Benign Papillary Lesions Research Articles

Study of the Immunohistochemical Expression of p63 in Benign Lesions and Carcinoma of the Breast at a Tertiary Hospital in South India.

Invasive breast carcinoma is among the most common female cancers worldwide, causing high morbidity and mortality. Considerable disagreement in the interpretation of diagnostically challenging breast lesions based on histology alone has been documented. One of the essential histopathological findings that help distinguish benign from malignant lesions is the presence of the myoepithelial cell layer. Myoepithelial markers such as tumor protein 63 (p63) help distinguish invasive carcinoma from benign proliferations. p63 antibody is superior to other myoepithelial markers as it selectively stains the nuclei and is negative in stromal cells. To study the expression of p63 in various histological subtypes and grades of breast carcinomas. After routine hematoxylin and eosin stain, 65 cases of breast lesions were subjected to immunohistochemistry for p63 antigen using Novacastra ready-to-use monoclonal antibody p6. All cases were analyzed for p63 expression, and its staining arrangement was interpreted. In all benign lesions, immunoreactivity was noted in the myoepithelial cells, forming a continuous layer surrounding the luminal epithelial cells. The benign papillary lesions showed p63 staining in the fibrovascular core of the papillary fronds and at the periphery. A few single myoepithelial cells stained by p63 were also seen scattered discontinuously in ductal carcinoma in situ (DCIS). All invasive carcinomas and encapsulated papillary carcinomas were completely devoid of peripheral p63 staining of myoepithelial cells. p63 is a specific nuclear marker of myoepithelial cells in the breast and can, therefore, aid in distinguishing invasive ductal carcinoma from DCIS or rare questionable hyperplastic lesions. They also play a significant role in distinguishing various papillary lesions of the breast and, hence, can be incorporated into routine reporting for definitive diagnosis and accurate treatment.

Papillary Lesions of the Breast: Addition of DWI and TIRM Sequences to Routine Breast MRI Could Help in Differentiation Benign from Malignant.

We aimed to investigate the magnetic resonance imaging (MRI) features of benign, atypical, or malignant papillary breast lesions and to assess the additional value of diffusion-weighted imaging (DWI) and turbo inversion recovery magnitude (TIRM) sequences to routine breast MRI. Differentiation between benign and malignant papillary breast lesions is essential for patient management. However, morphologic features and enhancement patterns of malignant papillary lesions may overlap with those of benign papilloma. Seventy-two papillary breast lesions (50 benign, 22 atypical or malignant) were included in the current study, retrospectively. We divided the patients into two groups: benign papillary breast lesions and atypical or malignant papillary breast lesions. Morphologic, dynamic, turbo inversion recovery magnitude (TIRM) values and diffusion features of the papillary lesions were compared between two groups. Benign papillary lesions were smaller in size (p=0.006 and p=0.005, for radiologists 1 and 2 respectively), closer to the areola (p=0.045 and 0.049 for radiologist 1 and 2 respectively), and had higher ADC values (p=0.001 for two radiologists) than the atypical or malignant group. ROC curves showed diagnostic accuracy for ADC (AUC=0.770 and 0.762, p = 0.0001 for two radiologists), and showed a cut-off value of ≤ 957 x 10-6 mm2/s (radiologist 1) and ≤ 910 x 10-6 mm2/s (radiologist 2). MRI is a useful method for differentiation between benign and malignant papillary breast lesions. Centrally located, lesser in size, and higher ADC values should be considered benign, whereas peripherally located, larger in size, and lower ADC values should be considered malignant.

Contribution of Diffusion-Weighted Imaging and ADC Values to Papillary Breast Lesions.

This study aimed to evaluate the role of apparent diffusion coefficient (ADC) values obtained from diffusion-weighted imaging (DWI) in the differentiation of malignant from benign papillary breast lesions. The magnetic resonance imaging (MRI) data of 94 breast papillary lesions confirmed by pathology were retrospectively analyzed. The differences in ADC values of papillary lesions under different enhancements in MRI and different pathological types were investigated, and the ADC threshold was determined by the receiver operating characteristic curve for its potential diagnostic value. The mean ADC values in borderline and malignant lesions (1.01 ± 0.20 × 10-3 mm2/s) were significantly lower compared to benign lesions (1.21 ± 0.27 × 10-3 mm2/s) (P < 0.05). The optimal threshold of the ADC value could be 1.00 × 10-3 mm2/s. The ADC values were statistically significant in differentiating between benign and malignant papillary lesions whether in mass or non-mass enhancement (P < 0.05). However, there were no statistical differences in the ADC values among borderline or any other histological subtypes of malignant lesions (P > 0.05). Measuring ADC values from DWI can be used to identify benign and malignant breast papillary lesions. The diagnostic performance of the ADC value in identifying benign and malignant breast lesions is not affected by the way of lesion enhancement. However, it shows no use for differential diagnosis among malignant lesion subtypes for now. The ADC value of 1.00 × 10-3 mm2/s can be used as the most appropriate threshold for distinguishing between benign and malignant breast papillary lesions.

The role of p63 Myoepithelial cell marker in papillary lesions of the breast

Background: To diagnose various histological types of papillary lesions of the breast according to the newer WHO classification and to study the expression of myoepithelial cell marker p63 in various papillary lesions. Material and Methods: The study was done on 21 patients with breast lesions between Jan 2015 to June 2016. Breast biopsies (incisional as well as excisional) were retrieved from the histopathology section of the department. Result: P63 showed a nuclear positivity in myoepithelial cells. It was retained in the benign papillary lesions with some exceptions and was almost completely lost in malignant papillary neoplasms Conclusion: P63 can be used to observe the characteristic pattern of nuclear staining and delineate the myoepithelial layer wherever needed.

Papillary breast lesions detected using conventional ultrasound and contrast-enhanced ultrasound: Imaging characteristics and associations with malignancy

ObjectiveThis study aimed to evaluate the imaging features of papillary breast lesions detected using conventional ultrasonography (US) and contrast-enhanced ultrasound (CEUS) and to correlate the pathological results. Furthermore, the diagnostic efficiencies of these imaging features to predict the malignancy potential of papillary lesions were explored. MethodsThe findings of the conventional US and CEUS of 74 consecutive papillary breast lesions were assessed retrospectively. The obtained data were analyzed using univariate and multivariate logistic regressions to evaluate the ability of each parameter and combined parameters in distinguishing the benign and atypical or malignant papillary lesions. ResultsAmong the imaging features of breast papillary lesions on conventional US and CEUS, two sonographic features (lesion size ≥1 cm and not circumscribed margin) on conventional US and four enhancement features (irregular enhancement, heterogeneous enhancement, enlargement of scope, and perfusion defect) on CEUS were found to be significantly different between the benign and atypical or malignant papillary lesions (P < 0.05). A multivariate logistic regression analysis further showed that only heterogeneous enhancement and enlarged enhancement scope were associated with malignancy. The sensitivity and specificity of heterogeneous enhancement, enlarged enhancement scope, and combined analysis for predicting atypical and malignant papillary lesions were 78.6 % and 39.1 %, 75 % and 37 %, and 75 % and 82.6 %, respectively. The combination of enhancement homogeneity and enhancement scope improved the diagnostic accuracy (AUC = 0.875). ConclusionsThe results suggested that the imaging features on conventional US and CEUS could help in identifying benign and malignant papillary lesions and predict their malignancy potential.

Therapeutic Outcomes and Risk Factors for Complications of Endoscopic Papillectomy: A Retrospective Analysis of a Single-Center Study.

PurposeEndoscopic papillectomy (EP) has been accepted as a viable alternative therapy to surgery in benign duodenal papillary lesions. However, postoperative complications limit its widespread clinical application. This study aimed to evaluate the overall safety of the EP procedure and identify significant risk factors of post-EP complications.Patients and MethodsWe retrospectively collected 76 patients who had undergone EP in Chinese PLA General Hospital from 2016 to 2019 and graded their postoperative complications. We assessed twelve patient-, disease- or procedure-related variables to identify risk factors related to the occurrence of post-EP complications using both univariate and multivariate analyses.ResultsAmong the 76 patients included in this study, the incidence of entire post-EP complications was 36.8%, most of which were in a mild form. In both univariate and multivariate analyses, the pathologic tumor types, especially high-grade intraepithelial neoplasia (HIN), and the placement of stents were significantly associated with the occurrence of post-EP complications. Patients with HIN tumors were more likely to have post-EP pancreatitis, bleeding, and overall complications (odds ratio (OR) 11.66, 95% confidence interval (CI) 2.91–62.5, P = 0.001; OR 6.52, 95% CI 1.45–46.77, P = 0.027; OR 9.81, 95% CI 2.75–44.04, P = 0.001, respectively). Pancreatic stent placement may contribute to the occurrence of post-EP pancreatitis (OR 7.61, 95% CI 1.37–64.53, P = 0.033). While biliary stent placement was found negatively related to the occurrence of post-EP bleeding and overall complications (OR 0.02, 95% CI 0–0.37, P = 0.016; OR 0.11, 95% CI 0.01–0.99, P = 0.05, respectively).ConclusionEP is a safe procedure for papillary lesion treatment with a low rate and generally mild postoperative complications. Two factors are significantly associated with the occurrence of complications. The selection of eligible patients and suitable procedures is important to reduce the complication rate and severity.

Spectrum of imaging findings of papillary breast disease: A radiopathological review in a tertiary center.

To evaluate the clinical and imaging findings of papillary breast neoplasm and review the pathologic correlation at a tertiary center.Retrospective study of patients diagnosed with benign and malignant papillary lesions between 2008 to 2018. 147 patients were identified with histology diagnosis of papillary lesions. The clinical, imaging, and pathological characteristics were reviewed.Patient cohort included 147 women diagnosed with papillary lesions (mean age at diagnosis 53.8 years) and were divided into 3 histology groups (benign, atypical, and malignant). Common clinical presentations were breast lump (n = 60) and nipple discharge (n = 29), 48 patients were asymptomatic.Only 37 were detected as a mass lesion on mammogram. The presence of mass lesion on mammogram was the most common feature in all 3 papillary lesion groups, and with the presence of asymmetric density, were the 2 mammographic features significantly associated (P < .05) with malignancy.All lesions were detected on ultrasound. The most common sonographic features for all 3 groups were the presence of a mass and irregular shape. Among all the sonographic features assessed, larger size, presence of vascularity and absence of dilated ducts were significantly associated (P < .05) with malignancy.Feature pattern recognition of the variety of benign, atypical and malignant papillary neoplasm on ultrasound and mammogram, with emphasis on size, presence of vascularity and dilated ducts on ultrasound and presence of mass, and architectural distortion on mammogram, is important in the assessment of patients with suspected ductal lesions to facilitate optimal treatment and surgical care.

Spectrum of Papillary Breast Lesions According to World Health Organization Classification of Papillary Neoplasms of Breast.

IntroductionPapillary breast lesions are segregated into benign and malignant based on the presence or absence of myoepithelial cells in the papillary cores. Papillary breast lesions are further classified into: intraductal papilloma, papilloma with atypical ductal hyperplasia (ADH)/ductal carcinoma in situ (DCIS), papillary DCIS, solid papillary carcinoma in situ, solid papillary carcinoma with invasion, invasive solid papillary carcinoma, encapsulated papillary carcinoma and encapsulated papillary carcinoma with invasion. In this study, we evaluated the spectrum of papillary breast lesions in resection specimens of the breast according to the latest World Health Organization (WHO) classification of breast tumors.MethodsThis was a retrospective cross-sectional study, and was conducted at Liaquat National Hospital for a period of six years, from January 2012 till December 2017. Data of patients that underwent surgeries for breast tumors were included in the study. All specimens were grossed, according to defined protocols, and representative sections were taken after inking resection margins. Hematoxylin and eosin-stained sections were examined by experienced histopathologists, and myoepithelial stains (p63 and myosin) were done in selected sections of all tumors. Histopathological classification of papillary tumors was performed according to WHO classification of breast tumors.ResultsThe study involved 190 excision specimens of papillary breast lesions. Mean age of the patients was 45.6±17.1 years. Most of the lesions were between two and five centimetres (69.1%). For invasive carcinomas (n = 76), the most frequent grade was II (52.6%). For in situ and invasive carcinomas (n = 129), lymphovascular invasion and axillary metastasis were noted in 5.4% and 9.3% cases, respectively. Among papillary breast lesions, 36.8% were benign (intraductal papilloma, solitary or multiple) while 63.2% harbored ADH, DCIS, or invasive carcinoma. Invasive papillary carcinoma was the most frequent malignant papillary lesion (20%), followed by solid papillary carcinoma with invasion (12.6%). We found significant associations between patient’s age and tumor size with histological type of papillary lesion as benign papillary lesions had smaller size and younger age compared to malignant papillary lesions.ConclusionWe noted a high frequency of malignancy in papillary breast lesions. Moreover, malignant papillary lesions were significantly associated with higher age and larger tumor size.

A retrospective observational study of intraductal breast papilloma and its coexisting lesions: A real-world experience.

BackgroundBreast intraductal papilloma is a heterogeneous group. The aim of the study is to investigate the intraductal breast papilloma and its coexisting lesions retrospectively in real‐world practice.MethodsWe retrospectively identified 4450 intraductal breast papilloma and its coexisting lesions.ResultsAbout 18.36% of intraductal papilloma coexisted with malignant lesions of the breast, 37.33% coexisted with atypia hyperplasia (AH), 25.24% coexisted with benign lesions, and only 19.10% coexisted without concomitant lesions. In addition, 36.80% of intraductal breast papilloma had nipple discharge, 51.46% had a palpable breast mass, and 16.45% had both nipple discharge and a palpable breast mass. About 28.18% experienced discomfort or were asymptomatic. Furthermore, 98.99% had ultrasound abnormalities, and 53.06% had intraductal hypoechogenicity upon ultrasound. 31.89% had mammographic distortion, and 14.45% had microcalcification upon mammography. Intraductal breast papilloma with malignancy had significant correlations with clinical manifestations.ConclusionCoexisting malignancy was also related to ultrasound abnormality (BIRADS 4C and 5), mammographic distortion, and microcalcification upon mammography but was not related to the intraductal hypoechoic upon ultrasound. Coexisting atypical hyperplasia correlated with nipple discharge but not palpable mass, mammographic distortion, or intraductal hypoechoic upon ultrasound. The coexisting AH was also related to abnormality upon ultrasound or microcalcification compared with the benign lesions. The intraductal papilloma coexists with malignancy or AH accounted for more than 50%, and the clinical information on papilloma and its coexisting lesions is nonspecific. We recommended surgical treatment for benign intraductal papillary lesions.

Factors associated with disease upgrading in patients with papillary breast lesion in core-needle biopsy.

Traditionally, surgical excision is recommended for benign papillary lesions in core-needle biopsy (CNB) because of their malignant potency. The aim of this study was to identify factors associated with disease upgrading to malignancy in patients with benign papillary lesions in CNB. A total of 179 female patients were evaluated retrospectively who were diagnosed as having a benign papillary lesion in CNB and underwent a subsequent surgical excision between January 2007 and December 2016. Ultrasonography-guided CNB was performed using a 14-gauge needle gun method. The rate of upgrade to malignancy was 10.6% (7.6% in papillary lesions without atypia vs. 33.3% in papillary lesions with atypia; P=0.001). The univariable analysis revealed that older age at diagnosis (≥50 years old), menopause, lesion size on ultrasonography, palpability, multifocality, and atypia in CNB were associated with upgrading. The multivariable analysis revealed that age ≥50 years (OR, 4.6; 95% CI, 1.5-14.1; P=0.008), lesion size of ≥2 cm (OR, 6.4; 95% CI, 1.9-21.1; P=0.002), and atypia in CNB (OR, 5.1; 95% CI, 1.5-18.2; P=0.011) were significantly associated with upgrading to malignancy. Upgrading to malignancy in patients with benign papillary lesions in CNB was associated with age ≥50 years, lesion size ≥2 cm, and atypia in CNB.

Development of breast papillary index for differentiation of benign and malignant lesions using ultrasound images

Papillary breast lesions include a wide spectrum of pathologies ranging from benign to malignant. The word papillary originates from finger-like projections, or papules, which are seen when these lesions are projected under a microscope. Papillary breast lesions have an array of radiological features at presentations; hence differentiation between benign and malignant based on imaging features is challenging. Histopathological diagnosis is crucial for the distinction and further management of the lesions. Traditionally, tumor and ductal excision is the treatment of choice for malignant and atypical or benign papilloma with imaging discordance. However, current clinical practice guidance advocates complete surgical excision, even for asymptomatic and purely benign papillomas diagnosed on core needle biopsy, as they are highly associated with atypia and malignant upstage on subsequent surgery. Computer aided diagnosis (CAD) is a non-invasive method of diagnosing medical signals/images using advanced image processing followed by soft computing techniques. In this study, we have developed a non-invasive CAD system for differentiating benign versus malignant papillary breast lesions using bi-dimensional empirical mode decomposition (BEMD) and the discrete cosine transform (DCT) followed by locality sensitive discriminant analysis (LSDA). The developed model is validated using a large collection of ultrasound images of papillary breast lesions, and achieved a maximum performance of 98.63% accuracy. We have also developed a breast papillary index, which may in the future be used as a substitute for the conventional soft computing techniques. The developed model can be utilized as a tool to assist radiologists in their routine clinical practice after validation with a larger database.

Breast papillary lesions: a retrospective analysis from oncology set up of Pakistan

Background: Papillary lesions of the breast are a heterogeneous group of breast lesions that are difficult to diagnose as benign or malignant. These lesions have varied morphologic features that carry differing prognostic implications for affected patients. Accurate diagnosis is required to ensure that effective treatment is achieved. Papillary lesions can have increased risk of carcinoma and recurrence, in these patients even for lesions yielding a benign concordant diagnosis of papilloma at percutaneous biopsy, surgical excision may be warranted. Malignant lesions are usually surgically treated. Depending on stage-adjuvant chemotherapy and/or radiation therapy is given.Methods: A retrospective study was conducted at Shaukat Khanum Memorial hospital and Research Centre Lahore Pakistan. We reviewed the electronic records of diagnostic and registered patients from January 2007 till December 2017 in women imaging section, in age range of 25 to 75 years. Total 150 diagnosed patients with benign or malignant breast papillary lesions were selected and their conventional breast imaging (mammography and ultrasound) and histopathology was retrospectively analyzed on SPSS.Results: Patients were predominantly asymptomatic or on follow-up to an abnormal mammogram. Of the 150 cases most of the patients had intra-ductal papilloma followed by invasive papillary carcinoma and intra cystic papillary carcinoma. Few patients had intra-ductal papillomatosis and invasive micro papillary carcinoma.Conclusions: Conventional breast imaging remains the first main stay and quite sensitive in detecting breast papillary lesions leading to early detection and management.

Treatment and Outcome of 341 Papillary Breast Lesions

BackgroundPapillary breast lesions constitute a pathological heterogeneous group and display diverse clinical and imaging features. This study was conducted to analyze the upgrade rate of intraductal papilloma diagnosed on core needle biopsy and to assess the possible risk factors associated with upgrade to higher-risk lesions. We also examined the long-term outcomes in patients who received resection of the papillary lesions.Materials and methodsThe clinical and pathology records of 324 female patients who were diagnosed with papillary lesions based on core needle biopsy (CNB) from February 2010 to October 2016 at our institution were retrospectively analyzed. Patients were grouped by initial diagnosis into two groups (papilloma with or without atypia) and followed-up for long-term outcomes. For the upgrade to higher-risk lesions after excision, upgraded lesions were compared with benign papillomas for the collected variables.ResultsA total of 341 lesions were included for final analysis, and all were available for follow-up. Papillomas with or without atypia diagnosed by CNB were found in 9 and 332 lesions, respectively. Papillomas without atypia on CNB were treated by open excision (n = 265) or vacuum-assisted biopsy (VAB) (n = 67), which yielded similar event-free rate (p = 0.19). The upgrade rate of this group to higher-risk lesions was 9.9%. Peripheral (p = 0.011) lesions in postmenopausal (p = 0.001) or older (p = 0.001) patients with papillomas without atypia based on CNB showed significantly higher upgrade rates. Papillomas with atypia on CNB were all managed by open excision, and concurrent malignancy was found in two lesions.ConclusionIn conclusion, our results support benign papillary lesions based on CNB require further treatment. Peripheral lesions occurring in older or postmenopausal women are at higher risk for upgrade.

IMMUNOHISTOCHEMICAL EXPRESSION OF EZH2 IN ATYPICAL PAPILLARY EPITHELIAL PROLIFERATIONS OF THE ORAL CAVITY: A POTENTIAL MARKER FOR MALIGNANT TRANSFORMATION

Background Enhancer of zeste homolog-2 (EZH2) is a member of the polycomb group PcG of proteins; the genes that are involved in transcriptional repression. Cell cycle regulation and cell proliferation is associated with EZH2 expression and EZH2 overexpression stimulates cell proliferation and invasiveness. Conversely, inhibition of EZH2 precludes cancer cell invasiveness through inhibition of cell proliferation. Atypical papillary epithelial proliferation (AEP) is a histologic diagnosis rendered for oral lesions with confounding microscopic features, neither overtly benign nor unequivocally malignant. Aim To evaluate EZH2 antibody expression through immunohistochemical testing to delineate the potential of malignant transformation in AEP by comparing and contrasting with unequivocally benign papillary lesions represented by inflammatory papillary hyperplasia (IPH) and malignant papillary lesions represented by papillary well differentiated squamous cell carcinoma (PSCC). Materials and Methods 10 cases each of AEP, IPH and PSCC were retrieved from the University of Florida, Oral Pathology Biopsy Service archive and stained with Anti-KMT6/EZH2 antibody. The cases were reviewed and the extent and pattern of EZH2 expression were assessed. The results were analyzed for statistical significance using Fischer's exact test. Results The pattern and intensity of EZH2 expression in AEP and PSCC demonstrated statistically significant differences when compared to IPH (p=0.002). In addition, the basal cell layer showed EZH2 expression in all the cases of AEP (100%) and PSCC (100%) but only 3 out of 10 (30%) in IPH (p=0.000), comparable to normal oral epithelial control tissue. Conclusion EZH2 expression in AEP is more similar to malignant processes than benign lesions. The pattern of basal cell layer expression of EZH2 could be a potential prognostic indicator of malignant transformation risk in oral AEP lesions. A subsequent study by our group to assess EZH2 expression with respect to clinical outcome in AEP lesions is ongoing.

Can we now reach a consensus on the management of benign papillary breast lesions?

Management of benign breast lesions diagnosed by core needle biopsy (CNB) remains a controversial topic. Specifically, there is no consensus on the management of intraductal papillomas, despite multiple studies to determine whether excision or observation should be the next best step (1-5). When CNB yields a diagnosis of intraductal papilloma with atypia, excisional biopsy of the lesion is generally performed. For intraductal papillomas without atypia, however, a large retrospective study recently published in the Annals of Surgical Oncology suggests that observation without excision is likely a safe alternative (6). This is based on a low rate of malignancy found on surgical excision of 327 lesions diagnosed as benign papillomas on CNB, as well as no incidence of cancer found on follow-up for those (n=61) who did not undergo excision.

Benign Papillary Breast Mass Lesions: Favorable Outcomes with Surgical Excision or Imaging Surveillance.

There is no consensus regarding the management of benign papillary breast lesions diagnosed on image-guided core needle biopsy (IGCNB). This is a retrospective review of 407 patients within Kaiser Permanente Northern California diagnosed between 2012 and 2013. The study focused on patients presenting with a mass lesion and who were diagnosed with a benign papillary breast lesion (BPBL) on IGCNB. Patients who did not have surgical excision of the IGCNB papilloma were followed for at least 2years. A total of 327 patients (80%) underwent surgical excision, 61 patients (15%) had follow-up imaging, and 19 patients (5%) had no surgery or imaging. Overall among women with surgical excision, 9.5% had a high-risk lesion, 3.4% had in situ cancer, and 2.4% had invasive cancer. An upgrade to an in situ cancer or invasive cancer was more common among women with a lesion greater than 1cm, a palpable breast mass, age > 50years, or if the lesion was > 5cm from the nipple. No cancers were diagnosed in 61 women followed by imaging surveillance. This is the largest, single-cohort study of benign papillary mass lesions diagnosed on IGCNB. On surgical excision, the overall rate of upgrade to in situ cancer and invasive cancer was low, and almost all cancers diagnosed had favorable features. Because no cancers were found in women who were followed by imaging, we conclude that outcomes for BPBL diagnosed on IGCNB are favorable whether surgical excision or surveillance is the treatment choice.

Benign proliferative epithelial lesions of oral mucosa are infrequently associated with α-, β-, or γ human papillomaviruses.

BackgroundOral papillomas and verruca vulgaris have been associated with human papillomavirus (HPV) infection. However, approximately half of these have remained HPV‐negative when tested for mucosal HPV genotypes. In this study, we evaluated presence of α‐, β‐, and γ‐HPVs in benign papillary and verrucous lesions.MethodsEighty‐three clinical lesions with suspected HPV etiology were analyzed for HPV types of genus α (n = 24), β (n = 46), and γ (n = 52). Immunohistochemistry was used for p16 as a possible surrogate marker of high‐risk HPV, accompanied by Ki‐67 proliferation marker.ResultsAltogether, α‐HPVs were detected in 6.4%, β‐HPVs in 2.4%, and γ‐HPV in 4.8%. The following genotypes were identified: HPV6, 8, 11, 16, 22, 161, and 170. Neither Ki‐67 nor p16 positivity alone were associated with HPV but combined staining showed significant inverse association (P = .042).ConclusionHPV infection is found only in a minority of benign verrucous and papillary oral lesions, with the predominance of α‐HPVs.Level of Evidence4

Management of papillary lesions without atypia of the breast diagnosed on needle biopsy.

Current surgical practice often leads to excision of all papillary lesions of the breast diagnosed on percutaneous biopsy. This study aims to identify a subset of patients with papillary lesions who may be able to avoid surgery. Between January 2000 and December 2015, 157 cases of papillary lesions with complete surgical excision pathology results were reviewed retrospectively to compare the clinical, imaging and pathology features. Of these, 50 patients with benign papillary lesions without atypia and 19 patients with benign papillary lesions with atypia on needle biopsy were analysed to determine the rate of upgrade to malignancy after surgery. Of the 50 patients with benign papillary lesions without atypia on biopsy, two (4%) were upgraded to low grade ductal carcinoma in situ after surgical excision. Both these patients had suspicious features on imaging. Of the 19 patients with papillary lesions with atypia diagnosed on needle biopsy, eight (42%) were upgraded to malignancy after surgery. The differences between benign, atypical and malignant papillary lesions were further compared. Malignant lesions were more suspicious radiologically (P = 0.001), more likely to have architectural distortion (P = 0.001), more peripherally located (P = 0.001) and were larger in size (P = 0.01). Patients diagnosed with malignant lesions were also older (P = 0.001). Younger patients diagnosed with small central benign papillary lesions without atypia on needle biopsy, and without suspicious imaging, may be managed conservatively with surveillance.

Solid papillary carcinoma with reverse polarity of the breast harbors specific morphologic, immunohistochemical and molecular profile in comparison with other benign or malignant papillary lesions of the breast: a comparative study of 9 additional cases

Solid papillary carcinoma with reverse polarity is a rare breast cancer of favorable prognosis that can be difficult to diagnose. We report here nine additional cases of this tumor, and we describe its morphologic, immunohistochemical and molecular profile in comparison to other types of papillary and micropapillary lesions of the breast that are intraductal papilloma with usual ductal hyperplasia, encapsulated papillary carcinoma, solid papillary carcinoma and invasive micropapillary carcinoma. We studied nine cases of this special papillary tumor and six of each other types mentioned above. We found that solid papillary carcinoma with reverse polarity harbor specific morphologic features as cuboid or tall cells with abundant eosinophilic cytoplasms located at the basal pole giving the impression of reverse nuclear polarity. Nuclei were sometimes grooved. Immunohistochemistry demonstrated the lack of myoepithelial cells, as in encapsulated papillary carcinoma and solid papillary carcinoma, questioning their invasive nature. Seven of nine solid papillary carcinoma with reverse polarity showed a low Ki67 proliferative index (Ki67 <5%). They showed expression of CK5/6 as in intraductal papilloma with usual ductal hyperplasia. They showed expression of calretinin and a low or lack of hormonal receptor (HR) expression that were not observed in other breast tumors studied. By whole-exome analysis, seven of nine solid papillary carcinomas with reverse polarity (78%) harbored a hotspot mutation in IDH2 (R172) that was totally absent in other groups. Six of nine tumors (67%) also harbored PRUNE2 mutation, including the two IDH2 wild-type cases. We also demonstrated for the first time in this breast tumor, immunostaining with a specific antibody IDH1/2 mutant R132/R172 (7/9) that can highlight IDH2 mutation. Moreover, transcriptomic analysis showed that proteoglycan pathway was significantly enriched. Our findings support the fact that solid papillary carcinoma with reverse polarity is a singular breast neoplasm that can be distinguished from other papillary breast tumors.

Imaging Findings in Papillary Breast Lesions: An Analysis of Ductal Findings on Magnetic Resonance Imaging and Ultrasound.

This study aims to analyze the imaging features of dilated ducts or ductal extension/relation of masses detected by ultrasound (US) and magnetic resonance imaging (MRI) and to correlate the results obtained through these 2 different imaging methods. Furthermore, the ability of the ductal relation pattern in differentiating benign and malignant lesions was explored. Magnetic resonance imaging and US findings of 56 patients who had a pathologic diagnosis of papillary lesion were examined. Ductal findings were classified into four types for both imaging methods: intraductal form, extraductal form, mixed form, and no ductal relation. The correlation between MRI and US was then analyzed with respect to ductal findings. Statistical analyses were performed to determine the value of ductal patterns determined by these 2 imaging methods in the differentiation of benign and malignant papillary lesions. A total of 56 cases with papillomatosis (n = 11), papillomas (n = 29), and papillary breast carcinomas (n = 16) were included. There was a statistically significant correlation between all ductal patterns on US and the corresponding ductal signs on MRI. Palpable masses were statistically more common in patients with papillary breast carcinoma compared with other groups (P < 0.01). Segmental contrast enhancement occurred at a significantly higher rate in papillary breast carcinoma and papillomatosis patients, as compared with papilloma patients (P < 0.05). Actual resolution of MRI is close to that of US in terms of the ability to demonstrate the ductal relation of masses. Segmental contrast enhancement on MRI and nonmass-like heterogeneous hypoechoic area or mass with multiple ductal extensions on US can be used in discriminating benign versus malignant papillary lesions. The absence of ductal sign in MRI indicates benignity.