Modern Pathology

The anaplastic lymphoma kinase (ALK) gene encodes a receptor tyrosine kinase and fusions involving this gene have been reported in a variety of mesenchymal neoplasms. ALK-altered tumors with epithelioid morphology have been described in epithelioid inflammatory myofibroblastic sarcoma, and epithelioid fibrous histiocytoma. Herein, we describe the clinicopathologic features of seven ALK-rearranged mesenchymal tumors with epithelioid morphology occurring predominately in the pediatric population. Tumors occurred in 4 females and 3 males with an age ranging from 1 month to 28 years...

Nested (NUC) and large nested (LNUC) subtypes of urothelial carcinoma of the upper urinary tract are exceedingly rare. This has contributed to the paucity of information regarding their clinicopathological and molecular characteristics. To address this knowledge gap, we explored the largest cohort to date of these rare tumors, comprising of resection specimens of 10 LNUC and 7 NUC, from seven participating institutions. Clinicopathological data was retrieved and documented. Whole exome sequencing and RNA sequencing was performed on the Illumina NovaSeq 6000 sequencer...

No abstract text is available yet for this article.

Somatostatin receptor type 2 (SSTR2) and thyroid stimulating hormone receptor (TSHR) display variable expression in primary thyroid tumors and have been implicated as theranostic targets. This study was designed to explore differential expression of SSTR2 and TSHR in oncocytic (Hurthle cell) carcinoma (OC) versus oncocytic adenoma (OA). We performed a retrospective review for oncocytic neoplasms treated at our institution from 2012 to 2019. Formalin-fixed paraffin embedded (FFPE) tissue blocks were utilized for tissue microarray (TMA) construction...

The microscopic evaluation of glands in the colon is of utmost importance in the diagnosis of inflammatory bowel disease (IBD) and cancer. When properly trained, deep learning pipelines can provide a systematic, reproducible, and quantitative assessment of disease-related changes in glandular tissue architecture. The training and testing of deep learning models require large amounts of manual annotations, which are difficult, time-consuming, and expensive to obtain. Here, we propose a method for the automated generation of ground truth in digital hematoxylin and eosin (H&E) stained slides using immunohistochemistry (IHC) labels...

Diffuse sclerosing variant papillary thyroid carcinoma (DS-PTC) is characterized clinically by a predilection for children and young adults, bulky neck nodes and pulmonary metastases. Previous studies have suggested infrequent BRAFV600E mutation but common RET gene rearrangements.Using strict criteria, we studied 43 DS-PTCs (1.9% of unselected PTCs in our unit). 79% harboured pathogenic gene rearrangements involving RET, NTRK3, NTRK1, ALK, or BRAF; with the remainder driven by BRAFV600E mutations. All ten pediatric cases were all gene-rearranged (p=0...

Pancreatic cancer is a lethal disease with increasing incidence and high recurrence rates, currently resistant to conventional therapies. Moreover, it displays extensive morphological and molecular intra- and intertumoral heterogeneity and a mostly low mutational burden, failing to induce significant antitumor immunity. Thus, immunotherapy has shown limited effect in pancreatic cancer, except in rare tumors with microsatellite instability, constituting <1% of the cases. Currently, new methods, including single cell and single nucleus RNA sequencing, have refined and expanded the two-group molecular classification based on bulk RNA sequencing (classical and basal-like subtypes), identifying hybrid forms and providing us with a comprehensive map of the tumor cell subsets that drive gene expression during tumor evolution, simultaneously giving us insight to therapy resistance and metastasis...

No abstract text is available yet for this article.

Digital pathology adoption allows for applying computational algorithms to routine pathology tasks. Our study aimed to develop a clinical-grade AI tool for precise multi-class tissue segmentation in colorectal specimens (resections and biopsies) and clinically validate the tool for tumor detection in biopsy specimens. The training dataset included 241 precisely manually annotated whole slide images from multiple institutes. The algorithm was trained for semantic segmentation of eleven tissue classes with an additional module for biopsy whole slide image (WSI) classification...

Recent statistics on lung cancer, including the steady decline of advanced diseases and the dramatically increasing detection of early-stage diseases and indeterminate pulmonary nodules (IPN), mark the significance of a comprehensive understanding of early lung carcinogenesis. Lung adenocarcinoma (ADC) is the most common histologic subtype of lung cancer, and atypical adenomatous hyperplasia (AAH) is the only recognized preneoplasia to ADC, which may progress to adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and eventually to invasive ADC...

Primary diffuse large B-cell lymphoma of the CNS (CNS-DLBCL) is an aggressive disease, with dismal prognosis despite the use of high dose methotrexate (MTX)-based polychemotherapy. Our study aimed to expand the biologic profiles of CNS-DLBCL and to correlate them with clinical/imaging findings to gain diagnostic insight and possibly identify new therapeutic targets. We selected 61 CNS-DLBCL whose formalin-fixed paraffin-embedded samples were available at first diagnosis. These were investigated by immunohistochemistry, cMYC rearrangements were explored by fluorescence in situ hybridization and CNS-DLBCL mutated genes were evaluated by next generation sequencing...

Adenoid cystic carcinoma (AdCC) is a rare triple-negative breast cancer analogous to its extramammary counterparts. Diagnosis of the more aggressive solid-basaloid variant (SB-AdCC) can be challenging due to poorly-defined histopathologic and molecular features. We characterized 22 invasive and in situ basaloid carcinomas by morphology, immunohistochemistry (IHC), genetics, and MYB status using multiple platforms, and assessed clinical behavior and neoadjuvant chemotherapy (NAT) responses. After consensus review, 16/22 cases were classified as SB-AdCC...

Endoscopic evidence of disease activity is a critical predictor of clinical relapse in patients with Crohn's disease (CD) and histologic disease activity is evolving as a similarly important endpoint for patient management. However, classical morphologic features of CD may overlap with postoperative inflammatory changes, confounding the evaluation of anastomotic biopsies. There is a clear unmet need for better characterization of diagnostic and clinically significant histological features of CD in these surgically altered sites...

Early detection of esophageal neoplasia via evaluation of endoscopic surveillance biopsies is key to maximizing survival for patients with Barrett's esophagus, but is hampered by the sampling limitations of conventional slide-based histopathology. Comprehensive evaluation of whole biopsies with 3D pathology may improve early detection of malignancies, but large 3D pathology datasets are tedious for pathologists to analyze. Here we present a deep learning-based method to automatically identify the most-critical 2D image sections within 3D pathology datasets for pathologists to review...

Next-generation sequencing (NGS) studies have demonstrated that co-occurring sporadic endometrioid endometrial and ovarian carcinomas (EEC/EOC) are clonally related, suggesting that they originate from a single primary tumor. Despite clonality, synchronous EEC/EOC when diagnosed at early stage behave indolently, similar to isolated primary EEC or isolated primary EOC. In the present study, we compared the DNA methylation signatures of co-occurring EEC/EOC to isolated primary EEC and isolated primary EOC. We also performed targeted NGS to assess the clonal relatedness of 7 co-occurring EEC/EOC (4 synchronous EEC/EOC and 3 metastatic EEC based on pathologic criteria)...

The etiology of head and neck squamous cell carcinoma (HNSCC) involves multiple carcinogens such as alcohol, tobacco, and infection with human papillomavirus (HPV). Because HPV infection influences the prognosis, treatment, and survival of patients with HNSCC, it is important to determine the HPV status of these tumors. In this paper, we propose a novel deep learning pipeline for HPV infection status prediction with state-of-the-art performance in HPV detection using only whole slide images (WSIs) of routine hematoxylin and eosin (H&E) stained HNSCC sections...

We developed a deep learning framework to accurately predict the lymph node status of cervical cancer patients based on hematoxylin and eosin (HE)-stained pathological sections of the primary tumor. In total, 1524 HE-stained whole slide images (WSIs) of primary cervical tumors from 564 patients were used in this retrospective, proof-of-concept study. Primary tumor sections (1161 WSIs) were obtained from 405 patients who underwent radical cervical cancer surgery at the Fudan University Shanghai Cancer Center (FUSCC) between 2008 and 2014; 165 and 240 patients were negative and positive for lymph node metastasis, respectively (including 166 with positive pelvic lymph nodes alone and 74 with positive pelvic and para-aortic lymph nodes)...

Adult granulosa cell tumors (AGCT) are a molecularly distinct group of malignant ovarian sex cord-stromal tumors (SCST) characterized by a nearly ubiquitous c.402C>G/p.C134W mutation in FOXL2 (hereafter referred to as "C134W"). In some cases, AGCT exhibits marked morphological overlap with other SCSTs, and have an identical immunophenotype, and molecular testing may be necessary to help confirm the diagnosis. However, molecular testing is time-consuming, relatively expensive, and unavailable in many pathology laboratories...

Sarcomas with BCOR genetic alterations (BCOR-associated sarcomas) represent a recently recognized family of soft tissue and bone tumors characterized by BCOR fusion, BCOR internal tandem duplication, or YWHAE::NUTM2B fusion. Histologically, the tumors demonstrate oval-spindle cell proliferation in a variably vascular stroma and overexpression of BCOR and SATB2. Herein, we describe three soft tissue sarcomas with KDM2B fusions that phenotypically and epigenetically match BCOR-associated sarcomas. The cases included one infant, one adolescent, and one older patient...

Testicular germ cell tumors (TGCTs) and sex cord-stromal tumors (SCSTs) are the most common testicular neoplasms. The morphologic spectrum of such tumors is wide, with several histologic subtypes within each group. Testicular tumors often represent a diagnostic challenge, requiring proper identification of their biologic potential for accurate risk stratification and selection of therapy. In the era of precision medicine, molecular biomarkers are increasingly assuming a critical role in the management of patients with cancer...