Infectious disease diagnosed by fine needle aspiration biopsy.

INTRODUCTION: Fine needle aspiration biopsies (FNABs) have become increasingly important in the assessment of infectious diseases. We assess the ability of cytopathology to predict the presence of a pathogen and review how often neoplasia occurs concurrently with infection. MATERIALS AND METHODS: A 3-year retrospective review of FNABs with concurrent culture results was performed at the Zuckerberg San Francisco General Hospital and Trauma Center. Rapid onsite evaluation was performed for all cases by a pathologist. The results of the special and immunohistochemical stains and polymerase chain reaction testing were correlated, when available. RESULTS: A total of 231 samples from 11 different tissue sites were submitted for microbial culture, of which 49 (21%) were positive for pathogenic organisms. Only 2 false-negative cases by cytology were found in immunosuppressed patients. A total of 38 patients had a diagnosis of neoplasia, with 2 (5%) having concurrent infection. Overall, the sensitivity and specificity of cytology in predicting the presence of infection was 96% (95% confidence interval, 86%-100%) and 42% (95% confidence interval, 34%-50%), respectively. Molecular testing was performed in 11 cases, 2 of which were positive for Mycobacterium tuberculosis complex and had cytologic findings of necrosis. Polymerase chain reaction and other ancillary tests were unable to further characterize 2 cases with acid-fast bacilli. CONCLUSIONS: Our study has shown that FNABs have high sensitivity in detecting infection and that negative cytology findings will correlate with a negative infectious workup. Although infection in the setting of neoplasia is uncommon, it should be considered if clinical data are available to suggest infection.

Expression of Hormone Receptors and HER-2 in Benign and Malignant Salivary Gland Tumors.

With the advent of targeted therapies, expression of sex hormone receptors and HER-2 in salivary gland tumors (SGTs) is of clinical interest. Previous reports of estrogen (ER) and progesterone (PR) receptor expression have varied. Androgen receptor (AR) and HER-2 overexpression are frequently reported in salivary duct carcinoma (SDC), but have not been studied systematically in other SGTs. This study examines ER, PR, AR, and HER-2 expression in SGTs. Immunohistochemistry for ER, PR, AR, and HER-2 was performed on 254 SGTs (134 malignant). ER, PR, and AR expression was scored using Allred system. HER-2 expression was scored using Dako HercepTest guidelines. FISH for HER-2 amplification was performed on select cases with HER-2 overexpression (2-3+). No SGT demonstrated strong expression of ER or PR. Combined strong AR and HER-2 expression was seen in 22 carcinomas: 14/25 SDC, 3/16 poorly differentiated, two oncocytic, and one each carcinoma ex pleomorphic adenoma, squamous cell, and intraductal carcinoma. Eighteen additional high grade carcinomas had HER-2 overexpression with absent, weak, or moderate AR expression; eight high grade carcinomas had isolated strong AR expression with 0-1+ HER-2 staining. Of 15 tested cases, six demonstrated HER-2 amplification by FISH, all of which had 3+ immunoreactivity. Neither benign nor malignant SGTs had strong expression of ER or PR. None of the benign SGTs overexpressed AR or HER-2. Coexpression of AR and HER-2 should not define SDC, but immunostaining should be considered in high grade salivary carcinomas, as some show overexpression and may benefit from targeted therapy.

Cytology cases of the week: an educational tool that improves trainee exposure to cytology.

INTRODUCTION: The Accreditation Council for Graduate Medical Education requires residents to examine 1500 cytology specimens by the end of residency. Cytology cases of the week (COWs) were instituted in 2010-2011 in an effort to increase trainee exposure to cytology. MATERIALS AND METHODS: Images of 2 to 5 cases with basic clinical information are sent to residents weekly. Residents have 1 week to respond by e-mail; after which, correct answers are e-mailed. Cytology resident in-service examination (RISE) scores were used to assess the effectiveness of COWs. Additionally, a feedback survey was distributed to trainees to determine the perception of COWs as a teaching tool. RESULTS: An unpaired two-sided t test showed residents who participated in COWs scored 15.4% higher on the RISE than residents who participated minimally or not at all over the 5-year period (P < 0.05). In 2014-2015 and 2015-2016, when COWs were minimally and not at all offered, we saw a significant decrease in average cytology RISE scores compared with prior years when COWs were offered (P < 0.05). There was no correlation between percentage of correctly submitted answers for COWs and RISE scores. The vast majority (83%) of trainees reported participating in COWs for self-study, and the majority (86%) felt participation in COWs increased their cytology knowledge. Major reasons for not participating included technical challenges and time limitations. CONCLUSIONS: COWs are an effective educational tool that increase resident fund of knowledge in cytology. Residents who participate in COWs perform higher on the RISE, regardless of percentage of correctly submitted answers.

Concomitant Epstein-Barr Virus-associated smooth muscle tumor and granulomatous inflammation of the liver.

Epstein-Barr Virus-associated smooth muscle tumor (EBV-SMT) is a rare mesenchymal tumor typically seen in immunocompromised patients. Here, we report a case of EBV-SMT and associated granulomatous inflammation in the liver of a 32-year-old man with history of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). To our knowledge, an association of these two lesions has not been previously reported. We review the literature and discuss pathogenesis, differential diagnosis and immunohistochemical (IHC) stains helpful for the diagnosis of this rare entity. Finally, we consider possible explanations for the concomitant presence of these lesions.

Natural History and Malignant Transformation in Recurrent Respiratory Papillomatosis: Human Papillomavirus (HPV), Dysplasia and an Autopsy Review.

INTRODUCTION: Recurrent respiratory papillomatosis (RRP) is a human papillomavirus (HPV) related disease in both children and adults, characterized by recurrent benign squamous papillomas of the respiratory mucosa. Malignant transformation is rare. The present report concerns the natural history of RRP in two children. MATERIALS AND METHODS: Clinical records, autopsy material and tissue from previous surgical excisions were reviewed in both cases. Select surgical and autopsy specimens were examined using p16 immunohistochemistry and in-situ hybridization for low and high risk HPV. RESULTS: Both children had pulmonary involvement with incidental invasive keratinizing squamous carcinoma of the lung at autopsy. Low-risk HPV was present in the papillomas and carcinoma at autopsy in both cases. CONCLUSIONS: The autopsy examinations in these two cases emphasize the serious, if uncommon, pulmonary complications of this disease. In conjunction with previously reported autopsies, destructive lung disease may be as frequent a cause of death as disseminated malignancy.

Spontaneous Hepatic Rupture Associated With Epstein-Barr Virus Negative Aggressive Natural Killer Cell Leukemia.

Aggressive natural killer cell leukemia (ANKL) is a rare subtype of large granular lymphocyte (LGL) leukemia, which typically presents in young adults of Asian descent. It is an aggressive disease, characterized initially by fever, pancytopenia and hepatosplenomegaly, which rapidly progresses to organ failure and death over the course of months. Spontaneous hemorrhagic complications have been reported to occur in ANKL in a handful of case reports, including lethal intestinal and cerebral hemorrhage as well as splenic rupture. Here, we present a case of a 49-year-old man with Epstein-Barr virus (EBV)-negative ANKL who developed fatal spontaneous hepatic rupture approximately 4 months after initial diagnosis. To the best of our knowledge, this is first reported case of hepatic rupture associated with ANKL.

Human papillomavirus testing in patients with invasive cervical carcinoma: An institutional experience.

INTRODUCTION: The 2012 American Cancer Society cervical cancer screening guidelines' preferred method of screening women ages 30 to 65 years is through cytology and human papillomavirus (HPV) co-testing every 5 years. Our objective was to review the performance of HPV testing in invasive cervical carcinoma in view of these recommendations. MATERIALS AND METHODS: The University of Chicago Pathology database was searched for surgical specimens with primary cervical carcinoma diagnosis from January 1, 2005 to March 30, 2013. All cases with HPV and Papanicolaou smear results within 5 years prior to initial diagnosis were selected for analysis. HPV DNA testing was performed on residual liquid-based screening cytology specimens using Digene Hybrid Capture 2 (Qiagen, Gaithersburg, MD). RESULTS: Seven patients met the inclusion criteria, including 5 cases of cervical squamous cell carcinoma (SCC) and 2 cases of cervical adenocarcinoma. One patient with SCC tested negative twice for high-risk HPV and 4 cases (2 cases of SCC and 2 cases of adenocarcinoma) tested positive for high-risk HPV. The remaining 2 cases of SCC alternatively tested positive and negative for high-risk HPV on different occasions. In 1 case of SCC, testing was initially positive, then negative, and finally positive prior to histologic diagnosis. In the other case of SCC, testing was initially positive, but negative on repeat testing. CONCLUSIONS: Though limited by sample size, our results demonstrate that false-negatives in HPV testing for primary cervical carcinoma can occur. False-negative HPV results have significant repercussions with the newly recommended extended screening intervals, particularly in the setting of negative cytology.

Lack of association of BRAF mutation with negative prognostic indicators in papillary thyroid carcinoma: the University of California, San Francisco, experience.

IMPORTANCE: Papillary thyroid carcinoma (PTC) is the most common endocrine neoplasm. B-type raf kinase (BRAF) V600E mutation has been proposed as a negative prognostic indicator in PTC, and patients harboring it should receive more aggressive initial therapy. OBJECTIVE: To assess the significance of BRAF V600E mutation in PTC in the largest US sample to date. DESIGN: We identified patients from our institution's pathology archives diagnosed as having PTC and meeting criteria for BRAF mutation testing. Medical records were analyzed for BRAF status (positive or negative) and a list of standardized clinicopathologic features. PARTICIPANTS: A total of 429 patients with PTC at an academic medical center. MAIN OUTCOMES AND MEASURES: Clinicopathologic features in patients with PTC with and without BRAF mutation. RESULTS: Of 429 cases with PTC, 314 (73.2%) were positive for the BRAF mutation and 115 (26.8%) tested negative. BRAF mutation was significantly associated with tumor margin positivity (P = .03) and lymph node metastasis (P = .002) on univariate analysis but not on multivariate study. BRAF mutation was a predictor of male sex (odds ratio [OR], 3.2; 95% CI, 1.4-7.2), total thyroidectomy (OR, 2.6; 95% CI, 1.1-6.2), and a negative predictor of follicular variant PTC (OR, 0.1; 95% CI, 0.1-0.4). There was no significant association between BRAF positivity and tumor multicentricity, lymphovascular invasion, extranodal extension, central neck involvement, advanced stage (stage III or IV), and distant metastasis. CONCLUSIONS AND RELEVANCE: BRAF V600E mutation has been extensively studied in relation to negative prognostic indicators in PTC, with no consistent relationship emerging. Two recent meta-analyses showed an overall association between BRAF status and aggressive disease features and called for tailoring treatment plans in patients accordingly. In this, the largest US study to date, BRAF status was not significantly associated with most clinicopathologic features suggestive of more aggressive disease.

Cervical squamous cell carcinoma metastatic to placenta.

A pregnant 29-year-old gravida 4, para 3 woman with Stage IIB cervical cancer was admitted at 33 weeks and 4 days of gestation and delivered a healthy neonate. Her placenta was small but otherwise grossly unremarkable. Microscopic examination revealed metastatic squamous cell carcinoma. An immunohistochemical stain for p16 was positive in the carcinoma cells, supporting metastasis from the cervical tumor. Cervical squamous cell carcinoma metastatic to placenta is very rare. We report a case and discuss metastatic cancer during pregnancy with recommendations for infant follow-up.