- Anatomic and Clinical Pathology
Board Certification: American Board of Pathology, Cytopathology (2019)
Fellowship: Stanford University Cytopathology Fellowship (2019) CA
Board Certification: American Board of Pathology, Anatomic and Clinical Pathology (2018)
Residency: Stanford University Department of Pathology (2018) CA
Medical Education: University of California San Diego School of Medicine (2014) CA
Residency, Stanford University, Anatomic and Clinical Pathology (2018)
MD, University of California-San Diego (2014)
BS, University of Southern California, Chemistry (2009)
BA, University of Southern California, Music (2009)
Clinicopathologic Features of Human Monkeypox Lymphadenitis.
View details for DOI 10.1111/his.14878
View details for PubMedID 36734592
Randomized controlled trial investigating use of submucosal injection of EverLift in rates of complete resection of non-pedunculated 4-9mm polyps.
International journal of colorectal disease
INTRODUCTION: Currently, cold snare polypectomy (CSP) without submucosal injection is recommended for removing polyps<10mm. Use of viscous submucosal agents has not been previously evaluated in CSP. We investigate the potential role of EverLift (GI Supply, Pennsylvania) in CSP.METHODS: The study is a single-center prospective randomized non-inferiority clinical trial evaluating CSP of non-pedunculated 4-9mm polyps, with or without submucosal injection of EverLift. Patients 18-80years of age presenting for colonoscopy were recruited. Eligible polyps underwent block randomization to CSP with or without EverLift. Following CSP, two biopsies were performed at the CSP site margin. The primary non-inferiority outcome was complete resection rate, defined by absence of residual polyp in the margin biopsies (non-inferiority margin-10%).RESULTS: A total of 291 eligible polyps underwent CSP, with 142 removed using EverLift. There was similar polyp size and distribution of pathology between the two groups. Overall, there was a low rate of positive margins with (1.4%) or without submucosal injection (2.8%), with no significant difference in complete resection (difference 1.28%, 95% CI:-2.66 to 5.42%), demonstrating non-inferiority of EverLift injection. Use of EverLift significantly increased CSP time (109.8 vs 38.8s, p<0.0001) and frequency of use of hemostatic clips (13.4 vs 3.6%, p=0.002).CONCLUSION: Submucosal injection of EverLift was non-inferior to CSP of 4-9mm polyps without injection and increased time for resection as well as use of hemostatic clips to control acute bleeding. Our results suggest that polypectomy of 4-9mm polyps can be safely performed without submucosal injection of EverLift.
View details for DOI 10.1007/s00384-022-04136-4
View details for PubMedID 35507047
Randomized controlled Trial Investigating cold snare aNd forceps polypectomY among small POLYPs in rates of complete resection: the TINYPOLYP Trial.
The American journal of gastroenterology
BACKGROUND: Optimizing complete resection during colonoscopy is important as residual neoplastic tissue may play a role in interval cancers. The United States Multi-Society Task Force recommends diminutive (<5mm) and small (6-9mm) polyps be removed by cold snare polypectomy (CSP). However, evidence is less clear whether CSP retains significant advantage over cold forceps polypectomy (CFP) for polyps <3mm.METHODS: This study is a single-center prospective non-inferiority randomized clinical trial evaluating CFP and CSP for nonpedunculated polyps <3mm. Patients >18 years of age undergoing colonoscopy for any indication were recruited. During each colonoscopy, polyps underwent block randomization to removal with CFP or CSP. Following polypectomy, two biopsies were taken from the polypectomy margin. The primary non-inferiority outcome was complete resection rate, defined by absence of residual polyp in the margin biopsies.RESULTS: A total of 179 patients were included. Patients had similar distribution in age, sex, race/ethnicity, as well as indication of procedure. A total of 279 polyps <3mm were identified, with 138 in the CSP group and 141 in the CFP group. Mean polypectomy time was longer for CSP compared to CFP (42.3 vs 23.2 seconds, p<0.001), though a higher proportion of polyps removed by CFP were removed in more than one piece compared to CSP (15.6 vs 3.6%, p<0.001). There were positive margin biopsies in 2 cases per cohort, with complete resection rate of 98.3% in both groups. There was no significant difference in cohorts in complete resection rates (difference in complete resection rates was 0.057%, 95% CI: -4.30 to 4.53%), demonstrating non-inferiority of CFP compared to CSP.CONCLUSIONS: Use of CFP was non-inferior to CSP in the complete resection of nonpedunculated polyps <3mm. CSP required significantly more time to perform compared to CFP. CFP should be considered an acceptable alternative to CSP for removal of polyps <3mm.
View details for DOI 10.14309/ajg.0000000000001799
View details for PubMedID 35467557
Immunohistochemical Characterization of 120 Testicular Sex Cord-Stromal Tumors With an Emphasis on the Diagnostic Utility of SOX9, FOXL2, and SF-1.
The American journal of surgical pathology
Sex cord-stromal tumors (SCSTs) account for the second most common category of testicular neoplasms and include several entities that may show overlapping morphologies and present diagnostic challenges. We analyzed a cohort of 120 testicular SCSTs and investigated the diagnostic utility of SRY-box transcription factor 9 (SOX9), forkhead box protein L2 (FOXL2), and steroidogenic factor 1 (SF-1) immunohistochemical stains. The results were compared with the more commonly used SCST markers, inhibin alpha, calretinin, and Wilms' tumor 1 (WT1). SF-1 was overall the most sensitive stain (91%), followed by inhibin alpha (70%), calretinin (52%), FOXL2 (50%), SOX9 (47%), and WT1 (37%), but sensitivities varied by tumor type. SOX9 and calretinin were more commonly positive in sex cord elements versus stromal elements (62% vs. 27% and 47% vs. 9%, respectively), whereas FOXL2 was more commonly positive in stromal elements versus sex cord elements (100% vs. 55%) when excluding Leydig cell tumors from the stromal category. Although no individual stain was diagnostically specific, some immunophenotypic patterns were noted that may help in the subclassification of SCSTs. We conclude that SOX9, FOXL2, and SF-1 are useful immunohistochemical stains for confirming sex cord-stromal differentiation in testicular tumors and provide increased sensitivity as well as additional diagnostic information, especially when combined with the more commonly used inhibin alpha, calretinin, and WT1 immunostains. Although morphology is paramount for subclassification of SCSTs, knowledge of certain immunohistochemical patterns may be helpful for diagnostically challenging cases.
View details for DOI 10.1097/PAS.0000000000001704
View details for PubMedID 34232606
Immunohistochemical ALK Expression in Granular Cell Atypical Fibroxanthoma: A Diagnostic Pitfall for ALK-Rearranged Non-neural Granular Cell Tumor.
The American Journal of dermatopathology
Atypical fibroxanthoma (AFX) is a neoplasm that most commonly occurs on sun-damaged skin of the head and neck in elderly patients and that usually exhibits indolent clinical behavior with complete excision. The granular cell variant of AFX demonstrates overlapping histopathologic features with dermal non-neural granular cell tumor (NNGCT), which typically arises on the extremities of young to middle aged adults with rare reports of regional metastasis. A subset of NNGCT harbors ALK rearrangements and expresses ALK by immunohistochemistry. Here, we present 2 cases of granular cell AFX occurring on the scalp of males aged 73 and 87 with ALK expression by immunohistochemistry and no evidence of an ALK rearrangement on fluorescence in situ hybridization, representing a diagnostic pitfall for NNGCT.
View details for DOI 10.1097/DAD.0000000000001931
View details for PubMedID 33767072
Metastatic squamous cell carcinoma transformed from prostatic adenocarcinoma following androgen deprivation therapy: A case report with clinicopathologic and molecular findings.
2020; 48 (12): E14-E17
Squamous cell carcinoma (SCC) of the prostate is a rare and clinically aggressive entity that may arise de novo or through transformation of prostatic adenocarcinoma, typically following hormonal or radiation therapy. Confirmation of prostatic origin, especially when evaluating a metastatic focus, often requires correlation with clinical and imaging findings, as the morphologic and immunohistochemical features of SCC are not organ-specific. Comprehensive genomic profiling (CGP) may provide additional information useful for confirming the primary site and for identifying potential targeted therapy options. CGP data may also contribute to our understanding of the molecular basis of squamous differentiation in prostatic malignancies. However, these data are limited, and to our knowledge, there are only three previously published cases of prostatic SCC with reported CGP findings. Herein, we report a case of metastatic keratinizing SCC diagnosed by core needle biopsy in a 68-year-old man with a history of prostatic adenocarcinoma status post radical prostatectomy and androgen deprivation therapy (ADT). NKX3.1 immunohistochemistry was negative. CGP was performed, and a TMPRSS2-ERG fusion, among other genetic alterations, was detected, supporting a diagnosis of metastatic SCC transformed from prostatic adenocarcinoma following ADT. This case supports the use of CGP or other molecular techniques not only to query potential targeted therapy options but also to refine the diagnosis and confirm the primary site of disease in cases with non-specific morphologic and immunophenotypic features, such as SCC.
View details for DOI 10.1002/dc.24539
View details for PubMedID 32628337
Targeted deep sequencing of cell-free DNA in serous body cavity fluids with malignant, suspicious, and benign cytology.
BACKGROUND: Liquid biopsy using cell-free DNA (cfDNA) presents new opportunities for solid tumor genotyping. While studies have demonstrated the utility of cfDNA from plasma, cfDNA from other body fluids remains underexplored.METHODS: We evaluated the molecular features and clinicopathologic correlates of cfDNA from serous body cavity fluids by performing hybrid capture-based next-generation sequencing (NGS) on cfDNA isolated from residual effusion supernatants. Twenty-one serous effusions from pleural (n=15), peritoneal (n=5), and pericardial (n=1) cavity were analyzed.RESULTS: The supernatants provided a median cfDNA concentration of 10.3ng/L. Notably, all effusions were sequenced successfully to a median depth >1000*, revealing a broad range of genetic alterations including single nucleotide variants, small insertions and deletions, amplifications, and fusions. Specifically, pathogenic alterations were identified in all malignant fluids (13/13), all fluids suspicious for malignancy (2/2), and 1 benign fluid (1/6) from a patient with metastatic cancer. To validate our findings, we examined matching results from 11 patients who underwent additional testing using formalin-fixed, paraffin-embedded (FFPE) specimens. In 8 patients, the paired results between FFPE and supernatant testing were concordant, whereas in the remaining 3 patients, supernatant analysis identified additional variants likely associated with resistance to targeted therapies. Additional comparison between FFPE and supernatant testing showed no difference in DNA concentration (P=.5), depth of coverage (P=.6), or allele frequency of pathogenic mutations (P=.7).CONCLUSION: cfDNA isolated from serous body cavity fluids represents a promising source of genomic input for targeted NGS.
View details for DOI 10.1002/cncy.22205
View details for PubMedID 31751001
A Clinicopathologic and Molecular Analysis of Fumarate Hydratase-Deficient Renal Cell Carcinoma in 32 Patients.
The American journal of surgical pathology
Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare and recently described entity associated with hereditary leiomyomatosis and RCC syndrome. FH-deficient RCC may show variable clinical and pathologic findings, but commonly presents with locally advanced and metastatic disease and carries a poor prognosis. We identified 32 patients with FH-deficient RCC, confirmed by FH immunohistochemistry (IHC) and/or FH mutation analysis, and performed a retrospective review of the clinical and pathologic features. Median age at presentation was 43 years (range, 18 to 69y), and the M:F ratio was 2.2:1. Median tumor size was 6.5cm (range, 2.5 to 28cm), and 71% presented at stage ≥pT3a. After a median follow-up of 16 months (range, 1 to 118mo) in 26 patients, 19% showed no evidence of disease, 31% were alive with disease, and 50% were dead of disease. The vast majority of cases showed multiple histologic growth patterns, with papillary (52%) being the most common predominant pattern, followed by solid (21%), cribriform/sieve-like (14%), sarcomatoid (3%), tubular (3%), cystic (3%), and low-grade oncocytic (3%). Viral inclusion-like macronucleoli with perinucleolar clearing were present in almost all cases (96%). All cases were evaluated using FH IHC, and 3 cases (9%) showed retained FH expression. Nineteen cases had germline or tumor mutation analysis confirming a FH mutation, with 79% (11/14) of cases showing mutations within coding regions and 21% (3/14) showing mutations within intronic splice-sites. By IHC, 97% (32/33) of cases were negative for CK7, 93% (27/29) were negative for p63, and 52% (15/29) were negative for GATA3. All cases stained were positive for PAX8 and showed retained succinate dehydrogenase B expression. Our overall findings show that FH-deficient RCC is considerably heterogenous in morphology and frequently behaves aggressively. Suspicion for this entity should be raised even in the absence of predominantly papillary architecture and characteristic nucleolar features. We have included cases with uncommonly seen features, including 4 cases with predominantly cribriform/sieve-like architecture as well as one case with pure low-grade oncocytic morphology (9y of clinical follow-up without evidence of disease). Although FH IHC is a useful tool for identifying cases of FH-deficient RCC, not all cases of FH-deficient RCC show loss of FH staining, and FH mutation analysis should be considered for patients with suspicious clinical or pathologic features, even in cases with retained FH IHC expression.
View details for DOI 10.1097/PAS.0000000000001372
View details for PubMedID 31524643
Evaluation of Diagnostic Accuracy and a Practical Algorithmic Approach for the Diagnosis of Renal Masses by FNA
2018; 126 (9): 782–96
View details for DOI 10.1002/cncy.22037
View details for Web of Science ID 000454533300006
Flow Immunophenotyping of Benign Lymph Nodes Sampled by FNA: Representative With Diagnostic Pitfalls
2018; 126 (9): 797–808
View details for DOI 10.1002/cncy.22038
View details for Web of Science ID 000454533300007
An integrated flow cytometry analysis of 286 mature B cell neoplasms identifies CD13 as a useful marker for diagnostic subtyping.
International journal of laboratory hematology
INTRODUCTION: CD13 is a myeloid associated antigen, which may be expressed by a subset of B cell lymphomas; however, the significance of its expression along with other B cell associated antigens is not well characterized.METHODS: Two hundred and eighty-six mature B cell neoplasms with flow cytometric analysis performed at the time of diagnosis were identified. Expression of CD13, CD45, CD19, CD20, CD5, CD10, CD38, CD22, CD23, FMC7, and kappa and lambda light chains was assessed for each case and correlated with clinicopathologic features.RESULTS: CD13 expression was associated specifically with cases of lymphoplasmacytic lymphoma (LPL) (16/26)- and FMC7-positive chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (11/30). No cases of follicular lymphoma (FL) expressed CD13 (0/48). Across all B cell neoplasms, CD13 expression positively correlated with FMC7 co-expression and kappa light chain restriction and negatively correlated with CD10 co-expression and lambda light chain restriction. No significant association of CD13 with overall or disease free survival in B cell neoplasms was seen.CONCLUSION: CD13 expression is present more often in LPL- and FMC7-positive CLL/SLL than other mature B cell lymphoma subtypes and absent in cases of FL and may be a useful feature for diagnostic subtyping.
View details for PubMedID 30066366
Cardiovascular pathology in 2 young adults with sudden, unexpected death due to coronary aneurysms from Kawasaki disease in childhood
2015; 24 (5): 310-316
Coronary artery aneurysms (CAA) may remain silent after Kawasaki disease (KD) until adulthood when myocardial ischemia can lead to sudden death. We postulated that there would be young adults with sudden, unexpected death due to CAA from KD who would have a state-mandated autopsy performed by the San Diego County Medical Examiner's Office (SDCMEO).We reviewed all autopsy cases <35years of age from 1997 to 2012 at the SDCMEO with a cardiovascular cause of death (n=154).We found 2 cases meeting inclusion criteria. Case 1 was a 22-year-old Korean male with chronic ischemic changes due to a partially occluded and diffusely calcified 15mm aneurysm at the bifurcation of the left main coronary artery. Interview of the mother revealed that this patient had been diagnosed with KD complicated by giant aneurysms at age two years. Case 2 was a 30-year-old Hispanic male with myocardial infarction due to thrombosis of a calcified left anterior descending artery aneurysm. Histologic findings included diffuse myocardial fibrosis and a recanalized aneurysm in the right coronary artery. Interview of the family revealed a KD-compatible illness in childhood. Immunohistochemical staining showed expression of transforming growth factor β pathway molecules in the aneurysmal arterial wall.In a medical examiner's office serving a population of approximately 3 million people, 2 of 154 (1.3%) cardiovascular deaths in persons <35years were attributed to cardiovascular complications of KD in childhood. Antecedent KD should be considered in the evaluation of all cases of sudden, unexpected death in young adults.
View details for DOI 10.1016/j.carpath.2015.02.006
View details for Web of Science ID 000361183400007
View details for PubMedID 25791439
View details for PubMedCentralID PMC4547904
Synthesis of Dihydropyrimidinones/Thiopyrimidinones: Nafion-Ga, an Efficient "Green" Lewis Acid Catalyst for the Biginelli Reaction
2014; 144 (12): 2012-2020
View details for DOI 10.1007/s10562-014-1364-8
View details for Web of Science ID 000345843700004
Differential Expression of miR-145 in Children with Kawasaki Disease
2013; 8 (3)
Kawasaki disease is an acute, self-limited vasculitis of childhood that can result in structural damage to the coronary arteries. Previous studies have implicated the TGF-β pathway in disease pathogenesis and generation of myofibroblasts in the arterial wall. microRNAs are small non-coding RNAs that modulate gene expression at the post-transcriptional level and can be transported between cells in extracellular vesicles. To understand the role that microRNAs play in modifying gene expression in Kawasaki disease, we studied microRNAs from whole blood during the acute and convalescent stages of the illness.RNA isolated from the matched whole blood of 12 patients with acute and convalescent Kawasaki disease were analyzed by sequencing of small RNA. This analysis revealed six microRNAs (miRs-143, -199b-5p, -618, -223, -145 and -145* (complementary strand)) whose levels were significantly elevated during the acute phase of Kawasaki disease. The result was validated using targeted qRT-PCR using an independent cohort (n = 16). miR-145, which plays a critical role in the differentiation of neutrophils and vascular smooth muscle cells, was expressed at high levels in blood samples from acute Kawasaki disease but not adenovirus-infected control patients (p = 0.005). miR-145 was also detected in small extracellular vesicles isolated from acute Kawasaki disease plasma samples. Pathway analysis of the predicted targets of the 6 differentially expressed microRNAs identified the TGF-β pathway as the top pathway regulated by microRNAs in Kawasaki disease.Sequencing of small RNA species allowed discovery of microRNAs that may participate in Kawasaki disease pathogenesis. miR-145 may participate, along with other differentially expressed microRNAs, in regulating expression of genes in the TGF-β pathway during the acute illness. If the predicted target genes are confirmed, our findings suggest a model of Kawasaki disease pathogenesis whereby miR-145 modulates TGF-β signaling in the arterial wall.
View details for DOI 10.1371/journal.pone.0058159
View details for Web of Science ID 000316936100081
View details for PubMedID 23483985
View details for PubMedCentralID PMC3590129
Precise Control of Protein Concentration in Living Cells
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2010; 49 (45): 8458-8461
View details for DOI 10.1002/anie.201003073
View details for Web of Science ID 000284015600031
View details for PubMedID 20878685