Carcinogenicity of butyraldehyde in rats by a two-year inhalation study.

We conducted a two-year inhalation study of butyraldehyde using F344/DuCrlCrlj rats. The rats were exposed to 0, 300, 1,000 and 3,000 ppm (v/v) for 6 hr/day, 5 days/ week for 104 weeks using whole-body inhalation chambers. The incidence of squamous cell carcinoma of the nasal cavity was increased in the 3,000 ppm groups of both male and female rats, with Fisher's exact test and the Peto test indicating that the incidence was significant. In addition to squamous cell carcinoma in the nasal cavity, in the 3,000 ppm groups one male had an adenosquamous carcinoma, one male had a carcinosarcoma, one male had a sarcoma NOS (Not Otherwise Specified), and one female had a squamous cell papilloma in the nasal cavity. The combined incidence of squamous cell carcinoma, adenosquamous carcinoma and carcinosarcoma was significantly increased in male rats and the combined incidence of squamous cell papilloma and carcinoma was significantly increased in female. Based on these results, we conclude that there is clear evidence of butyraldehyde carcinogenicity in male and female rats.

Spotlight on Carcinosarcoma of the Ovary: A Scoping Review.

Ovarian carcinosarcoma, also referred as malignant mixed Mullerian tumour, is an uncommon, highly aggressive and malignant neoplasm which makes up 1 to 4% of all ovarian tumours. It is biphasic involving both malignant sarcomatous (mesenchymal) and carcinomatous (epithelial) cells. There are various subtypes such as serous and endometrioid. However, the mesenchymal part is sarcomatous. About 90% of cases of ovarian carcinosarcoma spread outside the ovary. The two most accepted theories of origin for carcinosarcoma of the ovary are the collision and conversion theories. A third theory is the combination theory. Prognosis remains poor even when still localised in the ovary. In the last few years, there has been no change in the survival rate. The median survival rate is lower than 2 years. Clinical features mainly include lower abdominal pain and a palpable abdominal mass. Ovarian carcinosarcoma remains poorly understood and understudied. Being a rare tumour, elaborate therapeutic consensus is not available for ovarian carcinosarcoma. The main treatment involves cytoreductive surgery and then chemotherapy. The type of chemotherapy, role of radiotherapy and novel therapies need to be further studied. The main objective of this article is to review the current literature on carcinosarcoma of the ovary.

Teratoma combined with struma ovarii and sarcomatoid carcinoma: a case report and review of the literature.

This is a rare case of struma ovarii combined with sarcomatoid carcinoma. Because struma ovarii and ovarian sarcomatoid carcinoma have an extremely low incidence, this may be the first case of a combined occurrence of both. Therefore, this report describes its clinical manifestations, diagnosis, and treatment, analyzes the pathogenesis, and summarizes the previous literature in the hope that it can be helpful to other tumor-related medical personnel and provide material support for the formation of guidelines for this disease.

Ovarian Carcinoma: A Single-Centre Eight-Year Case-Series Study with Survival Analysis.

Introduction: This research describes an eight-year case-series of ovarian carcinoma by surgical (pTNM) staging and surgical procedure, explores the characteristics of ovarian surface epithelial cell (OSEC) tumours by histopathological type in a single centre of reference. Material and Methods: survival analysis with overall survivor probabilities for n=263 patients for 12 months and 60-month tumour free survival status (TFS). Results by staging (pTNM stage classification), histotype and for poor surgical candidate (PSC) status are shown. Histotype high grade serous carcinoma (HGSC) was the most frequently diagnosed type (63%). Results: 12-month survivor probabilities according to histotype, rank as follows: clear cell carcinoma (CCC) - 14%; rare carcinoma (RC) - 15%; carcinosarcoma (CS) - 29%; HGSC - 46%; low grade serous carcinoma (LGSC) - 74%; endometrioid carcinoma (EC) - 79%; mucinous carcinoma (MC) - 80% and borderline tumours (BLT) - 94%. At 60 months results are: RC and MC - 0%; CCC - 14%; HGSC - 16%; CS - 29%; LGSC - 62%; EC - 66%; and BLT - 94%. Overall median survival time is 26 months (CI95% 15 to 37); and 20 months when BLT excluded (CI95% CI 15 to 25). Conclusions: These results may guide further research for the OSEC pathology and its histotypes.

Single-cell transcriptomics reveals tumor landscape in ovarian carcinosarcoma. / 单细胞转录组学揭示卵巢癌肉瘤的肿瘤特征.

OBJECTIVES: The present study used single-cell RNA sequencing (scRNA-seq) to characterize the cellular composition of ovarian carcinosarcoma (OCS) and identify its molecular characteristics. METHODS: scRNA-seq was performed in resected primary OCS for an in-depth analysis of tumor cells and the tumor microenvironment. Immunohistochemistry staining was used for validation. The scRNA-seq data of OCS were compared with those of high-grade serous ovarian carcinoma (HGSOC) tumors and other OCS tumors. RESULTS: Both malignant epithelial and malignant mesenchymal cells were observed in the OCS patient of this study. We identified four epithelial cell subclusters with different biological roles. Among them, epithelial subcluster 4 presented high levels of breast cancer type 1 susceptibility protein homolog (BRCA1) and DNA topoisomerase 2-α (TOP2A) expression and was related to drug resistance and cell cycle. We analyzed the interaction between epithelial and mesenchymal cells and found that fibroblast growth factor (FGF) and pleiotrophin (PTN) signalings were the main pathways contributing to communication between these cells. Moreover, we compared the malignant epithelial and mesenchymal cells of this OCS tumor with our previous published HGSOC scRNA-seq data and OCS data. All the epithelial subclusters in the OCS tumor could be found in the HGSOC samples. Notably, the mesenchymal subcluster C14 exhibited specific expression patterns in the OCS tumor, characterized by elevated expression of cytochrome P450 family 24 subfamily A member 1 (CYP24A1), collagen type XXIII α1 chain (COL23A1), cholecystokinin (CCK), bone morphogenetic protein 7 (BMP7), PTN, Wnt inhibitory factor 1 (WIF1), and insulin-like growth factor 2 (IGF2). Moreover, this subcluster showed distinct characteristics when compared with both another previously published OCS tumor and normal ovarian tissue. CONCLUSIONS: This study provides the single-cell transcriptomics signature of human OCS, which constitutes a new resource for elucidating OCS diversity.

Uterine serous carcinoma and uterine carcinosarcoma: molecular features, clinical advances, and emerging therapies.

Endometrial cancer, including high-grade subtypes, has a rising incidence and mortality. Uterine serous carcinoma (USC) and uterine carcinosarcoma (UCS) make up a small but increasing proportion of endometrial cancer cases and account for a significant portion of endometrial cancer mortality. Despite being molecularly and clinically distinct, both USC and UCS have a poor prognosis. Thus far, there have been few therapeutic strategies directed at these endometrial cancer subtypes. This review summarizes the genomic and molecular features of USC and UCS, clinical advances in the treatment of primary advanced and recurrent endometrial cancer, and novel molecularly-driven treatment strategies.

Clinical evolution of bladder carcinosarcoma: A case report and literature review.

RATIONALE: Bladder carcinosarcoma (BC) is a malignant tumor composed of a mixture of malignant epithelial and stromal components. Carcinosarcoma mostly occurs in the upper respiratory tract and upper gastrointestinal tract and is less common in the urinary system. The incidence of malignant tumors of the urinary system is <3%. It rarely occurs in the bladder and accounts for approximately 0.31% of all malignant bladder tumors. A literature review and this report will help to further improve our understanding, diagnosis, and treatment of bladder carcinosarcoma (BC). PATIENT CONCERN: We describe the case of an 80-year-old female patient who was admitted to the hospital with a history of intermittent hematuria for 3 years. Furthermore, total cystectomy was refused when a BC was diagnosed. Palliative resection surgery was necessary because of the recurrent hematuria and abdominal pain. DIAGNOSES: Pathologically confirmed BC after surgery. INTERVENTIONS: The patient's first transurethral resection of bladder tumor (TURBT) was diagnosed as BC. However, the patient refused a total cystectomy. Two months after intravesical treatment with epirubicin, bladder tumor recurrence was observed during follow-up cystoscopy. The patient underwent a second TURBT for hemostatic treatment due to persistent hematuria. Due to hematuria and abdominal pain, a third TURBT was performed to reduce tumor size and stop bleeding. Finally, tumor recurrence resulted in bilateral hydronephrosis, and the patient underwent bilateral renal catheter drainage guided by B-ultrasound. OUTCOMES: Bladder carcinosarcoma caused uremia, electrolyte imbalance, and sepsis. Approximately 19 months after the discovery of the tumor, the patient died. LESSONS: Radical bladder resection is recommended once a BC is diagnosed. By reporting the cases and reviewing the literature in the database, we will summarize the epidemiology, origin, etiology, clinical features, existing treatments, and prognostic factors of BC, and propose new prospects for BC therapy.

Surgically resected sarcomatoid carcinoma of the lung: a nationwide retrospective study in 2010.

BACKGROUND: Sarcomatoid carcinoma of the lung is a rare histological type of non-small cell lung cancer with a poor prognosis. We aimed to investigate the clinicopathological characteristics and prognostic factors of surgically resected sarcomatoid carcinoma of the lung. METHODS: We retrospectively reviewed 14999 patients who underwent surgical resection for non-small cell lung cancer accumulated by the Japanese Joint Committee of Lung Cancer Registry in 2010. Clinicopathological characteristics and survival were compared between the sarcomatoid carcinoma and other non-small cell cancer groups. The prognostic factors in the sarcomatoid carcinoma group were identified using a multivariate Cox proportional hazard model. RESULTS: Patients with sarcomatoid carcinoma comprised 1.4% of all patients. The sarcomatoid carcinoma group demonstrated a more aggressive pathology with presentation at more advanced stages, requiring more frequent extensive surgical resections. The sarcomatoid carcinoma group had remarkably poorer overall and recurrence-free survival than the other non-small cell lung cancer group. Adjuvant chemotherapy was associated with improved survival for pathological stage II-III sarcomatoid carcinoma cases rather than for pathological stage I disease. In the multivariate analysis, larger tumor size, lymphatic permeation, and no adjuvant chemotherapy were associated with the sarcomatoid carcinoma group's overall and recurrence-free survival. CONCLUSIONS: Surgically resected sarcomatoid carcinoma of the lung has a higher aggressive and metastatic potential and a worse prognosis than other non-small cell lung cancers. Adjuvant chemotherapy, which was associated with enhanced survival in patients with pathological stage II-III of the disease, could be considered for treating patients with pathological stage II-III sarcomatoid carcinoma of the lung.

Pulmonary sarcomatoid carcinoma: A rare case report, diagnostic dilemma and review of literature.

RATIONALE: Pulmonary sarcomatoid carcinoma (PSC), a rare tumor, comprises 0.1% to 0.4% of all malignant lung tumors. Given the rarity of PSC, its clinical course, therapeutic guidelines, and patient outcomes remain largely unknown. Therefore, it is imperative to alert clinicians to this extremely rare and instructive early-onset cancer. PATIENT CONCERNS: This report describes a 28-year-old woman with PSC, who was initially misdiagnosed with Whipple's disease. A conclusive diagnosis of PSC was made following careful clinical examination, imaging, and histopathological evaluation of the patient's biopsy sample. Radiological imaging revealed multiple nodules and mass formations in the left upper lobe of the patient's lung, with the largest measuring of 5.4 × 3.2 cm. DIAGNOSIS: Histopathological examination indicated the presence of a malignant neoplasm associated with necrosis suggestive of sarcoma, which was pathologically staged as cT4N1M1. INTERVENTIONS AND OUTCOMES: A regimen of doxorubicin and ifosfamide was administered therapeutically, resulting in a stable disease state. LESSONS: The rarity and tumor origin challenge the diagnosis, which emphasizes the imperative role of histological examination, immunohistochemistry, and flow cytometry in achieving an accurate diagnosis. This report summarizes the existing publications to provide a comprehensive overview of PSC, including its clinical manifestations, radiographic imaging, pathologic features, diagnostic challenges, treatment strategies, and prognosis, and aims to improve the understanding of PSC.

Unexpected rare uterine carcinosarcoma with neuroendocrine differentiation: Reflections on clinical diagnosis and treatment of a case report.

RATIONALE: Uterine carcinosarcoma (UCS) is a rare and highly invasive malignant tumor.It exhibits an ectopic growth pattern of the uterus,and its histological features are biphasic differentiation of malignant epithelial components (cancer) and malignant mesenchymal components (sarcoma). The pathological pattern of high-component neuroendocrine differentiation is extremely rare. Due to the inherent heterogeneity of tumors, it increases the difficulty of accurate identification and diagnosis. The author introduces a rare case of primary endometrial carcinosarcoma (heterologous) with small cell neuroendocrine carcinoma (SCNEC) components. There is limited literature on this rare pathological differentiation pattern and a lack of guidelines for the best treatment methods, which prompts reflection on the diagnosis, optimal treatment strategies, and how preoperative diagnosis can affect patient prognosis for endometrial carcinosarcoma with neuroendocrine differentiation. PATIENT CONCERNS: The patient is an elderly woman who presents with abnormal vaginal bleeding after menopause. Transvaginal ultrasound examination shows that the uterus is slightly enlarged, and there is a lack of homogeneous echogenicity in the uterine cavity. Subsequently, a hysteroscopic curettage was performed, and a space-occupying lesion was observed on the anterior wall of the uterine cavity. DIAGNOSES: Preoperative endometrial biopsy revealed SCNEC of the endometrium. The patient underwent radical hysterectomy, and the postoperative pathological results showed that UCS (heterologous) was accompanied by SCNEC components (about 80%). INTERVENTION: The patient received radical hysterectomy, followed by adjuvant chemotherapy. OUTCOME: After 7 months of follow-up, no tumor recurrence or metastasis was found at the time of writing this article. LESSONS: The histological type of UCS (heterologous) with cell neuroendocrine carcinoma components is rare and highly invasive, with a high misdiagnosis rate in preoperative biopsy. There are currently no effective treatment guidelines for this type of case. The unusual appearance of SCNEC components in this case poses a challenge for both pathologists and surgeon. The rare differentiation pattern of this case exposes the complexity of its management and the necessity of prospective trials to determine the optimal treatment plan.

Case report: Characterization of the immunologic and molecular landscape in a unique presentation of invasive lobular carcinoma with concurrent uterine carcinosarcoma treated with immunotherapy.

Invasive lobular breast cancer (ILC) is characterized by a relatively high risk for late recurrence and a unique metastatic pattern with an increased risk for metastasis to gynecologic organs and peritoneum. We present a unique case of recurrent ILC with metastasis to the abdominal peritoneum as well as the uterine myometrium and cervix. Treatment was complicated by the discovery of concomitant uterine carcinosarcoma. This patient was effectively treated with a combination of hormonal therapy for her metastatic ILC and a combination of chemotherapy and immunotherapy for uterine carcinosarcoma. Molecular evaluation revealed a characteristic CDH1 mutation within the ILC and a PI3KCA mutation within the uterine carcinosarcoma, both of which have been linked to epithelial-to-mesenchymal transitions. Examination of the tumor immune microenvironment revealed proportionally more cytotoxic NK cells. This robust immune infiltration may be an indicator of the response to immunotherapy observed in this tumor or a result of the metastatic breast cancer within the uterus. This report provides a characterization of the molecular and immunologic landscape in this case with metastatic ILC and uterine carcinosarcoma.

Thymic carcinosarcoma with melanocytic differentiation in a dog.

Carcinosarcomas are very rare tumors in dogs. Although carcinosarcomas with melanocytic differentiation arising from organs other than the thymus have been described in humans, this type of tumor has not been reported in dogs in any part of the body. We observed such a tumor in the cranial mediastinum of an 11-year-old spayed female dachshund. The dog was admitted to the clinic because of coughing, sporadic regurgitation, and dyspnea. Thoracic ultrasonography and computed tomography revealed a large mediastinal mass that was surgically removed via sternotomy. The tumor was of thymic origin and demonstrated 3 distinct components: an epithelial component positive for pancytokeratin (AE1/AE3) and high molecular weight cytokeratin (CK5/CK6) with some cystic spaces; a mesenchymal component positive for vimentin; and in association with the epithelial part, a minor melanocytic component positive for Melan A. Histologic metastasis of the epithelial and melanocytic components was present within a tracheobronchial lymph node. The dog died 105 d after surgery, after an episode of acute dyspnea. Key clinical message: To the authors' knowledge, this is the first report of thymic carcinosarcoma with melanocytic differentiation.

Carcinosarcome thymique avec différenciation mélanocytaire chez un chienLes carcinosarcomes sont des tumeurs très rares chez le chien. Bien que des carcinosarcomes avec différenciation mélanocytaire provenant d'organes autres que le thymus aient été décrits chez l'homme, ce type de tumeur n'a été rapporté chez le chien dans aucune partie du corps. Nous avons observé une telle tumeur dans le médiastin cránien d'une femelle teckel stérilisée de 11 ans. Le chien a été admis à la clinique en raison de toux, de régurgitations sporadiques et de dyspnée. L'échographie thoracique et la tomodensitométrie ont révélé une masse médiastinale importante qui a été retirée chirurgicalement par sternotomie. La tumeur était d'origine thymique et présentait 3 composantes distinctes : une composante épithéliale positive pour la pancytokératine (AE1/AE3) et la cytokératine de haut poids moléculaire (CK5/CK6) avec quelques espaces kystiques; un composant mésenchymateux positif à la vimentine; et en association avec la partie épithéliale, un composant mélanocytaire mineur positif pour Melan A. Des métastases histologiques des composants épithéliaux et mélanocytaires étaient présentes dans un ganglion lymphatique trachéobronchique. Le chien est décédé 105 jours après l'intervention chirurgicale, à la suite d'un épisode de dyspnée aiguë.Message clinique clé :À la connaissance des auteurs, il s'agit du premier cas de carcinosarcome thymique avec différenciation mélanocytaire.(Traduit par Dr Serge Messier).

[Gallbladder carcinosarcoma associated with pancreaticobiliary maljunction with biliary dilation:a case report].

A 68-year-old female patient was referred to our hospital with acute cholangitis. Computed tomography revealed common bile duct dilatation, gallbladder fundal tumor, and gallbladder wall thickening attached to the tumor. Cholangiography revealed pancreaticobiliary maljunction with biliary dilation. The patient was diagnosed with pancreaticobiliary maljunction with biliary dilation and gallbladder cancer and underwent liver S4b+5 and bile duct resection and reconstruction. Pathological results revealed that the gallbladder fundal tumor included sarcoma, and the gallbladder wall thickening had adenocarcinoma;thus, the patient was diagnosed with gallbladder carcinosarcoma.

Unveiling the mille-feuille sign: a key to diagnosing ovarian carcinosarcoma in addition to ovarian metastasis from colorectal carcinoma on MRI.

PURPOSE: To clarify the diagnostic utility and formation of the Mille-feuille sign for ovarian carcinosarcoma (OCS) on MRI, and to evaluate the other MRI findings and serum markers compared to ovarian metastases from colorectal carcinoma (OMCRC). METHOD: Three blinded radiologists retrospectively reviewed MR images of 12 patients with OCS, 18 with OMCRC, and 40 with primary ovarian carcinoma (POC) identified by the electronic database of radiology reports. The interobserver agreement was analyzed using Fleiss' kappa test. Their MRI characteristics and tumor markers were compared using Fisher's exact test and Mann-Whitney's U test. Receiver operating characteristic curve analyses were used to determine the cutoff points for the ADC value. This study was approved by the institutional ethics committee. RESULTS: Interobserver agreement analysis was moderate or higher for all MRI characteristics. The frequency of Mille-feuille sign was comparable for both OCS and OMCRC groups, and predominantly higher than that of the POC group (p < 0.001, p < 0.001), respectively. Pathologically, the Mille-feuille sign in OCS reflected alternating layers of tumor cells with stroma and necrosis or intraluminal necrotic debris. Compared to OMCRC, intratumoral hemorrhage (p = 0.02), margin irregularity (p = 0.048), unilateral adnexal mass (p = 0.02), and low ADC values (p < 0.01) were more frequently observed and serum CEA levels was significantly lower (p = 0.007) in the OCS group. Under setting of the cutoff value of ADC at 0.871 × 10-3mm2/s, the discriminative ability for OCS showed 66.7% sensitivity, 94.4% specificity, and 81.0% accuracy, respectively. CONCLUSIONS: The Mille-feuille sign was seen in both OCS and OMCRC. MR findings of intratumoral hemorrhage, margin irregularity, unilateral adnexal mass, low ADC values, and low serum CEA levels can be useful in differentiating OCS from OMCRC.

Paraneoplastic leukocytosis secondary to carcinosarcoma: a report of two cases and literature review.

BACKGROUND: Neutrophilia is an increase in the number of neutrophils over 7.5×103/µL. An increase in leukocytes over 50×103/µL is called a leukemoid reaction; and when it is associated with a solid tumor, it is considered a paraneoplastic syndrome called paraneoplastic leukemoid reaction (PLR). It is a very rare clinical condition and it is very unusual for it to be associated with carcinosarcoma. We present two cases of a leukemoid reaction observed in the Medical Oncology Department of the University Hospital of Salamanca between May and September 2023. The main objectives of our article are to describe the unusual appearance of paraneoplastic leukocytosis at the diagnosis of carcinosarcoma carcinosarcoma, explain in a detailed way its diagnostic procedure and to show the poor prognosis to which it is associated. CASE DESCRIPTION: In our presentation, we describe two similar cases: first of all, a 60-year-old woman without relevant medical history. She was referred by her primary physician to the Department of Internal Medicine in August 2023 with asthenia, lumbar pain, and weight loss of 12 kg of 3 months of evolution. The physical examination revealed a palpable hypogastric mass. An abdominal, pelvic, and thoracic computed tomography (CT) scan revealed a heterogenous solid mass with necrotic areas originating in the uterus. The anatomopathological diagnosis was carcinosarcoma. The patient showed a progressive worsening in her renal function associated with hyperviscosity secondary to hyperleukocytosis caused by 170×103/µL neutrophils. In the second case we describe the diagnosis of a PLR secondary to a kidney carcinosarcoma. When the patient started chemotherapy, he presented 55.08×103/µL leukocytes, 53.16×103/µL neutrophils. Eight days after receiving chemotherapy, the patient was admitted as an emergency with oligoanuria and decreased consciousness. He presented creatinine 6.25 mg/dL, phosphate 12.4 mg/dL, leukocytes 1.05×103/µL, and neutrophils 0.71×103/µL. The clinical diagnosis was acute exacerbation of multifactorial mixed (renal and prerenal) chronic kidney disease associated with tumor lysis syndrome and grade 3 neutropenia. The patient presented a poor evolution, dying after 2 months. CONCLUSIONS: PLR is a severe paraneoplastic syndrome associated with different types of solid tumors. Its appearance at the time of diagnosis of a tumor implies a poor vital prognosis.

Preclinical in vitro and in vivo activity of the RAF/MEK clamp avutometinib in combination with FAK inhibition in uterine carcinosarcomas.

OBJECTIVES: Uterine carcinosarcomas (UCS) are rare, biologically aggressive tumors. Since UCS may harbor mutations in RAS/MAPK pathway genes we evaluated the preclinical in vitro and in vivo efficacy of the RAF/MEK clamp avutometinib in combination with the focal adhesion kinase (FAK) inhibitors defactinib or VS-4718 against multiple primary UCS cell lines and xenografts. METHODS: Whole-exome-sequencing (WES) was used to evaluate the genetic landscape of 5 primary UCS cell lines. The in vitro activity of avutometinib ± FAK inhibitor was evaluated using cell viability and cell cycle assays against primary UCS cell lines. Mechanistic studies were performed using western blot assays while in vivo experiments were completed in UCS tumor bearing mice treated with avutometinib ± FAK inhibitor by oral gavage. RESULTS: WES results demonstrated multiple UCS cell lines harbor genetic alterations including KRAS, PTK2, BRAF, MAP2K, and MAP2K1, potentially sensitizing to FAK and RAF/MEK inhibition. Four out of five of the UCS cell lines demonstrated in vitro sensitivity to FAK and/or RAF/MEK inhibition when used alone or in combination. By western blot assays, exposure of UCS cell lines to the combination of defactinib/avutometinib demonstrated decreased phosphorylated (p)-FAK as well as decreased p-ERK. In vivo, the combination of avutometinib/VS-4718 demonstrated superior tumor growth inhibition and longer survival compared to single agent treatment and controls starting at day 10 (p < 0.002) in UCS xenografts. CONCLUSION: The combination of avutometinib and defactinib demonstrates promising in vitro and in vivo anti-tumor activity against primary UCS cell lines and xenografts.

Salivary gland carcinosarcoma ex pleomorphic adenoma: a case report with molecular characterization.

True malignant mixed tumors, also known as salivary gland carcinosarcoma (SCS), are uncommon yet highly aggressive lesions associated with a poor prognosis. These tumors exhibit a distinctive biphasic structure characterized by both epithelial and mesenchymal components. Recent research has shown that the majority of SCS cases stem from pre-existing pleomorphic adenomas (PAs), suggesting a stepwise developmental pattern. In this report, we present a case of a 73-year-old female with SCS and describe the clinical, radiographic, and pathologic observations. Notably, the SCS was associated with a residual PA. The SCS displayed a CTNNB1::PLAG1 gene rearrangement, providing a molecular basis for its origin from the PA. Further DNA genomic analysis exposed mutations in BAP1, PER1, and LRPB1. Our findings provide support to the theory that SCS emerges from a pre-existing PA while highlighting the multiple genetic changes that could contribute to malignant transformation.

Acinic cell Carcinoma with high-grade Squamoglandular and Chondrosarcomatous Transformation Mimicking 'Carcinosarcoma ex-pleomorphic Adenoma': A Wrinkle in the Proposed Nomenclature Revision for Sarcomatoid Salivary Gland Neoplasms.

While acinic cell carcinoma (AciCC) can undergo high-grade transformation (HGT) to high-grade adenocarcinoma or poorly differentiated carcinoma, other morphologies such as spindle cell/sarcomatoid carcinoma are rare and not well-characterized. We herein report a novel case of AciCC with squamoglandular and chondrosarcomatous HGT mimicking a so-called 'carcinosarcoma ex-pleomorphic adenoma'. The patient is an 81-year-old male with a two-month history of neck swelling and referred otalgia who presented with a left parapharyngeal space mass extending into retropharyngeal space and pterygoid muscles. On resection, the tumor showed considerable morphologic diversity with high-grade serous and mucous acinar components as well as cribriform to solid apocrine-like components with comedonecrosis and squamous differentiation, all of which were embedded in a chondromyxoid background ranging from paucicellular and bland to a high-grade chondrosarcoma/pleomorphic sarcoma-like appearance. Only a minor conventional AciCC component was noted. Immunostains were negative for AR and only focally positive for GCDFP-15 arguing against a true apocrine phenotype, while PLAG1 and HMGA2 were negative arguing against an antecedent pleomorphic adenoma. On the other hand, SOX-10, DOG-1 and PAS after diastase highlighted serous acinar differentiation, and mucicarmine, and NKX3.1 highlighted mucous acinar differentiation. NR4A3 immunohistochemical staining and NR4A3 fluorescence in situ hybridization were positive in the carcinomatous and sarcomatoid components while sequencing analysis of both components revealed identical alterations involving TP53, PIK3CB, ARID1A, and STK11. This unique case warrants caution in designating all salivary sarcomatoid carcinomas with heterologous elements as part of the 'carcinoma ex-pleomorphic adenoma' family.