Fibroadenomas with atypia: causes of under- and overdiagnosis by aspiration biopsy.

Fibroadenoma (FA) is a common benign breast lesion frequently sampled by fine-needle aspiration biopsy (FNAB). Although the cytologic diagnosis is straightforward in most cases, cellular discohesion and atypia in FAs may lead to falsely atypical or positive FNAB diagnoses. Conversely, some adenocarcinomas mimic a fibroadenomatous pattern on FNAB, resulting in a false-negative diagnosis. We reviewed the cytologic and histologic findings in 25 cases with a preoperative FNAB diagnosis of FA, wherein excision was recommended based on atypia. Our aim was to analyze the spectrum of changes causing under- or overdiagnosis in such cases. The smears were assessed for cellularity, cellular discohesion, presence of dissociated intact cells and nucleoli, nuclear pleomorphism, oval bare nuclei, and stromal fragments. The histologic findings were correlated with FNAB features. At excision, 88% of FAs classified as atypical on FNAB were benign (FA with ductal hyperplasia and lactational change, myxoid FA, and other fibroepithelial lesions). Differentiating myxoid FA from colloid carcinoma was difficult due to the abundance of extracellular mucin in which the dissociated epithelial cells were floating. Two (8%) cases were carcinomas on excision; the reasons for underdiagnosis in one case reflected sampling, and in the other, interpretative error. There was one (4%) benign phyllodes tumor which lacked stromal fragments and single stromal cells on FNAB smears. The lesion was called atypical, based on the epithelial discohesion on the smears. We conclude that the majority of FAs with atypia on FNAB are benign lesions. Considering the grave consequences of a false-positive cytologic diagnosis, we recommend a conservative approach in interpreting FNAB smears which overall display a fibroadenomatous pattern.     

Fine-needle aspiration cytology of sclerosing adenosis of the breast: a retrospective review of cytologic features in conjunction with corresponding histologic features and radiologic findings

We retrospectively reviewed 25 fine-needle aspiration cases of sclerosing adenosis of the breast in conjunction with histologic features of the paired core-needle biopsy and radiologic findings. The original cytologic diagnoses were benign (n = 19), focally atypical (n = 3), and suspicious for carcinoma (n = 3). The frequent features, although not specific, were low-to-moderate cellularity, bland epithelial cells that focally formed cohesive groups/tubules or occasionally discohesive clusters or individual cells, and fragments of dense fibrous stroma. Some tubules had an angulated configuration. Myoepithelial cells were present in all cases but were scant or absent in small epithelial groups. These cytologic features closely reflected the histologic appearances (ie, compressed and attenuated tubules and sclerotic stroma), but may cause overinterpretation on cytologic smears, especially when angulated tubules, discohesive or individual epithelial cells, scanty myoepithelial cells, and nuclear atypia are noted concurrently. Familiarity with its cytologic features may prevent false-positive diagnosis. Histologic confirmation is recommended for difficult cases.     

Epithelial cell atypia in bronchoalveolar lavage specimens from lung transplant recipients.

In lung transplant recipients, bronchoalveolar lavage (BAL) is mainly performed to detect infectious agents. However, in addition to microorganisms, epithelial cell atypia may be identified, and determination of its significance is necessary. Specimens obtained at BAL in lung and heart-lung transplant recipients (LTRs) between 1991 and 1998 were examined for the presence of significant cytologic atypia in epithelial cells. Ten cases in 9 patients were identified, and these composed the core of our study. These transplant BAL specimens were compared with 4 BAL specimens with carcinoma from non-transplant patients (NTPs). Fourteen cytologic parameters were evaluated, and clinical and biopsy correlation was made in each case. Significant overlap in cytologic features, including background cellularity, number of atypical cell clusters, number of cells in each cluster, size of cell clusters, contour of clusters, 3-dimensionality, tenacious intercytoplasmic connections, multinucleation, nuclear size, nuclear/cytoplasmic ratio, nuclear membrane irregularity, chromatin pattern, intranuclear inclusions, and nucleolar characteristics, was observed between atypical LTR cases and NTP carcinoma cases. Clinically, all LTR cases derived from nonneoplastic conditions including harvest injury (diffuse alveolar damage), acute cellular rejection, and infections. Our study results show that evaluation of cytologic features alone does not permit differentiation of atypical cells found in nonneoplastic conditions from those in malignant conditions. Clinical and histologic correlation and awareness of the range of atypia seen in posttransplant syndromes is important in correct interpretation of these cases.     

Cytologic features of poorly differentiated 'insular' carcinoma of the thyroid, as revealed by fine-needle aspiration biopsy

The authors report on the cytologic features of six cases of poorly differentiated "insular" carcinoma (IC) of the thyroid, a recently described variety of thyroid tumor intermediate between well-differentiated and anaplastic neoplasms. It is characterized by trabecular and/or alveolar growth patterns, merging with follicular areas, and by the absence of pleomorphism in the tumor cells. Fine-needle aspiration biopsy (FNAB) materials (both smears and cell-block preparations) from six patients were reviewed after the diagnosis of IC was confirmed on the surgical specimen. The following cytologic features were consistently found: high cellularity and necrotic background; low grade of atypia; trabeculae and/or clusters, possibly associated with microfollicles, of cells with poorly defined cytoplasm; and cytoplasmic vacuoles containing thyroglobulin. Nuclear inclusions and grooving of the nuclear surface were additional features. Preoperative diagnosis suggestive of IC might be of value for planning surgical treatment and subsequent therapy.     

Breast tumor resembling the tall cell variant of papillary thyroid carcinoma: a case report

The breast tumor resembling the tall cell variant of papillary thyroid carcinoma is a very unusual mammary carcinoma whose histologic and predominant nuclear features mimic a papillary thyroid carcinoma. We report the case of a 64-year-old woman who presented with a palpable nodule in the right breast. Fine needle aspiration disclosed abundant cellularity with isolated cells, sheets, and papillary formations of epithelial cells with nuclear grooves. Histologically, the neoplastic cells were arranged in a solid to papillary architecture, with follicular-like and cribriform areas. The cells were columnar to cuboidal with eosinophilic cytoplasm, clear chromatin, nuclear grooves, and occasional nuclear pseudoinclusions. Tumor cells were positive for cytokeratins, alpha and beta-estrogen receptors, progesterone receptor, androgen receptor, CEA, and bcl-2. We searched for BRAF mutations with negative results. Recognizing the cytologic and histologic characteristics of these peculiar mammary tumors that mimic thyroid carcinomas can avoid unnecessary clinical investigations.     

Aspiration biopsy of mammary lesions with abundant extracellular mucinous material. Review of 43 cases with surgical follow-up

We reviewed 43 fine-needle aspiration biopsy (FNAB) smears with abundant extracellular mucinous material to determine whether accurate classification of mucinous lesions is achievable on FNAB: 26 had carcinoma (pure colloid carcinoma [CCA], 23; mixed CCA/invasive ductal carcinoma [IDC], 3); 17 had benign lesions on follow-up (benign MLL, 6; fibrocystic change [FCC], 6; myxoid fibroadenoma [MFA], 5). All carcinomas were identified correctly as malignant on FNAB. The initial cytologic diagnoses in benign cases were benign in 8, atypical in 8, and "suspicious" for carcinoma in 1. CCAs were moderate to markedly cellular with mild to moderate atypia and lacked oval bare nuclei. Marked nuclear atypia was confined predominantly to cases with mixed CCA/IDC. A distinct feature of CCA was thin-walled capillaries. FCCs and benign MLLs had overlapping cytologic features and showed variable cellularity and no or mild atypia. MFAs were markedly cellular with dyscohesion and variable atypia; stromal fragments and oval bare nuclei were present in every case. Mucinous lesions can be divided into 2 categories by FNAB: those that are adenocarcinomas and those that are not. CCAs have distinctive features that allow a definitive diagnosis on FNAB. Unnecessary surgery can be avoided in MFA by careful evaluation of smear characteristics. Cytologic features of FCC and MLL overlap. Owing to the documented association of MLL with carcinoma, we recommend that lesions that cannot be classified definitively as adenocarcinoma or MFA be considered for conservative excision, even in the absence of atypia.     

Nodular histiocytic/mesothelial hyperplasia: a potential pitfall

We present five cases of nodular histiocytic/mesothelial hyperplasia (two peritoneal, two pulmonary, and one pericardial) with identical microscopic features. All the lesions were biphasic and composed of cohesive monotonous epithelioid clusters of polygonal or oval cells with round or deeply grooved nuclei in association with darker cuboidal cells. Because of the increased cellularity and monotonous histologic pattern with some degree of cytologic atypia, neoplastic processes were seriously considered in the differential diagnoses. The majority of the cells marked as histiocytes by immunostain. A few scattered individual cells or small epithelial cell clusters were confirmed by calretinin stain to be mesothelial cells. The histologic patterns of the current lesions, irrespective of the location, were identical to nodular histiocytic/mesothelial hyperplasia. Histiocytic proliferations can be erroneously confused with primary mesothelial lesions or neoplasms such as granulosa cell tumor, eosinophilic granuloma, chronic myelogenous leukemia, and carcinoma. The purpose of this article is to describe the clinicopathologic features of nodular histiocytic/mesothelial hyperplasia and help familiarize pathologists with this lesion to prevent an erroneous diagnosis, particularly when it occurs in locations where mesothelial cells are not normally present.     

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.     

Passive seeding in metanephric adenoma: a review of pseudometastatic lesions in perinephric lymph nodes

Lymph node involvement derived from a discrete neoplastic process fundamentally implies tumor malignancy. However, rarely, inconsequential passive transport of benign neoplastic cells to the lymph node can occur and may cause confusion as to the nature of the neoplasm (ie, malignant vs benign). We describe a 10-cm right renal metanephric adenoma incidentally discovered in a 30-year-old woman during cesarean section for a triplet pregnancy. Subsequent nephrectomy following an equivocal needle biopsy diagnosis showed histologic features classic for metanephric adenoma, including the lack of cytologic atypia and mitoses. Necrosis present in this lesion appeared to be secondary to tumor physical disruption. The tumor cells were positive for Wilms tumor 1 (WT1) antigen, pankeratin, and CD57, focally positive for epithelial membrane antigen, and negative for cytokeratin 7, cytokeratin 34betaE12, and CD56. Electron microscopy confirmed the tumor's epithelial nature, and cytogenetics revealed a diploid 46XX karyotype. The tumor proliferation index with Ki-67 was only 3% to 5% and the proliferating cell nuclear antigen index was 0%. A single, concurrently resected hilar lymph node contained scattered subcapsular, sinusoidal, and focally intralymphovascular psammoma bodies along with occasional adherent epithelial cells. These cells were highlighted by pankeratin but were nonreactive to WT1 antigen, similar to the nonviable cells in the primary tumor. Clinical surveillance and follow-up showed no disease recurrence 4 years after nephrectomy. We postulate that the lymph node inclusions found in this case represent passive transport of neoplastic cells to the lymph node following manipulation of the renal mass. We conclude that this phenomenon is understudied and underrecognized and can easily be mistaken for metastasis.     

Cytologic differentiation between proliferative and nonproliferative breast disease in mammographically guided fine-needle aspirates.

Fine-needle aspiration biopsy (FNAB) is considered a valid diagnostic procedure in management of patients with breast lesions. It is also important to differentiate benign nonproliferative change from proliferative breast changes, since the risk of development of breast carcinoma in patients with atypical hyperplasia is 4-5 times that of general population. Therefore, the recognition of proliferative breast disease with atypia significantly impacts on the patient's subsequent management. To assess the feasibility of a cytologic grading system to further characterize benign breast lesions, cytologic preparation of 87 mammographically guided FNABs were studied. Cellular aspirates were evaluated for the cellular arrangement, the degree of cellular pleomorphism and anisonucleosis, presence of myoepithelial cells and nucleoli and the status of the chromatin pattern. Values ranging from 1 to 4 were assigned to each cytologic criterion, and a score based on the sum of the individual values was calculated for each case. The minimum score attainable was thus 6. In our chosen criteria cytologic diagnosis of nonproliferative disease was entertained when the total score ranged from 6 to 10. Proliferative disease without atypia was diagnosed with a total score ranging from 11 to 14. Atypical hyperplasia was reported when the total score ranged from 15 to 18. A cytologic diagnosis of malignancy was entertained when the total score ranged from 19 to 24. The cytologic diagnosis was then compared to the reported histologic diagnosis from the excisional biopsies and the data were statistically analysed. A high degree of concordance was found between the cytologic findings and the histologic diagnosis. This study suggests that it is possible to apply a cytologic grading system to further subclassify benign breast disease and distinguish these forms from neoplastic lesions.     

Histiocytic aggregates in benign nodular goiters mimicking cytologic features of papillary thyroid carcinoma (PTC)

Macrophages/histiocytes are commonly seen in fine-needle aspiration biopsy (FNAB) specimens of thyroid nodules with varying degrees of cystic change. In some cases the histiocytic component of a cystic thyroid nodule can occur as large tissue fragments with marked nuclear atypia, including elongated nuclei with chromatin clearing, nuclear grooves, and membrane thickening. These nuclear changes mimic cytologic features of papillary thyroid carcinoma (PTC), thus leading to diagnostic difficulty in interpretation of FNAB specimens of benign cystic thyroid nodules. We evaluated ethanol-fixed Papanicolaou-stained smears of 273 cases of FNAB thyroid specimens from goitrous nodules with cystic change. Twenty cases were selected due to the presence of large aggregates of histiocytic cells with the above-mentioned nuclear atypia. An immunostain for histiocytic cells using CD68 was performed on alcohol-fixed slides. Histiocytic cells in tissue fragments with nuclear atypia mimicking PTC nuclei showed strong cytoplasmic staining for CD68; thyroid follicular cells stained negative for CD68. We conclude that histiocytic cells in cystic goitrous nodules can show nuclear features, which appear similar to PTC nuclei. Immunostaining for CD68 may be of value in differentiating between benign cystic thyroid nodules with histiocytic aggregates that mimic cytologic features of papillary carcinoma, and PTC with cystic change.     

Odontogenic ghost cell tumor: A case report with cytologic findings

Odontogenic ghost cell tumor is a rare, neoplastic form of calcifying odontogenic cyst (Gorlin cyst) whose cytologic features have not been previously reported. We present a case of odontogenic ghost cell tumor diagnosed by fine-needle aspiration biopsy (FNAB). The aspirate was characterized by (1) tissue fragments with basaloid epithelial cells, (2) “ghost” cells, (3) scattered multinucleated giant cells, (4) rare, eosinophilic, densely hyalinized “dentinoid” material in close association with the basaloid cells, and (5) calcific debris. The aspirate was diagnosed as “consistent with odontogenic ghost cell tumor.” The cytologic features of odontogenic ghost cell tumor, as described, closely parallel the major histologic findings in this rare tumor. The differential diagnoses include other odontogenic tumors, squamous cell carcinoma, basaloid cell tumors of the salivary gland, and pilomatrixoma. Diagn. Cytopathol. 1998;18:199–203. © 1998 Wiley-Liss, Inc.     

Cytohistologic features of invasive micropapillary carcinoma in a young female

Invasive micropapillary carcinoma (IMPC) is a recently reported variant of breast carcinoma in women. There has been only a single report describing the cytologic features of IMPC in the literature. We report on the cytohistologic features of IMPC with diffuse involvement of two quadrants of the breast and axillary lymph node metastases in a 32-yr-old female. The cytologic appearance of IMPC was characterized by high cellularity, marked cell discohesion, and epithelial cells forming aggregates, morules, and angular and papillary clusters without fibrovascular cores and showing high nuclear/cytoplasmic ratio, irregular nuclear contours, and finely stippled chromatin. Occasional psammoma bodies were noted. Histologic examination showed a pure IMPC composed of clusters, morules, and aggregates of malignant epithelial cells surrounded by distinctly clear spaces separated by thin fibrovascular septa. The tumor involved both inner quadrants and axillary lymph nodes. A primary tumor elsewhere, particularly in the ovaries, was excluded. The patient has been disease-free 38 mo after the initial diagnosis.     

Role of immunocytochemistry,electron microscopy,and DNA analysis in fine-needle aspiration biopsy diagnosis of Wilms' tumor

We reviewed the cytologic features and results of ancillary studies in eight fine-needle aspiration biopsies (FNAB) performed by posterior approach in 8 patients with unresectable Wilms' tumor (WT). Chemotherapy was given following the FNAB diagnosis of WT, which was confirmed subsequently by histologic examination of surgically resected specimens. Indications for FNAB included: unresectable tumor, bilateral disease, initial presentation with metastatic disease, uncertainty regarding tumor site, and documentation of recurrence. Cytologic examination revealed blastemal cells (8/8 aspirates), spindle cells (3/8 aspirates), and epithelial differentiation or tubules (3/8 aspirates). There was no cytologic evidence of anaplasia in any of the cases. Immunocytochemical studies on cell blocks and/or smears showed cytokeratin positivity in 5/8 and vimentin positivity in 5/5 of the aspirates in which these studies were performed. Focal positivity for neuron-specific enolase (NSE) was seen in 3/3 aspirates. Stains for actin and leukocyte-common antigen were negative (0/3 and 0/2 aspirates, respectively). DNA ploidy analysis of the aspiration material by flow cytometry revealed near-diploid populations in three aspirates. Electron microscopic findings helpful for diagnosis included: cell junctions, microvilli, flocculent basement membrane-like material, cilia, autophagolysosomes, and lack of neuroectodermal differentiation. Diagnostic morphologic pitfalls for an incorrect diagnosis of neuroblastoma included nuclear molding (all aspirates), pseudorosette formation (one aspirate), and focal NSE positivity (3/3 aspirates). None of the tumors showed anaplasia on histologic examination. Cytologic recognition of the triphasic cellular components of WT (blastemal cells, spindle cells, and epithelial cells) can be helpful for a correct diagnosis; however, in 5/8 aspirates in this study, only the blastemal component was present. In these cases, immunocytochemical stains and electron microscopy proved useful in arriving at a correct FNAB diagnosis of WT. However, NSE positivity can be a pitfall for a diagnosis of neuroblastoma if the radiologic, clinical, and other cytologic features are not clearly delineated. Presence of cytokeratin and vimentin positivity would be helpful in the diagnosis of WT in such instances. Diagn Cytopathol 1996; 14:101–107. © 1996 Wiley-Liss, Inc.     

Sclerosing papillary lesion of the breast: a diagnostic pitfall for malignancy in fine needle aspiration biopsy

Papillary neoplasms of breast constitute a group of lesions that show broad spectrum of morphological changes, ranging from benign to malignant and posing challenges at all diagnostic levels. Some benign papillary lesions may form well-defined solid masses with a dominant sclerosed architecture, known as complex sclerosing papillary lesion or simply sclerosing papilloma. The purpose of this study is to apply the previously published criteria for papillary lesions and to identify the cytomorphologic findings that lead to false-positive diagnosis of these cases. We reviewed the fine needle aspiration biopsies (FNAB) of six histologically proven sclerosing papilloma that were called suspicious or malignant on FNAB. The patient age ranged from 40 to 69, with a mean of (43 +/- 6) yr. Three patients presented with a palpable lump and two patients had history of fibrocystic disease. All six patients had abnormal screening mammograms. FNAB was performed using a 23-gauge syringe attached to a commercial holder. FNA smears were markedly hypercellular with large number of epithelial fragments and papillary clusters, discohesive single cells that are hyperchromatic with mild to moderate nuclear pleomorphism. Bipolar cells were present in all cases, varying from low to abundant. Intraoperative consultation was requested on four cases. Touch preparations were made on two cases and were reported as suspicious based on the cellularity and nuclear atypia. All surgically excised specimens showed sclerosing complex papillary proliferative lesions with epithelial hyperplasia. In conclusion, FNA cytology of this proliferative lesions may be highly cellular and may display cellular atypia similar to breast carcinoma and thus leads to false-positive interpretation.     

Fine needle aspiration cytology of nodular fasciitis of the breast

We report a case of nodular fasciitis (NF) of the breast, which was cytologically diagnosed as a spindle cell proliferation with undetermined malignant potential. Owing to small size of the lesion (5.9 × 3.7 × 4.1 mm), only fine needle aspiration (FNA) cytology was performed under ultrasound guidance. The FNA smears were cellular, rich in single/clustered spindle cells but mammary ductal epithelial/myoepithelial cells were absent. These cytologic findings suggested spindle cell growth of mesenchymal origin. Pattern‐less arrangement of spindle cells, heterogeneous composition of the stromal matrix, lack of nuclear/cellular atypia, occasional mitosis but no aberrant mitotic figures, and lymphocyte infiltration indicated reactive rather than neoplastic nature of the lesion. Nonetheless, lumpectomy was conducted because the possibility of neoplasm was not completely ruled out. The histologic diagnosis of the resected nodule was NF. FNA specimens were reviewed thoroughly in an attempt to define the key cytomorphologic features of NF that are important for the correct diagnosis. Differential diagnoses from the lesions that show similar cytologic pictures are discussed in detail. Although NF arising from the breast is rare, cytopathologists should be aware of its clinical and cytopathologic characteristics. Knowledge of the possibility of NF in the breast and its cytologic findings may help cytopathologists to discern its reactive, not neoplastic, characteristics of the lesion. If the referring surgeon is alerted NF as a possibility along with other differential diagnoses, close observation would become a management option. In‐depth discussion of cytologic features and a review of the pertinent literature are also included. Diagn. Cytopathol. 2015;43:222–229. © 2014 Wiley Periodicals, Inc.     

Flache epitheliale Atypie

According to the WHO, flat epithelial atypia (FEA) is defined as a neoplastic epithelial proliferation of ductal type in either a single or in multiple terminal duct lobular unit(s) limited to the periphery of the ductules in a clinging growth pattern. The atypical cells may form between one and several layers of epithelial cells that show low grade cytologic atypia. FEA most often presents as mammographic microcalcifications, which are typically round (secretory type and psammomatous calcification in an eosinophilic matrix, so-called ossifying calcifications). Clinical relevance is dependent on whether the lesion appears in isolation or whether it is an excision biopsy or a minimally invasive biopsy. Currently available data suggest that the risk of subsequent breast carcinoma in the ipsilateral breast is very low following the diagnosis of FEA. The differential diagnosis should include atypical ductal hyperplasia, low-grade clinging ductal carcinoma in situ, blunt duct adenosis and apocrine metaplasia.     

Cytologic differential diagnosis of papillary pattern in breast aspirates: correlation with histology

Papillary neoplasms, fibroadenoma, fibrocystic change, low-grade ductal carcinoma, and apocrine carcinoma are among "gray zone" lesions in breast cytology. They often have cellular smears with a papillary or pseudopapillary pattern. To better define cytologic criteria useful in distinguishing these entities, we correlated them with histology. Papanicolaou and giemsa stained smears from 33 aspirates and their corresponding histology were reviewed. Of these, 28 had an initial cytologic diagnosis or suspicion of papillary neoplasm, while five cases were not diagnosed cytologically as papillary but the histologic diagnosis was a papillary neoplasm. Cytologic features evaluated included cellularity, architecture, apocrine/single/columnar cells, nuclear atypia, intranuclear inclusions, calcifications, background, myoepithelial cells, and bipolar, naked nuclei. Discriminating cytologic features grouped by final histologic diagnosis were as follows: Papillary neoplasm (14 cases): Hemorrhagic/cystic background, 3-dimensional papillary clusters, columnar cells, and fibrovascular cores. Myoepithelial cells within clusters and background naked, bipolar nuclei were inconspicuous. Fibroadenoma (4 cases): Two-dimensional branching clusters often with folding, moderate myoepithelial cells in clusters, moderate to numerous background bipolar nuclei, often forming doublets in smear background, cellular stroma. Ductal carcinoma (11 cases): Papillary ductal carcinoma in situ in 5 of 11 cases, cribriform/tubular architecture in 6 of 11. Absence or paucity of myoepithelial within clusters and background bipolar nuclei was noted. Fibrocystic change (4 cases): Two-dimensional clusters, moderate myoepithelial cells within clusters, and moderate bipolar nuclei in the background. The presence and quantity of myoepithelial cells, bipolar naked nuclei in the background, and ductal cell architecture were the only consistently useful cytologic features in distinguishing breast lesions with a papillary pattern. Ann Diagn Pathol 5:34-42, 2001.