The use of the 'borderline' category in the reporting of cervical cytopathology in the UK: results of a survey conducted under the aegis of the British Society for Clinical Cytology

Objective: To determine how the ‘borderline’ category was used by cytopathologists in the UK when reporting cervical smears. Methods: A questionnaire was sent by email to members of the British Society for Clinical Cytology. Results: There is wide variation in the use of the ‘borderline’ category in the UK but the majority of respondents (77.6%) used it when reporting smears that were either on the borderline between negative and low grade squamous dyskaryosis (‘borderline ?low grade’), or on the borderline between negative and high grade squamous dyskaryosis (‘borderline ?high grade’), or on the borderline between negative and glandular dyskaryosis ‘borderline ?glandular dyskaryosis’). A significant minority (15.7%), however, did not use ‘borderline’ when reporting smears that showed an abnormality that was possibly high grade squamous dyskaryosis. A majority (79.1%) of respondents thought that it would be useful to have separate reporting categories for ‘borderline ?low grade’ and ‘borderline ?high grade’. Conclusions: There is diversity in the use of the category ‘borderline’ in the UK. The proposed revised BSCC terminology with separate categories for borderline ?low grade, borderline ?high grades and borderline ? glandular dyskaryosis reflects the opinion of the majority of respondents to the questionnaire.     

Rehydration of air-dried smears. An alternative method for cytologic analysis of exfoliative cells

OBJECTIVE: To compare the cytologic characteristics of gastric mucosal cell smears prepared by air drying and rehydration prior to alcohol fixing with cells wet fixed in alcohol. STUDY DESIGN: Gastric mucosal cells were obtained from 55 consecutive patients undergoing gastroscopy. Paired smears were made, one immediately fixed in 95% ethanol for 20 minutes (wet fixed [WF]) and the other air dried for at least 20 minutes prior to rehydration with normal saline for 30 seconds and fixation in 95% ethanol for 20 minutes (air dried/rehydrated/fixed [ARF]). Both slides were stained by the Papanicolaou method. Coded slides were examined blind and graded 1 (superior), 2 (satisfactory) or 3 (poor) with respect to staining of chromatin, nuclear membrane, nucleoli, cytoplasm/cell border and group morphology. Histology confirmed a benign disease process or normal mucosa. RESULTS: Comparing grade 1 versus grades 2 and 3, ARF slides were significantly better than WF slides for all cytologic features (P < .05). Comparing grade 1 and 2 versus grade 3, there was no significant difference between ARF and WF slides (P > .05) (chi 2 analysis). CONCLUSION: The cytologic features of ARF smears of gastric cells were equal or superior to those of WF smears. This method of preparing smears is simpler and avoids some of the problems of ethanol fixation of wet smears.     

Apoptosis in breast cancer

OBJECTIVE: To evaluate apoptotic rates on fine needle aspiration (FNA) samples of infiltrating duct carcinoma of the breast and to determine whether cytologic grading improved with consideration of the apoptotic rate in comparison with histologic grading. STUDY DESIGN: We studied 35 women who underwent mastectomy following an FNA diagnosis of infiltrating ductal carcinoma. Concordance between cytologic and histologic grades was calculated. Next, cytologic grades were considered with the apoptotic rates and compared with the histologic grades. RESULTS: An overall concordance of 82.9% was noted between the cytologic and histologic grading systems, with maximum concordance in grade 1 and minimum in grade 3 breast cancers. A highly significant difference in the apoptotic rates, as calculated on cytology, existed between the three histologic grades, indicating a significant increase in apoptosis with rising histologic grade. Applying multiple regression analysis, a significant improvement of cytologic grade with consideration of the apoptotic rate was observed. CONCLUSION: Employing histologic grade as the yardstick, cytology was less sensitive for the purpose of grading breast ductal carcinoma. However, by considering the apoptotic rates, the sensitivity of cytologic grading significantly rose in relation to histologic grade. Larger studies are required to determine whether apoptosis can be incorporated into the existing cytologic grading systems to increase their sensitivity.     

High-throughput molecular analysis from leftover of fine needle aspiration cytology of mammographically detected breast cancer

We investigated whether residual material from diagnostic smears of fine needle aspirations (FNAs) of mammographically detected breast lesions can be successfully used to extract RNA for reliable gene expression analysis. Twenty-eight patients underwent FNA of breast lesions under ultrasonographic guidance. After smearing slides for cytology, residual cells were rinsed with TRIzol to recover RNA. RNA yield ranged from 0.78 to 88.40 μg per sample. FNA leftovers from 23 nonpalpable breast cancers were selected for gene expression profiling using oligonucleotide microarrays. Clusters generated by global expression profiles partitioned samples in well-distinguished subgroups that overlapped with clusters obtained using "biologic scores" (cytohistologic variables) and differed from clusters based on "technical scores" (RNA/complementary RNA/microarray quality). Microarray profiling used to measure the grade of differentiation and estrogen receptor and ERBB2/HER2 status reflected the results obtained by histology and immunohistochemistry. Given that proliferative status in the FNA material is not always assessable, we designed and performed on FNA leftover a multiprobe genomic signature for proliferation genes that strongly correlated with the Ki67 index examined on histologic material. These findings show that cells residual to cytologic smears of FNA are suitable for obtaining high-quality RNA for high-throughput analysis even when taken from small nonpalpable breast lesions.     

Fine needle aspiration biopsy of well-differentiated liposarcoma of the neck in a young female. A case report.

BACKGROUND: Well-differentiated liposarcomas are low grade, nonmetastasizing, malignant neoplasms composed primarily of mature adipose tissue. They are uncommon in the head and neck. CASE: A 24-year-old female presented to the ears, nose and throat clinic for evaluation of a recent, rapidly growing neck mass on the right side. Fine needle aspiration (FNA) biopsy of the mass showed that the smears had fragments of connective tissue with a mixture of mature-appearing fat traversed by bands of fibrous collagen and vessels. Nuclei within the fat and fibrous bands were mildly irregular, hyperchromatic and enlarged, with one or two small nucleoli. Infrequently present but readily identified, lipoblasts were scattered throughout the aspirate smears. A diagnosis of "atypical lipomatous neoplasm" was rendered. Subsequently, the mass was surgically removed. On histologic examination, the tumor was a well-differentiated liposarcoma. CONCLUSION: FNA biopsy of well-differentiated liposarcomas in the head and neck can present difficulties in the classification and diagnosis of this neoplasm.     

Quality assurance in cervical smears: 100% rapid rescreening vs. 10% random rescreening

OBJECTIVE: To compare 100% rapid rescreening of cervical smears with 10% random rescreening as a method of quality assurance. STUDY DESIGN: A total of 5215 smears, randomly selected from smears reported as negative by cytotechnologists during routine screening, underwent 100% rapid rescreening by senior cytotechnologists. Ten percent of these smears, selected at random, were rescreened by other senior cytotechnologists. The gold standard was defined by cytopathologists, who rescreened all 5215 smears. After excluding unsatisfactory smears detected by cytopathologists, 4271 were included in the analysis. RESULTS: The 100% rapid rescreening method identified 69.9%, 95.7% and 100%, respectively, of atypical squamous cells of undetermined significance, low grade squamous intraepithelial lesion and high grade squamous intraepithelial lesion cases reported by the cytopathologists. The 100% rapid rescreening method showed a sensitivity of 73.5% and specificity of 98.6%. The 10% rescreening method showed sensitivity of 40.9% and specificity of 98.8%. CONCLUSION: One hundred percent rapid rescreening is an efficient method of internal quality assurance in cervical smear diagnosis. It can reduce the false negative rate and therefore can provide greater certainty to women who have received negative results. Well-trained cytotechnologists are able to identify abnormal smears in 1-minute rapid rescreening.     

Grading follicular lymphoma on fine needle aspiration specimens. Comparison with proliferative index by DNA image analysis and Ki-67 labeling index

OBJECTIVE: To determine whether follicular lymphoma (FL) can be graded on fine needle aspiration (FNA) biopsies by determining the percentage of centroblasts in the neoplastic follicles on the smears. STUDY DESIGN: Eighty-nine cases of histologically confirmed cases of FL, including 31 grade 1, 46 grade 2 and 12 grade 3, were evaluated. Proliferative index (PI) by DNA image analysis (DIA) and Ki-67 labeling index (LI) were obtained on all cases. A minimum of 200 cells were counted per case (range, 200-800 cells) at 40x magnification, and the number of large cells (centroblasts) was expressed as a percentage of the total number of cells counted within the follicles. RESULTS: The percentage of centroblasts in the follicular aggregates was 9.7 +/- 2.9% in grade 1 FLs, 24.7 +/- 5.6% in grade 2 and 48.4 +/- 7.5% in grade 3. These differences were significant (P < .05). DNA image analysis of PI and Ki-67 LI differed significantly between grade 1 FLs and grade 2 and 3 FLs (P < .05), but there were no significant differences between grade 2 and 3 FLs. CONCLUSION: Determining the percentage of centroblasts in the follicular aggregates on FNA specimens is a good method of grading FLs. Using the percentage of centroblasts per follicular structure, FL grades 1, 2 and 3 were adequately distinguished. PI by DIA and Ki-67 LI clearly distinguished FL grade 1 from FL grades 2 and 3; however, it did not clearly distinguish between grades 2 and 3.     

The frequency of 'atypia of undetermined significance' interpretations for thyroid fine-needle aspirations is negatively correlated with histologically proven malignant outcomes

Objective: Cytopathologists' usage patterns for 'atypia of undetermined significance' (AUS) in thyroid fine-needle aspiration (FNA) are not well understood. AUS rates over a 5-year period were analyzed to quantify variability and identify correlations with experience and histologic outcomes. Study Design: A retrospective review of thyroid FNAs from a tertiary-care hospital from 2005 to 2009 was performed. Results were compiled for individual cytopathologists, stratified by year, and correlated with histologic outcomes. Results: Thyroid FNAs (5,327) were evaluated by 7 cytopathologists, with an overall AUS rate of 11.2%. The annual AUS rate remained relatively constant over this time period, though notable inter- and intrapathologist variability was seen. The AUS rate was significantly lower for those with cytopathology boards (10.3%) compared to those without (14.0%). There was no correlation between the AUS rate and cytopathologist experience or thyroid FNA volume. The AUS rate and malignant outcome were inversely related: the higher an individual's AUS rate was, the lower the rate of malignancy for that AUS cohort was. Conclusions: Individual cytopathologist AUS rates were variable and often exceeded the recommended target of 7%. The application of recently published defined diagnostic criteria, along with directed cytopathologist feedback, may reduce observer variability and appropriately lower AUS utilization.     

Cytologic findings with histologic correlation in 43 cases of mammary intraductal adenocarcinoma diagnosed by aspiration biopsy

OBJECTIVE: To review the cytologic and subsequent histologic findings in intraductal mammary adenocarcinoma (ductal adenocarcinoma in situ) (DCIS) to evaluate the role of aspiration biopsy (AB) in identifying and grading the disease. STUDY DESIGN: AB smears and tissue sections from 43 women with pure DCIS who underwent preoperative AB were reviewed. Smears were assessed for cellularity, cellular arrangement (including dissociation, nuclear size and pleomorphism), and presence of nucleoli and necrosis. RESULTS: Of the 43 cases, 22 were high grade (HG) DCIS, 7 cases were intermediate grade (IG), and 14 cases were low grade (LG). Cytologic findings of HG DCIS was as follows: high cellularity (22/22), clusters of pleomorphic cells with large nuclei and increased nuclear/cytoplasmic ratios (22/22), single cells (20/22), prominent nucleoli (22/22) and necrosis (diffuse in 15/22, focal in 7/22). All LG cases had moderately to highly cellular smears with cohesive, 3-dimensional sheets of uniform, small cells with inconspicuous nucleoli arranged around a central lumen, forming "punched-out" spaces. Single cells were prominent in 2 of 14 cases. IG DCIS showed intermediate features between LG and HG DCIS: 3-dimensional sheets with punched-out spaces, abundant single cells, moderate pleomorphism and focal necrosis. CONCLUSION: HG DCIS is easily identifiable on AB smears; however, distinction from invasive carcinoma may not be possible. The cytologic diagnosis of LG DCIS is difficult, and 50% of our cases were called atypical on AB. Recognition of cohesive cellular arrangements with crowding and punched-out spaces is crucial as single cells and prominent atypia are often lacking.     

Papillary breast lesions diagnosed on cytology. Profile of 65 cases

OBJECTIVE: To analyze the cytologic features of nipple discharge and fine needle aspiration (FNA) cytologic smears from breast lesions reported as showing papillary features and to correlate them with histopathologic features. STUDY DESIGN: The study group consisted of FNA smears and/or nipple discharge smears from 65 breast lesions diagnosed on cytology as duct papilloma, papillary lesion, fibrocystic condition, fibroadenoma, papillary neoplasm or papillary carcinoma. Cytomorphologic features assessed included cellularity, cell pattern (clusters, papillary, 3-dimensionality, etc.) and cell characteristics (monomorphism, pleomorphism, apocrine change, plasmacytoid features). Histological material was available for review and cytohistologic correlation in all cases. RESULTS: Forty-six specimens were FNA smears, and 16 were nipple discharge smears; in 3 cases FNA and nipple discharge cytologic smears were available for review. Cytologic study could predict the presence of a papillary pattern in all neoplasms with pure or focal papillary differentiation. There was an overlap in cytomorphologic features between papillary and nonpapillary benign lesions as well as between benign and malignant papillary neoplasms. Frank blood in the aspirate, cell dissociation and atypia, however, were more frequent in the last. CONCLUSION: Overlap of cytologic features in nonneoplastic and neoplastic benign papillary lesions and between benign and malignant papillary neoplasms necessitates histologic evaluation in all cases diagnosed as papillary on cytology. Since 49.2% of lesions showing papillary features on cytology prove to be malignant, all cases reported as papillary on cytology should be excised urgently for histologic assessment.     

Fine Needle Aspiration Cytology of High Grade T-Cell Lymphomas In Human T-Lymphotropic Virus Type 1 Carriers

We studied the fine needle aspiration (FNA) cytology of high grade peripheral T-cell lymphomas from eight human T-lymphotropic virus-1 (HTLV-1) positive patients. FNA smears from seven lymphomas showed a distinctive cytologic pattern with a dominance of rounded cells with irregular nuclei and a moderately basophilic cytoplasm. Irregular cells with a pale abundant cytoplasm were present in varying amounts. Some smears contained a few giant cells with cerebriform nuclei. In addition, plasma cells and eosinophils were found. Epithelioid cells were an inconstant finding. On histology these seven lymphomas were assigned to the pleomorphic medium-large cell subtype and all but one were of T-helper phenotype with rearrangements of the T-cell receptor. FNA smears from a lymph node in a patient with a previous histological diagnosis of lymphomatoid papulosis of the gingiva showed a monotonous pattern of large immunoblastic cells with some binucleated variants consistent with a diagnosis of high grade immunoblastic lymphoma, which was confirmed histologically. Our results show that peripheral T-cell lymphomas from HTLV-1 positive patients have cytological patterns which are distinctive enough to allow a conclusive diagnosis of high grade T-cell lymphoma. However, we do not think that the cytology of HTLV-1 positive lymphomas can be differentiated from that of virus-unrelated high grade T-cell lymphomas.     

Immunohistochemical studies with monoclonal antibodies B72.3 and MA5 on histologic and cytologic specimens from benign and malignant breast lesions

Monoclonal antibodies B72.3 and MA5 were tested by the avidin-biotin immunoperoxidase method in histologic sections of 38 benign, 22 precancerous and 22 cancerous breast lesions, as well as in fine needle aspiration (FNA) smears and cell blocks of 25 breast carcinomas. Neither B72.3 nor MA5 was specific for breast cancer cells: both also reacted with cells from benign and precancerous conditions. B72.3 as a "detector" of malignant cells or their precursors was superior to MA5, however: it was not reactive to cells in most benign breast lesions (mammary duct ectasia, fibroadenoma and ductal hyperplasia, with and without atypia). Cancerous cells had heterogeneous immunostaining with B72.3, which may lead to false-negative results in relatively hypocellular FNA samples. FNA samples prepared as both smears and cell blocks provided the most abundant cellular samples and the lowest false-negative immunostaining reaction of cancerous cells with B72.3.     

Fine needle aspiration cytology of spermatocytic seminoma. Report of a case

The clinical, radiologic, cytopathologic and histologic features of a case of spermatocytic seminoma in a 56-year-old man are reported and discussed. The cytologic findings in fine needle aspiration (FNA) smears suggested a diagnosis of spermatocytic seminoma, which was confirmed by subsequent histopathologic studies. The case suggests that spermatocytic seminoma can be suspected and distinguished from other types of seminoma and germ cell neoplasms by FNA cytology. The following criteria appear to be the most useful in making the cytodiagnosis: the presence of three different types of cells (large, medium and small), a clean background, an absence of a lymphoid component and "tigroid" substances and the relative paucity and clumping tendency of the neoplastic cells in the smears.     

Performance of the AutoPap Primary Screening System in the detection of high-risk cases in cervicovaginal smears

OBJECTIVE: To assess the performance of the AutoPap Primary Screening System (APSS) (TriPath Imaging, Inc., Burlington, North Carolina, U.S.A.) for the detection of high grade cervical squamous intraepithelial lesions and invasive cervical cancer. STUDY DESIGN: A total of 14,779 consecutive conventional Pap smears were processed by the APSS. All slides designated as "Review" by the device were manually screened according to the Bethesda System. The ranking scores obtained from the device were compared with the cytologic interpretations in all cases and with the final histologic diagnoses in the cases with cytologic severe abnormalities. RESULTS: The device classified 10,349 slides as Review (78%) and 2,912 (22%) as "No Further Review." In the 78% Review cases, the samples were ranked in descending order of potential abnormality, broken into quintiles. The correlation between the slide quintile ranks and the manual cytologic diagnosis indicated that 90% of abnormal smears were categorized by the device as in the first and second quintile rank, and the correlation between the rank report of the device and the histologic diagnosis showed that all cases of HSIL or invasive carcinoma were in the top two ranks. No significant abnormalities were observed in any of the smears categorized as No Further Review. CONCLUSION: This study confirmed the effectiveness of APSS for the detection of Pap smears with severe abnormalities.     

Open or closed nuclear membrane? A question to help distinguish malignant lymphoma from carcinoma and sarcoma

OBJECTIVE: To describe a cytomorphologic criterion that may help improve diagnostic safety in morphologic differentiation of non-Hodgkin's lymphoma (NHL) from carcinoma or sarcoma and investigate the significance of this cytomorphologic phenomenon. STUDY DESIGN: Eighty-two smears of NHL, carcinoma and sarcoma smears were examined. Forty-five smears were from patients with carcinoma and 35 from patients with NHL. The remaining 2 smears were from patients with sarcoma. RESULTS: In 40 of 46 smears of carcinoma or sarcoma the nuclear membrane was assessed as "open" by the observer. In 6 smears the membrane was assessed as "closed. " In 30 of 35 smears with histologically confirmed NHL, the membrane was estimated as being closed. In the remaining 5 smears it was assessed as open. The sensitivity of evaluating the parameter as open or closed membrane was 87% and the specificity was 86%. The negative predictive value was 89%, and the positive predictive value was 83%. CONCLUSION: We suggest that the presence of an open or closed nuclear membrane may be helpful in differentiation of malignant lymphoma from carcinoma or sarcoma and may help improve diagnostic safety in daily practice.     

Fine needle aspiration biopsy of peripheral congenital bronchial cyst

Bronchial cysts usually occur centrally near the mediastinum, but may present as a peripheral "coin" lesion requiring distinction from other causes of coin lesions of the lung. A case is reported in which fine needle aspiration (FNA) biopsy was used to make the diagnosis of such a peripheral bronchial cyst. FNA produced an opaque opalescent fluid; cytologic study of the smears showed abundant bipolar birefringent needle-shaped crystals an a few macrophages. Neither special staining of some smears nor cultures of part of the aspirate revealed the presence of any organism. The cytologic diagnosis was confirmed by histologic examination of the subsequent resection specimen.     

Cytologic evaluation of prognostic markers in breast carcinoma

To type breast carcinomaon on fine needle aspiration cytology (FNAC) material and correlate the results with histologic typing, to grade breast carcinoma on FNAC material and correlate the findings with Bloom-Richardson histologic grading, and to determine the estrogen receptor (ER) status in cases of breast carcinoma by immunocytochemical (ICC) staining of FNA cytologic material and correlate the findings with ER status, as determined by immunohistochemical (IHC) staining of tissue sections. STUDY DESIGN: Seventy-seven cases of breast carcinoma diagnosed on FNAC formed the basis of this study. Typing was done in all cases on the basis of cytologic features and grading in 62. (Fifteen cases were special types of breast carcinoma). In all cases, ER status was determined by immunostaining of cytologic smears. Results of tumor typing, grading and ER status on cytologic material were compared with the results of histologic typing, grading and immunostaining of histologic material obtained from mastectomy or wide excision specimens. RESULTS: Tumor typing was accurate in 73 of 77 cases (94.8%). Fifteen of 18 cases that were cytologically grade 3 were confirmed on histology, while 3 proved to be grade 2. Of 40 cytologic grade 2 cases, 26 were confirmed on histology, while 14 cases were grade 3. Three of 4 cytologically grade 1 cases were confirmed on histology while 1 was grade 2. The overall accuracy for cytologic grading was 71% (44 of 62 cases). Thirty-seven of 40 ER-positive cases (92.5%) were labeled ER positive on ICC. One case was ER negative on cytology, while in 2 cases the cellularity of the cytologic smear was insufficient to assess ER expression. Thirty-seven cases were negativefor ER on IHC. Nine of these showed ER positivity on ICC, 26 were negative, and 2 had cellularity that was inadequate for assessment of ER. Sensitivity and specificity rates for ER detection on ICC were 97.4% and 74.3%, respectively. CONCLUSION: Tumor typing, grading and evaluation of ER status on FNA C material in breast carcinomas are simple, quick and moderately reliable techniques that compare and correlate favorably with histologic typing, grading and ER status on IHC.     

Paratesticular spindle cell rhabdomyosarcoma diagnosed by fine needle aspiration cytology: a case report

BACKGROUND: Spindle cell rhabdomyosarcoma is a rare, newly identified subtype ofembryonal rhabdomyosarcoma with improved behavior and a predilection for the paratesticular area. Fine needle aspiration (FNA) cytology findings of embryonal rhabdomyosarcoma have been described. However, there is no previous report on the cytologic findings of spindle cell rhabdomyosarcoma at testicular or extratesticular sites. CASE: A 13-year-old boy presented with a large, right sided scrotal mass. Fine needle aspiration (FNA) was performed for rapid diagnosis. The smears revealed numerous spindle cells and large fragments of cytoplasmic processes with cross-striations and were diagnosed as spindle cell rhabdomyosarcoma. The histologic sections were also diagnosed as spindle cell rhabdomyosarcoma. CONCLUSION: The cytologic findings of this rare tumor have not been reported before. The cross-striations were easily identified in FNA smears, so the diagnosis of spindle cell rhabdomyosarcoma was made confidently. The histologic sections showed only spindle cells with different patterns of arrangement, resembling leiomyosarcoma. The cross-striations were not identified in the histologic sections. In this case cytologic diagnosis aided the histologic diagnosis.     

Fine needle aspiration cytologic findings in four cases of pilomatrixoma (calcifying epithelioma of Malherbe).

Four cases of pilomatrixoma studied by fine needle aspiration (FNA) biopsy prior to resection and histologic diagnosis were reviewed to identify the cytologic features useful in making the FNA cytodiagnosis. Cytopathology had initially correctly diagnosed two cases while misdiagnosing one as a carcinoma and one as a suspected carcinoma. The aspirates from all cases contained either clustered or isolated basaloid cells, with variably sized nuclei and prominent nucleoli. "Ghost cells" were also present in most smears stained with the Giemsa stain and could thus be very helpful for making the FNA diagnosis of pilomatrixoma. The occurrence of either foreign-body giant cells or calcium deposits in the aspirates could also contribute to suggesting the correct diagnosis of pilomatrixoma in some cases.