Small Round Blue Cell Research Articles

Desmoplastic small round cell tumor a case report of a rare intra-abdominal tumor of the young adult

Desmoplastic small round cell tumor is a rare and highly aggressive mesenchymal tumor described as a distinct clinico-pathological entity in 1989 by Gerald . These tumors occur mainly in the peritoneal cavity,although other primary sites, such as testicular, ovarian, thoracic, pulmonary, intracranial and head and neck regions have been reported. Clinical symptoms are non-specific. Diagnosis is based on histological analysis combined with immunohistochemical study. Histological study typically shows small round blue cells in nests separated by abundant desmoplastic stroma associated with a single chromosomal translocation t(11:22) (p 13; q 12) involving the EWSR1 and WT1 genes. The prognosis is particularly poor, with median survival ranging from 17 to 25 months. Management of this tumor remains difficult, and current regimens do not achieve a significant cure rate despite the use of aggressive treatments such as polychemotherapy.

Desmoplastic Small Round Cell Tumor: A Case Report

Introduction Desmoplastic small round cell tumor (DSRCT) is an ultra-rare and highly aggressive mesenchymal tumor that primarily affects the peritoneum, and to a lesser extent, the visceral organs in the abdominal cavity. This study presents a case of a patient who has been diagnosed with DSRCT and has been managed with VAC-IE chemotherapy. Case presentation A 43-year-old male presented with a complaint of epigastric pain for 20 days but no other clinical symptoms. A CT scan and an abdominal ultrasound showed multiple lesions in the peritoneum, and biopsies were taken from all the sites. Histological analysis revealed nests of small blue round cells surrounded by an abundant stroma. Immunohistochemistry results confirmed the disease to be a desmoplastic small round cell tumor. Conclusion This disease is yet to be fully understood, and the response of our case to VAC-IE chemotherapy has shown promising outcomes. This form of treatment can be further studied to establish and help in finding a treatment with a better prognosis.

Sarcomas With RAD51B Fusions Are Associated With a Heterogeneous Phenotype

RAD51B-rearranged sarcomas are rare neoplasms that exhibit a heterogeneous morphology. To date, 6 cases have been reported, all involving the uterus, including 4 perivascular epithelioid cell tumors (PEComas) and 2 leiomyosarcomas (LMS). In this study, we describe the morphologic, immunohistochemical, and molecular features of 8 additional sarcomas with RAD51B rearrangement, including the first extrauterine example. All patients were women with a median age of 57 years at presentation. Seven tumors originated in the uterus, and one in the lower extremity soft tissue, with a median tumor size of 12 cm. Histologically, 4 tumors showed predominantly spindle cell morphology with eosinophilic fibrillary cytoplasm, with or without nuclear pleomorphism, whereas 2 tumors exhibited pleomorphic epithelioid cells, featuring clear to eosinophilic, granular cytoplasm. Two neoplasms exhibited undifferentiated cytomorphology, including one with uniform small blue round cells. All tumors showed high-grade cytologic atypia and high mitotic activity (median: 30/10 high-power fields), whereas coagulative necrosis was noted in 6 cases and lymphovascular invasion in 2. By immunohistochemistry, 2 showed myoid and melanocytic markers in keeping with PEComa, whereas 4 cases were only positive for smooth muscle markers consistent with LMS (including 3 myxoid). The remaining 2 cases had a nonspecific immunoprofile. Five cases tested by targeted RNA sequencing (Archer FusionPlex, Illumina TruSight) showed different fusion partners (HMGA2, PDDC1, and CEP170). RAD51B rearrangements were identified by FISH in the remaining 3 cases. Targeted DNA sequencing in 2 cases was negative for TSC gene alterations. Clinical outcome, available in 5 patients (median follow-up, 19 months), revealed 3 local recurrences, 2 lung metastases, and 4 deaths due to disease. Our results expand the spectrum of sarcomas with RAD51B fusions, demonstrating variable clinical presentations, morphologic spectrum, and fusion partners. These tumors have a predilection for a uterine location, with either LMS, PEComa, or undifferentiated phenotypes, and are associated with an aggressive clinical course.

Embryonal and pineal tumours.

Embryonal and pineal tumours represent a diverse group of central nervous system (CNS) neoplasms. While many of the small round blue cell tumours that make up the embryonal neoplasms share similar histologic qualities, there are several morphologic and cytologic characteristics that are useful in distinguishing different tumour types. Similarly, pineal parenchymal tumours represent clinically diverse tumours, ranging from benign to overtly malignant. The most recent iteration of the World Health Organization Classification of CNS Tumours expanded greatly on the significance of molecular alterations in brain tumour diagnostics. In this article, we summarize the salient cytologic and histologic features of CNS embryonal and pineal tumours, and highlight diagnostically relevant molecular alterations within each tumour type.

Nuclear Protein in Testis (NUT) Carcinoma: A Comprehensive Immunohistochemical Analysis of 57 Cases With Consideration of Interpretation and Pitfall Recognition.

Nuclear protein in testis (NUT) carcinoma is an aggressive carcinoma defined by NUTM1 gene rearrangement. Diagnostic challenges include morphologic overlap with poorly differentiated squamous cell carcinoma, small cell carcinoma, thoracic SMARCA4-deficient undifferentiated tumor, and other small round blue cell tumors. To comprehensively study the immunohistochemistry (IHC) features of a large cohort of NUT carcinomas. Fifty-seven NUT carcinoma cases were identified from 2012-2022, including 38 thoracic/mediastinal, 13 head and neck/sinonasal, and 6 from other sites. Pathology reports and available slides were reviewed. Comprehensive IHC studies were performed on available cases. Keratin stains showed variable positivity and were entirely negative in 15% (8 of 55) of cases. p40 was only positive in 65% (24 of 37) of cases, implying inferior sensitivity when compared to p63 (87% sensitivity, 20 of 23 cases) and other squamous cell markers. Neuroendocrine markers were focally/weakly positive in few cases; however, INSM1 was positive in 54% (7 of 13) of cases, indicating a possible diagnostic pitfall. TTF-1 was mostly negative with focal positivity in 26% (10 of 38) of cases. Occasional CD34 (15%, 3 of 20 cases) and CD99 (21%, 3 of 14 cases) positivity could also cause potential diagnostic confusion. S100, desmin, CD45, and SALL4 were rarely positive. BRG1 and INI1 were retained in all cases. Ki-67 proliferative index was high (median, 60%). PD-L1 was negative in all tested cases. This comprehensive IHC study demonstrates the immunohistochemical spectrum of NUT carcinoma. The findings can help narrow the differential diagnosis and recognize potential pitfalls.

Atypical Teratoid Rhabdoid Tumor: 28-years institutional experience

Abstract Introduction/Objective Atypical teratoid/rhabdoid tumor (ATRT) is a malignant central nervous system tumor affecting young children, characterized by biallelic mutations of SMARCB1 (hSNF5/INI1), consisting of a varying mixture of rhabdoid cells, small round blue cell (SRBC) and epithelial/mesenchymal components. Combination of surgical resection, chemoradiotherapy and autologous stem cell transplantation (SCT) has led to significant improvement in survival. Methods/Case Report Cases of ATRT in the past 28 years have been re-examined, including H&E stains, immunohistochemistry, available molecular studies and clinical charts. Results (if a Case Study enter NA) A total of 23 cases of ATRT were recruited to include 20 pediatric (age 3-36 months, median 13.5 months) and 3 adult cases (27, 38 and 46 years). 73.9% were male. Two pediatric cases presented in patients with Pierre-Robin sequence and Phelan-McDermid syndrome and one adult had history of Choriocarcinoma. 72.7% of cases initially presented in the posterior fossa, with 3 cases presenting in temporal lobe, 1 in frontal lobe, 1 in 3rd ventricle and 1 in pituitary gland. Mean size at presentation was 4.7 cm (range 2-10 cm). Median survival was 12.5 weeks with 8 patients surviving 5-13 years. 10/22 cases developed recurrences and/or spinal drop metastasis. Median time to first recurrence/ drop metastasis was 3.5 months (range 0-66 months). Cases showed varying proportions of rhabdoid, SRBC, epithelioid and mesenchymal components. By immunohistochemistry, INI1 was lost in 19/19 cases. Keratins, GFAP and Synaptophysin were positive in 13/17, 14/20 and 17/21 cases, respectively. Interestingly, GAB-1 and YAP1 were positive in 5/6 and 4/4 cases, respectively. Five cases had SMARCB1 mutation on NGS, one had NF2 truncation and another showed variation of unknown significance involving mainly NOTCH1 gene. 21/22 patients underwent surgical resection, of which 17 additionally received a combination of chemoradiotherapy and SCT and 1/22 underwent palliation. Conclusion Our data highlights the spectrum of presentation and survival of cases of ATRT and the importance of INI1 immunohistochemistry in the diagnosis, especially for the occasional cases co-expressing GAB1 and YAP, a potential diagnostic pitfall with medulloblastoma.

Primary Chest Wall Ewing Sarcoma with Indolent Behavior in an Elderly Male

Abstract Introduction/Objective Ewing sarcoma (ES) is the second most common primary malignant bone tumor, primarily affecting children and young adults within the first two decades of life. Over 80% of cases are positive for CD99 and exhibit a characteristic t(11;22) translocation resulting in an EWSR1::FLI1 fusion. Extraosseous ES is extremely rare and most reported cases occur in patients less than 50 years old. We report an unusual case of extraosseous ES arising from the chest wall in an elderly male that showed slow interval progression on imaging studies. Methods/Case Report An 83-year-old male with a past medical history of COPD and tobacco use presented to the emergency department for a mechanical ground level fall and a worsening cough over the prior week. Of note, he was found to have a 6.1 cm pleural based mass seven years prior. The patient was ultimately discharged home with recommended oncologic follow-up for this long-standing chest wall mass due to an increase in size on imaging. A PET scan showed a hypermetabolic subpleural mass in the right lower chest wall measuring 7.6 cm with invasion through the adjacent ribs and intercostal spaces into the adjacent soft tissue. A core biopsy was performed, which demonstrated a small round blue cell tumor diffusely positive for CD99 and Bcl-2, lacking significant mitotic activity and necrosis. Given the unusual clinical features, a next generation sequencing (NGS) panel for sarcoma fusions was performed and identified an EWSR1::FLI1 fusion, supporting the diagnosis of ES/primitive neuroectodermal tumor (PNET). Results (if a Case Study enter NA) NA Conclusion ES is relatively common as a primary bone tumor in children and young adults, but is rare in the chest wall and pleura and is extremely rare in the elderly. The clinical course for ES is typically aggressive. Diagnosis of ES can be challenging as CD99 positivity is nonspecific. The characteristic t(11;22) EWSR1::FLI1 fusion can be identified through FISH or NGS. At 83 years old, this is, to our knowledge, the oldest patient reported in the literature with this diagnosis. The slow interval growth of this mass over a period of seven years is also unusual. These combined clinicopathologic features are exceedingly unique and expand upon the reported spectrum and behavior of the Ewing’s family of sarcomas. The use of broad NGS panels among pathologists may result in increased identification of ES in unusual clinical settings in the future, while also providing more confident pathologic classification in challenging situations.

Survival following complete resection of neuroblastoma in novel orthotopic rat xenograft model

Neuroblastoma accounts for 15% of pediatric cancer deaths, despite multimodal therapy including surgical resection. Current neuroblastoma rodent models are insufficient for studying the impact of surgery and combination treatments, largely due to the small size of mouse models. Human neuroblastoma SK-N-BE(2) cells were injected into the left adrenal gland of 5–6-week-old RNU homozygous nude rats. Rats were either monitored by MRI until humane endpoint was reached or after 5 weeks underwent operative tumor resection, followed by monitoring for recurrence and survival. Following neuroblastoma cell implantation, the majority of tumors grew to greater than 5000 mm3 within 5.5–6.5 weeks, meeting the humane endpoint. Surgical resection was successfully done in 8 out of 9 rats, extending survival following tumor implantation from a median of 42 days to 78 days (p < 0.005). Pathology was consistent with human neuroblastoma, showing small round blue cell tumors with Homer-Wright rosettes, high mitoses and karyorrhectic index, and strong PHOX2B staining. Thus, we have established a novel orthotopic xenograft rat model of neuroblastoma and demonstrated increased survival of rats after surgical tumor resection. This model can be used for the development of surgical techniques, such as the use of intraoperative molecular imaging or assessment of combination therapies that include surgery.

Primary intra-axial Ewing sarcoma of the central nervous system: report of a rare case with literature review

BackgroundPrimary intra-axial Ewing sarcoma (EWS) is extremely rare and a highly aggressive small blue round cell tumor in the central nervous system (CNS). We reported a case of primary intra-axial CNS-EWS in a 30-year-old male and presented an extensive literature review of CNS-EWS cases.Case presentationA 30-year-old male had been diagnosed with a grade 2 astrocytoma in the left frontal lobe a year ago and had received chemotherapy and radiotherapy. He presented with a right-sided mass, which was revealed to be a 6 cm contrast-enhancing lesion with heterogeneous hemorrhagic areas in the right frontal lobe. The patient underwent emergent craniotomy for surgical excision. Histologically, the tumor was composed of high-grade, small, blue, round cells forming trabecular islands and rosettes which were separated by fibrovascular tissues. In immunohistochemical (IHC) examination, the tumor cells were positive for CD99 and FLI-1. Fluorescence in situ hybridization analysis revealed the presence of EWSR1 gene rearrangement. The histopathological, IHC, and molecular findings were consistent with a diagnosis of EWS. Further imaging did not show evidence of another primary site. The patient was followed up without further therapy and succumbed to the disease three months after the diagnosis.ConclusionEWS is very rare but an aggressive neoplasm in the CNS. Chemoradiotherapy may promote secondary cancers but it is unclear whether the development of EWS was associated with chemoradiotherapy that our case had received for astrocytoma. EWS should be considered when diagnosing a CNS tumor that shows small, blue, round cell tumor morphology. A combination of IHC and molecular tests is required for accurate diagnosis to ensure that all patients receive the most appropriate treatment to optimize outcomes.

Challenging differential diagnoses in small biopsies from the sinonasal tract.

Sinonasal biopsy specimens are a challenging area in anatomic pathology. The small, often fragmented or crushed nature of these biopsies can hinder morphologic assessment. Additionally, many of the tumors in this area are rare and share morphologic, and sometime immunophenotypic similarities. In many cases, immunohistochemistry is helpful if not necessary to reach a specific diagnosis. In other cases, a specific diagnosis is not possible and a differential diagnosis must be given on a biopsy specimen despite access to a well-equipped immunohistochemistry laboratory. This review article groups some of the more challenging entities in the sinonasal region based on morphologic patterns. These include low grade squamoid lesions such as sinonasal (Schneiderian) papilloma and DEK::AFF2 rearranged carcinoma, glandular neoplasms such as intestinal and non-intestinal type sinonasal adenocarcinoma, high-grade carcinomas such as HPV-related multiphenotypic sinonasal carcinoma, NUT carcinoma and SWI/SNF deficient carcinomas, small round blue cell tumors such as teratocarcinosarcoma, neuroendocrine carcinoma and olfactory neuroblastoma, and finally, low grade spindle cell neoplasms such as glomangiopericytoma, biphenotypic sinonasal sarcoma and solitary fibrous tumor.

Burkitt lymphoma masquerading as nasopharyngeal angiofibroma

Primary nasopharyngeal (NP) lymphoma is a very rare tumor. Burkitt lymphoma is a subtype of non-Hodgkin’s B cell lymphoma. It is rare in the Waldeyer’s ring (3-5%). It is a highly aggressive, highly chemo sensitive lymphoma seen predominantly in childhood. Presenting a unique case of an 11 year old, male child presented to us with the chief complaints of bilateral nasal obstruction since 1 month, 6-7 episodes of nasal bleed since 1 week. Radiologically, a large soft tissue density mass lesion was seen in the region of nasopharynx, extending into the para/retro pharyngeal space. Excisional biopsy of the mass lesion histopathologic evaluation was suggestive of small round blue cell tumor, later confirmed to be Burkitt lymphoma after a bone marrow biopsy. Nasopharyngeal NHL should be kept in mind as a differential diagnosis, apart from inflammatory adenoid hypertrophy and benign tumors such as JNA while evaluating a nasopharyngeal mass in children. Nasopharyngeal NHL are highly chemo sensitive, therefore, an early diagnosis can aid timely commencement of chemotherapy and prevent progression and complications of the disease.

Disparate Outcomes, Biologic and Therapeutic Differences in Pediatric versus Adult Patients with Ewing Sarcoma

Introduction: Ewing sarcoma (ES) is a small blue round cell sarcoma affecting a wide age spectrum. Clinical advances predominately stem from pediatric research consortia clinical trials. In most series, adults have poorer outcomes when compared to children. The aim of this study was to perform a detailed evaluation of factors potentially accounting for this difference. Methods: A single institution retrospective chart review was conducted on patients with ES diagnosed from 2005 to 2015, identified using a free-text search engine with the keywords “Ewing sarcoma” as well as a corresponding pathologic database. Data were analyzed based on age, pediatric (age <18) and adult (age >18 years), using a multivariate analysis model. Results: Eighty-eight ES patients (34 pediatric, 54 adult) were identified with a median age of 13 (range 3–18) and 31 (range 19–70) in their respective cohorts. Five-year overall survival (OS) was higher in pediatric patients (73.5% vs. 48.1%, p = 0.0213). By stage, 5-year OS in pediatric versus adult patients was 65% versus 20% (p = 0.0530) in metastatic (n = 32) and 68.1% versus 58.8% (p = 0.278) in localized (n = 56) patients. Lung-only metastases were present in 83% of metastatic pediatric patients versus 35% of adult metastatic patients. Pediatric patients received more cycles of first-line chemotherapy (13.8 vs. 11.4, p = 0.001), independent of stage. More cycles of chemotherapy correlated with improved OS (HR: 0.864, CI: 0.773–0.967) and progression-free survival (HR: 0.897, CI: 0.808–0.996). Conclusions: Outcome differences were most notable in patients with metastatic disease, although not statistically significant. Our series found differences in presentation between pediatric and adult populations with adult patients receiving fewer cycles of chemotherapy. This may suggest that both variations in underlying disease biology and potentially differences in treatment may account for outcome disparities.

SDPS-08 OSSEOUS METASTASES IN H3G34-MUTANT DIFFUSE HEMISPHERIC GLIOMAS

Abstract Subset of patients with H3G34 gliomas may present with extra-CNS metastasis further complicating both diagnosis and treatment. We describe a case of a 19-year-old female presenting initially with focal motor seizure in right leg along with leg pain. MRI of the leg showed an ill-defined right distal femur expansile osteolytic lesion with central fluid signal, thick rim enhancement, endosteal scalloping, cortical invasion, and smooth enhancing periosteal reaction/soft tissue extension associated with surrounding enhancing marrow signal abnormality worrisome for lesion extension. Contrast brain MRI exhibited multiple frontal and partial lobe T2 FLAIR hyperintense lesions. The largest lesion demonstrated contrast enhancement, internal foci of restricted diffusion, and a focus of intratumoral hemorrhage. A whole-body PET/CT showed intensely FDG-avid lytic lesion in the right distal femur, with FDG activity along the biopsy tract. Hypermetabolic lytic metastases to the right femoral head and mid-sacral body were also observed. A craniotomy with brain lesion biopsy two months later indicated preliminary histopathology of malignant small round blue cell neoplasm. A biopsy from the distal right femur was non-diagnostic of malignancy but a sacral bone biopsy reported malignant small blue cell neoplasm, consistent with involvement by the patient's known cranial neoplasm. Final pathological diagnosis including molecular diagnostics was consistent with WHO grade 4 IDH-wildtype H3G34 mutant diffuse hemispheric glioma with osseous metastases. Patient was treated with chemoradiotherapy with temozolomide (TMZ). Following the sixth cycle of TMZ, MRI brain imaging was stable. Apart from holocephalic headaches, the patient had no significant medication side effects and was seizure-free. A second whole-body PET scan showed improvement and interval decrease in FDG uptake of the sacrum and right femoral head. Given the stress that patients with H3G34 can experience and the poor prognosis, it is imperative to expand our knowledge and ascertain accurate screening and diagnostic methodologies.

Childhood pilomatrixoma mimicking malignant small round blue cell tumor with positivity for CD99: Potential pitfall in cytology.

Pilomatrixoma is a relatively rare benign skin appendageal tumor, often presenting in the pediatric age group as a nodular lesion and most commonly involving the head and neck, making it amenable to primary fine needle aspiration (FNA) diagnosis. We report the clinical and histopathological findings of two cases of pilomatrixoma in children, both of which were initially misdiagnosed as small round blue cell tumors due to high cellularity and misinterpretation of the proliferating basaloid cells. Histopathology revealed basal cell proliferation and mitoses indicating that they were progressive, early lesions. The first case showed membranous positivity for CD99 which prompted a diagnosis of Ewing sarcoma. Awareness of the morphological spectrum including positivity for CD99 and careful evaluation of cell block histology could have averted the misdiagnosis. Pilomatrixoma should be included as an important differential diagnosis when faced with primitive-appearing cells on FNA, especially in children with mass lesions in the head and neck region.

Diagnostic Utility of GATA3 and ISL1 in Differentiating Neuroblastoma From Other Pediatric Malignant Small Round Blue Cell Tumors.

GATA3 and ISL1 may be valuable in the diagnostic work-up of neuroblastoma and may reliably be used to support the neuroblastic lineage of pediatric small round blue cell tumors. Furthermore, dual positivity helps in challenging scenarios, when there is equivocal imaging, overlapping IHC features, limited specimen, and the lack of facility for a molecular work up.

Ewing’s Sarcoma of Rectum – A Rare Case Report

A 16-year-old male presented with constipation, acute retention of urine and abdominal swelling associated with pain. Per-rectal examination revealed painful growth in lateral and anterior wall of rectum 4cm from anal verge. X-ray erect abdomen was done which showed Indistinct bowel gas pattern suggestive of Intestinal obstruction. Diversion transverse colostomy was done in view of acute intestinal obstruction. Investigations revealed large well defined exophytic heterogenous lesion arising from lateral wall of rectum with normal CEA levels. Biopsy revealed small round blue cell tumour which was positive for Pan CK and CD99. He was planned for 6 cycles of Neoadjuvant chemotherapy (NACT) with VAC IE followed by reassessment for local therapy followed by adjuvant chemotherapy with 8 cycles of VAC IE. He received 6 cycles of VAC IE and Definitive radiation therapy 45Gy in 25 fractions by 3DCRT. After completion of radiation therapy, he received 8 more cycles of VAC IE in TATA memorial hospital. We present this case report, due to the rarity of Extraosseous Ewing’s sarcoma (EES)of the rectum.

Small Round Blue Cell Tumours of the Sinonasal Area: Our 5 year Experience in a Tertiary Care Centre in India.

Purpose: The main purpose of this study is to understand the characteristics and management of sinonasal small round blue cell tumors and also to emphasise the role of immunohistochemistry in their diagnosis and on the outcomes after endoscopic/open excision in these patients. Methods: This is a retrospective study conducted at a tertiary care referral centre in India which included 38 patients with sino nasal for a period of 5 years. All the patients were evaluated clinically and radiologically. All cases were confirmed diagnostically with histopathological examination and immunohistochemistry following surgical excision either by endoscopic or open approach. Some of the cases underwent post operative radiotherapy. Results: In our study, among 176 cases diagnosed with Sino nasal malignancies, 38 (21.6%) cases were diagnosed with sinonasal small round blue cell tumors with male to female ratio 1.4:1. Most common histopathological type among all the sinonasal small round blue cell tumors that presented to us was esthesioneuroblastoma i.e., 8 (21%) patients followed by pituitary macroadenoma in 7(8.4%) patients. Other types are undifferentiated squamous cell carcinoma 10(13.1%), craniopharyngioma 8(10.5%), lymphoma 3(7.9%), synovial/spindle cell sarcoma, malignant melanoma and adenocarcinoma 1(2.6%) each. Schwannoma, rhabdomyosarcoma, neuroendocrine carcinoma and neurofibroma 2 (5.2%) each. Conclusion: Sinonasal small round blue cell tumors are extremely rare tumours. Histopathological diagnosis with immunohistochemistry is characteristic of various tumors and is conclusive for diagnosis. Knowledge of these tumor entity is essential as early diagnosis helps in further management in preventing spread to vital structures and improving outcome. Most of the tumors have a multimodality treatment approach which includes surgical excision, radiotherapy and chemotherapy.

NKX3.1 immunohistochemistry and methylome profiling in mesenchymal chondrosarcoma: additional diagnostic value for a well-defined disease?

Mesenchymal chondrosarcoma (MCS) is a rare and highly aggressive tumour of soft tissue and bone that is defined by an underlying and highly specific fusion transcript involving HEY1 and NCOA2. Histologically, the tumours show a biphasic appearance consisting of an undifferentiated blue and round cell component as well as islands of highly differentiated cartilage. Particularly in core needle biopsies, the chondromatous component can be missed and the non-specific morphology and immunophenotype of the round cell component can cause diagnostic challenges. We applied NKX3.1 immunohistochemistry which was recently reported as a highly specific marker as well as methylome and copy number profiling to a set of 45 well characterised MCS cases to evaluate their potential diagnostic value. Methylome profiling revealed a highly distinct cluster for MCS. Notably, the findings were reproducible also when analysing the round cell and cartilaginous component separately. Furthermore, four outliers were identified by methylome profiling for which the diagnosis had to be revised. NKX3.1 immunohistochemistry showed positivity in 36% of tumours, the majority of which was rather focal and weak. Taken together, NKX3.1 expression showed a low sensitivity but a high specificity in our analysis. Methylome profiling on the other hand represents a sensitive, specific and reliable tool to support the diagnosis of MCS, particularly if only the round cell component is obtained in a biopsy and the diagnosis is not suspected. Furthermore, it can aid in confirming the diagnosis in case RNA sequencing for the HEY1::NCOA2 fusion transcript is not available.

Cancer histotypes and trends in Azare, Northeast Nigeria: impact of diagnostic support disparity in data reporting.

Definitive, affordable, and timely diagnosis of cancer is key to providing data for surveillance and control programmes. Care disparities have been shown to contribute to poorer survival, especially in resource-constrained populations. Here, we describe the profile of histologically diagnosed cancers in our hospital and highlight the possible effects of inadequate diagnostic support on data reporting. We designed a retrospective cross-sectional descriptive study to review histopathology reports archived at the Department of Pathology of our hospital spanning from January 2011 to December 2022. Cases diagnosed as cancer were retrieved and classified by systems, organs and histology types alongside the patient's age and gender. The trend in the volume of pathology requests and the corresponding malignant diagnosis yield over the period was also documented. Data generated were analyzed statistically using appropriate statistics and presented as proportions and means, with the level of statistical significance set at p < 0.05. There were 488 cancers out of 3,237 histopathology requests received within the study period. Of these 316 (64.7%) were females. Overall mean age was 48.8 ± 18.6 years with a peak age at the sixth decade, females being significantly younger (46.1 versus 53.5 years; p < 0.001). The top five cancers were breast (22.7%), cervical (12.7%), prostate (11.7%), skin (10.7%) and colorectal cancers (8%). Among females, breast, cervical and ovarian cancers predominated, whereas prostate, skin and colorectal cancers, were commonest among males in decreasing order. Paediatric malignancies accounted for 3.7% of all the cases, most being small round blue cell tumours. The volume of pathology requests rose remarkably from 95 cases in 2014 to 625 cases in 2022 with a corresponding increase in cancer case diagnoses. Cancer subtypes and ranking in this study are similar to those from urban populations in Nigeria and Africa, despite the low number of cases recorded. Efforts to reduce the disease burden are warranted.

CD43-positive, EWSR1::FLI1 -rearranged Soft Tissue Sarcoma in a Pediatric Patient With History of B-Cell Acute Lymphoblastic Leukemia.

Ewing sarcoma is a small round blue cell tumor typically characterized by an EWSR1 rearrangement and expression of CD99 and NKX2.2, without expression of hematopoietic markers such as CD45. CD43 is an alternative hematopoietic immunohistochemical marker often utilized in the workup of these tumors and its expression typically argues against Ewing sarcoma. We report a 10-year-old with history of B-cell acute lymphoblastic leukemia presenting with an unusual malignant shoulder mass with variable CD43 positivity, but with an EWSR1::FLI1 fusion detected by RNA sequencing. Her challenging workup highlights the utility of next-generation DNA-based and RNA-based sequencing methods in cases with unclear or conflicting immunohistochemical results.