Ductal adenoma of the breast--a review of fifteen cases

The term ductal adenoma has been recently introduced to describe a solid benign lesion of breast ducts. This study describes the clinical, morphologic, and immunohistochemical features of 15 cases of ductal adenoma. Ductal adenomas are usually single, occasionally multiple, lesions occupying medium- and large-sized breast ducts. They may occur in women of all ages, although the majority of patients are 60 years of age or greater. Ductal adenomas usually present clinically as breast lumps which may mimic carcinoma; less commonly, they are associated with nipple discharge. Patients in this series showed no family or previous history of breast disease and had uneventful follow-up after local excision. Despite often showing worrying pseudoinfiltration and cytologic atypia, the immunohistochemical demonstration of a myoepithelial layer and intact basement membrane around the tubules was clear evidence of the benign nature of the lesions. We conclude that most ductal adenomas evolve by sclerosis of benign intraduct papillary lesions, although processes similar to sclerosing adenosis and, possibly, duct ectasia may contribute to the pathogenesis of a proportion of cases. It is hoped that a wider appreciation of the entity of ductal adenoma will reduce the diagnostic uncertainty that continues to surround these and related lesions.     

Fine-needle aspiration of the breast: A review of 1,995 cases with emphasis on diagnostic pitfalls

Between 1985 to 1989, 1, 95 fine-needle aspirations of palpable breast lesions were performed at our institution. In all cases, the aspirates were procured by cytopathologists using 22- or 23-gauge needles. Direct smears were immediately stained with Diff-Quik and Papanicolaou and assessed for specimen adequacy (criteria as followed in this institution). Tissue follow-up was available in 1,117 cases. The cytologic diagnoses rendered in these cases were: malignant, 690 cases (60.2%); suspicious for carcinoma, 49 cases (4.3%); benign, 343 cases (29.9%), and insufficient specimen, 35 cases (3.1%). There were 28 false-negative and 2 false-positive results. Considering only cases definitively diagnosed as benign or malignant, the sensitivity was 96%, specificity 99%, positive predictive value 99%, negative predictive value 94%, and overall efficiency 97%. Of those specimens considered suspicious, only 11 cases (22%) were proved not to be malignant after excisional biopsy. These were three fibroadenomas, three ductal hyperplasias, two adenosis tumors, two mucocele-like lesions, and one nipple adenoma. The two lesions that resulted in true false-positive diagnoses were an apocrine cyst with atypia and sclerosing adenosis with radial scar. The clinical and cytologic features of the benign conditions that resulted in false suspicious and positive diagnoses and those features that distinguish them from carcinoma are presented.     

乳腺良恶性病变中CD10表达及意义

目的 探讨CD10免疫标记乳腺肌上皮细胞的可行性。方法 收集50例乳腺良恶性病变的石蜡包埋标本(腺瘤、纤维腺瘤、叶状肿瘤、纤维囊性病、导管内乳头状瘤、乳头腺瘤、导管内癌、小叶内癌、浸润性导管癌、浸润性小叶癌)，采用免疫组化(S-P法)检测CD10在上述病变中的表达。结果 在乳腺良性病变中，CD10阳性的肌上皮细胞连续地环绕在普通型增生的小导管的周围。但在囊性扩张或不典型上皮增生的导管周围，CD10阳性细胞不连续，甚至不见阳性细胞。导管原位癌的癌细胞巢外周的阳性细胞由完整到不完整，甚至完全缺失。在浸润性癌中癌巢周围不见阳性细胞，在早期浸润性癌中可见残存的阳性细胞。除少许癌细胞和肌纤维母细胞表达CD10外，其余癌细胞、肌纤维母细胞、血管平滑肌细胞和上皮细胞均不表达CD10。结论 CD10标记肌上皮细胞具有较高的敏感性和特异性，可以作为肌上皮细胞的有效标记物。     

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.     

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.     

Cellular composition of the nipple aspirate specimen of breast fluid. I. The benign cells.

A nipple aspirator device was used to obtain breast secretions for cytologic examination, as well as for viral and biochemical analysis. Examination of the first 1,456 specimens from 796 women revealed ductal epithelium in 54%. Ductal epithelial cells were often absent in specimens from normal women; however, 78.5% of women with benign breast disease on tissue biopsy had specimens containing ductal epithelium. Apocrine metaplastic cells were a further indication of the presence of breast disease, and were rarely found in specimens from asymptomatic women. Foam cells were often abundant in specimens from normal breasts, but were found in decreased numbers in specimens from women benign breast disease. Differences in the occurrence of ductal epithelial cells, apocrine metaplastic cells, and foam cells suggest an alteration in the rate of maturation of ductal epithelium in women with both benign and malignant breast disease. The finding of a relative abundance of cells in nipple aspirate specimens from women with breast disease and few or no cells in specimens from women with normal breasts is believed to be of great importance in the cytologic evaluation of nipple aspirate specimens.     

Atypical ductal hyperplasia and ductal carcinoma in situ of the breast associated with perineural invasion

Perineural invasion is a histologic feature usually diagnostic of invasion in malignancies. In the breast, however, it has been associated with benign lesions such as sclerosing adenosis (SA), complex sclerosing lesion/radial scar (CSL/RS), and ductal carcinoma in situ (DCIS). This article describes perineural invasion associated with atypical ductal hyperplasia (ADH), florid hyperplasia without atypia (FH), and DCIS. All cases with a diagnosis of perineural invasion were selected from a series of 10,000 breast consult cases. Invasive mammary carcinomas were excluded. Fourteen cases of perineural invasion were found and associated with the following diagnoses: ADH (5), DCIS (3), FH (5), and ductal adenoma (1). Nine cases developed in CSL/RS, 4 cases in SA, and 1 case in a previous biopsy site of ductal adenoma; lesions were all less than 3 mm. The glands involving nerves showed cytologic and architectural features of the adjacent ADH, DCIS, and FH. Immunostaining for protein gene product (PGP) 9.5 marked nerves, and smooth muscle actin antibody highlighted the myoepithelial cells around glands. Perineural invasion seen in association with DCIS and ADH, in a background of CSL/RS and SA, may pose difficulty in diagnosis, especially in small biopsy specimens. It should be assessed with care to avoid misinterpretation as invasive mammary carcinoma.     

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.     

Needle aspiration cytology of pancreatic cystic lesions

Forty-two histologically confirmed cases of pancreatic cystic lesions with cytologic evaluation by needle aspiration biopsy (NAB) were reviewed. There were 21 inflammatory pseudocysts (IPC), nine mucinous cystic neoplasms (MCN), six microcystic serous adenomas (MSA), one macrocystic serous adenoma, and five papillary solid and cystic neoplasms (PSCN). Correct cytodiagnosis was made in all cases of IPC and MCN. The contents of IPCs were characterized by turbid or blood-tinged fluid containing cellular debris, numerous foamy macrophages, and other inflammatory cells. There were few or no epithelial lining cells. The aspirates from MCNs showed gelatinous mucoid material containing mucus-secreting cells that were present singly, in clusters, or in sheets. Depending on the individual case, benign or malignant columnar cells, or an admixture of these cells, were present in a mucinous background. The preoperative needle aspirates of five MSAs were acellular. In one case of MSA and in one example of macrocystic serous adenoma, small monolayered sheets of benign cubic epithelial cells were seen in the needle aspirates. Similar cytologic findings were noted in the materials obtained by intraoperative NAB performed under direct vision of the aforementioned five MSAs. Difficulties were encountered in typing three PSCNs that yielded in NAB cells resembling those of an islet cell tumor. They were diagnosed as low-grade neoplasms (PSCN vs. islet cell tumor). In two other patients, a cytodiagnosis of PSCN was correctly made as the NAB revealed monomorphic tumor cells wrapping around small capillary blood vessels. Diagn. Cytopathol. 1997;17:177–182. © 1997 Wiley-Liss, Inc.     

Tubular carcinoma of the breast: Cytologic features in fine-needle aspirations and application of monoclonal anti-α-smooth muscle actin in diagnosis

Twenty fine-needle aspirations (FNAs) of histologically proven tubular carcinoma of the breast (TCB) were reviewed, and the staining distribution of α-smooth muscle actin (SMA) was evaluated to see if this improved FNA sensitivity. In 18 cases, the aspirates were cellular, consisting predominantly of epithelial cells arranged in cohesive tubular structures that appeared angular or twisted. Single epithelial cells were present in varying numbers in 14 cases (70%). Cribriform fragments corresponding to in situ ductal carcinoma were noted in 9 cases (45%). Individual, bare nuclei were present in seven cases (35%). The initial cytologic diagnoses were 10 carcinomas, eight suspicious for carcinoma, and two cases were misinterpreted as fibroadenoma. In 8 of 14 cases, the epithelial fragments stained negatively for SMA, whereas in six cases some fragments (<10%) stained positively. These findings were in contrast to a reticulated staining pattern noted in almost all of the epithelial fragments in nine fibroadenomas and three fibrocystic changes. Eighteen well-differentiated invasive ductal carcinomas stained negatively, whereas four had occasional positively staining fragments. We conclude that TCB displays distinct cytomorphologic features that can be recognized or at least suggested by FNA. Awareness of the cytologic characteristics—angulated tubular structures with or without single epithelial cells—coupled with mammographic/ultrasound findings, is necessary to avoid a misdiagnosis. Alpha-smooth muscle actin staining may help in selected cases. © 1994 Wiley-Liss, Inc.     

Expression of Sialyl-Tn in fine-needle aspirates from mammographically detected breast lesions: A marker of malignancy?

Malignant transformation is frequently associated with abnormal expression of cell surface carbohydrates. Sialyl-Tn (STn) is a core carbohydrate antigen of tumor-associated mucin formed by the premature 2-6 sialylation of N-acetylgalactosamine. In an attempt to verify whether this antigen is restricted to malignant cells, we studied 30 cases of fine-needle aspiration (FNA) cytology from mammographically detected breast lesions. The rationale for choosing this material was the acknowledged difficulty in diagnosing cytologically small breast lesions, especially epithelial intraductal proliferations. The cases were divided in benign lesions (two fibroadenomas and ten ductal hyperplasias) and malignant lesions (16 ductal carcinomas). Ten of sixteen malignant cases (62.5%) were positive for STn. Five of fourteen benign cases (35.7%) were also positive for STn (two fibroadenomas and three ductal hyperplasias). The most consistent positive results in benign lesions resulted from cases that displayed apocrine metaplasia, although positivity has also been observed in ductal cells without metaplasia. We did not find statistical significant differences among STn expression in benign and malignant breast lesions detected by FNA (P = 0.14). Thus, we conclude that STn is neither specific nor sensitive for detection of malignancy in FNA from mammographically detected breast lesions. Diagn. Cytopathol. 1998;18:325–329. © 1998 Wiley-Liss, Inc.     

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.     

Reactivity of a monoclonal antibody with tissues and tumors from the human breast. Immunohistochemical localization of a new antigen and clinicopathologic correlations.

The reactions of a monoclonal antibody to the MCF7 breast cancer cell line were immunohistochemically studied on a variety of breast tumors, primary and metastatic, on mammary epithelium and on nonneoplastic breast lesions. A high proportion of positive reactions was observed in ductal, lobular, and tubular carcinomas as well as in mammary Paget's disease. Mucinous, medullary, and papillary carcinomas showed a low incidence of reactivity. Carcinomas with metaplasia, carcinoids, and nonepithelial breast tumors were unreactive with the antibody. Positive immunostaining was documented also in nodal and extranodal metastatic lesions. The staining of nodal metastases was correlated with the positive reaction of the primary tumor. Reactivity was widely distributed in normal breast epithelial cells and in benign breast lesions. Staining of nonneoplastic mammary epithelial was associated with reactivity of adjacent neoplastic tissues. Staining differences between nonneoplastic and neoplastic mammary tissues were related to the intensity and cytologic distribution of the labeling. Heterogeneous reactivity of morphologically similar cells was documented in nonneoplastic and neoplastic breast epithelial cells as well as in nodal and extranodal breast carcinoma metastases. Immunohistologically detectable antigen was not correlated with prognostic factors such as histologic grade or nodal status. A retrospective study of T1NO cases failed to substantiate any prognostic value for the reactivity of primary breast tumors with this monoclonal antibody.     

Adenomyoepithelioma of the breast: a cytologic dilemma. Report of a case and review of the literature

Adenomyoepithelioma of the breast is a rare benign tumor made up of epithelial and myoepithelial cells. The cytologic features of this lesion are not well defined. This report describes the cytologic features of a case of adenomyoepthelioma characterized by hypercellularity and the presence of many atypical epithelial cells, leading to the erroneous diagnosis of adenocarcinoma. Review of the cytology literature shows that this condition frequently mimics the cytologic features of a number of benign and malignant breast lesions, thus representing not only an important potential pitfall in the diagnosis of carcinoma but also a differential diagnosis to consider in a variety of breast lesions.     

Perineural and intraneural involvement in ductal carcinoma in-situ of breast: Case report

Invasion of peripheral nerves by epithelial cells has been traditionally regarded as a feature diagnostic of malignancy, its presence therefore being often sought to document a diagnosis of carcinoma, particularly in the breast. Perineural involvement (PNI) by benign breast disease is not often seen and the etiology is uncertain. The first reported case of nerve invasion in a benign breast lesion was by Ackerman in 1957. Subsequent reports have further confirmed this finding in the breast. The most challenging observation is when the glands involving nerves show cytologic and architectural features of the adjacent atypical duct hyperplasia (ADH) or ductal carcinoma in situ (DCIS). Here, we describe a case of ductal carcinoma in situ grade 2 with nerve involvement in a lumpectomy specimen in a 59-year-old woman. To the best of our knowledge, only five cases of atypical duct hyperplasia by Gobbi et al. and four cases of ductal carcinoma in situ, 3 by Gobi et al. and 1 by Tsang and Chan, associated with nerve involvement, have been reported in English medical literature. Two layers of epithelial cells with the immunohistochemical demonstration of the preservation of a continuous myoepithelial layer in the mammary ducts within the nearby small nerves, is the main clue to confirm the in-situ nature of the inclusions. It is necessary to be aware of this phenomenon in breast lesions to avoid over-diagnosis and inappropriate surgery.     

Ductal epithelial proliferations of the breast: a biological continuum? Comparative genomic hybridization and high‐molecular‐weight cytokeratin expression patterns

According to current concepts, benign proliferative breast disease (BPBD) is a direct precursor of breast cancer, in a spectrum ranging from ductal hyperplasia to overtly invasive carcinoma. In this study, comparative genomic hybridization (CGH) was used to screen ductal hyperplasia and other BPBD lesions and ductal carcinoma in situ (DCIS) for common genomic abnormalities, to test the relationship between these hyperplastic and neoplastic lesions. Immunohistochemistry for cytokeratin 5/6 was used as a diagnostic adjunct to distinguish ductal hyperplasia from DCIS. A total of 42 cases of BPBD comprising ductal hyperplasia of the usual type (n=14), papilloma (n=22), tubular adenoma (n=3), and adenosis (n=3), as well as 52 cases of DCIS, were studied. All cases of BPBD consistently displayed the presence of a subpopulation of cytokeratin 5/6-expressing basal-type cells within the proliferative lesion, whereas all of the non-high-grade and most of the high-grade DCIS lesions lacked cytokeratin 5/6-positive cells. Whereas gross genomic alterations, as determined by CGH, were undetectable in BPBD, distinct genetic changes characterized all cases of DCIS, with one exception. These results confirm the usefulness of cytokeratin 5/6 immunohistology in the diagnosis of BPBD and neoplastic breast lesions and support the view that BPBD and DCIS are not closely related entities and that BPBD is not an obligate direct precursor of DCIS.     

Diagnostic Value of Silver-Stained Interphasic Nucleolar Organizer Regions in Breast Tumors

Seventy-six specimens of normal breast tissue and benign and malignant breast lesions were studied to assess the mean area occupied by silver-stained proteins of the nucleolar organizer regions (MNORA) of the nucleolus. The assessment was performed with a computer-assisted image analyzer. The results indicate that only 30% of malignant lesions have a MNORA value greater than that of normal breast tissue or benign lesions. On the other hand, MNORA values of ductal carcinoma in situ were significantly greater than those of epitheliosis (papillomatosis). MNORA values were also significantly different in grade I and grade III invasive ductal carcinomas, the latter exhibiting the highest MNORA values of all the cases observed. Evaluation of MNORA values may therefore help in differentiating benign epithelial proliferations from ductal carcinomas in situ. Furthermore, because there is evidence that MNORA values are indicative of the cell duplication rate, MNORA values may ultimately be considered an objective prognostic parameter in addition to grading for invasive ductal carcinomas.     

Columnar lesions: a frequent diagnosis in breast pathology!

Lesions characterized by the presence of columnar epithelial cells lining the terminal duct lobular units (TDLUs) of the breast are being encountered with increasing frequency in breast biopsies performed because of the presence of mammographic microcalcifications. Those lesions in the large majority of the cases are benign. They should be classified into two categories: columnar cell change or columnar cell hyperplasia. Their specific immunophenotype (ER and PR +, Bc12 +) distinguish them from apocrine lesions. Some of them present in addition, cytologic atypia or architectural atypia. When architectural atypia is associated, a careful search for atypical ductal hyperplasia or for low grade DCIS needs to be performed, especially on vacuum assisted macrobiopsies for an appropriate management of the patient.     

Inconclusive or erroneous fine‐needle aspirates of breast with adequate and representative material: A cytologic/histologic study

Adequately cellular and representative fine‐needle aspirates (FNAs) of breast have a high diagnostic accuracy. There is, however, a recognized category designated as “gray zone” where a definitive diagnosis cannot be reached. We reviewed our experience in this category to identify useful diagnostic parameters. Twenty‐four such FNAs with surgical follow‐up were retrieved from AUBMC files (2003–2009). Cytology slides were reviewed blindly. All cases were females, 29–73 years. There were three erroneous and 21 inconclusive diagnoses. The majority (15) was invasive adenocarcinomas: two cribriform, four tubular, one lobular, and eight not otherwise specified. The remaining cases were papillary and fibroepithelial tumors (three each), ductal carcinoma in situ, cribriform (two), and one adenomyoepithelioma (AME). Useful diagnostic features included: (1) Biphasic cell population with focal nuclear atypia and intranuclear and cytoplasmic vacuolar inclusions (AME). (2) Complex clusters of epithelial cells with cribriform architecture (cribriform carcinoma). (3) Rigid tubular epithelial structures with abrupt change in diameter, ending in pointed tips with abnormal branching (tubular carcinoma). (4) Cellular stromal fragments (fibroepithelial tumors). (5) Papillary fibrovascular cores, columnar cells, and three‐dimensional papillary epithelial fragments (papillary tumors). Myoepithelial cells classically described in benign aspirates were not always a discriminatory factor. The “gray zone” in breast FNA is usually due to overlapping cytologic features of some benign and malignant lesions. Useful distinguishing cytologic features are described. Diagn. Cytopathol 2014;42:405–415. © 2013 Wiley Periodicals, Inc.     

Flat epithelial atypia of the breast

Flat epithelial atypia is a presumably neoplastic alteration of terminal duct-lobular units that is characterized by the replacement of the native luminal epithelium by ductal cells demonstrating low-grade cytologic atypia. The atypical cells maintain a "flat" pattern of growth without evidence of architectural atypicality. Morphologic, immunohistochemical, and molecular investigations support that flat epithelial atypia represents an early step in the evolution of low-grade ductal carcinomas. It is frequently seen in association with atypical ductal hyperplasia, low-grade ductal carcinoma in situ, invasive tubular carcinoma, and lobular neoplasia. The risk for subsequent breast carcinoma remains to be defined, but flat epithelial atypia likely represents a nonobligate precursor with an extended time course to progression. Certain benign alterations may superficially mimic its appearance; careful attention to cytologic and architectural characteristics can help one distinguish these unrelated entities from flat epithelial atypia.