Effects of Estradiol/Micronized Progesterone vs. Conjugated Equine Estrogens/Medroxyprogesterone Acetate on Breast Cancer Gene Expression in Healthy Postmenopausal Women.

Recent studies suggest estradiol (E2)/natural progesterone (P) confers less breast cancer risk compared with conjugated equine estrogens (CEE)/synthetic progestogens. We investigate if differences in the regulation of breast cancer-related gene expression could provide some explanation. This study is a subset of a monocentric, 2-way, open observer-blinded, phase 4 randomized controlled trial on healthy postmenopausal women with climacteric symptoms (ClinicalTrials.gov; EUCTR-2005/001016-51). Study medication was two 28-day cycles of sequential hormone treatment with oral 0.625 mg CEE and 5 mg of oral medroxyprogesterone acetate (MPA) or 1.5 mg E2 as percutaneous gel/day with the addition of 200 mg oral micronized P. MPA and P were added days 15-28/cycle. Material from two core-needle breast biopsies in 15 women in each group was subject to quantitative PCR (Q-PCR). The primary endpoint was a change in breast carcinoma development gene expression. In the first eight consecutive women, RNA was extracted at baseline and after two months of treatment and subjected to microarray for 28856 genes and Ingenuity Pathways Analysis (IPA) to identify risk factor genes. Microarray analysis showed 3272 genes regulated with a fold-change of >±1.4. IPA showed 225 genes belonging to mammary-tumor development function: 198 for CEE/MPA vs. 34 for E2/P. Sixteen genes involved in mammary tumor inclination were subject to Q-PCR, inclining the CEE/MPA group towards an increased risk for breast carcinoma compared to the E2/P group at a very high significance level (p = 3.1 × 10-8, z-score 1.94). The combination of E2/P affected breast cancer-related genes much less than CEE/MPA.

Breast Cancer Survival Defined by Biological Receptor and Menopausal Status in Vietnamese Women.

Little is known about breast cancer in Vietnamese women. Previous studies have reported the frequencies of prognostic factors of breast cancer in this population. The aim of this study was to examine the prognostic factors associated with the survival rates of patients with breast cancer treated at the National Cancer Hospital, Hanoi, Vietnam. We recruited 248 women with operable breast cancer treated with surgery and adjuvant therapy. Tumor tissue samples were stained by many immunohistochemical approaches and analyzed for estrogen receptor, progesterone receptor, and HER2 gene amplification status. A Cox model was used to determine the relationship between survival and the prognostic factors. The disease-free survival rate, overall survival rate, and cancer-specific survival rate were 75.8%, 80.6%, and 86.4%, respectively, at 5 years and 62.3%, 68.1%, and 78.9%, respectively, at 10 years. The lung was the most common metastatic site. Women with factors associated with a poor prognosis (eg, advanced clinical stage, high tumor grade, progesterone receptor [PR] negativity, HER2 amplification) had significantly lower survival rates. Patients with PR-negative breast cancer had significantly worse survival rates compared to those who were PR positive, according to multivariate analysis (hazard ratio = 1.77, 95% confidence interval: 1.01-3.11, P = .045); however, there was only a statistically significant difference in postmenopausal patients. The PR was a prognostic factor in postmenopausal women with breast cancer, but not in premenopausal women.

Diagnosing synovial sarcoma by fine-needle aspiration cytology and molecular techniques.

OBJECTIVE: Synovial sarcomas (SS) are rare soft tissue tumours defined by the SYT-SSX fusion gene. The tumours are composed of mesenchymal cells with varying degrees of epithelial differentiation. Cytomorphological descriptive studies are limited to small series and single cases. In this study we systematically examined the cytological features of SS diagnosed at our institution. METHODS: SS diagnosed by fine-needle aspiration (FNA) cytology at our institution between 2006 and 2018 were reviewed by a panel of senior cytopathologists. Clinical and cytopathological characteristics were categorised and described. RESULTS: A total of 38 SS FNAs were identified from 35 patients. The cytomorphology was uniform, presenting as highly cellular smears of clusters and individual cells with mixed round, oval and spindle cells. We frequently observed pericapillary arrangement and occasionally pink background stroma was seen. Glandular formation or epithelial components were identified in the majority of cases which on histology were subtyped as biphasic SS. Pleomorphism and mitoses were rare. Immunocytochemical analysis was frequently positive for vimentin, epithelial membrane antigen, Bcl2 and, in recent cases, TLE1. Pan-cytokeratins and CK7 could occasionally be positive in biphasic cases. The diagnostic SYT-SSX fusion gene was detected in all FNA specimens using polymerase chain reaction or fluorescence in situ hybridisation. CONCLUSIONS: SS have distinct and uniform cytopathological features. Molecular genetic analysis for SYT-SSX are invaluable for diagnosing SS with FNA and should be implemented in cytopathological laboratories that routinely perform soft tissue diagnostics.

Detection of central nervous system involvement in childhood acute lymphoblastic leukemia by cytomorphology and flow cytometry of the cerebrospinal fluid.

BACKGROUND: Therapy directed at the central nervous system (CNS) is an essential part of the treatment for childhood acute lymphoblastic leukemia (ALL). The current evaluation of CNS involvement based on cytomorphological examination of the cerebrospinal fluid (CSF) alone is not as sensitive with low cell counts as flow cytometric immunophenotyping (FCI) of the CSF. However, the importance of low CSF blasts counts at diagnosis is uncertain. We sought to determine the significance of FCI in relation to conventional morphological examination. PROCEDURE: We retrospectively compared FCI of the CSF with cytomorphology at diagnosis or relapse of childhood ALL. All patients were diagnosed 2000-2012 in Stockholm or Umeå, Sweden. Clinical data were collected from medical records and the Nordic leukemia registry. Treatment assignment was based on morphological examination only. RESULTS: The cohort was comprised of 214 patients with ALL. CSF involvement was detected by both methods in 20 patients, in 17 by FCI alone, and in one patient by cytomorphology alone. The relapse rate was higher for patients with negative cytology but positive FCI compared to those without CNS involvement using both methods. The difference was especially marked in the current protocol. However, none of the patients with negative CSF cytology but positive FCI had a CNS relapse. CONCLUSIONS: FCI of the CSF increased the detection rate of CNS involvement of ALL approximately two times compared to cytomorphology. Patients with low-level CNS involvement may benefit from additional intensified systemic or CNS-directed therapy, but larger studies are needed.

Ki67 measured in metastatic tissue and prognosis in patients with advanced breast cancer.

The purpose of this study is to determine the prognostic role of Ki67 evaluated in relapse biopsies from patients with metastatic breast cancer (MBC). Two hundred and ten patients diagnosed with MBC in Stockholm, Sweden between 1998 and 2009 and with Ki67 assessed at time of first systemic relapse (mKi67) were retrospectively identified and divided into two groups according to mKi67 fraction (low ≤20 %, high >20 %). Post-relapse survival was compared between the groups using Kaplan-Meier and Cox regression methods. Death rate as function of continuous mKi67 was also evaluated. Furthermore, the prognostic role of intra-individual change in Ki67 between primary tumor and matched metastasis was explored by Kaplan-Meier plots. One hundred and twenty-five patients had low and 85 had high mKi67. Median survival was 25 and 17 months in low- and high-mKi67 group, respectively [hazard ratio (HR) 0.69, 95 % confidence intervals (CI) 0.51-0.92, P = 0.01]. In a multivariate model adjusted for prognostic confounders, low-mKi67 showed a non-significant trend toward better survival (HR 0.85, 95 %CI 0.62-1.16, P = 0.30). Nevertheless, mKi67 independently correlated with survival when compared with primary tumor proliferation (HR 0.56, 95 %CI 0.38-0.81, P = 0.002). The 2-year death rate steeply increased as mKi67 increased. Moreover, the change from high in primary tumor to low in metastasis significantly correlated with longer survival when compared with stable Ki67 levels (HR 0.48, 95 %CI 0.31-0.76, P = 0.002). In this cohort of MBC patients, mKi67 inversely but not independently correlated with survival. However, a significant association between mKi67 and survival was shown regardless of primary tumor proliferation.

Fine-Needle Aspiration Biopsy as a Diagnostic Modality for Orbital Adnexal Lymphoma.

INTRODUCTION: The aim of this study was to evaluate fine-needle aspiration biopsy (FNAB) as a diagnostic tool for lymphoproliferative orbital lesions in light of recent improvements in cytomorphological and immunologic analyses. METHOD: Retrospective case series including all orbital FNABs with a lymphoproliferative outcome at Karolinska University Hospital, Stockholm, Sweden during the period 2005-2015. RESULTS: Of the 38 patients included, 31 (82%) were conclusively diagnosed as having lymphoma according to the first FNAB. Disease in 20 patients (65%) could be subclassified. The diagnosis in 7 patients (18%) was either inconclusive, suggestive of lymphoma, or reactive lymphatic infiltrate. These 7 patients were re-investigated, and the initial suspected diagnosis of malignant lymphoma was confirmed in four. Two of the remaining 3 patients were initially diagnosed as having non-lymphoproliferative disease; however, this was later changed to a lymphoproliferative diagnosis following reinvestigation, while the results of both reFNAB and incisional biopsy were inconclusive in the third. CONCLUSION: In the majority of the 38 patients, a definitive diagnosis of lymphoma could be made based on FNAB alone, using cytomorphological and immunological workup, and subclassification was possible in 20 patients (65%). Primary low-grade malignant orbital lymphomas are traditionally treated with low-dose radiotherapy regardless of subtype, and incisional biopsy was not needed to initiate treatment. Our findings suggest that FNAB is a valid first option for the diagnosis of suspected orbital lymphomas due to the minimal risk of complications compared to incisional biopsy, and the fact that it can be performed as an outpatient procedure with no anesthesia.

Prevalence of cystic metastases in a consecutive cohort of surgically removed branchial cleft cysts.

BACKGROUND: Solitary cystic lesion of the neck may often be the only initial presenting symptom for branchial cleft cysts and cystic metastases. AIMS/OBJECTIVES: To analyse the malignancy rate detected in patients undergoing surgical treatment for lateral branchial cleft cyst. MATERIAL AND METHODS: The records of all patients with surgical procedure code ENB40 (Excision of lateral branchial cleft cyst- or fistula) between 2003 and 2019 were reviewed. After excluding 150 patients, 436 patients were included for final analysis. Re-evaluation of the cytology including HPV-analysis was performed in those who had a malignant cyst. RESULTS: Cystic metastases were demonstrated histologically after surgical excision in 13 patients (3%). In patients over 18 years of age, the prevalence of cystic metastasis regardless of the primary tumour type was 3.3%. CONCLUSION AND SIGNIFICANCE: When the investigation protocol for solitary cystic lesions of the neck is followed, the negative predictive value for malignancy is 97%. All adult patients with a cytologic verified diagnosis of branchial cyst should be examined with HPV-analysis of the cystic sample before excision of the cyst. Failure of predicting a malignancy is often associated with cytology of poor cellularity which may be improved by more frequent use of ultrasound guided fine-needle aspiration cytology (FNAC).

HER2 status in operable breast cancers from Vietnamese women: Analysis by immunohistochemistry (IHC) and automated silver enhanced in situ hybridization (SISH).

BACKGROUND: HER2 amplification has been reported to occur in 19-30% of breast cancers in women from Western countries. Little is known about the HER2 status in breast cancers from Vietnamese women. The aim of this study was to assess the HER2 status in Vietnamese women with operable breast cancer using immunohistochemistry and silver in situ hybridization techniques. MATERIAL AND METHOD: Tissue blocks from 242 Vietnamese women with invasive primary breast carcinoma were stained by immunohistochemistry (IHC) and a dual silver in situ hybridization (SISH) for assessing HER2 status. The analysis followed international recommendations with a semi-quantitative grading of the reaction in four levels, "0", "1+", "2+" and "3+". The HER2 gene amplification was assessed by calculating the ratio of HER2/chromosome 17 in 20 tumor cell nuclei. A ratio of <1.8 was classified as non-amplification and a ratio >2.2 indicated tumors with gene amplification. A ratio between 1.8 and 2.2 was equivocal. RESULTS: Using IHC, 39% of the tumors strongly expressed "3+" the HER2 protein. An intermediate level "2+" of the protein was found in 11% while 50% showed no or low "0/1+" levels of protein expression. Gene amplification was found in 95% and 46% of the tumors with high "3+" and intermediate "2+" levels of protein expression, respectively. Thus, 41% of the patients had tumors with HER2 amplification. The concordance between IHC and SISH was 87%. Gene amplification was more frequent in ER negative than in ER positive tumors, 57% versus 33%, respectively. Additionally, tumors from postmenopausal women were amplified in 55% as compared to 36% in premenopausal women. CONCLUSIONS: HER2 gene amplification was found in 41% of Vietnamese breast cancers; this level is considerably higher than that previously found in a series of Swedish breast cancer women. The HER2-positive tumors were more often found in post-menopausal women than in ER negative tumors.

Difference in hormone receptor content in breast cancers from Vietnamese and Swedish women.

BACKGROUND: The aim of the present study was to compare both estrogen (ER) and progesterone receptor (PgR) content in operable breast cancers from Vietnamese and Swedish patients. MATERIAL AND METHODS: Primary breast cancer tissues were randomly selected from 249 Vietnamese patients treated in Hanoi, Vietnam between 2002 and 2004 and 1 257 Swedish patients treated in Stockholm, Sweden between 2002 and 2003. Clinical information was available for all patients in the study. The hormone receptor content in tumors from Vietnam was analyzed by immunohistochemistry using an automated slide stainer (Bench MarkXT, Ventana) in combination with anti-ER (SP1 250), and anti-PgR (clone 1E2) rabbit monoclonal antibody. Tumors with ≥ 10% stained nuclei were considered as receptor positive. Tumors from Swedish patients were analyzed with an enzyme immunoassay with a cut-off point of ≥ 0.10 fmol/µg DNA as positive. The hormone receptor frequencies between populations were compared according to clincopathology features. RESULTS: The ER positive rate was higher in premenopausal and lower in postmenopausal Vietnamese patients as compared to Swedish patients with similar menopausal status (71% versus 58%, OR 1.75, p = 0.007; 44% versus 72%, OR 0.32, p < 0.001, respectively). PgR positive tumors were found in 58% and 25% of pre- and postmenopausal Vietnamese patients, respectively. The corresponding figures for Swedish patients were 73% and 66%, respectively. CONCLUSIONS: There were significant differences in the frequency of ER/PgR positivity between Vietnam and Swedish breast cancer patients. These differences were independent on menopausal status and age of patients at diagnosis can not be explained by these factors and they can be contributed to knowledge about both basic biology features and prognoses.

Clear-cell chondrosarcomas: Fine-needle aspiration cytology, radiological findings, and patient demographics of a rare entity.

BACKGROUND: Clear-cell chondrosarcomas (CCCSs) constitute a very rare subtype of chondrosarcoma. CCCS may radiologically mimic chondroblastoma, and given the difference in surgical approach, it is important to distinguish these two entities preoperatively. DESIGN: Using the institutional digital records, we identified histologically verified CCCS between 1996 and 2013, where preoperative fine-needle aspiration (FNA) cytology was available. Clinical characteristics were categorized and described, and FNAs were reviewed by a panel of senior cytopathologists. In addition, corresponding radiological imaging was reviewed by senior radiologists, and a literature review on CCCS and chondroblastoma was conducted. RESULTS: A total of seven CCCS FNAs were identified from six patients. The cytomorphology showed low to intermediate cellular smears of clusters and single round or oval tumor cells. Tumor cells had rounded (sometimes binucleated) nuclei with limited pleomorphism and rich vacuolated cytoplasm. Chondroid background matrix was always found. While CCCS patients had a significantly higher age at diagnosis compared to chondroblastoma, no age cut-off would distinctly separate the two. CONCLUSIONS: CCCS has distinguished cytomorphological features on FNA smears. CCCS should be considered as a possible differential diagnosis in adults (>25 years) with a radiological suspicion of chondroblastoma. Since radiology and patient age cannot conclusively distinguish CCCS from chondroblastoma, FNA may prove an important tool for correct preoperative diagnosis of CCCS.

Diagnostic and prognostic potential of MIB-1 proliferation index in thyroid fine needle aspiration biopsy.

Fine needle aspiration biopsy (FNAB) is the preferred technique for the initial diagnostic evaluation of thyroid lesions, which nevertheless poses a diagnostic challenge for all clinicians involved. The latter necessitates the use of molecular markers on thyroid cytology. MIB-1 is a molecular marker already used in the cytological evaluation of various tumors. In this study, we assessed whether MIB-1 proliferation index adds diagnostic information to the conventional cytological analysis of thyroid nodules and prognostic information in thyroid cancers. MIB-1 index for various thyroid lesions was retrospectively reviewed in a series of 504 patients. Furthermore, the prognostic value of MIB-1 index was investigated for 183 of the patients with papillary thyroid cancer (PTC). MIB-1 index was significantly higher in anaplastic thyroid cancer (ATC) compared to other tumor types (p<0.01). No significant difference in MIB-1 index was observed between thyroid adenomas and follicular carcinomas. In PTC, MIB-1 index equal to or >4% was found to be an independent factor significantly associated with higher risk of distant metastasis and disease-related mortality (p<0.05). Conclusively, this study shows that preoperative MIB-1 index assessment in FNAB of thyroid nodules offers little diagnostic information as far as follicular tumors are concerned. In cases of PTC, though, MIB-1 may serve as a prognostic indicator of disease spreading and poor survival and hence influence the planning of the overall treatment scheme.

Effects of drospirenone and norethisterone acetate combined with estradiol on mammographic density and proliferation of breast epithelial cells-A prospective randomized trial.

OBJECTIVE: There are no previous data on the influence of drospirenone (DRSP) in combination with estradiol (E2) on the breast in postmenopausal women. The objective of this study was to evaluate the effect of DRSP or norethisterone acetate (NETA) in continuous combination with E2 on two surrogate markers for breast cancer - mammographic breast density and proliferation of breast epithelial cells - in healthy postmenopausal women. STUDY DESIGN: 120 healthy, naturally postmenopausal women were randomized to either 2 mg of DRSP or 0.5 mg of NETA in continuous combination with 1 mg of oral E2. The women underwent mammography and fine-needle aspiration biopsy of the breast at baseline and after six months of treatment. MAIN OUTCOME MEASURES: Digitized mammographic breast density and breast cell proliferation. RESULTS: There was a significant increase in mammographic breast density after treatment in both groups (median increase 5.5% for E2/DRSP and 2.3% for E2/NETA, respectively, p < 0.001), but with no significant difference between groups. The proliferation of breast epithelial cells also increased in both groups (p < 0.001, respectively), with a significantly larger increase in the E2/DRSP group than in the E2/NETA group (2.5% versus 0.7%, respectively, p < 0.05). Systolic blood pressure had decreased significantly after 6 months of treatment in the E2/DRSP group (p < 0.05) but not in the E2/NETA group. CONCLUSIONS: Breast density increased to a similar degree with E2/DRSP and E2/NETA. Proliferation of breast epithelial cells also increased significantly in both groups but was slightly more pronounced in the E2/DRSP group.

FNA cytology of solitary fibrous tumors and the diagnostic value of STAT6 immunocytochemistry.

BACKGROUND: Solitary fibrous tumors (SFTs) are rare mesenchymal tumors commonly located in the pleura, soft tissues, or meninges and are characterized by the NGFI-A-binding protein 2 (NAB2)-signal transducer and activator of transcription 6 (STAT6) fusion gene. Recent studies have indicated that nuclear STAT6 immunohistochemistry is a specific marker for SFTs. METHODS: The authors reviewed fine-needle aspiration (FNA) specimens from extracranial SFTs diagnosed at their institution between 1993 and 2017. Histologic blocks and available formalin-fixed smears of FNA specimens from SFTs were investigated for STAT6 immunoreactivity using a monoclonal antibody. STAT6 immunocytochemistry was also investigated in schwannomas and spindle cell lipomas. Cytopathologic and clinical characteristics were described. RESULTS: Nineteen benign and 9 malignant SFTs were identified. Both benign and malignant SFTs had a female predominance (female-to-male ratio, 2.8:1 and 1.25, respectively). Localization varied, and approximately one-half of the extrapleural tumors were located in the extremities and frequently were intramuscular. Benign and malignant primary tumors had limited differences in cytologic presentation, the most notable feature being nuclear pleomorphism. Cytomorphologic features included low-to-moderate cellularity of mixed oval, elongated, round, and stellate cells with pink collagenous stroma and hypercellular clusters with infrequent atypia. In metastatic SFTs, the cytopathology was suggestive of sarcoma. Immunohistochemistry revealed nuclear STAT6 immunoreactivity in SFTs (n = 5) with cytoplasmic reactivity in cytologic mimickers. CONCLUSIONS: Benign and malignant SFTs have common cytopathologic features, and the ability to distinguish between them is limited. Nuclear STAT6 immunoreactivity is a valuable cytologic marker for SFTs. Cancer Cytopathol 2018;126:36-43. © 2017 American Cancer Society.

High Ki-67 index in fine needle aspiration cytology of follicular thyroid tumors is associated with increased risk of carcinoma.

PURPOSE: Preoperative distinction of follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA) is a diagnostic challenge. Our aim was to investigate whether the Ki-67 proliferation index in fine needle aspiration material can contribute to the diagnosis of FTC. METHODS: We analyzed retrospectively cytological Ki-67 index determined in routine clinical setting and clinical data for 61 patients with FTC, 158 patients with FTA and 15 patients with follicular tumor of uncertain malignant potential (FT-UMP) surgically treated and diagnosed by histopathology at Karolinska University Hospital 2006-2017 (Cohort A). A previously published cohort of 109 patients with follicular tumors was re-analyzed as well (Cohort B). RESULTS: In Cohort A, patients with FTC had a higher Ki-67 index (p < 0.001), larger tumor size (p < 0.001) and higher age at diagnosis (p = 0.036) compared to patients with FTA or FT-UMP. Hürthle cell differentiation, present in 50 FTA, 20 FTC and 8 FT-UMP, was associated with higher Ki-67 index (p = 0.009). Multivariate analysis of Cohort A identified a high Ki-67 index (odds ratio [OR]: 1.215, p < 0.001) and large tumor size (OR: 1.038, p < 0.001) as independent predictors of FTC. Results remained consistent after exclusion of Hürthle cell tumors and in pooled analysis of Cohort A + B. The area under curve of the Ki-67 index for predicting FTC was 0.722 and a cut-off for Ki-67 index at above 5% resulted in a specificity at 93% and sensitivity at 31%. Subgroup analysis of FTCs in Cohort A showed an association of higher Ki-67 index to extrathyroidal extension (p = 0.001) as well as widely invasive subtype (p = 0.019) based on the WHO 2017 classification. CONCLUSIONS: Pre-operative Ki-67 index may add diagnostic information for a subset of patients with follicular thyroid tumors.

Testosterone inhibits estrogen/progestogen-induced breast cell proliferation in postmenopausal women.

OBJECTIVE: During the past few years serious concern has been raised about the safety of combined estrogen/progestogen hormone therapy, in particular about its effects on the breast. Several observations suggest that androgens may counteract the proliferative effects of estrogen and progestogen in the mammary gland. Thus, we aimed to study the effects of testosterone addition on breast cell proliferation during postmenopausal estrogen/progestogen therapy. DESIGN: We conducted a 6-month prospective, randomized, double-blind, placebo-controlled study. A total of 99 postmenopausal women were given continuous combined estradiol 2 mg/norethisterone acetate 1 mg and were equally randomly assigned to receive additional treatment with either a testosterone patch releasing 300 microg/24 hours or a placebo patch. Breast cells were collected by fine needle aspiration biopsy at baseline and after 6 months, and the main outcome measure was the percentage of proliferating breast cells positively stained by the Ki-67/MIB-1 antibody. RESULTS: A total of 88 women, 47 receiving active treatment and 41 in the placebo group, completed the study. In the placebo group there was a more than fivefold increase (P<0.001) in total breast cell proliferation from baseline (median 1.1%) to 6 months (median 6.2%). During testosterone addition, no significant increase was recorded (1.6% vs 2.0%). The different effects of the two treatments were apparent in both epithelial and stromal cells. CONCLUSIONS: Addition of testosterone may counteract breast cell proliferation as induced by estrogen/progestogen therapy in postmenopausal women.

A Review of the Use of Fine-Needle Aspiration Biopsy of Mammary Tumors for Diagnosis and Research.

The article "Aspiration Biopsy of Mammary Tumors in Diagnosis and Research - A Critical Review of 2,200 Cases" by Zajicek et al. [Acta Cytol 1967;11:169-175] is composed of two separate parts as can be seen from the title. Both are, however, of great historical interest. The first describes the early days of fine-needle aspiration cytology diagnosis of breast lesions in particular carcinomas. The results are still impressive with a diagnostic accuracy close to 90%. The second deals with the effect of negative pressure on cell viability during the aspiration procedure. These studies were aimed at evaluating the usefulness of aspirated tumor cells to analyze the effects of therapy and the origin of tumor cells.

Human papillomavirus DNA detection in fine-needle aspirates as indicator of human papillomavirus-positive oropharyngeal squamous cell carcinoma: A prospective study.

BACKGROUND: Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (SCC) has a better outcome than most head neck squamous cell carcinomas (HNSCCs) and an HPV-positive lymph node metastasis likely has an HPV-positive oropharyngeal SCC origin. Determining HPV-status in cervical lymph nodes by fine-needle aspiration cytology (FNAC) may be useful for diagnosis. METHODS: FNACs from 66 patients with neck masses were prospectively examined for HPV DNA and HPV16 mRNA by a polymerase chain reaction (PCR)-based assay, and the data correlated to diagnosis and HPV-status obtained from histopathological specimens. RESULTS: Aspirates from 17 of 66 patients, later diagnosed with HPV-positive oropharyngeal SCC, were HPV16 DNA-positive. HPV16 mRNA was detected in all cases with extractable RNA. All remaining FNACs, including 18 branchial cleft cysts, were HPV DNA-negative. HPV DNA status in the aspirates showed perfect concordance with corresponding biopsies. CONCLUSION: HPV16 DNA detection in fine-needle aspirations from neck masses is reliable and HPV16 DNA in a metastasis is a strong indicator of an HPV-positive oropharyngeal SCC. © 2016 Wiley Periodicals, Inc. Head Neck 39: 419-426, 2017.

Fine-needle aspiration cytology and immunocytochemistry of orbital masses.

A series of 85 fine-needle aspiration (FNA) biopsies from orbital space occupying lesions of 82 patients are reviewed. A total of 32 benign lesions and 49 malignant lesions were conclusively diagnosed. In two cases the aspirates were insufficient for diagnosis. Of two cases, which were cytologically suspicious for lymphoma, a repeat FNA resulted in a conclusive diagnosis of lymphoma in one case, while the second case proved to be a pseudotumor on an open biopsy material. Of the 32 benign lesions seven were fibrosis, six pseudotumors, four epidermal cysts, four meningiomas, and three pleomorphic adenomas. The remaining cases included two hematomas, one granuloma, three inflammations, and one malformation. In 43 of 49 malignant tumors cytomorphology was corroborated with immunocytochemistry. Thirty five of these were low- or high-grade lymphomas, nine metastases, two sarcomas, two plasmacytomas, and one chloroma. All lymphomas were of B phenotype with monoclonal light chain expression. The rate of cell proliferation as measured by Ki-67 immunostaining varied between 4-25% and 30-80% for low- and high-grade lymphomas, respectively. These results confirm previous reports on the usefulness of FNA biopsy in diagnosing orbital masses and emphasize the value of immunocytochemistry in tumor characterization.

Fine-Needle Aspiration Biopsy in Orbital Lesions: A Retrospective Study of 225 Cases.

PURPOSE: To describe and analyze results from the fine-needle aspiration biopsy (FNAB) technique, used as a diagnostic tool, in patients with orbital lesions. DESIGN: Retrospective case series. METHODS: setting: Institutional (Karolinska Hospital, Stockholm). STUDY POPULATION: 207 patients with 210 orbital lesions. INTERVENTION: 225 FNABs of the orbit. MAIN OUTCOME MEASURES: Successful diagnosis from FNAB. RESULTS: Of the 210 orbital lesions evaluated with FNAB, a successful cytologic diagnosis was achieved in 176 (84%). In more than half of the orbital lesions (54%), the FNAB diagnosis in addition to imaging appearance, clinical appearance, and clinical history provided sufficient information for treatment, and the patient did not require an incisional or excisional biopsy. Ninety-seven patients underwent additional excisional or incisional biopsy; FNAB diagnoses and the histopathologic diagnoses corresponded in 87% of the cases with an intraclass correlation coefficient of 0.84 (95% confidence interval [CI] 0.76-0.90). The difference was statistically significant between the ability to make a successful cytologic FNAB diagnosis in palpable lesions vs nonpalpable lesions (successful diagnosis in 90% [CI = 85%-95%] vs 75% [CI = 66%-84%]; P < .01). Neither the orbital quadrant location, nor the radiologic appearance (diffuse vs encapsulated), nor size of the lesion affected the success of FNAB diagnoses (all P > .7). There was a complication in 6 cases (3%). All complications were temporary and none led to permanent damage. CONCLUSIONS: FNAB proved effective and exceedingly safe. With the current healthcare climate of minimally invasive surgery and cost control, FNAB should be considered as a valid alternative to open surgery in the evaluation and management of orbital lesions.