Bio

Clinical Focus


  • Anatomic Pathology

Academic Appointments


  • Assistant Professor - Med Center Line, Pathology

Professional Education


  • Fellowship:Brigham and Women's Hospital Anesthesiology Residency (2014) MA
  • Residency:Brigham and Women's Hospital (2013) MA
  • Board Certification: Anatomic Pathology, American Board of Pathology (2013)
  • Medical Education:Stanford University School of Medicine Registrar (2010) CA

Publications

All Publications


  • Evidence of a Monoclonal Origin for Bilateral Serous Tubal Intraepithelial Neoplasia. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists Meserve, E. E., Strickland, K. C., Miron, A., Soong, T. R., Campbell, F., Howitt, B. E., Crum, C. P. 2018

    Abstract

    Serous tubal intraepithelial carcinoma (STIC) is found in 10% to 60% of cases of tuboovarian high-grade serous carcinoma (HGSC) and is presumed to be the site of origin, linking many HGSCs to the fallopian tube. Bilateral STIC is present in 20% of cases. Because clonal Tp53 mutations are a defining feature of HGSC, including their associated STICs, we analyzed 4 cases of bilateral serous tubal intraepithelial neoplasia (STIN), including STIC and Tp53-mutated serous tubal intraepithelial lesions (STILs), associated with HGSC to determine whether they contained the same or different p53 mutations. Extracted DNA from STINs, concurrent HGSCs and control tissues was analyzed for mutations in all exons of Tp53. Sequencing was successful in 3 of the 4 cases, and an identical Tp53 mutation was detected in the HGSC and bilateral STINs in 2 of these 3 cases. One STIN was morphologically a STIL. These findings confirm that a subset of bilateral STINs share the same Tp53 mutation, implying that at least one of the STINs is an intraepithelial metastasis from either the contralateral STIN or HGSC. This study complements others addressing the multiple origins of STIN in the setting of existing HGSC. It further underscores the fact that potential overlap in biologic behavior between STILs and STICs as well as timing and direction of metastatic spread has yet to be resolved.

    View details for DOI 10.1097/PGP.0000000000000534

    View details for PubMedID 29901519

  • Assessment of a Chemotherapy Response Score (CRS) System for Tubo-Ovarian High-Grade Serous Carcinoma (HGSC). International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists Ditzel, H. M., Strickland, K. C., Meserve, E. E., Stover, E., Konstantinopoulos, P. A., Matulonis, U. A., Muto, M. G., Liu, J. F., Feltmate, C., Horowitz, N., Berkowitz, R. S., Gupta, M., Hecht, J. L., Lin, D. I., Jochumsen, K. M., Welch, W. R., Hirsch, M. S., Quade, B. J., Lee, K. R., Crum, C. P., Mutter, G. L., Nucci, M. R., Howitt, B. E. 2018

    Abstract

    A chemotherapy response score (CRS) system was recently described to assess the histopathologic response and prognosis of patients with tubo-ovarian high-grade serous carcinoma (HGSC) receiving neoadjuvant chemotherapy. The current study was performed as an independent assessment of this CRS system. We retrospectively identified advanced stage HGSC patients who received neoadjuvant chemotherapy and underwent interval debulking. If available, a hemotoxylin and eosin slide from the omentum and the adnexa was selected for the study. Slides were independently scored by 13 pathologists using the 3-tiered CRS system. Reviewers then received web-based training and rescored the slides. Overall survival and progression-free survival were estimated using the Kaplan-Meier method and compared using the log-rank test. A total of 68 patients with omental (n=65) and/or adnexal (n=59) slides were included in the study. Interobserver reproducibility was moderate for omentum (kappa, 0.48) and poor for adnexa (kappa, 0.40), which improved for omentum (kappa, 0.62) but not for adnexa (kappa, 0.38) after online training. For omental slides, a consensus CRS of 1/2 was associated with a shorter median progression-free survival (10.9mo; 95% confidence interval, 9-14) than a CRS of 3 (18.9mo; 95% CI, 18-24; P=0.020). In summary, a 3-tiered CRS system of hemotoxylin and eosin-stained omental deposits can yield prognostic information for HGSC patients receiving neoadjuvant chemotherapy, and web-based training improved reproducibility but did not alter determination of clinical outcomes. The CRS system may allow oncologists to identify potential nonresponders and triage HGSC patients for heightened observation and/or clinical trials.

    View details for DOI 10.1097/PGP.0000000000000513

    View details for PubMedID 29750700

  • Solitary fibrous tumour of the female genital tract: a clinicopathological analysis of 25 cases HISTOPATHOLOGY Yang, E. J., Howitt, B. E., Fletcher, C. M., Nucci, M. R. 2018; 72 (5): 749–59

    Abstract

    Solitary fibrous tumour (SFT) is an uncommon spindle cell neoplasm of fibroblastic origin, first described as a tumour of the pleura and now well established at extrapleural sites. However, SFT in the female genital tract is rare and therefore not fully characterised. Here, we describe a series of 25 SFTs arising throughout the gynaecological tract, including the vulva (14 cases), vagina (one), cervix (one), uterus (six), ovary (two), and fallopian tube (one).The tumours showed classic histology as well as known variant morphological features, including a fatty component, diffuse stromal hyalinisation, myxoid stroma, and giant-cell angiofibroma-like features. Eleven (11/25, 44%) were considered to be histologically malignant on the basis of mitotic counts of ≥4 per 10 high-power fields. Follow-up data were available for nine (3-56 months; mean 25 months). Six patients are alive with no evidence of disease, and three are alive with disease. Both SFT and other spindle cell lesions of the gynaecological tract were stained for STAT6. Ninety per cent of SFTs showed nuclear expression of STAT6. The majority of other tumour types were negative for STAT6, except for a subset of inflammatory myofibroblastic tumours (1/3; 33%), fibroma/thecoma (3/56; 5%), and sclerosing stromal tumour (1/3; 33%), which showed weak/focal staining.Gynaecological SFT can be diagnosed reliably with careful morphological evaluation and judicious use of immunohistochemical stains, and should be considered in the diagnostic workup of spindle cell tumours of unclear lineage in the female genital tract.

    View details for DOI 10.1111/his.13430

    View details for Web of Science ID 000427248900004

    View details for PubMedID 29106748

  • Mesonephric proliferations of the female genital tract PATHOLOGY Howitt, B. E., Nucci, M. R. 2018; 50 (2): 141–50

    Abstract

    The mesonephric (Wolffian) duct regresses in females during embryological development. Remnants of this duct may persist typically along the lateral walls of the cervix, vagina, adnexa, and uterine corpus. These mesonephric epithelia may expand into hyperplastic proliferations and rarely form neoplasms. The spectrum of morphology, immunophenotype, clinical presentation, and molecular characteristics of mesonephric lesions is reviewed, with attention to distinction from entities in the differential diagnosis.

    View details for DOI 10.1016/j.pathol.2017.11.084

    View details for Web of Science ID 000426351600004

    View details for PubMedID 29269124

  • WITHDRAWN: International Society of Gynecological Pathologists (ISGyP) Endometrial Cancer Project: Guidelines From the Special Techniques and Ancillary Studies Group. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists Cho, K. R., Cooper, K., Croce, S., Djordevic, B., Herrington, S., Howitt, B., Hui, P., Ip, P., Koebel, M., Lax, S., Quade, B. J., Shaw, P., Vidal, A., Yemelyanova, A., Clarke, B., Hedrick Ellenson, L., Longacre, T. A., Shih, I., McCluggage, W. G., Malpica, A., Oliva, E., Parkash, V., Matias-Guiu, X. 2018

    Abstract

    Ahead of Print article withdrawn by publisher.

    View details for DOI 10.1097/PGP.0000000000000496

    View details for PubMedID 29521846

  • Frequency of "incidental" serous tubal intraepithelial carcinoma (STIC) in women without a history of or genetic risk factor for high-grade serous carcinoma: A six-year study. Gynecologic oncology Meserve, E. E., Mirkovic, J., Conner, J. R., Yang, E., Muto, M. G., Horowitz, N., Strickland, K. C., Howitt, B. E., Crum, C. P. 2017

    Abstract

    Objective The purpose of this study was to determine the prevalence of incidentally discovered serous tubal intraepithelial carcinoma in women without a genetic risk for or history of high grade serous carcinoma (HGSC) in the gynecologic tract.All pathology reports at our institution that included bilateral salpingectomies from January 2006-December 2011 were examined in women >50years old in which the entire tube or the distal one-third was examined histologically with the complete (proximal and distal fallopian tube) or modified (distal one third of the tube) SEE-FIM protocol. Cases were divided into: Group 1, a history of or known risk factors (BRCA1 or BRCA2 mutations) for HGSC and Group 2, those without these attributes for whom a STIC would be unexpected (incidental). Women undergoing unspecified "risk-reducing" procedures were included in Group 1.Of 4051 identified total, 2268 had complete examination of the distal fallopian tube and were age 50 or above. Of these, 1747 were in group 2. Two STICs were identified (0.1%), one associated with a grade 2 endometrial endometrioid adenocarcinoma and one with a low-grade ovarian serous carcinoma in the setting of a serous borderline tumor.Incidental STICs in women over age 50 are uncommon. However, the significance of lesser tubal atypias (0.3% in this study), risk of STIC in women with no epithelial pathology and the risk imposed by coexisting endometrioid neoplasia are unclear and require further study.

    View details for DOI 10.1016/j.ygyno.2017.04.015

    View details for PubMedID 28479065

  • Universal Screening for Mismatch-Repair Deficiency in Endometrial Cancers to Identify Patients With Lynch Syndrome and Lynch-like Syndrome. International journal of gynecological pathology Watkins, J. C., Yang, E. J., Muto, M. G., Feltmate, C. M., Berkowitz, R. S., Horowitz, N. S., Syngal, S., Yurgelun, M. B., Chittenden, A., Hornick, J. L., Crum, C. P., Sholl, L. M., Howitt, B. E. 2017; 36 (2): 115-127

    Abstract

    Although consensus has yet to be reached on universal mismatch-repair (MMR) protein immunohistochemical (IHC) screening for Lynch syndrome (LS) in endometrial cancer (EC), an increasing number of institutions have adopted universal screening protocols similar to those used for colorectal carcinoma. Here we describe our institution's experience with a prospective universal screening protocol in which all ECs resected over a period of 19 months (n=242) were screened for MLH1, PMS2, MSH2, and MSH6 deficiencies using IHC, followed by MLH1 promoter methylation testing when appropriate. When consent was obtained, tumor samples underwent next-generation sequencing. A total of 11 unmethylated MMR-deficient cases (4.5% of cohort) were identified through IHC screening. Germline testing was performed in 10 cases and confirmed LS in 4 patients (1.7% of cohort). Of our 4 confirmed LS cases, 1 did not meet traditional LS screening criteria (eg, age below 50 y, Revised Bethesda criteria). In addition, universal screening identified 6 germline-negative MMR-deficient nonmethylated cases, 4 of which occurred in women older than 50. Although our next-generation sequencing data suggest somatic mutations in 4 of these cases, it is possible that these cases may represent cases of "Lynch-like syndrome." We conclude that a subset of LS cases could be missed using traditional screening guidelines. The value of screening for Lynch-like syndrome has yet to be determined. Although the cost-effectiveness of universal screening in EC has yet to be elucidated, we conclude that universal IHC screening is currently a reasonable, and arguably superior, approach to screening for LS.

    View details for DOI 10.1097/PGP.0000000000000312

    View details for PubMedID 27556954

  • Identification and Characterization of 2 Testicular Germ Cell Markers, Glut3 and CyclinA2 APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY Howitt, B. E., Brooks, J. D., Jones, S., Higgins, J. P. 2013; 21 (5): 401-407

    Abstract

    Testicular germ cell tumors (TGCT) are the most common type of testicular tumor and encompass different histologic types that greatly influence treatment and prognosis. Immunohistochemical studies may be required for accurate classification, particularly when these tumors present at extragonadal sites, and to aid in distinguishing histologic types. Traditional markers for identifying and distinguishing TGCT include PLAP, CD117, AFP, and CD30. More recently, the addition of OCT3/4 and SALL4 has increased sensitivity for immunohistochemical detection of germ cell tumors. We examined gene expression data from a previously published microarray study that compared normal testis mRNA expression to various TGCT. We also performed a search of the literature to identify less well-characterized markers. Glut3 and cyclinA2 showed promise as TGCT markers. Therefore, we evaluated expression of glut3 and cyclinA2 by immunohistochemistry using tissue microarrays (TMAs). Of 66 seminomas included in the TMA, 64 (97%) showed positive nuclear staining for cyclinA2 and 58 (88%) were strongly positive. Strong positive staining for cyclinA2 was also seen in the spermatocytic seminoma. All 20 of the embryonal carcinomas stained positively with cyclinA2, and 19 (95%) displayed strong nuclear staining for cyclinA2. Twenty of the 20 embryonal carcinomas stained for glut3 in a strong membranous pattern. Of 8 yolk sac tumors, 100% stained with glut3. We also evaluated glut3 and cyclinA2 staining on a general TMA containing 486 samples representing 156 different tumors. CyclinA2 stained a number of other tumor types, but the majority of these were weak or focal staining. Glut3 was rarely positive in other tumors; interestingly, most of these were of ovarian origin. We conclude that glut3 is a sensitive (96%) and specific (92%) marker for embryonal carcinomas and yolk sac tumors. Although cyclinA2 is a sensitive marker of seminomas and embryonal carcinomas (98%), its specificity is lower if focal and weak staining of nongerm cell tumors is considered positive. The sensitivity and specificity of glut3 are comparable with that seen for SALL4.

    View details for DOI 10.1097/PAI.0b013e31827b505f

    View details for Web of Science ID 000324837800004

    View details for PubMedID 23343953