RESUMO
Carcinosarcoma is an extremely rare variant of squamous cell carcinoma characterized by biphasic histology defined by epithelial and mesenchymal components. Because of the aggressive nature, early risk of metastasis, and high mortality, this tumor is associated with poor prognosis. Surgery is considered as the main modality of treatment, although radiotherapy can be discussed in inoperable cases. The present paper describes a rare case of carcinosarcoma of buccal mucosa.
Assuntos
Carcinoma de Células Escamosas , Carcinossarcoma , Humanos , Mucosa Bucal/patologia , Carcinossarcoma/diagnóstico , Carcinossarcoma/cirurgia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/cirurgiaRESUMO
BACKGROUND: Uterine Carcinosarcomas (UCS) are a rare type of cancer composed of an admixture of high-grade carcinomatous and sarcomatous elements. Clinicopathological prognostic factors in UCS are well established, but studies that approach the impact of biomarkers in this unusual disease are scarce. The study objective was to evaluate the prevalence and prognostic impact of a panel of prominent biomarkers in uterine carcinosarcoma (UCS) using an immunohistochemical characterization with four biomarkers. METHODS AND FINDINGS: The internal database of a single Brazilian institution was carefully explored to select women diagnosed with UCS who were submitted to surgery and postoperative chemotherapy with carboplatin and paclitaxel between January 2012 and December 2017. Tissue microarrays containing UCS samples were evaluated by immunohistochemistry for L1CAM, CDX2, p53 and microsatellite instability markers. A total of 57 cases were included. The mean age was 65.3 years (standard deviation, SD 7.0). L1CAM was negative (score 0, no staining) in 27 (47.4%) patients. Of L1CAM-positive, 10 (17.5%) showed weak (score 1, <10%), 6 (10.5%) showed moderate (score 2, between 10-50%), and 14 (24.6%) showed strong L1CAM staining (score 3, â§50%). dMMR occurred in 3 (5.3%) cases. The p53 was aberrantly expressed in 15 (26.3%) tumors. CDX2 was positive in 3 (5.3%) patients. The three-year progression-free survival (PFS) rate in the general population of the study was 21.2% (95% CI: 11.7-38.1) and the three-year overall survival (OS) rate was 29.4% (95% CI: 18.1-47.6). By multivariate analysis, the presence of metastases and CDX2-positive were significantly associated with poorer PFS (p < 0.001 and p = 0.002, respectively) and OS (p < 0.001 and p = 0.009, respectively). CONCLUSION: The strong influence of CDX2 on prognosis requires further investigation. Biological or molecular variability may have impaired the assessment of the impact of the other markers on survival.
Assuntos
Carcinossarcoma , Molécula L1 de Adesão de Célula Nervosa , Neoplasias Uterinas , Humanos , Feminino , Idoso , Prognóstico , Proteína Supressora de Tumor p53/genética , Estudos Retrospectivos , Neoplasias Uterinas/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Fator de Transcrição CDX2/genéticaRESUMO
PURPOSE: To investigate outcomes of adjuvant treatments for non-endometrioid endometrial carcinomas (NEEC), as previous studies are limited by its rarity and heterogeneity. PATIENTS AND METHODS: Patients with endometrial serous carcinoma (SC), clear cell carcinoma (CCC) and carcinosarcoma were identified between 2004 and 2018 from SEER database. Propensity score matching (PSM) along with inverse probability treatment weighting (IPTW) technique were employed to balance confounding factors. Multivariate, exploratory subgroup and sensitivity analyses were conducted to evaluate the impact of adjuvant treatment on overall survival (OS) and cause-specific survival (CSS). RESULTS: The cohort comprised 5577 serous, 977 clear cell, and 959 carcinosarcomas. Combined chemotherapy and radiotherapy (CRT), chemotherapy alone, and radiotherapy alone were respectively administered in 42.21%, 47.27% and 10.58% of the whole cohort. Prior to adjusting, chemotherapy plus brachytherapy yielded the most beneficial effect among various strategies. After PSM-IPTW adjustment, CRT still demonstrated beneficial effect on OS and CSS. Subgroup analysis indicated CRT improved survival among various TNM stages, particularly with uterine carcinosarcoma. In the sensitivity analyses for serous histology, brachytherapy with or without chemotherapy appeared to benefit stage I-II patients. In stage III-IV SC patients, chemotherapy plus brachytherapy was still associated with improved survival outcomes. When nodal metastases were identified, additional external beam radiotherapy (EBRT) to CT was more utilized with survival improvement. CONCLUSION: In NEEC patients, combined CRT yielded beneficial effects than any single mode. Both chemotherapy and brachytherapy promoted survival in early stage SC patients. Late stage SC patients may benefit from chemotherapy plus either EBRT or brachytherapy.
Assuntos
Carcinoma Endometrioide , Carcinossarcoma , Neoplasias do Endométrio , Feminino , Humanos , Radioterapia Adjuvante/métodos , Pontuação de Propensão , Estadiamento de Neoplasias , Carcinoma Endometrioide/tratamento farmacológico , Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/radioterapia , Quimioterapia Adjuvante/métodos , Carcinossarcoma/radioterapia , Carcinossarcoma/tratamento farmacológico , Estudos RetrospectivosRESUMO
Colorectal carcinosarcoma is an exceedingly rare subtype of colorectal cancer that displays the histological and molecular features of both mesenchymal and epithelial tumors. Due to its rarity, there are no guidelines regarding the systemic treatment of this disease. This report describes a case of a 76-year-old woman with colorectal carcinosarcoma with extensive metastatic burden treated with carboplatin and paclitaxel. After four cycles of chemotherapy, the patient had an excellent clinical and radiographical response to treatment. To the best of our knowledge, this is the first report addressing the use of carboplatin and paclitaxel in this disease. We reviewed seven published case reports of metastatic colorectal carcinosarcoma where various systemic treatments were offered. Remarkably, there are no previously published reports where even a partial response was noted, which underscores the aggressiveness of this disease. While further studies are required to validate our experience and assess long-term outcomes, this case suggests an alternative treatment regimen for metastatic colorectal carcinosarcoma.
Assuntos
Carcinossarcoma , Neoplasias Colorretais , Feminino , Humanos , Idoso , Carboplatina/uso terapêutico , Paclitaxel/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinossarcoma/tratamento farmacológico , Carcinossarcoma/patologia , Neoplasias Colorretais/tratamento farmacológicoRESUMO
Uterine serous carcinoma (USC) and carcinosarcomas (CSs) are rare, highly aggressive variants of endometrial cancer. No reliable tumor biomarkers are currently available to guide response to treatment or detection of early recurrence in USC/CS patients. Circulating tumor DNA (ctDNA) identified using ultrasensitive technology such as droplet digital polymerase chain reaction (ddPCR) may represent a novel platform for the identification of occult disease. We explored the use of personalized ctDNA markers for monitoring USC and CS patients. Tumor and plasma samples from USC/CS patients were collected at the time of surgery and/or during the treatment course for assessment of tumor-specific somatic structural variants (SSVs) by a clinical-grade next-generation sequencing (NGS) platform (i.e., Foundation Medicine) and a droplet digital PCR instrument (Raindance, ddPCR). The level of ctDNA was quantified by droplet digital PCR in plasma samples and correlated to clinical findings, including CA-125 serum and/or computed tomography (CT) scanning results. The genomic-profiling-based assay identified mutated "driver" target genes for ctDNA analysis in all USC/CS patients. In multiple patients, longitudinal ctDNA testing was able to detect the presence of cancer cells before the recurrent tumor was clinically detectable by either CA-125 or CT scanning. Persistent undetectable levels of ctDNA following initial treatment were associated with prolonged progression-free and overall survival. In a USC patient, CA-125 and TP53 mutations but not PIK3CA mutations become undetectable in the plasma at the time of recurrence, suggesting that more than one customized probe should be used for monitoring ctDNA. Longitudinal ctDNA testing using tumor-informed assays may identify the presence of residual tumors, predict responses to treatment, and identify early recurrences in USC/CS patients. Recognition of disease persistence and/or recurrence through ctDNA surveillance may allow earlier treatment of recurrent disease and has the potential to change clinical practice in the management of USC and CS patients. CtDNA validation studies in USC/CS patients prospectively enrolled in treatment trials are warranted.
Assuntos
Carcinossarcoma , DNA Tumoral Circulante , Cistadenocarcinoma Seroso , Neoplasias Uterinas , Feminino , Humanos , DNA Tumoral Circulante/genética , Recidiva Local de Neoplasia/genética , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/genética , Neoplasias Uterinas/terapia , Biomarcadores Tumorais/genética , Mutação , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/terapia , Carcinossarcoma/diagnóstico , Carcinossarcoma/genética , Carcinossarcoma/terapiaRESUMO
Uterine carcinosarcoma (UCS) frequently expresses human epidermal growth factor receptor 2 (HER2) and metastasizes. However, little is known about changes in the HER2 expression status in metastatic lesions and its impact on clinical outcomes. In 41 patients with synchronous or metachronous metastases and matched primary UCSs, we assessed the HER-2 expression using immunohistochemistry and scored it per the 2016 American Society of Clinical Oncology/College of American Pathologists guidelines, modified for UCS. We compared HER2 scores between paired primary and metastatic lesions and reviewed the association between clinicopathological characteristics and impact on overall survival. HER2 scores of 3+, 2+, 1+, and 0 were observed in 12.2 %, 34.2 %, 26.8 %, and 26.8 % of primary tumors, respectively, and 9.8 %, 19.5 %, 43.9 %, and 26.8 % of metastatic tumors, respectively. HER2 intratumoral heterogeneity occurred in 46.3 % and 19.5 % of the primary and metastatic lesions, respectively. The agreement rate of the HER2 score was 34.2 % in the four-tiered scale, while it was 70.7 % in the two-tiered scale (score 0 vs. score ≥ 1+) with fair agreement (к = 0.26). Patients with HER2 discordance showed significantly shorter overall survival (hazard ratios = 2.38, 95 % confidence interval 1.01-5.5, p = 0.049). HER2 discordance was not associated with specific clinicopathological characteristics. Discordance in HER2 status between primary and metastatic tumors in UCS was frequently observed regardless of clinicopathological characteristics and was a poor prognostic factor. Even if one tumor (primary or metastatic) is HER2 negative, HER2 testing of other tumors may be beneficial in terms of patient treatment options.
Assuntos
Neoplasias da Mama , Carcinossarcoma , Humanos , Feminino , Receptor ErbB-2/metabolismo , Metástase Linfática , Projetos de Pesquisa , Biomarcadores TumoraisRESUMO
A 71-year-old female was treated with carboplatin and paclitaxel for an endometrial carcinosarcoma. The patient demonstrated an unusual type 1 allergic reaction on carboplatin, which started with an erythematous urticarial venous pattern proximal from the venous catheter with carboplatin.
Assuntos
Carcinossarcoma , Neoplasias do Endométrio , Feminino , Humanos , Idoso , Carboplatina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinossarcoma/tratamento farmacológico , Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/tratamento farmacológico , Paclitaxel/uso terapêuticoRESUMO
AIMS: To report novel observations in five mesonephric-like adenocarcinomas (MLAs) of the female genital tract. METHODS AND RESULTS: We report two endometrial MLAs in association with endometrioid carcinoma and atypical hyperplasia and three (one endometrial, two ovarian) cases with a sarcomatoid component (mesonephric-like carcinosarcoma). Pathogenic KRAS mutations, which are characteristic of MLA, were identified in all cases although interestingly, in one of the mixed carcinomas, this was confined to the endometrioid component. The concurrent MLA, endometrioid carcinoma and atypical hyperplasia components in one case harboured identical EGFR, PTEN and CCNE1 mutations, suggesting that the atypical hyperplasia gave rise to a Müllerian carcinoma with both endometrioid and mesonephric-like components. The carcinosarcomas all contained a component of MLA and a sarcomatous component with chondroid elements. In the ovarian carcinosarcomas, the coexisting epithelial and sarcomatous components shared some mutations including KRAS and CREBBP, suggesting that they are clonally related. Furthermore, in one case CREBBP and KRAS mutations detected in the MLA and sarcomatous components were also detected in an associated undifferentiated carcinoma component, suggesting that it was clonally related to the MLA and sarcomatous components. CONCLUSIONS: Our observations provide additional evidence that MLAs have a Müllerian origin and characterise mesonephric-like carcinosarcomas in which chondroid elements appear to be characteristic. In reporting these findings, we provide recommendations for distinction between a mesonephric-like carcinosarcoma and a MLA with a spindle cell component.
Assuntos
Adenocarcinoma , Carcinoma Endometrioide , Carcinossarcoma , Feminino , Humanos , Carcinoma Endometrioide/patologia , Hiperplasia/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Carcinossarcoma/genética , Carcinossarcoma/patologia , Endométrio/patologiaRESUMO
PURPOSE: To investigate the efficacy and safety of trastuzumab deruxtecan, an antibody-drug conjugate targeting human epidermal growth factor receptor 2 (HER2) with a topoisomerase I inhibitor payload, in patients with uterine carcinosarcoma (UCS) expressing HER2. PATIENTS AND METHODS: Patients with recurrent UCS with HER2 immunohistochemistry scores ≥1+ previously treated with chemotherapy were included. Patients were assigned to the HER2-high (immunohistochemistry score ≥2+; n = 22) or low (immunohistochemistry score of 1+; n = 10) groups for primary and exploratory analyses, respectively. Trastuzumab deruxtecan 6.4 or 5.4 mg/kg was administered intravenously once every 3 weeks until unacceptable toxicity or disease progression. Dose modification was based on the updated recommended phase II dose for breast cancer to be 5.4 mg/kg. The primary end point was the objective response rate by central review in the HER2-high group. Secondary end points included the overall response rate (ORR) in the HER2-high group by investigator assessment, ORR in the HER2-low group, progression-free survival (PFS), overall survival (OS), and safety. RESULTS: The ORR by central review in the HER2-high and HER2-low groups were 54.5% (95% CI, 32.2 to 75.6) and 70.0% (95% CI, 34.8 to 93.3) and those by investigator assessments were 68.2% and 60.0%, respectively. The median PFS and OS in the HER2-high and HER2-low groups were 6.2 and 13.3 months and 6.7 months and not reached, respectively. Grade ≥ 3 adverse events occurred in 20 patients (61%). Grades 1-2 and 3 pneumonitis/interstitial lung disease occurred in eight (24%) and one (3%) patient, respectively. CONCLUSION: Trastuzumab deruxtecan has efficacy in patients with UCS, regardless of HER2 status. The safety profile was generally consistent with that previously reported. Toxicities were manageable with appropriate monitoring and treatment.
Assuntos
Carcinossarcoma , Imunoconjugados , Feminino , Humanos , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinossarcoma/genética , Carcinossarcoma/terapia , Imunoconjugados/efeitos adversos , Receptor ErbB-2/metabolismo , Trastuzumab , Neoplasias Uterinas/genética , Neoplasias Uterinas/terapiaRESUMO
OBJECTIVES: Human epidermal growth factor receptor 2 (HER2) status in endometrial cancer is usually determined by immunohistochemistry and/or in situ hybridization. We employed a novel HER2 gene protein assay (GPA) to simultaneously assesses HER2 gene amplification and protein expression in high-grade endometrial cancers. METHODS: We performed GPA in 180 endometrial cancers, including 106 serous carcinomas, 34 carcinosarcomas, and 40 mixed epithelial carcinomas. HER2 status was determined using the 2018 HER2 guidelines for breast carcinoma, and HER2 intratumoral heterogeneity (ITH) was examined. Clinicopathologic characteristics were collected and correlated with HER2 status. RESULTS: HER2 positivity was noted in 32% of serous carcinomas, significantly higher than in carcinosarcomas (5.9%) and mixed carcinomas (12.5%). HER2 ITH was detected in 32% of serous carcinomas, significantly greater than in carcinosarcomas (8.8%) and mixed carcinomas (10%). Patients with carcinosarcoma had a significantly lower overall survival than patients with serous or mixed epithelial carcinoma, but HER2 status caused no difference in survival in patients with serous carcinoma. CONCLUSIONS: HER2 GPA can be used to accurately determine HER2 status in endometrial cancers and is a highly valuable tool for identifying HER2 heterogeneity.
Assuntos
Carcinossarcoma , Cistadenocarcinoma Seroso , Neoplasias do Endométrio , Feminino , Humanos , Genes erbB-2 , Amplificação de Genes , Receptor ErbB-2/metabolismo , Neoplasias do Endométrio/patologia , Carcinossarcoma/genética , Biomarcadores Tumorais/genéticaRESUMO
A 12-year-old castrated male Cane Corso dog was presented with cervical swelling, lethargy, anorexia, and cough. An extensive neck mass with necrotic cysts was observed, severely adherent to surrounding tissues. Based on diagnostic imaging including ultrasound, computed tomography, and fine-needle aspiration cytology, paraesophageal abscess was tentatively diagnosed. However, after the mass was surgically removed, a diagnosis of thyroid carcinosarcoma composed of neoplastic cell populations with epithelial and mesenchymal origins was made via histopathology and immunohistochemistry. The dog died of a recurrent mass with pulmonary metastasis 105 d after surgery. This report describes a rare type of canine thyroid cancer, thyroid carcinosarcoma, preoperatively masquerading as an abscess and postoperatively confirmed by histopathology. Key clinical message: Thyroid carcinosarcoma, despite its rarity in dogs, should be included in the differential diagnoses of cervical mass especially with an aggressive progression.
Carcinosarcome thyroïdien déguisé en abcès paraoesophagien chez un chien Cane Corso. Un chien Cane Corso mâle castré de 12 ans a été présenté avec de l'enflure cervicale, de la léthargie, de l'anorexie et une toux. Une masse étendue du cou avec des kystes nécrotiques a été observée, adhérente fortement aux tissus environnants. Sur la base de l'imagerie diagnostique comprenant l'échographie, la tomodensitométrie et la cytologie par aspiration à l'aiguille fine, un abcès paraoesophagien a été provisoirement diagnostiqué. Cependant, après l'ablation chirurgicale de la masse, un diagnostic de carcinosarcome thyroïdien composé de populations de cellules néoplasiques d'origine épithéliale et mésenchymateuse a été posé par histopathologie et immunohistochimie. Le chien est décédé d'une masse récurrente avec métastase pulmonaire 105 jours après la chirurgie. Ce rapport décrit un type rare de cancer de la thyroïde canine, le carcinosarcome thyroïdien, se faisant passer pour un abcès en préopératoire et confirmé en postopératoire par histopathologie.Message clinique clé:Le carcinosarcome thyroïdien, malgré sa rareté chez le chien, doit être inclus dans les diagnostics différentiels de masse cervicale surtout à évolution agressive.(Traduit par Dr Serge Messier).
Assuntos
Carcinossarcoma , Doenças do Cão , Neoplasias da Glândula Tireoide , Masculino , Cães , Animais , Abscesso/veterinária , Bengala , Carcinossarcoma/veterinária , Neoplasias da Glândula Tireoide/veterináriaRESUMO
Adenocarcinoma of the endometrium (also known as endometrial cancer, or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. It is estimated that 65,950 new uterine cancer cases will have occurred in 2022, with 12,550 deaths resulting from the disease. Endometrial carcinoma includes pure endometrioid cancer and carcinomas with high-risk endometrial histology (including uterine serous carcinoma, clear cell carcinoma, carcinosarcoma [also known as malignant mixed Müllerian tumor], and undifferentiated/dedifferentiated carcinoma). Stromal or mesenchymal sarcomas are uncommon subtypes accounting for approximately 3% of all uterine cancers. This selection from the NCCN Guidelines for Uterine Neoplasms focuses on the diagnosis, staging, and management of pure endometrioid carcinoma. The complete version of the NCCN Guidelines for Uterine Neoplasms is available online at NCCN.org.
Assuntos
Adenocarcinoma de Células Claras , Carcinoma Endometrioide , Carcinossarcoma , Neoplasias do Endométrio , Neoplasias Uterinas , Feminino , Humanos , Carcinoma Endometrioide/patologia , Carcinossarcoma/diagnóstico , Carcinossarcoma/terapia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/terapia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/terapia , Neoplasias Uterinas/patologiaRESUMO
BACKGROUND: Primary maxillary sinus carcinosarcoma (CS) is an extremely rare malignant tumor characterized by biphasic histologic components, lack of standardized treatment, high recurrence rate, and poor prognosis. This paper presents a case of primary maxillary sinus CS and its treatment. CASE PRESENTATION: A 39-year-old female patient complained of right facial pain and maxillary teeth numbness on March 21, 2018. Computed tomography examination revealed a malignant mass with osteolytic destruction. Preoperative biopsy suggested sarcomatoid carcinoma or CS. A total right maxillectomy under general anesthesia was performed on April 12, 2018. The final staging was T3N0M0 (ACJJ 2019). Postoperative radiotherapy and chemotherapy were performed. On May 26, 2018, the patient received the first cycle of doxorubicin plus ifosfamide. Two days before radiotherapy, the patient received an intra-oral prosthesis. From June 20, 2018, to August 22, 2018, the patient received concurrent chemoradiotherapy: radiotherapy (60 Gy in 30 fractions) and the second cycle of doxorubicin. Then, the patient received four cycles of doxorubicin plus ifosfamide. The patient was followed for 39 months with no evidence of disease. CONCLUSION: Using multidisciplinary therapy, clinical-stage T3N0M0 (ACJJ 2019) maxillary sinus CS may achieve a good prognosis.
Assuntos
Carcinossarcoma , Neoplasias do Seio Maxilar , Feminino , Humanos , Adulto , Seio Maxilar/diagnóstico por imagem , Ifosfamida/uso terapêutico , Seguimentos , Neoplasias do Seio Maxilar/patologia , Neoplasias do Seio Maxilar/cirurgia , Carcinossarcoma/terapia , Carcinossarcoma/tratamento farmacológico , Doxorrubicina/uso terapêuticoRESUMO
Trichoblastic carcinosarcoma is a seldom biphasic adnexal tumor with malignant epithelial and mesenchymal components. The authors report the first tumor on the neck developed from preexistent trichoblastoma showing aggressive, recurrent behavior. An 82-year-old man presented with a solitary 3-cm exophytic lesion. Histology verified the diagnosis of trichoblastic carcinosarcoma. Four years earlier, a trichoblastic carcinoma arising in a preexisting trichoblastoma was excised at the same location. Despite successful surgical treatments, three local recurrences within 4 years were diagnosed. After the second relapse, the patient agreed on adjuvant radiation. Twelve months later, another relapse was excised in toto. In the last surgical specimen, only the mesenchymal component was found. Copy number variation analysis of the preexisting tumor and two recurrences revealed the same entity and additional chromosomal aberrations in the recurrences. Adnexal carcinosarcomas are seldom, yet presumably underdiagnosed biphasic tumors with aggressive growth potential. They should have adequate preoperative clarification with wide tumor excision, as radiosensitivity seems to be of limited effect.
Assuntos
Carcinossarcoma , Doenças do Cabelo , Neoplasia de Células Basais , Neoplasias Cutâneas , Masculino , Humanos , Idoso de 80 Anos ou mais , Variações do Número de Cópias de DNA , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/cirurgia , Doenças do Cabelo/patologia , Carcinossarcoma/diagnóstico , Carcinossarcoma/genética , Carcinossarcoma/cirurgiaRESUMO
Inactivating mutations of SMARCA4 and accompanying loss of BRG1 immunoexpression were recently identified in majority of sinonasal teratocarcinosarcomas (TCS). These rare and aggressive neoplasms have potential for nodal metastasis, presenting opportunities for diagnosis on fine needle aspiration cytology (FNAC). However, their cytological features have not been described till date. A 22-year-old male was diagnosed to have SMARCA4-deficient TCS on a nasal mass biopsy, and was started on neoadjuvant chemotherapy. Four months later, FNAC from cervical lymph nodes showed predominantly discohesive tumor cells with moderate to abundant cytoplasm and enlarged vesicular nuclei with prominent nucleoli. Occasional cohesive fragments showed ovoid to spindled tumor cells attached to fibrovascular cores. Few loosely cohesive cells with scant cytoplasm and nuclei having stippled chromatin, and rhabdoid cells were also seen. Frequent mitoses, apoptosis and nuclear streaking were evident. Overt squamous or glandular differentiation was absent. Tumor cells showed loss of BRG1 immunostaining and ß-catenin immunopositivity on a cell block, consistent with metastatic SMARCA4-deficient TCS. The diversity of cell types in SMARCA4-deficient TCS can result in a broad spectrum of cytological features that overlap with that of other regional metastatic tumors including neuroendocrine carcinoma, olfactory neuroblastoma and melanoma. Further, all components of TCS as seen in the primary tumor may not be present in nodal metastases. Thus, SMARCA4-deficient TCS should be considered in the differential diagnosis of metastatic poorly/undifferentiated malignancies in cervical lymph node aspirates, and appropriate ancillary tests viz. BRG1 immunostaining employed for accurate diagnosis.
Assuntos
Carcinossarcoma , Neoplasias Nasais , Teratoma , Humanos , Masculino , Adulto Jovem , Biomarcadores Tumorais/genética , Biópsia por Agulha Fina , Carcinossarcoma/diagnóstico , Carcinossarcoma/genética , DNA Helicases/genética , Neoplasias Nasais/patologia , Proteínas Nucleares/genética , Fatores de Transcrição/genéticaRESUMO
OBJECTIVES: Carcinosarcomas are highly aggressive gynecologic malignancies containing both carcinomatous and sarcomatous elements with heterogeneous HER2/neu expression and limited therapeutic options. We compared the efficacy of trastuzumab deruxtecan (DS-8201a), a novel HER2/neu-targeting antibody-drug conjugate (ADC) to an ADC isotype control (MAAA-9199) against primary uterine and ovarian carcinosarcomas in vitro and in vivo. METHODS: Twelve primary carcinosarcoma (CS) cell lines were evaluated for HER2/neu surface expression by immunohistochemistry (IHC) and by flow cytometry, and gene amplification by fluorescence in situ hybridization (FISH) assays. The in vitro experiments included cytotoxicity and bystander killing effect assays on three cell lines of variable HER2/neu expression. In vivo activity was studied in a mouse CS xenograft model of 3+ HER2/neu uterine CS. RESULTS: In vitro studies showed that DS-8201a was highly effective against uterine and ovarian CS cell lines demonstrating 3+ HER2/neu expression compared to MAAA-9199 control; there was no significant improvement in the 0 HER2/neu CS cell line. However, DS-8201a induced efficient bystander killing of 0 HER2/neu tumor cells when admixed with 3+ HER2/neu cells. In vivo studies confirmed that DS-8201a was more effective than MAAA-9199 in 3+ HER2/neu-expressing CS xenografts. CONCLUSION: DS-8201a may represent a novel and highly effective ADC against HER2/neu-expressing CS.
Assuntos
Carcinossarcoma , Imunoconjugados , Neoplasias Ovarianas , Humanos , Feminino , Camundongos , Animais , Inibidores da Topoisomerase I/farmacologia , Inibidores da Topoisomerase I/uso terapêutico , Hibridização in Situ Fluorescente , Receptor ErbB-2/genética , Anticorpos Monoclonais Humanizados/uso terapêutico , Linhagem Celular Tumoral , Trastuzumab/uso terapêutico , Imunoconjugados/uso terapêutico , Neoplasias Ovarianas/patologia , Carcinossarcoma/patologiaRESUMO
Oesophageal carcinosarcoma (OCS) is a rare oesophageal cancer, expressing both carcinomatous and sarcomatous elements. Although believed to have a better prognosis, no standard guidelines exist for its diagnosis and management. We report a case of a 60-year male presenting with progressive dysphagia and weight loss. Endoscopy and contrast-enhanced computed tomography of the chest revealed a large polypoidal intraluminal growth at the mid-oesophagus. Endoscopic biopsy revealed a sarcoma of the oesophagus. The patient underwent McKeown minimally invasive oesophagectomy. Final histopathology was suggestive of OCS. Postoperatively, the patient received adjuvant chemoradiation. At 20-month follow-up, he was asymptomatic with no radiological evidence of recurrence.
Assuntos
Carcinossarcoma , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Masculino , Carcinossarcoma/diagnóstico , Carcinossarcoma/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/cirurgia , EsofagectomiaRESUMO
BACKGROUND: Carcinosarcoma of the ovary (OCS) and uterus (UCS) are rare highly aggressive malignancies. Ataxia-telangiectasia-and-Rad3-related (ATR) kinase and homologous recombination play a pivotal role in DNA damage repair. Homologous recombination deficiency (HRD) has been demonstrated in >30% of OCS/UCS. We investigated the preclinical activity of elimusertib, a selective ATR kinase inhibitor, against carcinosarcoma (CS) cell lines and xenografts. METHODS: Sensitivity to elimusertib was evaluated in vitro against nine whole exome-sequenced (WES) primary CS cell lines and in vivo against HRD CS xenografts. Western blots were performed to determine baseline ATR and p-ATR protein expression in CS, and ATR pathway downstream effectors and apoptosis markers in CS HRD cell lines after Elimusertib treatment. RESULTS: Out of the 9 CS cell lines, 3 harbored HRD and 6 homologous recombination proficient (HRP) features. Most of CS (i.e., 7/9 = 85%) were found to be sensitive to Elimusertib in vitro. Among the 5 primary CS cell lines with a high-grade pure serous epithelial component, HRD cell lines were more sensitive to elimusertib than HRP tumors (mean IC50 ± SEM HRD CS = 61.3 nM ±15.2 vs HRP = 361.6 nM ±24.4 (p = 0.01)). Baseline ATR and p-ATR protein expression was higher in HRD CS cell lines. Elimusertib showed tumor growth inhibition in HRD CS xenografts (p < 0.0001) and increased overall animal survival (p < 0.0001). Western blot demonstrated dose-dependent inhibition of ATR, p-ATR and its downstream effector p-CHK1, and a dose-dependent increase in caspase-3 expression. CONCLUSIONS: Elimusertib is preclinically active in vitro and in vivo against primary CS cell lines and xenografts, respectively. CS models harboring HRD or with pure/mixed endometrioid histology demonstrated higher sensitivity to ATR inhibition. Clinical trials with elimusertib in CS patients are warranted.
