Antonio Cajigas

Human Papillomavirus Infection and Cervical Cytology in HIV‐Infected and HIV‐Uninfected Rwandan Women

BACKGROUND Data on human papillomavirus (HPV) prevalence are essential for developing cost-effective cervical cancer prevention programs. METHODS In 2005, 710 human immunodeficiency virus (HIV)-positive and 226 HIV-negative Rwandan women enrolled in an observational prospective cohort study. Sociodemographic data, CD4+ cell counts, and cervical specimens were obtained. Cervicovaginal lavage specimens were collected from each woman and tested for >40 HPV types by a polymerase chain reaction assay; HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 were considered primary carcinogenic HPV types. RESULTS The prevalence of HPV was higher in HIV-positive women than in HIV-negative women in all age groups. Among HIV-infected women, 69% were positive for >or=1 HPV type, 46% for a carcinogenic HPV type, and 10% for HPV-16. HPV prevalence peaked at 75% in the HIV-positive women aged 25-34 years and then declined with age to 37.5% in those >or=55 years old (Ptrend<.001). A significant trend of higher prevalence of HPV and carcinogenic HPV with lower CD4+ cell counts and increasing cytologic severity was seen among HIV-positive women. CONCLUSIONS We found a higher prevalence of HPV infection in HIV-positive than in HIV-negative Rwandan women, and the prevalence of HPV and carcinogenic HPV infection decreased with age.

Fine Needle Aspiration Cytology of Orbital Masses

OBJECTIVE To review our experience with fine needle aspiration of orbital lesions. STUDY DESIGN Over an eight-year period, 24 orbital fine needle aspiration (FNA) samples were recorded, 22 of them adequate for interpretation. RESULTS There were two benign tumors. There were 14 malignant tumors, 5 primary, 8 metastatic and 1 malignant and originating in the nasal cavity, invading the orbit. In two cases the original tissue diagnosis was incorrect and was revised by the fine needle aspirate. There were six nonneoplastic cases. In one case an infectious agent was identified, and another showed atypical lymphoid cells. Of the two nondiagnostic cases, one was compatible clinically with an orbital pseudotumor, and the other had no available follow-up. A specific diagnosis was achieved in 18 of 24 instances, or 75% of the cases. CONCLUSION FNA is useful in the workup of an orbital lesion, leading to prompt diagnosis and treatment.

Risk Factors for Cervical Precancer and Cancer in HIV-Infected, HPV-Positive Rwandan Women

Background Although cervical cancer is an AIDS-defining condition, infection with human immunodeficiency virus (HIV) may only modestly increase the risk of cervical cancer. There is a paucity of information regarding factors that influence the natural history of human papillomavirus (HPV) in HIV-infected women. We examined factors associated with cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) in Rwandan women infected with both HIV and HPV (HIV+/HPV+). Methods In 2005, 710 HIV+ Rwandan women ≥25 years enrolled in an observational cohort study; 476 (67%) tested HPV+. Each woman provided sociodemographic data, CD4 count, a cervical cytology specimen and cervicovaginal lavage (CVL), which was tested for >40 HPV genotypes by MY09/MY11 PCR assay. Logistic regression models calculated odds ratios (OR) and 95% confidence intervals (CI) of associations of potential risk factors for CIN3+ among HIV+/HPV+ women. Results Of the 476 HIV+/HPV+ women 42 (8.8%) were diagnosed with CIN3+. Factors associated with CIN3+ included ≥7 (vs. 0-2) pregnancies, malarial infection in the previous six months (vs. never), and ≥7 (vs. 0-2) lifetime sexual partners. Compared to women infected by non-HPV16 carcinogenic HPV genotypes, HPV16 infection was positively associated and non-carcinogenic HPV infection was inversely associated with CIN3+. CD4 count was significantly associated with CIN3+ only in analyses of women with non-HPV16 carcinogenic HPV (OR = 0.62 per 100 cells/mm3, CI = 0.40-0.97). Conclusions In this HIV+/HPV+ population, lower CD4 was significantly associated with CIN3+ only in women infected with carcinogenic non-HPV16. We found a trend for higher risk of CIN3+ in HIV+ women reporting recent malarial infection; this association should be investigated in a larger group of HIV+/HPV+ women.

Esophageal carcinoma metastatic to the retina. Diagnosis of a case by cytologic examination of intraocular vitreous washings.

BACKGROUND The most common primary tumors of the eye are melanomas in adults and retinoblastomas in children. Although generally not recognized, metastases to the eye are more frequent than primary tumors. RESULTS Occult esophageal carcinoma metastasized to the retina in a 51-year-old woman. The cytologic diagnosis of carcinoma was established on intraocular vitreous washings. Further workup disclosed an adenocarcinoma of the esophagus, confirmed by brushings and biopsy. CONCLUSION The cytologic features of the intraocular aspirate allowed a rapid and reliable diagnosis that led to further investigation.

The Application of Molecular Diagnostics to Stained Cytology Smears

Detection of mutational alterations is important for guiding treatment decisions of lung non-small-cell carcinomas and thyroid nodules with atypical cytologic findings. Inoperable lung tumors requiring further testing for staging and thyroid lesions often are diagnosed using only cytology material. Molecular diagnostic tests of these samples typically are performed on cell blocks; however, insufficient cellularity of cell blocks is a limitation for test performance. In addition, some of the fixatives used while preparing cell blocks often introduces artifacts for mutation detection. Here, we applied qClamp xenonucleic technology and quantitative RT-PCR to cells microdissected directly from stained cytology smears to detect common alterations including mutations and translocations in non-small-cell carcinomas and thyroid lesions. By using this approach, we achieved a 1% molecular alteration detection rate from as few as 50 cells. Ultrasensitive methods of molecular alteration detection similar to the one described here will be increasingly important for the evaluation of molecular alterations in clinical scenarios when only tissue samples that are small are available.

Cisplatin DNA Adduct Detection and Depurination Measured by 32P DNA Radiolabeling and Two-Dimensional Thin-Layer Chromatography: A Time and Concentration Study

Abstract Platinum-based chemotherapies cause the formation of DNA adducts and have profound effects on DNA. This study measured cis-diamminedichloroplatinum II (cisplatin) DNA adducts by 32P-radiolabeling DNA, enzymatically digesting radiolabeled DNA, separating the formed adducts on two-dimensional thin-layer chromatography, and quantitating the adducts with autoradiography and densitometry. HeLa DNA was incubated with cisplatin at varying concentrations (6.25–325 nM) and times (0 min to 72 hr). Cisplatin rapidly depurinated dGMP and dAMP (90%, 15–min incubation with 325 nM cisplatin). Partial depurination of dGMP (15%) and dAMP (25%) occurred with lower cisplatin concentrations at equal incubation times. a minimum of four new adducts, with relatively rapid migratory patterns, were detected at high cisplatin concentrations with short incubation times. These results indicate that the depurination of DNA correlates with DNA adduct formation and that the quantification of these adducts may be applicable to monitoring tumor and host cell response to cisplatin chemotherapy.

THE FORMATION AND MEASUREMENT OF DNA NEUROADDUCTION IN ALCOHOLISM : CASE REPORT

We present a case report of an intoxicated alcoholic driver who sustained fatal motor vehicle injuries. We subsequently quantified ethanol-derived acetaldehyde (ACE) DNA products in his brain, which may represent a major contributor to clinical alcoholic use and complications. Further, ACE DNA neuroadducts may indicate chronic exposure to alcohol, as demonstrated by 32P-prelabeled DNA and two-dimensional thin-layer chromatography. ACE and other unknown neuroadducts were evident in the histologically normal frontal, parietal, and caudate lobes. DNA neuroadduct formation was extensive and similar in three separate brain regions with normal histology. Contributing neuroadduction by chronic drug abuse is also possible, though the deceaseds terminal acute blood screens for recent drug abuse were negative. The mechanism of alcohol neurotoxicity remains unknown, but biochemical nonenzymatic changes of DNA at the nucleic acid level (adduct formation) can alter gene function and stability. DNA neuroadduct detection may represent an important determinant in quantifying neurotoxicity from drug abuse or alcoholism in the absence of history, the presence of negative blood, tissue, and urine assays for recent drug and alcohol use, and the absence of neuropathology.

A rare case of chondroma of the parotid gland.

Patient: A 39-year-old Hispanic woman. History of Present Illness: The patient had swelling of the left side of her neck, which she had first noticed 3 to 4 months before consultation and which did not subside after 2 courses of antibiotics. She reported no tenderness, dysphagia, odynophagia, dysphonia, otalgia, fevers, chills, or weight changes. Past medical history: The patient had a past history of gastroesophageal reflux disease, arthritis (knee and cervical disease), and a prior abnormal Pap smear result (high grade squamous intraepithelial lesion). The cervical lesion was treated with a loop electrosurgical excision procedure (LEEP). Her past surgical history is remarkable for cholecystectomy and a left breast biopsy with benign results. Social history: Noncontributory. Family history: Noncontributory. Physical exam: The patient harbored a firm, nontender, fully mobile 2- to 3-cm left parotid tail mass without other abnormalities; her facial nerve function was intact in all branches. Principle Laboratory Findings: See [Image 1][1], [Image 2][2], [Image 3][3], [Image 4][4], [Image 5][5], and [Image 6][6]. * FNA : fine needle aspiration LEEP : loop electrosurgical excision procedure CT : computed tomography [1]: #F1 [2]: #F2 [3]: #F3 [4]: #F4 [5]: #F5 [6]: #F6

Fine needle aspiration of an unusual malignant mixed tumor in the parotid gland.

OBJECTIVE The use of fine needle aspiration (FNA) biopsy in the triage of salivary gland tumors has been well established. The sensitivity and specificity of FNA biopsy for tumor diagnosis is generally very good. However, the diagnosis can be challenging due to the limited amount of tissue sampled, the occasional overlapping tumor morphology, and the presence of a malignant counterpart of a benign tumor. METHODS FNA biopsy was performed with ultrasound guidance. Air-dried slides and alcohol-fixed slides were made for Diff-Quik staining and Papanicolaou staining, respectively. The syringes were rinsed and a cell block was prepared. The resected specimen was fixed in 10% formalin and processed by routine histology techniques. RESULTS We report a rare case of a salivary gland neoplasm with 2 distinct components: adenoid cystic carcinoma and pleomorphic adenoma. These 2 components are clearly identifiable in both cytological materials from fine needle aspiration and histological analysis of surgical resection. CONCLUSION Pleomorphic adenoma is the most common salivary gland tumor for patients in all age groups. The characteristic cytological feature is fibrillary extracellular matrix intermixed with epithelial cells. Malignant transformation occurs in 5% to 10% of cases. Rarely, pleomorphic adenoma exists as one component of a hybrid tumor. The surgical resection will be needed in those cases. The final diagnosis relies on the combination of the clinical information, histological findings and molecular study.

Metastatic Salivary Duct Carcinoma of the Submandibular Gland Presenting as a Poorly Differentiated Carcinoma of Unknown Primary: A Case Report

A 53 year old male presented to his primary care doctor with a palpable neck mass for the past four months. At that time he was given antibiotics with no change in the mass. The patient was a 20 pack-year, current smoker. He was sent for an ultrasound-guided fine needle aspirate (FNA) of the mass. The FNA of a right level I lymph node was performed and findings were consistent with a poorly differentiated carcinoma, possibly reflecting a primary salivary gland lesion or less likely a pulmonary lesion. Upon follow-up physical exam the patient was found to have mild asymmetry and firmness of the right base of tongue as well as a 1.0 x 1.0 cm, firm submandibular mass. The patient was referred to otorhinolaryngology. A PET scan was performed and showed multiple avid cervical lymph nodes in the right neck, focal activity in the supero-medial aspect of the right submandibular gland, as well as very small bilateral lung nodules. At this point, a primary site in the submandibular gland was favored; yet the aerodigestive tract was not excluded. Pleural fluid was sent for cytological analysis and subsequently the patient underwent a diagnostic laryngoscopy, biopsy, esophagoscopy, and right selective neck dissection.