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Objectives The diagnostic efficacy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic solid masses varies widely depending on the presence of rapid onsite evaluation (ROSE) and the type of cytology preparations. The present study aims to compare the diagnostic efficacy of cytology smears (CS) and cell block (CB) with ROSE versus Thinprep slides (TpS) with CB without ROSE in diagnosing pancreatic solid masses. Methods Performed retroprospective review of 56 patients (2017-2018) with surgically confirmed pancreatic neoplasms including cytology preparation type and comparison of diagnostic efficacies. Results Out of 56 patients who underwent surgical resection, 30 patients were diagnosed with pancreatic ductal adenocarcinoma (PDAC) and 26 with pancreatic neuroendocrine tumor (PNET) or solid pseudopalliary neoplasm (SPN). Out of 30 surgically removed PDACs, 20 patients had prior cytology specimens while 10 had surgical core biopsies. Of the 20 cytology specimens, 12 patients had ROSE with concurrent CS and CB, and all cases were diagnosed as positive. Out of the 8 patients without ROSE, 3 patients (1 with bile duct brush, 2 with TpS and CB) were diagnosed as positive. The diagnostic efficacy was 100% (12/12) in patients with ROSE and CS compared to 37.5% (3/8) in patients without ROSE. In 26 non-PDAC cases, 21 patients had cytology specimens and 5 had surgical biopsies. Seventeen cases with ROSE and immunohistochemical stains (IHC) on CB were diagnosed as positive, while 4 cases without ROSE and IHC received atypical diagnoses, resulting in a decreased diagnostic efficacy from 100% (17/17) to 0% (0/4). Conclusion ROSE with CS and CB are superior to TpS and CB in diagnosing solid pancreatic masses. ROSE with IHC on CB is crucial for diagnosing PNET and SPN, while CS and CB are important for PDAC diagnosis.

A 25-year-old female underwent emergent laparoscopic salpingectomy when she presented with an ectopic pregnancy (G1P0). A bone marrow biopsy performed for moderate persistent thrombocytopenia (60-105 K/μL) showed normocellularity, maturing trilineage hematopoiesis, and mildly increased morphologically normal megakaryocytes reported as consistent with idiopathic thrombocytopenic purpura (ITP). However, on further inquiry, the patient stated that her sister, father, paternal aunt, and paternal grandfather have/had low platelets. Her father had been diagnosed with myelodysplasia (MDS). Her paternal grandmother had died of acute myeloid leukemia (AML). Thus, although her marrow morphology revealed no evidence of overt dysplasia and despite her normal karyotypic study, a sample was sent for RUNX1 sequence analysis. A splice site mutation (c.967 + 2_967 + 5delTAAG) in RUNX1 was detected and initially interpreted as a somatic mutation. However, given the strong family history of thrombocytopenia and MDS/AML, a sample from her father was also sent for RUNX1 sequence analysis, and the identical intronic sequence variant in the RUNX1 gene was detected in him. This confirmed the RUNX1 mutation to be germline. In the context of autosomal dominant thrombocytopenia in the patient’s family, the finding of this variant in the affected patient and her similarly affected father was consistent with a pathogenic role. Since this patient was of reproductive age actively trying to have children, these molecular genetic findings had important implications. She elected to undergo in vitro fertilization in order to choose embryos without the RUNX1 mutation for implantation. Considering that her father and paternal grandmother developed MDS/AML, and because familial platelet disorder with predisposition to AML appears to show “anticipation,” she would require close future monitoring for blastic transformation. This case illustrates the significance of careful history taking and high suspicion index that can lead to simplified targeted cost-effective molecular testing resulting in the correct diagnosis without necessarily employing large gene panels.

Acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) not only are the most common cancer in children, but also among the most curable. Contemporary therapy has achieved highly successful survival rates by risk stratification into low- and high-risk treatment groups. This has permitted tailoring therapy intensity to produce higher remission rates, even in unfavorable prognostic groups. Accurate diagnosis, subclassification, and identification of relevant prognostic factors for lymphoblastic malignant neoplasms, using a multiparametric approach including immunophenotyping, cytogenetic and molecular analysis, and more traditional pathologic criteria, provides information that allows each patient to receive appropriate treatment.

Primary cutaneous CD30+ T-cell lymphoproliferative disorders (LPD) represent a complex spectrum of related conditions that are not very well understood. Many may progress to more aggressive or systemic lymphomas. The factors involved in the progression of these LPDs are largely unknown. Advances in robust high throughput proteomics techniques permit elucidation of the molecular mechanisms underlying disease development and progression. In this study we applied a quantitative proteomics methodology involving isotope coded affinity tag reagents (ICAT™), 3-dimensional liquid chromatography (3-D LC), and tandem mass spectrometry (MS/MS) to evaluate the differential protein expression patterns of two unique T-cell lymphoma derived cell lines. The Mac-1 and Mac-2A are clonally related cell lines derived from the same cutaneous T-cell lymphoma (CTCL) at relatively indolent versus aggressive stages of tumor progression, respectively. Equivalent quantities of total cell lysates obtained from the two cell lines were labeled with cleavable ICAT™ and dialyzed prior to digestion with proteinase K. The labeled peptides were then subjected to strong cation-exchange (SCX) chromatography followed by further purification of each offline fraction using avidin affinity chromatography. These cysteine enriched ICAT™ labeled peptides were analyzed by reverse phase nanospray LC-MS/MS. Differential expression of 490 unique proteins was determined. Of these, a total of 59 proteins showed a 1.5 fold or greater increase in abundance while 86 proteins exhibited a similar decrease in the clinically aggressive lymphoma cells as compared to the more indolent form. Functional classification of the differentially expressed proteins revealed increased expression of those involved in cell signaling (neurotrophic tyrosine kinase receptor, ATP binding cassette transporter 1, SH3 protein interacting with NCK), transcription (HFK1, general transcription factor IIIC), and cell adhesion (ICAM, protocadherin) in the advanced lymphoma. There was also decreased expression in the advanced lymphoma of proteins which were involved in apoptosis (caspase 8), cell signaling (STAT4, LIM kinase), cell cycle regulation (CDC10 homolog, ankyrin 3), cell adhesion (laminin, periostin), and ion transport (voltage-gated potassium channel). Overexpression of MALT1/paracaspase that leads to activation of the NF-kappaB pathway was observed in the advanced lymphoma. Proteins such as Smad4 which is involved in regulation of the TGF-beta signaling pathway and ubiquitin specific protease of the ubiquitin-proteasomal degradation pathway that in turn regulates Smads were differentially expressed. Some of the proteins identified by MS were selected for confirmation by Western blot analysis. This study implicates deregulation of multiple signal transduction pathways during progression of CTCL and provides novel insights into the underlying molecular pathogenetic mechanisms involved.