A Rare Case of Squamous Cell Carcinoma of the Bladder Presenting as a Metastatic Right Ventricular Mass

A 74-year-old woman presented with bilateral lower extremity swelling, worsening dyspnea on exertion, and mild hemoptysis. An echocardiogram at time of admission showed a mass in the right ventricle. The pathology of a sample obtained via transvenous biopsy was consistent with squamous cell carcinoma; no primary source could initially be identified. Severe thrombocytopenia, likely consumptive, precluded surgical intervention, so the patient underwent palliative radiation. Unfortunately, she developed fatal respiratory failure. Upon autopsy, the bladder was found to contain polyps of invasive squamous cell carcinoma, similar in morphology to the tumor mass in the heart. Her lungs contained multiple tumor emboli at different stages, which was likely the final cause of her death. Squamous cell carcinoma metastases to the endocardium are extremely rare and without defined treatment. Surgery can improve prognosis in those with primary tumors that are benign or without metastases. In those with symptomatic metastatic tumors, palliative debulking can done although generally will not improve prognosis. It is currently unknown whether radiation improves survival. In this case, irradiation did destroy a portion of the tumor as the final pathology showed extensive necrosis of the tumor; unfortunately, it did not change her symptoms and did not change the final outcome

Hierarchical Classification System for Breast Cancer Specimen Report (HCSBC) -- an end-to-end model for characterizing severity and diagnosis

Automated classification of cancer pathology reports can extract information from unstructured reports and categorize each report into structured diagnosis and severity categories. Thus, such system can reduce the burden for populating tumor registries, help registration for clinical trial as well as developing large dataset for deep learning model development using true pathologic ground truth. However, the content of breast pathology reports can be difficult for categorize due to the high linguistic variability in content and wide variety of potential diagnoses >50. Existing NLP models are primarily focused on developing classifier for primary breast cancer types (e.g. IDC, DCIS, ILC) and tumor characteristics, and ignore the rare diagnosis of cancer subtypes. We then developed a hierarchical hybrid transformer-based pipeline (59 labels) - Hierarchical Classification System for Breast Cancer Specimen Report (HCSBC), which utilizes the potential of the transformer context-preserving NLP technique and compared our model to several state of the art ML and DL models. We trained the model on the EUH data and evaluated our model's performance on two external datasets - MGH and Mayo Clinic. We publicly release the code and a live application under Huggingface spaces repositor

Enhanced down-regulation of ALCAM/CD166 in African-American breast cancer

Background: Variation in tumor biology in African-American (AA) and Caucasian (CAU) women with breast cancer is poorly defined. Activated leukocyte cell adhesion molecule (ALCAM) is a bad prognostic factor of breast cancer yet it has never being studied in the AA population. We tested the hypothesis that ALCAM expression would be markedly lower in cases of AA breast cancer when compared to CAU. Methods: Cases of breast cancer among AA (n = 78) and CAU (n = 95) women were studied. Immunohistochemical staining was used to semi-quantitatively score ALCAM expression in tumor and adjacent non-tumor breast tissues. Clinico-pathological characteristics including histological type, histological grade, tumor size, lymph node metastasis, estrogen receptor (ER), progesterone receptor (PR), and HER2-neu status were abstracted, and their association with ALCAM expression tested. Results: Univariate analysis revealed that the level of ALCAM expression at intercellular junctions of primary tumors correlates with histological grade (AA; p = 0.04, CUA; p = 0.02), ER status (AA; p = 0.0004, CAU; p = 0.0015), PR status (AA; p = 0.002, CUA p = 0.034) and triple-negative tumor status (AA; p = 0.0002, CAU; p = 0.0006,) in both ethnic groups. Multivariate analysis demonstrated that ethnicity contribute significantly to ALCAM expression after accounting for basal-like subtype, age, histological grade, tumor size, and lymph node status. Compared to CAU tumors, the AA are 4 times more likely to have low ALCAM expression (p = 0.003). Conclusions: Markedly low expression of ALCAM at sites of cell-cell contact in primary breast cancer tumors regardless of differentiation, size and lymph node involvement may contribute to the more aggressive phenotype of breast cancer among AA women

Distribution of p63, a novel myoepithelial marker, in fine-needle aspiration biopsies of the breast: an analysis of 82 samples

BACKGROUND. The presence of myoepithelial cells (MECs) in fine-needle aspiration biopsies (FNAB) of the breast constitute an important criterion used to diagnose benign breast lesions. However, MECs sometimes have a distorted cytomorphology, and most of the previously evaluated myoepithelial markers do not have satisfactory sensitivity and specificity. p63, a recently characterized p53 homolog, is a nuclear transcription factor that is expressed in basal cells of multilayered epithelia and myoepithelial cells of the breast. The authors analyzed the immunocytochemical distribution of p63 in a series of 82 breast FNABs (30 benign lesions and 52 malignant breast lesions). METHODS. Eighty-two archival, Papanicolaou-stained smears of breast lesions were retrieved from the files of the authors’ institutions. Immunocytochemistry was performed according to the streptavidin-biotin-peroxidase complex technique using the antibody 4A4 (against all p63 isoforms). Two pathologists evaluated the distribution of p63 positive cells. Only nuclear reactivity was considered specific. RESULTS. In benign lesions, p63 decorated the nuclei of MECs in all samples. p63 also stained naked nuclei in fibroadenomas. In malignant lesions, p63 was positive in MECs overlying malignant cell clusters in all 8 samples of ductal carcinoma in situ (DCIS), in 9 of 16 samples of pure invasive carcinomas (IC), and in 16 of 20 samples that contained both DCIS and IC. In 18 samples (36%), a variable population of p63 positive, malignant cells was observed. p63 failed to decorate stromal, neural, adipocytic, and smooth muscle cells in all samples. CONCLUSIONS. p63 is a reliable nuclear marker of MECs in breast aspirates. Regardless of the fact that variable proportions of p63 positive, malignant cells were observed in 36% of breast carcinoma aspirates, p63 may be a useful adjunct antibody to confirm the presence of MECs in FNABs of benign breast lesions.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/5386/2001

Prognostic biomarkers in patients with human immunodeficiency virusâ positive disease with head and neck squamous cell carcinoma

BackgroundWe examined the prognostic value of a panel of biomarkers in patients with squamous cell carcinoma of the head and neck (SCCHN) who were human immunodeficiency virus (HIV) positive (HIVâ positive head and neck cancer) and HIV negative (HIVâ negative head and neck cancer).MethodsTissue microarrays (TMAs) were constructed using tumors from 41 disease siteâ matched and ageâ matched HIVâ positive head and neck cancer cases and 44 HIVâ negative head and neck cancer controls. Expression of tumor biomarkers was assessed by immunohistochemistry (IHC) and correlations examined with clinical variables.ResultsExpression levels of the studied oncogenic and inflammatory tumor biomarkers were not differentially regulated by HIV status. Among patients with HIVâ positive head and neck cancer, laryngeal disease site (P = .003) and Clavienâ Dindo classification IV (CD4) counts <200 cells/μL (P = .01) were associated with poor prognosis. Multivariate analysis showed that p16 positivity was associated with improved overall survival (OS; P < .001) whereas increased expression of transforming growth factorâ beta (TGFâ β) was associated with poor clinical outcome (P = .001).ConclusionDisease site has significant effect on the expression of biomarkers. Expression of tumor TGFâ β could be a valuable addition to the conventional risk stratification equation for improving head and neck cancer disease management strategies.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139994/1/hed24911.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139994/2/hed24911_am.pd

Inhibition of Progenitor Dendritic Cell Maturation by Plasma from Patients with Peripartum Cardiomyopathy: Role in Pregnancy-associated Heart Disease

Dendritic cells (DCs) play dual roles in innate and adaptive immunity based on their functional maturity, and both innate and adaptive immune responses have been implicated in myocardial tissue remodeling associated with cardiomyopathies. Peripartum cardiomyopathy (PPCM) is a rare disorder which affects women within one month antepartum to five months postpartum. A high occurrence of PPCM in central Haiti (1 in 300 live births) provided the unique opportunity to study the relationship of immune activation and DC maturation to the etiology of this disorder. Plasma samples from two groups (n = 12) of age- and parity-matched Haitian women with or without evidence of PPCM were tested for levels of biomarkers of cardiac tissue remodeling and immune activation. Significantly elevated levels of GM-CSF, endothelin-1, proBNP and CRP and decreased levels of TGF- were measured in PPCM subjects relative to controls. Yet despite these findings, in vitro maturation of normal human cord blood derived progenitor dendritic cells (CBDCs) was significantly reduced (p < 0.001) in the presence of plasma from PPCM patients relative to plasma from post-partum control subjects as determined by expression of CD80, CD86, CD83, CCR7, MHC class II and the ability of these matured CBDCs to induce allo-responses in PBMCs. These results represent the first findings linking inhibition of DC maturation to the dysregulation of normal physiologic cardiac tissue remodeling during pregnancy and the pathogenesis of PPCM