ModPath Chat

In this episode, Dr. Brooke Howitt from Stanford University discusses her team’s recent study on PTEN expression in tubo-ovarian high-grade serous carcinoma (HGSCs). PTEN deficiency (complete or sub-clonal loss) as detected by immunohistochemistry was identified in 13 of the 62 HGSCs (21%) and was significantly correlated with reduced expression of estrogen receptor and worse first progression-fre...

Screening lymph nodes for metastases in colorectal cancer (CRC) can be a cumbersome task, but it is amenable to artificial intelligence (AI)-assisted diagnostic solutions. Prof. Inti Zlobec and Dr. Amjad Kahn from the Institute of Pathology in Bern, Switzerland discuss their newly proposed deep learning-based tool for the evaluation of CRC lymph node metastases in digitized whole-slide images. The...

Fundic gland polyps (FGPs) develop sporadically (frequently after proton pump inhibitor therapy) or in the setting of a hereditary polyposis syndrome, such as familial adenomatous polyposis (FAP). In the later setting, FGPs often demonstrate low-grade dysplasia and are frequently associated with APC mutations. Sporadic FGPs with dysplasia also demonstrate frequent APC mutations. Our guest, Dr. Won...

Psammomatoid ossifying fibroma (PsOF) is a benign fibro-osseous neoplasm that predominantly affects frontal and ethmoid bones, with a preference for adolescents and young adults. The clinical and morphologic features of PsOF overlap with other fibro-osseous lesions, and additional molecular markers may help increase their diagnostic accuracy. Chromosomal breakpoints at bands Xq26 and 2q33 have bee...

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Over the previous two decades, tremendous progress has been made in our understanding of the molecular pathogenesis of DLBCL. Unfortunately, these advances have not yet been translated into improvements in targeted therapy. In this podcast, our guest, Dr. Daniel J. Hodson of Cambridge University, discusses recen...

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 15...

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. O...

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. P...

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 evolv...

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, a...

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 bas...

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 no...

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 acti...

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 (defec...

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.

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, papil...

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 Hi...

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. 

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 s...

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 Swe...

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...

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 ost...

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 r...

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 likeliho...

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’ estima...