Concurrent myasthenia gravis-related cervical thymoma in a patient with diffuse large B-cell lymphoma: a case report

Background Cervical thymoma is a rare thymic epithelial neoplasm. Evidence supports an increased risk of second primary malignancies in patients with thymoma. We report a rare case of a patient with synchronous cervical thymoma and diffuse large B-cell lymphoma. Case presentation An 81-year-old Thai woman was referred for further treatment of diffuse large B-cell lymphoma at Siriraj Hospital, Bangkok, Thailand. While waiting for a review of the original pathological examination of a mass in the left neck and a mass in the left arm, the attending physician noticed ptosis of the upper eyelids, which was proven to be caused by myasthenia gravis. The final pathology review confirmed that the arm mass was diffuse large B-cell lymphoma, but the neck mass was cervical thymoma, type B1, not diffuse large B-cell lymphoma. Interestingly, the patient reported that the arm mass had been present for 2 years, while the neck mass had grown rapidly in the past month. A diagnostic challenge had arisen when the initial morphological evaluation was not performed with care, causing the first pathologist to misinterpret that the neoplastic cells in both masses were the same. Conclusion Concurrent cervical thymoma and diffuse large B-cell lymphoma were proven after a careful pathology review, leading to better clinical management.

Harbingers of Aggressive Prostate Cancer: Precision Oncology Case Studies

Primary prostate cancer (PCa) can show marked molecular heterogeneity. However, systematic analyses comparing primary PCa and matched metastases in individual patients are lacking. We aimed to address the molecular aspects of metastatic progression while accounting for heterogeneity of primary PCa. In this pilot study, we collected 12 radical prostatectomy (RP) specimens from men who subsequently developed metastatic castration-resistant prostate cancer (mCRPC). We used histomorphology (Gleason grade, focus size, stage) and immunohistochemistry (IHC) (ERG and p53) to identify independent tumors and/or distinct subclones of primary PCa. We then compared molecular profiles of these primary PCa areas to matched metastatic samples using whole exome sequencing (WES) and amplicon-based DNA and RNA sequencing. Based on combined pathology and molecular analysis, seven (58%) RP specimens harbored monoclonal and topographically continuous disease, albeit with some degree of intra-tumor heterogeneity; four (33%) specimens showed true multifocal disease; and one displayed monoclonal disease with discontinuous topography. Early (truncal) events in primary PCa included SPOP p.F133V (one patient), BRAF p.K601E (one patient), and TMPRSS2:ETS rearrangements (nine patients). Activating AR alterations were seen in eight (67%) mCRPC patients, but not in matched primary PCa. Hotspot TP53 mutations, found in metastases from three patients, were readily present in matched primary disease. Alterations in genes encoding epigenetic modifiers were observed in several patients (either shared between primary foci and metastases or in metastatic samples only). WES-based phylogenetic reconstruction and/or clonality scores were consistent with the index focus designated by pathology review in six out of nine (67%) cases. The three instances of discordance pertained to monoclonal, topographically continuous tumors, which would have been considered as unique disease in routine practice. Overall, our results emphasize pathologic and molecular heterogeneity of primary PCa, and suggest that comprehensive IHC-assisted pathology review and genomic analysis are highly concordant in nominating the ″index″ primary PCa area.

Impact of Pathology Review in Adverse Histological Characteristics and pT Stages of Upper Tract Urothelial Cancer in a Multicenter Study

PurposePathology reviews for upper urinary tract cancer (UTUC) remained scarce in the literature. Here, we reported the interobserver variation among the review and local pathologies of featured histologic characteristics for UTUC.MethodsPatients who underwent definitive surgical treatments for UTUC were retrospectively reviewed for eligibility of pathology review. In the Taiwan UTUC Collaboration cohort, 212 cases were reviewed, of which 154 cases were eligible for pathology review. Agreement between original pathology and review pathology was measured by the total percentage of agreement and by simple kappa statistics. The prognostic impact was analyzed by the Cox regression model with the estimation of hazard ratios (HR) and 95% confidence intervals.ResultsThere were 80 women and 74 men enrolled in this study, and the median age at treatment was 71.7 years. The agreement is moderate agreement for surgical margin status (87.7%; κ = 0.61), tumor grade (82.5%; κ = 0.43), tumor invasiveness (76.6%; κ = 0.45), lymphovascular invasion (70.8%; κ = 0.42) and T stage (67.5%; κ = 0.52). The interobserver agreements for perineural invasion and variant histology identification were slight. Kaplan–Meier analysis for disease-free survival revealed comparable results in local and review pathology for localized (Tis, Ta, T1–2) or advanced T stage (T3–4).ConclusionsPathology review of UTUC had minimal impact on clinical practice based on current available disease treatment guidelines. However, significant interobserver variations were observed in featured adverse histopathological characters.

Automated Hematoxylin and Eosin Staining with Leica AutoStainer XL v1

PURPOSE: To stain formalin fixed paraffin tissue for microscopic evaluation. Hematoxylin will stain the nuclei of the tissue blue/purple and Eosin will stain cytoplasmic elements a spectrum of brilliant pink. QUALITY CONTROL: Fixation: 10% Neutral Buffered Formalin Technique: Paraffin sections at 5 microns Control: PCRL PROCEDURE: Station #Time in StationExact Time?Solution Name185:00NoXylene175:00NoXylene165:00NoXylene150:20No100% Alcohol140:20No100% Alcohol130:20No95% Alcohol120:20No70% AlcoholWash 11:20NoWater83:30YesHematoxylinWash 20:30YesWaterWash 30:30YesWater90:10YesAcid AlcoholWash 40:30YesWater100:10YesAmmonia WaterWash 50:30YesWater112:00Yes95%70:20YesEosin60:30Yes95%50:30Yes100%40:30Yes100%30:30NoXylene21:00NoXylene11:00NoXylene RESULTS: Nuclei……………………………………………..……………Blue/Purple Cytoplasmic Elements………………………………….Shades of brilliant pink For digital storage and possible pathology review slides are scanned on the Leica Aperio slide scanner. The file output is .svs and can be viewed by downloading freely available software from Leica.

Real-time polarization microscopy of fibrillar collagen in histopathology

Over the past two decades, fibrillar collagen reorganization parameters such as the amount of collagen deposition, fiber angle and alignment have been widely explored in numerous studies. These parameters are now widely accepted as stromal biomarkers and linked to disease progression and survival time in several cancer types. Despite all these advances, there has not been a significant effort to make it possible for clinicians to explore these biomarkers without adding steps to the clinical workflow or by requiring high-cost imaging systems. In this paper, we evaluate previously described polychromatic polarization microscope (PPM) to visualize collagen fibers with an optically generated color representation of fiber orientation and alignment when inspecting the sample by a regular microscope with minor modifications. This system does not require stained slides, but is compatible with histological stains such as H&E. Consequently, it can be easily accommodated as part of regular pathology review of tissue slides, while providing clinically useful insight into stromal composition.

Intraoperative Digital Analysis of Ablation Margins (DAAM) by Fluorescent Confocal Microscopy to Improve Partial Prostate Gland Cryoablation Outcomes

Partial gland cryoablation (PGC) aims at destroying prostate cancer (PCa) foci while sparing the unaffected prostate tissue and the functionally relevant structures around the prostate. Magnetic Resonance Imaging (MRI) has boosted PGC, but available evidence suggests that ablation margins may be positive due to MRI-invisible lesions. This study aimed at determining the potential role of intraoperative digital analysis of ablation margins (DAAM) by fluoresce confocal microscopy (FCM) of biopsy cores taken during prostate PGC. Ten patients with low to intermediate risk PCa scheduled for PGC were enrolled. After cryo-needles placement, 76 biopsy cores were taken from the ablation margins and stained by the urologist for FCM analysis. Digital images were sent for “real-time” pathology review. DAAM, always completed within the frame of PGC treatment (median time 25 min), pointed out PCa in 1/10 cores taken from 1 patient, thus prompting placement of another cryo-needle to treat this area. Standard HE evaluation confirmed 75 cores to be cancer-free while displayed a GG 4 PCa in 7% of the core positive at FCM. Our data point out that IDAAM is feasible and reliable, thus representing a potentially useful tool to reduce the risk of missing areas of PCa during PGC.