poor, especially for children and women. At least 70 to 75 percent of health expenditure comes from out of pocket expenses. Childhood cancers as a growing public health challenge and is increasingly being recognized worldwide, including the developing nations. Tremendous progress has been made in the treatment and cure of childhood cancers mostly in the developed world, most cases die of childhood cancers in our society. We look at fifty two cases of small round blue cell tumour of childhood (SRBCT) a diverse group of childhood cancers that have considerable overlap in epidemiology, morphology and immunophenotype over a three year period. Methods We reviewed the histology report and paraffin blocks of patients diagnosed as SRBCT of childhood in the department of pathology, from 2014-2017. We identified fifty two patients diagnosed as SRBCT during the study period. The information extracted includes age, sex, cancer type, treatment modality and outcome of all patients. We subjected the blocks to nine immunohistochemical stains to rule out differentials using Genemed biotechnology protocol. The stains include Cytokeratin, EMA, S-100, CD99, Desmin, CD10, CD20, BCL2 and Synaptophysin.. Results The age range in this study was 2-15 years with a mean of 7.2 years. The most common site for SRBCT was the head and neck region accounting for more than 46%. This is followed by the abdomen accounting for 19%. The commonest SRBCT after immunohistochemical stains was Burkitt's lymphoma 16(30.7%), retinoblastoma 8(15.4%), alveolar rhabdomyosarcoma 7(13.5%), Follicular lymphoma 5(9.6%), ES/PNET 5(9.6%), nephroblastoma 4(7.7%), neuroblastoma 4(7.7%) and synovial sarcoma 3(5.8%). All patients 52(100%) undergo chemotheraphy, 36(69%) undergo both surgery and chemotheraphy while 8(15.4%) sign against medical advice. All patients pay through out of pocket expences with no access to insurance. Thirty three patients (63%) died during chemotheraphy. Most patients are lost to follow up due to financial burden and unavailability of standard oncology services. Conclusion While tremendous progress has been made in the treatment of childhood cancers in the developed world, it still remains an important health problem in our societies largely because of multifactorial reasons creating a huge health disparity and contributing to under five mortality in our environment. Reducing poverty and creating better health facilities through knowledge sharing and collaboration with reduce this disparity. Citation Format: Kasimu U. Adoke, Faruk Mohammed. Small round blue cell tumour of childhood. A case of health disparity in Nigeria in the survival of patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4248.

Genomic and Proteomic Alterations in Desmoplastic Small Round Blue-Cell Tumors.

Desmoplastic small round blue-cell tumors (DSRCTs) are sarcomas that contain the t(11;22) (p13;q12) translocation EWS-WT1 fusion protein. Because this is a rare tumor type, prospective clinical trials in DSRCT are challenging. Patients are treated in a manner similar to those with Ewing sarcoma; however, differences in prognosis and clinical presentation suggest fundamental differences in biology and potentially different therapeutic implications. This study aimed to characterize the molecular characteristics of DSRCT tumors to explore unique therapeutic options for this extremely rare and aggressive cancer type. Thirty-five DSRCT tumors were assessed using next-generation sequencing, protein expression (immunohistochemistry), and gene amplification (chromogenic in situ hybridization or fluorescence in situ hybridization). Three patients had tumor mutational load, which was calculated as somatic nonsynonymous missense mutations sequenced with a 592-gene panel. Gene expression data were obtained for an additional seven DSRCT tumors. Molecular alterations were compared with 88 Ewing sarcomas. The most common alterations that distinguished DSRCTs from Ewing sarcoma included higher androgen receptor (AR), TUBB3, epidermal growth factor receptor, and TOPO2A expression. Independent analysis by RNA sequencing confirmed higher AR expression from an independent data set of EWS-WT1 fusion-positive DSRCTs compared with Ewing sarcoma and a pan-cancer analysis. DSRCTs had somatic mutations that were identified in TP53 and FOXO3, averaged five mutations per megabase, and no programmed death-ligand 1 expression was detected in any DSRCT samples. The current analysis provides the first comparative analysis, to our knowledge, of molecular aberrations that distinguish DSRCT from Ewing sarcoma. High AR expression seems to be a defining event in these malignancies, and additional investigation of the responsiveness of AR inhibitors in this disease is encouraged.

Adult with colon alveolar rhabdomyosarcoma

The Purpose of the present study is to present a case of alveolar rhabdomyosarcoma in an 81-year-old patient. An 81-year-old woman presents changes in bowel habits, as well as a mobile mass in the abdomen, fixed to deep planes. Resection is performed. Immunohistochemistry was positive to Myo D1, Anti CD99 and Synaptophysin. Rhabdomyosarcoma may be present in adults, for which it should be discarded in case of small round blue cell tumors. Immunohistochemistry is useful to make a differential diagnosis of the tumor. Survival rates rises when using chemotherapy and surgery.

Performance Characteristics of Cerebrospinal Fluid Cytology: An Analysis of Responses From the College of American Pathologists Nongynecologic Cytopathology Education Program.

- Cerebrospinal fluid cytology is a critical diagnostic tool for the diagnosis of many conditions affecting the central nervous system. - To assess the performance characteristics of cerebrospinal fluid cytology samples by evaluating participant interpretations within the College of American Pathologists Nongynecologic Cytopathology Education program. - Participant interpretations (N = 46 264) evaluated in the College of American Pathologists Nongynecologic Cytopathology Education Program were examined for concordance with the general category and with the reference diagnosis. Two nonlinear mixed models were used to analyze the concordance rates. - The overall concordance rates for the general category and reference diagnosis were 92.1% and 81.0%, respectively. In the malignant category, the concordance rates with the reference diagnosis were lowest for diagnoses of nonhematopoietic small blue round cell tumors (54.8%) and metastatic malignancy (77.5%); the concordance rate with the reference diagnosis was highest for leukemia/lymphoma (94.0%). In the benign category, the concordance rate was lowest for normal cerebrospinal fluid reference diagnoses (58.6%), followed by acute and chronic inflammation (64.6%), fungal infection (80.8%), and macrophages (85.3%). Significant differences in concordance were uncovered when performance was evaluated by participant type and stain technique. Leukemia/lymphoma was the most common diagnosis for misclassified nonhematopoietic small blue round cell tumor cases and negative or inflammatory cerebrospinal fluid cases. - This study illustrates the difficulties in achieving accurate diagnoses from cerebrospinal fluid specimens, particularly for nonhematopoietic small blue round cell tumors and normal and inflammatory cerebrospinal fluid specimens.

AN UNUSUAL MASS OF THE CHEST WALL IN A 7 YEARS OLD CHILD: AN ASKIN'S TUMOUR

Askin’s tumour is a primitive neuroectodermal tumour developing from the soft tissues of the chest wall. It is commonly misdiagnosed due to features similar to other round blue cell tumours. The approach for its diagnosis and treatment is complex and requires a multidisciplinary team. The recommended treatment is chemotherapy and surgical excision mainly. The prognosis is dependent on many factors. We managed a child of Askin’s tumour using modalities such as neoadjuvant chemotherapy and surgical excision and found a good response.Key words: Chest wall mass, Askin’s tumour, Ewing sarcoma

Fine-needle aspiration of bilateral small round blue cell tumors in neck in a 65-year-old man: Significance of a wider differential.

Fine-needle aspiration of bilateral small round blue cell tumors in neck in a 65-year-old man: Significance of a wider differential.

Unusual Presentations of Gynecologic Tumors: Primary, Extrauterine, Low-Grade Endometrioid Stromal Sarcoma.

- Low-grade endometrial stromal sarcomas, when uterine in location, are relatively easy to diagnose because of characteristic morphology and patterns of myometrial invasion. However, when they occur at extrauterine sites, they fall under the broad umbrella of small round blue cell tumors, making diagnosis challenging, especially when they have variant morphologic features and lack the characteristic pattern of invasion. - To provide an insight into the sites of occurrence of low-grade endometrioid stromal sarcomas, the variant morphologic patterns, clues to diagnosis, and the usefulness of immunohistochemistry as an aid to facilitate correct diagnosis. The outcome of these tumors, in comparison with their uterine counterpart, is also discussed. - Existing peer-reviewed literature was reviewed. - Low-grade endometrioid stromal sarcoma is an uncommon neoplasm that can be misdiagnosed because of its rarity, unusual location, and presence of numerous variant histologic patterns that mimic other tumors. Knowledge of those features; consideration of this tumor in the differential diagnosis of small, round blue cell tumors at any location in a woman; and an appropriate use of immunohistochemistry can help facilitate the diagnosis.

Immunohistochemical characterization of small round blue cell tumors of childhood at Ile-Ife, Nigeria: A 10-Year retrospective study

Background: Immunostains when used in correlation with clinical site of tumours and morphology permits accurate and specific diagnosis of these undifferentiated tumours. Materials and Methods: A ten-year retrospective research of the histopathological and immunohistochemical features of small round blue cell tumours (SRBCT) in OAUTHC was analyzed. Pathology reports of all SRBCT and their blocks were retrieved and recut slides reviewed to determine each tumour types. Acute myelocytic lymphoma/leukeamias and Glioblastoma multiformis were excluded from SRBCT of childhood. Eighty four (84) cases that fulfilled the inclusion criteria were analyzed using immunohistochemistry. Results: The age range of presentation was 0-15 years (Mean 5.98±3.964 year S.D.). Retinoblastoma and Wilms' tumours were the commonest histological sub-types with a percentage of 20.0% each followed by Burkitt lymphoma (17.6%), rhabdomyosarcoma (9.8%) which was the only soft tissue sarcoma found. The least represented was supra-tentorial CNS-PNET (1.2%). Eighty four blocks of SRBCT were subjected to different panels of immunohistochemistry. Of all these tumours 36 cases had a change in diagnosis: 23 cases had an initial, pre-immunohistochemical umbrella diagnosis ranging from NHL, SRBCT to no pathological diagnosis at all. Seven (7) cases with initial diagnosis ranging from Ewing's sarcoma (1 case), retinoblastoma (1 case) to rhabdomyosarcoma (5 cases) were finally confirmed with immunostains as Burkitt lymphoma (BL) while one case of BL was finally confirmed as rhabdomyosarcoma. The last five of the 36 cases were totally non-neoplastic lesions but had histology diagnosis ranging from NHL, spinal cell sarcoma to periosteal osteosarcoma. The immunostains done on these 5 cases revealed erythroid hyperplasia with dyserythropoiesis, cellular neurofibroma, fibrous dysplasia, reactive follicular hyperplasia and normal retinal tissue. Conclusion: Application of immunohistochemistry does indeed enhance the diagnostic accuracy of these undifferentiated tumors.

Primary uterine primitive neuroectodermal tumor

Primitive neuroectodermal tumors (PNETs) are rare malignant tumors and extremely rare in uterine corpus. We report a case of primary uterine PNET in Taiwan. A 68-year-old woman presented with vaginal bleeding and abdominal fullness for 2 weeks. Computed tomography revealed one 8.0 cm uterine corpus tumor with carcinomatosis peritonei and ascites. The cancer antigen 125 level was high (280.7 IU/ml). Pathology of endometrial biopsy diagnosed PNET according to the characteristic of small blue round cells with Homer-Wright rosettes and Friend leukemia integration 1 transcription factor (FLI-1) positive. She received dose-dense chemotherapy with paclitaxel and carboplatin, but the response was poor and the PENT metastasized to liver. PNETs belong to small blue round cell tumor group that is difficult to be diagnosed on histopathology. The immunohistochemistry for CD99 and FLI-1 provides high sensitivity and specificity for diagnosis, respectively. No optimal treatment is established due to rarity. The prognosis is poor, usually <3 years survival.

Solitary Fibrous Tumors in Pediatric Patients: A Rare and Potentially Overdiagnosed Neoplasm, Confirmed by STAT6 Immunohistochemistry.

Pathological diagnosis of solitary fibrous tumor (SFT) in the pediatric population is challenging, as it occurs uncommonly in this age-group and resembles other spindle cell neoplasms. SFT contains a NAB2-STAT6 fusion gene, which can be reliably detected using STAT6 immunohistochemistry. Positive staining is highly sensitive and specific. We sought to investigate the utility of STAT6 immunohistochemistry, to show how commonly SFT was historically recognized at 3 academic pediatric institutions, to reclassify them when appropriate, and to demonstrate features of major mimics of SFT. Our series included cases with a previous diagnosis of SFT or for which SFT was among key considerations, from 3 major academic pediatric hospitals seen over the past 30 years. Of 18 tumors identified, only 3 tumors from 2 patients demonstrated positive STAT6 staining as well as the typical histology and immunophenotype seen in SFT. The remaining 15 tumors were reclassified based on morphology, additional immunohistochemistry and fluorescence in situ hybridization as desmoid-type fibromatosis (3 tumors), nerve sheath/neural tumors (3 tumors), low-grade fibromyxoid sarcoma, medallion-like dermal fibroma, poorly differentiated Sertoli cell tumor, nodular/proliferative fasciitis, calcifying fibrous tumor, aneurysmal bone cyst of soft tissue, STAT6-negative SFT with adipocytic differentiation, undifferentiated small round blue cell tumor, and scar (1 tumor each). Our study confirms that SFT is rare in the pediatric population and that it is potentially overdiagnosed. STAT6 immunohistochemistry is recommended to confirm the diagnosis of SFT in the pediatric population.