RESUMO
OBJECTIVE: Histopathologic characteristics after neoadjuvant chemotherapy (NACT) may correlate with outcome. This study evaluates histopathologic features after immunotherapy and NACT/bevacizumab, and associated clinical outcomes. METHODS: Evaluable tissue from IMagyn050/GOG3015/ENGOT-ov39 patients from prespecified anatomic sites from interval cytoreductive surgery (ICS) after NACT/bevacizumab plus atezolizumab/placebo underwent central histopathologic scoring and analyzed with clinical outcomes. RESULTS: The predefined population had 243 evaluable NACT patients, with 48.1% tumors being PD-L1-positive. No statistically significant differences in PFS (16.9 months vs. 19.2 months, p = 0.21) or OS (41.5 months vs. 45.1 months, p = 0.67) between treatment arms were seen. Substantial residual tumor (RT) (3+) was identified in 26% atezolizumab vs. 24% placebo arms (p = 0.94). Most showed no (1+) necrosis (82% vs. 96%, respectively, p = 0.69), moderate (2+) to severe (3+) fibrosis (71% vs. 75%, respectively, p = 0.82), and extensive (2+) inflammation (53% vs. 47% respectively, p = 0.48). No significant histopathologic differences were identified by tissue site or by arm. Multivariate analyses showed increased risk for progression with moderate and substantial RT (13.6 mon vs. 21.1 mon, hazard ratio 2.0, p < 0.01; 13.6 mon vs. 21.1 mon, HR 1.9, p < 0.01, respectively); but decreased risk for death with extensive inflammation (46.9 mon vs. 36.3 mon, HR 0.65, p = 0.02). Inflammation also correlated with greater likelihood of response to NACT/bevacizumab plus immunotherapy (odds ratio 2.9, p < 0.01). Modeling showed inflammation as a consistent but modest predictor for OS. CONCLUSIONS: Detailed histologic assessment of ICS specimens appear to identify characteristics, such as inflammation and residual tumor, that may provide insight to certain clinical outcomes. Future work potentially leveraging emerging tools may provide further insight into outcomes.
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Terapia Neoadjuvante , Humanos , Feminino , Terapia Neoadjuvante/métodos , Bevacizumab/administração & dosagem , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Método Duplo-Cego , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adulto , Imunoterapia/métodos , Procedimentos Cirúrgicos de Citorredução , Neoplasia Residual , Intervalo Livre de ProgressãoRESUMO
Endometrial somatically derived yolk sac tumors are characterized by yolk sac morphology with AFP, SALL-4, and/or Glypican-3 immunoexpression. Yolk sac marker expression, however, is not limited to tumors with overt yolk sac histology. Three hundred consecutive endometrial malignancies were assessed for immunomarkers of yolk sac differentiation. Of these, 9% expressed ≥1 yolk sac marker, including 29% of high-grade tumors. Only 3 (1%) met morphologic criteria for yolk sac differentiation; these were originally diagnosed as serous, high-grade NOS, and dedifferentiated carcinoma. Two were MMR-intact and comprised exclusively of yolk sac elements, while the dedifferentiated case was MMR deficient and had a background low-grade endometrioid carcinoma; this case also showed BRG1 loss. All 3 were INI1 intact. Nonspecific yolk sac marker expression was seen in 14 carcinosarcomas, 4 endometrioid, 2 serous, 1 clear cell, 1 dedifferentiated, 1 mixed serous/clear cell, and 1 mesonephric-like carcinoma. INI1 was intact in all cases; one showed BRG1 loss. Twenty were MMR-intact, and 4 were MMR deficient. All MMR-deficient cases with yolk sac marker expression, both with and without true yolk sac morphology, had no evidence of residual disease on follow-up, whereas 82% of MMR-intact cases developed recurrent/metastatic disease. In summary, endometrial somatically derived yolk sac tumors were rare but under-recognized. While AFP immunostaining was specific for this diagnosis, Glypican-3 and SALL-4 expression was seen in a variety of other high-grade carcinomas. INI1 loss was not associated with yolk sac morphology or immunomarker expression in the endometrium, and BRG1 loss was rare. All patients with MMR-deficient carcinomas with yolk sac immunoexpression +/- morphology were disease-free on follow-up, whereas the majority of MMR-intact cancers showed aggressive disease.
Assuntos
Biomarcadores Tumorais , Tumor do Seio Endodérmico , Neoplasias do Endométrio , Imuno-Histoquímica , Fatores de Transcrição , Humanos , Feminino , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/metabolismo , Biomarcadores Tumorais/análise , Tumor do Seio Endodérmico/patologia , Tumor do Seio Endodérmico/metabolismo , Idoso , Pessoa de Meia-Idade , Fatores de Transcrição/análise , Idoso de 80 Anos ou mais , Adulto , Glipicanas/análise , Glipicanas/metabolismo , Diferenciação Celular , alfa-Fetoproteínas/análise , Incidência , Gradação de Tumores , DNA Helicases/análise , Proteínas Nucleares/análise , Proteínas Nucleares/metabolismo , Proteína SMARCB1/análise , Carcinoma/patologia , Carcinoma/químicaRESUMO
Since the establishment of 4 molecular subgroups of endometrial carcinoma (EC), there has been significant interest in understanding molecular classification in the context of histologic features and diagnoses. ECs with undifferentiated, spindle, and/or sarcomatous components represent a diagnostically challenging subset of tumors with overlapping clinical and histologic features. We examined the clinicopathologic, morphologic, immunohistochemical, and molecular features of these tumors identified in our institutions' pathology databases using immunohistochemistry and targeted sequencing. Disease-specific survival (DSS) and progression-free survival (PFS) were analyzed using Kaplan-Meier curves and log-rank tests. One hundred sixty-two ECs were included: carcinosarcomas (UCS; n=96), dedifferentiated/undifferentiated EC (DDEC/UDEC; n=49), and grade 3 endometrioid EC with spindled growth (GR3spEEC) (n=17). All molecular subgroups were represented in all histologic subtypes and included 12 (7%) POLE -mutated ( POLE mut), 43 (27%) mismatch repair-deficient (MMRd), 77 (48%) p53-abnormal (p53abn), and 30 (19%) no specific molecular profile (NSMP) tumors. However, the molecular classification (irrespective of histologic diagnosis) was a significant predictor for both DSS ( P =0.008) and P≤0.0001). POLE mut EC showed an excellent prognosis with no recurrences or deaths from the disease. MMRd tumors also showed better outcomes relative to NSMP and p53abn tumors. In conclusion, molecular classification provides better prognostic information than histologic diagnosis for high-grade EC with undifferentiated and sarcomatous components. Our study strongly supports routine molecular classification of these tumors, with emphasis on molecular group, rather than histologic subtyping, in providing prognostication.
Assuntos
Biomarcadores Tumorais , Neoplasias do Endométrio , Gradação de Tumores , Humanos , Feminino , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/classificação , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/genética , Idoso , Pessoa de Meia-Idade , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Idoso de 80 Anos ou mais , Imuno-Histoquímica , Intervalo Livre de Progressão , Carcinossarcoma/patologia , Carcinossarcoma/mortalidade , Carcinossarcoma/classificação , Carcinossarcoma/genética , Adulto , Valor Preditivo dos Testes , Diferenciação Celular , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/classificação , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/genética , Mutação , Estudos Retrospectivos , Fatores de TempoRESUMO
Autoimmune and systemic inflammatory diseases represent a heterogeneous group of immune-mediated conditions with a wide range of clinical presentations and various affected organs. Autoimmune diseases can present in the breast as localized disease or as part of systemic involvement. Although breast involvement is uncommon, the spectrum of imaging findings can include breast masses, axillary adenopathy, calcifications, and skin changes, the appearance of which can mimic breast cancer. Common etiologies include diabetic mastopathy, systemic lupus erythematosus, scleroderma, rheumatoid arthritis, idiopathic granulomatous mastitis, sarcoidosis, and Immunoglobulin-G4 related mastopathy. This educational review will present multimodality imaging findings of breast manifestations of systemic inflammatory and autoimmune diseases and coexisting complications. It will also review how these disorders may affect breast cancer risk and breast cancer treatment options, including radiation therapy.