Round Blue Cell Tumors Research Articles

Stemness Correlates Inversely with MHC Class I Expression in Pediatric Small Round Blue Cell Tumors.

Simple SummaryTumors occurring at a young age are distinct from tumors in older individuals, clinically and pathologically. As small round blue cell tumors (SRBCTs), they often show a resemblance to stem cells and immature precursor cells during embryonal development. Recently, immunotherapy has become an option for a subset of patients with limited success. We observed that in almost all the pediatric SRBCT types investigated (n = 1134) there was an inverse relationship, when comparing genes highly expressed in stem cells with genes encoding MHC class I molecules. MHC class I molecules are important in tumor cell recognition by cytotoxic T cells. We suspect that these tumors are derived from multipotent precursor cells that naturally show a low MHC class I expression and a lack of immune recognition necessary for prenatal proliferation and development.Recently, immunotherapeutic approaches have become a feasible option for a subset of pediatric cancer patients. Low MHC class I expression hampers the use of immunotherapies relying on antigen presentation. A well-established stemness score (mRNAsi) was determined using the bulk transcriptomes of 1134 pediatric small round blue cell tumors. Interestingly, MHC class I gene expression (HLA-A/-B/-C) was correlated negatively with mRNAsi throughout all diagnostic entities: neuroblastomas (NB) (n = 88, r = −0.41, p < 0.001), the Ewing’s sarcoma family of tumors (ESFT) (n = 117, r = −0.46, p < 0.001), rhabdomyosarcomas (RMS) (n = 158, r = −0.5, p < 0.001), Wilms tumors (WT) (n = 224, r = −0.39, p < 0.001), and central nervous system-primitive neuroectodermal tumors CNS-PNET (r = −0.49, p < 0.001), with the exception of medulloblastoma (MB) (n = 76, r = −0.24, p = 0.06). The negative correlation of MHC class I and mRNAsi was independent of clinical features in NB, RMS, and WT. In NB and WT, increased MHC class I was correlated negatively with tumor stage. RMS patients with a high expression of MHC class I and abundant CD8 T cells showed a prolonged overall survival (n = 148, p = 0.004). Possibly, low MHC class I expression and stemness in pediatric tumors are remnants of prenatal tumorigenesis from multipotent precursor cells. Further studies are needed to assess the usefulness of stemness and MHC class I as predictive markers.

A rare case report of renal ewing sarcoma/primitive neuroectodermal tumor with ACTH production

BackgroundEwing sarcoma/primitive neuroectodermal tumor (PNET) of the renal is extremely rare. The common cause of ectopic ACTH syndrome is pulmonary neuroendocrine tumors, such as small cell carcinomas and carcinoid tumors. Here, we present an unusual case of ectopic ACTH syndrome and hypothyroidism caused by Ewing sarcoma/PNET of the right kidney.Case presentationA 19-year-old girl presented with a history of right lumbar pain and discomfort for 2 months, aggravated for 2 days. Abdominal contrast-enhanced computed tomography and computed tomography angiography showed an upper pole occupancy of the right kidney occupancy with subepithelial hemorrhage. Preoperative hormone levels including plasma total cortisol (PTC), adrenocorticotrophic hormone (ACTH) and thyroid hormone measurements were abnormal, indicating that the patient had Cushing syndrome and hypothyroidism. The patient underwent right radical nephrectomy. Histopathological analysis revealed a renal small round blue cell tumor (consistent with a primitive neuroectodermal tumor), with positive immunohistochemistry for CD99 and Ki67 (about 10%) and molecular pathology for EWSR1 gene fusions. PTC, ACTH and thyroid hormone returned to normal after surgery.ConclusionsWe report a rare ectopic ACTH syndrome and hypothyroidism due to renal Ewing sarcoma/PNET. The clinical manifestation of renal Ewing sarcoma/PNET is non-specific and the diagnosis relies on pathological morphology, immunohistochemistry and fusion gene detection. At present, surgery combined with radiotherapy and chemotherapy is used in the treatment, but the prognosis is still not optimistic.

Transmission Electron Microscopy: A Surgical Pathology Tool for Neuroblastoma.

Pediatric small round blue cell tumors (PSRBCT) are an intriguing and challenging collection of neoplasms. Light microscopy of small round blue cell tumors identifies small round cells. They harbor a generally hyperchromatic nucleus and relatively scanty basophilic cytoplasm. Pediatric small round blue cell tumors include several entities. Usually, they incorporate Wilms tumor, neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, retinoblastoma, lymphoma, and small cell osteosarcoma, among others. Even using immunohistochemistry, the differential diagnosis of these neoplasms may be controversial at light microscopy. A faint staining or an ambiguous background can deter pathologists from making the proper diagnostic decision. In addition, molecular biology may provide an overwhelming amount of data challenging to distinguish them, and some translocations may be seen in more than one category. Thus, transmission electron microscopy (TEM) can be extremely valuable. Here we emphasize the modern protocol for TEM data of the neuroblastoma. Tumor cells with tangles of cytoplasmic processes containing neurosecretory granules can diagnose neuroblastoma.

Extraosseous Ewing Sarcoma in a Pelvic Region: A Case Report

Ewing sarcoma; neoadjuvant chemotherapy; radiation therapy.

A multicenter evaluation of treatment patterns and outcomes for Adamantinoma-like Ewing sarcoma.

e23500 Background: Sarcomas are a rare and heterogenous group of malignancies comprised of &gt; 150 histologic subtypes. Adamantinoma-like Ewing sarcoma (ALES) is a rare, small round blue cell tumor that represents a variant of Ewing sarcoma (EWS). First described 20 years ago, ALES harbors a EWS subset defining EWS-related translocation; however, ALES has a complex epithelial differentiation component defining it as a distinct clinical entity. Most ALES cases arise in the head and neck, but it has also been reported in the extremities and thorax. Given the rarity of ALES, there is a paucity of literature to guide treatment and describe outcomes. Methods: We performed a retrospective review (January 1, 2010-January 1, 2022) at two sarcoma centers in the United States and identified 4 cases of ALES. Tumor and patient characteristics were described, and patient outcomes were assessed. Results: Four patients were identified. 3 (75%) were male. Median age at diagnosis was 37 years (range 23-57). Primary site of ALES was head and neck (50%) and thorax (50%). Median tumor size was 4 cm (2.7-5.5 cm). All patients underwent resection of their primary tumor, and two (50%)received adjuvant radiation therapy. All pts received/are receiving adjuvant chemotherapy. 75% of patients were treated with Vincristine, Doxorubicin, and Cyclophosphane (VDC) alternating with Ifosfamide &amp; Etoposide (IE) for 12-14 cycles. One patient received 4 cycles of adjuvant carboplatin and etoposide and radiation after an initial diagnosis of basaloid carcinoma but recurred 47 months later and diagnosed at ALES at that time. That patient underwent re-resection followed by adjuvant chemotherapy with Vincristine, Doxorubicin, and Ifosfamide (VAI). Median follow-up from initial diagnosis was 25 months (3-39 months). All patients are alive with no evidence of disease. Conclusions: Similar to treatment of EWS, a multidisciplinary strategy is paramount. VDC/IE is a reasonable treatment strategy. Further multicenter collaboration is essential to define clinical characterization of this rare sarcoma subtype and to guide treatment particularly in the relapsed or refractory setting.[Table: see text]

Deep learning-based microarray cancer classification and ensemble gene selection approach.

Malignancies and diseases of various genetic origins can be diagnosed and classified with microarray data. There are many obstacles to overcome due to the large size of the gene and the small number of samples in the microarray. A combination strategy for gene expression in a variety of diseases is described in this paper, consisting of two steps: identifying the most effective genes via soft ensembling and classifying them with a novel deep neural network. The feature selection approach combines three strategies to select wrapper genes and rank them according to the k‐nearest neighbour algorithm, resulting in a very generalisable model with low error levels. Using soft ensembling, the most effective subsets of genes were identified from three microarray datasets of diffuse large cell lymphoma, leukaemia, and prostate cancer. A stacked deep neural network was used to classify all three datasets, achieving an average accuracy of 97.51%, 99.6%, and 96.34%, respectively. In addition, two previously unreported datasets from small, round blue cell tumors (SRBCTs)and multiple sclerosis‐related brain tissue lesions were examined to show the generalisability of the model method.

Osteosarcoma/Ewing Sarcoma

Osteosarcoma/Ewing Sarcoma

Ewing sarcoma and related FET family translocation-associated round cell tumors: A century of clinical and scientific progress.

The year 2021 marked the centenary of the first publication of a cancer termed diffuse endothelioma of bone by James Ewing. Its unique features were apparent even in the first case series he described. This new diagnosis was clearly distinct from osteogenic sarcoma and myeloma, which were already well recognized at the time. We undertake this summary to better understanding Ewing sarcoma, contrasting the logarithmic evolution of the standard of care of systemic therapy for this and related diagnoses to the exponential understanding of the molecular biology of this family of tumors. We also outline in this manuscript how the finding of genomic relatives within Ewing sarcoma itself and related tumors, first noted nearly 40 years ago, helps us appreciate the need to find therapeutic plans that are specific for each small round blue cell tumor subtype. The advent of next generation sequencing regarding previously unknown small round blue cell tumor subtypes in many ways puts us back in the shoes of James Ewing in 1921, searching anew for clues leading to better treatments for increasingly rare cancer subsets.

Retroperitoneal blue cell round tumor (Ewing sarcoma in a 35years old male)- case report.

IntroductionEwing sarcoma is a highly aggressive tumor. It's common presentation is primary bone tumor, but very rarely as soft tissue sarcoma both of which are under the spectrum of Ewing sarcoma family of tumors (EFT).Case presentationA 35 years old male who presented with advanced locally spreading tumor. He was diagnosed after presenting with epigastric pain and melena, CT abdomen revealed the retroperitoneal mass. CT guided core biopsy taken and was diagnosed as Ewing sarcoma. The patient presented with mass already grown so he was not a surgical candidate. Patient was managed symptomatically till he was sent for palliative care in a Sarcoma centre in Jordon and passed away on October 2021.DiscussionEwing Sarcoma family of tumors are group of small round blue cell tumors that are histogenetically related. The better known is Ewing ‘s sarcoma (EWS). It is a malignant small blue round cell tumor with variable degree of neuroectodermal differentiation. Retroperitoneal tumor are mostly malignant and accounts for one third of soft tissue sarcoma. They usually present as large masses at the time of the diagnosis. So they do not produce symptoms until they grow large enough to compress or invade contagious structures.ConclusionES-EWS is an aggressive tumor with high incidence of local recurrence and distant metastasis that's why is was given its poor prognosis characteristic. Multimodality treatment including surgical resection, chemotherapy and High dose radiotherapy will help in better survival rate.

Serous fluid: Metastatic sarcomas, melanoma, and other non-epithelial neoplasms.

While most tumors metastatic to the serous membranes are of epithelial origin, cytologists should be aware that non-epithelial neoplasms can also cause malignant effusions including sarcomas, melanomas, germ cell tumors, and, more rarely, brain tumors. The differential diagnosis of a malignant effusion is accordingly broad, especially for the small round blue cell tumors that includes not only mesenchymal tumors, but also non-mesenchymal tumors, such as neuroblastoma and Wilms tumor. Diagnosing non-epithelial malignancies in effusion specimens based entirely upon their cytomorphologic features is difficult because these neoplasms often exhibit considerable morphological overlap and their cytomorphology can differ from the original tumor. As malignant cells have a tendency to round up in body fluids these non-epithelial neoplasms can therefore mimic reactive mesothelial cells and metastatic adenocarcinoma. The use of ancillary studies including immunostaining, FISH, and molecular studies is thus often critical to reach a definitive diagnosis. This review article will be incorporated finally as one of the chapters in CMAS (CytoJournal Monograph/Atlas Series) #2. It is modified slightly from the chapter by the initial authors in the first edition of Diagnostic Cytopathology of Serous Fluids.

Dysregulated heparan sulfate proteoglycan metabolism promotes Ewing sarcoma tumor growth.

The Ewing sarcoma family of tumors is a group of malignant small round blue cell tumors (SRBCTs) that affect children, adolescents, and young adults. The tumors are characterized by reciprocal chromosomal translocations that generate chimeric fusion oncogenes, the most common of which is EWSR1-FLI1. Survival is extremely poor for patients with metastatic or relapsed disease, and no molecularly targeted therapy for this disease currently exists. The absence of a reliable genetic animal model of Ewing sarcoma has impaired investigation of tumor cell/microenvironmental interactions in vivo. We have developed a new genetic model of Ewing sarcoma based on Cre-inducible expression of human EWSR1-FLI1 in wild-type zebrafish, which causes rapid onset of SRBCTs at high penetrance. The tumors express canonical EWSR1-FLI1 target genes and stain for known Ewing sarcoma markers including CD99. Growth of tumors is associated with activation of the MAPK/ERK pathway, which we link to dysregulated extracellular matrix metabolism in general and heparan sulfate proteoglycan catabolism in particular. Targeting heparan sulfate proteoglycans with the specific heparan sulfate antagonist Surfen reduces ERK1/2 signaling and decreases tumorigenicity of Ewing sarcoma cells in vitro and in vivo. These results highlight the important role of the extracellular matrix in Ewing sarcoma tumor growth and the potential of agents targeting proteoglycan metabolism as novel therapies for this disease.

The Small Round Blue Cell Tumors of Sinonasal Tract: Pathologists Grey Zone.

One of the most challenging diagnostic categories in the sinonasal tract includes small-blue-round-cell tumors. These are malignant tumors which show many overlapping histomorphology and immunohistochemistry (IHC) findings. Limited, small biopsy of these not completely excisable tumors adds to the diagnostic confusion. A cross-sectional study was done for 2 years (January 2018-December 2020) in a tertiary care institute, which included 70 cases of tumors of which 49 cases were malignant. All paraffin-embedded blocks were subjected to hematoxylin and eosin stain and IHC followed by molecular study wherever needed. Of the total cases, small-blue-round-cell tumor constituted the major category comprising 20 rare and interesting cases which included sinonasal undifferentiated carcinoma (4 cases), malignant lymphoma (2 cases of diffuse large B-cell lymphoma and 2 cases of extranodal natural killer/T-cell lymphoma), rhabdomyosarcoma (2 cases), olfactory neuroblastoma (2 cases), malignant melanoma (2 cases), plasmacytoma (2 cases), atypical Ewing's sarcoma (EWS) (1 case), EWS (1 case), nuclear protein in testis (NUT) carcinoma (1 case), and small-cell neuroendocrine carcinoma (1 case). Tumors of the sinonasal tract are very diverse, more so in small-round-cell tumor which present with a undifferentiated morphology. Thus, accurate diagnosis needs clinicoradiological parameters and special ancillary techniques such as IHC and molecular study in addition to histopathology for early diagnosis and therapy to prevent significant morbidity and mortality caused in these tumors.

Desmoplastic small round cell tumour (DSRCT): A rare entity that highlights the importance of immunohistochemistry

Desmoplastic small round cell tumour (DSRCT) is a rare malignant tumour of mesenchymal origin1 with a strong male predominance; the mean age at diagnosis is 22 years.2 We present a case of a 31-year-old female with a pelvic mass and widespread lymphadenopathy at laparotomy. Frozen section of mass and pelvic node were performed and reported as a malignant small round blue cell tumour. Paraffin sections showed variably sized nests of small, monotonous, hyperchromatic cells with indistinct borders, numerous mitoses, and prominent desmoplastic stroma.

A small round blue cell tumour of the rib: A case report of Ewing sarcoma

Ewing sarcoma is a prototypical small round blue cell tumour with a characteristic EWSR1 translocation. We report a case of Ewing sarcoma arising in the rib of an 81-year-old female. The tumour was comprised of uniform small round cells which demonstrated an organoid growth pattern with a suggestion of rosette-like structures. Immunohistochemistry showed positive staining for CD99, vimentin and desmin; stains for cytokeratins, melanocytic markers, neuroendocrine markers, CD45, CD138, NFP and CD34 were negative. EMA and BCL2 demonstrated weak, patchy staining. FISH studies demonstrated an EWSR1 fusion, supporting the diagnosis of Ewing sarcoma. Desmin positivity, although recognised in Ewing sarcoma, has been reported in only 2% of cases.1 The main differential diagnosis based on morphology and immunohistochemistry was between Ewing sarcoma and synovial sarcoma due to CD99 positivity and focal EMA and BCL2 staining. However, EWSR1 translocations are not associated with synovial sarcoma.2 Recently a proportion of ‘undifferentiated round cell sarcomas’ with similar morphology to Ewing sarcoma have been divided into specific entities largely based on their molecular characteristics. These include CIC-rearranged sarcomas, sarcomas with BCOR alterations and round cell sarcomas with EWSR1-non ETS fusions.3

Prevalence of Tumors in the Posterior Cerebral Fossa in Children and Adults, as well as their Histological Kinds: a Cross-Sectional Study

Aim: To determine the prevalence of posterior fossa tumors in children and adults, as well as their histological kinds. Study design: A cross-sectional study Place and duration: From February 2012 to January 2019, the Department of Neurosurgery at Riyadh Care Hospital Methodology: We undertook a descriptive analysis of patients with posterior fossa space-occupying lesions. The neurosurgical intervention was done in all of the instances due to the critical location. Specimens were sent for histological evaluation after surgery. The data from these patients, as well as histology reports, were examined. The data was analyzed using SPSS version 21. Results: Males made up 57.14 percent (n=48) of the 84 patients, while children made up 41.66 percent (n=35). The most common tumor was schwannoma, seen in 34.52 percent (n=29) of cases, 72.41 percent of adults, and 27.58 % of children. In 22.61 %, 15.47 %, and 14.28 % of cases, meningioma, pilocytic astrocytoma (PCA), and Meduloblastoma were found, respectively. Metastasis was only seen in adults, and malignant round blue cell tumors were only found in children. Astrocytoma and schwannoma were prevalent in adults. Children were more likely to develop Meduloblastoma, Pilocytic astrocytoma, and malignant round blue cell tumors. Conclusion: High-grade Astrocytoma and Schwannoma are dominantly present in adults. Malignant round blue cell tumor, Pilocytic astrocytoma Medulloblastoma is more prevalent in children. Metastasis was only observed in adults. Because of their location, risk of excision, and involvement of the brain stem structures and fourth ventricle, posterior fossa tumors are widely known for their significant morbidity and mortality. Early diagnosis is now possible due to modern diagnostic and therapy technologies, which help to lower mortality rates and improve postoperative prognosis. Keywords: posterior cerebral fossa tumors, children, adults

DIFFUSE LARGE B-CELL LYMPHOMA OF THE HEART

Diffuse large B-cell lymphoma (DLBCL) of the heart accounts for only 1% of primary cardiac tumors. Histopathologic examination becomes the primary key for diagnosis and immunohistochemical evaluation for non-Hodgkin lymphoma (NHL) subtype determination is able to predict disease progression and therapeutical modality. Case description: 70-year-old man complained of shortness of breath. Echocardiographic examination revealed mass occupied the left atrium measured 5.9 x 2.9 cm inherent with interatrial septum and mass with a stem in the right atrium measured 4.6 x 2.4 cm. Intraoperative, considerable amount of extracardiac mass was found, mass extension was unable to be determined. Thoracic surgeon decided to sample the extracardiac mass without performing cardiac surgery. The histopathologic features showed round blue cell tumor resembling a NHL. Immunohistochemical staining were consistent with diffuse NHL, large cell, high grade lymphoma, suitable for DLBCL. Round blue cell tumor of extracardiac mass with positive expression of LCA and CD 20 is suitable for B-cell non-Hodgkin lymphoma. Ki-67 immunohistochemical staining revealed a 70-80% proliferation index which indicates a high-grade lymphoma and defining diagnosis and treatment of DLBCL.

Comprehensive profiling of mRNA splicing indicates that GC content signals altered cassette exon inclusion in Ewing sarcoma.

ABSTRACTEwing sarcoma (EwS) is a small round blue cell tumor and is the second most frequent pediatric bone cancer. 85% of EwS tumors express the fusion oncoprotein EWS-FLI1, the product of a t(11;22) reciprocal translocation. Prior work has indicated that transcription regulation alone does not fully describe the oncogenic capacity of EWS-FLI1, nor does it provide an effective means to stratify patient tumors. Research using EwS cell lines and patient samples has suggested that EWS-FLI1 also disrupts mRNA biogenesis. In this work we both describe the underlying characteristics of mRNA that are aberrantly spliced in EwS tumor samples as well as catalogue mRNA splicing events across other pediatric tumor types. Here, we also use short- and long-read sequencing to identify cis-factors that contribute to splicing profiles we observe in Ewing sarcoma. Our analysis suggests that GC content upstream of cassette exons is a defining factor of mRNA splicing in EwS. We also describe specific splicing events that discriminate EwS tumor samples from the assumed cell of origin, human mesenchymal stem cells derived from bone marrow (hMSC-BM). Finally, we identify specific splicing factors PCBP2, RBMX, and SRSF9 by motif enrichment and confirm findings from tumor samples in EwS cell lines.

Primary desmoplastic small round cell tumor of the submandibular gland: a case report and literature review

BackgroundDesmoplastic small round cell tumor (DSRCT) is a sporadic, highly malignant tumor with a poor prognosis. The abdomen and pelvis have been reported as the primary localization sites. However, to the best of our knowledge, there are few reports on primary DSRCT in the submandibular gland.Case presentationWe report a case of a 26-year-old Chinese man with a mass in the right submandibular gland. Imaging studies showed a hypoechoic mass in the right submandibular region. Intraoperative pathology revealed that the tumor tissue was composed of small round tumor cells and a dense desmoplastic stroma. On immunostaining, the tumor cells showed markers of epithelial, mesenchymal, myogenic, and neural differentiation. The EWSR1 gene rearrangement was detected by fluorescence in situ hybridization. Based on the overall morphological features and immunohistochemical findings, a final diagnosis of DSRCT was made. The patient was treated with comprehensive anti-tumor therapy mainly based on radiotherapy and chemotherapy.ConclusionsDSRCT is an uncommon malignant neoplasm with rare submandibular gland involvement. In this report, we have described a case of DSRCT in the submandibular gland and reviewed the literature on DSRCT over the past 5 years. Considering the importance of differential diagnosis between DSRCT, especially with rare extra-peritoneal involvement, and small round blue cell tumors, a full recognition of the clinicopathological features will help to better diagnose this neoplasm.

Multidisciplinary Management of Medulloblastoma: Consensus, Challenges, and Controversies.

Medulloblastoma is a highly aggressive "small round blue cell tumor" of the posterior fossa predominantly seen in children. Historically aggressive multimodality regimens have achieved encouraging outcomes with the caveat of severe long-term toxicities. The last decade has unleashed a revolution in terms of evolved understanding of this heterogeneous disease entity in terms of molecular biology. Medulloblastoma as of today is grouped into one of four canonical molecular subgroups (WNT, SHH, Group 3, and Group 4) each characterized by different putative cells of origin, characteristic aberrations at the molecular level, radiogenomics, and outcomes. Our understanding continues to grow in this regard. The future promises much in terms of personalized medicine in tailoring therapy to the needs of individual patients based on their clinical and molecular profile in order to maximize individual and population based outcomes at the cost of minimizing toxicity.

Diagnostic Challenges of Uncommon Paediatric Head and Neck MassesA Case Series

Paediatric head and neck masses pose diagnostic challenge to the clinicians owing to the wide spectrum of lesions including congenital (developmental), inflammatory and neoplastic lesions. In this case series, uncommon paediatric head and neck mass lesions that were diagnosed in a tertiary care hospital over a period of three years from January 2017 to December 2019, had been included, emphasizing on the diagnostic challenges encountered. First case was of Cervical Chondrocutaneous Branchial Remnant (CCBR) that was misdiagnosed as branchial cyst clinically. Second case was a lymphoepithelial cyst that masqueraded as an acute suppurative lymphadenitis in Fine Needle Aspiration Cytology (FNAC) due to florid inflammation. Third case was an aggressive poorly differentiated malignant neoplasm of left nasal cavity namely Nuclear protein in Testis (NUT) carcinoma that had to be differentiated from several other small round blue cell tumors. Fourth was a case of lipoblastoma which could be mistaken for myxoid liposarcoma. The last two cases were vascular tumors, one of them was juvenile capillary hemangioma with a benign clinical course while the other was an intermediate grade tumor namely kaposiform hemangioendothelioma. A wholesome clinical, radiological and pathological evaluation will help to solve the diagnostic dilemmas in this group of lesions.