SMARCB1 (INI-1) deficient sinonasal carcinoma of the right maxillary sinus - A rare entity.

INTRODUCTION AND IMPORTANCE: SMARCB1 (INI-1) is a vital tumour suppressor gene on chromosome 22q11.2, preventing tumour development in the SWI/SNF complex. Mutations cause SMARCB1-deficient tumours with distinct features. Loss of INI-1 expression is seen in malignancies, including sinonasal carcinoma and atypical teratoid/rhabdoid tumours. Recently recognized as a separate entity, SMARCB1-deficient sinonasal carcinomas (SDSC) are rare, clinically aggressive, and mimic other malignancies, emphasizing their significant diagnosis due to poorer prognosis, particularly in the elderly. CASE PRESENTATION: A 66-year-old male presented with a 4-month-old right cheek swelling, diagnosed initially as a sinonasal neoplastic mass. The biopsy revealed sinonasal mucosal fragments infiltrated by a tumour with plasmacytoid morphology. Immunohistochemistry (IHC) of the tumour cells was positive for p63 and pan-cytokeratin and showed INI-1 loss. Subsequent subtotal maxillectomy was performed, and the patient received adjuvant chemotherapy and radiotherapy. At a thirteen-month follow-up, the patient achieved his daily activities with no signs of recurrence. CLINICAL DISCUSSION: The loss of protein expression in sinonasal cancer is predominantly attributed to the homozygous deletion of SMARCB1. SDSC, a profoundly invasive malignant carcinoma, tends to infiltrate sinuses and extend into the intracranial regions. The IHC findings of our case were in coherence with previous studies in SMARCB1. The prognosis is particularly unfavourable in males and advanced tumours. CONCLUSION: The tumour's microscopic and immunohistochemical characteristics indicated the SDSC. Due to its aggressive nature and high mortality rates, dealing with a paranasal mass, one should be suspicious of this tumour.

Conventional Spinal Chordomas: Investigation of SMARCB1/INI1 Protein Expression, Genetic Alterations in SMARCB1 Gene, and Clinicopathological Features in 89 Patients.

The partial loss of SMARCB1/INI1 expression has recently been reported in skull base conventional chordomas, with possible therapeutic implications. We retrospectively analyzed 89 patients with conventional spinal chordomas to investigate the differences in the immunohistochemical expression of SMARCB1/INI1 and the underlying genetic alterations in the SMARCB1 gene. Moreover, we assessed the correlation of clinicopathological features (age, gender, tumor size, tumor location, surgical margins, Ki67 labelling index, SMARCB1/INI1 pattern, previous surgery, previous treatment, type of surgery, and the Charlson Comorbidity Index) with patient survival. Our cohort included 51 males and 38 females, with a median age at diagnosis of 61 years. The median tumor size at presentation was 5.9 cm. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) rates were 90.8% and 54.9%, respectively. Partial SMARCB1/INI1 loss was identified in 37 (41.6%) patients with conventional spinal chordomas (27 mosaic and 10 clonal). The most frequent genetic alteration detected was the monoallelic deletion of a portion of the long arm of chromosome 22, which includes the SMARCB1 gene. Partial loss of SMARCB1/INI1 was correlated with cervical-thoracic-lumbar tumor location (p = 0.033) and inadequate surgical margins (p = 0.007), possibly due to the high degree of tumor invasiveness in this site. Among all the considered clinicopathological features related to patient survival, only tumor location in the sacrococcygeal region and adequate surgical margins positively impacted DFS. In conclusion, partial SMARCB1/INI1 loss, mostly due to 22q deletion, was detected in a significant number of patients with conventional spinal chordomas and was correlated with mobile spine location and inadequate surgical margins.

SMARCB1-Retained and SMARCB1-Deficient SNUC are Genetically Distinct: A Pilot Study Using RNA Sequencing.

Background Understanding the genetic basis for the molecular classification of sinonasal undifferentiated carcinoma (SNUC) based on SMARCB1 may improve our understating regarding the nature of the disease. The objective of the study was to compare the genetic profile of SMARCB1-retained (SR-SNUC) and SMARCB1-deficient SNUC (SD-SNUC). Methods Formalin-fixed, paraffin-embedded tissue from treatment-naive patients with SNUC were selected. Three cases of SR-SNUC, four cases of SD-SNUC, and four samples of nontumor tissue (control samples) were selected. Ribonucleic acid (RNA) sequencing was performed. Results SR-SNUC had a higher number of variants (1 variant for every 15,000 bases) compared with SD-SNUC (1 variant every 29,000 bases). The ratio of missense to silent mutation ratio was higher for SR-SNUC (0.8) as compared with SD-SNUC (0.7). Approximately 1,500 genes were differentially expressed between SR-SNUC and SD-SNUC. The genes that had a higher expression in SR-SNUC included TPD52L1, B3GNT3, GFY, TJP3, ELL3, CYP4F3, ALDH3B2, CKMT1B, VIPR1, SLC7A5, PPP2R2C, UPK3B, MUC1, ELF5, STY7, and H2AC14. The gene that had a higher expression in SD-SNUC was ZFHX4. Most of these genes were related to either protein translation or immune regulation. The most common ( n = 3, 75%) mechanisms of loss of SMARCB1 gene in SD-SNUC was loss of heterozygosity. Conclusion RNA sequencing is a viable and informative approach for genomic profiling of archival SNUC samples. Both SR-SNUC and SD-SNUC were noted to have distinct genetic profiles underlying the molecular classification of these diseases.

Myoepithelioma-Like Tumor of the Vulvar Region: A Clinicopathologic Study of Four Cases.

Myoepithelioma-like tumors of the vulvar region (MELTVR) are solid tumors found in the vulva of adult women. They have a similar histopathology to myoepithelioma but differ in immunohistochemical phenotype and genetic changes. In this study, we report four examples of MELTVR, occurred in the external genitalia and mons pubis of adult women aged 32 to 39 years. The tumors presented as subcutaneous masses without obvious tenderness. The tumors were composed of a mixture of myxoid and nonmyxoid components, and myxoid areas accounted for 5% to 80% of the tumor volume. The tumor cells were spindle-shaped or epithelioid, with abundant cytoplasm, vesicular nuclei, and small nucleoli. The nuclear atypia was mild to moderate, with 0 to 10 mitotic figures per 10 high-power fields. Immunohistochemically, all four tumors showed consistent positivity for EMA, calponin and ER; three tumors exhibited PR expression. All tumors were negative for S100 protein and SMA. AE1/AE3 expression was absent in all except one tumor, which showed rare positivity. SMARCB1/INI1 expression was deficient in all tumors. EWSR1 and FUS rearrangements were absent. All tumors were treated through surgery. All patients were alive without recurrence on most recent follow-up. Together, this overview of four additional tumors of MELTVR offers further insight into this rare and poorly understood disease.

Outcomes of SMARCB1-deficient sinonasal carcinoma: Largest single-center cross-sectional study.

BACKGROUND: We evaluate outcomes of SMARCB1-deficient sinonasal carcinomas in the largest single-institution study. METHODS: Retrospective cross-sectional study of patients with SMARCB1-deficient sinonasal carcinoma between 1998 and 2024. Disease-specific survival (DSS) and recurrence-free probability (RFP) at 1 and 5 years were measured by Kaplan-Meier method. RESULTS: There were 47 patients with a median age of 53. Initial pathological diagnosis was altered in 33%. Twelve (34%) patients received neoadjuvant chemotherapy, with one partial response. Curative surgical approach was undertaken in 73%. Definitive chemoradiation was administered in 20%. DSS at 1 and 5 years was 93% and 45%, respectively. RFP at 1 and 5 years was 73% and 33%, respectively. On multivariate analysis, cranial nerve involvement (p = 0.01 for DSS) remained significantly worse for DSS and overall survival. CONCLUSIONS: SMARCB1-deficient tumors had limited response to neoadjuvant chemotherapy. Cranial nerve involvement was associated with worse prognosis. Optimal treatment is unclear. Surgery should be offered to patients with resectable disease.

A Case of SMARCB1-Deficient Sinonasal Carcinoma With Clear Cell Morphology.

SMARCB1 is a gene known to cause carcinogenesis in many soft tissue tumors, including malignant rhabdoid tumors and epithelioid sarcoma. Since the first report of a subtype of sinonasal carcinoma characterized by a deficiency of the SMARCB1 gene in 2014 to date, fewer than 200 cases have been reported. We report a case of SMARCB1-deficient sinonasal carcinoma with clear cell morphology. In our case, there are no evident basaloid or plasmacytoid/rhabdoid tumor cells, which are typical histopathological features of SMARCB1-deficient sinonasal carcinoma. SMARCB1-deficient sinonasal carcinoma is prone to recurrence and has a very poor prognosis. As the development of molecularly targeted agents progresses, therapeutic efficacy is expected to improve. Simultaneously, the importance of early and accurate diagnosis of SMARCB1-deficient sinonasal carcinoma will increase. With the limited information provided by biopsy specimens, it is necessary to confirm the loss of SMARCB1 expression by immunohistochemistry and investigate the presence of SMARCB1 gene deletion by molecular genetics, considering the possibility of SMARCB1-deficient sinonasal carcinoma even in atypical cases without basaloid or plasmacytoid/rhabdoid cell morphology, as in our case.

[SMARCB1-deficient renal medullary carcinoma with revealed by a supra-clavicular metastatic lymph node]. / Carcinome médullaire rénal SMARCB1-déficient révélé par une métastase ganglionnaire sus-claviculaire.

We report the case of a 14 year-old teenager who has SC hemoglobinosis and presented with a tumor syndrome with a retro-peritoneal mass, a supraclavicular lymph node and a mid-renal lesion. The microscopic examination revealed an undifferentiated tumor proliferation infiltrating the lymph node parenchyma. This tumor proliferation was INI1/SMARCB1-deficient, and expressed cytokeratins. Given the fact that the histopathological data showed an undifferentiated INI1-deficient carcinoma and that the patient has a kidney lesion and a sickle cell trait, the final diagnosis was lymph node metastasis of SMARCB1-deficient renal medullary carcinoma (OMS 2022).

Congenital Disseminated Malignant Rhabdoid Tumor Mimicking a Vascular Lesion.

A congenital disseminated malignant rhabdoid tumor (MRT) is an exceedingly rare and aggressive pediatric cancer marked by the presence of malignant rhabdoid cells in various organs, including the brain, kidneys, and soft tissues, at birth. It is often detected prenatally or shortly post-birth. The malignancy's aggressiveness results in a bleak prognosis, offering limited treatment options and low survival rates. Early diagnosis and comprehensive medical intervention are crucial, but managing this condition is complicated by its rarity. We herein presented a case of a 37 and 1/7 week gestation male infant with a rapidly growing arm soft tissue mass within two weeks, diagnosed as an MRT. Post-delivery examinations revealed multiple lesions in the lungs, kidney, liver, and adrenal glands. Notably, chemotherapy yielded a significant improvement in the arm lesion, contrasting with other lesions showing a limited response. This observation suggests potential tumor heterogeneity, emphasizing the necessity of diverse therapeutic regimens. Our case underscores the complexities of congenital disseminated MRT, prompting a reevaluation of treatment strategies for enhanced efficacy in managing this challenging pediatric cancer.

Central nervous system embryonal tumors with EWSR1-PLAGL1 rearrangements reclassified as INI-1 deficient tumors at relapse.

PURPOSE: Central nervous system (CNS) embryonal tumors are a diverse group of malignant tumors typically affecting pediatric patients that recently have been better defined, and this paper describes evolution of a unique type of embryonal tumor at relapse. METHODS: Two pediatric patients with CNS embryonal tumors with EWSR1-PLAGL1 rearrangements treated at Arkansas Children's Hospital with histopathologic and molecular data are described. RESULTS: These two patients at diagnosis were classified as CNS embryonal tumors with EWSR1-PLAGL1 rearrangements based on histologic appearance and molecular data. At relapse both patient's disease was reclassified as atypical teratoid rhabdoid tumor (ATRT) based on loss of INI-1, presence of SMARCB1 alterations, and methylation profiling results. CONCLUSION: CNS embryonal tumors with EWSR1-PLAGL1 rearrangements acquire or include a population of cells with SMARCB1 alterations that are the component that predominate at relapse, suggesting treatment aimed at this disease component at diagnosis should be considered.

Elusive and Aggressive: Unraveling SMARCB1/INI1-Deficient Undifferentiated Carcinoma With Rhabdoid Features Arising From the Colon: A Case Report and Comprehensive Literature Review.

Undifferentiated carcinomas are highly aggressive tumors with a dismal prognosis. A subset of these tumors has been associated with inactivation or mutations of the Switch/Sucrose Nonfermenting (SWI/SNF) remodeling complex. Our understanding of the relationship between the clinicopathological features and molecular profiling of SWI/SNF-deficient undifferentiated carcinoma is still evolving due to its rarity. We herein present a rare tumor of undifferentiated carcinoma with SMARCB1/INI1 deficiency arising from the colon. The histology revealed a tumor composed of sheets of discohesive, high-grade epithelioid cells with rhabdoid morphology along with anaplastic giant cells. Additionally, there was a significant infiltration of inflammatory cells in the background. Immunohistochemical (IHC) analysis supported the diagnosis of carcinoma with loss of INI1 expression, the tumor was mismatch repair protein proficient. Molecular analysis demonstrated an oncogenic KRAS mutation (p.G12D), whereas it was wild-type BRAF, and wild-type NRAS. The diagnosis of SWI/SNF-deficient undifferentiated carcinoma can be challenging. Correlation with clinical findings, in conjunction with IHC work-up and molecular analysis, is of utmost importance to arrive at the appropriate diagnosis and exclude potential mimics.

Two Cases of Atypical Teratoid/Rhabdoid Tumor in the Spinal Cord: Loss of SMARCB1 in a Child and Loss of SMARCA4 in an Adult.

We compare two cases of primary spinal atypical teratoid/rhabdoid tumor (AT/RT), which rarely occurs in adults marked by SMARCA4 inactivation, and SMARCB1 inactivation for pediatric cases. AT/RT represents a highly malignant neoplasm comprising poorly differentiated constituents and rhabdoid cells, with SMARCB1(INI1) or infrequently SMARCA4 (BRG1) inactivation. These tumors are predominantly found in children but are rare in adults. While AT/RT can arise anywhere in the central nervous system, spinal cord localization is comparatively scarce. Despite mutation or loss of SMARCB1 at the 22q11.2 locus serving as the genetic hallmark of AT/RTs, infrequent cases of SMARCA4 inactivation with intact SMARCB1 protein expression are significant. We present each case of primary spinal tumors in a child and an adult, showing loss of the SMARCB1 and SMARCA4 proteins, respectively. Both tumors met the AT/RT diagnostic criteria. The histopathology demonstrated the presence of rhabdoid cells in both cases. Diagnosing primary spinal AT/RT with SMARCB1 protein loss remains a challenge. Nevertheless, the presence of SMARCB1 positivity alone must be noted to be insufficient to exclude the possibility of AT/RT diagnosis. In cases in which the diagnosis of AT/RT is highly suspected clinically, additional testing is warranted, including SMARCA4 analysis.

Decoding the rhabdoid riddle in liver: A rare case of primary hepatic malignant rhabdoid tumor with a comprehensive literature review.

Malignant rhabdoid tumor of the liver is a rare, highly aggressive primary hepatic malignancy occurring primarily in infants. Establishing a definitive diagnosis is challenging due to its rarity, non-specific clinicoradiologic findings, and overlapping morphologic features. Herein, we present the cytomorphologic and immunocytochemical characteristics of a rare case of primary hepatic Malignant rhabdoid tumor (MRT) in an infant. A 5-month-old female child presented with progressively increasing firm mass in the upper abdomen, progressive pallor, sudden onset respiratory distress, and difficulty feeding. On examination, the child had massive, firm nodular hepatomegaly. Ultrasonography of the abdomen revealed a heterogeneously hypoechoic lesion in the left lobe of the liver. Serum alpha-fetoprotein levels were within normal limits. An ultrasound-guided fine-needle aspiration cytology (FNAC) from the liver mass showed predominantly dispersed large, markedly pleomorphic tumor cells with round to oval eccentrically placed nuclei, prominent nucleoli, and moderate cytoplasm. On immunocytochemistry, tumor cells showed positivity for vimentin, cytokeratin, and EMA and demonstrated a loss of INI1, confirming the diagnosis of MRT. The index report highlights the distinctive clinicopathological features of a hepatic malignant rhabdoid tumor along with the key differential diagnoses, which may pose a diagnostic conundrum. A high index of clinical suspicion and a thorough understanding of its cytomorphological and immunochemical characteristics are crucial for an accurate diagnosis.

SMARCB1/INI1-deficient epithelioid and myxoid neoplasms in paratesticular region: Expanding the clinicopathologic and molecular spectrum.

SMARCB1/INI1-deficient soft tissue tumors with epithelioid and myxoid features are diverse and mainly include soft tissue myoepithelial tumor, extraskeletal myxoid chondrosarcoma, and the recently described myoepithelioma-like tumor of the vulvar region and myxoepithelioid tumor with chordoid features. Because of their overlapping features, the accurate diagnosis and classification of these tumors are often challenging. Herein, we report two unique cases of SMARCB1/INI1-deficient soft tissue neoplasm with epithelioid and myxoid features occurring in male paratesticular region. The first case was a 52-year-old man presented with an intermittent painful left paratesticular mass for 1 year. The second case was a 41-year-old man presented with a painless paratesticular mass on the right side for 3 months. Both patients underwent an orchiectomy. After 6 and 26 months of follow-up, both were alive with no evidence of recurrence or metastasis. In both cases, the tumor was relatively well-demarcated and showed monomorphic round to epithelioid cells arranged in a nested, trabecular, reticular, and corded pattern, setting in a myxohyalinized and vascularized matrix. The tumor cells showed relatively uniform round nuclei with vesicular chromatin and variably prominent nucleoli. No rhabdoid cells were identified. Mitoses numbered 3 and 2 per 10 high-power fields. Tumor necrosis or lymphovascular invasion was absent. Immunohistochemically, both tumors expressed epithelial membrane antigen (focal), calponin (focal), and CD99. SMARCB1/INI1 expression was deficient in both cases. In addition, case 1 diffusely expressed pan-cytokeratin, and case 2 diffusely expressed CD34 and synaptophysin. Molecular genetically, case 1 showed SMARCB1 homozygous deletion as detected by fluorescence in-situ hybridization (FISH), and case 2 demonstrated SMARCB1 copy number deletions by next-generation sequencing and SMARCB1 monoallelic deletion by FISH. Both cases lacked EWSR1 rearrangements by FISH. The overall clinicopathologic profiles of the two cases made it difficult to classify them as one of the established categories of SMARCB1/INI1-deficient mesenchymal tumors. Our study further expands the clinicopathologic and molecular spectrum of SMARCB1/INI1-deficient epithelioid and myxoid neoplasms and highlights the challenges to diagnose these tumors.

SMARCB1/INI1-Deficient Poorly Differentiated Carcinoma of the Colon With Rhabdoid Features-A Rare Tumor With Serrated Phenotype: Case Report and Review of Literature.

Poorly differentiated colonic carcinoma with rhabdoid features is a rarely described entity. Our knowledge regarding the molecular phenotype of the tumor is evolving. We herein report a similar tumor with rhabdoid differentiation identified in the splenic flexure, which on histological examination showed a poorly differentiated phenotype with epithelioid to spindled morphology, tumor giant cells, and rhabdoid differentiation. The tumor was mismatch repair-proficient, deficient of INI1/SMARCB1, KRAS mutated (A146×), BRAFV600E mutated (c.1799T > A), and NRAS wild-type, indicating serrated differentiation in the tumor. The patient died after 3.5 months post-surgery. INI1-deficient poorly differentiated carcinoma of the colon is a rare, aggressive colonic malignancy showing a serrated phenotype. Routine identification and subtyping are important keeping in mind the distinct tumor phenotype, resistance to conventional chemotherapy, and dismal prognosis.

Case report metastatic SMARCB1 (INI1)-deficient gastric undifferentiated carcinoma in pleural effusion: A case report and literature review.

INI1-deficient gastric undifferentiated carcinoma is a rare tumour that may present as high-grade epithelioid morphology without apparent rhabdoid tumour cells. Syncytial tumour cells may be a crucial clue in such cases, especially in cytological specimens. Cell block and immunocytochemical staining can be valuable tools in achieving an accurate diagnosis.

Primary cutaneous SMARCA4-deficient undifferentiated malignant neoplasm: A rare case report and literature review.

Primary cutaneous SMARCA4-deficient undifferentiated malignant neoplasm (SD-UMN) is a rare and recently described entity characterized by the loss of expression of the SMARCA4 (BRG1) protein, which is involved in chromatin remodeling. SD-UMN presents a diagnostic challenge due to its rarity and unique histopathological and immunohistochemical features. In this report, we present a case of primary cutaneous SD-UMN in a 67-year-old man who presented with a rapidly growing, ulcerated, and bleeding nodule on his right cheek. Histopathological examination revealed a highly cellular dermal tumor consisting of pleomorphic epithelioid cells with prominent mitotic figures and necrosis, lacking any morphological evidence of differentiation. Immunohistochemical analysis showed a complete loss of SMARCA4 and SMARCA2 expression, while INI-1 expression remained intact. p53 was diffusely expressed, and p16 was completely absent. In addition, a range of markers, including high-molecular-weight cytokeratin, p63, SOX10, INSM1, MCPyV, NKX2.2, CD99, CDX2, CD56, ERG, NUT, desmin, androgen receptor, chromogranin, CD34, and CD43 were all negative. To date, only two cases of primary cutaneous SMARCA4-deficient undifferentiated tumors have been reported in the literature. Therefore, this case report adds to the limited body of knowledge on the clinical and histopathological features of this novel entity. The report highlights the importance of considering SD-UMN in the differential diagnosis of undifferentiated cutaneous tumors.

Immunotherapy in SMARCB1 (INI-1)-deficient sinonasal carcinoma: Two case reports.

BACKGROUND: SMARCB1/INI-1 deficient sinonasal carcinoma (SDSC) is a rare subset of sinonasal undifferentiated carcinoma with a poor prognosis. Here, we present two case reports of SDSC patients. We also review the literature on this tumor. This is the first published report of SDSC treatment with immunotherapy. CASE SUMMARY: Here we present two patient cases of SDSC in which initial consultation and diagnosis were complicated but SDSC was ultimately diagnosed. One patient received a traditional treatment of surgery and adjuvant chemoradiotherapy, while the other patient received additional immunotherapy; the prognoses of these two patients differed. We review previous diagnostic literature reports and SDSC treatments and provide a unique perspective on this rare type of tumor. CONCLUSION: SDSC is a rare, diagnostically challenging carcinoma with a consistently poor prognosis, early distant metastases, and frequent recurrence. Timely diagnosis and intervention are critical for treatment, for which the standard of care is surgery followed by adjuvant chemoradiotherapy, though immunotherapy may be an effective new treatment for SDSC.

Malignant rhabdoid tumor of kidney in an adult patient with positive family history of rhabdoid tumor: A case report and review of literature.

INTRODUCTION AND IMPORTANCE: Malignant rhabdoid tumor of kidney (MRTK) is almost exclusive to children. Only 10 cases of adult MRTK have been reported. Here, we present a case of MRTK in an adult patient and discuss its clinical findings, diagnostic challenges, and treatment outcome. We also perform literature review on this issue. CASE PRESENTATION: Our patient was a 29-year-old woman presented with fever and hematuria. She also mentioned atypical teratoid/rhabdoid tumor of cerebellum in her deceased child. Initial diagnostic work up led to left partial nephrectomy with the pathology report of high grade undifferentiated tumor. Early tumor recurrence necessitated left radical nephrectomy with extensive excision of adjacent tissues. Pathology for second specimen considering disease course and family history was MRTK. Even though chemotherapy was administered, she died few months later due to multiple metastases. CLINICAL DISCUSSION: Although diagnosis is challenging in all 11 reported cases -including our case- of adult MRTK, immunohistochemistry (i.e., negative reaction for INI-1) in conjunction with clinical and radiological findings are the main tool to reach diagnosis. Treatment options are much more diverse, ranging from surgery to immunotherapy, tyrosine kinase inhibitors, chemotherapy, and combination of these modalities. Prognosis remains dismal with the mean survival period of 7 months. CONCLUSION: Although extremely rare, MRTK might happen in adults. We report the first case of adult MRTK with positive family history of rhabdoid tumor of CNS, underscoring the importance of family history in reaching the diagnosis and highlighting the role of genetics in this rare disease.