Small Round Blue Cell Research Articles

Mixed epithelial and stromal tumours of the kidney with malignant transformation: a clinicopathological study of four cases

Mixed epithelial and stromal tumour of the kidney is a complex benign neoplasm in which malignancy rarely arises. In this study, we report four mixed epithelial and stromal tumours in which sarcoma or carcinoma developed. In the first, a multifocal adenocarcinoma arose and areas of transition from benign to malignant epithelium were observed. Oestrogen and progesterone receptors were diffusely present in the nuclei of the spindle cell stroma of the benign component. The second was a sarcoma in which benign epithelial elements were intermixed. Outside the renal parenchyma, clusters of small benign glands surrounded by oestrogen receptor-positive benign stroma were present, supporting the diagnosis of mixed epithelial and stromal tumour. Fluorescence in situ hybridisation for SYT-SSX translocation and immunohistochemical results, specifically TLE1 -ativity, argued against primary renal synovial sarcoma. The patient died 24 months after surgery. The third tumour consisted of small blue round cells, positive for epithelial membrane antigen, BCL2, CD99, and FLI1. Throughout the tumour, the presence of benign appearing branching tubules in fibromuscular stroma, reactive for smooth muscle actin, desmin and progesterone receptor, supported the diagnosis of mixed epithelial and stromal tumour in which a small round blue cell sarcoma with EWSR1 rearrangement arose. In the fourth tumour, adenocarcinoma with papillary architecture arose in a typical mixed epithelial and stromal tumour. In summary, we present four cases of mixed epithelial and stromal tumour with malignant transformation, two showing carcinomatous and the other two with sarcomatous transformation. Identification of typical benign looking elements and the absence of SYT-SSX translocation are helpful in recognition of this entity.

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 > 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 & 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]

Long-term control and safety of larotrectinib in a cohort of adult and pediatric patients with tropomyosin receptor kinase (TRK) fusion primary central nervous system (CNS) tumors.

2010 Background: Neurotrophic tyrosine receptor kinase ( NTRK) gene fusions are known oncogenic drivers in a variety of tumor types. Larotrectinib is a highly selective, CNS-active TRK inhibitor that demonstrated an objective response rate (ORR) of 30% and a 24-week disease control rate (DCR) of 73% across 33 evaluable adult and pediatric patients with TRK fusion primary CNS tumors, as of July 2020 (Doz et al, Neuro Oncol 2021). We report updated data on an expanded dataset of patients. Methods: Patients with TRK fusion primary CNS tumors in two clinical trials (NCT02637687, NCT02576431) were included. Larotrectinib was administered at 100 mg twice daily (BID) in adults and 100 mg/m2 (max 100 mg) BID in pediatric patients. Response was investigator-assessed. Results: As of July 2021, 38 adult and pediatric patients with TRK fusion primary CNS tumors were identified: high-grade glioma (HGG; n =23), low-grade glioma (LGG; n =9), and other (n =6; includes glioneuronal, neuroepithelial, diffuse leptomeningeal, neuroblastoma, recurrent small round blue cell, and not otherwise specified). Median age at enrollment was 10.8 years (range 1.3–79.0; 28 [74%] patients < 18 years old). The gene fusions involved NTRK2 (n = 28), NTRK1 (n = 6), and NTRK3 (n = 4). Sixteen (42%) patients received one prior line of systemic therapy and 16 (42%) received ≥2 prior lines. The ORR for 37 evaluable patients was 30% (95% confidence interval [CI] 16–47): three complete responses, eight partial responses, 21 stable disease (16 patients ≥24 weeks), and five progressive disease. The 24-week DCR was 73% (95% CI 56–86) for all patients, 68% (95% CI 45–86) for patients with HGG, and 89% (95% CI 52–100) for patients with LGG. Twenty-five of 31 patients (81%) with measurable disease at baseline had tumor shrinkage. Median time to response was 1.9 months. Median duration of response (DoR) was not reached; median follow-up was 25.6 months. The 12-month DoR rate was 64%. Median progression-free survival (PFS) was 16.5 months (95% CI 6.7–not estimable); median follow-up was 27.4 months. Median overall survival (OS) was not reached; median follow-up was 26.7 months. The 24-month OS rate was 65%. Treatment duration ranged from 0.1+ to 38.7+ months. Twenty-two patients (58%) progressed on treatment and three continued treatment post-progression for ≥4 weeks. Treatment-related adverse events (TRAEs) were reported in 21 patients (55%); the majority of these patients (18/21 [86%]) reported Grade 1 or 2 TRAEs. No Grade 3 or higher treatment-related neurological adverse events were reported. There were no treatment discontinuations due to TRAEs. Conclusions: Larotrectinib achieved a high DCR, rapid and durable responses, and a manageable safety profile in patients with TRK fusion primary CNS tumors. These results support testing for NTRK gene fusions in patients with CNS tumors. Clinical trial information: NCT02637687, NCT02576431.

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.

NUTM1-fusion positive malignant neoplasms of the genitourinary tract: A report of six cases highlighting involvement of unusual anatomic locations and histologic heterogeneity.

Tumors with NUTM1 fusions occur predominantly in the thoracic cavity and head and neck region. However, recent literature expanded the location of NUTM1-translocated malignancy to soft tissue, brain, and visceral organs. In this study, we describe the first series of six NUTM1-translocated carcinomas and sarcomas occurring in the genitourinary tract. The sites of origin were kidney (n= 2), bladder (n= 3), and penis (n= 1). All tumors occurred in adulthood (range: 30-78 years). The histologic features were heterogeneous, showing epithelial, spindle cell, or primitive small blue round cell morphology. Glandular architecture, keratinization, rhabdoid cells, or myxoid-to-edematous stromal component were also noted. In three cases, features were in keeping with a carcinoma (two from kidney and one from bladder), whereas the remaining three were classified as malignant undifferentiated neoplasm (MUN)/sarcoma. Fusion partners detected in four cases tested by either FISH and/or RNA sequencing were BRD4 in two kidney tumors, MXD1 in a bladder sarcoma, and MXD4 in a penile sarcoma. NUT immunostain showed diffuse spiculated positivity in five cases. Immunopositivity for various cytokeratins was noted in two tumors. The outcome of NUTM1-rearranged genitourinary malignancy was dismal: four of five cases with follow-up developed distant metastasis, and three suffered disease-specific death. In conclusion, NUTM1-rearranged carcinoma and sarcoma can affect the genitourinary tract, including kidney, bladder, and penis. Histologic features and keratin immunoexpression are highly variable. A NUTM1-fusion positive malignancy may be included in the differential diagnosis of a MUN of the genitourinary tract given the dismal outcome and the existing BET-targeted therapy for tumors with BRD3/4::NUTM1 fusion.

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.

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

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.

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.

Unusual sites of metastases at initial presentation in Ewing-like sarcoma of extremity in an elderly male

Ewing and Ewing-like sarcoma are high-grade sarcomas with the histological presence of small round blue cells with a higher propensity for hematogenous metastases. The most common pattern is appendicular skeleton involvement with or without metastases. In this case report, we present a 55-year-old gentleman with Ewing-like sarcoma of the left femur with metastases to rare sites.

The Effects of Variable Selection and Dimension Reduction Methods on the Classification Model in the Small Round Blue Cell Tumor Dataset

Objective: The purpose of this study is to investigate and compare the effects of different dimension reduction methods (PCA, ICA, PCA + Forward Selection, ICA + Forward Selection) on the K-NN classifier using open access gene expression data of small round blue cell tumor types.Methods: In this study, open access gene expression data of small round blue cell tumor types was used for investigate and compare the effects of different dimension reduction methods. In the study, PCA, ICA, PCA + Forward Selection, ICA + Forward Selection were used as different dimension reduction methods together with K-NN classification method.Results: Accuracy values obtained from the dimension reduction model made with PCA on K-NN model; for EWS, BL, NB, and RMS type tumors with 93.51%, 91.14%, 92.31%, and 94.74% respectively. Accuracy values obtained from the dimension reduction model made with PCA + Forward Selection on K-NN model; for EWS, BL, NB, and RMS type tumors with 96.25%, 96.25%, 95.06% and 95.47%, respectively. Accuracy values obtained from the dimension reduction model made with ICA on K-NN model; for EWS, BL, NB, and RMS type tumors with 91.89%, 90.67%, 88.31% and 89.47% respectively. Accuracy values obtained from the dimension reduction model made with ICA+ Forward Selection on K-NN model; for EWS, BL, NB, and RMS type tumors with 93.51%, 91.14%, 92.31% and 94.74% respectively.Conclusion: In this study, the model created with PCA gives higher results than the model created with ICA. In addition, according to the results of the models obtained by applying the Forward selection method on these 2 models, the forward selection method has increased the classification performance.

WT1 and Cyclin D1 Immunohistochemistry: A Useful Adjunct for Diagnosis of Pediatric Small Round Blue Cell Tumors on Small Biopsies

Pediatric small round blue cell tumors (SRBCTs) are a heterogeneous group of neoplasms with overlapping morphological appearance. Accordingly, their diagnosis is one of the most difficult in the field of surgical pathology. The most common tumors include rhabdomyosarcoma, Ewing’s sarcoma, neuroblastoma, lymphoblastic lymphoma and Wilms’ tumor (the blastemal component). Over time their diagnosis has become more difficult due to the increasing use of small biopsies. However, the advent of immunohistochemistry has improved the quality of diagnosis in most cases by the application of an adequate panel of immunomarkers. Recently, WT1 and Cyclin D1 have been shown to be useful in the differential diagnosis of SRBCTs on surgically-resected specimens, showing a diffuse cytoplasmic positivity of the former in all RMSs and a diffuse nuclear staining of the latter in both EWS and NB. The aim of the present study was to investigate the expression of WT1 and Cyclin D1 on small biopsies from a series of 105 pediatric SRBCTs to evaluate their diagnostic utility. Both immunomarkers were differentially expressed, with a diffuse and strong cytoplasmic staining for WT1 limited to all cases of RMS, and a diffuse nuclear staining for cyclin D1 restricted to all cases of EWS and NB. Notably, the expression of WT1 and cyclin D1 was also retained in those cases in which the conventional tumor markers (myogenin, desmin and MyoD1 for RMS; CD99 for EWS; NB84 for NB) were focally expressed or more rarely absent. The present study shows that WT1 and Cyclin D1 are helpful immunomarkers exploitable in the differential diagnosis of pediatric SRBCTs on small biopsies, suggesting their applicability in routine practice.