Pathology of R4 spiculated lesions in the breast screening programme

Small spiculated carcinomas are indistinguishable from benign radial scar/complex sclerosing lesions on mammography, leading to a radiological assessment of R4 (suspicious, probably malignant). The cytological and pathological features of 80 screen detected R4 spiculated lesions were reviewed. The analysis showed that there were 46 radial scars, of which 38 were benign and 8 (17%) contained foci of ductal carcinoma in situ (DCIS), and 34 spiculated carcinomas. The majority of radial scars showed some degree of epithelial hyperplasia (assessed semi-quantitively) but the cellularity of the lesion as a whole was not related to the presence of DCIS. In 20 cases no aspiration was attempted for cytology but 40% were inadequate and only one lesion containing DCIS had cytology C4 or C5. Diagnosis of radial scar was made in all cases by localization biopsy. The carcinomas ranged in size between 4 and 15 mm (mean 8.9 mm) and were of grade 1 (21 = 63%) or grade 2 (12 = 37%). There were 16 infiltrating ductal carcinomas of no special type, 12 tubular carcinomas, three lobular carcinomas, two ductal and lobular mixed, and one mucinous carcinoma. Only one patient with carcinoma was node-positive. For the carcinomas, 12 (35%) yielded C5 (malignant) cytology allowing pre-operative diagnosis.     

Fibroadenoma of the breast: diagnostic pitfalls of fine-needle aspiration.

On fine-needle aspiration (FNA), fibroadenomas have a characteristic cytological appearance, although occasional cases are misinterpreted as carcinomas and vice versa. In a review of 521 breast aspirates correlated with the subsequent histology, six of 87 fibroadenomas (7%) were malignant or suspicious of malignancy on FNA (false positives). Following cytological review, four were still suspicious of malignancy because of cellular dyscohesion and prominent nucleoli, while two were fibroadenomas. On FNA, four of 145 carcinomas (3%) were diagnosed as fibroadenomas (false negatives). On review, three were malignant or suspicious of malignancy, while one was consistent with a fibroadenoma. Three false negative diagnoses were due to underappreciation of single malignant cells present between epithelial groupings typical of a fibroadenoma, while one was due to undersampling of the carcinoma. Cytologically, some fibroadenomas are sufficiently atypical that histological confirmation is necessary to exclude a malignancy. Misinterpreting carcinomas as fibroadenomas could be avoided by careful study of the morphology of isolated cells.     

Significance of the diagnostic categories “atypical” and “suspicious for malignancy” in the cytologic diagnosis of solid pancreatic masses

Endoscopic ultrasound guided (EUS) fine‐needle aspiration (FNA) investigation of solid pancreatic lesions has been shown to have good sensitivity and specificity. Many lesions can be definitely classified as benign or malignant but some can only be cytologically classified as “atypical” or “suspicious for malignancy”. Risk for malignancy in these indeterminate categories has not been well categorized. The cytology records of four University Medical centers were searched for all EUS guided FNAs of solid pancreatic lesions. All cases with a diagnosis of “atypical”, or “suspicious for malignancy” were selected for analysis when histologic biopsy or over 18 months clinical follow‐up was available. Two hundred and ninety‐two cases with a diagnosis of “atypical” or “suspicious for malignancy” and adequate follow‐up were obtained from the combined data of the four institutions. The percentage malignant for the categories “atypical” and “suspicious for malignancy” were 79.2 and 96.3%, respectively. If the category “atypical” was classified as benign and “suspicious for malignancy” was classified as malignant, the resulting positive predictive value was 96.3 (95% CI: 92.6–98.5) and the negative predictive value 20.8 (95% CI: 13.4–30.0). The categories of “atypical” and “suspicious for malignancy” stratify risk for malignancy in a fashion, which may aid in patient counseling and selection of follow‐up protocols. Classification of “suspicious for malignancy” as malignant optimizes diagnostic sensitivity and specificity. Diagn. Cytopathol. 2014;42:292–296. © 2014 Wiley Periodicals, Inc.     

Are epithelial cells in fat or connective tissue a reliable indicator of tumor invasion in fine-needle aspiration of the breast?

The diagnosis of breast carcinoma tumor invasion by fine-needle aspiration (FNA) cytology continues to be controversial. To assess the reliability of predicting tumor invasion by FNA, we examined the cytologic smears of 183 FNAs of benign and malignant solid epithelial lesions of the breast for which histologic follow-up was available. The study group consisted of 94 invasive carcinomas, eight pure ductal carcinomas in situ (DCIS), and 81 benign lesions (fibroadenoma, fibrocystic changes, papilloma, adenosis). Epithelial cellularity, presence of epithelial cells in dispersed fat droplets and presence of epithelium within intact fragments of fibrofatty connective tissue were tabulated. Epithelial cellularity in dispersed fat was semiquantitatively scored. The cytologic diagnosis of the epithelial cells in all cases was recorded as benign, malignant, or indeterminant for malignancy. Findings showed that 95.5% of invasive carcinomas, 100% of DCIS, and 68.1% of benign lesions contained epithelial cells in dispersed fat; 80.8% of invasive carcinomas, 66.7% of DCIS, and 60.7% of benign lesions contained epithelial cells in intact fibrofatty connective tissue. Corrected score of epithelium within fat was 0.781 for invasive carcinoma, 0.727 for DCIS, and 0.562 for benign lesions. The difference in values for all parameters was not statistically significant between invasive carcinoma and DCIS, but reached significance between invasive carcinoma and benign lesions. Eighteen cases (7/94 invasive carcinoma, 5/8 DCIS, 6/81 benign lesions) contained atypical epithelial cells indeterminant for malignancy, all of which had epithelial cells present in dispersed fat when dispersed fat was present on the slides, indicating that this criterion was not helpful in discriminating between a benign and malignant diagnosis. We conclude that the presence of epithelial cells either admixed within dispersed fatty droplets or seemingly within fragments of fibrofatty connective tissue is not a reliable indicator of tumor invasion in FNA of the breast, and is frequently found in both benign and malignant breast lesions. The presence of epithelial cells in intact or dispersed fat is most likely a mechanical artifact of aspiration and/or smear preparation. Diagn. Cytopathol. 16:137–142, 1997. © 1997 Wiley-Liss, Inc.     

Fine needle aspiration cytology in young women with breast cancer: diagnostic difficulties

BACKGROUND: Breast carcinoma is the most common malignancy in women worldwide. Though fine needle aspiration cytology (FNAC) plays an important role in preoperative diagnosis, there may be diagnostic delays in affected young women due to a lower index of suspicion. METHODS: The files of the Departments of Pathology, Singapore General Hospital, Singapore, and Prince of Wales Hospital, Hong Kong, were searched for cases of breast carcinoma in women aged 35 years or less. Those with prior FNA procedures comprised our study group. The FNA smears were reviewed and classified into five categories: inadequate, benign, equivocal, suspicious, malignant. The findings were correlated with subsequent histology. RESULTS: Thirty-four women aged 35 years and below underwent 35 FNACs, with one woman having bilateral FNA procedures. Upon review, one (2.9%) was classified as inadequate, one (2.9%) benign, five (14.3%) equivocal, five (14.3%) suspicious, 21 (60%) malignant and slides were not available for review for two (5.6%) cases. For six benign and equivocal cytological diagnoses, subsequent histology disclosed pure ductal carcinoma in situ (DCIS, 1 case), mucocoele-like lesions with DCIS (2 cases), invasive and in situ ductal carcinoma with neuroendocrine features (1 case) and two cases of invasive ductal carcinoma. CONCLUSION: Diagnostic difficulties in cytological interpretation of aspirates from breast carcinoma in young women may lead to unwanted delays, which occurred in six (17.6%) of 34 women in our series. Low grade cancers posing a pitfall in cytological diagnosis have to be considered.     

Breast calcifications with percutaneous vacuum-assisted biopsy diagnosis of malignancy or atypical hyerplasia: correlations with surgical findings

Percutaneous, stereotactic, vacuum-assisted biopsy has become a widely used alternative to open surgical biopsy for the initial diagnosis of breast calcifications. We retrospectively assessed the accuracy of the technique in the diagnoses of malignancy and atypical hyperplasia by correlation with the findings of the subsequent surgical excision. We studied 330 consecutive cases of breast calcifications, 216 (65.5%) of which were determined to be benign and 114 (34.5%) to be malignant or atypical at vacuum-assisted biopsy using an 11 gauge instrument. Of the latter 93 were available for comparison with the subsequent surgery, the specific diagnoses as revealed by percutaneous biopsy were as follows: 11 cases of atypical ductal hyperplasia (ADN), 67 cases of ductal carcinoma in situ (DCIS), 6 infiltrating ductal carcinomas (IFDC), 2 cases of atypical lobular hyperplasia and 7 of lobular carcinoma in situ (LCIS). At histological analysis after surgical excision, 3 (27%) of 11 cases previously diagnosed as ADH and 6 (9%) of 67 cases diagnosed as DCIS were shown to actually be higher grade lesions (DCIS/IFDC and IFDC, respectively). Of the 7 lesions diagnosed at vacuum-assisted biopsy as LCIS, surgery and histological analysis showed one infiltrating globular carcinoma and two DCIS. A total of 21 lesions (4 ADH, 14 DCIS, 1 IFDC, 2 LCIS) were completely removed at percutaneous biopsy; the remaining cases were found totally concordant. These data Indicate a substantial accuracy of the percutaneous biopsy: some lesions (particularly those thought to be ADH and DCIS) can be underestimated for sampling error.     

Cytopathology of retrograde renal pelvis brush specimens: An analysis of 40 cases with emphasis on collecting duct carcinoma and low-intermediate grade transitional cell carcinoma

We report our experience with 40 retrograde renal brush samples of pelvic-calyceal lesions with confirmatory tissue studies. On-site cytopathologic evaluation was performed in 38 of these specimens. The final histologic diagnoses included 24 cases of transitional cell carcinoma (TCC), 17 of which were low-intermediate grade tumors. All 24 cases were diagnosed cytologically as TCC (22), or as suspicious for TCC (2). Three cases classified as collecting duct carcinomas were resected; the cytologic specimens in 2 of these cases were interpreted as TCC, and one as reactive change. There were three renal cell carcinomas (RCC); cytologically, one was considered a papillary neoplasm, one suspicious for malignancy, and one as reactive. Two cases of atypical renal cysts were reported as suspicious for malignancy in both cytologic and histologic material. There was one case of metastatic colon carcinoma identified in the brush specimen. Finally, tissue studies in the remaining 7 cases showed reactive/inflammatory changes; however, four of the corresponding pelvic brush specimens were considered abnormal. A review of the above cases is reported with the objective of presenting the cytologic features seen in collecting duct carcinoma, low-intermediate grade TCC, and diagnostically difficult cases with cyto/histomorphologic discrepancies. The contribution of on-site assessment to diagnostic accuracy is also discussed. Diagn Cytopathol 1996;15:312–321. © 1996 Wiley-Liss, Inc.     

Accuracy of cytologic diagnoses made from touch imprints of image-guided needle biopsy specimens of nonpalpable breast abnormalities

We investigated the diagnostic utility and accuracy of touch imprints (TIs) prepared from core-needle biopsy (CNB) specimens of nonpalpable breast abnormalities. We reviewed air-dried, Diff-Quik-stained TIs prepared from 172 consecutive CNB specimens obtained with stereotactic or sonographic guidance. Using criteria established for fine-needle aspirates, TIs were categorized as benign, atypical, suspicious, malignant, or unsatisfactory (i.e., showing fewer than six benign epithelial cell clusters or cell distortion). Cytologic diagnoses of TIs were then correlated with the histologic diagnoses of corresponding CNB specimens. CNB specimens were histologically diagnosed as carcinoma (102 cases), benign (59 cases), low-grade phyllode tumor (six cases), and atypical ductal hyperplasia (five cases). TIs were cytologically diagnosed as malignant (63 cases), benign (35 cases), suspicious (19 cases), atypical (18 cases), and unsatisfactory (37 cases). Correlation of the cytologic and histologic diagnoses showed that five TIs diagnosed as benign were false-negative results for histologically diagnosed carcinomas (four cases) and phyllodes tumor (one case). False-negative results were attributed to poor representation of malignant cells. Two TIs diagnosed as suspicious were false results for two histologically diagnosed fibroadenomas. The false suspicious findings resulted from TIs with high cellularity, cytologic atypia, or no familiar (i.e., as seen on fine-needle aspirates) smear pattern. Unsatisfactory TIs were noted in both benign (44%) and malignant (11%) CNB specimens. When lesions categorized as suspicious were grouped with the malignant cases and those classified as atypical were grouped with the negative cases, TI sensitivity and specificity, were 83% and 95%, respectively. Fibroadenomas are difficult to identify on TIs and are likely to be misdiagnosed as suspicious. While high- and intermediate-grade carcinomas are easily categorized using TIs, low-grade carcinomas are best categorized as suspicious because of overlapping cytologic features with proliferative breast lesions. Increased experience with cytologic analysis of TIs improves the accuracy of cytologic diagnoses.     

Clinical value of DNA image cytometry in effusions with atypia.

Malignant cells in serosal effusions provide essential information about the extent of malignant disease. The main aim of this study was to examine the additional diagnostic value of DNA image cytometry for cases with uncertainty in the cytological diagnosis. In addition, the feasibility of automated nuclei detection was investigated. Out of 457 cases, 33 samples in 32 patients were diagnosed with "atypia" (probably benign) and 21 as "suspicious for malignancy." DNA image cytometry was performed on these 54 cases and on an additional group of 14 cytologically malignant cases. The results show that automatic classification is useful for separation of control cells, i.e., lymphocytes and neutrophilic granulocytes from other mononuclear cells. In 21 cases an insufficient number of control cells were measured. Seventy-two percent of the cytologic malignant cases were aneuploid. In contrast, in none of the cases with "atypia" and in only 2 of the cases "suspicious for malignancy" was aneuploidy present (2 of the remaining 32, 6%). From the cases with follow-up, a malignancy in the pleural fluid was present in 2 out of 17 cases with "atypia" and in 5 out of 10 with a "suspicious for malignancy" cytologic diagnosis, respectively. In conclusion, the additional diagnostic value of DNA image cytometry in cases with a cytological diagnosis of "atypia" or "suspicious for malignancy" is limited. Diagn. Cytopathol. 1999;21:112-116.     

Needle core biopsy can reliably distinguish between benign and malignant papillary lesions of the breast

AIMS: To review 21 screen-detected papillary lesions in which the core biopsy findings suggested a papillary lesion and to correlate pathological and radiological findings in order to assess the risks of associated malignancy and the need for surgical intervention. The appropriate management of non-malignant papillary breast lesions detected on needle core biopsy (NCB) is currently uncertain. METHODS AND RESULTS: Forty-seven papillary breast lesions with a histological diagnosis of papilloma, papilloma with atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS), multiple papillomas, 'papillomatosis' or papillary carcinoma (invasive or in situ) were identified from records at the Leeds Breast Screening and Assessment Unit. The cases were diagnosed between between May 1995 and May 2002. In 21 cases the previous NCB contained a papillary proliferation which had been categorized as either 'B2', benign, 'B3', of uncertain malignant potential, or 'B4', suspicious of malignancy. All of the 19 'B3' or 'B4' cases and one of the two 'B2' lesions had undergone open surgical biopsy. All cases with a previous 'B4' were malignant on subsequent excision. All excised cases with a previous 'B3' or 'B2' were found benign, although four of the 'B3's derived from papillomata associated with an atypical proliferation amounting to ADH. In three of these four (75%) the papillary proliferation had been associated with epithelial hyperplasia of usual type (HUT) on the core and the radiological features were of a mass lesion detected on incident round screen which had increased in size. CONCLUSION: Our results confirm the accuracy of NCB in the diagnosis of screen-detected papillary lesions of the breast. Surgical excision may not always be necessary following a 'B3' core biopsy.     

Fine-needle aspiration of cystic lesions of the kidney. Morphologic spectrum and diagnostic problems in 41 cases

Although imaging studies show the nature of most cystic lesions of the kidney (RCs), many RCs require fine-needle aspiration (FNA) for accurate diagnosis. Interpretation of the FNAs remains challenging. The FNA specimens of 41 RCs were reviewed and correlated with imaging studies. Final diagnoses for 30 cytologically benign lesions were simple cyst (28), acquired cystic kidney (1), and cystic renal carcinoma (1). The fluid from the benign cysts displayed macrophages, epithelial cells from the cyst lining, tubular cells, neutrophils, and Liesegang rings. Fluid from the acquired cystic kidney and the cystic renal cell carcinoma showed features similar to those of the benign cysts. The 9 cases with "suspicious" cytology included 5 complex cystic lesions displaying rare but atypical epithelial cell clusters, 3 low-grade renal cell carcinomas with many mildly atypical papillary clusters of epithelial cells, and 1 simple benign cyst with many tubular cells. The 2 cytologically malignant lesions were cystic renal cell carcinomas with abundant tumor cells with partially clear cytoplasm and atypical nuclei admixed with abundant macrophages and lymphocytes; 1 case developed in a kidney with acquired cystic disease. Simple cysts remain the most frequently aspirated RCs, but complex cystic lesions are increasingly recognized. Since many RCs are composed of independent loculi, a nonrepresentative sample is a potential problem, and cytologic-radiologic correlation becomes mandatory. The "suspicious" patterns identified in this study should serve as diagnostic guidelines and set the foundation for future validation.     

Fine-needle aspiration cytology of metaplastic carcinoma of the breast

BACKGROUND: Metaplastic carcinoma of the breast encompasses a heterogeneous group of tumours with variable components of sarcomatoid, squamous or poorly differentiated carcinomas. AIM: To review a series of 19 cytological preparations of metaplastic carcinomas to assess diagnostic cytological features. METHODS: 17 cases of fine-needle aspirates of histologically proven metaplastic carcinomas (4 monophasic spindle cell carcinomas, 4 squamous cell carcinomas and 11 biphasic tumours) were reviewed, with an emphasis on the presence of poorly differentiated carcinoma, squamous cell carcinoma, atypical spindle cells, benign stromal fragments and necrosis. RESULTS: All cases were diagnosed as malignant, with 68% of cases showing moderate to high cellularity, and 47% showing necrosis. If the tumours were analysed according to the constituting components histologically, 7, 15 and 8 cases, respectively, possess poorly differentiated carcinoma cells, sarcomatoid malignant cells and squamous carcinoma cells, whereas these components were cytologically identified in 11, 10 and 7 cases, respectively. Dual tumour populations were identified in only 5 of the 11 biphasic carcinomas in the cytological preparations; and the stromal material was cytologically identified in the only case with chondroid stroma. CONCLUSIONS: Identification of metaplastic carcinoma in cytology remains problematic. There seems to be morphological overlap between various components. The identification of dual components, unequivocal squamous carcinoma cells and chondroid stroma is helpful for diagnosis, but it is uncommon. The presence of poorly differentiated carcinoma cells with a suggestion of focal spindle morphology is another clue to the suggestion of metaplastic carcinoma.     

Nucleolar organizer regions distribution in fine needle aspiration cytological smears from breast lesions

Fine needle aspiration (FNA) cytology is now an integral part of the pre-operative investigation of breast lesions and the therapeutic protocol is today often planned on the basis of cytodiagnosis. However, from time to time the cytological picture may be equivocal or inconclusive. In recent years, nucleolar organizer region (NOR) scores have been explored for potential value in the diagnosis of malignancy as the scores in malignant nuclei are seen to be higher than in benign or reactive nuclei. With a view to applying NOR scoring in the evaluation of cytologically equivocal cases, we adopted the argyrophil technique for staining NOR s (AgNOR) in FNA cytological smears of 56 breast lesions, comprising 31 benign and 25 malignant lesions. Histological correlation was possible in 26 of these cases (17 malignant and 9 benign) and AgNOR scoring was done on paraffin sections of these as well. There was a significant difference between mean AgNOR scores in benign and malignant lesions in the cytological smears (P < 0.001). The AgNOR scores ranged from 2.5 to 5.0 per cell in benign lesions and 5.8 to 17.2 per cell in malignant lesions. None of the cases fell into the gray zone of overlap. One malignant lesion that was cytologically equivocal showed a mean AgNOR score of 6.08. The AgNOR scores on histological sections also showed a statistically significant difference (P < 0.001) between benign and malignant lesions with mean scores ranging from 1.34 to 2.58 dots per cell in benign lesions and scores of 2.42 to 5.28 dots per cell in malignant lesions. However, the scores overlapped in four cases and therefore it was considered unsuitable for routine diagnostic work. From this preliminary study, we conclude that an FNA AgNOR score of 5.0 and less strongly favours a benign lesion whereas a score above 5.0 would be in favour of a malignant lesion. A larger study would be needed to verify our impression that AgNOR scoring can be useful in cytologically equivocal cases.     

Is core needle biopsy superior to fine‐needle aspiration biopsy in the diagnosis of papillary breast lesions?

Since the 1980s core needle biopsy (CNB) has gained remarkable popularity and in many institutions it has replaced fine-needle aspiration biopsy (FNAB). However, similar to FNAB, limitation remains in the ability of this procedure to reliably diagnose a small, but prognostically significant, number of breast lesions. These include entities such as atypical ductal hyperplasia, fibro-epithelial tumors, radial scar, papillary lesions, and lobular neoplasia. To assess the diagnostic accuracy of CNB vs. FNAB in the same breast lesions, we reviewed our cases of papillary lesions of the breast. In a retrospective study, we identified 36 cases of FNAB and 11 cases of CNB diagnosed as papillary lesions and compared the results with their corresponding surgical specimen. Interpretation ranged from papillary vs. atypical papillary lesions favoring benign vs. malignant tumors, respectively. Occasionally, definitive diagnosis of papillary carcinoma was entertained. Immunohistochemical staining with smooth muscle actin was used to evaluate the presence or absence of a myoepithelial cell layer. FNAB had benign findings in 21 lesions, atypical in 10, and malignant in five. Of the five lesions yielding malignant features, four had invasive carcinoma and one had micropapillary ductal carcinoma in situ (DCIS). Surgery revealed invasive carcinoma in three of the cases interpreted as atypical papillary lesions and invasive cancer and micropapillary DCIS in three of the cases diagnosed as benign lesions. Similar results were obtained with CNB. DCIS was found in one out of six of the cases diagnosed as papilloma. Out of the four cases that were interpreted as atypical papillary lesion, surgery revealed invasive carcinoma in one case and one case had micropapillary DCIS. Diagnosis of malignancy was confirmed by histology in one case interpreted as papillary carcinoma by CNB. This study suggested that both FNAB and CNB share similar diagnostic challenges and a follow-up surgical excision is indicated when diagnosis of a papillary lesion is entertained by both procedures.     

Comparative features of ductal carcinoma in situ and infiltrating ductal carcinoma of the breast on fine-needle aspiration biopsy

To evaluate the usefulness of fine-needle aspiration biopsy of the breast in separating ductal carcinoma in situ (DCIS) from infiltrating ductal carcinoma, the authors reviewed 16 preoperative fine-needle aspiration biopsies from biopsy-proven exclusive DCIS and 39 fine-needle aspiration biopsies from infiltrating ductal carcinomas with or without an in situ component. Seven (44%) of the DCIS and eight (21%) of the infiltrating ductal carcinomas had inadequate material for diagnosis on the aspiration biopsy. Five (32%) of the DCIS and 29 (74%) of the infiltrating ductal carcinomas caused suspicion or had positive results for malignancy. Four (25%) of the DCIS and two (5%) of the infiltrating ductal carcinomas showed atypical cells. Morphologic features of the atypical or malignant cells in the adequate specimens from these two lesions were similar except that the cells from the infiltrating ductal carcinomas showed more irregular nuclear spacing (94% vs. 44%, P less than 0.01) and more pronounced nuclear overlapping (65% vs. 33%) than those from the DCIS. In addition, the fine-needle aspiration biopsies of the DCIS tended to be hypocellular (less than 10 cells/10X) (44% vs. 6.5%, P less than 0.05) and to contain benign epithelial cells (22% vs. 6.5%) and macrophages (33% vs. 13%). Although the suspicion of DCIS might be raised when hypocellularity, benign epithelial cells, and macrophages are noted in a fine-needle aspiration biopsy of the breast that has positive results or causes suspicion for malignancy, fine-needle aspiration biopsy cannot be relied upon to distinguish DCIS from infiltrating ductal carcinoma.     

ThinPrep evaluation of fluid samples aspirated from cystic ovarian masses

The cytological evaluation of ovarian cystic fluid using ThinPrep has not been reported. To determine the diagnostic accuracy of ThinPrep cytology in distinguishing between benign and nonbenign ovarian cystic lesions, we examined 65 fluid samples aspirated during intraoperative consultation with subsequent histologic correlation. One ThinPrep slide was prepared from each sample aspirated from surgically removed ovarian cystic masses and reviewed blindly by a panel of three cytopathologists. The parameters used in cytological evaluation were cellularity, cell types, cellular arrangement, and background. Four samples were acellular and excluded from the study. The consensus cytologic diagnoses were compiled for 61 cases which were assigned to one of the following diagnostic categories: negative for malignant cells (40 cases), atypical cytology (13 cases), and suspicious or positive for malignancy (8 cases). Histologic correlation of the cytological benign/negative cases showed that 26/40 (65%) were histologically benign and 14/40 were false-negative (35%, 5 carcinomas and 9 borderline tumors) with 10 of these cases being mucinous tumors. Most false-negative cytologic samples (11/14 or 79%) did not have an epithelial component. Of the 21 cytological nonbenign diagnoses (atypical/suspicious/positive), 15 (71%) were confirmed on histology (10 carcinomas and 5 borderline tumors). However, a nonbenign cytologic diagnosis was rendered in 6 histologically benign cases, including 2 serous cystadenomas, 1 mucinous cystadenoma, 1 serous cystadenofibroma, 1 endometriosis, and 1 corpus luteal cyst. The diagnostic sensitivity by ThinPrep evaluation of ovarian cystic masses is 81% (26/32) for benign and 52% (15/29) for nonbenign lesions. Our results concluded that ThinPrep examination of ovarian cystic fluid is not accurate in distinguishing benign from malignant cysts, given the significant number of false-negative diagnoses. Major contributing factors include sparse cellularity of the fluid samples and mucinous differentiation of the tumors.     

The significance of the diagnosis of atypia in breast fine-needle aspiration

The diagnosis of atypia in breast fine-needle aspiration (FNA) continues to be an area of debate in cytology practice. The aim of this study was to assess the clinical significance of this term and to evaluate potential morphological criteria, which would determine the patient's outcome. A computer-based search was carried out to retrieve breast FNAs performed between 1990 and 2000 that were diagnosed as atypical. Cases followed by surgical resection were reexamined for the presence of morphological features potentially differentiating benign and malignant lesions. Out of 1,568 breast FNAs, there were 64 cases (4%) with a diagnosis of atypia. Thirty-eight cases had surgical follow-up material that revealed malignancy in 14 cases (37%) and benign lesions in 24 cases (63%). The benign diagnostic categories included fibrocystic change (12/24), fibroadenoma (3/24), tubular adenoma (2/24), and nonspecific findings (7/24). The malignant diagnoses included ductal carcinoma (9/14), lobular carcinoma (3/14), ductal carcinoma in situ (DCIS; 1/14), and tubular carcinoma (1/14). The evaluation of cytological criteria used to differentiate benign from malignant lesions (i.e., cellularity, loss of cohesion, myoepithelial cells, nuclear enlargement, nuclear overlap, prominent nucleoli) revealed significant overlap between benign and malignant cases, particularly in cases of fibroadenoma, tubular adenoma, and proliferative breast disease. The surgical follow-up of four hypocellular cases revealed lobular carcinoma in two cases and ductal carcinoma in the remaining two cases. Our study confirmed that the diagnosis of atypia is clinically significant because it is associated with a high probability of malignancy. No morphological criterion is able to reliably differentiate benign and malignant lesions in cases diagnosed with atypia. Diagnosis of atypia is particularly significant in hypocellular cases. We recommended that breast FNAs with a diagnosis of atypia be evaluated further histologically.     

Mammary mucinous lesions: congeners, prevalence and important pathological associations

A retrospective histopathological study was undertaken to determine the prevalence of mucin filled ducts and their associated mucinous proliferation in 962 breast cancers and 335 benign lesions. A total of 38 (3%) cases with mucin filled ducts was identified and 27 (2%) of these showed mucin extravasation into the adjacent stroma, changes characteristic of mucocoele-like lesions. This constitutes the largest series reported to date. Of the mucocoele-like lesions 12 were prototypic screen-detected cases; 11 of which were mammographically detected on account of suspicious microcalcification and eight cases (67%) exhibited mucinous atypical ductal hyperplasia without overt malignancy. A further 12 mucocoele-like lesions were incidental findings in screen-detected (11) and symptomatic (one) cancers, the majority of which were invasive ductal carcinomas of no special type. In six of these cases (50%), mucinous atypical ductal hyperplasia or ductal carcinoma in situ was present. Thirty mucinous carcinomas constituted 3% of all cancers and three cases had associated mucocoele-like lesions. Mucinous atypical ductal hyperplasia or ductal carcinoma in situ was also associated with 11 cases of mucinous carcinoma. In six mucinous carcinomas, amorphous microcalcification with a similar appearance to that of benign mucocoele-like lesions was identified in the mucin, suggesting a possible link between the two lesions. Mucin-filled ducts or mucocoele-like lesions were almost twice as frequent in screen-detected as in symptomatic lesions. The presence of mucinous atypical ductal hyperplasia in screen-detected mucocoele-like lesions, a decade earlier than the peak of mucinous carcinoma, is a possible risk factor for subsequent invasive malignancy. Mucin-filled ducts, mucocoele-like lesions, mucinous atypical ductal hyperplasia or ductal carcinoma in situ and mucinous carcinoma may represent different stages of the same disease process. Our findings suggest that patients with mucin-filled ducts of mucocoele-like lesions merit close follow-up.     

Value of p53 immunostaining in pancreatico-biliary brush cytology specimens

Brush cytology is routinely used in the assessment of pancreatico-biliary strictures but the technique has limited diagnostic sensitivity in malignant lesions. It has been suggested that ancillary techniques, such as the identification of p53 immunoreactivity, might improve diagnostic accuracy. p53 protein expression was examined in 143 consecutive brush cytology specimens from patients with pancreatic or bile duct strictures and correlated with conventional cytological assessment and clinicopathologic follow-up data. Sixty-three of 89 (70.8%) malignant strictures were identified cytologically while 45 cases (50.6%) were p53 immunoreactive. One case of bile duct adenoma with high-grade dysplasia was reported as consistent with adenocarcinoma cytologically and was p53 negative. There was one false-positive diagnosis with conventional cytology and, in a separate case, with p53 immunostaining. Nineteen specimens (13.3%) were considered atypical cytologically and p53 expression proved accurate in only 12 cases (four immunopositive carcinomas and eight negative benign strictures). In conclusion, p53 immunostaining proved less sensitive than conventional cytology in this series and its routine diagnostic use could not be supported.     

The importance of intracytoplasmic DPAS positivity in fine needle aspirates of breast lesions

AIMS: For many years the presence of strong intracytoplasmic periodic acid Schiff (PAS) positive, diastase resistant (DPAS) staining within atypical cells has been used in this laboratory as a marker for carcinoma in fine needle aspirates from breast lesions. The aim of the current study was to document such DPAS positivity across the spectrum from benign to malignant breast disease and assess its value in the upgrading of cytology reports. METHODS: Over a six month period, 315 aspirates were studied, each having sufficient cellular material for DPAS staining to be carried out on one whole slide. DPAS staining was recorded semiquantitatively as negative, equivocal, or positive (+, ++, or +++). The cytology results were correlated with any subsequent histology performed on these patients. RESULTS: DPAS positive material was seen in both intracellular and extracellular locations. Care was needed in its interpretation. Occasional cells with apparently genuine intracytoplasmic positivity (+) were found in both benign and malignant cases. Frequent or particularly strong intracellular DPAS positivity (++, +++) correlated best with malignancy. Two cases were reliably upgraded from immediate reports suspicious of malignancy to final reports diagnostic of malignancy on the basis of the intracytoplasmic DPAS staining. CONCLUSION: Strict criteria are required for the interpretation of intracytoplasmic DPAS positivity and routine cytological appearances should also be taken into account. Weak positivity in occasional cells, especially in flat epithelial sheets, may be seen in benign lesions and is not reliable as a marker of malignancy. DPAS positivity with internal structure and producing nuclear indentation, especially in dissociated or atypical cells, correlates well with malignant histology and can be reassuring in the cytological diagnosis of malignancy.