Breast Imaging Reporting and Data System Classification for Central-Type Intra-Ductal Papillary Masses: Current Problems and Evaluation of Modified Parameters.

The Breast Imaging Reporting and Data System (BI-RADS) standards have limitations regarding classifying and managing central intra-ductal papillary masses. Changes to the standards are necessary to provide early and effective treatment. To summarize the ultrasonographic imaging features of central mammary ductal papillary masses, this retrospective study included 56 participants. In identifying benign versus malignant lesions, the most significant indicators were angular edges and the long diameter of the tumor parallel to the duct. In the comparison of diagnostic efficacy for central mammary ductal tumors, the post-operative pathologic malignant upgrade rate of BI-RADS was 33.3%, and that of the new standard criteria was 14.2%. The angle of the wall of the tumor relative to the duct was most helpful. When BI-RADS is used to evaluate a papillary mass in a central duct, it is more accurate when the tumor is parallel to the duct than parallel to the skin.

Histopathological evaluation of minor salivary gland papillary-cystic tumours: focus on genetic alterations in sialadenoma papilliferum and intraductal papillary mucinous neoplasm.

AIMS: Minor salivary gland tumours showing a predominant papillary-cystic structure are rare, and constitute a mixture of various types of neoplasm; thus, the histopathological assessment of these tumours poses a significant diagnostic challenge. We aimed to delineate the histological characteristics of these tumours and further mutational aspects with a particular focus on sialadenoma papilliferum (SP) and intraductal papillary mucinous neoplasm (IPMN). METHODS AND RESULTS: We retrieved 28 papillary-cystic tumours of the minor salivary glands, and performed histological re-evaluation and mutation analyses of several key oncogenes. The histological classifications were as follows: SP (n = 10), SP-like intraductal papillary tumour (SP-IPT) (n = 2), IPMN (n = 9), intraductal papilloma, cystadenoma, and cystadenocarcinoma (two, three and two respectively). Whereas SP typically consisted of a combination of exophytic squamous epithelium and endophytic intraductal papillary infoldings, SP-IPT lacked the exophytic component. SP and SP-IPT frequently harboured BRAF V600E mutations (75.0%), which were identified in both squamous and ductal components. IPMN was characterised by a well-demarcated cystic lesion filled exclusively with a papillary proliferation of mucinous cells and a high rate of AKT1 E17K mutations (88.9%). Intraductal papillomas were unilocular cystic lesions with intraluminal papillary growth of bland columnar cells. In contrast, both cystadenomas and cystadenocarcinomas showed a multicystic appearance with a papillary configuration. Cystadenocarcinomas invaded the surrounding tissue and were composed of markedly atypical tumour cells. CONCLUSION: The appropriate interpretation of histological findings and specific genetic alterations (e.g. BRAF V600E and AKT1 E17K in SP and IPMN) would be useful for the correct diagnosis of minor salivary gland papillary-cystic tumours.

Upstaging papillary lesions to carcinoma on surgical excision is not impacted by patient race.

BACKGROUND: The management of papillary lesions is controversial with studies showing different rates of upstaging to malignancy. There is a paucity of research into race as an independent risk factor. The aim of this study is to identify if race is correlated with upstaging to malignancy with a secondary focus of analyzing for other personal and tumor specific risk factors for upstaging. METHODS: We performed a retrospective review of 123 papillary lesions with univariate analysis to identify risk factors for upstaging. RESULTS: The incidence of papillary lesions found on core needle biopsy was 6%. Atypical papillary lesions were most likely to be upstaged to malignancy at a rate of 27.7%. Papillary lesions and papillary lesions with hyperplasia were also upstaged to cancer at a lower rate of 8.3% and 12.5%, respectively. A univariate analysis of all papillary lesions and a separate analysis of atypical lesions demonstrated a higher likelihood of upstage based on BIRADS classification. Race, age, size of tumor and other radiographic features were not associated with an increased risk for upstaging to malignancy. CONCLUSIONS: Atypia remains the most significant contributor to the risk of upstaging papillary lesions to malignancy. Our research supports the practice of excising all atypical papillary lesions with selected excision of those without atypia. In our cohort, there was no association between race and risk of upstaging to malignacy.

Intraductal papillomas on core biopsy can be upgraded to malignancy on subsequent excisional biopsy regardless of the presence of atypical features.

Intraductal papillary lesions of the breast constitute a heterogeneous entity, including benign intraductal papilloma (IDP) with or without atypia and malignant papillary carcinoma. Differentiating between these diagnoses can be challenging. We re-evaluated core biopsy specimens that were diagnosed as IDP and the corresponding surgical excision specimens, and assessed the potential risk for the diagnosis to be modified to malignancy based on excision. By sorting the pathology database of the National Cancer Center Hospital, Tokyo, we identified 146 core biopsy cases that were histologically diagnosed as IDP between 1997 and 2013. The re-evaluated diagnosis was IDP without atypia in 79 (54%) patients, IDP with atypia in 66 (45%), and ductal carcinoma in situ (DCIS) in 1 (1%). Among the 34 patients (23%) who underwent surgical excision subsequent to core biopsy, histological diagnosis was upgraded to carcinoma, excluding lobular carcinoma in situ (LCIS), in 14 (41%) cases, including 4 (33%) of 12 IDPs without atypia and 10 (45%) of 22 IDPs with atypia. Complete surgical excision should be kept in mind for all IDPs diagnosed on core biopsy, not only IDPs with atypia but IDPs without atypia, especially when clinical or imaging diagnosis findings cannot rule out the possibility of malignancy, because papillary lesions comprise a variety of morphological appearances.

Papillary and neuroendocrine breast lesions: the WHO stance.

In this review, we highlight adaptations in the WHO 2012 classification of papillary and neuroendocrine breast lesions as compared with the previous 2003 version. Consensus criteria for distinguishing atypical ductal hyperplasia from ductal carcinoma in situ within an intraductal papilloma are proposed. The absence of myoepithelial cells around the wall of an encapsulated papillary carcinoma, although raising consideration of an indolent tumour with minimal invasion, is currently regarded as in-situ disease for staging purposes. The majority of solid papillary carcinomas are classified as in-situ tumours, but lesions with irregular tumour islands within desmoplastic stroma may be considered to be invasive. The diagnosis of solid papillary carcinoma without further qualification as either in-situ or invasive disease is discouraged. When invasive papillary carcinoma is seen in the breast, metastatic papillary carcinoma from other organ sites needs to be excluded. WHO 2012 classifies neuroendocrine breast tumours as well-differentiated neuroendocrine tumour, small-cell carcinoma, and invasive breast carcinoma with neuroendocrine differentiation. There is currently no clinical impact of identifying neuroendocrine differentiation in conventional invasive breast carcinomas, apart from acknowledging its frequent occurrence in subtypes such as the hypercellular variant of mucinous carcinoma and solid papillary carcinoma.

Cell blocks of breast FNAs frequently allow diagnosis of invasion or histological classification of proliferative changes.

Two major limitations of breast fine needle aspiration (FNA) compared with core needle biopsies (CNB) are the inability to determine whether a cancer is invasive and to classify proliferative lesions. We studied 40 consecutive "rapid cell blocks" from breast FNAs with surgical pathology follow-up to test whether cell blocks can overcome these limitations. Of 25 carcinomas, invasion could be identified in the cell block sections in 11 (44%). One cystosarcoma phyllodes was suspected based on the cell block sections. Cell blocks from 12 of 14 benign breast FNAs showed sufficient cells to assign a histologic diagnosis of no hyperplasia (1 case, confirmed on follow-up) and usual hyperplasia (11 cases; confirmed in eight of 11 on follow-up). Specific histologic diagnoses included intraductal papilloma (2 cases), and in situ lobular neoplasia (2 cases). Cell blocks complement smears and monolayers and appear to overcome major limitations of breast FNA.

Double immunostaining with p63 and high-molecular-weight cytokeratins distinguishes borderline papillary lesions of the breast.

Papillary breast lesions remain a source of diagnostic confusion because the full range of epithelial proliferations may arise within, or secondarily involve, papilloma. The expression of p63 and high-molecular-weight cytokeratins (HMWCK) was studied simultaneously in 33 papillary lesions including intraductal papilloma (IP, n = 10), atypical papilloma (AP, n = 8) and intraductal papillary carcinoma (IPC, n = 15) by double immunostaining. The myoepithelial cell nuclei were stained dark brown whereas the cytoplasms of usual ductal hyperplasia (UDH) and myoepithelium were stained purple. The myoepithelial layer was recognized as a dark brown dotted line at the epithelial stromal junction in all IP (10/10), most AP (7/8) and some IPC (7/15), suggesting that the retained myoepithelial layer in the papillary processes does not necessarily guarantee benignity. However, the malignant epithelial cells in AP and IPC were typically recognized as monotonous populations unstained with either chromogen. These monotonous cells contrasted with the proliferating cells of UDH in papilloma, which had intense purple cytoplasm in a mosaic-like fashion. The present data suggest that the double immunostaining with the two popular antibodies p63 and HMWCK is a useful tool for reproducible classification of papillary breast lesions.

International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas.

Non-inflammatory cystic lesions of the pancreas are increasingly recognized. Two distinct entities have been defined, i.e., intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN). Ovarian-type stroma has been proposed as a requisite to distinguish MCN from IPMN. Some other distinct features to characterize IPMN and MCN have been identified, but there remain ambiguities between the two diseases. In view of the increasing frequency with which these neoplasms are being diagnosed worldwide, it would be helpful for physicians managing patients with cystic neoplasms of the pancreas to have guidelines for the diagnosis and treatment of IPMN and MCN. The proposed guidelines represent a consensus of the working group of the International Association of Pancreatology.

Time-domain optical mammography SoftScan: initial results.

RATIONALE AND OBJECTIVES: Near-infrared (NIR) technology appears promising as a noninvasive technique for breast cancer screening and diagnosis. The technology capitalizes on the relative transparency of human tissue in this spectral range and its sensitivity to the main components of the breast: water, lipid, and hemoglobin. In this study, the authors report quantitative measurements of these components and the functional contrast between healthy and diseased tissue. MATERIALS AND METHODS: A four-wavelength time domain optical imaging system was used to perform noninvasive NIR measurements in the breast of 49 women both pre- and postmenopausal, ages 24-80. Algorithms based on a diffusive model of light transport provided absolute bulk and local values of breast constituent concentrations. RESULTS: Important variations in the functional and structural NIR properties of the breast were observed. Demographics trend were noticed in accordance with breast physiology. In the 23 cases imaged with suspicious masses, the optical images were consistent with the mammographic findings. Substantial contrast between masses and adjacent tissue is observed. Moreover, consistent differences between malign and benign cases are found with optical imaging. CONCLUSION: The results of this pilot study illustrate the sensitivity of optical techniques to the composition of the breast. In addition, preliminary data suggest that benign and malignant tumors can potentially be noninvasively differentiated with optical imaging. Moreover, statistically significant discrimination based on deoxy-hemoglobin content between malign and benign cases was found with optical imaging (P = .0184, one-tailed t test).

Central atypical papillomas of the breast: a clinicopathological study of 119 cases.

The clinicopathological features of central intraductal papillomas of the breast presenting with florid usual ductal hyperplasia or atypical ductal hyperplasia (ADH) were analyzed in a retrospective series of 119 patients, whose lesions were sent to the Armed Forces Institute of Pathology from 1976 to 1990. After histological review considering predefined morphological and quantitative criteria, the 119 central papillomas were classified into 22 papillomas with florid usual ductal hyperplasia (18%), 40 papillomas with focal atypia (34%), 24 atypical papillomas (20%) and 33 carcinomas arising in a papilloma (28%). After a median period of follow-up of 110 months, 16 recurrences (5 papillomas, 2 carcinomas arising in a papilloma, 4 ductal carcinomas in situ, 5 invasive carcinomas) occurred. No statistically significant difference was observed in relation to recurrence for the various categories of papillomas. The presence of epithelial hyperplasia, ADH or lobular neoplasia in the surrounding breast as well as infarction of the papilloma were significant predictive factors of recurrence ( P=0.02 and P=0.005, respectively, log-rank test). The main reason for the observed low rate of significant recurrences in this series was that epithelial atypia (whether comprising 20% or 60% of the papillary lesion) was, in most of the cases, localized in a confined lesion that was completely excised.

Can true papillary neoplasms of breast and their mimickers be accurately classified by cytology?

BACKGROUND: The cytologic accuracy in assessing malignancy in papillary breast neoplasms (PBNs) is controversial. This is further complicated by overlapping features observed in other breast lesions that produce papillary-like tissue fragments. METHODS: The authors reviewed 22 fine-needle aspirates (FNAs) from histologically proven papillary neoplasms: papillary carcinoma (PCA; 10 aspirates) and intraductal papilloma (IDP; 12 aspirates). They also reviewed 8 FNAs in which a papillary neoplasm was suggested by cytology but not confirmed by follow-up biopsy: fibroadenoma (6), mucinous carcinoma (1), and cribriform ductal carcinoma in situ (1). RESULTS: Papillary carcinoma can be distinguished from IDP by the higher cellularity, more complex papillae with thin disorganized fronds, mild to moderate nuclear atypia, and prominent dissociation with many single papillae. Fibrovascular cores (FVCs) were more common in PCA than IDP in which detached fibrous tissue fragments were frequently seen. Atypical IDP exhibited features intermediate between PCA and IDP. Apocrine metaplasia was variably present in IDP, atypical IDP, and fibroadenoma but absent in all carcinomas. Intraductal papilloma can be distinguished from fibroadenoma by their broad ruffled branches, scalloped borders, and tiny tongue-like projections. True papillae were commonly covered by tall columnar cells. Myoepithelial cells were few in IDP but were numerous in fibroadenoma. The epithelial fragments in nonpapillary lesions presented as cellular spheres and/or complex sheets with finger-like projections but lacked FVCs and columnar cells. CONCLUSIONS: Papillary breast neoplasms can be accurately classified by cytology. Closer evaluation of the tissue fragments architecture and the background can help in separating PBN from their mimics.

Histology of cystic tumors of the pancreas.

The cystic tumors of the pancreas constitute a considerable diagnostic challenge because of their overlapping clinical, radiologic, and pathologic features. They may be difficult to differentiate from one another and from benign lesions such as pseudocysts. Because many of the tumors in this group are potentially curable, correct diagnosis is essential for proper patient management. Even when correctly diagnosed, thorough microscopic evaluation is required for the mucin-producing tumors to correctly determine their degree of malignant progression in any given case. Most recently, molecular analysis of these tumors has demonstrated definitively that the serous and mucinous types of cystic neoplasms of the pancreas are unrelated pathogenetically. Conversely, molecular data indicate similarities between the mucinous types of cystic tumors and ductal adenocarcinoma of the pancreas, but the essential molecular differences that underlie the differences in biological behavior are as yet undetermined.

Diagnosis and fine needle aspiration of intraductal papillary mucinous tumor by endoscopic ultrasound.

A recently established clinical entity, intraductal papillary mucinous tumor (IPMT) of the pancreas embraces a spectrum of pathology ranging from benign to malignant disease. IPMT must be differentiated from other cystic neoplasms of the pancreas, as well as inflammatory cystic lesions. As the pancreas lies in close proximity to the gastric and duodenal walls, endoscopic ultrasonography (EUS) is ideally suited for imaging the pancreas. Additionally, EUS facilitates fine needle aspiration of pancreatic cysts and/or a dilated pancreatic duct for cytologic and tumor marker analysis. This article presents a brief history of IPMT, differential diagnosis, current imaging modalities, findings of cytologic and tumor marker analysis, prognosis, and treatment strategy. Special emphasis is dedicated to the role of EUS, as well as EUS with fine needle aspiration.

[Intraductal mucin-secreting tumors of the pancreas. Nosologic discussion of two cases of villous tumor of Wirsung's duct and a case of mucinous ductal ectasia]. / Les tumeurs mucosécrétantes intracanalaires du pancréas. Discussion nosologique à propos de deux cas de tumeur villeuse du canal de Wirsung et d'un cas d'ectasie canalaire mucineuse.

Intraductal mucin-producing tumors of the pancreas are rare, recently described tumors; they have a better prognosis than usual ductal carcinomas of the pancreas. We report two cases of villous tumor of the main pancreatic duct and one case of mucinous ductal ectasia, with histochemical and immunohistochemical study.