Original ContributionsPulmonary atypical carcinoid: Predictors of survival in 106 cases
Abstract
Pulmonary neuroendocrine tumors (NE) include a spectrum of tumors from typical carcinoid (TC) to atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCLC). Little is known about prognostic predictors for AC because of its rarity. Survival analysis was performed on 106 ACs with clinical follow-up from the AFIP and the Pathology Panel of the International Association for the Study of Lung Cancer (IASLC). The tumors fulfilled the 1999 WHO/IASLC criteria for AC of a NE tumor with a mitotic rate of 2 to 10 per 2 mm2 of viable tumor or coagulative necrosis. Multiple clinical and histologic features were analyzed by Kaplan-Meier and Cox regression analysis. Of the clinical features, higher stage (P = .003) and a tumor size of 3.5 cm or greater (P = .003) were associated with a worse prognosis. Features that were histologically unfavorable by univariate analysis were mitotic rate (P = .002), pleomorphism (P = .018), and aerogenous spread (P = .007). Histologically favorable features by univariate analysis were the presence of palisading (P = .008), papillary (P = .039), pseudoglandular (P = .026), and rosette (P = .022) patterns. Female gender showed a trend toward a poorer prognosis (P = .085) and was included in the multivariate model. Multivariate analysis stratified for stage showed mitoses (P < .001), a tumor size of 3.5 cm or greater (P = .017), and female gender (P = .012) to be the only negative independent predictors of prognosis and the presence of rosettes (P = .016) to be the only independent positive predictor. We further divided the AC into subgroups of low (2 to 5 mitoses/2 mm2) and high (6 to 10 mitoses/2 mm2) mitotic rate and compared the survival with TC and with LCNEC. Within the category of AC, the patients with a higher mitotic rate had a significantly worse survival than those with a lower mitotic rate (P < .001) stratified for stage. Five- and 10-year survival rates for AC (61% and 35%, respectively) stratified for stage were significantly worse than for TC and better than that for LCNEC and SCLC. Chemotherapy or radiation therapy was given in 12 of 52 and 14 of 52 cases, respectively, but the data were insufficient to evaluate tumor response. We conclude that AC is an aggressive neuroendocrine neoplasm with survival intermediate between TC and LCNEC and SCLC. Higher mitotic rate, tumor size of 3.5 cm or greater, female gender, and presence of rosettes are the only independent predictors of survival. Surgical resection remains the treatment of choice, and the role of chemotherapy and radiation therapy remains to be proven. HUM PATHOL 31:1255-1265. This is a US Government work. There are no restrictions on its use.
References (0)
Cited by (229)
Common practice issues in pulmonary cytology/small biopsy: Diagnostic pitfalls and appropriate use of immunohistochemical stains
2024, Human Pathology ReportsWith the increasing emphasis on early detection of lung carcinoma in clinical practice, the utilization of small biopsies including cytology specimens has become more prevalent and an integral part of the diagnostic process. While holding immense significance for patient care and decision-making, the accurate identification of lung carcinoma from these small biopsies poses challenges. There is a significant overlap in the characteristics among benign, reactive, and malignant processes. This is aggravated by the absence of distinguishing biomarkers. Preserving specimen material for additional cytogenetic and molecular testing has also gained prominence to enable targeted precision medicine.
The focus of our review is directed towards understanding the morphologic attributes and potential diagnostic mimickers associated with the most frequent types of lung carcinoma observed in small biopsies. Additionally, we emphasize the importance of proper immunohistochemical staining practices to preserve tissue for further molecular testing.
Management of non-hepatic distant metastases in neuroendocrine neoplasms
2023, Best Practice and Research: Clinical Endocrinology and MetabolismNeuroendocrine neoplasms represent an uncommon disease with an increasing incidence. Thanks to improvements in diagnostic and therapeutic methods, metastases previously considered uncommon, such as bone metastases, or even very rare, such as brain, orbital and cardiac metastases, are more frequently found in daily practice. Due to the great heterogeneity of these neoplasms, there is a lack of high-quality evidence on the management of patients with these types of metastases. The aim of this review is to provide the current state of the art, reviewing neuroendocrine neoplasm specific studies and useful information from other tumor types and to propose a treatment recommendation with algorithms to consider in daily clinical practice.
Early-Stage Primary Lung Neuroendocrine Tumors Treated With Stereotactic Body Radiation Therapy: A Multi-Institution Experience
2023, International Journal of Radiation Oncology Biology PhysicsCurrent guidelines recommend surgery as standard of care for primary lung neuroendocrine tumor (LNET). Given that LNET is a rare clinical entity, there is a lack of literature regarding treatment of LNET with stereotactic body radiation therapy (SBRT). We hypothesized that SBRT could lead to effective locoregional tumor control and long-term outcomes.
We retrospectively reviewed 48 tumors in 46 patients from 11 institutions with a histologically confirmed diagnosis of LNET, treated with primary radiation therapy. Data were collected for patients treated nonoperatively with primary radiation therapy between 2006 and 2020. Patient records were reviewed for lesion characteristics and clinical risk factors. Kaplan-Meier analysis, log-rank tests, and Cox multivariate models were used to compare outcomes.
Median age at treatment was 71 years and mean tumor size was 2 cm. Thirty-two lesions were typical carcinoid histology, 7 were atypical, and 9 were indeterminate. The most common SBRT fractionation schedule was 50 to 60 Gy in 5 daily fractions. Overall survival at 3, 6, and 9 years was 64%, 43%, and 26%, respectively. Progression-free survival at 3, 6, and 9 years was 88%, 78%, and 78%, respectively. Local control at 3, 6, and 9 years was 97%, 91%, and 91%, respectively. There was 1 regional recurrence in a paraesophageal lymph node. No grade 3 or higher toxicity was identified.
This is the largest series evaluating outcomes in patients with LNET treated with SBRT. This treatment is well tolerated, provides excellent locoregional control, and should be offered as an alternative to surgical resection for patients with early-stage LNET, particularly those who may not be ideal surgical candidates.
Neuroendocrine neoplasms of the lung
2022, Practical Pulmonary Pathology: A Diagnostic ApproachThe pathologic diagnosis of neuroendocrine tumors of the lung requires integration of histologic and cytologic findings with clinical and radiologic consideration. Despite advances in diagnosis, challenges remain in their accurate classification. A search of relevant literature in PubMed was conducted with terms that included neuroendocrine, lung, and the terms in the chapter subheadings of individual entities combined with lung. In addition, a review of archived cases in the file of Weill Cornell Pathology was conducted.
Neuroendocrine tumors, including preinvasive lesions, were described from the perspective of classification, clinical presentation, pathology, ancillary studies, molecular findings, and treatment impact. New information focused on diagnostic criteria for large cell neuroendocrine carcinoma including overlap with small cell carcinoma and adenocarcinoma, mitotic counting, specificity of CD56, utility of INSM1, and potential diagnostic pitfalls. Molecular advances have led to new insights on the origin and classification of neuroendocrine tumors, especially of neuroendocrine carcinomas. The integration of clinical and radiologic findings to enhance diagnostic certainty was addressed.
Emerging knowledge supports the classification of neuroendocrine tumors into low, intermediate, and high grade categories. Use of Ki-67 to distinguish high from low grade lesions is established but not as a replacement for mitotic counting in well-preserved samples and excisions. Molecular data in large cell neuroendocrine carcinoma show some heterogeneity in this category with potential treatment implications. New data support the observation that most carcinoids and atypical carcinoids do not progress into higher grade lesions; however, this may occur in a small subset of cases. In addition, there appear to be atypical carcinoid tumors with mitotic rates higher than 10 in 2 mm2; their biologic behavior needs to be better defined. The consideration of rare entities in the differential diagnosis of neuroendocrine tumors is prompted by unusual epidemiology, histology, and clinical presentation.
Prognostic factors of metastatic neuroendocrine carcinoma under first-line treatment with platinum etoposide with a focus on NEC score and Rb expression: Results from the multicentre RBNEC study of the Groupe d'Etude des Tumeurs Endocrines (GTE) and the ENDOCAN-RENATEN network
2021, European Journal of Cancer: Neuroendocrine carcinomas (NECs) are aggressive malignant diseases. Platinum-etoposide (PE) combination is the standard first-line treatment, whatever the primary location. The NEC score and also retinoblastoma protein (Rb) status have been suggested to be predictive/prognostic factors in NEC.
The primary objective of our multicentric retrospective study was to evaluate the prognostic relevance of the NEC score and Rb status, assessed by immunohistochemistry in PE-treated patients with metastatic NEC.
Seven centres participated. The inclusion criteria were NEC, whatever the primary site, metastatic stage, first-line treatment with PE and tissue samples available. Rb status was determined centrally.
We report multicentric data from 185 metastatic patients (37% women, median age 63). There were 108 small-cell NECs (SCNECs, 58.4%), 50 large-cell NECs (LCNECs, 27%) and 27 not otherwise specified NECs (nosNECs, 14.6%). The primary sites were the thorax (37%), gastroenteropancreatic sites (38%), unknown (15%) and other (9%). The mean Ki-67 index was 76% (range 20–100). Rb status was interpretable in 122 cases. Rb expression was lost in 74% of the cases: 84% of SCNEC vs. 60% and 63% of LCNEC and nosNEC, respectively (p = 0.016). Objective response was seen in 70% of SCNEC, 45% of LCNEC and 48% of nosNEC (p < 0.001) and in 62% of Rb-negative tumours vs. 46% of Rb-positive tumours (p = 0.3). There was no difference in median progression-free survival or overall survival (OS) as per Rb status. Age, NEC score and response to chemotherapy were the main factors associated with OS in our cohort.
In our series, Rb status had no prognostic impact in PE-treated metastatic patients with NEC, whereas age, NEC score and response to chemotherapy were the main factors associated with OS
Retrospective study of lung carcinoid: experience in a third level Spanish hospital
2021, Revista Espanola de PatologiaLos carcinoides pulmonares son un tipo de cáncer relativamente infrecuente, representando únicamente un 1-2% de las neoplasias torácicas, encuadrándose dentro de las neoplasias neuroendocrinas. En nuestro trabajo, pretendemos exponer nuestra experiencia en el manejo y seguimiento de un tumor tan infrecuente como el carcinoide pulmonar, resaltando la poca evidencia actual y las dudas que pueden surgir en su manejo.
Presentamos un estudio descriptivo retrospectivo, que incluye a todos los pacientes diagnosticados de tumor carcinoide entre enero de 2013 y enero de 2018. Se recogieron de forma retrospectiva variables demográficas, histológicas y clínicas. Se realizó un análisis descriptivo de las variables y un análisis de supervivencia. Para los análisis estadísticos se utilizó el programa informático SPSS, versión 21.
Se incluyeron un total de 42 pacientes diagnosticados de tumor carcinoide en el periodo del estudio. La edad media de presentación fue de 66,26 (desviación típica de 12,31). Con una mediana de seguimiento de 60 meses, la mediana de supervivencia global fue de 59,12 meses. En el análisis de supervivencia el único factor que se relacionó con una mayor supervivencia de forma estadísticamente significativa fue el estadio tumoral al diagnóstico.
Los tumores carcinoides son considerados infrecuentes, lo que dificulta obtener datos sobre los mismos de forma objetiva. Por ello, consideramos que trabajos como el nuestro pueden ayudar a entender mejor la evolución de esta neoplasia.
Pulmonary carcinoids are relatively rare neuroendocrine neoplasms, accounting for only 1-2% of malignant thoracic tumours. We describe our experience in the management and follow-up of such an infrequent tumour, with special emphasis on possible problems that might arise.
We present a descriptive retrospective study of all patients diagnosed with carcinoid tumour between January 2013 and January 2018. Demographic, histological and clinical data were collected and analyzed. Survival was recorded. SPSS version 21 was used for the statistical analysis.
42 patients with an average age of 66.26 years were included. The mean period of follow-up was 60 months and the average survival 59.12 months. The only statistically significant factor related to an improved survival time was tumour stage at diagnosis.
Carcinoid tumours are infrequent, which makes the objective collecting of data difficult. For this reason, we hope that the present study will contribute to a better understanding of their evolution.