Currently, PAX8 is the most commonly used immunomarker for gynecologic carcinomas; however, it lacks specificity. By mining The Cancer Genome Atlas mRNA expression profile data, Drs. Ding and Liu’s team identified SOX17 as a potential specific marker for gynecologic tumors. The authors performed immunohistochemical staining on tissue microarrays from 416 ovarian and endometrial cancer cases and 1544 solid tumors from other organs. Like PAX8, SOX17 was highly expressed in most subtypes of ovarian...
Apr 04, 2023•14 min
Primary ovarian mucinous tumors represent a heterogeneous group of neoplasms that can be diagnostically challenging. Our guest, Dr. Pavel Dundr and his coauthors analyzed 124 tumors that were originally diagnosed as mucinous borderline tumors (MBTs) or mucinous carcinomas (MCs), with an emphasis on interobserver diagnostic agreement and assessment of the potential utility of molecular profiling. Only a moderate agreement in diagnosis was found between the 13 observers on the study (k 0.524, for ...
Mar 20, 2023•21 min
Extranodal extension (ENE) is a significant prognostic factor for human papillomavirus (HPV)-negative head and neck squamous cell carcinoma. However, it remains controversial whether ENE is prognostically relevant in HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). The host discusses with Dr. Nora Katabi from Memorial Sloan Kettering Cancer Center her team’s recent study on the topic. Patients with ENE had shortened overall survival (OS), disease-specific survival (DSS), and disease-f...
Feb 14, 2023•17 min
Immunohistochemistry (IHC) and microsatellite instability (MSI) testing constitute the two major test modalities currently in use for detecting deficient mismatch repair (dMMR). Each is associated with caveats and limitations that can be consequential. Most notably, the traditional approach of defining mismatch repair protein IHC abnormality by complete loss of staining in all tumor cells is evolving. Partial or clonal loss is becoming recognized as a manifestation of gene abnormality; in some c...
Feb 01, 2023•31 min
The group of precursors that lead to HPV-independent, p53-wild-type squamous cell carcinoma is largely unexplored. Nonetheless, a subset of lesions with verruciform acanthosis and altered squamous maturation has been characterized using diverse nomenclature such as VAAD, vLSC, DEVIL, and VAM. These lesions are associated with invasive squamous cell carcinoma and verrucous carcinoma of the vulva, and they harbor recurrent alterations in oncogenes like PIK3CA, HRAS, and NOTCH1. Dr. Carlos Parra-He...
Jan 17, 2023•27 min
Adenoid Ameloblastoma is a very rare benign odontogenic tumor characterized microscopically by epithelium resembling conventional ameloblastoma, with additional duct-like structures, epithelial whorls, and cribriform architecture. Dentinoid deposits, clusters of clear cells, and ghost-cell keratinization may also be present.These tumors do not harbor BRAF or KRAS mutations and their molecular basis appears distinct from conventional ameloblastoma but remains unknown. Dr. Carolina Cavalieri Gomes...
Nov 24, 2022•18 min
Although prophylactic lymph node dissections do not improve survival, the prognostic implications of a positive sentinel node and the benefits of removing nodal metastases for loco-regional disease control remain important. There is a strong interest in novel approaches that can improve patients’ selection for sentinel lymphnode biopsies(SLNB) given that 85% of these procedures are negative and non-therapeutic. The host discusses with Dr. Alexander Meves his recent review in Modern Pathology on ...
Nov 10, 2022•26 min
Flat lesions of the urothelium with histologic features that falls short of the threshold for urothelial carcinoma in situ (CIS) remains a challenging problem in diagnostic surgical pathology. Among these are flat urothelial hyperplasia, urothelial dysplasia, and atypia of unknown significance; lesions that have struggled under evolving classifications, changing criteria, and limited clinical actionability, all confounded by the recognized lack of diagnostic reproducibility. In this episode of M...
Oct 27, 2022•30 min
Locally recurrent prostate cancer from 53 patients that failed radiation therapy and underwent salvage radical prostatectomy was analyzed for clinicopathological and genomic characteristics. Most radiorecurrent tumors were enriched in cribriform morphologies (invasive cribrifom PCa and intraductal carcinoma with cribriform pattern) and demonstrated potentially targetable genomic alterations (defects in DDR genes: TP53, BRCA2, PALB2, ATR etc.). The guest, Dr. Rajal Shah of UTSW, discusses how und...
Oct 13, 2022•18 min
Establishing an efficient and standardized workflow for performing molecular classification on ECs, and reporting both the molecular and histologic findings in an integrative manner, is imperative. Dr. Brooke Howitt discusses with the host her institution’s effort to implement rapid and routine molecular classification on all ECs diagnosed at Stanford.
Sep 29, 2022•18 min
Most succinate dehydrogenase (SDH)-deficient RCCs demonstrate classic morphology characterized by bland eosinophilic cells with intracytoplasmic inclusions. Increasingly, "variant" morphologic features are recognized. Drs. Anthony Gill and Talia Fuchs discuss with the host their findings in a recent publication in Modern pathology where features such as high-grade nuclear features, necrosis, papillary, solid, and tubular architecture are present. These features appear to be associated with more ...
Sep 15, 2022•21 min
The vast majority of image-detected breast abnormalities are currently diagnosed by percutaneous core needle biopsy (CNB). While management of frankly malignant lesions diagnosed by CNB is now well-defined, there is less consensus on the optimal management of high-risk and selected benign lesions diagnosed by CNB. In this episode, Dr. Benjamin Calhoun from University of North Carolina in Chapel Hill eloquently discusses the evidence for and against immediate excision of such lesions....
Sep 01, 2022•22 min
Modern Pathology have recently launched a new series of reviews addressing controversial issues in pathology. In this episode of ModPath CHAT, Dr. Elizabeth Montgomery, a world renowned expert in gastrointestinal pathology gives her point of view on the utility of ancillary testing for risk stratification of Barrett’s esophagus and dysplasia.
Aug 18, 2022•22 min
Ki-67 assessment is a key step in the diagnosis of neuroendocrine neoplasms (NENs) from all anatomic locations. The application of digital pathology coupled with machine learning has been shown to be highly accurate and reproducible for the evaluation of Ki-67 in NENs. The guest, Dr. Claudio Luchini from the University of Verona in Italy, discusses his recently published systematic review on the subject of Ki-67 assessment in pancreatic NENs (PanNENs) employing digital image analysis (DIA). The ...
Aug 04, 2022•18 min
In a subset of patients with metastatic colorectal cancer (mCRC), the peritoneum is the predominant site of dissemination. While cure can be achieved by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), this procedure is associated with long-term morbidity and high relapse rates. In this episode of ModPath CHAT, Drs. Siesing and Jirstrom from Lund University in Sweden discuss their recent study in Modern Pathology on the topic. Multi-region immunohistochemical pr...
Jul 21, 2022•15 min
Uterine leiomyosarcoma is the most common uterine mesenchymal malignancy. The majority present at stage I with variable clinical outcome. In this episode of ModPath Chat, Dr. David Chapel discusses his recently published multi-institutional study proposing a novel risk stratification model (shown below) for low stage uterine leiomyosarcoma. Risk score = (coagulative necrosis)(1) + (mitoses > 25 per 2.4mm2)(2) + (atypical mitoses)(2) + (lymphovascular invasion)(3) + (serosal abutment)(5)...
Jul 07, 2022•17 min
In this episode the audience will enjoy a great discussion of the growing potential of methylome and copy number profiling, a technique well established for the classification of brain tumors, in bone and soft tissue tumors diagnosis. Nuclear overexpression of FOS and FOSB have emerged as a reliable surrogate markers to detect rearrangements of the transcription factors FOS and FOSB in osteoid osteoma and osteoblastoma. Limitations in specificity and sensitivity remains with some osteosarcoma sh...
Jun 23, 2022•22 min
While AML and cysts are the most common renal manifestations in patients with inherited TSC syndromes, approximately 4% will develop renal cell carcinoma (RCC). These include RCC with clear cytoplasm, papillary architecture, and prominent smooth muscle stroma; RCC with granular eosinophilic cytoplasm and macrocystic architecture; and RCC resembling the eosinophilic variant of chromophobe RCC. In recent years and in five studies in the March 2022 issue of Modern Pathology , sporadic counter...
May 31, 2022•19 min
The host discusses with Dr. Sanjay Mukhopadhyay and Dr. Monisha Sudarshan from Cleveland Clinic their recent Modern Pathology editorial on the findings by F. Zhou et al. ( https://doi.org/10.1038/s41379-021-00875-x ). The concept of tumor spread through air spaces (STAS) has been recently introduced and is gaining momentum. On permanent sections, STAS has been associated with an increased likelihood of lymph node metastases and aggressive behavior. However, the validity of using STAS diagnosis o...
May 17, 2022•18 min
Dr. Inti Zlobec, professor of digital pathology at the Institute of Pathology in the University of Bern, discusses her team’s recent publication in Modern Pathology on the role of image analysis in assessing area of extracellular mucin and predicting consensus molecular subtypes (CMS) in colorectal carcinoma. The utilized deep learning algorithm had an excellent agreement with pathologists’ estimates of mucin areas. Coupled with MSI, mucinous area estimates may predict CMS classification using o...
May 03, 2022•15 min
An informative discussion with Dr. Buttner on the significance of newly acquired genetic insights into pulmonary invasive mucinous adenocarcinoma (IMA). In the latest WHO classification, IMA is defined as a primary lung adenocarcinoma with tumor cells showing goblet cell- or columnar cell-morphology with abundant intracytoplasmic mucin. Due to its distinctive clinical features, i.e., peripheral location and a high frequency of multifocal, multilobular, and bilateral occurrence it has been define...
Apr 19, 2022•21 min
Traditional pathology have played an integral role in the delivery of diagnosis, semi-quantitative or qualitative assessment of protein expression, and classification of disease. Technological advances have recently paved the way for the development of digital pathology-based approaches for quantitative pathologic assessments, namely whole slide imaging (WSI) and artificial intelligence (AI)–based solutions, allowing us to explore and extract information beyond human visual perception. In this e...
Apr 06, 2022•28 min
A subset of clinically benign uterine polyps shows atypical morphologic features worrisome for, but not diagnostic of, Mullerian adenosarcoma. The guest, Dr Marisa Nucci discusses her team’s finding in their recently published study in Modern Pathology. The authors propose the term "atypical uterine polyps" for these lesions, which show biologic overlap with early Mullerian adenosarcoma but lack molecular alterations characteristic of clinically aggressive adenosarcoma. Study by Nucci ...
Mar 22, 2022•18 min
Breast implant anaplastic large cell lymphoma (ALCL) is a T-cell neoplasm arising around textured breast implants. Our host discusses with Drs. Medeiros and Miranda their recent report on eight cases of Epstein–Barr virus (EBV)-positive large B-cell lymphoma associated with breast implants. Their data suggest a pathogenetic role for breast implants (as well as EBV) in the pathogenesis of this type of implant-associated lymphomas. Study by Medeiros and Miranda et al. Epstein–Barr-virus-positive l...
Mar 08, 2022•25 min
Professor Gregory Lauwers from Moffitt Cancer Center discusses his team’s recent study comparing index and metachronous gastric cancers in 42 Korean patients. Gastric adenocarcinomas were classified into 5 subtypes: EBV-associated, MMR deficient (MMRD), E cadherin aberrant, p53-aberrant [p53(+)], and p53 non-aberrant [p53(neg)]. Although no significant difference in the frequency of most molecular subtypes was found between index and metachronous lesions, the number of MMRD gastric cancers more ...
Feb 22, 2022•18 min
Drs. Timothy D’Alfonso, David Ho, and Lee K.Tan from Memorial Sloan Kettering in NY discuss their recent Modern Pathology study describing a new machine learning algorithm that can help pathologists assess shaved margins from lumpectomy specimens. A uniquely developed Deep Multi-Magnification Network (DMMN) was utilized in Whole Slide Images (WSI) in the hope to triage negative margins and allow pathologists to focus on shaves that are positive for DCIS and/or Invasive carcinoma....
Feb 09, 2022•19 min
Professor Holger Moch shares with our audience his most inspiring career journey as a physician scientist and a luminary in the field of renal cancers. An enjoyable historical look back at the evolution of the field and the progress in renal tumor classifications.
Jan 25, 2022•30 min
In this episode of ModPath CHAT, Dr. George J Netto reviews five of the highly cited manuscripts that were published in Modern Pathology in 2021.
Dec 28, 2021•13 min
Identification of molecular alterations in NTRK 1-3 has become increasingly important with the emergence of histology-agnostic, US Food and Drug Administration-approved, effective inhibitors. The host discusses with Dr. Jaclyn Hechtman, director of clinical diagnostic development at Neogenomics, her practical insights on how testing for NTRK fusion can best be implemented and communicated within the multidisciplinary healthcare team.
Dec 07, 2021•23 min
Dr. Dehner discusses his four decades journey with an entity that he first described in 1977. Since his initial description of Pleuropulmonary Blastoma (PPB), the neoplasm has become one of the defining entities of DICER1 Syndrome, a rare autosomal dominant familial tumor predisposition disorder with heterozygous DICER1 germline mutation. A fascinating historical perspective and most informative ModPath Chat episode on the wide spectrum of neoplasms that can be encountered in the syndrome awaits...
Nov 23, 2021•33 min
