ObjectiveTo establish a CT-based radiomics nomogram model for classifying pulmonary cryptococcosis (PC) and lung adenocarcinoma (LAC) in patients with a solitary pulmonary solid nodule (SPSN) and assess its differentiation ability.Materials and MethodsA total of 213 patients with PC and 213 cases of LAC (matched based on age and gender) were recruited into this retrospective research with their clinical characteristics and radiological features. High-dimensional radiomics features were acquired from each mask delineated by radiologists manually. We adopted the max-relevance and min-redundancy (mRMR) approach to filter the redundant features and retained the relevant features at first. Then, we used the least absolute shrinkage and operator (LASSO) algorithms as an analysis tool to calculate the coefficients of features and remove the low-weight features. After multivariable logistic regression analysis, a radiomics nomogram model was constructed with clinical characteristics, radiological signs, and radiomics score. We calculated the performance assessment parameters, such as sensitivity, specificity, accuracy, negative predictive value (NPV), and positive predictive value (PPV), in various models. The receiver operating characteristic (ROC) curve analysis and the decision curve analysis (DCA) were drawn to visualize the diagnostic ability and the clinical benefit.ResultsWe extracted 1,130 radiomics features from each CT image. The 24 most significant radiomics features in distinguishing PC and LAC were retained, and the radiomics signature was constructed through a three-step feature selection process. Three factors—maximum diameter, lobulation, and pleural retraction—were still statistically significant in multivariate analysis and incorporated into a combined model with radiomics signature to develop the predictive nomogram, which showed excellent classification ability. The area under curve (AUC) yielded 0.91 (sensitivity, 80%; specificity, 83%; accuracy, 82%; NPV, 80%; PPV, 83%) and 0.89 (sensitivity, 81%; specificity, 83%; accuracy, 82%; NPV, 81%; PPV, 82%) in training and test cohorts, respectively. The net reclassification indexes (NRIs) were greater than zero (p < 0.05). The Delong test showed a significant difference (p < 0.0001) between the AUCs from the clinical model and the nomogram.ConclusionsThe radiomics technology can preoperatively differentiate PC and lung adenocarcinoma. The nomogram-integrated CT findings and radiomics feature can provide more clinical benefits in solitary pulmonary solid nodule diagnosis.