Malignant giant solitary fibrous tumour of the mediastinum; masquerading Triton tumour

Background Malignant Solitary fibrous tumour (SFT) is an uncommon mesenchymal tumour with aggressive clinical behaviour as compared to its benign counterpart. There are only a handful of reports of extra-pleural malignant SFT arising from the mediastinum. Case presentation A 68-year-old male, presented with a history of cough and breathlessness for 2 weeks. Computed tomography (CT) scan revealed a large 11.6 × 11.3x18cm anterior mediastinal mass with extension to right hemithorax. The patient underwent excision of the mass after a biopsy confirmation of mesenchymal tumour. Histological examination of resection specimen revealed a spindle cell tumour with hypo and hypercellular areas, arranged in fascicular, focal storiform and hemangio-pericytomatous vasculature pattern. Moderate to marked nuclear atypia, frequent mitosis and areas of necrosis were noted. On immunohistochemistry (IHC), the tumour cells were positive for CD34, Bcl2, MIC2 (dot-like) and focally for S100 and Desmin. Although, the possibility of a malignant peripheral nerve sheath tumour with heterologous rhadomyosarcomatous differentiation (Triton tumour) was considered, however IHC for STAT6 confirmed it to be a malignant SFT. The patient developed recurrence within 1 year after surgery and despite multi-modality treatment (Re-excision, Chemotherapy and Radiotherapy) succumbed within 14 months from point of presentation. Conclusion Malignant SFT is a rare aggressive tumour that should be considered as a differential diagnosis in the mediastinum and a broad panel of IHC markers including STAT6 may be required to confirm the diagnosis.

Incidence of Prostatic Carcinoma in Transurethral Resection Specimen

Objective: This study done to identify the rates of incidentally detected prostate cancer in patients undergoing surgical management of Benign Prostatic Hyperplasia (BPH). Methods: This cross section study was done on all transurethral resections of the prostate (TURP) cases. One hundred and eighty one men, aged 45 to 94 year, underwent TURP and their specimens were sent for the histopathological analysis. Those with a known diagnosis of prostate cancer prior to TURP were excluded (𝑛 = 5) from the analysis. Results: Hundred eighty-one patients had prostatic enlargement; fifteen patients (8.29%) patients were found to have prostate adenocarcinoma. Grade of disease ranged from Gleason score 7 to 10. Majority of them (fourteen patients) aged 65 year or above. Conclusion: Prostate carcinoma is showing high grade at the diagnosis and widely frequent (8.29%) in TURP, especially in-patient above 65 years (11.0%) and therefore a screening program advised.

Concurrent Adjacent Merkel Cell Carcinoma and Chronic Lymphocytic Leukemia without Simultaneous Merkel Cell Polyomavirus Detection: A Case Series

Background: The association between Merkel cell carcinoma (MCC) and chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL) is well established in the literature. A majority of MCCs are known to be associated with Merkel cell carcinoma polyomavirus (MCPyV), which is postulated to be a possible causative agent linking these two entities. We aim to identify the presence of MCPyV in patients with concurrent adjacent MCC and CLL/SLL. Methods: Archived pathology materials of three cutaneous or surgical excisions with concurrent MCC and CLL/SLL were reviewed. Additional 12-µm sections from paraffin-embedded tissue of these resections were matched with original hematoxylin and eosin-stained slides and used to extract foci from each tumor separately. DNA was extracted from these tissues, and polymerase chain reaction (PCR), utilizing a primer set within a highly conserved “small T” viral DNA region, was done to detect MCPyV. Results: Out of 140 cases of cutaneous or surgical excisions with MCC identified in our electronic medical records (EMR), three had coexisting neighboring CLL/SLL in the same resection specimen. In one case out of three, MCPyV was detected in MCC but not in CLL/SLL. The remaining two cases showed no detection of MCPyV in either MCC or CLL/SLL. Conclusion: MCPyV was not concurrently associated with adjacent MCC and CLL/SLL, indicating that it is not driving simultaneous tumorigenesis, at least in a subset of these cases.

Surgical management of a COVID-19-associated necrotic pneumonia

At the outset of the pandemic, SARS-CoV-2 was thought to present simply as persistent cough and fever. However, with time, the medical community noted a myriad of associated symptoms well-described in the literature. Medical complications were particularly common in elderly populations and many early publications described pneumonia, organ failure, acute respiratory distress syndrome, hypercoagulability/microthrombosis and superimposed bacterial/viral infections. There is, however, a lack of literature describing surgical complications of COVID-19 and as such little knowledge regarding safe surgical interventions. This case describes the presentation/management of a patient who developed COVID-19-associated necrotising pneumonia. Video-assisted thoracoscopy lobectomy was performed following CT demonstration of necrotising pneumonia. Pathological evaluation of the surgical resection specimen demonstrated the microarchitecture of a severely diseased COVID-19 lung-fibrosis. This case demonstrates the safe management of a necrotic lung using a minimal access approach in the context of COVID-19 infection.

Diagnostic Accuracy in Bronchial Carcinoid tumors is Dependent of Biopsy Size

Objective: Recently, 60% discordancy was reported for distinction between typical carcinoid and atypical carcinoid in preoperative biopsy compared to the resection specimen. This study investigated the impact of biopsy surface size, obtained with flexible and rigid bronchoscopy, on diagnostic accuracy of typical and atypical carcinoid. Methods: Biopsy-resection paired specimens of patients referred for treatment to Amsterdam University Medical Centers were retrieved. Bronchial biopsies were obtained either by flexible or rigid biopsy. The definitive diagnosis was based on the resection specimen. Diagnosis according to the 2015 WHO classification, mitoses and necrosis in biopsy and resection specimen, were independently re-evaluated by two pathologists. Results: After screening 298 patients, 64 biopsy-resection pairs with available tissue were included of which 34 (53%) were biopsied with flexible and 30 (47%) with rigid biopsy. In 35 (55%) patients, the tumor classification between the biopsy and resection specimen was concordant. The discordance in the remaining 29 cases (45%) was caused by misclassification of atypical as typical carcinoid in bronchoscopy specimens, predominantly in small flexible biopsies (59%, p=0.021). Of biopsies measuring <2 mm2, 79% were classified as discordant and 52% of the discordant biopsies measured <4 mm2. Conclusion: Histological classification in central carcinoid tumors is discordant in 45% of the biopsies, with increasing diagnostic accuracy in larger biopsies. Distinguishing carcinoid tumor into typical or atypical carcinoid on biopsies <4 mm2 should be discouraged. A cumulative biopsy surface of at least 4 mm2 tumor is preferred to increase the diagnostic accuracy which helps in optimal treatment planning.

Neuroendocrine neoplasms of the lung: a pathology update

Summary Purpose Neuroendocrine tumors and neuroendocrine carcinomas in the lung are distinct and separate entities featuring neuroendocrine differentiation, for which an accurate classification is clinically warranted. Materials and methods Three perspectives were addressed: (i) diagnostic tools, with the terminology to be used in either resection specimen or small-sized material; (ii) the so-called carcinoid tumors with elevated proliferation rates (mitotic and/or Ki-67 activity); (iii) predictive biomarkers based on immunohistochemical characterization. Results We herein provide a pathology update on lung neuroendocrine neoplasm classification that will appear in the forthcoming 5th edition of the WHO Blue Book, including a short discussion about biomarkers, which are presently given full consideration in clinical practice. Conclusion The WHO classification on lung neuroendocrine neoplasms is the cornerstone to provide the best clinical management of patients and is the starting point for any investigative insight.

A novel, computer-aided, scanning platform agnostic solution for grading carcinomas in breast biopsy whole slide images.

e12575 Background: The determination of breast cancer grade remains a problematic diagnostic issue in biopsies due to limited tissue sampling and the inherent inter-observer variability associated with the Nottingham (histologic) score. Significantly, biopsy grading corresponds only moderately with that based on excision specimens, with discordance rates of 21-30.0%, which is a concern for cases managed neoadjuvantly or with minimally ablative therapy. Although the advent of digital pathology has encouraged endeavors to automate breast cancer detection and grading, no method has yet received regulatory approval for clinical use or proven to be a platform agnostic solution. Methods: This study was the blinded clinical validation a novel, FDA breakthrough designation approved automated device-based predictive solution which uses a surrogate scale to determine breast carcinoma grade in core biopsies using H&E slide whole slide images (WSIs) only. Non-preselected malignant breast core biopsy clinical cases (n=173 WSIs; 107 cases) covering a broad spectrum of breast cancer morphological subtypes were scanned at x20 magnification on both on Aperio high-throughput T2/T3 systems (.SVS files) and Roche-Ventana DP200 scanners (.BIF files). The diagnostic gold standard reference was the reports of tertiary referral center breast subspecialty consultant histopathologists. Diagnostic outputs were also compared to case-matched resection specimen grades. Comparison of diagnostic outcomes with pathologists as gold standard was done using inter observer agreement (cohen kappa) with 95% CI and statistically significant chi-squared test p-value for two different scanner platforms. Results: Although biopsy-based diagnostic concordance with pathologists was very good, the device actually delivered a much better concordance between case-matched biopsy and resection specimen (accuracy: 95%, cohen kappa: 0.91) relative to pathologists’ assessments (accuracy: 80%). Conclusions: This indicates that the use of a single continuous surrogate grading scale is much less affected by limited tissue sampling than conventional ordinal morphological scales. This level of performance was independent of file format analyzed, demonstrating the device’s platform agnosia.

Prediction of Tumor Cellularity in Resectable PDAC from Preoperative Computed Tomography Imaging

Background: PDAC remains a tumor entity with poor prognosis and a 5-year survival rate below 10%. Recent research has revealed invasive biomarkers, such as distinct molecular subtypes, predictive for therapy response and patient survival. Non-invasive prediction of individual patient outcome however remains an unresolved task. Methods: Discrete cellularity regions of PDAC resection specimen (n = 43) were analyzed by routine histopathological work up. Regional tumor cellularity and CT-derived Hounsfield Units (HU, n = 66) as well as iodine concentrations were regionally matched. One-way ANOVA and pairwise t-tests were performed to assess the relationship between different cellularity level in conventional, virtual monoenergetic 40 keV (monoE 40 keV) and iodine map reconstructions. Results: A statistically significant negative correlation between regional tumor cellularity in histopathology and CT-derived HU from corresponding image regions was identified. Radiological differentiation was best possible in monoE 40 keV CT images. However, HU values differed significantly in conventional reconstructions as well, indicating the possibility of a broad clinical application of this finding. Conclusion: In this study we establish a novel method for CT-based prediction of tumor cellularity for in-vivo tumor characterization in PDAC patients.

Predictive value of endoscopic esophageal findings for residual esophageal cancer after neoadjuvant chemoradiotherapy

Background Endoscopic evaluation of the esophageal mucosa may play a role in an active surveillance strategy after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. This study investigated the yield of endoscopic findings for detection of residual disease. Methods Patients from the multicenter preSANO cohort, who underwent nCRT followed by surgery for esophageal or junctional cancer, were included. Upper endoscopy was performed 6 and 12 weeks after nCRT. Patients with residual disease at 6 weeks underwent immediate surgery. Endoscopic records were reviewed for presence of stenosis, suspicion of residual tumor, scar tissue, and ulceration. Presence and type of endoscopic findings were compared with outcome of the resection specimen. Results 118 of 156 patients (76 %) had residual disease in the resection specimen. Endoscopic suspicion of residual tumor was significantly associated with presence of residual disease. At 6 weeks, 40/112 patients with residual disease and 4/33 patients with complete response had endoscopic suspicion of residual tumor (36 % vs. 12 %; P = 0.01), while this was reported in 16/73 and 0/28 patients, respectively, at 12 weeks (22 % vs. 0 %; P < 0.01). Positive predictive value of endoscopic suspicion of residual tumor was 91 % at 6 weeks and 100 % at 12 weeks. Endoscopic findings of non-passable stenosis, passable stenosis, scar tissue, or ulceration were not associated with residual disease. Conclusions Endoscopic suspicion of residual tumor was the only endoscopic finding associated with residual disease. Based on its positive predictive value, this endoscopic finding may contribute to the diagnostic strategy used in active surveillance.