PEComas: the past, the present and the future Martignoni, Guido; Pea, Maurizio; Reghellin, Daniela ...
Virchows Archiv : an international journal of pathology,
02/2008, Letnik:
452, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The perivascular epithelioid cell (PEC) is a cell type constantly present in a group of tumors called PEComas. PEC expresses myogenic and melanocytic markers, such as HMB45 and actin. Recently, ...recurrent chromosomal alterations have been demonstrated in PEC. At present, PEComa is a widely accepted entity. In the past 10 years, the use of this term has allowed to report and describe numerous cases permitting to start highlighting the biology of this group of lesions. PEComas are related to the genetic alterations of tuberous sclerosis complex (TSC), an autosomal dominant genetic disease due to losses of TSC1 (9q34) or TSC2 (16p13.3) genes which seem to have a role in the regulation of the Rheb/mTOR/p70S6K pathway. There are some open questions about PEComas regarding its histogenesis, the definition of epithelioid angiomyolipoma and the identification of the histological criteria of malignancy. An innovative therapeutic trial using rapamycin is under way for tumors occurring in TSC such as renal angiomyolipoma and lymphangioleiomyomatosis. Its success could provide the rationale for the use of the same drug in other lesions composed of PECs, especially in the malignant ones.
Eosinophilic, solid and cystic (ESC) renal cell carcinoma (RCC) is characterized by a solid and cystic architecture with cells showing abundant eosinophilic cytoplasm with hobnail arrangement and a ...cytokeratin 7-negative/cytokeratin 20-positive immunophenotype. Recent studies have suggested that bi-allelic events affecting TSC genes might play an important role for such tumors. However, only indirect evidence of the clonal origin of TSC mutation has been gathered so far. Therefore, in this paper we aimed to perform multi-regional tumor sampling molecular analysis in four ESC RCC cases that had been completely embedded, three sporadic and one occurring in a patient with tuberous sclerosis complex (TSC). Histologically, the 4 cases showed cystic and solid architecture and cells with abundant eosinophilic cytoplasm with cytoplasmic stippling and round to oval nuclei. Immunohistochemistry showed at least focal expression of cytokeratin 20 in all tissue samples and negative cytokeratin 7, as well as diffuse positivity for S100A1 and at least focal expression of cathepsin K in three out of four cases. The sporadic cases showed the same somatic TSC1 mutations in all tissue samples analyzed, while the TSC-associated case showed the same TSC1 alteration in both normal tissue and all tumor samples analyzed, proving the germline nature of the alteration. In conclusion, our data demonstrate that clonal TSC loss is a key event in ESC RCC and support considering ESC RCC as an entity given its distinct morphologic, immunophenotypical and molecular characteristics.
Background Limited data are available for pancreatic neuroendocrine carcinomas (NEC) defined by 2010 World Health Organization (WHO) criteria (mitotic count >20 mitoses/10 high-power fields and/or a ...Ki67 index of >20%), because most studies encompass heterogeneous cohorts of extrapulmonary/gastrointestinal NEC. Our aim was to evaluate the clinicopathologic characteristics, treatment, and prognosis of patients with pancreatic NEC defined by the 2010 WHO criteria. Methods We conducted a retrospective analysis of 59 patients with a histologic diagnosis of NEC between 1990 and 2012. All cases were re-reviewed and classified according to the WHO 2010 classification and the WHO 2000 criteria. Results All patients had stage III pancreatic NEC ( n = 34; 58%) or IV pancreatic NEC ( n = 25; 43%). Overall, 49 (83%) had poorly differentiated (PD) and 10 (17%) had a well-differentiated (WD) morphology. Fifteen patients (26%) were operated with curative intent (R0/R1), and 8 (14%) were R2 resections. Median disease-specific survival (DSS) for the entire cohort was 14 months. Median DSS did not differ between patient not undergoing resection and those undergoing R2 resection (10 vs 12 months; P > .46), but DSS was greater for patients who underwent R0/R1 resection compared with those with no resection/R2 resection (35 vs 11 months; P < .005). WD morphologic NEC had a greater survival than PD ones (43 vs 12 months; P = .004). Performance status, R2 resection/no resection, PD morphologic NEC, and no medical treatment were independent predictors of poor survival. Conclusion Pancreatic NEC constitute a heterogeneous group of tumors. Although NEC is an aggressive disease, curative resection in localized disease is associated with improved survival. Morphologic WD pancreatic NEC represents a subgroup with what seems to be a markedly improved survival. Within the NEC category, tumor treatment should be individualized considering tumor morphology as well as the other 2010 WHO criteria.
The aim of our study was to define tissue and plasma miRNA signatures, which could potentially serve as diagnostic and prognostic markers in endometrioid endometrial cancer (EEC) and to investigate ...miRNA profiles in regard to clinicopathological characteristics. Tissue and plasma samples were collected from 122 women (77 EEC and 45 controls). Expression profiling of 866 human miRNAs and 89 human viral miRNAs was performed in 24 samples and was followed by qPCR validation in 104 patients. Expression of 16 miRNAs was analyzed in 48 plasma samples. Microarray study revealed regulation of 21 miRNAs in EEC tissues comparing to normal endometrium. Altered expression of 17 miRNAs was confirmed by qPCR performed in 104 tissue samples. Seven miRNAs were upregulated and two were downregulated in EEC plasma samples. Expression of a number of miRNAs was associated with International Federation of Gynecology and Obstetrics stage, grade, relapse and nodal metastases. Two miRNA signatures: miR‐92a/miR‐410 and miR‐92a/miR‐205/miR‐410 classified tumor tissues with higher accuracy in comparison to single miRNAs (AUC: 0.977, 95% CI: 0.927–0.996 and 0.984, 95% CI: 0.938–0.999, respectively). miRNA signature composed of miR‐205 and miR‐200a predicted relapse with AUC of 0.854 (95% CI: 0.691–0.951). Tissue miRNA signatures were independent prognostic markers of overall (miR‐1228/miR‐200c/miR‐429, HR: 2.98) and progression‐free survival (miR‐1228/miR‐429, HR: 2.453). Plasma miRNA signatures: miR‐9/miR‐1228 and miR‐9/miR‐92a, classified EEC plasma samples with high accuracy yielding AUCs of 0.909 (95% CI: 0.789–973) and 0.913 (95% CI: 0.794–0.976), respectively. We conclude that miRNA signatures hold a great promise to become noninvasive biomarkers for early EEC detection and prognosis.
What's new?
Endometrial cancer is the most common cancer of the female reproductive tract. In this study the authors identified microRNA (miRNA) signatures that allow distinguishing between endometrioid endometrial cancer (EEC) and control tissues and plasma samples. The microRNA signatures were also significantly associated with disease relapse as well as overall and progression‐free survival. Moreover, the work revealed associations of several miRNAs with clinicopathological characteristics, which contributes to the understanding of miRNAs involvement in EEC pathogenesis. The study suggests that miRNA signatures hold a great promise to become non‐invasive biomarkers for early EEC detection and prognosis.
Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are non-invasive neoplasms that are often observed in association with invasive pancreatic cancers, but their ...origins and evolutionary relationships are poorly understood. In this study, we analyze 148 samples from IPMNs, MCNs, and small associated invasive carcinomas from 18 patients using whole exome or targeted sequencing. Using evolutionary analyses, we establish that both IPMNs and MCNs are direct precursors to pancreatic cancer. Mutations in SMAD4 and TGFBR2 are frequently restricted to invasive carcinoma, while RNF43 alterations are largely in non-invasive lesions. Genomic analyses suggest an average window of over three years between the development of high-grade dysplasia and pancreatic cancer. Taken together, these data establish non-invasive IPMNs and MCNs as origins of invasive pancreatic cancer, identifying potential drivers of invasion, highlighting the complex clonal dynamics prior to malignant transformation, and providing opportunities for early detection and intervention.
Neuroendocrine carcinoma of the breast is considered a rare entity, and for this reason there are no data from prospective clinical trials on its optimal management. Early stage tumors are usually ...treated with the same strategy used for the other types of invasive breast cancer. Anthracycline‐ and taxane‐based regimens represent the most frequently administered chemotherapy in neoadjuvant and adjuvant setting, as well as for metastatic disease, although combinations of platinum compounds and etoposide have been widely used, in particular for small‐cell histology and tumors with a high proliferation index. For metastatic disease, a multimodality therapeutic strategy can be considered on an individual basis, with chemotherapy, endocrine therapy, peptide receptor radionuclide therapy, radiation therapy, surgery, or a combination of the above. In the near future, a better knowledge of the biology of these tumors will hopefully provide new therapeutic targets for personalized treatment. In this review, we discuss the current evidence and the future perspectives on diagnosis and treatment of neuroendocrine carcinoma of the breast.
Implications for Practice:
Neuroendocrine carcinoma of the breast (NECB) is a distinct entity of breast cancer. Clinical features and morphology are not helpful to distinguish NECB from other subtypes of breast cancer; therefore, immunohistochemistry markers for neuroendocrine differentiation, mainly chromogranin and synaptophysin, should be routinely used to confirm the diagnosis, especially in cases of mucinous or solid papillary carcinoma in which the suspicion of NECB may be relevant. Adjuvant treatment should be offered according to the same recommendations given for the other types of invasive breast cancer. An accurate diagnosis of NECB is also important in the metastatic setting, in which a multimodality approach including specific therapies such as peptide receptor radionuclide therapy can be considered.
摘要
乳腺神经内分泌癌被认为是罕见疾病, 因此其最佳治疗缺乏相关的前瞻性临床试验数据。对于早期肿瘤, 常采用与其他类型的浸润性乳腺癌相同的治疗策略。以蒽环类和紫杉烷类为基础的方案是新辅助治疗和辅助治疗最常用的方案, 对于转移性肿瘤也是如此; 但在针对小细胞组织学和高增殖指数肿瘤进行治疗时, 已广泛使用联合铂类化合物和依托泊甙的方案。对于转移性疾病, 应基于个体化治疗原则考虑采用多学科治疗策略, 包括化疗、内分泌治疗、多肽受体放射性核素治疗、放射治疗、手术或联合使用以上方案。在不久的将来, 更深入地了解这些肿瘤的生物学将有望为个体化治疗提供更多治疗靶点。我们在本综述中讨论了乳腺神经内分泌癌诊断和治疗的现有证据和未来展望。The Oncologist 2016;21:28–32
对临床实践的提示: 乳腺神经内分泌癌 (NECB) 是一种独特的乳腺肿瘤。NECB 的临床特征和形态学均难以将其与其他乳腺癌亚型区分开来, 因此神经内分泌分化的免疫组化标记物 (主要是嗜铬粒蛋白和突触素) 应常规用于该病的确诊, 尤其是在怀疑可能与 NECB 相关的粘液性或实性乳头状癌中。辅助治疗应按照其他浸润性乳腺癌指南的建议实施。NECB 的准确诊断在转移性疾病中同样重要, 对于这类患者应考虑采用包括特异性治疗方案如多肽受体放射性核素治疗在内的多学科治疗方案。
This review discusses the current evidence and the future perspectives on diagnosis and treatment of neuroendocrine carcinoma of the breast. A multimodality therapeutic strategy can be considered on an individual basis, with chemotherapy, endocrine therapy, peptide receptor radionuclide therapy, radiation therapy, surgery, or a combination. A better knowledge of the biology of these tumors will hopefully provide new therapeutic targets for personalized treatment.
Background
Data on long-term actual survival in patients with surgically resected pancreatic ductal adenocarcinoma (PDAC) are limited. The aim of this study was to evaluate the actual 5-year ...disease-specific survival (DSS) and post-recurrence survival (PRS) in patients who underwent pancreatectomy for PDAC.
Methods
Data from patients who underwent upfront surgical resection for PDAC between 2009 and 2014 were analyzed. Exclusion criteria included PDAC arising in the background of an intraductal papillary mucinous neoplasm and patients undergoing neoadjuvant therapy. All alive patients had a minimum follow-up of 60 months. Independent predictors of PRS, DSS, and survival > 5 years were searched.
Results
Of the 176 patients included in this study, 48 (27%) were alive at 5 years, but only 20 (11%) had no recurrence. Median PRS was 12 months. In the 154 patients after disease recurrence, independent predictors of shorter PRS were total pancreatectomy, G3 tumors, early recurrence (< 12 months from surgery), and no treatment at recurrence. Median DSS was 36 months. Independent predictors of DSS were CA19-9 at diagnosis > 200 U/mL, total pancreatectomy, N + status, G3 tumors and perineural invasion. Only the absence of perineural invasion was a favorable independent predictor of survival > 5 years.
Conclusion
More than one-quarter of patients who underwent upfront surgery for PDAC were alive after 5 years, although only 11% of the initial cohort were cancer-free. Long-term survival can also be achieved in tumors with more favorable biology in an upfront setting followed by adjuvant chemotherapy.
Neuroendocrine carcinomas(NEC) of the pancreas are defined by a mitotic count > 20 mitoses/10 high power fields and/or Ki67 index > 20%, and included all the tumors previously classified as ...poorly differentiated endocrine carcinomas. These latter are aggressive malignancies with a high propensity for distant metastases and poor prognosis, and they can be further divided into small- and large-cell subtypes. However in the NEC category are included also neuroendocrine tumors with a well differentiated morphology but ki67 index > 20%. This category is associated with better prognosis and does not significantly respond to cisplatin-based chemotherapy, which represents the gold standard therapeutic approach for poorly differentiated NEC. In this review, the differences between well differentiated and poorly differentiated NEC are discussed considering both pathology, imaging features, treatment and prognostic implications. Diagnostic and therapeutic flowcharts are proposed. The need for a revision of current classification system is stressed being well differentiated NEC a more indolent disease compared to poorly differentiated tumors.
Background and aims
Clinicopathological characteristics of gastric cancer (GC) are changing, especially in the West with a decreasing incidence of distal, intestinal-type tumours and the ...corresponding increasing proportion of tumours with Laurén diffuse or WHO poorly cohesive (PC) including signet ring cell (SRC) histology. To accurately assess the behaviour and the prognosis of these GC subtypes, the standardization of pathological definitions is needed.
Methods
A multidisciplinary expert team belonging to the European Chapter of International Gastric Cancer Association (IGCA) identified 11 topics on pathological classifications used for PC and SRC GC. The topics were debated during a dedicated Workshop held in Verona in March 2017. Then, through a Delphi method, consensus statements for each topic were elaborated.
Results
A consensus was reached on the need to classify gastric carcinoma according to the most recent edition of the WHO classification which is currently WHO 2010. Moreover, to standardize the definition of SRC carcinomas, the proposal that only WHO PC carcinomas with more than 90% poorly cohesive cells having signet ring cell morphology have to be classified as SRC carcinomas was made. All other PC non-SRC types have to be further subdivided into PC carcinomas with SRC component (< 90% but > 10% SRCs) and PC carcinomas not otherwise specified (< 10% SRCs).
Conclusion
The reported statements clarify some debated topics on pathological classifications used for PC and SRC GC. As such, this consensus classification would allow the generation of evidence on biological and prognostic differences between these GC subtypes.
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