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Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a rare epithelial tumor with a biallelic mutation involving any subunit of the SDH complex. Mostly, it has low-grade morphology and a favorable prognosis. We present a case of a 36-year-old woman with weight loss, night sweats, and symptomatic anemia. Her imaging showed a hypo-enhancing heterogeneous right renal mass with invasion of the renal vein and inferior vena cava. Microscopically, the tumor had focal low-grade areas (5%) and extensive areas with high-grade features, including rhabdoid (85%) and sarcomatoid (10%) dedifferentiation. Cytoplasmic inclusions, foci of extracellular mucin, coagulative necrosis, and inflammatory infiltrate were present. The tumor cells, including rhabdoid differentiated, were focally positive for AE1/AE3. Tumor cells showed loss of SDHB immunostaining, consistent with diagnosis. Genetics testing was recommended, but the patient expired due to metastatic carcinoma. Prior studies suggest that sarcomatoid transformation and coagulative necrosis increase the risk of metastasis by up to 70% in SDH-deficient RCC. Follow-up with surveillance for other SDH-deficient neoplasms is recommended in cases of germline mutation. Here, we report the first case of SDH-deficient RCC with concomitant rhabdoid and sarcomatoid features and a detailed review of diagnostic difficulties associated with high-grade tumors. [ABSTRACT FROM AUTHOR]

Primary meningioma at extracranial head and neck sites is uncommon. Since fine needle aspiration (FNA) is often the first line diagnostic modality for the evaluation of masses in the head and neck, extracranial meningiomas can create a significant diagnostic pitfall for FNA. We report a case of meningioma with rhabdoid features and BAP1 loss in a 26-year-old woman, presenting as a large neck mass along the carotid sheath. FNA biopsy of the mass demonstrated a highly cellular specimen with clusters of uniform, epithelioid cells with round to ovoid nuclei and moderate nuclear to cytoplasmic ratio. An extensive immunohistochemical panel performed on cell block sections showed that the tumor cells were weakly EMA positive, progesterone receptor was focally positive, and SSTR2A was diffuse and strongly positive. BAP1 immunohistochemistry showed a diffuse loss of expression in the tumor cells. After the cytologic diagnosis of meningioma, a tissue biopsy was performed, and the diagnosis of meningioma with rhabdoid features and BAP1 loss was confirmed. We also perform a literature review of meningioma cases presenting as a neck mass and evaluated by FNA. Our case highlights the significant diagnostic challenges that can be caused by extracranial meningiomas on FNA and the importance of ancillary studies to avoid diagnostic pitfalls. [ABSTRACT FROM AUTHOR]

This article presents a case study of a patient with a rare vascular tumor called epithelioid hemangioendothelioma (EHE). The study describes the characteristics of EHE cells and discusses the challenges in diagnosing this tumor due to its variability and lack of specific markers. The article also compares EHE with other malignancies and emphasizes the importance of using vascular markers and molecular studies to confirm the diagnosis. The prognosis for EHE in the lungs or pleura is generally poor, and treatment usually involves surgery with or without chemoradiation. [Extracted from the article]

SMARCB1-deficient sinonasal adenocarcinoma is a rare variant of SWI/SNF-deficient malignancies with SMARCB1 loss and adenocarcinoma features. More than 200 high-grade epithelial sinonasal malignancies were retrieved. A total of 14 cases exhibited complete SMARCB1 (INI1) loss and glandular differentiation. SMARCA2 and SMARCA4 were normal, except for one case with a loss of SMARCA2. Next-generation sequencing (NGS) and/or fluorescence in situ hybridization (FISH) revealed an alteration in the SMARCB1 gene in 9/13 cases, while 2/13 were negative. Two tumors harbored SMARCB1 mutations in c.157C > T p.(Arg53Ter) and c.842G > A p.(Trp281Ter). One harbored ARID1B mutations in c.1469G > A p.(Trp490Ter) and MGA c.3724C > T p.(Arg1242Ter). Seven tumors had a SMARCB1 deletion. One carried an ESR1 mutation in c.644-2A > T, and another carried a POLE mutation in c.352_374del p.(Ser118GlyfsTer78). One case had a PAX3 mutation in c.44del p.(Gly15AlafsTer95). Histomorphology of SMARCB1-deficient adenocarcinoma was oncocytoid/rhabdoid and glandular, solid, or trabecular in 9/14 cases. Two had basaloid/blue cytoplasm and one showed focal signet ring cells. Yolk sac tumor-like differentiation with Schiller-Duval-like bodies was seen in 6/14 cases, with 2 cases showing exclusively reticular-microcystic yolk sac pattern. Follow-up of a maximum of 26 months (median 10 months) was available for 8/14 patients. Distant metastasis to the lung, liver, mediastinum, bone, and/or retroperitoneum was seen in 4/8 cases. Locoregional failure was seen in 75% of patients, with 6/8 local recurrences and 3 cervical lymph node metastases. At the last follow-up, 5 of 8 (62%) patients had died of their disease 2 to 20 months after diagnosis (median 8.2 months), and 3 were alive with the disease. The original diagnosis was usually high-grade non-intestinal-type adenocarcinoma or high-grade myoepithelial carcinoma. A correct diagnosis of these aggressive tumors could lead to improved targeted therapies with potentially better overall disease-specific survival. [ABSTRACT FROM AUTHOR]

Background Metastatic RCC with sarcomatoid and/or rhabdoid (S/R) dedifferentiation is an aggressive disease associated with improved response to immune checkpoint therapy (ICT). The outcomes of patients treated with VEGFR-targeted therapies (TT) following ICT progression have not been investigated. Patients and Methods Retrospective review of 57 patients with sarcomatoid (S), rhabdoid (R), or sarcomatoid plus rhabdoid (S + R) dedifferentiation who received any TT after progression on ICT at an academic cancer center. Clinical endpoints of interest included time on TT, overall survival (OS) from initiation of TT, and objective response rate (ORR) by RECIST version 1.1. Multivariable models adjusted for epithelial histology, IMDC risk, prior VEGFR TT, and inclusion of cabozantinib in the post-ICT TT regimen. Results 29/57 patients had S dedifferentiation and 19 had R dedifferentiation. The most frequently used TT was cabozantinib (43.9%) followed by selective VEGFR TT (22.8%). The median time on TT was 6.4 months for all, 6.1 months for those with S dedifferentiation, 15.6 months for R dedifferentiation, and 6.1 months for S + R dedifferentiation. Median OS from initiation of TT was 24.9 months for the entire cohort, and the ORR was 20.0%. Patients with R dedifferentiation had significantly longer time on TT than those with S dedifferentiation (HR 0.44, 95% CI, 0.21-0.94). IMDC risk was associated with OS. Conclusions A subset of patients with S/R dedifferentiation derive clinical benefit from TT after they have progressive disease on ICT. Patients with R dedifferentiation appeared to derive more benefit from TT than those with S dedifferentiation. [ABSTRACT FROM AUTHOR]

Small cell undifferentiated (SCU) histology and alpha-fetoprotein (AFP) levels below 100 ng/mL have been reported as poor prognostic factors in hepatoblastoma (HB); subsequent studies reported SMARCB1 mutations in some SCU HBs confirming the diagnosis of rhabdoid tumor. The Children's Hepatic tumors International Collaboration (CHIC) database was queried for patients with HB who had AFP levels less than 100 ng/mL at diagnosis or were historically diagnosed as SCU HBs. Seventy-three of 1605 patients in the CHIC database were originally identified as SCU HB, HB with SCU component, or HB with low AFP levels. Upon retrospective review, they were re-classified as rhabdoid tumors (n = 11), HB with SCU component (n = 41), and HB with low AFP (n = 14). Seven were excluded for erroneously low AFP levels. Overall survival was 0% for patients with rhabdoid tumors, 76% for patients with HB with SCU component, and 64% for patients with HB with AFP less than 100 ng/mL. Patients with HB with SCU component or low AFP should be assessed for SMARCB1 mutations and, if confirmed, treated as rhabdoid tumors. When rhabdoid tumors are excluded, the presence of SCU component and low AFP at diagnosis were not associated with poor prognosis in patients diagnosed with HB.

Introduction: This investigation assessed whether the following factors were associated with radiographic local progression in bone metastases from renal cell carcinoma (RCC): (1) high-risk histologic features (2) lesional surgery (3) biologically effective dose (BED) of radiation therapy. Methods and materials: A single-institution database identified all patients who underwent surgery and radiation therapy for bone metastases from RCC to the appendicular skeleton and pelvis from 2006 to 2016. Thirty-six patients underwent radiotherapy for 80 metastases. While all patients had surgical stabilization, 17/36 also had lesional surgery to address the metastatic lesion. Progression of each individual lesion was determined using the application of RECIST criteria to imaging at last follow-up. Results: The rate of progressive disease was 8/25 (32%) in the high-risk group versus 5/55 (9%) in the standard-risk group (p ​= ​0.019). The rate of progression among high-risk metastases undergoing lesional surgery was 0/9 versus 8/16 (50%) having non-lesional surgery (p ​= ​0.0218). The rate of progression among standard-risk metastases undergoing lesional surgery was 1/16 (6%) versus 4/39 (10%) with non-lesional surgery (p ​= ​1.00). High-risk histologic features (OR: 10.592, 95% confidence interval: 1.347–83.271, p ​= ​0.025) and as well as a reduction in risk with every additional Gray of BED (OR: 0.902, 95% confidence interval: 0.827–0.984, p ​= ​0.021) were found to predict progressive disease. Conclusions: Bone metastases from renal cell carcinoma with high-risk histologic features are associated with less favorable response to radiotherapy than those with standard-risk histology. Delivery of a higher BED was associated with lower odds of progression.

NUT carcinoma and thoracic SMARCA4‐deficient undifferentiated tumour are unique entities in the 5th edition of the World Health Organisation (WHO) Classification of Thoracic Tumours, whose definitions include molecular genetic abnormalities. These aggressive tumours require rapid work‐ups on biopsies, but a broad list of differential diagnoses poses challenges for practising pathologists. This review provides an update on their key clinicopathological and molecular characteristics, as well as controversies regarding tumour classification and diagnostic strategy. Phenotypical assessment plays a substantial role in diagnosis because recurrent and predictable clinicopathological findings exist, including robust immunohistochemical phenotypes. Accurate diagnosis is crucial for appropriate management and a clearer understanding of the disease. [ABSTRACT FROM AUTHOR]

While the neural crest cell population gives rise to an extraordinary array of derivatives, including elements of the craniofacial skeleton, skin pigmentation, and peripheral nervous system, it is today increasingly recognized that Schwann cell precursors are also multipotent. Two mammalian paralogs of the SWI/SNF (switch/sucrose nonfermentable) chromatin-remodeling complexes, BAF (Brg1-associated factors) and PBAF (polybromo-associated BAF), are critical for neural crest specification during normal mammalian development. There is increasing evidence that pathogenic variants in components of the BAF and PBAF complexes play central roles in the pathogenesis of neural crest–derived tumors. Transgenic mouse models demonstrate a temporal window early in development where pathogenic variants in Smarcb1 result in the formation of aggressive, poorly differentiated tumors, such as rhabdoid tumors. By contrast, later in development, homozygous inactivation of Smarcb1 requires additional pathogenic variants in tumor suppressor genes to drive the development of differentiated adult neoplasms derived from the neural crest, which have a comparatively good prognosis in humans. [ABSTRACT FROM AUTHOR]

ALK-rearranged renal cell carcinoma (ALK-RCC) is a very rare novel molecularly defined entity in the recently published fifth edition of the World Health Organization classification of tumours. We describe a case of ALK-RCC in a 76-year-old female. The tumour was composed of discohesive rhabdoid cells and pleomorphic, multinucleated cells (equivalent to ISUP/WHO grade 4). The tumour showed expression with PAX8, Keratin 7 and alpha methylacyl CoA racemase. ALK (D5F3 clone) was strongly and diffusely positive. ALK-FISH showed significant split signals of ALK, confirming the diagnosis. RNA sequencing showed TPM3::ALK rearrangement. Including the current case, there are 14 reported ALK-RCC cases with the same TPM3 fusion partner gene. Review of these published cases highlights their morphological heterogeneity and stresses the importance of running ALK immunohistochemistry on difficult cases to classify renal tumours. This is important while identification of ALK-RCC has clinical significance due to the availability of targeted therapy with ALK inhibitors. [ABSTRACT FROM AUTHOR]

Extrarenal malignant rhabdoid tumors are rare, aggressive lesions that primarily affect infants and children with characteristic SMARCB1/INI1 mutations. While rhabdoid tumors are most commonly found in the kidneys and central nervous system, they have been reported in virtually every soft tissue in the body. A 20-year-old previously healthy male presented with a 4-month history of left upper extremity weakness and pain and a 1-week history of lower extremity weakness. MRI showed a combined intradural and extradural mass arising from the C8 root and involving the lower trunk of the brachial plexus. CT guided biopsy followed with onsite cytologic analysis initially concerning for plasma cell etiology. Full body PET/CT showed no evidence of metastases. The tumor was surgically resected and debulked. Extensive immunohistochemical testing on the resected specimen revealed a diagnosis of extrarenal malignant rhabdoid tumor. Recurrence invading paraspinous muscles, left lateral paravertebral space, left apical lung, and brachial plexus was noted within 2 months. Radiation and chemotherapy were initiated. Here we present imaging findings, image-guided biopsy, surgical management, and pathologic diagnosis of a rare case of extrarenal, extracranial malignant rhabdoid tumor of the brachial plexus and surrounding paraspinous muscles in a young adult male. [ABSTRACT FROM AUTHOR]

We present a rare case of rhabdoid squamous cell carcinoma (RSCC) on the scalp of a non-immunosuppressed male patient in his late 60s. This aggressive variant of squamous cell carcinoma (SCC) is characterized by tumor cells with eccentrically located nuclei and abundant eosinophilic cytoplasm, as observed on histopathological examination. While rhabdoid morphology has been reported in various anatomical sites, its occurrence in primary cutaneous tumors is exceptionally uncommon, with fewer than 10 cases documented to date. Immunohistochemically, the neoplasm demonstrated positivity for p40, cytokeratin 5/6 (CK5/6), and vimentin, while retaining integrase interactor 1 (INI1) expression and showing negativity for muscle differentiation markers. Loss of p53 staining suggested its role in the progression to a more aggressive phenotype. The DecisionDx-SCC assay (Castle Biosciences, Friendswood, TX, US) classified the tumor as Class 2B, indicating the highest biological risk for metastasis and poor outcomes. Despite the limited number of reported cutaneous RSCC cases, this variant appears to exhibit high aggressiveness, mirroring other visceral tumors with rhabdoid features. We discuss potential molecular events underlying this transformation. This case highlights the importance of recognizing this rare variant and its implications for patient management and prognosis., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: Dr. Gomez has served as a consultant and speaker for Castle Biosciences. Castle Biosciences laboratory services were used for tumor prognostication in this study. However, Castle Biosciences had no role in the study design, data interpretation, or manuscript preparation. No financial or other incentives were received from Castle Biosciences in connection with this study., (Copyright © 2024, Bobkova et al.)

Rhabdoid meningioma is a rare type of meningeal neoplasm in humans. This study reports the clinical, pathological, and ultrastructural features of 4 cases of canine meningioma with rhabdoid features. The cases were female and 8 to 12 years of age. Biopsies from complete surgical resections were examined for all cases. The whole brain with tumor recurrence was collected at necropsy in 2 dogs. Histologically, the tumors consisted of discohesive sheets of oval-polygonal cells with abundant eosinophilic cytoplasm and occasional paranuclear hyaline-like inclusions. Cells were intensely immunopositive for vimentin, negative for melan A and S100 protein in all cases, and showed variable immunolabeling for cytokeratin in 2 cases. Focal glial fibrillary acidic protein (GFAP)-immunopositive cells were present in 1 case. Ultrastructurally, the rhabdoid cells in case 1 contained prominent cytoplasmic whorls of intermediate filaments, recapitulating the ultrastructural features of rhabdoid meningioma in humans. In cases 2 and 3, the meningioma cells contained interdigitating cell processes folded in a maze-like fashion resembling rhabdoid-like meningioma in humans. In case 4, the voluminous cytoplasm contained many round-to-flattened mitochondria admixed with rough endoplasmic reticulum, indicating a predominant oncocytic differentiation and not the rhabdoid differentiation suggested by light microscopy. Thus, rhabdoid morphology occurs in different types of meningiomas, and ultrastructural findings are essential for a correct diagnosis. [ABSTRACT FROM AUTHOR]

Intrahepatic cholangiocarcinoma with rhabdoid morphology is rare, and only three case reports have been published to date, none of which discuss the genetic changes in the rhabdoid component. We present a case of intrahepatic cholangiocarcinoma with focal rhabdoid features and SMARCA4-deficiency detected using immunohistochemistry. A Japanese man in his 60s without viral hepatitis was diagnosed with an avascular tumor in the liver, measuring 4.4 cm in the greatest dimension. The tumor was mostly composed of moderately differentiated adenocarcinoma, focal poorly differentiated adenocarcinoma, and an undifferentiated rhabdoid component. Immunohistochemical analysis showed an inclusion-like staining pattern for keratin AE1/AE3 and vimentin in the rhabdoid component. BRG1/SMARCA4 was detected in the differentiated component but not in the poorly- and undifferentiated components. Our novel findings reflecting the morphological and genetic heterogeneity of intrahepatic cholangiocarcinoma and will aid the research on drugs targeting the aberrant SWItch/Sucrose NonFermentable complex. [ABSTRACT FROM AUTHOR]

Abstract Background Undifferentiated carcinoma of the biliary tract are highly aggressive malignancies. In other organs, a subgroup of undifferentiated carcinoma related to SWI/SNF complex–deficiency have been described. Case presentation A 30-year-old woman presented with rising inflammatory markers (C-reactive protein (CRP)). Ultrasound examination revealed a large tumor of the liver. A computed tomography scan was performed and was primarily interpreted as a tumor-forming liver abscess, possibly caused by gallbladder perforation. Subsequent liver segment resection was performed. Microscopic examination showed an undifferentiated carcinoma with rhabdoid morphology and prominent inflammatory infiltrate in the gallbladder base. With SWI/SNF immunohistochemistry, intact expression of SMARCB1, SMARCA4, ARID1A, but loss of SMARCA2 and PBRM1 was detected. Next-generation-sequencing detected KRAS, PBRM1 and ARID1B mutations, a deleterious splice-site mutation in the POLE-gene and a mutation in the TP53-gene. Conclusions We were able to demonstrate loss of SMARCA2 expression and mutations characteristic of an SWI/SNF-deficient carcinoma in a tumor derived from the gallbladder. This is the first reported case of an undifferentiated carcinoma with rhabdoid features in the gallbladder carrying a POLE mutation and SWI/SNF-deficiency of PBRM1 and SMARCA2.

Abstract Background Renal Cell Carcinoma (RCC) metastasizes in approximately 20–30% cases. The most common sites for metastases are the lungs, bones, liver, and brain. Metastases of RCC in the gastrointestinal tract (GIT) are very rare. Metastatic RCC has a poor prognosis. We herein present a case series of three patients with metastatic disease in the colon, duodenum, and pancreas following complete resection of RCC. Methods Hematoxylin and Eosin and immunohistochemical slides of 3 cases of RCC metastatic to GIT were reviewed. These cases were diagnosed between 2002 and 2019 at French Medical Institute for Mothers and Children (FMIC), Kabul, Afghanistan, and Aga Khan University Hospital (AKUH), Karachi, Pakistan. We also present a detailed review of published literature. Results We reviewed cases of three patients, two females and one male, with a mean age of 57.3 years (range 40–67 years) who underwent nephrectomy for RCC. They developed metastases in the colon, pancreas, and duodenum, respectively 12–168 months (median time 156 months) following primary tumor resection. The patient with metastatic RCC in colon presented with abdominal pain and constipation. An ulcerated mass was found on colonoscopy 30 cm from the anal verge. Diagnosis of RCC with rhabdoid features was confirmed in both primary and metastatic tumors. The second patient developed a metastatic nodule in the head of pancreatic while the third patient developed metastatic nodules in the duodenum and pancreas which were detected by Computed Tomography (CT) scanning. Histopathological examination confirmed the presence of clear cell RCC in the metastatic nodules in both cases. Conclusion Metastatic RCC should be considered in the differential diagnosis of mass in the gastrointestinal (including pancreaticobiliary) tract especially in presence of a past history of RCC. These patients should be screened thoroughly by physical examination and appropriate imaging studies.

The small cell undifferentiated component of hepatoblastoma is an uncommon histologic component and is distinguished from small cell undifferentiated like pattern (originally called hepatoblastoma and now recognized to be malignant rhabdoid tumor) by the bi-allelic SMARCB1 mutations or copy number alterations in the latter. AT-rich interactive domain-containing protein 1A (ARID1A) is a part of the ATP-dependent switch/sucrose non-fermentable complex assembly, but mutations have not been reported as drivers of malignant rhabdoid tumor. ARID1A mutations in hepatocellular carcinoma are associated with poor prognosis but its significance in hepatoblastoma is unknown. We report a unique case of hepatoblastoma in a 19-month-old female with an unusual/atypical small cell undifferentiated component with ARID1A and beta-catenin mutations. It had an aggressive clinical course despite treatment, with metastases to the left psoas muscle, perihepatic and paratracheal lymph nodes, spinal cord, and leptomeninges. Leptomeningeal metastases resulted in diffuse cerebral edema and death. The initial diagnostic biopsy did not reveal rhabdoid cells while all metastatic foci showed cells with rhabdoid morphology in the autopsy specimens. Although this rhabdoid component resembled malignant rhabdoid tumor morphologically, molecular analyses failed to show mutations or deletions of SMARCB1. [ABSTRACT FROM AUTHOR]

Atypical teratoid/rhabdoid tumors (ATRTs) are malignant central nervous system tumors that affect early childhood (< 3 years), and mostly located in the infratentorial space. Owing to an infrequent occurrence, their radiological features have not been completely defined. Nevertheless, these are characteristically intra-axial except for few instances in the cerebellopontine angle region. We describe a case of a 10-year-old boy who harbored an extra-axial, dural-based ATRT in the right parietal region. The lesion was totally excised followed by adjuvant chemo-radiotherapy. At 10-month follow-up, he was well with no recurrence. The report intends to highlight an atypical imaging presentation of ATRT in an older child, and adds to the radiological spectrum. This uncommon pathology should be borne in mind, even in a supratentorial dural-based location. [ABSTRACT FROM AUTHOR]

Abstract Background Sarcomatoid differentiation in renal cell carcinoma (RCC) with vena caval tumour thrombus has been shown to be associated with aggressive behaviours and poor prognosis; however, evidence of the impact of rhabdoid differentiation on prognosis is lacking. This study evaluated the impact of sarcomatoid differentiation and rhabdoid differentiation on oncological outcomes for RCC with vena caval tumour thrombus treated surgically. Methods We retrospectively analysed patients treated surgically for RCC with vena caval tumour thrombus at our institute from Jan 2015 to Nov 2018. Prognostic variables were evaluated for associations with progression-free survival (PFS) and cancer-specific survival (CSS) by Kaplan–Meier survival analysis and log-rank test. Univariate and multivariate analyses were performed to determine independent prognostic variables. Results We identified 125 patients with RCC and vena caval tumour thrombus, including 17 (13.6%) with sarcomatoid differentiation alone, 8 (6.4%) with rhabdoid differentiation alone and 3 (2.4%) with both sarcomatoid and rhabdoid differentiation. Compared to pure RCC, patients with sarcomatoid differentiation but not rhabdoid differentiation have worse PFS (p = 0.018 and p = 0.095, respectively). The univariate and multivariate analyses both showed sarcomatoid differentiation as a significant predictor of PFS. Compared to pure RCC, patients with sarcomatoid differentiation (p = 0.002) and rhabdoid differentiation (p = 0.001) both had significantly worse CSS. The univariate analysis showed sarcomatoid differentiation, rhabdoid differentiation, metastasis and blood transfusion as significant predictors of CSS (All, p

SMARCB1-deficient sinonasal adenocarcinoma is a rare variant of SWI/SNF-deficient malignancies with SMARCB1 loss and adenocarcinoma features. More than 200 high-grade epithelial sinonasal malignancies were retrieved. A total of 14 cases exhibited complete SMARCB1 (INI1) loss and glandular differentiation. SMARCA2 and SMARCA4 were normal, except for one case with a loss of SMARCA2. Next-generation sequencing (NGS) and/or fluorescence in situ hybridization (FISH) revealed an alteration in the SMARCB1 gene in 9/13 cases, while 2/13 were negative. Two tumors harbored SMARCB1 mutations in c.157C > T p.(Arg53Ter) and c.842G > A p.(Trp281Ter). One harbored ARID1B mutations in c.1469G > A p.(Trp490Ter) and MGA c.3724C > T p.(Arg1242Ter). Seven tumors had a SMARCB1 deletion. One carried an ESR1 mutation in c.644-2A > T, and another carried a POLE mutation in c.352&#95;374del p.(Ser118GlyfsTer78). One case had a PAX3 mutation in c.44del p.(Gly15AlafsTer95). Histomorphology of SMARCB1-deficient adenocarcinoma was oncocytoid/rhabdoid and glandular, solid, or trabecular in 9/14 cases. Two had basaloid/blue cytoplasm and one showed focal signet ring cells. Yolk sac tumor-like differentiation with Schiller-Duval-like bodies was seen in 6/14 cases, with 2 cases showing exclusively reticular-microcystic yolk sac pattern. Follow-up of a maximum of 26 months (median 10 months) was available for 8/14 patients. Distant metastasis to the lung, liver, mediastinum, bone, and/or retroperitoneum was seen in 4/8 cases. Locoregional failure was seen in 75% of patients, with 6/8 local recurrences and 3 cervical lymph node metastases. At the last follow-up, 5 of 8 (62%) patients had died of their disease 2 to 20 months after diagnosis (median 8.2 months), and 3 were alive with the disease. The original diagnosis was usually high-grade non-intestinal-type adenocarcinoma or high-grade myoepithelial carcinoma. A correct diagnosis of these aggressive tumors could lead to improved targeted therapies with potentially better overall disease-specific survival., (© 2023. The Author(s).)

Dedifferentiation in renal cell carcinoma (RCC), either sarcomatoid or rhabdoid, is an infrequent event that may occur heterogeneously in the setting of any RCC histology and is associated with poor outcomes. Sarcomatoid dedifferentiation is associated with inferior survival with angiogenesis targeted therapy and infrequent responses to cytotoxic chemotherapy. However, immune checkpoint therapy has significantly improved outcomes for patients with sarcomatoid dedifferentiation. Biologically, sarcomatoid dedifferentiation has increased programmed death-ligand 1 (PD-L1) expression and an inflamed tumor microenvironment, in addition to other distinct molecular alterations. Less is known about rhabdoid dedifferentiation from either a clinical, biological, or therapeutic perspective. In this focused review, we will discuss the prognostic implications, outcomes with systemic therapy, and underlying biology in RCC with either sarcomatoid or rhabdoid dedifferentiation present.

Integrase interactor 1 (INI1)-deficient carcinomas, recently described in several sites including the head and neck, are associated with basaloid or rhabdoid histology and aggressive behavior irrespective of origin. INI1-deficient thyroid carcinoma is extremely rare. We present here the phenotype and genotype of an INI1-deficient thyroid carcinoma and report on the INI1 protein expression in various thyroid lesions. Case report with clinicopathologic and molecular characterization and INI1 assessment in 184 thyroid lesions. A 67-year-old woman presented with globus sensation due to a large thyroid mass with extrathyroid extension, focal necrosis and cervical and mediastinal nodal involvement. Histologically, tumor cells had a solid, alveolar and pseudopapillary architecture in a myxoid stroma, exhibited monomorphic epithelioid and focal rhabdoid/plasmacytoid morphology and lacked glandular, squamous or follicular cell differentiation. Tumor cells were positive for AE1/AE3 and CK18 but negative for TTF1, thyroglobulin and PAX8. INI1 nuclear expression was absent. A frameshift SMARCB1/INI1 mutation was detected. In addition, TET2 and Notch1 mutations were present but alterations of BRAF, RET, PAX8/PPAR8 or RAS were not identified. Patient death occurred 14 months after diagnosis from post-therapeutic complications. None of the 184 benign and malignant thyroid lesions tested, including 12 poorly and undifferentiated thyroid carcinomas, were INI1-deficient. INI1-deficient thyroid carcinoma shares the phenotype, genotype and biology of other INI1-deficient tumors. Epithelioid and plasmacytoid/rhabdoid changes are most frequent whereas basaloid morphology is not reported, in contrast with sinonasal tumors. Poorly differentiated and undifferentiated thyroid tumors with epithelioid or rhabdoid morphology should be tested for INI1 protein expression to better characterize these aggressive neoplasms and identify patients eligible for targeted therapy. [ABSTRACT FROM AUTHOR]

Introduction: Atypical teratoid rhabdoid tumors (ATRT), an uncommon malignant intracranial tumor with aggressive behavior are mostly seen in posterior fossa in young pediatric age-group. Case Presentation: We present an infrequent location of this tumor in the pineal region in a 5-month-old infant. Also, the lesion was non-enhancing which was highly atypical of an ATRT. It was near-totally excised with the child placed in sitting position. However, within a short interval, a tumor recurrence was noted. Conclusion: The case possibly represents an extended spectrum of congenital childhood brain tumors. Importantly, it highlights an atypical imaging of ATRT in very young children. [ABSTRACT FROM AUTHOR]

Undifferentiated embryonal sarcoma of the liver (UESL) is a rare aggressive neoplasm that occurs predominantly in children. Like mesenchymal hamartoma of the liver (MHL), UESL harbors recurrent rearrangements involving 19q13.3 and 19q13.4, a region of the genome that contains a primate-specific cluster of micro-RNAs. Here, we present a case of a high-grade neoplasm that arose in the left hepatic lobe of a 5-year-old male and gave rise to widespread lymph node, visceral, and soft tissue metastases. The tumor was composed of sheets, tubules, and papillae of epithelioid cells with rhabdoid morphology. INI1 and BRG1 expression were retained. Tumor cells diffusely expressed epithelial markers, including multiple keratins. While the morphologic and immunophenotypic features were suggestive of poorly differentiated carcinoma with rhabdoid features, the tumor was found to harbor the t(11;19)(q13;q13.3) translocation characteristic of UESL, as well as a TP53 mutation. Given the clinical presentation, imaging, clinical course, the tumor was classified as UESL with unusual, carcinoma-like histopathologic features. In the context of an unclassified high-grade hepatic tumor in a young child, molecular or cytogenetic testing for chromosome 19q13 alterations should be considered. [ABSTRACT FROM AUTHOR]

The rhabdoid tumor (RT) predisposition syndromes 1 and 2 (RTPS1 and 2) are rare genetic conditions rendering young children vulnerable to an increased risk of RT, malignant neoplasms affecting the kidney, miscellaneous soft-part tissues, the liver and the central nervous system (Atypical Teratoid Rhabdoid Tumors, ATRT). Both, RTPS1&2 are due to pathogenic variants (PV) in genes encoding constituents of the BAF chromatin remodeling complex, i.e. SMARCB1 (RTPS1) and SMARCA4 (RTPS2). In contrast to other genetic disorders related to PVs in SMARCB1 and SMARCA4 such as Coffin-Siris Syndrome, RTPS1&2 are characterized by a predominance of truncating PVs, terminating transcription thus explaining a specific cancer risk. The penetrance of RTPS1 early in life is high and associated with a poor survival. However, few unaffected carriers may be encountered. Beyond RT, the tumor spectrum may be larger than initially suspected, and cancer surveillance offered to unaffected carriers (siblings or parents) and long-term survivors of RT is still a matter of discussion. RTPS2 exposes female carriers to an ill-defined risk of small cell carcinoma of the ovaries, hypercalcemic type (SCCOHT), which may appear in prepubertal females. RT surveillance protocols for these rare families have not been established. To address unresolved issues in the care of individuals with RTPS and to propose appropriate surveillance guidelines in childhood, the SIOPe Host Genome working group invited pediatric oncologists and geneticists to contribute to an expert meeting. The current manuscript summarizes conclusions of the panel discussion, including consented statements as well as non-evidence-based proposals for validation in the future. [ABSTRACT FROM AUTHOR]

Objectives: The SWI/SNF complex core subunit SMARCB1 is inactivated in a variety of neoplasms that share characteristic "rhabdoid" cytomorphology. The aim of this study was to evaluate SMARCB1-deficient soft tissue neoplasms on cytology to identify diagnostic clues.Methods: Eleven SMARCB1-deficient tumors, including six epithelioid sarcomas, three malignant rhabdoid tumors, one epithelioid malignant peripheral nerve sheath tumor (MPNST), and one poorly differentiated chordoma with fine-needle aspiration (FNA), serous effusion, or touch prep (TP) from two institutions, were included. Targeted next-generation sequencing (NGS) was performed in two cases.Results: Evaluation of FNA (n = 4), effusion (n = 4), and TP (n = 3) in nine adult and two pediatric patients demonstrated cellular samples (n = 11), epithelioid cells with rhabdoid morphology (n = 9), eccentrically located nuclei with prominent nucleoli (n = 7), and cytoplasmic bodies (n = 4); two patients were diagnosed on FNA with cell block. Immunohistochemistry (IHC) demonstrated SMARCB1 loss in all cases and keratin and/or EMA expression in all but the epithelioid MPNST; NGS identified SMARCB1 inactivation in both cases.Conclusions: SMARCB1-deficient soft tissue neoplasms comprise a variety of tumors with epithelioid morphology and frequent expression of keratin and/or EMA. Recognition of characteristic rhabdoid morphology on cytology can prompt IHC and/or NGS testing for SMARCB1 deficiency and help establish the diagnosis. [ABSTRACT FROM AUTHOR]

Background: Undifferentiated carcinoma of the biliary tract are highly aggressive malignancies. In other organs, a subgroup of undifferentiated carcinoma related to SWI/SNF complex–deficiency have been described. Case presentation: A 30-year-old woman presented with rising inflammatory markers (C-reactive protein (CRP)). Ultrasound examination revealed a large tumor of the liver. A computed tomography scan was performed and was primarily interpreted as a tumor-forming liver abscess, possibly caused by gallbladder perforation. Subsequent liver segment resection was performed. Microscopic examination showed an undifferentiated carcinoma with rhabdoid morphology and prominent inflammatory infiltrate in the gallbladder base. With SWI/SNF immunohistochemistry, intact expression of SMARCB1, SMARCA4, ARID1A, but loss of SMARCA2 and PBRM1 was detected. Next-generation-sequencing detected KRAS, PBRM1 and ARID1B mutations, a deleterious splice-site mutation in the POLE-gene and a mutation in the TP53-gene. Conclusions: We were able to demonstrate loss of SMARCA2 expression and mutations characteristic of an SWI/SNF-deficient carcinoma in a tumor derived from the gallbladder. This is the first reported case of an undifferentiated carcinoma with rhabdoid features in the gallbladder carrying a POLE mutation and SWI/SNF-deficiency of PBRM1 and SMARCA2. [ABSTRACT FROM AUTHOR]

Background: Renal Cell Carcinoma (RCC) metastasizes in approximately 20-30% cases. The most common sites for metastases are the lungs, bones, liver, and brain. Metastases of RCC in the gastrointestinal tract (GIT) are very rare. Metastatic RCC has a poor prognosis. We herein present a case series of three patients with metastatic disease in the colon, duodenum, and pancreas following complete resection of RCC.Methods: Hematoxylin and Eosin and immunohistochemical slides of 3 cases of RCC metastatic to GIT were reviewed. These cases were diagnosed between 2002 and 2019 at French Medical Institute for Mothers and Children (FMIC), Kabul, Afghanistan, and Aga Khan University Hospital (AKUH), Karachi, Pakistan. We also present a detailed review of published literature.Results: We reviewed cases of three patients, two females and one male, with a mean age of 57.3 years (range 40-67 years) who underwent nephrectomy for RCC. They developed metastases in the colon, pancreas, and duodenum, respectively 12-168 months (median time 156 months) following primary tumor resection. The patient with metastatic RCC in colon presented with abdominal pain and constipation. An ulcerated mass was found on colonoscopy 30 cm from the anal verge. Diagnosis of RCC with rhabdoid features was confirmed in both primary and metastatic tumors. The second patient developed a metastatic nodule in the head of pancreatic while the third patient developed metastatic nodules in the duodenum and pancreas which were detected by Computed Tomography (CT) scanning. Histopathological examination confirmed the presence of clear cell RCC in the metastatic nodules in both cases.Conclusion: Metastatic RCC should be considered in the differential diagnosis of mass in the gastrointestinal (including pancreaticobiliary) tract especially in presence of a past history of RCC. These patients should be screened thoroughly by physical examination and appropriate imaging studies. [ABSTRACT FROM AUTHOR]

Malignant rhabdoid tumor (MRT) is one of very aggressive neoplasm commonly seen in kidney. An 8 months old boy presented with fever, abdominal distension, multiple vomiting and reduced oral intake. CT Angiography revealed a hyper dense mass involving multiple segments of the liver and associated rupture. He had near normal Sr. AFP (Alpha-Feto protein) levels. An emergent laparotomy revealed a tumour arising from the left lobe of liver which had ruptured already and the surface was bleeding. There was a large haemoperitoneum. A left hemi-hepatectomy was done. Post operative course was turbulent. He never recovered enough to be given chemotherapy. Prognosis was explained, the parents took the child home against medical advice. He died at home a few weeks later. Histopathological examination (HPE) revealed to be malignant rhabdoid tumour of the liver.

The SMARCB1/INI1 gene was first discovered in the mid-1990s, and since then it has been revealed that loss of function mutations in this gene result in aggressive rhabdoid tumors. Recently, the term “rhabdoid tumor” has become synonymous with decreased SMARCB1/INI1 expression. When genetic aberrations in the SMARCB1/INI1 gene occur, the result can cause complete loss of expression, decreased expression, and mosaic expression. Although SMARCB1/INI1-deficient tumors are predominantly sarcomas, this is a diverse group of tumors with mixed phenotypes, which can often make the diagnosis challenging. Prognosis for these aggressive tumors is often poor. Moreover, refractory and relapsing progressive disease is common. As a result, accurate and timely diagnosis is imperative. Despite the SMARCB1/INI1 gene itself and its implications in tumorigenesis being discovered over two decades ago, there is a paucity of rhabdoid tumor cases reported in the literature that detail SMARCB1/INI1 expression. Much work remains if we hope to provide additional therapeutic strategies for patients with aggressive SMARCB1/INI1-deficient tumors.

The SMARCB1/INI1 gene was first discovered in the mid-1990’s, and since then it has been revealed that loss of function mutations in this gene result in aggressive rhabdoid tumors. Recently, the term “rhabdoid tumor” has become synonymous with decreased SMARCB1/INI1 expression. When genetic aberrations in the SMARCB1/INI1 gene occur, the result can cause reduced, complete loss, and mosaic expression. Although SMARCB1/INI1-deficient tumors are predominantly sarcomas, this is a diverse group of tumors with mixed phenotypes, which can often make the diagnosis challenging. Prognosis for these aggressive tumors is often poor. Moreover, refractory and relapsing progressive disease is common. As a result, accurate and timely diagnosis is imperative. Despite the SMARCB1/INI1 gene itself and its implications in tumorigenesis being discovered over two decades ago, there is a paucity of rhabdoid tumor cases reported in the literature that detail SMARCB1/INI1 expression. Much work remains if we hope to provide additional therapeutic strategies for patients with aggressive SMARCB1/INI1-deficient tumors.

Angiomatoid fibrous histiocytoma (AFH) is an uncommon soft-tissue neoplasm that arises mostly in the extremities of young people and generally carries a good prognosis. Intracranial location is unusual and frequently associated with myxoid change. EWSR1 gene fusions with members of the CREB family (CREB1, ATF1, and CREM) are well-established events in AFH. These fusions have also been described in other neoplasms including intracranial myxoid mesenchymal tumor, and it is still uncertain whether the latter is a distinct entity or if it represents a myxoid variant of AFH. Here, we describe a rare falcine AFH presenting in a 50-year-old woman. The most striking feature of this tumor was its diffuse rhabdoid morphology with focal high mitotic activity, raising the consideration of rhabdoid meningioma (WHO grade III). The tumor cells were moderately positive for EMA and negative for progesterone receptor and SSTR2 prompting additional studies. Desmin was strongly positive and CD99 showed membranous immunoreactivity. BAP1, INI-1, and BRG1 expressions were retained. Next-generation sequencing analysis demonstrated an EWSR1–ATF1 gene fusion, supporting the diagnosis of an unusual rhabdoid variant of AFH. After gross total resection of this tumor, the patient remains free of disease 5 months after the surgery without additional treatment. [ABSTRACT FROM AUTHOR]

Atypical teratoid/rhabdoid tumors (ATRTs) are very aggressive childhood malignancies of the central nervous system. The underlying genetic cause are inactivating bi-allelic mutations in SMARCB1 or (rarely) in SMARCA4. ATRT-SMARCA4 have been associated with a higher frequency of germline mutations, younger age, and an inferior prognosis in comparison to SMARCB1 mutated cases. Based on their DNA methylation profiles and transcriptomics, SMARCB1 mutated ATRTs have been divided into three distinct molecular subgroups: ATRT-TYR, ATRT-SHH, and ATRT-MYC. These subgroups differ in terms of age at diagnosis, tumor location, type of SMARCB1 alterations, and overall survival. ATRT-SMARCA4 are, however, less well understood, and it remains unknown, whether they belong to one of the described ATRT subgroups. Here, we examined 14 ATRT-SMARCA4 by global DNA methylation analyses. We show that they form a separate group segregating from SMARCB1 mutated ATRTs and from other SMARCA4-deficient tumors like small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) or SMARCA4 mutated extra-cranial malignant rhabdoid tumors. In contrast, medulloblastoma (MB) samples with heterozygous SMARCA4 mutations do not group separately, but with established MB subgroups. RNA sequencing of ATRT-SMARCA4 confirmed the clustering results based on DNA methylation profiling and displayed an absence of typical signature genes upregulated in SMARCB1 deleted ATRT. In summary, our results suggest that, in line with previous clinical observations, ATRT-SMARCA4 should be regarded as a distinct molecular subgroup. [ABSTRACT FROM AUTHOR]

Abstract The case of a heavy ex‐smoking man in his early 70s who presented with haemoptysis and died following rapid progression is presented. The tumour excised by surgery was mostly composed of monotonous large rhabdoid cells showing prominent nucleoli and eosinophilic cytoplasm. On immunohistochemistry with SMARCA4 (BRG‐1), the tumour cells showed significant loss of expression. The tumour was diagnosed as a SMARCA4‐deficient thoracic sarcoma. This is a disease that progresses rapidly and has a poor prognosis. However, the search for specific treatments using synthetic lethality is underway. Clinical and pathological characteristics can be identified with examination of more cases, and when the tumour is suspected, it is necessary to actively perform immunohistochemical examination.

Renal cell carcinoma with rhabdoid features is a rare histopathologic variant recently documented. It is a very aggressive tumor and associated with a higher mortality rate and poor prognosis. A 22 years old female patient presents with a rare case of clear cell renal cell carcinoma with rhabdoid features successfully managed with right radical nephrectomy and paracaval lymph node excision. The patient was alive, healthy and three years of flow up for the patient was free from metastasis. Despite rhabdoid features are lethal tumors and are associated with higher grades, radical nephrectomy with lymph node dissection increases survival rate.

The presence of sarcomatoid or rhabdoid features (which are associated with advanced disease and poor prognosis) is rarely observed in the subtypes of renal cell carcinoma (RCC). The SWI/SNF chromatin-remodeling complex, which is composed of evolutionarily conserved core subunits including SMARCB1/INI1 (SMARCB1), SMARCA4/BRG1 (SMARCA4), SMARCC1/BAF155 (SMARCC1), and SMARCC2/BAF170 (SMARCC2), can be regarded as the prototype of an epigenetic regulator of gene expression that is involved in tumor suppression. We analyzed the histological, immunohistochemical, and clinicopathological status in 72 cases of RCC with sarcomatoid or rhabdoid features, focusing on the expression status of the subunits of SWI/SNF chromatin-remodeling complex proteins. Cases with lost or reduced expression were defined as showing aberrant expression. The frequency of aberrant SMARCA4 immunoexpression of a sarcomatoid or rhabdoid component in clear cell RCC (ccRCC) (47/50, 94%) was significantly higher than that in non-ccRCC (4/9, 44%) (p < 0.001). In ccRCC without sarcomatoid or rhabdoid features, aberrant SMARCA4 immunoexpression was observed in 33 of 48 (67%) cases. Immunoreactivities for SMARCB1, SMARCA2, and SMARCC2 were retained in almost all subtypes of RCC. The patients with aberrant SMARCA4 expression in RCC with sarcomatoid or rhabdoid features achieved shorter progression-free survival compared with the patients with retained SMARCA4 expression (all subtypes of RCC, p = 0.0212; ccRCC, p = 0.0265). These results suggest that in ccRCC, aberrant SMARCA4 expression is one of the adverse prognostic factors or a high-grade malignant transforming factor. The evaluation of SMARCA4 immunoexpression may be a useful diagnostic tool to help distinguish ccRCC from non-ccRCC. [ABSTRACT FROM AUTHOR]

The case of a heavy ex‐smoking man in his early 70s who presented with haemoptysis and died following rapid progression is presented. The tumour excised by surgery was mostly composed of monotonous large rhabdoid cells showing prominent nucleoli and eosinophilic cytoplasm. On immunohistochemistry with SMARCA4 (BRG‐1), the tumour cells showed significant loss of expression. The tumour was diagnosed as a SMARCA4‐deficient thoracic sarcoma. This is a disease that progresses rapidly and has a poor prognosis. However, the search for specific treatments using synthetic lethality is underway. Clinical and pathological characteristics can be identified with examination of more cases, and when the tumour is suspected, it is necessary to actively perform immunohistochemical examination.We present the case of a heavy ex‐smoking man in his early 70s who presented with haemoptysis and died following rapid progression. The excised tumour was diagnosed as a SMARCA4‐deficient thoracic sarcoma. This is a disease that progresses rapidly and has a poor prognosis. [ABSTRACT FROM AUTHOR]

SCCOHT is an aggressive malignancy linked to alterations of SMARCA4. We describe the diagnosis and therapy of a 32 year old who received multi-agent chemotherapy and underwent a second look operation with HIPEC followed by high-dose chemotherapy with stem cell transplant. Supportive care, oncofertility, and genetic counseling are described. [ABSTRACT FROM AUTHOR]

Background: Sarcomatoid differentiation in renal cell carcinoma (RCC) with vena caval tumour thrombus has been shown to be associated with aggressive behaviours and poor prognosis; however, evidence of the impact of rhabdoid differentiation on prognosis is lacking. This study evaluated the impact of sarcomatoid differentiation and rhabdoid differentiation on oncological outcomes for RCC with vena caval tumour thrombus treated surgically.Methods: We retrospectively analysed patients treated surgically for RCC with vena caval tumour thrombus at our institute from Jan 2015 to Nov 2018. Prognostic variables were evaluated for associations with progression-free survival (PFS) and cancer-specific survival (CSS) by Kaplan-Meier survival analysis and log-rank test. Univariate and multivariate analyses were performed to determine independent prognostic variables.Results: We identified 125 patients with RCC and vena caval tumour thrombus, including 17 (13.6%) with sarcomatoid differentiation alone, 8 (6.4%) with rhabdoid differentiation alone and 3 (2.4%) with both sarcomatoid and rhabdoid differentiation. Compared to pure RCC, patients with sarcomatoid differentiation but not rhabdoid differentiation have worse PFS (p = 0.018 and p = 0.095, respectively). The univariate and multivariate analyses both showed sarcomatoid differentiation as a significant predictor of PFS. Compared to pure RCC, patients with sarcomatoid differentiation (p = 0.002) and rhabdoid differentiation (p = 0.001) both had significantly worse CSS. The univariate analysis showed sarcomatoid differentiation, rhabdoid differentiation, metastasis and blood transfusion as significant predictors of CSS (All, p < 0.05). In the multivariate analysis, sarcomatoid differentiation (HR 3.90, p = 0.008), rhabdoid differentiation (HR 3.01, p = 0.042), metastasis (HR 3.87, p = 0.004) and blood transfusion (HR 1.34, p = 0.041) all remained independent predictors of CSS.Conclusions: Sarcomatoid differentiation and rhabdoid differentiation are both independent predictors of poor prognosis in RCC with vena caval tumour thrombus treated surgically. [ABSTRACT FROM AUTHOR]

SMARCA4-deficient thoracic sarcoma (SMARCA4-DTS) is a recently described entity with a poor prognosis that is defined by certain genetic alterations in the BAF chromatin remodeling complex, specifically SMARCA4 and SMARCA2. We present a case of a SMARCA4-DTS in a 59 year-old male with a heavy smoking history who was found to have an unexpected right upper lobe lung mass on routine chest radiograph after a visit to his primary care physician. This led to a biopsy with a diagnosis of poorly differentiated carcinoma at an outside institution. The patient was subsequently seen at our facility for surgical intervention. The right upper lobectomy contained a 7.2-cm poorly differentiated malignancy with slightly discohesive cells arranged in sheets and nests, abundant geographic necrosis, and with many areas showing rhabdoid morphology. The tumor was focally reactive for CK7, AE1/3, Cam5.2, and SALL4 and showed scattered reactivity for CD34 and SOX2. There was complete loss of reactivity for both SMARCA4 and SMARCA2. The histology and immunophenotype were all consistent with the diagnosis of a SMARCA4-DTS. Next-generation sequencing showed a frameshift mutation in the SMARCA4 gene and no abnormality with the SMARCA2 gene. Interestingly, this tumor was confined to the pulmonary parenchyma with no invasion of the visceral pleura nor the mediastinum and with no clinically apparent metastases at the time of presentation. This case is presented to add to the cohort of cases described to date and to discuss the immunohistochemical and molecular findings with regard to SMARCA2. [ABSTRACT FROM AUTHOR]

Epithelioid cell features mimicking carcinomas characterize a variety of histogenetically, phenotypically, and molecularly distinct subsets of mesenchymal neoplasms. In a pathogenetic sense, epithelioid soft tissue tumors basically fall into three main genetic categories: (1) switch/sucrose non-fermenting (SWI/SNF) complex-deficient tumors (with epithelioid sarcoma as their prototype); (2) epithelioid neoplasms driven by specific rare gene fusions (such as sclerosing epithelioid fibrosarcoma with EWSR1 fusions and GLI1-related malignant epithelioid soft tissue neoplasms); and (3) a heterogeneous group encompassing epithelioid variants of diverse other entities. Notably, lesions in the first and third groups may display variable, occasionally prominent, rhabdoid cell morphology, thus further complicating their differential diagnosis. This review summarizes the main clinicopathological, phenotypic, and genotypic features of these diseases and discusses their pertinent differential diagnostic considerations. [ABSTRACT FROM AUTHOR]

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare CNS cancer that typically occurs in children younger than 3 years of age. Histologically, AT/RTs are embryonal tumors that contain a rhabdoid component as well as areas with primitive neuroectodermal, mesenchymal, and epithelial features. Compared to other CNS tumors of childhood, AT/RTs are characterized by their rapid growth, short symptomatic prodrome, and large size upon presentation, often leading to brain compression and intracranial hypertension requiring urgent intervention. For decades, the mainstay of care has been a combination of maximal safe surgical resection followed by adjuvant chemotherapy and radiotherapy. Despite advances in each of these modalities, the relative paucity of data on these tumors, their inherently aggressive course, and a lack of molecular data have limited advances in treatment over the past 3 decades. Recent large-scale, multicenter interdisciplinary studies, however, have significantly advanced our understanding of the molecular pathogenesis of these tumors. Multiple clinical trials testing molecularly targeted therapies are underway, offering hope for patients with AT/RT and their families. [ABSTRACT FROM AUTHOR]

Rhabdoid tumor commonly occurs in the kidney and has an aggressive clinical course with high mortality. Extrarenal rhabdoid tumours can involve a number of organs, but poorly differentiated follicular carcinoma with rhabdoid phenotype is an extremely rare clinical entity. The 18F-FDG PET feature of this thyroid malignancy is not available in the literature to the best of our knowledge. But, this feature has significant clinical relevance in management of such patients. We present such a case. [ABSTRACT FROM AUTHOR]