Immunohistochemical analysis of morules in colonic neoplasms: morules are morphologically and qualitatively different from squamous metaplasia.

Morules develop in several neoplasms and have been considered as a type of squamous metaplasia despite the absence of keratinization and intercellular bridges. The objective of this study was to clarify the pathological significance of morules and to distinguish morules from squamous metaplasia in colonic neoplasms. Ten cases of morule-associated colonic neoplasms (4 adenocarcinomas, 1 adenoma with carcinoma in situ, and 5 adenomas), and 3 cases of squamous metaplasia in colonic adenocarcinoma were examined morphologically and immunohistochemically. Morules were well-defined structures composed of small, oval to short-spindled cells with bland nuclei, and frequently associated with intranuclear inclusions that were positive for biotin and biotin-binding enzymes (pyruvic acid carboxylase and propionyl CoA carboxylase). On immunohistochemical examination, morules characteristically showed nuclear overexpression of beta-catenin, cyclin D1 and p63, low Ki-67 labeling index (<1%), cytoplasmic overexpression of CD10, and no expression of cytokeratin 20. These molecules were useful for the differentiation of morules. Furthermore, p63 and 34betaE12 positivities in morules suggested that they have a basal/stem cell phenotype. Thus, morules were morphologically and qualitatively different from squamous metaplasia. We consider that morules in colonic neoplasms are cell clusters with a basal/stem cell phenotype, and have less proliferative and less invasive potential than other cancer cells.     

Histiocytoid breast carcinoma: an apocrine variant of lobular carcinoma

Two cases of in situ and invasive histiocytoid breast carcinoma are described. The invasive components of both tumours showed architectural and cytological similarities to lobular carcinoma. The in situ components showed areas of classical lobular carcinoma in situ, areas of lobular carcinoma with apocrine features and areas with transitional features. It is concluded that histiocytoid carcinoma represents an apocrine variant of lobular carcinoma. Differentiation of this tumour from chronic sclerosing inflammation may be difficult in both primary and secondary lesions.     

Cytological features of lung adenocarcinoma with micropapillary pattern in the pleural or pericardial effusion: analysis of 5 cases

Micropapillary pattern is a distinct histopathological pattern, and usually shows a high frequency of lymphatic invasion and lymph node metastases. This pattern is also reported in lung adenocarcinoma, however, only one cytological report of lung adenocarcinoma with micropapillary pattern has been reported. In this study, we analyzed the cytological features of this type of carcinoma in the pleural or pericardial effusion. This study was comprised of 5 consecutive cases of lung adenocarcinoma with micropapillary pattern, in which the tumor cells were present in the pleural or pericardial effusion and whose diagnoses were histopathologically confirmed. The characteristic cytological findings in the pleural or pericardial effusion were as follows: i) tightly cohesive small nests of tumor cells showing papillary structure without fibrovascular core, ii) these nests were comprised of approximately 5-20 tumor cells, iii) cauliflower-like and acinar-like structures were also observed, iv) intracytoplasmic vacuoles were observed in 40% of the cases, and v) the neoplastic cells had large round to oval nuclei containing coarse chromatin and occasional conspicuous nucleoli. It has been reported that the presence of micropapillary structure and intracytoplasmic vacuolation are also characteristic cytological features of micropapillary carcinoma of the urinary bladder, therefore, they are thought to be common cytological features of carcinomas with micropapillary pattern. Consequently, detection of these features can lead to a cytodiagnosis of lung adenocarcinoma with micropapillary pattern in the pleural or pericardial effusion. Recognition of these features is important because this type of tumor shows an aggressive clinical course.     

Mixed tumours of the skin: a histopathological, enzyme-histochemical and immunohistochemical study

Twenty-eight cases of mixed tumour of the skin were studied and subclassified into three types: eccrine (1 case), indeterminate (7), and apocrine type (20). The indeterminate type was defined as mixed tumours having tubulo-alveolar patterns with two layers of epithelium, but without apocrine secretion or pilosebaceous differentiation. Enzyme-histochemical studies were performed on four cases (one indeterminate, three apocrine): in the indeterminate type the tubular epithelial cells showed eccrine differentiation while in the apocrine type tubules were found showing the direction of differentiation to be toward the apocrine gland, but tubules with eccrine differentiation were intermingled in all three. Immunohistochemically, no differences were observed between the indeterminate and the apocrine type: hints of eccrine features were observed in both groups. Thus, the indeterminate type could be an eccrine tumour and the apocrine type showed direction of differentiation toward both eccrine and apocrine glands. It is concluded that mixed tumours of the skin are fundamentally eccrine neoplasmas, and that the apocrine features may represent apocrine metaplasia.     

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.     

Morule with biotin-containing intranuclear inclusions in thyroid carcinoma

One thousand and sixty cases of thyroid carcinoma were reviewed to compare morules with squamous metaplasia clinicopathologically and immunohistochemically. Morules and squamous metaplasia were found in five (0.47%) and 32 cases (3.0%) respectively. The five patients with morules were all female (age 20–36 years) including four with papillary carcinoma and one with follicular carcinoma. The 32 patients with squamous metaplasia consisted of 30 females and 2 males (age 14–78 years), all of whom had papillary carcinoma except for one follicular carcinoma. The morules demonstrated characteristic 'optically clear nuclei' (OCN), which ultrastructurally showed filamentous structures in the nuclei. The OCN were immunohistochemically demonstrated to contain intranuclear biotin. Furthermore, the morule often accompanied with the OCN was positive for Ulex Europaeus agglutinin I (UEA-I) but negative for bovine muzzle epidermal keratin (EK). On the contrary, squamous metaplasia unaccompanied with the OCN was negative for UEA-I, but positive for EK. Follow-up information revealed that one of the five patients with morules had died of the disease, one was alive with pulmonary metastasis, and three were disease-free. Eight of 32 patients with squamous metaplasia had died of the disease; of the others who were alive, four patients have had recurrence.     

Apocrine adenosis: a precursor of aggressive breast cancer?

AIM--To investigate overexpression of c-erbB2, expression of the p53 protein product and proliferation rates in benign breast lesions with specific reference to apocrine adenosis. METHODS--Twenty one cases of apocrine adenosis were stained with monoclonal antibodies to p185, the protein product of the c-erbB2 oncogene, the protein product of the p53 tumour suppressor gene and to the cell cycle related protein Ki67. Three cases were associated with concomitant ductal carcinoma in situ of large cell type and two were associated with invasive tubular or cribriform carcinoma. RESULTS--Twelve (57.1%) cases showed membrane staining for c-erbB2 oncoprotein of apocrine cells within sclerosing adenosis and six (28.6%) had occasional p53 protein positive cells. One case not associated with carcinoma showed extensive staining of apocrine metaplasia outside the area of apocrine adenosis. The proliferation rate, as measured by Ki67 staining, was increased in some of the lesions and all lesions showed at least some of the cells to be in the cell cycle. CONCLUSIONS--The expression of abnormal oncogene products and increased proliferation in some of these apocrine lesions questions the supposed degenerative nature of the atypia seen in such cases and suggests that there may be an association between these lesions and large cell ductal carcinoma in situ and hence invasive carcinoma.     

Histiocytoid breast carcinoma: an enigmatic lobular entity

Histiocytoid breast carcinoma is an uncommon entity that is mostly regarded as a variant of lobular carcinoma. Its occurrence with apocrine lobular carcinoma in situ and consistent expression of gross cystic disease fluid protein 15 suggest apocrine differentiation. Its recognition is often challenging, particularly when histiocytoid tumour cells occur in a metastatic site before the primary diagnosis of breast carcinoma, or in limited core biopsy or cytology material. In the breast, its bland histological appearances can lead to a benign diagnosis. Clues to the correct conclusion include finding tumour cells with more cytological atypia, the presence of cytoplasmic vacuoles and secretions, coexistence with more traditional invasive lobular carcinoma patterns and/or lobular neoplasia, and the use of immuohistochemistry to confirm their epithelial nature. Close clinicoradiological correlation and awareness of histological mimics are needed to achieve an accurate diagnosis of this enigmatic condition that should be appropriately subsumed within the invasive lobular histological subtype.     

Sclerosing polycystic adenosis of the parotid gland: Report of one case diagnosed by fine‐needle cytology with in situ malignant transformation

Sclerosing polycystic adenosis (SPA) is a rare pathological condition affecting the salivary glands, first described by Smith etal. in 1996. Even though this lesion is being increasingly diagnosed, less than 50 cases have been published in the world literature to date. In line with numerous other pathological analogies between breast and salivary gland lesions, SPA shares with fibrocystic disease of the breast many histopathological features, i.e., fibrosis, oncocytic (apocrine) changes, hyperplasia of ductal and acinar epithelium, cystic dilation of ducts, and, often, atypical epithelial changes. Most of the described cases have followed a benign clinical course, despite the frequent possibility of atypical hyperplasia in more than 50% of the cases and of the more than occasional in situ malignant transformation. In this article, we introduce a new case occurring in the parotid gland of a 57‐year‐old male showing atypical epithelial hyperplasia and low‐grade in situ mucoepidermoid carcinoma. Fine‐needle cytology (FNC) was performed on the lesion and, when a diagnosis of SPA was prospected, the variegated cytological features of the obtained sample posed several differential diagnostic problems. The spectrum of pathological lesions entering differential diagnosis comprised sebaceous adenoma, Warthin's tumors with presence of sebaceous remnants, and low‐grade mucoepidermoid carcinoma. Histopathological examination disclosed SCA with intraductal neoplastic transformation resembling noninvasive low‐grade mucoepidermoid carcinoma. The cytological diagnosis of SPA should be entertained whenever a polymorphous picture is found on FNC samples comprising oncocytic/apocrine changes, sebaceous cells, cystic background, and epithelial hyperplasia with low‐grade cytological atypias. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Micropapillary variant of urothelial carcinoma of the urinary bladder; a clinicopathological and immunohistochemical study

AIMS: To investigate whether prognosis in micropapillary urothelial carcinoma is related to the proportion of the micropapillary component (MPC), and to identify the immunohistochemical features of MPC. METHODS AND RESULTS: This study presents a clinicopathological analysis of 20 patients with micropapillary urothelial carcinoma of the bladder with cystectomy specimens for evaluation. Tumours were stratified on the extent of MPC: focal, <10%; moderate, 10-50%; extensive, >50%; and this was correlated with tumour stage and prognosis. Sixteen males and four females were aged 56-81 years (mean 69 years). All cases had high-grade morphology in the micropapillary carcinoma and typical urothelial carcinoma. All cases with extensive MPC (n = 4) were of a high pathological stage (pT3 or pT4) and died of disease (DOD) or other causes. Eighty percent with moderate MPC (eight of 10 cases) were pT3 or pT4 and 50% DOD or are alive with disease. Eighty-four percent with focal MPC (five of six cases) were pT1 or pTa. In high-stage cases, the most invasive component was MPC. High-stage cases had an 85% risk of being advanced at presentation with micropapillary carcinoma. All pT2 or lower stage cases had micropapillary carcinoma on prior transurethral resections of bladder tumour (TURB). High-stage carcinomas had 30% and 54%, respectively, of surface MPC and urothelial carcinoma in situ, in comparison with 85% and 28% in lower stage carcinomas. Immunohistochemical staining was similarly positive in MPC and typical urothelial carcinoma with cytokeratin (CK)7, CK20, epithelial membrane antigen, carcinoembryonic antigen and cytokeratin 34betaE12. CA125 staining was seen only in MPC in 43% of cases. CONCLUSIONS: Micropapillary urothelial carcinoma is a high-grade carcinoma in which the prognosis is related to the proportion and location of the MPC. Cases with moderate or extensive MPC are at high risk of being advanced at presentation. Cases with <10% MPC and surface MPC have a high chance of detection at an early stage. The morphology and immunohistochemical profile of the MPC suggest that it is a form of glandular differentiation in urothelial carcinoma.     

Fine-needle aspiration biopsy of invasive micropapillary carcinoma of the breast: a report of five cases

Invasive micropapillary carcinoma of the breast is an uncommon variant of infiltrating ductal carcinoma. Observing its distinctive cytologic appearance and aggressive behavior is important for early diagnosis by fine-needle aspiration cytology (FNAC). There are only a few reported cases in the literature. Five women presented with breast masses. FNAC showed malignant epithelial tumors, and mastectomy materials showed invasive micropapillary carcinoma for all of them. Three patients had axillary lymph node metastases. Invasive micropapillary carcinoma, with its angulated papillary clusters lacking a fibrovascular core, and irregular crowded nuclei, has a distinctive cytologic appearance which correlates with its histological features. A differential diagnosis from other primary or metastatic papillary lesions of the breast may be possible using immunohistochemistry and some cytologic features. The limited experience with invasive micropapillary carcinoma should not discourage others from undertaking further studies.     

Carcinoma ex pleomorphic adenoma (CXPA): immunoprofile of the cells involved in carcinomatous progression

AIMS: To characterize the cellular component in pleomorphic adenoma (PA) that undergoes malignant transformation in carcinoma ex pleomorphic adenoma (CXPA). METHODS AND RESULTS: A panel of antibodies against cytoskeletal proteins was applied in 16 cases of CXPA: intracapsular carcinoma (five cases), minimally invasive (four cases) and frankly invasive (seven cases). The CXPAs were classified into two main groups according to their predominant cellular component as detected by the panel of antibodies: (i) carcinomas with only epithelial differentiation (75% of the cases), and (ii) carcinomas with a myoepithelial component (25%). CXPA with only epithelial differentiation showed two types of malignant areas in the part of the tumour that was confined by the PA capsule: (i) intraductal carcinoma areas characterized by ductal structures containing both benign myoepithelial cells positive for alpha-smooth muscle actin (alpha-SMA), vimentin and cytokeratin (CK)14 and proliferating atypical luminal cells reactive for CK7, CK8 and CK19, and (ii) carcinoma areas composed only of epithelial cells reactive for CK7, CK8 and CK19. In the latter, the cells presented morphological and immunohistochemical characteristics similar to those found in areas of invasive carcinoma outside the PA capsule. CXPAs with a myoepithelial component were composed mainly or exclusively of cells that expressed vimentin and alpha-SMA. In this group, ductal structures reminiscent of PA filled by malignant cells were not identified. CONCLUSION: Most CXPAs consist only of epithelial cells that have an immunoprofile comparable to ductal luminal cells of PA. These malignant luminal cells arise in the duct-like structures as intraductal carcinoma and probably only at this early stage of development should the lesion be considered as a non-invasive carcinoma.     

Metaplastic breast carcinoma on fine-needle cytology samples: a report of three cases

Metaplastic breast carcinoma (MBC) may have a varied presentation on fine-needle cytology samples. We herewith describe three cases of MBC found in our series. One of these cases showed a peculiar mixture of malignant ductal, apocrine type, and squamous epithelial cells with fascicles of spindle cells with variable degree of atypia and was diagnosed as metaplastic carcinoma of the carcino-sarcomatous type. The other two lesions were characterized by an abundant chondroid extracellular matrix to which were variably admixed carcinomatous and chondroid-type cells, with variable degree of atypia. Both these latter cases were defined as matrix-producing metaplastic carcinomas. Because of the various presentation of MBC on fine-needle cytology samples and the possible influence of needle "sampling" on the cytological specimen, the spectrum of differential diagnoses to be considered may encompass a number of benign and malignant entities, like keratinous subareolar cysts, malignant fibroepithelial lesions with myxo-chondroid stroma, and true sarcomas of the breast, with cartilaginous metaplasia. It is the Authors' feeling that, with optimal samples, the cytomorphological findings of this rare variant of breast carcinoma permit its accurate pre-operative diagnosis.     

Pancreatic mucinous lesions: a retrospective analysis with cytohistological correlation

The diagnosis of mucinous pancreatic lesions, which include mucinous noncystic adenocarcinoma, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), and mucinous metaplasia, is critical, given different clinical management and prognosis. This retrospective study is done to assess the cytological features and pitfalls associated with these entities in cytological samples.A search for pancreatic cytology specimens with histological confirmation of the various pancreatic mucinous lesions was done from 1988 to 2005: 9 mucinous adenocarcinoma, 14 IPMN, 11 MCN, and 3 mucinous metaplasia. The majority (35/37) had been endoscopic ultrasound-guided fine-needle aspirations. The cellularity, background extracellular mucin, epithelial architecture, mucinous nature of the epithelium, cell shape, and nuclear features were evaluated on the cytology material. Of the 22 cytological features evaluated, the presence of three-dimensional clusters, micropapillary structures, and nuclear atypia, which includes nuclear crowding, increased N/C ratio, anisonucleosis, nuclear membrane contour irregularity, clumpy chromatin, and prominent nucleoli, was found to be consistently associated with mucinous adenocarcinoma. There were no statistically significant cytological features, which helped in differentiating IPMN, MCN, and mucinous metaplasia. There was a relatively high false-positive rate in the IPMN group (5/14, 36%). Review of the histological specimen showed severe dysplastic epithelial change in these cases. One false-positive case of mucinous metaplasia (1/3, 33%) showed marked intraepithelial acute inflammation.The cytological diagnosis of mucinous pancreatic lesions remains challenging, except for mucinous noncystic adenocarcinoma. The findings were largely nonspecific in the differentiation between IPMN, MCN, mucinous metaplasia, and incidentally sampled gastrointestinal epithelium. False-positive diagnosis of adenocarcinoma occurs not infrequently in the setting of IPMN with severe dysplastic epithelial change and in lesions with associated acute inflammation, and can be a pitfall in the diagnosis of these lesions.     

Well-differentiated thymic carcinoma: a clinico-pathological study

Summary Well-differentiated thymic carcinoma (WDTC) is a recently described epithelial tumour of the thymus previously classified as cortical or predominantly epithelial thymoma. The authors have reviewed a series of 15 cases of WDTC with the aim of further defining the clinicopathological features of this neoplasm. Histologically, the number of lymphocytes was always low; perivascular spaces and epithelial palisading around blood vessels and/or along fibrous septa were prominent features; 6 cases (40%) were associated with areas of typical cortical thymoma. All cases showed slight to moderate cytological atypia and nuclear grooving was frequently detected. Mitotic activity was variable but usually low. Clinically, all but 3 cases (80%) were invasive at surgery; myasthenia gravis was present in 9 cases (60%); 5 patients (33.3%) died due to disease and 2 additional patients (13.3%) had tumor recurrence. Our study indicates that WDTC has fairly distinctive clinicopathological features and that it is histologically and histogenetically related to cortical thymoma. The definition “well-differentiated carcinoma” is justified because of low-grade cytological atypia and retention of some organotypical histological features, in a tumour otherwise often displaying aggressive and sometimes clear-cut malignant clinical behaviour.     

Expression of androgen receptors and inhibin/activin alpha and betaA subunits in breast apocrine lesions

The importance of androgens and their receptors inhibin and activin remains unknown for mammary epithelial cells. We investigated the role of these hormones in breast apocrine lesions (BAL) using immunohistochemistry to study androgen receptors (AR) and the inhibin/activin alpha and betaA subunits. Forty-two cases of BAL were evaluated, including 22 cases of fibrocystic disease (FCD) showing prominent apocrine changes, 10 intraductal papillomas with extensive apocrine metaplasia, 5 cases of apocrine carcinoma in situ (CIS), and 5 cases of apocrine carcinoma. Fifty non-apocrine lesions were included as controls: 20 cases of FCD, 5 cases of DCIS, and 25 cases of invasive ductal carcinoma. AR was more frequently expressed in BAL than in non-apocrine lesions (p=0.001). AR expression was not related to tumor progression. AR showed a significant positive correlation with betaA subunits (r=0.832, p<0.001), and an inverse correlation with alpha subunits (r=-0.233). The alpha and betaA subunits demonstrated a significant inverse correlation with each other (r=-0.271, p=0.0048). As the expression of the alpha and betaA subunits reflects inhibin and activin A, respectively, AR and activin A may be implicated in apocrine morphogenesis, but not in tumor progression.     

Morules in cribriform-morular variant of papillary thyroid carcinoma: Immunohistochemical characteristics and distinction from squamous metaplasia

Morules are a diagnostic clue to the cribriform-morular variant (C-MV) of papillary thyroid carcinoma, and are superficially similar to squamous metaplasia. In order to clarify the histogenesis of morules and differentiate them from squamous metaplasia, we immunohistochemically compared the morules in five cases of C-MV with squamous metaplasia in six cases of diffuse sclerosing variant (DSV) of papillary thyroid carcinoma. The squamous metaplastic cells were immunopositive for low- and high-molecular-weight cytokeratin, whereas the morular cells were negative or focally positive. Vimentin-positive cells were observed focally in the morules and squamous metaplasia, except for one case of CMV that showed intense positivity. The morular cells showed weak cytoplasmic positivity for beta-catenin, and the cell membrane was not highlighted. Some nuclei of the morular cells were also positive for this antibody. Beta-catenin was intensively positive along the cell membrane of the metaplastic cells, and did not react against the nuclei or cytoplasm. Bcl-2 was positive in the morular cells, but negative in the metaplastic cells. S-100 protein-positive dendritic cells were observed in the metaplastic nests, but not in the morules. We argue that morules appear in connection with nuclear and cytoplasmic aberrant localization of beta-catenin, and are not an early form of squamous metaplasia.     

Cytophotometric analysis of nuclear DNA-content in so-called obliterating mastopathy with epithelial hyperproliferation

INTRODUCTION: Histogenesis, microscopic appearance, and clinical significance of so-called "obliterating mastopathy with epithelial hyperproliferation" are described. This focal lesion, which was recently re-evaluated by Hamperl (1975), may simulate scirrhous carcinoma in X-ray mammography. In histologic specimens similarities to special types of tubular carcinomas may cause problems in differential diagnosis. In order to gain a better insight into their behavior, cytophotometric DNA-analysis was applied to 10 selected cases. MATERIALS AND METHODS: DNA-determination was performed on Feulgen stained sections by means of a Leitz microspectrophotometer MPV 1. The plug technique was used after careful focussing of cell nuclei. Intraductal and extraductal epithelial proliferations have been analyzed in separate series. RESULTS: In four series of extraductal pseudoinfiltration and in six series of intraductal hyperproliferation, normoploid DNA-patterns were found. One series of apocrine metaplasia and one of atypical intraductal proliferation were read as borderline cases, but one case of atypical apocrine metaplasia revealed an aneuploid DNA-pattern, thus indicating the malignant nature of the lesions. DISCUSSION: "Obliterating mastopathy with epithelial hyperproliferation" is regarded a high risk disease which may progress to invasive carcinoma. According to the gross morphologic appearance of the focal lesions, the term "pseudoscirrhus" is proposed. Therapeutic approach depends mainly on the degree of epithelial hyperproliferation and cellular atypia. Focal lesions should be removed by wide excision, whereas in cases of multicentric development, subcutaneous mastectomy and plastic augmentation is recommended.     

Fine‐needle aspiration of gray zone lesions of the breast: Fibroadenoma versus ductal carcinoma

While breast lesions have characteristic cytological features, some lesions, particularly adenocarcinoma and fibroadenoma, may present with overlapping features causing erroneous diagnoses. The current study aimed to define significant cytomorphologic features predictive of fibroadenoma and adenocarcinoma, respectively. Further, we intended to evaluate the predictive characteristics for differentiation between gray zone lesions and to identify root causes contributing to misdiagnoses. First, direct smears prepared from 14 histology‐confirmed fibroadenomas and 14 adenocarcinomas were reviewed and characteristics of commonly encountered morphologic features were assessed. We then retrospectively and blindly reviewed nine cytohistologic discrepant cases using the significant characteristic as a guideline, in order to assess whether these discrepant cases could be correctly categorized. Morphologic characteristics predictive of fibroadenoma included moderate cellularity, large, folded cellular sheets/aggregates, staghorn projections, smooth and round borders, monolayers, honeycomb arrangement, smaller nuclear size, and background bipolar cells. Predictive characteristics of adenocarcinoma included high cellularity, loose cohesive sheets/aggregates, pointed projections, irregular borders, larger nuclear size, irregular nuclear membrane, prominent nucleoli, and single atypical epithelial cells. Retrospective, blind review correctly re‐classified seven out of nine cytohistologic discrepant cases, including five false negative cases and two false positive cases. Root causes contributing to the misdiagnoses were large branching sheets of carcinoma mimicking folded sheets of fibroadenoma; fibroblasts mimicking myoepithelial cells; apocrine cells mimicking carcinoma cells; and not recognizing the loose myxoid matrix presenting as soap bubbles in fibroadenoma. In conclusion, this study identified significant characteristics that can assist in achieving accurate diagnosis in a subpopulation of breast aspirates that present with overlapping features. Diagn. Cytopathol. 2013;41:806–811. © 2012 Wiley Periodicals, Inc.