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1.
Int J Gynecol Cancer ; 32(11): 1402-1409, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36343971

RESUMO

OBJECTIVES: To evaluate differences in survival and recurrence patterns in stage I-IV uterine carcinosarcoma patients treated with surgery followed by adjuvant chemotherapy alone, radiation alone, or a combination of both chemotherapy and radiation therapy. METHODS: A multicenter retrospective analysis of patients with surgically staged carcinosarcoma receiving adjuvant therapy from January 2000 to December 2019 was conducted. Inclusion criteria were patients with carcinosarcoma who had received primary surgical treatment, followed by adjuvant therapy with chemotherapy alone, radiation therapy alone, or a combination of chemoradiation. Patients were excluded for incomplete surgical staging data, adjuvant brachytherapy alone, adjuvant chemotherapy and brachytherapy without external beam radiation therapy, receipt of neoadjuvant chemotherapy and/or pre-operative pelvic radiation, and death due to non-cancer causes. Sites of recurrence were analyzed by adjuvant treatment modality using Pearson's χ2 test. Progression-free and overall survival were calculated using Kaplan-Meier estimates. Multivariate analysis was performed using Cox proportional hazards model. RESULTS: Of 176 evaluable patients, 27% (n=47) had stage I, 14% (n=24) stage II, 37% (n=66) stage III, and 22% (n=39) stage IV disease. Among them, 33% (n=59) received chemotherapy alone, 17% (n=29) received radiation therapy alone, and 50% (n=88) received chemoradiation. Patients with stage I disease recurred less frequently (64%) versus stage II (83%), stage III (85%), and stage IV (90%) (p<0.001). Stage I disease demonstrated improved progression-free and overall survival relative to all other stages (p<0.01). Across all stages, patients receiving chemoradiation experienced superior progression-free (p=0.01) and overall survival (p=0.05) versus single modality therapy. However, when analyzed in a stage-specific manor, stage III disease derived the greatest survival benefit from chemoradiation versus all other stages (p<0.01). On multivariant analysis, only stage and receipt of chemoradiation were independent predictors of survival. CONCLUSION: Stage I disease demonstrated improved survival compared with other stages regardless of adjuvant treatment modality. Chemoradiation was associated with improved survival and better distant and local disease control for all stages of disease. Patients with stage III disease derived the most benefit from chemoradiation.


Assuntos
Carcinossarcoma , Neoplasias Uterinas , Feminino , Humanos , Estudos Retrospectivos , Histerectomia , Estadiamento de Neoplasias , Neoplasias Uterinas/radioterapia , Neoplasias Uterinas/tratamento farmacológico , Carcinossarcoma/patologia , Quimioterapia Adjuvante , Radioterapia Adjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
2.
Pan Afr Med J ; 42: 284, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405654

RESUMO

Carcinosarcoma of the gallbladder is a rare cancer characterized by presence of a carcinomatous and a sarcomatous component. In our work, we report the case of a 66-year-old male patient, presenting with isolated abdominal pain evolving for more than 6 months. contrast-enhanced computed tomography enabled identification of a gallbladder mass, invading liver, duodenum and abdominal wall. A cholecystectomy, extended to liver, duodenum and abdominal wall was performed. The final diagnosis of gallbladder carcinosarcoma was obtained by pathological assessment. Gallbladder carcinosarcoma has a poor prognosis. Since it is rare, no established chemotherapy or radiation protocols exist. Further studies about case series are needed to establish better therapeutic protocols. Gallbladder carcinosarcoma is a rare cancer with a rapid progression making therapeutic decisions difficult. All these factors contribute to the poor prognosis of this cancer.


Assuntos
Carcinossarcoma , Neoplasias da Vesícula Biliar , Humanos , Masculino , Idoso , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/patologia , Carcinossarcoma/diagnóstico , Carcinossarcoma/terapia , Carcinossarcoma/patologia , Colecistectomia , Tomografia Computadorizada por Raios X
3.
Curr Treat Options Oncol ; 23(11): 1590-1600, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36205807

RESUMO

OPINION STATEMENT: Rare endometrial cancers are high-grade, aggressive malignancies which are often diagnosed at an advanced stage, and account for disproportionately more deaths than their more common low-grade counterparts. Standard of care includes a combination of surgery, radiation, and chemotherapy. Surgery consists of complete hysterectomy, and more recent evidence supports replacing a full lymphadenectomy with sentinel node mapping. Paclitaxel and carboplatin remain the mainstays of chemotherapy, while current studies incorporating immunotherapy will inform future practice. Whether and how to incorporate radiation remains controversial, and certain histologic subtypes, such as carcinosarcomas, may benefit from radiation more than others. Owing to their relative rarity, it is difficult to conduct clinical trials in this patient population, which has hindered the development of effective therapies for rare malignancies. Molecular profiling has offered insight into the pathogenesis of rare endometrial cancers, providing actionable targets for personalized therapy.


Assuntos
Carcinossarcoma , Neoplasias do Endométrio , Feminino , Humanos , Carboplatina/uso terapêutico , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/etiologia , Neoplasias do Endométrio/terapia , Carcinossarcoma/patologia , Excisão de Linfonodo/efeitos adversos , Paclitaxel/uso terapêutico
4.
J Vet Med Sci ; 84(12): 1579-1584, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36261364

RESUMO

A 12-year-old female Himalayan cat underwent an ovariohysterectomy to remove an intra-abdominal mass. Histologic examination using immunohistochemical staining revealed that the mass was comprised of epithelial and mesenchymal components. Within the lesion, multinucleated giant cells (MGCs) were observed diffusely. MGCs were positive for vimentin and Iba-1 and negative for cytokeratin AE1/AE3 and CD204. In addition, MGCs were negative for Ki-67, indicating nonneoplastic cells. Osteoclast-like MGC (OLMGC) phenotype with tartrate-resistant acid phosphatase positivity was also seen. These findings suggested that the uterine tumor was carcinosarcoma with OLMGCs. Uterine tumors in humans, such as leiomyosarcoma and carcinosarcoma, with OLMGC infiltration, are well-known pathologic entities; however, they are rare in animals and to our knowledge, have not been previously reported in cats.


Assuntos
Carcinossarcoma , Doenças do Gato , Leiomiossarcoma , Neoplasias Uterinas , Animais , Gatos , Feminino , Carcinossarcoma/veterinária , Carcinossarcoma/patologia , Doenças do Gato/cirurgia , Doenças do Gato/patologia , Células Gigantes/patologia , Leiomiossarcoma/patologia , Leiomiossarcoma/veterinária , Osteoclastos , Neoplasias Uterinas/cirurgia , Neoplasias Uterinas/veterinária , Neoplasias Uterinas/patologia
5.
Curr Oncol ; 29(10): 7607-7623, 2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36290878

RESUMO

Uterine carcinosarcoma (UCS) is a highly aggressive gynecologic malignancy. Recurrent or persistent/progressive disease is usually fatal. We aimed to investigate the management and prognosis of these patients. Clinical records of UCS patients from June 1987 to April 2020 were retrospectively reviewed. The stage was re-assigned with the FIGO 2009 staging system. Univariate and multivariate analyses were used to identify the independent predictors of survival after recurrence (SAR) and cancer-specific survival (CSS). Of the 168 patients, 98 experienced treatment failure. The median time to treatment failure (TTF) was 8.1 months (range: 0.0-89.1). The median follow-up time of censored patients was 32.0 months (range: 16.8-170.7). The 5-year SAR rates of those with recurrent or persistent/progressive disease were 7.6%. On multivariate analysis, salvage therapy mainly using radiotherapy (HR 0.27, 95% CI: 0.10-0.71) or chemotherapy (HR 0.41, 95% CI: 0.24-0.72) or chemoradiotherapy (CRT) (HR 0.33, 95% CI: 0.15-0.75) were associated with improved SAR, whereas disseminated recurrence was associated with significantly worse SAR (HR 3.94, 95% CI: 1.67-9.31, p = 0.002). Salvage therapy using radiotherapy or chemotherapy or CRT significantly improved SAR. Surgery significantly improved CSS but not SAR, adjusting for confounding factors.


Assuntos
Carcinossarcoma , Neoplasias Uterinas , Humanos , Feminino , Carcinossarcoma/patologia , Carcinossarcoma/cirurgia , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/patologia , Prognóstico
6.
Diagn Pathol ; 17(1): 76, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36199118

RESUMO

Skin metastasis of ovarian cancer is extremely rare. We report an unusual case of ovarian carcinosarcoma with cutaneous metastasis of carcinomatous component that displayed distinct clinical manifestation. A 48-year-old woman presented to the dermatologist complaining of a new onset of erythematous, plaque-like skin rash with multiple small nodules on the left inner thigh, the area measuring 8 × 5cm. While the patient had no history of dermatologic conditions, she underwent a total hysterectomy and bilateral salpingo-oophorectomy, omentectomy, and lymph node dissection 16 months ago with a pathology confirmed stage IIIC ovarian carcinosarcoma. Of note, the carcinomatous component, mainly adenocarcinoma with hybrid features of seromucinous, endometrioid and minor high-grade serous carcinoma, involved bilateral fallopian tubes, omentum, and parametrium with extensive lymph node metastases. A skin biopsy specimen revealed an adenocarcinoma involving epidermis, dermis, and subcutaneous tissue with nodular contours, consistent with metastatic carcinomatous component of carcinosarcoma. Both carcinomatous component of primary ovarian carcinosarcoma and metastatic adenocarcinoma in the skin demonstrated Pax8, WT-1, and ER positivity and a mutation pattern of p53. The patient passed away 15 months after identification of skin metastasis. This case represents a unique example of cutaneous metastasis of ovarian carcinosarcoma with distinct clinical manifestation and detailed histopathological description. Alertness to the possibility of cutaneous metastasis, in combination with clinical history, morphological and immunohistochemical findings, is critical for a definitive classification.


Assuntos
Adenocarcinoma , Carcinossarcoma , Neoplasias Ovarianas , Neoplasias Cutâneas , Carcinossarcoma/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Neoplasias Cutâneas/patologia , Proteína Supressora de Tumor p53
7.
Cancer Genomics Proteomics ; 19(6): 747-760, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36316041

RESUMO

BACKGROUND/AIM: This study aimed to investigate the clinicopathological, prognostic and molecular characteristics of uterine mesonephric-like carcinosarcoma (MLCS). PATIENTS AND METHODS: We collected clinical, pathological, and genetic information from 12 MLCS patients, and analyzed their differences from mesonephric-like adenocarcinoma (MLA) and conventional endometrial carcinosarcoma (CECS). RESULTS: The epithelial component was exclusively MLA in all MLCS cases. Metastatic and recurrent tumors consisted predominantly or exclusively of MLA in the majority of MLCS cases. Patients with MLCS and MLA presented with more advanced-stage disease than those with CECS. They also exhibited post-treatment recurrence and lung metastases more frequently than CECS. Disease-free survival rates of MLCS and MLA were shorter than those of CECS. Tumor protein 53 gene mutations were detected in four MLCS cases. CONCLUSION: The predominance or exclusive presence of MLA in metastatic and recurrent tumors highlights the possibility that MLA may determine the clinical outcomes of patients with MLCS. Further studies are required to provide direct molecular evidence of the monoclonal origin of uterine MLCS.


Assuntos
Adenocarcinoma , Carcinossarcoma , Neoplasias do Endométrio , Feminino , Humanos , Prognóstico , Carcinossarcoma/genética , Carcinossarcoma/patologia , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Adenocarcinoma/patologia
8.
Am J Dermatopathol ; 44(11): 846-849, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36075572

RESUMO

ABSTRACT: Merkel cell carcinoma with a sarcomatous component is very rare, with only 12 cases reported in the literature, often with overtly malignant myoid differentiation. We report a case of metastatic Merkel cell carcinosarcoma presenting in a lymph node 6 months after a diagnosis of cutaneous Merkel cell carcinoma with conventional histologic features. The metastatic lesion showed a unique biphasic appearance with admixed populations of neuroendocrine epithelial cells and fascicles of mitotically active spindle cells with mild cytological atypia. In addition to the immunomorphological features, a common molecular profile between the epithelial and mesenchymal components further supported the notion of carcinosarcoma in this case. To the best of our knowledge, a bland sarcomatous component has not been previously described in Merkel cell carcinosarcoma, which can be easily overlooked as a reactive stromal reaction microscopically.


Assuntos
Carcinoma de Célula de Merkel , Carcinossarcoma , Neoplasias Cutâneas , Carcinoma de Célula de Merkel/cirurgia , Carcinossarcoma/patologia , Carcinossarcoma/cirurgia , Humanos , Células de Merkel/patologia , Pele/patologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia
9.
Am J Case Rep ; 23: e937548, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36176184

RESUMO

BACKGROUND Sarcomatoid carcinoma is a rare tumor that can occur in different organs and anatomical locations. Colonic sarcomatoid carcinoma, also known as carcinosarcoma, is an extremely rare tumor, with only 32 cases reported world-wide. The pathogenesis and guidelines for treatment are poorly understood due to the rarity and invasiveness of the disease. CASE REPORT A 77-year-old woman presented with worsening lower abdominal pain and associated fever after having initially been diagnosed with stump appendicitis and associated phlegmon 3 weeks prior, which was treated with antibiotics. Repeat imaging revealed an extraluminal versus perforated colonic mass with associated phlegmon. The patient's condition continued to worsen, with development of obstructive-like symptoms, resulting in operative intervention involving a R2 right hemicolectomy, stapled ileo-colostomy, and partial omentectomy. The patient had an uneventful remainder of her hospitalization other than continued lower abdominal pain. After initial discharge, the patient presented to an outside hospital due to continued deterioration of health, with findings of an additional mass, likely secondary to the previous lymphadenopathy. Ultimately, goals of care were discussed, and the decision was made to provide palliative care, and the patient died due to her illness 32 days after the initial procedure. CONCLUSIONS Carcinosarcoma is an extremely rare tumor with scant research guiding treatment guidelines. Current guidelines gathered from previous case reports suggest treating colorectal carcinosarcoma as adenocarcinoma. Additional research and studies are needed to establish appropriate therapeutic guidelines for carcinosarcoma.


Assuntos
Carcinoma , Carcinossarcoma , Dor Abdominal , Idoso , Antibacterianos , Carcinossarcoma/diagnóstico , Carcinossarcoma/patologia , Carcinossarcoma/cirurgia , Celulite (Flegmão) , Colo Ascendente/patologia , Feminino , Humanos
10.
Mol Carcinog ; 61(10): 924-932, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35848137

RESUMO

The genetic concordance and heterogeneity of the two components of pulmonary carcinosarcoma (PCS), carcinoma, and sarcoma, have not been fully elucidated because of its rare occurrence. We performed targeted sequencing of the carcinoma and sarcoma components of four PCSs to identify genetic similarities and differences. Formalin-fixed paraffin-embedded tissue samples were macroscopically or microscopically dissected. DNA was extracted from each component, and genetic alterations were analyzed separately. Moreover, we performed RNA-seq analysis on both components of one PCS to compare differences in gene expression profiles. The carcinoma part consisted of adenocarcinoma in two cases, squamous cell carcinoma in one, and adenosquamous carcinoma in the last. TP53 mutation was observed in three samples from the trunk, although it was detected only in the sarcoma part in one case. No specific driver gene mutation was observed; however, KRAS mutations were observed in one case in the trunk. RNA-seq analysis revealed that the rhabdomyosarcoma component expressed various genes related to muscle development, whereas the carcinoma component did not; and that gene expression overall was completely different between the two components. Our study revealed that the two different components of PCS shared common gene mutations in most cases. Although gene expression was different among components, if driver genes such as KRAS were detected in PCS, molecular targeted therapy could be beneficial even when the tumor contains a sarcoma component.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Carcinossarcoma , Neoplasias Pulmonares , Sarcoma , Carcinoma de Células Escamosas/genética , Carcinossarcoma/genética , Carcinossarcoma/metabolismo , Carcinossarcoma/patologia , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo
11.
PLoS One ; 17(7): e0271526, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35862371

RESUMO

OBJECTIVE: This study aimed to determine 5-year progression-free and overall survival in patients with uterine carcinosarcoma, to determine clinical and surgical-pathologic features, to recognize patterns of recurrence and to identify prognostic factors influencing progression-free survival (PFS) and overall survival (OS). DESIGN: This was a single institution, retrospective 10-year review of patients treated at Tygerberg Hospital in South Africa with pathologically confirmed uterine carcinosarcoma. METHODS: A total of 61 patients were studied. Demographic, clinicopathological, treatment and outcome information were obtained. Kaplan-Meier survival analysis and Cox proportional hazards models were used to determine the effects of variables on PFS and OS. RESULTS: Eighteen patients (29%) presented as FIGO stage I disease, 5 patients (8%) as stage II, 16 patients (26%) as stage III and 22 patients (36%) as stage IV disease. Fifty of the 61 patients (82%) had surgery. Five-year PFS and 5-year OS were 17.3% (CI 8.9%-27.9%) and 19.7% (CI 10.6%-30.8%), respectively. Seventeen patients presented with recurrence of which 5 (29.4%) were local and 12 (70.6%) were outside the pelvis. In the univariate analysis, tumour diameter ≥ 100mm (HR 4.57; 95% CI 1.59-13.19; p-value 0.005) was associated with 5-year PFS and in univariate analysis of OS, a positive family history (HR 0.42; 95% CI 0.18-0.99; p-value 0.047), receiving a full staging operation (HR 0.37; 95% CI 0.18-0.78; p-value 0.008) and receiving any other modality of treatment, with or without surgery, (HR 0.48; 95% CI 0.27-0.85; p-value 0.012) were associated with better survival. An abnormal cervical smear (HR 2.4; 95% CI 1.03-5.6; p-value 0.041), late-stage disease (HR 3.48; 95% CI 1.79-6.77; p-value < 0.001), presence of residual tumour (HR 3.66; 95% CI 1.90-7.02; p-value < 0.001), myometrial invasion more than 50% (HR 2.29; 95% CI 1.15-4.57; p-value 0.019), cervical involvement (HR 3.38; 95% CI 1.64-6.97; p-value 0.001) and adnexal involvement (HR 3.21; 95% CI 1.56-6.63; p-value 0.002) were associated with a higher risk of death. In the multivariate analysis, full staging operation was associated with a risk of progression of disease (HR 3.49; 95% CI 1.17-10.41; p-value 0.025). Advanced stage (HR 4.2; 95% CI 2.09-8.44; p-value < 0.001) was associated with a higher risk of death. Any other modality of treatment (HR 0.28; 95% CI 0.15-0.53; p-value < 0.001) and full staging laparotomy (HR 0.27; 95% CI 0.12-0.59; p-value 0.001) was a protective factor for death. CONCLUSIONS: Carcinosarcoma is an aggressive cancer with poorer survival in this specific cohort than has been described in other contemporary cohorts. Biological or genetic factors are a possible explanation for lower overall survival in this population. Although it is also possible that later diagnosis and poor access to health care contribute to poorer survival. Most recurrences occur outside of the pelvis. Full staging surgery (including pelvic lymphadenectomy) and additional use of other modalities (either for radical or palliative intent) improve survival.


Assuntos
Carcinossarcoma , Neoplasias Uterinas , Carcinossarcoma/patologia , Carcinossarcoma/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Uterinas/cirurgia
12.
BMJ Case Rep ; 15(7)2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35858746

RESUMO

Herein, we report a man in his 70s with gallbladder mass. Microscopically, the tumour demonstrated moderately differentiated adenocarcinoma, sarcoma with focal chondroid differentiation and high-grade neuroendocrine tumour component arising in an intracholecystic papillary neoplasm. The patient did not receive adjuvant chemotherapy in the setting of complete surgical resection. Patient presented with extensive metastasis after 47 months and died 3 months later. Due to the low incidence and poor prognosis of this tumour, it is essential to gather all the individual experience-based information. To our knowledge, this is the first reported case of carcinosarcoma arising from intracholecystic papillary-tubular neoplasm.


Assuntos
Adenocarcinoma , Carcinoma Neuroendócrino , Carcinossarcoma , Neoplasias da Vesícula Biliar , Adenocarcinoma/patologia , Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/cirurgia , Carcinossarcoma/patologia , Carcinossarcoma/cirurgia , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Masculino
13.
Br J Cancer ; 127(6): 1034-1042, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35715633

RESUMO

BACKGROUND: Ovarian carcinosarcoma (OCS) is an uncommon, biphasic and highly aggressive ovarian cancer type, which has received relatively little research attention. METHODS: We curated the largest pathologically confirmed OCS cohort to date, performing detailed histopathological characterisation, analysis of features associated with survival and comparison against high-grade serous ovarian carcinoma (HGSOC). RESULTS: Eighty-two OCS patients were identified; overall survival was poor (median 12.7 months). In all, 79% demonstrated epithelial components of high-grade serous (HGS) type, while 21% were endometrioid. Heterologous elements were common (chondrosarcoma in 32%, rhabdomyosarcoma in 21%, liposarcoma in 2%); chondrosarcoma was more frequent in OCS with endometrioid carcinomatous components. Earlier stage, complete resection and platinum-containing adjuvant chemotherapy were associated with prolonged survival; however, risk of relapse and mortality was high across all patient groups. Histological subclassification did not identify subgroups with distinct survival. Compared to HGSOC, OCS patients were older (P < 0.0001), more likely to be FIGO stage I (P = 0.025), demonstrated lower chemotherapy response rate (P = 0.001) and had significantly poorer survival (P < 0.0001). CONCLUSION: OCS represents a distinct, highly lethal form of ovarian cancer for which new treatment strategies are urgently needed. Histological subclassification does not identify patient subgroups with distinct survival. Aggressive adjuvant chemotherapy should be considered for all cases, including those with early-stage disease.


Assuntos
Carcinossarcoma , Condrossarcoma , Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/patologia , Carcinossarcoma/patologia , Carcinossarcoma/cirurgia , Condrossarcoma/patologia , Cistadenocarcinoma Seroso/tratamento farmacológico , Feminino , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia
14.
Int J Mol Sci ; 23(11)2022 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-35682908

RESUMO

Endometrial cancer (EC) is the most common gynaecological malignancy. Nucleolin (NCL) is involved in rDNA transcription, cell proliferation, and apoptosis, with high expression associated with worse overall survival (OS) in other adenocarcinomas. Our aims were to assess NCL gene and protein expression and explore the differential expression of NCL-associated genes (NAGs) in endometrial carcinogenesis. Endometrial samples were obtained from 157 women to include healthy, hyperplastic (EH), EC, and metastatic groups. RT-qPCR and immunohistochemistry were employed to assess NCL gene and protein levels. In silico analysis of NAGs in TCGA and GEO datasets was performed, with the prognostic value determined via Human Protein Atlas. NCL mRNA level of EC was lower than in healthy post-menopausal endometrium (p < 0.01). EH samples had lower NCL immuno-expression scores than healthy pre-menopausal (p < 0.001), benign post-menopausal (p < 0.01), and EC (p < 0.0001) samples. Metastatic lesions demonstrated higher NCL quick scores than primary tissue (p = 0.04). Higher NCL Immuno quick scores carried a worse OS in high-grade EC (p = 0.01). Interrogating Uterine Corpus Endometrial Carcinoma (TCGA-UCEC) and Uterine Carcinosarcoma (TCGA-UCS) cohorts revealed NCL to be the most highly upregulated gene in carcinosarcoma, with S100A11, LMNB2, RERG, E2F1 and CCNA2 representing key dysregulated NAGs in EC. Since NCL is implicated in transforming hyperplastic glands into cancer, with further involvement in metastasis, it is suggested to be a promising target for better-informed diagnosis, risk stratification, and management of EC.


Assuntos
Carcinossarcoma , Hiperplasia Endometrial , Neoplasias do Endométrio , Lesões Pré-Cancerosas , Carcinogênese/metabolismo , Carcinossarcoma/patologia , Hiperplasia Endometrial/genética , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/patologia , Endométrio/metabolismo , Feminino , Humanos , Hiperplasia/metabolismo , Fosfoproteínas , Lesões Pré-Cancerosas/patologia , Proteínas de Ligação a RNA
16.
Crit Rev Oncol Hematol ; 175: 103701, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35533817

RESUMO

The uterine carcinosarcoma (UCS) is a rare entity with poor prognosis. Treatment of FIGO I-II UCS usually consists of surgery with or without adjuvant treatment. Due to the high metastatic potential, aggressive combined modality adjuvant treatment approaches, consisting of chemo- and radiotherapy, have been of interest. Our systematic review aims to compare survival, disease control and toxicity profiles in patients receiving adjuvant chemoradiation to other adjuvant strategies (e.g.observation, chemotherapy or radiotherapy). A total of ten studies were included for a combined cohort size of 6520 patients. Generally, the studies showed a trend towards improved disease control and survival in patients undergoing adjuvant multimodal treatment, although statistical significance was often not reached. Selection bias and non-randomized treatment allocation pose serious challenges to extrapolate these outcomes to clinical practice. We recommend additional prospective research on the role of adjuvant chemoradiation in FIGO I-II UCS.


Assuntos
Carcinossarcoma , Neoplasias Uterinas , Carcinossarcoma/tratamento farmacológico , Carcinossarcoma/patologia , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Humanos , Estadiamento de Neoplasias , Estudos Prospectivos , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias Uterinas/patologia , Útero/patologia
17.
Int J Mol Sci ; 23(7)2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35409155

RESUMO

Endometrial cancer (EC) is one of the most common gynecologic cancers worldwide. There were 417,367 newly diagnosed cases and 97,370 deaths due to this disease worldwide in 2020. The incidence rates have increased over time, especially in countries with rapid socioeconomic transitions, and EC has been the most prevalent gynecologic malignancy in Taiwan since 2012. The new EC molecular classifications of The Cancer Genome Atlas (TCGA) Research Network include clear-cell carcinoma, serous carcinoma, and carcinosarcoma, while undifferentiated/dedifferentiated EC (UDEC) is not mentioned, and most previous clinical trials for EC have not included UDEC. UDEC is rare, has an aggressive growth pattern, tends to be diagnosed at an advanced stage, and is resistant to conventional chemotherapy. In this review, case series or case reports on the clinical features and genomic/epigenetic and expression profiles on UDEC data are summarized in order to identify potential molecular targets for current and future research.


Assuntos
Carcinoma , Carcinossarcoma , Cistadenocarcinoma Seroso , Neoplasias do Endométrio , Carcinoma/patologia , Carcinossarcoma/genética , Carcinossarcoma/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Taiwan
18.
Int J Surg Pathol ; 30(8): 891-899, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35360975

RESUMO

POLE mutation-type endometrial cancer is characterized by an extremely high tumor mutation burden. Most POLE mutation-type endometrial cancers are histologically endometrioid carcinomas, and POLE mutation-type carcinosarcomas are rare among endometrial cancers. We report a case of endometrial and pelvic cancer in a 53-year-old woman who was analyzed using next-generating sequencing. The endometrial lesion harbored a p.T457del POLE mutation with an elevated tumor mutation burden and low microsatellite instability. The pelvic lesion showed divergent histological features, consisting of high-grade endometrioid carcinoma, neuroendocrine carcinoma, and chondrosarcoma. In addition to the common POLE mutation detected in the endometrial lesion, the pelvic lesion in each element showed additional gene mutations in a hierarchical manner. Therefore, it is indicated that the p.T457del POLE mutation is a pathogenic mutation and may be related to POLE mutation-induced carcinogenesis and divergent morphogenesis in endometrial cancer.


Assuntos
Neoplasias Ósseas , Carcinoma Endometrioide , Carcinossarcoma , Neoplasias do Endométrio , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/patologia , Carcinossarcoma/genética , Carcinossarcoma/patologia , Mutação
19.
J Am Soc Cytopathol ; 11(4): 210-217, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35414490

RESUMO

INTRODUCTION: Limited data are present to study the cytologic findings of Mullerian carcinosarcoma (MCS) in serous fluid samples and clinicopathologic features that are associated with cytology yield. MATERIALS AND METHODS: We studied 30 MCS patients diagnosed on surgical resection samples, and reviewed their cytomorphology and immunophenotypes on concurrent serous fluid cytology samples. Clinicopathologic features were also compared between cases with positive or negative cytology. RESULTS: Fourteen out of 30 patients showed positive cytology, including 12 patients with only carcinomatous components and 2 with sarcomatous cells. Cytomorphology of MCS was mostly consistent with adenocarcinoma, with psammoma bodies occasionally present. The 2 cases with sarcomatous cells showed spindle cells without signs of heterologous differentiation. PAX8 was positive in 10 of 11 cases, and WT1 was positive in 8 of 11 cases including the case with negative PAX8. In 1 case, PAX8 and WT1 were only positive in the sarcomatous but not in carcinomatous cells. MOC31 showed consistent positivity in carcinomatous cells, which appeared to be more sensitive than B72.3 (positive in 72.7%). In addition, sarcomatous cells showed CD10 positivity in 1 case. Clinically, patients who developed body cavity effusions or with higher stage diseases were more likely to have positive cytology. CONCLUSIONS: Cytologic diagnosis of MCS in the serous fluid is challenging due to the rare presence of sarcomatous component. Staining both PAX8 and WT1 is recommended to confirm their Mullerian origin, although both markers may be positive only in sarcomatous cells. Cytology yield of MCS is highly associated with the disease stage.


Assuntos
Adenocarcinoma , Carcinossarcoma , Adenocarcinoma/patologia , Carcinossarcoma/diagnóstico , Carcinossarcoma/patologia , Citodiagnóstico , Humanos , Imuno-Histoquímica
20.
Pathol Oncol Res ; 28: 1610134, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401056

RESUMO

Introduction: Gallbladder carcinosarcoma with osteoclast-like multinucleated giant cells is known to be most uncommon form of gallbladder cancer. Owing to its rarity, the pathogenesis of gallbladder carcinosarcoma with osteoclast-like multinucleated giant cells is largely unknown. Case Presentation: We present a case of carcinosarcoma with osteoclast-like multinucleated giant cells in the gallbladder. A 57-year-old woman visited our hospital due to jaundice. An examination revealed calculous cholecystitis and gallbladder carcinoma. After cholecystectomy, macroscopic examination disclosed one whitish mass and another distinct brown and pendulous mass in the body of the gallbladder. A pathological examination revealed that each mass had a different histological type: adenosquamous carcinoma and carcinosarcoma with osteoclast-like multinucleated giant cells. Immunohistochemistry revealed that these osteoclast-like multinucleated giant cells are CD68(+), CD163(-), and MIB-1(-). In addition, the osteoclast-like multinucleated giant cells showed the strong expression of RANK and sarcoma cells around the osteoclast-like multinucleated giant cells, were positive for RANKL. Furthermore, RUNX2 was positive for some sarcoma cells. The result indicated that osteoclastic and osteoblast-like differentiation occurred in our case. Conclusion: To our knowledge, this is the first case to show the interaction of RANK-RANKL signaling in gallbladder carcinosarcoma with osteoclast-like multinucleated giant cells.


Assuntos
Carcinossarcoma , Neoplasias da Vesícula Biliar , Carcinossarcoma/patologia , Feminino , Neoplasias da Vesícula Biliar/patologia , Células Gigantes/metabolismo , Células Gigantes/patologia , Humanos , Pessoa de Meia-Idade , Osteoclastos/patologia , Relatório de Pesquisa
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