Publications by authors named "Kim R Geisinger"

97 Publications

STRIDES - STudying Risk to Improve DisparitiES in Cervical Cancer in Mississippi - Design and baseline results of a Statewide Cohort Study.

Prev Med 2021 Jul 20;153:106740. Epub 2021 Jul 20.

National Cancer Institute, Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, Rockville, MD, United States of America. Electronic address:

Cervical cancer rates in Mississippi are disproportionately high, particularly among Black individuals; yet, research in this population is lacking. We designed a statewide, racially diverse cohort of individuals undergoing cervical screening in Mississippi. Here, we report the baseline findings from this study. We included individuals aged 21 years and older undergoing cervical screening with cytology or cytology-human papillomavirus (HPV) co-testing at the Mississippi State Health Department (MSDH) and the University of Mississippi Medical Center (UMMC) (December 2017-May 2020). We collected discarded cytology specimens for future biomarker testing. Demographics and clinical results were abstracted from electronic medical records and evaluated using descriptive statistics and chi-square tests. A total of 24,796 individuals were included, with a median age of 34.8 years. The distribution of race in our cohort was 60.2% Black, 26.4% White, 7.5% other, and 5.9% missing. Approximately 15% had abnormal cytology and, among those who underwent co-testing at MSDH (n = 6,377), HPV positivity was 17.4% and did not vary significantly by race. Among HPV positives, Black individuals were significantly less likely to be HPV16/18 positive and more likely to be positive for other high-risk 12 HPV types compared to White individuals (20.5% vs. 27.9%, and 79.5% and 72.1%, respectively, p = 0.011). Our statewide cohort represents one of the largest racially diverse studies of cervical screening in the U.S. We show a high burden of abnormal cytology and HPV positivity, with significant racial differences in HPV genotype prevalence. Future studies will evaluate cervical precancer risk, HPV genotyping, and novel biomarkers in this population.
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http://dx.doi.org/10.1016/j.ypmed.2021.106740DOI Listing
July 2021

Donor-Derived Neuroendocrine Carcinoma Transmission to Two Kidney Transplant Recipients Demonstrated by Short Tandem Repeat Analysis: A Case Report.

Transplant Proc 2021 May 3;53(4):1337-1341. Epub 2021 Apr 3.

Department of Pathology and Laboratory Medicine, East Carolina University, Brody School of Medicine and Vidant Medical Center, Greenville, North Carolina, United States. Electronic address:

Cancer transmission from a donor organ to a transplant recipient is a rare but not infrequently fatal event. We report a case of lung cancer transmission from a deceased donor to 2 kidney recipients. Approximately 1 year after uneventful kidney transplantation, both recipients developed acute kidney failure. Computed tomography imaging of abdomen and pelvis for both recipients showed masses in the transplanted kidneys along with innumerable masses in the livers. Pathologic examinations for both cases demonstrated high-grade neuroendocrine carcinoma with "mirror image" histologic findings in the transplant kidneys with liver metastases. Short tandem repeat (STR) analyses were performed to determine the origin of the tumors. STRs of both tumors were nearly identical to that of the donor, proving that both tumors were from the same donor. Immunohistochemical analyses showed that both tumors were positive for thyroid transcription factor 1, supporting a lung primary. One recipient died as a direct sequela to metastatic tumor, and the other required transplant nephrectomy and chemotherapy. Awareness of this largely nonpreventable complication and prompt molecular testing if cancer transmission is suspected are important.
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http://dx.doi.org/10.1016/j.transproceed.2021.03.002DOI Listing
May 2021

Racial differences in HPV type 16 prevalence in women with ASCUS of the uterine cervix.

Cancer Cytopathol 2020 08 3;128(8):528-534. Epub 2020 Apr 3.

National Cancer Institute, Rockville, Maryland.

Background: Understanding racial influences on human papillomavirus (HPV) distribution in women with atypical squamous cells of undetermined significance (ASCUS) cytology via partial genotyping in a statewide population can inform HPV-based prevention efforts.

Methods: Women aged 21 to 65 years with any cytology result and partial HPV genotyping for ASCUS triage between January 1, 2014, and December 31, 2017, were included. All women attended a Mississippi State Department of Health clinic. Age, race, cytopathologic, and HPV data were extracted from the electronic health record and analyzed. Cytologic specimens were processed with ThinPrep and HPV testing with the Cobas 4800 assay. HPV genotypes were evaluated in hierarchical categories. Chi-square tests and multinomial logistic regression models evaluated associations between race and type prevalence.

Results: There were 43,106 women who underwent cervical cancer screening with cytology and ASCUS triage. Of these, 34,363 (80.2%) had normal cytology, 4672 (10.9%) had ASCUS, 2683 (6.3%) had a low-grade squamous intraepithelial lesion, and 633 (1.5%) had a high-grade squamous intraepithelial lesion. Blacks represented 69.3% of the sample and had a higher proportion of HPV-positive ASCUS (6.5%) in comparison with whites (5.6%). Blacks had significantly decreased odds of HPV-16 (odds ratio [OR], 0.66; 95% confidence interval [CI], 0.6-0.9; P = .002) and significantly increased odds for 12 other types (OR, 1.37; 95% CI, 1.2-1.5; P < .0001) in comparison with whites.

Conclusions: In a diverse population, significant differences in HPV genotypes are shown by race. Importantly, blacks with ASCUS are less likely to be positive for HPV-16 in comparison with whites. Ongoing work is evaluating the individual genotype prevalence and genotype-specific risk of precancer by race.
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http://dx.doi.org/10.1002/cncy.22267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728239PMC
August 2020

Best Practices Recommendations for Diagnostic Immunohistochemistry in Lung Cancer.

J Thorac Oncol 2019 03 18;14(3):377-407. Epub 2018 Dec 18.

Department of Histopathology, Royal Brompton and Harefield National Health Service Foundation Trust and National Heart and Lung Institute, Imperial College, London, United Kingdom.

Since the 2015 WHO classification was introduced into clinical practice, immunohistochemistry (IHC) has figured prominently in lung cancer diagnosis. In addition to distinction of small cell versus non-small cell carcinoma, patients' treatment of choice is directly linked to histologic subtypes of non-small cell carcinoma, which pertains to IHC results, particularly for poorly differentiated tumors. The use of IHC has improved diagnostic accuracy in the classification of lung carcinoma, but the interpretation of IHC results remains challenging in some instances. Also, pathologists must be aware of many interpretation pitfalls, and the use of IHC should be efficient to spare the tissue for molecular testing. The International Association for the Study of Lung Cancer Pathology Committee received questions on practical application and interpretation of IHC in lung cancer diagnosis. After discussions in several International Association for the Study of Lung Cancer Pathology Committee meetings, the issues and caveats were summarized in terms of 11 key questions covering common and important diagnostic situations in a daily clinical practice with some relevant challenging queries. The questions cover topics such as the best IHC markers for distinguishing NSCLC subtypes, differences in thyroid transcription factor 1 clones, and the utility of IHC in diagnosing uncommon subtypes of lung cancer and distinguishing primary from metastatic tumors. This article provides answers and explanations for the key questions about the use of IHC in diagnosis of lung carcinoma, representing viewpoints of experts in thoracic pathology that should assist the community in the appropriate use of IHC in diagnostic pathology.
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http://dx.doi.org/10.1016/j.jtho.2018.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422775PMC
March 2019

Precancerous cervical lesions and HPV genotypes identified in previously unsatisfactory cervical smear tests after inexpensive glacial acetic acid processing.

Int J Gynaecol Obstet 2019 Jan 2;144(1):85-89. Epub 2018 Nov 2.

School of Graduate Studies and School of Nursing, University of Mississippi Medical Center, Jackson, MI, USA.

Objective: To determine the effectiveness of using glacial acetic acid (GAA) to convert unsatisfactory bloody ThinPrep (TP) cervical smear test to satisfactory, and identify associated missed diagnoses and high-risk HPV (hrHPV) genotypes.

Methods: In a retrospective descriptive cross-sectional analysis, all TP tests performed in Mississippi, USA, 2012-2016, were evaluated for unsatisfactory results owing to blood. Tests that were converted to satisfactory by GAA treatment, and corresponding anomalies and HPV genotypes were identified.

Results: Among 106 384 TP tests, there were 1460 (1.37%) unsatisfactory results, of which 1442 (98.77%) were converted to satisfactory after GAA treatment. Laboratory preprocessing with GAA increased costs minimally. Precancerous lesions were detected in 166 (11.51%) of 1442 GAA-treated samples, of which 12 (7.2%) were high-grade lesions, 110 (66.3%) were atypical squamous cells of undetermined significance, and 63 (57.3%) tested positive for hrHPV. Of 60 genotyped samples, 39 (65%) had non-HPV16 and non-HPV18. Including mixed infections, 48 (80%) contained less-common hrHPV types, reflecting an unexpected distribution in bloody specimens.

Conclusions: GAA pretreatment of bloody TP tests would reduce the incidence of unsatisfactory results and missed high-grade lesions, and prevent the cost of repeat tests and delayed treatment. Clinicians without access to GAA should consider HPV testing.
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http://dx.doi.org/10.1002/ijgo.12699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431532PMC
January 2019

The histopathological classification, diagnosis and differential diagnosis of mucinous appendiceal neoplasms, appendiceal adenocarcinomas and pseudomyxoma peritonei.

Histopathology 2017 Dec 19;71(6):847-858. Epub 2017 Sep 19.

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.

The vermiform appendix is the primary site of several distinctive benign and malignant neoplasms. Some can produce the clinical syndrome of pseudomyxoma peritonei (PMP). A consensus on their terminology was reached by an international panel of pathologists and clinicians working under the auspices of the Peritoneal Surface Oncology Group International (PSOGI), and this review discusses the application of the PSOGI classification to routine reporting. We discuss diagnosis and differential diagnosis together with implications for patient management, covering low-grade appendiceal mucinous neoplasms, high-grade appendiceal mucinous neoplasms, serrated polyps, adenomas and adenocarcinomas. We do not cover goblet cell tumours or neuroendocrine neoplasms in this paper.
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http://dx.doi.org/10.1111/his.13324DOI Listing
December 2017

The Use of Immunohistochemistry Improves the Diagnosis of Small Cell Lung Cancer and Its Differential Diagnosis. An International Reproducibility Study in a Demanding Set of Cases.

J Thorac Oncol 2017 02 18;12(2):334-346. Epub 2016 Dec 18.

Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.

Introduction: The current WHO classification of lung cancer states that a diagnosis of SCLC can be reliably made on routine histological and cytological grounds but immunohistochemistry (IHC) may be required, particularly (1) in cases in which histologic features are equivocal and (2) in cases in which the pathologist wants to increase confidence in diagnosis. However, reproducibility studies based on hematoxylin and eosin-stained slides alone for SCLC versus large cell neuroendocrine carcinoma (LCNEC) have shown pairwise κ scores ranging from 0.35 to 0.81. This study examines whether judicious use of IHC improves diagnostic reproducibility for SCLC.

Methods: Nineteen lung pathologists studied interactive digital images of 79 tumors, predominantly neuroendocrine lung tumors. Images of resection and biopsy specimens were used to make diagnoses solely on the basis of morphologic features (level 1), morphologic features along with requested IHC staining results (level 2), and all available IHC staining results (level 3).

Results: For the 19 pathologists reading all 79 cases, the rate of agreement for level 1 was 64.7%, and it increased to 73.2% and 77.5% in levels 2 and 3, respectively. With IHC, κ scores for four tumor categories (SCLC, LCNEC, carcinoid tumors, and other) increased in resection samples from 0.43 to 0.60 and in biopsy specimens from 0.43 to 0.64.

Conclusions: Diagnosis using hematoxylin and eosin staining alone showeds moderate agreement among pathologists in tumors with neuroendocrine morphology, but agreement improved to good in most cases with the judicious use of IHC, especially in the diagnosis of SCLC. An approach for IHC in the differential diagnosis of SCLC is provided.
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http://dx.doi.org/10.1016/j.jtho.2016.12.004DOI Listing
February 2017

A Histomorphologic Grading System That Predicts Overall Survival in Diffuse Malignant Peritoneal Mesothelioma With Epithelioid Subtype.

Am J Surg Pathol 2016 09;40(9):1243-8

Departments of *Pathology †Surgery ‡Biostatistical Sciences, Wake Forest Baptist Health, Winston-Salem, NC §Department of Pathology, The University of Mississippi Medical Center, Jackson, MS ∥Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.

Diffuse malignant peritoneal mesothelioma (MPeM) is rare and arises from peritoneal serosal surfaces. Although it shares similar histomorphology with its counterpart, malignant pleural mesothelioma, etiologies, clinical courses, and therapies differ. Nuclear grading and level of mitoses have been correlated with prognosis in malignant pleural mesothelioma with epithelioid subtype. Whether nuclear grading and level of mitoses correlate with prognosis in MPeM is still unknown. Our study utilizes a 2 tier system incorporating nuclear features and level of the mitoses to stratify cases of MPeM with epithelioid subtype. Fifty-one cases of MPeM with clinical follow-up underwent retrospective microscopic review. From that subset, 46 cases were of epithelioid subtype, which were then stratified into a low-grade or high-grade tier. Survival times were calculated on the basis of Kaplan-Meier analysis. The low-grade tier had higher overall survival with a median of 11.9 years and 57% at 5 years when compared with the high-grade tier with a median of 3.3 years and 21% at 5 years (P=0.002). Although not statistically significant, the low-grade tier had higher progression-free survival with a median of 4.7 years and 65% at 5 years when compared with the high-grade tier with a median of 1.9 years and 35% at 5 years (P=0.089). Our study is first to specifically evaluate and correlate nuclear features and level of mitoses with overall survival in MPeM with epithelioid subtype.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029445PMC
http://dx.doi.org/10.1097/PAS.0000000000000696DOI Listing
September 2016

Histological grading in lung cancer: one system for all or separate systems for each histological type?

Eur Respir J 2016 Mar;47(3):720-3

Dept of Pathology, University of Mississippi Medical Center, Jackson, MS, USA.

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http://dx.doi.org/10.1183/13993003.00035-2016DOI Listing
March 2016

Mucoepidermoid carcinoma of the thyroid with concomitant papillary carcinoma: comparison of findings on fine-needle aspiration biopsy and histology.

Endocr Pathol 2014 Dec;25(4):427-32

Department of Pathology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA.

We report two cases of mucoepidermoid carcinoma (MEC) of the thyroid gland coexisting with, and possibly arising in, papillary thyroid carcinoma (PTC). In the first case, CT-guided fine-needle aspiration (FNA) was performed on a paratracheal mass representing extrathyroidal invasion of a right thyroid lobe tumor. The aspirate showed papillary fronds and cells in honeycombed arrangements with fine chromatin, enlarged nuclei, nuclear grooves, and intranuclear inclusions in a background of mucus and blood; a diagnosis of PTC was rendered initially. However, examination of histologic sections of the mass showed nests of malignant squamous cells with interspersed mucous cells and extracellular mucin, concordant with MEC, as well as PTC. A retrospective review of the FNA specimen identified MEC. In the second case, ultrasound-guided FNA was performed on a right thyroid lobe nodule. The aspirate contained two populations of epithelial cells: larger cells showing foci of both squamous and glandular differentiation that were interpreted as MEC and smaller follicular cells with nuclear changes characteristic of PTC; both were addressed in the diagnostic report. Primary MEC of the thyroid is a rare neoplasm typically exhibiting indolent clinical behavior, although our first case demonstrated extensive local invasion. It is thought to arise from squamous metaplasia associated with PTC, Hashimoto thyroiditis, or other inflammatory or neoplastic processes. In thyroid FNAs, the presence of neoplastic mucous cells and extracellular mucin plus malignant squamous cells is diagnostic of MEC. As MEC is thought to arise in PTC, the finding of the latter in these aspiration specimens is not unexpected.
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http://dx.doi.org/10.1007/s12022-014-9338-3DOI Listing
December 2014

Oncocytoma-like renal tumor with transformation toward high-grade oncocytic carcinoma: a unique case with morphologic, immunohistochemical, and genomic characterization.

Medicine (Baltimore) 2014 Oct;93(15):e81

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (SJS); University of Mississippi Medical Center, Jackson, MS (KRG); Department of Pathology, Wake Forest Baptist Health, Winston-Salem, NC (AC, AS); 23andMe, Mountain View (JH); Invitae, San Francisco (FM), CA; Transgenomic (BLL); Creighton University School of Medicine (ZG), Omaha, NE; and Caris Life Sciences, Phoenix, AZ (AG, RPB, ZG).

Renal oncocytoma is a benign tumor with characteristic histologic findings. We describe an oncocytoma-like renal tumor with progression to high-grade oncocytic carcinoma and metastasis. A 74-year-old man with no family history of cancer presented with hematuria. Computed tomography showed an 11 cm heterogeneous multilobulated mass in the right kidney lower pole, enlarged aortocaval lymph nodes, and multiple lung nodules. In the nephrectomy specimen, approximately one third of the renal tumor histologically showed regions classic for benign oncocytoma transitioning to regions of high-grade carcinoma without sharp demarcation. With extensive genomic investigation using single nucleotide polymorphism-based array virtual karyotyping, multiregion sequencing, and expression array analysis, we were able to show a common lineage between the benign oncocytoma and high-grade oncocytic carcinoma regions in the tumor. We were also able to show karyotypic differences underlying this progression. The benign oncocytoma showed no chromosomal aberrations, whereas the high-grade oncocytic carcinoma showed loss of the 17p region housing FLCN (folliculin [Birt-Hogg-Dubé protein]), loss of 8p, and gain of 8q. Gene expression patterns supported dysregulation and activation of phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (Akt), mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK), and mechanistic target of rapamycin (serine/threonine kinase) (mTOR) pathways in the high-grade oncocytic carcinoma regions. This was partly attributable to FLCN underexpression but further accentuated by overexpression of numerous genes on 8q. In the high-grade oncocytic carcinoma region, vascular endothelial growth factor A along with metalloproteinases matrix metallopeptidase 9 and matrix metallopeptidase 12 were overexpressed, facilitating angiogenesis and invasiveness. Genetic molecular testing provided evidence for the development of an aggressive oncocytic carcinoma from an oncocytoma, leading to aggressive targeted treatment but eventual death 39 months after the diagnosis.
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http://dx.doi.org/10.1097/MD.0000000000000081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616290PMC
October 2014

Reproducibility of histopathological diagnosis in poorly differentiated NSCLC: an international multiobserver study.

J Thorac Oncol 2014 Sep;9(9):1354-62

Departments of *Pathology and ††††Epidemiology and Biostatistics, VU University Medical Centre, Amsterdam, The Netherlands; †Department of Pathology, Faculty of Medicine, Tsukuba, Japan; ‡Rutgers New Jersey Medical School, Newark, New Jersey; §Department of Pathology, Mount Sinai Medical Center, New York, New York; ‖Elisabeth Brambilla, CHU Albert Michallon, Institut de Biologie, Département d'Anatomie et Cytologie Pathologiques, Grenoble Cedex, France; ¶Brigham and Women's Hospital, Boston, Massachusetts; #Department of Pathology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea; **Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania; ††Piedmont Pathology Associates, Hickory, North Carolina, and University of North Carolina, Chapel Hill, North Carolina; ‡‡Department of Medicine and Pathology, University of Colorado Cancer Center, Aurora, Colorado; §§Division of Pathology, The Cancer Institute, Japanese Foundation Cancer Research, Tokyo, Japan; ‖Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom; ¶¶Department of Pathology, CHU A Michallon, INSERM U 823-Institut A Bonniot-University J Fourier, Grenoble, France; ##Department of Pathology, Cancer Center Hospital, Tsukuba, Japan; ***Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Japan; †††Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York; ‡‡‡Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale Tumori, and Università degli Studi of Milan, Milan, Italy; §§§Institut für Pathologie, Jena, Germany; ‖‖‖Duke University Medical Center, Durham, North Carolina; ¶¶¶University of Texas MD Anderson Cancer Center, Houston, Texas; ###Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan; ****Department of Oncology and Radiothe

Introduction: The 2004 World Health Organization classification of lung cancer contained three major forms of non-small-cell lung cancer: squamous cell carcinoma (SqCC), adenocarcinoma (AdC), and large cell carcinoma. The goal of this study was first, to assess the reproducibility of a set of histopathological features for SqCC in relation to other poorly differentiated non-small-cell lung cancers and second, to assess the value of immunohistochemistry in improving the diagnosis.

Methods: Resection specimens (n = 37) with SqCC, large cell carcinoma, basaloid carcinoma, sarcomatoid carcinoma, lymphoepithelial-like carcinoma, and solid AdC, were contributed by the participating pathologists. Hematoxylin and eosin (H&E) stained slides were digitized. The diagnoses were evaluated in two ways. First, the histological criteria were evaluated and the (differential) diagnosis on H&E alone was scored. Second, the added value of additional stains to make an integrated diagnosis was examined.

Results: The histologic criteria defining SqCC were consistently used, but in poorly differentiated cases they were infrequently present, rendering the diagnosis more difficult. Kappa scores on H&E alone were for SqCC 0.46, large cell carcinoma 0.25, basaloid carcinoma 0.27, sarcomatoid carcinoma 0.52, lymphoepithelial-like carcinoma 0.56, and solid AdC 0.21. The κ score improved with the use of additional stains for SqCC (combined with basaloid carcinoma) to 0.57, for solid AdC to 0.63.

Conclusion: The histologic criteria that may be used in the differential diagnosis of poorly differentiated lung cancer were more precisely refined. Furthermore, additional stains improved the reproducibility of histological diagnosis of SqCC and AdC, uncovering information that was not present in routine H&E stained slides.
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http://dx.doi.org/10.1097/JTO.0000000000000264DOI Listing
September 2014

Significance of signet ring cells in high-grade mucinous adenocarcinoma of the peritoneum from appendiceal origin.

Hum Pathol 2014 Aug 4;45(8):1597-604. Epub 2014 Apr 4.

Department of Pathology, Wake Forest Baptist Health, Winston-Salem, NC, 27157.

Significance of signet ring cells in mucinous adenocarcinoma of the peritoneum from appendiceal origin has never been specifically studied. We retrospectively reviewed cases of mucinous adenocarcinoma of the peritoneum from appendiceal origin (n = 55) and collected clinical follow-up data. Signet ring cells were identified in 29 of 55 cases. No low-grade mucinous adenocarcinoma case (n = 11) had signet ring cells, whereas 29 of 44 high-grade mucinous adenocarcinoma cases did. Cases of high-grade mucinous adenocarcinoma were subdivided into 3 groups: (1) high-grade mucinous adenocarcinoma without signet ring cells (n = 15), (2) high-grade mucinous adenocarcinoma with signet ring cells only within mucin pools (n = 20), and (3) high-grade mucinous adenocarcinoma with signet ring cells invading tissue (n = 9). Overall survival (OS) and progression-free survival were subsequently evaluated. Five-year OS for cases of high-grade mucinous adenocarcinoma without signet ring cells and high-grade mucinous adenocarcinoma with signet ring cells within mucin pools were similar at 31.8% (SE, 14.4%) and 35.8% (SE, 13.9%), respectively. A significant survival difference was seen for cases of high-grade mucinous adenocarcinoma with signet ring cells invading tissue with a median OS of 0.5 years versus 2.9 and 2.4 years (P = .04 and P = .03), respectively, for cases of high-grade mucinous adenocarcinoma without signet ring cells and high-grade mucinous adenocarcinoma with signet ring cells within mucin pools. Finding signet ring cells floating in extracellular mucin pools made no prognostic difference when compared with cases of high-grade mucinous adenocarcinoma without signet ring cells. In contrast, high-grade mucinous adenocarcinoma with signet ring cells invading tissue was significant for worse survival, and thus, we propose reporting signet ring cell tissue invasion particularly when extensive.
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http://dx.doi.org/10.1016/j.humpath.2014.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107056PMC
August 2014

Classification of thymic epithelial neoplasms is still a challenge to thoracic pathologists: a reproducibility study using digital microscopy.

Arch Pathol Lab Med 2014 May;138(5):658-63

From the Departments of Pathology (Drs Wang and Moreira), Epidemiology and Biostatistics (Dr Sima), and Surgery (Dr Huang), Memorial Sloan-Kettering Cancer Center, New York, New York; the Department of Pathology, Mount Sinai School of Medicine, New York, New York (Dr Beasley); the Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland (Dr Illei); the Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York (Dr Saqi); The Christie Hospital, and School of Cancer and Enabling Sciences, Department of Histopathology, University of Manchester School of Medicine, Manchester, United Kingdom (Dr Nonaka); and the Department of Pathology and Laboratory Medicine, University of North Carolina-Chapel Hill, Chapel Hill (Dr Geisinger).

Context: Thymic epithelial tumors are rare, constituting interpretive challenges for pathologists. Digital imaging can be useful as an educational tool for these rare tumors.

Objectives: To evaluate the diagnostic reproducibility of thymic tumors among thoracic pathologists.

Design: Twenty cases of thymoma or thymic carcinoma were scanned into the Aperio system. The images were sent to pathologists with expertise in thoracic pathology at 6 different centers, who were asked to classify the tumors according to the 2004 World Heath Organization classification and to diagnose invasion. Interobserver agreement was evaluated. After discussion of the first 20 cases, a second set of 10 cases was evaluated.

Results: There was agreement for the diagnosis of thymoma and thymic carcinoma in 70% of cases (n = 14); in the remaining 6 cases, there was disagreement for cases of B3 thymoma (n = 5) and type A thymoma (n = 1) and thymic carcinoma. The overall κ was 0.39. When invasion was evaluated, the overall κ was 0.45. In the second round of the study, after discussion of diagnostic criteria, the interobserver agreement for the diagnosis of thymoma versus thymic carcinoma was 0.67 and that for the determination of invasion was 0.57-suggesting interpretative improvement.

Conclusion: The reproducibility of diagnosis of thymic epithelial tumors, using digital imaging, is comparable to that in previous studies using glass slides. Digital imaging is a good tool for remote consultation and for educational purposes. This technology could be used to train pathologists with low-level experience in thymic epithelial tumors and to foster collaborative work in the field.
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http://dx.doi.org/10.5858/arpa.2013-0028-OADOI Listing
May 2014

Eosinophilic replacement infiltrates in cystic Hashimoto's thyroiditis: a potential diagnostic pitfall.

Endocr Pathol 2014 Sep;25(3):332-8

Piedmont Pathology Associates, Hickory, NC, USA,

A 50-year-old woman underwent a fine-needle aspiration biopsy for progressive enlargement of the left thyroid lobe which was cystic and solid on ultrasound exam. The smears contained innumerable eosinophilic leukocytes along with lymphocytes, Hurthle cells, cells from a papillary thyroid carcinoma (PTC), and atypical glandular and squamous cells. The cytologic interpretation was Hashimoto's thyroiditis (HT), suspicious for epithelial neoplasm. The associated diagnostic comment stated concern for a sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) arising in a PTC. Thyroidectomy demonstrated a PTC, HT with multiple lymphoepithelial cysts, and extensive multifocal infiltrates of eosinophils, generally confined to the cyst walls. As the cytologic findings mimicked a SMECE, we report these specimens as a most unusual diagnostic pitfall.
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http://dx.doi.org/10.1007/s12022-014-9304-0DOI Listing
September 2014

Vulvar seborrheic keratosis: is there a relationship to human papillomavirus?

J Low Genit Tract Dis 2014 Apr;18(2):190-4

1Piedmont Pathology Associates, Hickory, NC; 2Department of Pathology and Laboratory Medicine, University of North Carolina-Chapel Hill, Chapel Hill, NC; and 3Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR.

Objective: We sought to determine the prevalence of human papillomavirus (HPV) subtypes in vulvar seborrheic keratoses (SK) by polymerase chain reaction (PCR) in women with a theoretically low risk of recent HPV transmission. We also attempted to identify which histopathologic features best correlated with HPV and specific subtypes.

Methods: Twenty-eight cases of vulvar SK in women older than 50 years old were retrospectively pulled from our files from a 7-year period. Cases were histologically examined for the presence of 7 features: parakeratosis, horn cysts, pigmentation, "clonal" cells, papillomatosis, "whorls," and reticulation of rete. For controls, PCR was performed on all cases for HPV detection and typing. Ten cutaneous SK and 7 vulvar condyloma acuminata were also evaluated for HPV by PCR.

Results: Twenty-one vulvar SK had sufficient genetic material for HPV PCR analysis. Only 3 (14.29%) were positive for HPV, 2 were type 6, and 1 was an unknown type. All cutaneous SK were negative and all condyloma acuminatum were positive for HPV. There was no histologic feature that separated HPV-positive from HPV-negative vulvar SK, although there was a tendency for parakeratosis to be associated with HPV positivity.

Conclusions: The rate of HPV positivity in vulvar SK in women older than 50 years is much lower than expected and not statistically significantly associated with specific histologic features. One explanation may be that vulvar SK have diminishing levels of HPV genetic material in the relatively older ages of the patients in our study. Alternatively, vulvar SK may have no relationship to HPV, and strict histologic criteria may separate vulvar SK from condyloma acuminatum. In this instance, the few cases of HPV-positive vulvar SK may reflect incidental persistence of HPV in vulvar epidermis. Furthermore, these possibilities may vary among different populations, for example, based on patient age.
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http://dx.doi.org/10.1097/LGT.0b013e3182952357DOI Listing
April 2014

Perioperative systemic chemotherapy for appendiceal mucinous carcinoma peritonei treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

J Surg Oncol 2014 Jun 28;109(7):740-5. Epub 2013 Dec 28.

Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina.

Background: The role of systemic chemotherapy (SC) in conjunction with cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in appendiceal mucinous carcinoma peritonei (MCP) is unknown.

Methods: A retrospective review (1999-2011) of MCP patients who had undergone CS/HIPEC with or without perioperative SC.

Results: Twenty-two low-grade MCP patients treated with CS/HIPEC and SC were matched to patients who received CS/HIPEC alone. Median overall survival (OS) was 107 months for patients treated with perioperative SC compared to 72 without (P = 0.46). CS/HIPEC was performed on 109 patients with high-grade MCP: 70 were treated with perioperative SC, while 39 were not. Median OS (22.1 vs. 19.6 months, P = 0.74) and progression-free survival (PFS) (10.9 vs. 7.0 months, P = 0.47) were similar in patients treated with SC compared to CS/HIPEC alone. Progression while on pre-operative SC was seen in eight patients (17%), while four (8%) had a partial response. Treatment with post-operative SC was associated with longer PFS (13.6 months) compared to pre-operative SC (6.8 months, P < 0.01) and CS/HIPEC alone (7.0 months, P = 0.03).

Conclusions: Post-operative SC appears to improve PFS in patients with high-grade appendiceal MCP treated with CS/HIPEC. In contrast, there is no evidence to support the routine use of perioperative SC in low-grade disease.
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http://dx.doi.org/10.1002/jso.23547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010799PMC
June 2014

Serous epithelium, serious interpretations.

Cancer Cytopathol 2012 Aug 23;120(4):220-2. Epub 2012 Jul 23.

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http://dx.doi.org/10.1002/cncy.21221DOI Listing
August 2012

Predicting pulmonary adenocarcinoma outcome based on a cytology grading system.

Cancer Cytopathol 2012 Feb;120(1):35-43

1Memorial Sloan-Kettering Cancer Center, Department of Pathology, New York, New York, USA.

Background: Pulmonary adenocarcinoma (AD) has a variety of architectural patterns. Recently, a 3-tiered histological pattern-based grading system was developed for stage I lung AD, stratifying patients into low, intermediate, and high risk for recurrence. However, cytology may serve as the primary method for diagnosis in patients with inoperable disease. Attempts to correlate architecture between parallel cytological and histological preparations have not been successful. Therefore, we evaluated cytomorphologic features of previously histologically graded AD to identify features of potential prognostic significance.

Methods: One hundred and thirteen fine-needle aspirations with excised adenocarcinomas were reviewed. In the liquid-based preparation, we evaluated cell arrangements(flat sheets vs 3-D clusters vs single cells), nuclear features (size variability, shape, and contour),nucleoli (prominent or inconspicuous), presence of nuclear inclusions, chromatin (fine, coarse,or clumped), and quality of background. The features were tested by multivariate analysis to identify associations with histological grade and disease-free survival (DFS), and a cytological score was generated.

Results: Nuclear size, chromatin pattern, and nuclear contours showed a significant association with histological grade and DFS. These features were included in the composite cytological score (range,0-5). By grouping the cytological scores, we stratified the tumors into low (median DFS, 100%), intermediate(median DFS, 78%), and high (median DFS, 55%) rate of recurrence (P ¼ .008). There was a good correlation with the histological grading system.

Conclusions: In liquid-based preparations, distinctive cytological features of pulmonary adenocarcinoma correlate with levels of histological differentiation and can be combined into a score with prognostic significance.
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http://dx.doi.org/10.1002/cncy.20185DOI Listing
February 2012

Is intraoperative imprint cytology evaluation still feasible for the evaluation of sentinel lymph nodes for lobular carcinoma of the breast?

Ann Surg Oncol 2012 Mar 31;19(3):929-34. Epub 2011 Aug 31.

Department of Surgical Oncology, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA.

Background: The evaluation of sentinel lymph nodes (SLNs) from a patient with lobular breast cancer is challenging. Metastatic lobular cancer is difficult to identify in SLNs because of its low-grade cytomorphology and its tendency to resemble lymphocytes. Intraoperative imprint cytology (IIC) is a rapid, reliable method for evaluating SLNs intraoperatively. We sought to reexamine our experience with this technique in the identification of invasive lobular breast cancer SLN metastases.

Methods: A retrospective review of a prospectively maintained database of IIC results of 1010 SLN mapping procedures for breast cancer was performed. From this cohort we reviewed SLN cases of lobular cancer. The SLNs were evaluated intraoperatively by bisecting the SLN. Imprints were made of each cut surface and stained with hematoxylin and eosin (H&E) and Diff-Quik. Permanent sections were evaluated with up to 4 H&E-stained levels and cytokeratin immunohistochemistry. IIC results were compared with final pathologic results.

Results: A total of 67 cases of pure invasive lobular cancer were identified. The sensitivity was 71%, specificity was 100%, and accuracy was 92%. No statistically significant differences in sensitivity, specificity, or accuracy were identified between the intraoperative detection of lobular carcinoma vs ductal carcinoma. The specificity has remained the same since 2004. However the accuracy (82% vs 92%; P = .09) and sensitivity (52% vs 71%; P = .02) has improved since 2004.

Conclusions: As we have previously shown, the sensitivity and specificity of IIC in evaluating lobular carcinoma is feasible and accurate. IIC continues to be a viable alternative to frozen section for intraoperative evaluation.
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http://dx.doi.org/10.1245/s10434-011-2038-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733474PMC
March 2012

Benefits of a combined approach to sampling of renal neoplasms as demonstrated in a series of 351 cases.

Am J Surg Pathol 2011 Jun;35(6):827-35

Department of Pathology, Wake Forest University Baptist Medical Center, Medical Center Boulevard, Winston-Salem, NC 27157, USA.

Percutaneous radiofrequency ablation is increasingly used for curative treatment of primary cancers of the kidney. We reviewed our experience of percutaneous sampling performed under computed tomographic guidance with fine needle aspiration biopsy (FNAB) and core biopsy (CB), and we report on the complementary roles of these 2 techniques in a series of 351 consecutive patients undergoing radiofrequency ablation for renal neoplasms. Both FNAB and CB were obtained in 290 cases, of which 156 patients (54%) were positive for neoplasm in both specimens, and 27 (9%) were negative for tumor in both specimens. In 58 (20%) patients, the FNABs were positive, but the CBs were negative, and the reverse occurred in 11 patients (4%). When suspicious interpretations by FNAB and CB are included as positives in the calculations, both their complementary nature and the relative higher diagnostic yield of FNAB persisted. In 25 cases with FNABs positive for neoplasm, the CB allowed a more specific tumor classification. The 19 cases of FNAB which were read as negative/benign had corresponding CBs that were also negative/benign in 13 cases; yet, 6 were diagnostic of renal cell carcinoma not otherwise specified (1 case), renal cell carcinoma clear cell/conventional (4 cases), and non-Hodgkin lymphoma (1 case). These and additional findings illustrate the complementary value of the combination of the 2 biopsy methods for a reliable pretherapy morphologic confirmation of specific renal neoplasms. FNAB has relatively greater sensitivity and utility for on-site evaluation, whereas CB provides an additional sample for more specific subclassification and additional studies.
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http://dx.doi.org/10.1097/PAS.0b013e31821920c8DOI Listing
June 2011

Non-contrasted computed tomography for the accurate measurement of liver steatosis in obese patients.

Dig Dis Sci 2011 Jul 12;56(7):2145-51. Epub 2011 Feb 12.

Division of Gastroenterology and Transplant Hepatology, University of California, San Francisco, 505 Parnassus Street, San Francisco, CA 94143, USA.

Background: Hepatic macrosteatosis (HMS) is prevalent among high BMI patients, but a lack of validation of non-invasive measures of liver fat hampers non-alcoholic liver disease (NAFLD) investigation in general. Recent work suggests BMI adjusted, non-contrasted computed tomography (nc-CT) attenuation data (Hounsfield units) reflects liver fat accumulation in a normal weight population. However, this and other CT-based HMS studies have only approximated macrosteatosis (%) histologically, but have not validated findings with chemical liver triglyceride (TG) concentrations (mg/gram protein). Also, all previous CT based steatosis studies excluded high BMI subjects, whose habitus may affect properties of the scan. We hypothesized that in high BMI patients nc-CT attenuation measurements expressed in Hounsfield units (HU) accurately estimate liver triglyceride concentrations as well as histological macrosteatosis.

Methods: With informed consent, 15 patients underwent nc-CT scan of the abdomen prior to weight loss surgery with intraoperative wedge and core needle liver biopsy. Mean left lobe nc-CT Hounsfield units (CT(L)), liver TG (mg/g Pr), HMS (%), BMI (kg/m(2)), liver-spleen index (CT(L/S) = hepatic HU/splenic HU), and liver-spleen difference (CT(L-S) = hepatic HU - splenic HU) were a priori outcomes.

Results: In 15 patients (11 female) with a BMI of 44.4 ± 1.1 (mean ± SEM), CT(L/S), CT(L-S), and CT(L) measures were significantly associated with liver TG concentrations (r = -0.80, P < 0.001; r = -0.80, P < 0.001; and r = -0.71, P < 0.01, respectively; Table 1). Macrosteatosis (%) and liver triglyceride concentration were positively associated (r = 0.83; P < 0.0001). BMI did not correlate strongly to liver triglyceride (r = 0.44, P = NS).

Conclusion: Estimates of liver fat obtained by nc- CT scans (esp. CT(L/S), CT(L-S)) correlate to chemical measurement of liver triglyceride concentrations, suggesting non-contrasted CT may be a suitable non-invasive "gold standard" for hepatic steatosis quantification in these patients.
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http://dx.doi.org/10.1007/s10620-011-1602-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112485PMC
July 2011

International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma.

J Thorac Oncol 2011 Feb;6(2):244-85

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Introduction: Adenocarcinoma is the most common histologic type of lung cancer. To address advances in oncology, molecular biology, pathology, radiology, and surgery of lung adenocarcinoma, an international multidisciplinary classification was sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification is needed to provide uniform terminology and diagnostic criteria, especially for bronchioloalveolar carcinoma (BAC), the overall approach to small nonresection cancer specimens, and for multidisciplinary strategic management of tissue for molecular and immunohistochemical studies.

Methods: An international core panel of experts representing all three societies was formed with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons. A systematic review was performed under the guidance of the American Thoracic Society Documents Development and Implementation Committee. The search strategy identified 11,368 citations of which 312 articles met specified eligibility criteria and were retrieved for full text review. A series of meetings were held to discuss the development of the new classification, to develop the recommendations, and to write the current document. Recommendations for key questions were graded by strength and quality of the evidence according to the Grades of Recommendation, Assessment, Development, and Evaluation approach.

Results: The classification addresses both resection specimens, and small biopsies and cytology. The terms BAC and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) for small solitary adenocarcinomas with either pure lepidic growth (AIS) or predominant lepidic growth with ≤ 5 mm invasion (MIA) to define patients who, if they undergo complete resection, will have 100% or near 100% disease-specific survival, respectively. AIS and MIA are usually nonmucinous but rarely may be mucinous. Invasive adenocarcinomas are classified by predominant pattern after using comprehensive histologic subtyping with lepidic (formerly most mixed subtype tumors with nonmucinous BAC), acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype. Variants include invasive mucinous adenocarcinoma (formerly mucinous BAC), colloid, fetal, and enteric adenocarcinoma. This classification provides guidance for small biopsies and cytology specimens, as approximately 70% of lung cancers are diagnosed in such samples. Non-small cell lung carcinomas (NSCLCs), in patients with advanced-stage disease, are to be classified into more specific types such as adenocarcinoma or squamous cell carcinoma, whenever possible for several reasons: (1) adenocarcinoma or NSCLC not otherwise specified should be tested for epidermal growth factor receptor (EGFR) mutations as the presence of these mutations is predictive of responsiveness to EGFR tyrosine kinase inhibitors, (2) adenocarcinoma histology is a strong predictor for improved outcome with pemetrexed therapy compared with squamous cell carcinoma, and (3) potential life-threatening hemorrhage may occur in patients with squamous cell carcinoma who receive bevacizumab. If the tumor cannot be classified based on light microscopy alone, special studies such as immunohistochemistry and/or mucin stains should be applied to classify the tumor further. Use of the term NSCLC not otherwise specified should be minimized.

Conclusions: This new classification strategy is based on a multidisciplinary approach to diagnosis of lung adenocarcinoma that incorporates clinical, molecular, radiologic, and surgical issues, but it is primarily based on histology. This classification is intended to support clinical practice, and research investigation and clinical trials. As EGFR mutation is a validated predictive marker for response and progression-free survival with EGFR tyrosine kinase inhibitors in advanced lung adenocarcinoma, we recommend that patients with advanced adenocarcinomas be tested for EGFR mutation. This has implications for strategic management of tissue, particularly for small biopsies and cytology samples, to maximize high-quality tissue available for molecular studies. Potential impact for tumor, node, and metastasis staging include adjustment of the size T factor according to only the invasive component (1) pathologically in invasive tumors with lepidic areas or (2) radiologically by measuring the solid component of part-solid nodules.
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http://dx.doi.org/10.1097/JTO.0b013e318206a221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4513953PMC
February 2011

Aspiration cytomorphology of fetal adenocarcinoma of the lung.

Am J Clin Pathol 2010 Dec;134(6):894-902

Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.

Fetal adenocarcinoma (FA) of the lung is an exceedingly rare malignancy. Many patients with the well-differentiated form are relatively young and with the high-grade variant are older. We describe the cases of 4 women with FA examined by fine-needle aspiration biopsy. Aspirates were moderately cellular with malignant, mostly aggregated cells. Glands and acini were present. The columnar neoplastic epithelial cells had homogeneous round nuclei with fine chromatin, smooth membranes, and indistinct nucleoli. With the rapid Romanowsky stain, subnuclear vacuoles were evident in some tumor cells; at times, this was associated with a focal extracellular tigroid pattern. Morule formation was present in the 3 specimens. Immunochemically, all tumors manifested epithelial and neuroendocrine differentiation. Cytomorphologic attributes included the following: (1) distinct subnuclear vacuoles, sometimes with an associated tigroid picture; (2) small, uniform, round nuclei; (3) morules; and (4) neuroendocrine differentiation in glandular epithelial cells.
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http://dx.doi.org/10.1309/AJCP4T5SWATQLKTQDOI Listing
December 2010

Metastatic hepatocellular carcinoma mimicking acinic cell carcinoma of the parotid gland: a case report.

Acta Cytol 2010 Sep-Oct;54(5 Suppl):889-92

Department of Pathology, Wake Forest University Baptist Medical Center, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA.

Background: Fine needle aspiration (FNA) is becoming increasingly important in the diagnosis of salivary gland lesions. One of the diagnostic difficulties that arise from FNAs is the distinction between primary and metastatic tumors. We describe a case where a right cheek/parotid mass was originally diagnosed as acinic cell carcinoma (ACC) upon biopsy. Later, an FNA resampling of the mass was diagnosed as hepatocellular carcinoma (HCC), and indeed, a subsequently performed computed tomography scan showed that the patient had a previously unknown liver mass.

Case: A 75-year-old man presented with a pathologic mandibular fracture. An initial needle core biopsy of the lesion showed neoplastic cells with abundant granular cytoplasm and prominent nucleoli and was diagnosed as ACC. The patient shortly thereafter developed an abdominal lesion that upon FNA was found to be cytologically similar to the parotid mass. Immunohistochemical stains showed that the abdominal mass was Hep Par 1 positive, and HCC was diagnosed. An FNA resampling of the parotid lesion was then performed, and stains showed that it was also Hep Par 1 positive. The lesion was rediagnosed as metastatic HCC and not ACC. Radiologic scans of the patient then showed a liver mass as well as multiple bony lesions.

Conclusion: A right cheek/parotid mass initially diagnosed as ACC was later found to be metastatic HCC. At times, the judicious use of immunohistochemical stains is necessary to distinguish primary salivary gland neoplasias from metastatic tumors.
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December 2010

Outcomes of patients with esophageal cancer staged with [¹⁸F]fluorodeoxyglucose positron emission tomography (FDG-PET): can postchemoradiotherapy FDG-PET predict the utility of resection?

J Clin Oncol 2010 Nov 27;28(31):4714-21. Epub 2010 Sep 27.

Wake Forest University Health Sciences, Winston-Salem, NC 27103, USA.

Purpose: To determine whether [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) can delineate patients with esophageal cancer who may not benefit from esophagectomy after chemoradiotherapy.

Patients And Methods: We reviewed records of 163 patients with histologically confirmed stage I to IVA esophageal cancer receiving chemoradiotherapy with or without resection with curative intent. All patients received surgical evaluation. Initial and postchemoradiotherapy FDG-PET scans and prognostic/treatment variables were analyzed. FDG-PET complete response (PET-CR) after chemoradiotherapy was defined as standardized uptake value ≤ 3.

Results: Eighty-eight patients received trimodality therapy and 75 received chemoradiotherapy. Surgery was deferred primarily due to medical inoperability or unresectable/metastatic disease after chemoradiotherapy. A total of 105 patients were evaluable for postchemoradiotherapy FDG-PET response. Thirty-one percent achieved a PET-CR. PET-CR predicted for improved outcomes for chemoradiotherapy (2-year overall survival, 71% v 11%, P < .01; 2-year freedom from local failure [LFF], 75% v 28%, P < .01), but not trimodality therapy. On multivariate analysis of patients treated with chemoradiotherapy, PET-CR is the strongest independent prognostic variable (survival hazard ratio [HR], 9.82, P < .01; LFF HR, 14.13, P < .01). PET-CR predicted for improved outcomes regardless of histology, although patients with adenocarcinoma achieved a PET-CR less often.

Conclusion: Patients treated with trimodality therapy found no benefit with PET-CR, likely because FDG-PET residual disease was resected. Definitive chemoradiotherapy patients achieving PET-CR had excellent outcomes equivalent to trimodality therapy despite poorer baseline characteristics. Patients who achieve a PET-CR may not benefit from added resection given their excellent outcomes without resection. These results should be validated in a prospective trial of FDG-PET-directed therapy for esophageal cancer.
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http://dx.doi.org/10.1200/JCO.2010.30.7702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020701PMC
November 2010

Cushing's syndrome and nocardiosis associated with a pulmonary carcinoid tumor: report of a case and review of the literature.

Diagn Cytopathol 2011 May 20;39(5):359-62. Epub 2010 Sep 20.

Department of Pathology, Wake Forest University School of Medicine, Winston Salem, NC, USA.

Ectopic hormone production is an uncommon complication of neoplastic lung disease. Rarely, patients may present with signs and symptoms of systemic endocrine dysfunction related to a hormone-secreting tumor. Bronchopulmonary carcinoids are the most common neoplasm implicated in ectopic ACTH-dependent Cushing's syndrome. Persistent hypercortisolism, such as that which occurs in Cushing's syndrome, causes immunosuppression and makes patients vulnerable to opportunistic infections. We present a case of a 42-year-old woman diagnosed with ACTH-dependent Cushing's syndrome which was originally thought to stem from a pituitary lesion as interpreted on magnetic resonance imaging. Her symptoms persisted after undergoing hypophysectomy, and further work-up involving a fine needle aspiration of the left lung revealed an ACTH-producing carcinoid tumor. Before treatment could be administered, the patient developed several new suspicious nodules in the left lung that were shown by fine needle aspiration to be infectious in nature. A Gram stain revealed numerous Gram positive branching organisms, and culture of the specimen grew Nocardia asteroides. Her pulmonary infection was treated with antibiotics and she underwent successful ablation of the carcinoid tumor.
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http://dx.doi.org/10.1002/dc.21428DOI Listing
May 2011

Sentinel lymph node intraoperative imprint cytology in patients with breast cancer-costly or cost effective?

Ann Surg Oncol 2010 Nov 22;17(11):2920-5. Epub 2010 Jun 22.

Department of Surgical Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.

Background: Sentinel lymph node (SLN) biopsy is now standard of care for breast cancer patients. Intraoperative imprint cytology (IIC) provides results to the surgeon, which may lead to a lymphadenectomy under the same anesthetic when it is positive for metastases. Thus, a positive IIC can spare the patient a second operation and the charges associated with it. The aim of this study is to assess the cost effectiveness of IIC in breast cancer patients.

Materials And Methods: This study evaluated 98 patients who underwent a SLN biopsy between July 2008 and May 2009. The patients were divided into 1 of 3 groups based on the results of IIC and permanent sections: (1) true-negative (TN) IIC, (2) true-positive (TP) IIC, and (3) false-negative (FN) IIC. Total charges for each patient were extracted retrospectively, and nonparametric tests assessed differences in the charges between the three groups.

Results: The median total charges per patient for each population were the following: (1) $14,764.62, (2) $19,025.89, and (3) $29,750.64 (P < 0.05). A difference of more than $10,000 exists in total charges per patient between the node-positive population who did not benefit from IIC (FN) and the node-positive population who did benefit from IIC (TP).

Conclusions: IIC is a cost-effective evaluation of breast cancer patients. The difference in total charges between the FN and TP groups outweighs the cost of the IIC. In addition to the reduced costs incurred by the patient and the hospital, IIC spares the patient the psychological and physical stress of a second operation.
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http://dx.doi.org/10.1245/s10434-010-1130-0DOI Listing
November 2010

Are pathologists accurately diagnosing eosinophilic esophagitis in children? A 9-year single academic institutional experience with interobserver observations.

Int J Surg Pathol 2011 Jun 18;19(3):290-6. Epub 2010 May 18.

Wake Forest University School of Medicine, Winston-Salem, NC, USA.

Our aims were to evaluate (a) whether the incidence of eosinophilic esophagitis (EE) in children has increased, (b) whether the histologic diagnosis of EE has been accurate, and (c) potential interobserver variability in the counting of intraepithelial eosinophils in esophageal biopsies. A total of 1215 pediatric endoscopic esophageal biopsies were performed. In total, 289 biopsies were reviewed by one pathologist based on one of the following original histologic diagnoses: EE, reflux esophagitis (RE), or acute/chronic inflammation. EE was diagnosed when at least one high-power field (HPF) contained > or = 20 intraepithelial eosinophils. According to the first pathologist, 104 biopsies had a histologic diagnosis of EE; the prevalence remained relatively stable, ranging from 5.5 to 11 per 100 biopsies annually. In 36 cases, the reporting pathologist correctly diagnosed EE, and in another 34, EE was included in the differential diagnosis. From January 1997 to December 1998, the pathologist either correctly diagnosed EE or included it in the differential diagnosis in 6/13 cases. In contrast, from January 2004 to December 2005, 32/37 cases were included. In 34/104 cases, EE was misdiagnosed as RE. No case of RE was misdiagnosed as EE.A total of 58 cases had pathology reports that quantified the densest number of eosinophils per HPF. The agreement rate was 94.8%, with a kappa value of 0.888. The incidence of EE in children has been stable from January 1997 to December 2005. Overall, pathologists recognized EE in two thirds of cases. The increased diagnostic accuracy over time suggests pathologists are more aware of EE.
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http://dx.doi.org/10.1177/1066896910363707DOI Listing
June 2011
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