Rapid diagnosis and tumor margin assessment during pancreatic cancer surgery with the MasSpec Pen technology

Intraoperative delineation of tumor margins is critical for effective pancreatic cancer surgery. Yet, intraoperative frozen section analysis of tumor margins is a time-consuming and often challenging procedure that can yield confounding results due to histologic heterogeneity and tissue-processing artifacts. We have previously described the development of the MasSpec Pen technology as a handheld mass spectrometry–based device for nondestructive tissue analysis. Here, we evaluated the usefulness of the MasSpec Pen for intraoperative diagnosis of pancreatic ductal adenocarcinoma based on alterations in the metabolite and lipid profiles in in vivo and ex vivo tissues. We used the MasSpec Pen to analyze 157 banked human tissues, including pancreatic ductal adenocarcinoma, pancreatic, and bile duct tissues. Classification models generated from the molecular data yielded an overall agreement with pathology of 91.5%, sensitivity of 95.5%, and specificity of 89.7% for discriminating normal pancreas from cancer. We built a second classifier to distinguish bile duct from pancreatic cancer, achieving an overall accuracy of 95%, sensitivity of 92%, and specificity of 100%. We then translated the MasSpec Pen to the operative room and predicted on in vivo and ex vivo data acquired during 18 pancreatic surgeries, achieving 93.8% overall agreement with final postoperative pathology reports. Notably, when integrating banked tissue data with intraoperative data, an improved agreement of 100% was achieved. The result obtained demonstrate that the MasSpec Pen provides high predictive performance for tissue diagnosis and compatibility for intraoperative use, suggesting that the technology may be useful to guide surgical decision-making during pancreatic cancer surgeries.

Histopatholgy and Clinical Implication of Treatment-Related Changes After Gamma Knife Radiosurgery in Patients With Brain Metastases

A late-onset treatment-related changes (TRCs), which represent radiographic radiation necrosis (RN), frequently occur after stereotactic radiosurgery (SRS) for brain metastases and often need surgical treatment. This study aimed to validate the true pathology and investigate clinical implication of surgically resected TRCs on advanced magnetic resonance imaging (MRI).Retrospective analyses of 86 patients who underwent surgical resection after radiosurgery of brain metastases were performed. Fifty-four patients displayed TRCs on preoperative MRI, comprising pure RN in 19 patients (TRC-RN group) and mixed viable tumor cells in 35 patients (TRC-PD group). Thirty-two patients revealed the consistent diagnosis of progressive disease in both MRI and histopathology (PD-PD group). The TRC-PD group showed larger prescription isodose volume (9.4 cm3) than the TRC-RN (4.06 cm3, p=0.014) group and a shorter time interval from SRS to preoperative MRI diagnosis (median 4.07 months) than the PD-PD group (median 8.77 months, p=0.004). Progression-free survival was significantly different among the three groups (p<0.001), but not between TRC-RN and TRC-PD (post hoc test, p=1.00), while no difference was observed in overall survival (p=0.067).Brain metastases featured as TRCs after SRS frequently contained viable tumor cells. However, this histologic heterogeneity had a minor impact on benign prognosis of TRCs after surgical resection.

Female Adnexal Tumor of Probable Wolffian Origin: Clinicopathologic and Immunohistochemical Study of 11 Cases

Context.— Female adnexal tumor of probable Wolffian origin (FATWO) often is a diagnostic challenge given its rarity, histologic heterogeneity, and lack of specific immunoprofile. Objective.— To further understand the clinicopathologic and immunohistochemical features of this rare entity. Design.— We studied the clinical, morphologic, and immunohistochemical features of a cohort of 11 FATWO cases from our institute. Results.— Patients' age ranged from 25 to 76 years (mean, 55 years). Tumor size ranged from 0.5 to 18 cm (mean, 2.7 cm). Histopathologically, most tumors presented with low-grade cytologic features with low mitotic activity and lack of necrosis. Three main growth patterns were appreciated: solid, tubular, and sievelike patterns. Higher-grade nuclear atypia, increased mitotic activity, and focal necrosis were seen in 2 cases. These 2 cases were clinically considered malignant FATWO mainly because of their extra-adnexal involvement. Immunohistochemical studies found that tumor cells were positive for CD10 (11 of 11, 100%), AE1/3 (8 of 8, 100%), CAM 5.2 (4 of 5, 80%), and cytokeratin 7 (CK7; 7 of 10, 70%); and focally positive for calretinin (4 of 10, 40%), inhibin (4 of 10, 40%), epithelial membrane antigen (EMA; 3 of 9, 33%), and steroidogenic factor-1 (SF-1; 2 of 8, 25%). Lack of immunoreactivity to PAX8 and GATA3 in almost all cases indicates that FATWO is different from the tumors derived from the Müllerian or mesonephric origins. All patients with available follow-up had favorable prognosis. Conclusion.— The broad spectrum of clinical presentation, various morphologic features, and overlapping immunophenotype suggest that FATWO is a diagnosis of exclusion until it is further defined at the molecular and immunohistochemical levels.

The 2016 Edition of the WHO Classification of Primary Brain Tumors: Applicable to Assess Individual Risk of Recurrence in Atypical Meningioma? A Single-Center Experience

Background and Study Aims/Object Despite the relevance of molecular criteria for brain tumor diagnosis and prognosis, meningioma grading is still solely based on histologic features. Atypical meningiomas (AMs; WHO grade II) display a great histologic heterogeneity and individual courses of disease can differ significantly. This study aimed to identify clinically aggressive AMs that are prone to early recurrence after gross total resection (GTR) by assessing a specific histologic score. Patients and Methods A retrospective analysis of 28 consecutive patients (17 females and 11 males; mean age of 62 years [range: 35–88 years]) treated in our institution between January 2006 and December 2015 was performed. Basic demographic and clinical characteristics were assessed. A scoring scale was designed to address the histologic diversity by summing up the individual histologic features in every tumor sample. According to that, points were awarded as follows: major AM defining criterion (3 points) and minor criterion (1 point). Results The subclassification based on our specific histologic score revealed no significant difference in frequency of one (46.4%) or two (42.9%) AM defining features; three criteria were less frequently seen (10.7%). Mean follow-up was 61.89 ± 9.03 months. Local recurrence occurred in 35.7% after a mean time of 37.4 ± 22.6 months after primary surgery. Age > 60 years was significantly associated with a shorter progression-free survival (PFS). There was a trend toward shorter PFS with increasing scores, tantamount with the presence of several AM defining histologic criteria in one sample. No tumor relapse was seen when diagnosis was based only on minor criteria. Conclusion AMs display a histologic diversity. There is a trend toward shorter PFS with increasing numbers of AM defining histologic features. The inclusion of this score in the decision algorithm regarding further treatment for patients >60 years after GTR might be helpful and should be evaluated in further studies.

Histopathology and Clinical Implication of Treatment-related Image Changes After Surgical Resection of Brain Metastases Previously Treated with Gamma Knife Radiosurgery

INTRODUCTION The true pathology and clinical implication of treatment-related image changes (TRICs) after stereotactic radiosurgery (SRS) for brain metastases (BM) have not been established. This study compared the surgical pathology and outcomes of intracranial metastatic lesions featured as TRICs or progressive disease (PD) in advanced magnetic resonance imaging (MRI).METHODS A total of 86 patients who underwent surgical resection of brain metastases previously treated with gamma knife radiosurgery (GKS) from 2009 to 2019 were retrospectively reviewed and classified by MRI findings and histopathology.RESULTS Among 54 patients with TRICs in preoperative MRI, the histopathology of pure radiation necrosis (RN) was confirmed in 19 patients (TRIC-RN) and mixed or predominant viable tumor cells in 35 patients (TRIC-PD). Thirty-two patients diagnosed with PD exhibited the metastatic histology well correlated with imaging (PD-PD). The TRIC-PD group showed larger prescription isodose volume (9.4 cm3) than the TRIC-RN (4.06 cm3, p=0.014) group and shorter time interval from GKS to preoperative MRI diagnosis related to neurological deficits (median 4.07 months) than the PD-PD group (median 8.77 months, p=0.004). Significant differences in progression-free survival were confirmed among the three groups (p<0.001) but not between TRIC-RN and TRIC-PD (post hoc test, p=1.00), whereas no significant difference was observed in overall survival (p=0.067). CONCLUSIONS The brain metastatic lesions diagnosed as TRICs after GKS frequently contained viable tumor cells, while they exhibited the benign prognosis as RN after surgical resection. These findings suggest that TRICs on advanced MRI can serve as a prognostic factor, regardless of the histologic heterogeneity.

Development and validation of a CT-texture analysis nomogram for preoperatively differentiating thymic epithelial tumor histologic subtypes

Background Thymic epithelial tumors (TETs) are the most common primary tumors in the anterior mediastinum, which have considerable histologic heterogeneity. This study aimed to develop and validate a nomogram based on computed tomography (CT) and texture analysis (TA) for preoperatively predicting the pathological classifications for TET patients. Methods Totally TET 172 patients confirmed by postoperative pathology between January 2011 to April 2019 were retrospectively analyzed and randomly divided into training (n = 120) and validation (n = 52) cohorts. Preoperative clinical factors, CT signs and texture features of each patient were analyzed, and prediction models were developed using the least absolute shrinkage and selection operator (LASSO) regression. The performance of the models was evaluated and compared by the area under receiver-operator characteristic (ROC) curve (AUC) and the DeLong test. The clinical application value of the models was determined via the decision curve analysis (DCA). Then, a nomogram was developed based on the model with the best predictive efficiency and clinical utility and validated using the calibration plots. Results Totally 87 patients with low-risk TET (LTET) (types A, AB, B1) and 85 patients with high-risk TET (HTET) (types B2, B3, C) were enrolled in this study. We separately constructed 4 prediction models for differentiating LTET from HTET using clinical, CT, texture features, and their combination. These 4 prediction models achieved AUCs of 0.66, 0.79, 0.82, 0.88 in the training cohort and 0.64, 0.82, 0.86, 0.94 in the validation cohort, respectively. The DeLong test and DCA showed that the Combined model, consisting of 2 CT signs and 2 texture parameters, held the highest predictive efficiency and clinical utility (p < 0.05). A prediction nomogram was subsequently developed using the 4 independently risk factors from the Combined model. The calibration curves indicated a good consistency between the actual observations and nomogram predictions for differentiating TET classifications. Conclusion A prediction nomogram incorporating both the CT and texture parameters was constructed and validated in our study, which can be conveniently used for the preoperative individualized prediction of the simplified histologic subtypes in TET patients.

Histologic Heterogeneity of Extirpated Renal Cell Carcinoma Specimens: Implications for Renal Mass Biopsy

Pathologic characteristics of extirpated renal cell carcinoma (RCC) specimens <7 cm were reviewed to get better information on technical nuances of renal mass biopsy (RMB). Specimens were stratified according to tumor stage, nuclear grade, size, histology, presence of lymphovas-cular invasion (LVI), necrosis, and sarcomatoid features. When considering pT1 (0–7 cm) tumors pT1b (4–7 cm), RCC masses were more likely to have necrosis (43% vs 16%, P < 0.001), LVI (6% vs 2%, P = 0.024), high-grade nuclear elements (29% vs 17%, P < 0.001), and sarcomatoid features (2% vs 0%, P = 0.006) compared with pT1a (0–4 cm) tumors. Additionally, pT3a tumors were more highly associated with necrosis (P = 0.005), LVI, sarcomatoid features, and high-grade disease (P for all < 0.001) when compared to pT1 masses. For masses <4 cm, pT3a cancers were more likely to demonstrate necrosis (38% vs 16%, P < 0.001), LVI (10% vs 2%, P = 0.037), high-grade nuclear elements (31% vs 17%, P = 0.05), and sarcomatoid features (3% vs 0%, P = 0.065) compared to pT1a tumors. Similarly, for masses 4–7 cm, pathologic T3a tumors were significantly more likely to have sarcomatoid features (16% vs 2%, P < 0.001) and LVI (28% vs 6%, P < 0.001) compared to pT1b tumors. In summary, pT3a tumors and those RCC masses >4 cm exhibit considerable histologic heterogeneity and may harbor elements that are not easily appreciated with limited renal sampling. Therefore, if RMB is considered for renal masses greater than 4 cm or those that abut sinus fat, a multi-quadrant biopsy approach is necessary to ensure adequate sampling and characterization of the mass.

Histologic Heterogeneity of Extirpated Renal Cell Carcinoma Specimens: Implications for Renal Mass Biopsy

Pathologic characteristics of extirpated renal cell carcinoma (RCC) specimens <7 cm were reviewed to get better information on technical nuances of renal mass biopsy (RMB). Specimens were stratified according to tumor stage, nuclear grade, size, histology, presence of lymphovascular invasion (LVI), necrosis, and sarcomatoid features. When considering pT1 (0–7 cm) tumors, pT1b (4–7 cm) RCC masses were more likely to have necrosis (43% vs 16%, P < 0.001), LVI (6% vs 2%, P = 0.024), high-grade nuclear elements (29% vs 17%, P < 0.001), and sarcomatoid features (2% vs 0%, P = 0.006) compared with pT1a (0–4 cm) tumors. Additionally, pT3a tumors were more highly associated with necrosis (P = 0.005), LVI, sarcomatoid features, and high-grade disease (P for all < 0.001) when compared to pT1 masses. For masses ≤ 4 cm, pT3a cancers were more likely to demonstrate necrosis (38% vs 16%, P < 0.001), LVI (22% vs 2%, P < 0.001), high-grade nuclear elements (45% vs 17%, P < 0.001), and sarcomatoid features (12% vs 0%, P < 0.001) compared to pT1a tumors. Similarly, for masses 4–7 cm, pathologic T3a tumors were significantly more likely to have sarcomatoid features (12% vs 2%, P = 0.006) and LVI (22% vs 6%, P = 0.003) compared to pT1b tumors. In summary, pT3a tumors and those RCC masses >4 cm exhibit considerable histologic heterogeneity and may harbor elements that are not easily appreciated with limited renal sampling. Therefore, if RMB is considered for renal masses greater than 4 cm or those that abut sinus fat, a multi-quadrant biopsy approach is necessary to ensure adequate sampling and characterization of the mass.