Faculty Bibliography

Meningioma is the most common intracranial neoplasm, yet there is no effective therapy for recurrent/refractory meningiomas after surgery and radiation. Prostate-specific membrane antigen (PSMA) is an enzyme upregulated on endothelial cells of multiple neoplasms and is being investigated as a theranostic target. Until now, PSMA has not been studied in meningiomas. We aimed to verify PSMA endothelial expression in meningiomas, detect tumor grade variability, and investigate the relationship of PSMA signal with tumor recurrence. We analyzed 96 archival meningiomas including 58 de novo and 38 recurrent specimens. All specimens were stained routinely and immunostained for CD31 and PSMA. Slides were scanned and analyzed producing raw data for images of PSMA, CD31, PSMA/CD31, and PSMA/vasculature. PSMA expression was seen within 98.9% of meningioma samples. In the total cohort, higher-grade tumors had increased expression of raw PSMA and PSMA/CD31, and PSMA/vasculature ratios compared to grade 1 tumors. PSMA expression and PSMA/vasculature ratios (p = 0.0015) were higher in recurrent versus de novo tumors among paired samples. ROC curves demonstrated PSMA/CD31, PSMA/vasculature, and raw CD31 as indicators of tumor recurrence. Thus, PSMA is expressed within endothelial cells of meningiomas, is increased with tumor grade and recurrence, and persists with prior irradiation.

Ultrasound (US) guided core needle biopsy (CNB) for mass lesions resulting in a diagnosis of ductal carcinoma in situ (DCIS) is often considered radiologically discordant and generates surgical planning difficulty. One hundred cases of US-guided CNB for mass lesions diagnosed as DCIS were collected from 2013 to 2021. Histological features were reviewed and correlated with radiology and surgical excision findings. Thirty (30%) were high-grade (HG), and seventy (70%) were low- to intermediate-grade. Seventy-one (71%) cases had a histological correlate of a mass-forming lesion, including 26 (26%) were associated with benign mass-forming lesions (category 1) such as papilloma, complex sclerosing lesion/radial scar, fibroadenoma, sclerosing adenosis, and ruptured cyst; 23 (23%) were HG with solid pattern, comedo necrosis, and stromal desmoplasia (category 2); and 22 (22%) had predominantly papillary architecture (category 3). Twenty-nine (29%) were discordant with no histologic correlate of a mass lesion (category 4). Follow-up excisions were available in 79 cases. Invasive carcinoma was identified in 14 cases (18%), of which 8 were from the radiologically discordant category (35%), 3 (17%) associated with HG DCIS with desmoplasia, 2 (10%) associated with benign mass lesion and 1(5%) was predominantly papillary architecture. US-guided CNB for mass-forming lesions with a DCIS diagnosis on CNB can be grouped into four categories. Radiology-pathology correlation is essential. This categorization emphasized rad-path correlation and had a clear difference in upgrade rate on follow-up excision. Rad-path discordant biopsy cases were more likely to be associated with a missed invasive carcinoma (p < 0.05).

Breast cancer is the most diagnosed cancer in humans. In recent years, myxoid and proportionated stroma have been described as clinically significant in many cancer subtypes. Here computational portraits of tumor-associated stromata were created from a machine learning (ML) classifier using QuPath to evaluate proportionated stromal area (PSA), myxoid stromal ratio (MSR), and immune stroma proportion (ISP) from whole slide images (WSI). The ML classifier was validated in independent training (n = 40) and validation (n = 109) cohorts finding MSR, PSA, and ISP to be associated with tumor stage, lymph node status, Nottingham grade, stromal differentiation (SD), tumor size, estrogen receptor (ER), progesterone receptor (PR), and receptor tyrosine-protein kinase erbB-2 (HER-2). Overall, MSR correlated better with the clinicopathologic profile than PSA and ISP. High MSR was found to be associated with high tumor stage, low ISP, and high Nottingham histologic score. As a computational biomarker, high MSR was more likely to be associated with luminal B like, Her-2 enriched, and triple-negative biomarker status when compared to luminal A like. The supervised ML superpixel approach demonstrated here can be performed by a trained pathologist to provide a faster and more uniformed approach to the analysis to the tumoral microenvironment (TME). The TME may be relevant for clinical decision-making, determining chemotherapeutic efficacy, and guiding a more overall precision-based breast cancer care.

Plasma cell myeloma (PCM) is defined as a clonal disease of terminally differentiated plasma cells that secrete immunoglobulin. The biologic underpinnings of IgA-type multiple myeloma's (IgAMM) aggressive nature, including its increased morbidity and mortality, have not been elucidated. We describe the clinical, phenotypic, and cytogenetic characteristics of IgA-MM. Flow-cytometry analysis was performed to phenotype clonal plasma cell populations, and interface with fluorescent in situ hybridization (iFISH) to exploit cytogenetics to determine risk stratification; 68.1% of cases were of intermediate or high risk. On flow cytometry, samples from our IgA-PCM cohort revealed less frequent CD56 expression when compared to samples with other PCM subtypes. Our study demonstrated lower frequency of CD56 expression (52.8%). We hypothesize that loss of CD56 may play a significant role in the aggressive behavior of IgA-PCM due to the loss of cell-to-cell adhesion resulting in a higher propensity for extramedullary presentation.

A 60-year-old female presented with asymptomatic failing mandibular dental implants. Computed tomography (CT) showed a partially calcified, hypointense lesion within the soft tissues, measuring 1.3 x 0.8 x 1.0 cm along the buccal cortex. Incisional biopsy demonstrated a basaloid type of tumor composed of sheets of cells with plump ovoid nuclei, distinct nucleoli, and scant eosinophilic cytoplasm. Mitoses were present, averaging about 2 per 10 high power fields with scattered individual apoptotic cells. Numerous laminated calcified bodies (Liesegang rings) were observed with confluence of these bodies to form larger foci of dystrophic mineralization. These features clearly established the malignant nature of this tumor. Immunohistochemically, the tumor was positive for synaptophysin, focally positivity for CAM 5.2 and had a Ki-67 proliferation index of approximately 25%. This is the first report of a tumor with features of a malignant variant of calcifying epithelial odontogenic tumor and neuroendocrine differentiation.

Whether sentinel lymph node biopsy (SLNB) should be performed in patients with microinvasive breast cancer (MIBC) has been a matter of debate over the last decade. MIBC has a favorable prognosis and while metastasis to the axilla is rare, it can impact treatment recommendations. In this study we evaluated clinical and histological features in both MIBC and background DCIS including ER, PR, and HER-2, number of foci of MIBC, the extent of the DCIS, nuclear grade, presence of comedo necrosis, as well as surgical procedures, adjuvant treatment and follow up to identify variables which predict disease free survival (DFS), as well as the factors which influence clinical decision making. Our study included 72 MIBC patients with a mean patient follow-up time of 55 months. Three patients with MIBC had recurrence, and two deceased, leaving five patients in total with poor long-term outcomes and a DFS rate of 93.1%. Performing mastectomy, high nuclear grade, and negativity for ER and HER-2 were found to be associated with the use of SLNB, although none of these variables were found to be associated with DFS. One positive lymph node case was discovered following SLNB in our study. This suggests the use of SLNB may provide diagnostic information to some patients, although these are the anomalies. When comparing patients who had undergone SLNB to those which had not there was no difference in DFS. Certainly, the use of SLNB in MIBC is quite the conundrum. It is important to acknowledge that surgical complications have been reported, and traditional metrics used for risk assessment in invasive breast cancer may not hold true in the setting of microinvasion.

Breast cancers represent complex ecosystem-like networks of malignant cells and their associated microenvironment. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are biomarkers ubiquitous to clinical practice in evaluating prognosis and predicting response to therapy. Recent feats in breast cancer have led to a new digital era, and advanced clinical trials have resulted in a growing number of personalized therapies with corresponding biomarkers. In this state-of-the-art review, we included the latest 10-year updated recommendations for ER, PR, and HER2, along with the most salient information on tumor-infiltrating lymphocytes (TILs), Ki-67, PD-L1, and several prognostic/predictive biomarkers at genomic, transcriptomic, and proteomic levels recently developed for selection and optimization of breast cancer treatment. Looking forward, the multi-omic landscape of the tumor ecosystem could be integrated with computational findings from whole slide images and radiomics in predictive machine learning (ML) models. These are new digital ecosystems on the road to precision breast cancer medicine.

We report a collection of lung findings in a patient with a remote history of cigarette smoking, but now engaged in heavy nicotine vaping with daily edible and combustible cannabis use. Computed tomography (CT) imaging demonstrated numerous, small, and bilateral nodules with ground-glass appearance. The largest nodule is demonstrated in the right upper lung lobe. Clinically the differential diagnosis at this time included hypersensitivity pneumonitis and sarcoidosis. Atypical infection, particularly of a fungal etiology, and metastatic malignancy were also considered. Initial pathology of the right lung needle biopsy revealed alveolar septal thickening with associated atypical pneumocyte proliferation, suggestive of atypical adenomatous hyperplasia (AAH). Subsequently the patient underwent wedge resection of the right upper, middle and lower lobes. Pathology examination revealed pulmonary Langerhans cell histiocytosis (PLCH) in the upper and lower lobes, with CD1a staining highlighting the aggregates of Langerhans cells. Vascular changes were also present including intimal thickening of muscular pulmonary arteries, consistent with pulmonary hypertensive changes. Background lung parenchyma demonstrated respiratory bronchiolitis, smoking-related interstitial fibrosis, an organizing thrombus in muscular artery and associated pneumocyte hyperplasia.