Intraductal tubulopapillary neoplasm of the pancreas on fine needle aspiration: Case Report with Differential Diagnosis

Intraductal tubulopapillary neoplasm (ITPN) is a rare primary pancreatic neoplasm accounting for less than 1% of all pancreatic exocrine neoplasms and 3% of intraductal neoplasms of the pancreas. Data on this entity are still limited. Here, we report a case of ITPN with cytopathologic and histopathologic findings. A 41‐year‐old woman with a 2.2 cm cyst in the head of the pancreas for five years was referred to our institution. The endoscopic ultrasound‐guided fine‐needle aspiration produced cytospins were moderately cellular with a few fragments of markedly atypical epithelium. The neoplastic cells displayed high‐grade nuclear atypia with enlarged, eccentric nuclei, anisonucleosis and prominent nucleoli, irregular nuclear membranes, high nucleus to cytoplasmic (N/C) ratios, and a moderate amount of cytoplasm with no intracytoplasmic mucin. Histologically, the lesion was found to be an ITPN with focal high‐grade dysplasia. No invasive carcinoma was identified. The neoplastic cells exhibited luminal immunolabeling for MUC‐1, but were negative for MUC‐2, trypsin, chymotrypsin, and P53. Approximately 5% of the neoplastic cells showed Ki‐67 immunoreactivity. ITPN of pancreas may be a source of markedly atypical epithelial cells in pancreatic cystic aspiration. Clinical and radiographic findings, molecular mutational analysis, in combination with cytological features are essential to differentiate it from other disease entities. Diagn. Cytopathol. 2014;42:156–160. © 2012 Wiley Periodicals, Inc.     

Cytologic features of pancreatic adenocarcinoma with “vacuolated cell pattern.” report of a case diagnosed by endoscopic ultrasound‐guided fine‐needle aspiration

The “vacuolated cell pattern” has only been recently described as a distinct morphologic variant of pancreatobiliary adenocarcinoma. Herein, we report the endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) cytologic features of a case of pancreatic adenocarcinoma with “vacuolated cell pattern” occurring in a 60‐year‐old man. The aspirate smears and cell block sections from the EUS‐FNA of a 23.5 mm hypoechoic pancreatic head mass were highly cellular, showing variably‐sized crowded three‐dimensional cell clusters, flat sheets, and numerous highly atypical single cells. The background was bloody and showed necrotic debris, but no discernible mucus. The most striking feature of the aspirate was the presence of numerous very large (20–50 µm) vacuoles, occupying the entire cytoplasm, pushing the nuclei to the side and indenting them, that imparted a cribriform appearance to the sheets of neoplastic cells. The non‐vacuolated neoplastic cells were large, had abundant dense (squamoid) cytoplasm, irregularly contoured hyperchromatic nuclei, and prominent macronucleoli. Histologic evaluation of the pancreatectomy specimen showed a “vacuolated cell pattern” adenocarcinoma composed of poorly formed glands, solid sheets, and infiltrating single cells with pleomorphic nuclei and large cytoplasmic vacuoles. To our knowledge, this is the first report describing the cytologic features of this rather uncommon morphologic variant of pancreatic adenocarcinoma. Recognition of this morphologic variant of pancreatic adenocarcinoma in ESU‐FNA samples allows its differentiation from primary and metastatic signet‐ring cell carcinomas. Diagn. Cytopathol. 2014;42:302–307. © 2014 Wiley Periodicals, Inc.     

Intraductal tubulopapillary neoplasm of the pancreas suspected by endoscopic ultrasonography–fine‐needle aspiration cytology: Report of a case confirmed by surgical specimen histology

Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is rare compared with intraductal papillary mucinous neoplasm (IPMN). These entities are distinguished by endoscopic ultrasonography (EUS)–fine‐needle aspiration cytology (FNAC) on the basis of mucin production and the presence of a tubular or papillary growth pattern. In addition, there are several tumor types that should be distinguished from ITPN, such as solid pseudopapillary neoplasm, acinar cell carcinoma, and pancreatic neuroendocrine tumor. Herein, a case of an 80‐year‐old man with ITPN, which was suspected based on EUS‐FNAC findings at the time of review and confirmed by histological examination of the surgically resected specimen, has been presented. There have only been three reported cases that included the cytology of ITPN in the English language literature, all of which propose diagnostic features of ITPN based on cytological specimens. Here, a previously undescribed diagnostic feature of ITPN revealed by EUS–FNAC—tubules in contact with fibrovascular structures—correlated well with the histological findings of the surgically resected specimen, has been shown. Diagn. Cytopathol. 2015;43:1003–1006. © 2015 Wiley Periodicals, Inc.     

Cytological findings and BCL10 expression in pancreatic acinar cell carcinoma

BCL10 was recently demonstrated to be a biomarker for pancreatic acinar cell carcinoma, but whether altered BCL10 expression can be detected in cell block specimens is unclear. Here, we report a pancreatic acinar cell carcinoma with cytological findings that showed BCL10 expression in a cell block. A 72‐year‐old man presented with a pancreatic tumor and underwent endoscopic ultrasound‐fine needle aspiration (EUS‐FNA) with additional passes performed for cell block preparation. The EUS‐FNA cytology showed loose cohesive clusters with focal acinar‐ or gland‐like‐structures and prominent nucleoli. The preoperative diagnosis was well differentiated adenocarcinoma, and he underwent a pancreaticoduodenectomy. Histological examination revealed an acinar tumor structure with tumor cells staining positive for BCL10 and trypsin. The cell block specimen also demonstrated strong and diffuse BCL10‐positive staining. Based on these findings, this tumor was diagnosed as acinar cell carcinoma of the pancreas. This case demonstrates that BCL10 expression within cell blocks facilitates a differential diagnosis of acinar cell carcinoma. Diagn. Cytopathol. 2017;45:247–251. © 2016 Wiley Periodicals, Inc.     

Metastatic tonsillar squamous cell carcinoma masquerading as a pancreatic cystic tumor and diagnosed by EUS‐guided FNA

Metastatic carcinoma to the pancreas is uncommon and head and neck squamous carcinoma metastatic to the pancreas is extremely rare. Metastatic squamous cell carcinoma to the pancreas presents a unique diagnostic challenge: in addition to mimicking the rare primary squamous cell carcinoma of the pancreas based on cytologic, histologic, and immunohistochemical features, it may be mistaken for a cystic neoplasm of the pancreas because of its high predilection for cystic degeneration in metastatic sites. Herein, we report a case of tonsillar squamous cell carcinoma with a cystic pancreatic metastasis diagnosed by ultrasound‐guided fine needle aspiration biopsy (EUS‐FNA). This represents a third reported case of metastatic squamous cell carcinoma to the pancreas from the head and neck region. Metastatic squamous cell carcinoma should be considered in the differential diagnosis of EUS‐FNA during evaluation of pancreatic cystic lesion.     

Primary pancreatic leiomyosarcoma with metastasis to the liver diagnosed by endoscopic ultrasound‐guided fine needle aspiration and fine needle biopsy

Primary pancreatic leiomyosarcomas are rare tumors of the pancreas that are usually diagnosed after resection or by biopsy. One case in the literature has utilized endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) cytology. We report a second case of a primary pancreatic leiomyosarcoma that yielded diagnostic material on EUS‐FNA cytology. A 72‐year‐old female presented with 3–4 months of abdominal pain. A CT scan showed a large heterogeneous, lobulated pancreatic head and uncinate mass and multiple hypoattenuating liver lesions. An EUS‐FNA was performed on one of the liver lesions with a 25‐gauge needle, yielding an adequate sample with lesional cells. The initial read was a spindle cell neoplasm. A subsequent endoscopic ultrasound‐guided fine needle biopsy with a 22‐gauge needle was performed on the pancreatic head mass to rule out two primaries and to provide tissue for a mitotic index in the case of gastrointestinal tumor. Both the cell block of the EUS‐FNA and the core biopsy were equally cellular and showed interlacing spindle cells that stained positive for SMA and negative for DOG‐1, CD 117, and CD34. In addition, the core biopsy of the pancreas stained positive for Desmin. A diagnosis of a primary pancreatic leiomyosarcoma was made and the patient was started on systemic chemotherapy. Primary pancreatic leiomyosarcomas are rare pancreatic tumors that may yield diagnostic material by EUS‐FNA with a 25‐gauge needle. Diagn. Cytopathol. 2016;44:1070–1073. © 2016 Wiley Periodicals, Inc.     

A case of intraductal tubulopapillary neoplasm of pancreas with severe calcification,a potential pitfall in diagnostic imaging

We experienced a case of intraductal tubulopapillary neoplasms (ITPN) of the pancreas with severe calcification, which complicated image diagnosis. A pancreas head tumor was detected in a Japanese female in her 50s. Early enhancement by contrast‐enhanced CT and coarse calcification suggested a neuroendocrine tumor, although the obstruction and dilation of the main pancreatic duct appeared to be an intraductal tumor. An endoscopic ultrasound‐guided fine needle aspiration biopsy specimen revealed adenocarcinoma tissue. Pancreaticoduodenectomy was performed, and the patient has been well without evidence of recurrence for over 10 months. Pathological examination on the resected specimen revealed that the tumor showed papillary and tubulo‐cribriform growth patterns. Together with typical immunohistochemical results, the final diagnosis of ITPN was made. Characteristically, this case showed extensive calcification of both psammoma body‐type and non psammoma body‐type with foamy macrophage aggregation. This is the first report of ITPN with two types of calcification and macrophage. Since calcification might be one of the characteristic histological findings in ITPN as shown in our case, the possibility of ITPN should be also considered when calcification is detected in pancreatic lesions by various imaging modalities.     

EUS‐FNA diagnosis of pancreatic serous cystadenoma with the aid of cell blocks and α‐inhibin immunochemistry: A case series

Serous cystadenoma (SCA) is an uncommon benign pancreatic neoplasm that is most often managed conservatively with follow‐up rather than surgical excision. Therefore, to avoid the serious complications of pancreatic surgery, SCA should be diagnosed accurately at the preoperative level. Preoperative SCA diagnosis requires a multimodal diagnostic approach that includes imaging, cystic fluid biochemical analysis and/or endoscopic ultrasound fine‐needle aspiration (EUS‐FNA). In this brief report, we describe six EUS‐FNA cases from five patients that were reported as “benign, consistent with serous cystadenoma”. Samples were hypocellular, composed of loose clusters and single cuboidal, bland‐looking cells among epithelial sheets representing gastrointestinal contamination. Cell blocks were prepared and all six FNA cases revealed cuboidal cells with a positive α‐inhibin immunophenotype, consistent with a diagnosis of SCA. As EUS‐FNAs of SCA commonly result in non‐diagnostic interpretations, cell block preparations with subsequent immunochemistry can increase their diagnostic accuracy and guide patient management.     

Diagnostic challenge: Intraductal neoplasms of the pancreatobiliary system

To help pathologists avoid misdiagnosis of intraductal neoplasms arising from the pancreatobiliary system, we report two cases that illustrate diagnostic pitfalls. The first is of a 66-year-old man who complained of appetite loss. An early examination led to a diagnosis of intraductal papillary mucinous neoplasm. Macroscopically, a multilocular cyst without visible mucin was identified. Histologically, the compartments consisted of complex fusion of tubular glands surrounded by dilated pancreatic duct. The neoplasm resembled an acinar cell cystadenocarcinoma. However, the neoplastic cells were negative for trypsin. Thus, the final histopathologic diagnosis was an unusual cystic variant of intraductal tubulopapillary neoplasm (ITPN) of the pancreas. The second case is of a 71-year-old man who complained of right upper quadrant pain. Although bile duct stone was suspected, a polypoid nodule was extracted. Histologically, the nodule was composed of tubular glands, with some complex fusion and focal dysplasia, consistent with carcinoma. In addition, lack of MUC-5AC expression led to an initial impression of ITPN of the bile duct. However, the neoplasm showed dysplastic cells based on the columnar cells resembling pyloric glands, indicating the sequential progression. Thus, the final histopathological diagnosis was intraductal papillary neoplasm of the bile duct with high-grade intraepithelial neoplasia. Because phenotypic variants of intraductal neoplasms of the pancreatobiliary system exist, ITPN and ITPN-mimicking tumor must be carefully differentiated from other intraductal neoplasms.     

The role of endoscopic ultrasound and endoscopic ultrasound-guided fine-needle aspiration in distinguishing pancreatic cystic lesions

Distinguishing mucinous from nonmucinous cystic lesions of the pancreas often constitutes a diagnostic dilemma. The clinical management differs between such lesions; therefore it is important to make an accurate preoperative diagnosis. Various centers have reported conflicting results regarding their ability to detect mucin-producing neoplastic cells and appropriately reach a diagnosis based on endoscopic ultrasound (EUS) guided FNA. The aim of this study is to assess the ability of EUS-FNA cytology to diagnose and differentiate mucinous from nonmucinous pancreatic cystic lesions. We reviewed records of patients who underwent EUS of pancreatic cystic lesions. If FNA was performed and mucinous neoplasm was suspected, aspirate was evaluated for cytomorphology and presence of mucin. FNA results were compared to final histologic diagnosis if surgery was performed.Cytologic diagnosis was provided for 28/30 (93%). By comparing EUS-FNA diagnoses with final surgical pathology, FNA accurately diagnosed in 10/11 cases with sensitivity and specificity for detection of malignancy of 100 and 89, respectively, while the accuracy for identification of mucinous cystic neoplasms was 100%. Our results indicate that in the appropriate clinical and imaging setting, EUS-FNA cytology with analysis for mucin production by tumor cells is an important test in distinguishing pancreatic cystic lesions and guiding further management.     

胰腺导管内乳头状黏液性肿瘤的诊断和鉴别诊断

目的探讨胰腺导管内乳头状黏液性肿瘤的临床病理学特征及其与黏液囊性肿瘤的鉴别诊断要点。方法复习17例导管内乳头状黏液性肿瘤的临床病理学特征,与13例黏液囊性肿瘤对照;行HE染色及免疫组织化学EnVision法染色,检测肿瘤内黏液素MUC（1、2、5AC）的表达。结果17例导管内乳头状黏液性肿瘤中10例发生在男性;13例位于胰头。大体切面可观察到15例肿瘤与胰腺主导管相通。镜下可见到胰腺导管增生呈乳头状,并有上皮轻至重度不典型增生的改变。无卵巢样间质,肿瘤内交错出现萎缩或正常的胰腺腺泡和胰岛。9例主要表达MUC2,4例主要表达MUC5AC,4例伴有浸润癌者主要表达MUC1。13例黏液囊性肿瘤中11例发生于中老年女性;胰尾部10例,胰头1例,全胰腺2例;肿瘤与主导管不相通。组织学特征是含有卵巢样间质。肿瘤细胞主要表达MUC5AC,不表达MUC2,伴有浸润癌的2例,癌组织也表达MUC1。结论导管内乳头状黏液性肿瘤预后较好,患者性别、年龄、肿瘤部位、卵巢样间质、与主胰管是否相通及表达MUC2和（或）MUC1检测均可帮助诊断,并与黏液囊性肿瘤鉴别。后者主要表达MUC5AC。MUC1阳性提示侵袭性生物学行为。     

Fine-needle aspiration cytology of pancreatic somatostatinoma: the importance of immunohistochemistry for the cytologic diagnosis of pancreatic endocrine neoplasms

Pancreatic somatostatinoma is a rare pancreatic endocrine neoplasm representing as little as 1% of pancreatic endocrine neoplasms (PENs). The histologic features of this tumor are like those of other PENs, except that it commonly forms acinar structures and often has cells with abundant, granular cytoplasm. We have recently encountered two of these neoplasms sampled by endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA). We discuss the cytologic and immunohistochemical findings of these two cases and the cytologic similarities these neoplasms share with pancreatic acinar-cell carcinoma (PACC). We review the cytologic features of PEN and PACC and discuss the importance of cell block immunohistochemistry in the diagnosis of pancreatic neoplasia sampled by EUS-guided FNA.     

胰腺胶样癌四例临床病理学分析

目的 探讨胰腺胶样癌的临床病理学特征、诊断、鉴别诊断及分子生物学特点.方法 分析4例胰腺胶样癌的临床特点,对标本进行病理形态学观察、免疫组织化学EnVision法和K-ras基因突变检测.结果 4例胶样癌中3例发生在胰头部,患者均为男性;另1例在胰体尾部,为女性;平均发病年龄为56.5岁.其中2例首发症状为腹痛,1例为尿糖增高,1例为查体发现.3例大体形态为囊实性结节,囊内含黏液,1例大体呈实性.低倍镜下,纤维及胰腺组织中可见边界清楚的黏液结节,大的黏液湖中可见纤细的纤维结缔组织间隔成多个小黏液湖;肿瘤细胞漂浮在黏液湖中,呈小巢或条索状,或腺管状,也可看到印戒细胞漂浮其中.3例癌周可见肠型胰腺导管内乳头状黏液性肿瘤(IPMN),仅例1伴发胰胆管型IPMN.免疫组织化学染色3例MUC2细胞膜阳性,1例MUC1阳性.3例中例1和例3发现K-ras基因突变,突变位点均位于12密码子Gly12Asp(GGT＞GAT)和Gly12Arg( GGT＞ CGT).结论 胰腺胶样癌是少见的胰腺导管腺癌亚型,经常伴发于IPMN和胰腺黏液性囊性肿瘤,应与普通胰腺导管腺癌、印戒细胞癌及假性囊肿等病变相鉴别.免疫组织化学MUC2多阳性表达,MUC1多为阴性,K-ras基因突变率较低.     

Perivascular Epithelioid Cell Tumor (PEComa) of Pancreas Diagnosed Preoperatively by Endoscopic Ultrasound‐Guided Fine‐Needle Aspiration

Perivascular epithelioid cell tumors (PEComas) of the pancreas are extremely rare mesenchymal tumors and to our knowledge, only 17 cases have been reported in the English literature to date. We report our experience with a new case of primary pancreatic PEComa diagnosed preoperatively by endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) complemented by tissue cell block and immunohistochemistry. The patient was a 54‐year‐old female whose chief complaint was intermittent severe right upper quadrant abdominal pain. Computed‐tomography (CT) imaging revealed a mass between the head and the body of the pancreas. EUS‐FNA smear preparation was obtained but was nondiagnostic. However, examination of the tissue cell block showed sheets of epithelioid cells with abundant eosinophilic cytoplasm and immunohistochemistry studies revealed positivity for both melanocytic (HMB‐45 and Melan‐A) and smooth muscle markers (actin and desmin). A diagnosis of PEComa was made and an uncomplicated middle pancreatectomy was performed. Our case and review of the literature demonstrates that EUS‐FNA complemented with tissue cell block increases cellular yield, improved preoperative diagnostic accuracy, and may assist the surgeon in planning conservative surgical management. Diagn. Cytopathol. 2017;45:59–65. © 2016 Wiley Periodicals, Inc.     

Pancreatic neuroendocrine microadenomatosis: A case report of cytology and histology correlation

Pancreatic neuroendocrine neoplasia is categorized by grade, size, and functional status. Neuroendocrine microadenoma (NEMA) is defined as a neuroendocrine tumor (NET) that measures less than 0.5 cm in diameter. Multiple NEMAs are termed neuroendocrine adenomatosis (NEMAtosis). The surgical pathology and clinical aspects of pancreatic NEMAtosis have been reported, but there has been no report regarding EUS‐FNA cytology of NEMAtosis. We report a case of NEMAtosis with cytologic correlation and illustrate the diagnostic challenges and potential pitfalls. The pre‐operative cytology can be problematic. The main differential diagnosis of the EUS‐FNA specimen includes NET, normal pancreas, and islet cell hyperplasia/aggregation associated with chronic pancreatitis. The helpful cytopathologic feature of NEMAtosis is the presence of two intermingled populations of loosely‐cohesive neuroendocrine cell clusters and tight acinar cell groups arranged in microacinar and/or grape‐like structures. Although neuroendocrine cells and acinar cells possess different cytomorphology, the distinction is not always straightforward because both types of cells are small and cytologically bland. Cytologic assessment of both architecture and individual cell morphology is imperative to avoid interpretation error and further guide appropriate clinical management. Diagn. Cytopathol. 2017;45:143–147. © 2016 Wiley Periodicals, Inc.     

Diagnosis of metastatic pancreatic mesenchymal tumors by endoscopic ultrasound‐guided fine‐needle aspiration

Involvement of the pancreas by metastatic sarcoma is rare, and can prove challenging to differentiate from sarcomatoid carcinomas which occur more commonly. The endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) technique has been successfully used for the diagnosis of pancreatic carcinomas whether primary or metastatic, and is now considered the most effective noninvasive method for the identification of pancreatic metastases. However, to date very few reports detail the diagnosis of mesenchymal neoplasms by EUS‐FNA. Herein, we report a series of four patients who underwent EUS‐FNA of the pancreas, where the diagnosis of metastatic sarcoma was made based on morphology and ancillary studies. The cases include metastases of leiomyosarcoma, liposarcoma, alveolar rhabdomyosarcoma, and solitary fibrous tumor. The history of a primary sarcoma of the chest wall, mediastinum, and respectively lower extremity was known for the first three of these patients while in the case of the solitary fibrous tumor a remote history of a paraspinal “hemangiopericytoma” was only elicited after the EUS‐FNA diagnosis was made. We conclude that EUS‐FNA is efficient and accurate in providing a diagnosis of sarcoma, even in patients without a known primary sarcoma, thus allowing institution of therapy without additional biopsies. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Primary pancreatic diffuse large B‐cell lymphoma diagnosed by endoscopic ultrasound guided FNAC: A rare entity

Primary pancreatic lymphoma (PPL) is an uncommon neoplasm which can clinico‐radiologically mimic carcinoma. But the management of these patients differs from that of a carcinoma. Endoscopic ultrasound (EUS) guided fine‐needle aspiration (FNA) serves as a potential tool to identify pancreatic lymphomas and thus prevent an invasive diagnostic test. This case report describes the presentation and diagnosis of primary pancreatic lymphoma. A 37‐year‐old female presented with nausea, vomiting with signs of icterus and elevated liver function test and Bilirubin. Abdominal computed tomography (CT) revealed a hypodense lesion in the head of the pancreas. EUS guided FNA was performed and cytological material was collected. The lesion was diagnosed as Non‐Hodgkin Lymphoma (NHL) and subtyped as diffuse large B‐cell lymphoma‐germinal centre (DLBCL‐GCB) base on immunohistochemistry on cell block. The patient was started on rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (RCHOP) regimen. EUS guided FNA along with ROSE, cell bock, and immunocytochemistry helps in the diagnosis of primary pancreatic lymphoma.     

Fine-needle aspiration cytology of intraductal papillary-mucinous tumors: a retrospective analysis

Intraductal papillary-mucinous tumor (IPMT) of the pancreas has become the accepted terminology for a group of mucin-producing epithelial proliferations lying within ectatic segments of the main pancreatic duct or its large branches. These neoplasms generally are associated with an indolent course, characteristic endoscopic ultrasonographic (EUS) findings, and a variable histo- and cytomorphology ranging from hyperplasia to carcinoma. Cytological specimens obtained by endoscopic ultrasound-guided or percutaneous fine-needle aspiration (FNA) are characterized by a background containing abundant mucin in which are entrapped single or loosely cohesive clusters of neoplastic cells characteristically showing a goblet-cell morphology. The degree of nuclear atypia, cell crowding, and cell shape varies between smears within a single case and between cases. Cytomorphological examination, when coupled with EUS features, is accurate for the diagnosis of these lesions but often it underdiagnoses the grade of the neoplasm.     

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.