The ATHENA HPV study underrepresents "other" high-risk HPV genotypes when compared with a diverse New York City population.

OBJECTIVE: Persistent infection with oncogenic high risk HPV (hrHPV) types causes virtually all cases of cervical cancer. HPV 16 and 18 have been targeted for individual genotyping and vaccination because of their presence in 71% of invasive cervical cancers worldwide. Montefiore Medical Center, Bronx, New York serves a population known for ethnic and racial diversity. Given this diversity it is possible that HPV genotypes not individually detected by current testing are causing significant disease. METHODS: We conducted a retrospective analysis of liquid based cervicovaginal cytology and Cobas HPV results reported between October 5, 2015 and March 30, 2016. This included 20 483 samples from patients aged 16-95 (average age 42), with racial distribution including: African-American 32.4%, Other (includes denied, unknown, mixed, Hispanic) 52.1%, Caucasian 14.5%, Asian 0.7%, American Indian/Alaskan Native 0.3%. In all, 14 938 samples (72.9%) were submitted for clinically requested COBAS 4800 HPV testing, which separately reports HPV 16, 18 and a pool of 12 other hrHPV. RESULTS: A total of 3180 (21.5%) tested hrHPV positive. The percentage of patients with cytologic diagnosis of HSIL (high-grade squamous intraepithelial lesion) that were positive only for HPV 16 was 19.4% vs 1.8% for all cytologic diagnoses. However, only one of the HSIL cases was HPV 18 positive along with other hrHPV (OHR). Surprisingly, a majority (64.5%) was positive for only OHR. CONCLUSIONS: Further evaluation is needed to determine if this pool of other hrHPV includes individual genotypes that in our population carry a higher risk of persistence and progression to cancer.

SurePath Specimens Versus ThinPrep Specimen Types on the COBAS 4800 Platform: High-Risk HPV Status and Cytology Correlation in an Ethnically Diverse Bronx Population.

OBJECTIVE: To compare the cytologic preparations of 130 cervical specimens (from women of various ethnicities at high risk for human papillomavirus [HPV] infection) using the SurePath (SP) collection system with specimens gathered using the ThinPrep (TP) system, as processed on the Cobas 4800 analyzer, to determine which collection method more accurately identifies HPV infection. METHODS: In our prospective study, specimens were collected from 130 women of various ethnicities residing in or near Bronx County, NY. The SP-collected specimen was first processed for cytologic findings; if clinical HPV testing was requested on that specimen, it was tested using Hybrid Capture II (HC2) methodology. We tested the remnant SP-collected cell concentrate using the Cobas analyzer. Then, the TP-collected and SP-collected specimens were tested in the same run on that analyzer, and the results were compared. We also compared the results with the concurrent cytologic findings. RESULTS: The results were concordant for overall HR-HPV status in 93.8% of cases. Also, a statistically significant lower cycle threshold value was observed with Cobas testing of specimen concentrates tested via the BD SurePath Pap Test (P = .001), suggesting higher sensitivity compared with specimens tested via the ThinPrep Pap Test. CONCLUSION: Cobas 4800 HPV testing of SP-collected specimen concentrates yields comparable results to TP-collected specimen concentrates. Based on the limited data that we derived, SP collection may be a more favorable methodology than TP collection for HPV testing of individuals at high risk in our ethnically diverse, urban patient population.

Role of US-guided fine-needle aspiration with on-site cytopathologic evaluation in management of nonpalpable breast lesions.

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the accuracy of ultrasound (US)-guided fine-needle aspiration (FNA), with radiographic follow-up or surgical excision, in conjunction with on-site cytopathologic support in the management of nonpalpable breast lesions. MATERIALS AND METHODS: The findings of 266 consecutive mammographically or sonographically identified, nonpalpable lesions (228 patients) that underwent US-guided FNA were examined retrospectively. Clustered microcalcifications did not undergo biopsy with this method. Patients who underwent follow-up excisional biopsy or mammography with a duration of at least 24 months were included in the study. RESULTS: In all, 117 lesions met criteria for inclusion, of which 85 (73%) were diagnosed as benign at cytopathologic evaluation and underwent mammographic follow-up of at least 24 months (range, 24-67 months; mean, 36 months). Thirty-two lesions (27%) had either malignant or atypical cytopathologic findings, for which surgery was recommended. Eleven (9%) of the 32 had malignant cytopathologic findings from initial US-guided FNA, which were confirmed at surgical excision. The remaining 21 lesions (18%) were diagnosed as atypical on the basis of US-guided FNA results. Of these, 18 lesions underwent excisional biopsy: Two were diagnosed as carcinoma (not otherwise specified), and 16 were diagnosed with a variety of benign disorders. The remaining three patients with atypical lesions chose mammographic follow-up rather than surgical diagnosis, and their conditions have remained stable for more than 24 months. Of the 85 benign cases, one changed during follow-up (12 months) and underwent repeat biopsy, with malignancy noted. The sensitivity of US-guided FNA in identifying malignant lesions was 93% (13 of 14), and the specificity of a benign finding was 100% (102 of 102). The positive and negative predictive values of US-guided FNA supported by on-site cytopathologic evaluation were 100% (13 of 13) and 99% (102 of 103), respectively. CONCLUSION: Supported by appropriately trained on-site cytopathologists and in conjunction with follow-up mammography, US-guided FNA appears to be efficacious in the management of patients with abnormal radiographic findings. It is quick, relatively inexpensive, and minimally invasive, and, in the presence of competent cytopathologists, should be the modality of choice.

Cervical papanicolaou smear abnormalities and Chlamydia trachomatis in sexually active adolescent females.

STUDY OBJECTIVE: To examine the effect of cervical Chlamydia trachomatis infection on the prevalence of Papanicolaou (Pap) smear abnormalities in adolescent females. DESIGN: Retrospective study performed by examination of previously obtained cervical C. trachomatis cultures and Pap smear results. SETTING: Urban adolescent health care clinic in the Bronx, New York. PARTICIPANTS: Sexually active females, aged 13 to 23 (mean age: 17.9 years), attending the clinic for evaluation of sexually transmitted diseases. INTERVENTION: Patients who had undergone a gynecological examination with performance of cervical Pap smears and culture for C. trachomatis were enrolled in the study. MAIN OUTCOME MEASURE: Determine the prevalence of cervical C. trachomatis infection and compare cervical smear abnormalities in those with and without infection. RESULTS: Of a study population of 257 females, 24 patients (9.3%) were culture positive for C. trachomatis and 58 patients (22.6%) had significant cervical smear abnormalities, i.e., atypical squamous cells of undetermined significance (ASCUS), low grade squamous intraepithelial lesion (LGSIL), or high grade squamous intraepithelial lesion (HGSIL). The 24 patients infected with C. trachomatis showed the following cervical smear abnormalities: within normal limits-37.5%, benign cellular changes-41.7%, ASCUS-12. 5%, and LGSIL-8.3%. A total of 233 patients (90.7%) were culture negative for C. trachomatis and showed the following cervical smear abnormalities: within normal limits-37.3%, benign cellular changes-39.9%, ASCUS-13.3%, LGSIL-8.6%, and HGSIL-.9%. Statistical analysis suggested no significant differences between the two groups (P >.9 by the Kruskal-Wallace test). CONCLUSIONS: The isolation of C. trachomatis from the cervix of sexually active adolescent females at a single point in time does not impact on the prevalence of significant cervical smear abnormalities.

Cervical Papanicolaou smear abnormalities in inner city Bronx adolescents: prevalence, progression, and immune modifiers.

BACKGROUND: The aim of this study was to quantify the prevalence of cervical smear abnormalities in sexually active adolescents and identify the effect of immune-modifying conditions. METHODS: Two hundred seventy-one females ages 13-22 years attending a clinic for sexually transmitted disease (STD) evaluation had cervical Papanicoloau (Pap) smears and completed sexual history questionnaires. Results of all follow-up Pap smears were obtained. Medical charts were available for 54 patients with cytologic follow-up and were reviewed for the presence of immune-modifying conditions. Follow-up smear results for patients with and without immune-modifying conditions were compared. Abnormality rates for all cervical smears seen in 1995 at Montefiore Medical Center were also obtained. RESULTS: The smear abnormality rate for adolescents was 20. 7% (abnormal squamous cells of undetermined significance [ASCUS], 12. 2%; low grade squamous intraepithelial lesion [LGSIL], 7.7%; high grade squamous intraepithelial lesion [HGSIL], 0.7%) compared with all adult females, for whom the rate was 13.2% (ASCUS, 9.9%; LGSIL, 2.5%; HGSIL, 0.6%; carcinoma 0.2%) (P < 0.0002). Of 20 initial ASCUS patients, 6 (30%) showed LGSIL or HGSIL on follow-up. Chart review allowed the clinical immune status of 54 patients to be determined. Of 14 patients with an immune-modifying condition (9 HIV positive patients, 3 receiving oral steroids, 1 liver transplant patient receiving steroids, and 1 with intestinal lymphangiectasia), 11 (78. 6%) developed or maintained an abnormality on cytologic follow-up. Of 40 patients with no identifiable immune-modifying condition, 11 (27.5%) developed or maintained an abnormality on cytologic follow-up (P < 0.00082). CONCLUSIONS: Sexually active adolescents are at higher risk of developing a significant cervical smear abnormality, especially LGSIL. Patients with an atypical Pap smear or immune-modifying condition require more attentive gynecologic monitoring. Cancer (Cancer Cytopathol)

Non-Hodgkin lymphoma in acquired immunodeficiency syndrome manifesting as bilateral hypopyon.

Orbital lymphoma is a rare event. This is the first case report of a patient with acquired immunodeficiency syndrome-associated lymphoma, in which orbital lymphoma presented as bilateral hypopyon. This was the terminal manifestation of a highly aggressive disease, which progressed despite appropriate treatment.

Cytologic criteria for the brush diagnosis of gastric adenocarcinoma.

BACKGROUND: The cytologic diagnosis of gastric adenocarcinoma often is difficult, and the role of gastric brushing in the detection of gastric malignancy is controversial. The purpose of this study was to identify the key cytologic criteria that are most useful for establishing a diagnosis of adenocarcinoma in gastric brushing specimens. METHODS: One hundred gastric brushings were reviewed retrospectively. Fifty of the specimens were obtained from patients with histologically confirmed benign lesions. The other 50 specimens were obtained from patients with histologically confirmed gastric adenocarcinoma. All 100 brushing specimens were reviewed without knowledge of the histologic diagnosis. Each specimen was assessed for the presence or absence of 16 different cytologic features that have been identified in the published literature as being useful for separating benign conditions from malignancy. A multiple logistic linear regression analysis was performed to determine which combination of criteria was the most useful for diagnosing gastric adenocarcinoma. RESULTS: Three key cytologic criteria were identified as being the most useful for diagnosing gastric adenocarcinoma: single atypical cells with intact cytoplasm, eccentric nuclei, and atypical naked nuclei. When at least 2 of these cytologic criteria were present, the sensitivity and specificity for detecting adenocarcinoma were 88% and 100%, respectively. Two minor cytologic criteria also were identified: nuclear hyperchromasia and nuclear molding. CONCLUSIONS: Our statistical analysis demonstrates that gastric adenocarcinoma can be diagnosed with a high degree of accuracy using gastric brushing specimens when specific cytologic criteria are applied.

Evaluation of esophageal cytology using a neural net-based interactive scanning system (the PAPNET system): its possible role in screening for esophageal and gastric carcinoma.

A neural net-based, semiautomated, interactive computerized cell analysis system (The PAPNET system, Neuromedical Systems, Suffern, NY) was used to examine cells from 138 esophageal smears obtained by lavage, brushings, or balloon from as many patients. From each smear, trained human observers examined 128 cell images selected by the machine. Abnormal cells were identified in all 35 patients with cancer, whether esophageal, gastric, oral, or metastatic. Further, in 11 smears, the displayed images allowed the recognition of effects of radiotherapy and, in 14 smears, the diagnosis of a specific tumor type, such as squamous cell carcinoma (8 patients) or adenocarcinoma (6 patients). In 3 additional cases, the diagnosis of "carcinoma, not further specified," was established. One case of esophageal carcinoma in situ, not previously recognized on a smear or in the biopsy specimen, and one case of gastric adenocarcinoma, not recognized in the smear, were identified in PAPNET-generated images. The possible application of the apparatus to the triage of smears and population screening for esophageal and gastric carcinoma precursors is discussed.

Urine cytology of primary and secondary urinary bladder adenocarcinoma.

BACKGROUND: Primary and secondary adenocarcinomas of the urinary bladder are uncommon, and the urine cytology of these tumors has rarely been described. Familiarity with the cytomorphology of these neoplasms may facilitate their detection in urine cytology specimens. METHODS: The authors reviewed 46 urine samples (19 voided, 19 instrumented, and 8 bladder washings) from 41 patients with biopsy-proven primary urinary bladder adenocarcinoma (n = 11) or metastatic adenocarcinoma (n = 35) from the prostate (n = 17), colon (n = 10), breast (n = 3), kidney (n = 3), or uterus (n = 1), or from unknown origin (n = 1). Cytomorphology, the role of cytology, and causes for negative diagnoses were evaluated. RESULTS: Cytologic diagnoses of malignancy, adenocarcinoma not otherwise specified, and adenocarcinoma of a specific type were given in 87%, 28%, and 39% of cases, respectively. Columnar cells, coarse chromatin, and necrosis were found in adenocarcinoma of the colon. Syncytial and acinar arrangements, round or oval nuclei, vesicular chromatin, and prominent nucleoli were commonly found in adenocarcinoma of the prostate. These features permitted us to make a specific diagnosis in 90% of cases of adenocarcinoma of the colon and 41% of cases of adenocarcinoma of the prostate. Cytologic examination failed to lead to a diagnosis of malignancy in 18% of primary adenocarcinoma cases. CONCLUSIONS: A large number of adenocarcinomas of the colon and prostate have sufficient cytologic features to suggest the correct diagnosis in urine samples. The cytomorphology of primary bladder adenocarcinoma is not as easily characterized. The submucosal nature of some metastatic deposits and tumor differentiation influence the diagnostic accuracy.

Correlation of the ratio of CD4+/CD8+ cells in lymph node fine needle aspiration biopsies with HIV clinical status. A preliminary study.

OBJECTIVE: To test the hypothesis that lymph node (LN) fine needle aspiration biopsy (FNAB) may provide reliable measures of human immunodeficiency virus (HIV) disease status. STUDY DESIGN: HIV+ participants in this study had persistent generalized lymphadenopathy without clinical evidence of lymphoma or nodal infections due to organisms other than HIV. Seven males and five females ranging in age from 23 to 55 and at HIV Centers for Disease Control (CDC) stages A2-C3 were enrolled in this study. From each participant, LN and blood samples were submitted for cytologic examination and flow cytometric analysis of lymphocyte subsets. Flow cytometry measures included T, B, CD4+, CD8+ and natural killer (NK) cells. The percentages of T, B and NK cells in LN and blood samples were different and reflected the expected distribution of these cell types in the respective tissues. RESULTS: The percentages of CD4+ and CD8+ cells in blood and LN were different, but this variation was not statistically significant. In contrast, the ratio of CD4+/CD8+ cells in LN and blood was different and statistically significant (P < .001) for patients in CDC categories A2-B2 but not different for categories B3-C3. More important, there was a significant (r = .76) correlation between the ratio of CD4+/CD8+ cells in LN with CDC stage. CONCLUSION: FNAB, in combination with flow cytometry, may prove to be an important tool in HIV clinical staging. However, further assessment, including clinical follow-up and participation of additional patients, is necessary and currently under way.

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.

Cytologic findings in thyroglossal duct carcinoma.

Approximately 150 cases of thyroglossal duct carcinoma, predominantly of the papillary type, have been reported, but the preoperative fine-needle aspiration (FNA) diagnosis of such neoplasms has rarely been cited. The authors describe FNA findings in four samples obtained from three patients who were 29, 50, and 83 years of age, histologically diagnosed as papillary (n = 2) and squamous (n = 1) thyroglossal duct carcinomas. Atypia and squamous cell carcinoma were the FNA diagnoses in the patients with papillary carcinomas. The remaining case was correctly diagnosed as keratinizing squamous cell carcinoma. Cellularity was scant in two cases and moderate in one, and all displayed a cystic background. The authors also reviewed FNA features in 11 papillary and 2 Hurthle cell carcinomas from the English language literature; diagnostic findings were present in less than one third of the cases. In conclusion, familiarity with the FNA findings of thyroglossal duct carcinoma is limited by its rarity. The presence of large, atypical squamous cells, or psammoma bodies, in the FNA material of a midline anterior cystic neck mass should suggest papillary thyroglossal duct carcinoma.

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.

Exfoliative respiratory cytology in the diagnosis of leukemias and lymphomas in the lung.

Leukemias and lymphomas involving the lung were diagnosed by means of exfoliative cytology in 31 specimens from 20 patients. Initial diagnostic categorizations included 29 specimens "positive for malignancy," including two thought to represent "carcinoma vs. lymphoma," and two considered suspicious for lymphoma. Previous diagnoses of lymphoma (13 patients) and acute myelogenous leukemia (AML) (2 patients) were available. In 5 additional patients, exfoliative respiratory cytology yielded the first diagnosis of hematopoietic malignancy. Cytologic diagnosis included nine large-cell and six small-cell non-Hodgkin's lymphomas (NHL), three Hodgkin's lymphomas (HD), and two AML. Key cytologic features included markedly pleomorphic and monomorphic cell populations in HD and NHL, respectively, as well as lack of tumor cell cohesion and necrosis in all cases. Cytologically, acute leukemia may be difficult to differentiate from large-cell NHL, and small-cell NHL from reactive/benign small lymphocytes. Blood, scant cellularity, crush artifacts, and apparent molding may affect diagnostic accuracy. Immunocytochemistry in cell block sections of sputa and washings is useful in the diagnostic workup in selected cases. Although involvement of the respiratory system by leukemias and lymphomas is uncommon and not always preceded by a history of malignancy, cytologic diagnosis is usually prompt, reliable, and accurate.

Primary and metastatic high-grade carcinomas of the salivary glands: a cytologic-histologic correlation study of twenty cases.

We reviewed the clinical and fine-needle aspiration (FNA) findings in 20 patients with poorly differentiated carcinomas presenting initially as parotid or as submandibular masses. There were 11 primary tumors and nine metastatic malignancies in 14 males and six females ranging in age from 39 to 89 yr (median = 66). The tumor types included three primary carcinomas with oncocytic features, three additional cases of high-grade parotid carcinoma, one case of primary neuroendocrine carcinoma, two examples of malignant mixed tumor, one high-grade mucoepidermoid carcinoma, and a single example of malignant lymphoepithelial lesion. Six patients with metastatic carcinoma had previous diagnoses of malignancy. In the three remaining individuals, primary carcinomas of the lung (two cases), and an unknown primary site presented initially as parotid masses. Five examples of metastatic squamous cell carcinoma, one metastatic basal cell carcinoma, and two metastatic renal cell carcinomas were identified. One parotid lymphoepithelioma was interpreted cytologically as an atypical lymphoproliferative process suggestive of Hodgkin's disease. Nineteen cases (95%) were correctly classified as carcinoma at the time of FNA. High-grade carcinomas aspirated from the parotid may be primary, but are frequently metastatic to either the gland, or to an intraparotid lymph node. Our experience indicates that some metastatic carcinomas present at this site, without a previous history of malignancy. Distinguishing primary from metastatic lesions has important therapeutic implications.

Small cell neuroendocrine carcinoma of the endometrium.

Ten cases of endometrial small cell neuroendocrine carcinoma are described. The ages of the patients ranged from 50 to 75 years (mean, 64 years). Most of the tumors were bulky, intraluminal masses that invaded at least half of the myometrial wall. Small cells were the only malignant element in two tumors. In the other eight, there were admixed elements of adenocarcinoma (five), adenosquamous carcinoma (two), or heterologous mesodermal mixed tumor (one). Histologic examination of metastatic deposits in six cases revealed solely small cells in all but one. Immunohistochemical evidence of neuroendocrine differentiation was demonstrated in all tumors using the markers chromogranin, synaptophysin, leu-7, or neuron-specific enolase. Six of these tumors were originally interpreted as mesodermal mixed tumors with a homologous, stromal-type sarcomatous component at initial pathologic examination, but were reclassified as carcinoma. Clinical follow-up of these 10 patients and an additional seven well-documented patients reported in the literature provided strong evidence for the aggressive nature of this neoplasm. Endometrial small cell neuroendocrine carcinoma is a rare, but aggressive neoplasm that can commonly be mistaken for a homologous-type mesodermal mixed tumor.

Fine needle aspiration cytology of peripheral lymph node cryptococcosis. A report of three cases.

Aspiration cytology of lymph nodes allows rapid diagnosis of disseminated cryptococcosis. Three cases of lymph node cryptococcosis diagnosed by aspiration cytology in three patients with acquired immunodeficiency syndrome are presented. The organisms were easily seen with a routine modified Wright and Papanicolaou stain as variably sized yeasts, 5-15 microns in greatest diameter, with thick capsules. Many of the organisms showed narrow base budding. In one case occasional pseudohyphae were observed. The diagnoses were confirmed easily with mucicarmine stain.

Papillary neoplasms of the breast: fine-needle aspiration findings in cystic and solid cases.

Papillary neoplasms of the breast are uncommon; at the time of needle aspiration, the diagnostic yield from such lesions can be initially classified as cystic or solid. We describe the fine-needle aspiration findings in four cystic papillary neoplasms (three intracystic papillary carcinomas and one intracystic papilloma) and three solid masses (two sclerosing ductal lesions and one infiltrating ductal carcinoma with prominent papillary component). The smears were examined with respect to the following features: cellularity, architectural pattern in cell groups, cytologic pleomorphism, degree of cohesiveness, morphology and size of individual cells, anisonucleosis, nuclear-cytoplasmic ratio, irregularity of nuclear contour, chromatin texture, macronucleoli, the presence of bipolar nuclei, apocrine cells, and multinucleated giant cells. A combination of cytologic and clinical characteristics may be helpful in distinguishing benign from malignant papillary lesions.