Benign Papillary Neoplasms Research Articles

Quantitative proteomics and immunohistochemistry uncover NT5DC2 as a diagnostic biomarker for papillary urothelial carcinoma

The accurate diagnosis of papillary urothelial carcinoma (PUC) is frequently challenging due to benign mimickers. Other than morphology-based diagnostic criteria, reliable biomarkers for differentiating benign and malignant papillary urothelial neoplasms remain elusive, so we sought to discover new markers to address this challenge. We first performed tandem mass spectrometry-based quantitative proteomics using diverse papillary urothelial lesions, including PUC, urothelial papilloma (UP), inverted urothelial papilloma, and cystitis cystica. We prioritized potential diagnostic biomarkers using machine learning, and subsequently validated through immunohistochemistry (IHC) in two independent cohorts. Metabolism, transport, cell cycle, development, and immune response functions were differentially enriched between malignant and benign papillary neoplasms. RhoB and NT5DC2 were shortlisted as optimal candidate markers for PUC diagnosis. In our pilot study using IHC, NT5DC2 was subsequently selected as its expression consistently differed in PUC (p = 0.007). Further validation of NT5DC2 using 49 low-grade (LG) urothelial lesions, including 15 LG-PUCs and 17 UPs, which are the most common mimickers, concordantly revealed lower IHC expression levels in LG-PUC (p = 0.0298). Independent external validation with eight LG-PUCs and eight UPs confirmed the significant downregulation of NT5DC2 in LG-PUC (p = 0.0104). We suggest that NT5DC2 is a potential IHC biomarker for differentiating LG-PUC from its benign mimickers, especially UP.

Unusual recurrent metastasizing benign breast papilloma: a case report

BackgroundPapillary breast lesions may be benign, atypical, and malignant lesions. Pathological and clinical differentiation of breast papillomas can be a challenge. Unlike malignant lesions, benign breast papillomas are not classically associated with lymph node and distant metastasis. We report a unique case of a recurrent, benign breast papilloma presenting as an aggressive malignant tumor.Case presentationOur patient was a 56-year-old postmenopausal African American woman who was followed in the breast clinic with a long history of multiple breast papillomas. She underwent multiple resections over the course of 7–9 years. After being lost to follow-up for 2 years, she once again presented with a slowly enlarging left breast mass. Subsequent imaging revealed a predominantly cystic mass in the left breast, as well as a suspicious hypermetabolic internal mammary node and a hypermetabolic nodule in the pretracheal space. Biopsy of the internal mammary node demonstrated papillary neoplasm with benign morphology and immunostains positive for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2/Neu. Due to the clinical picture concerning for malignancy, the patient was then started on endocrine therapy with palbociclib and letrozole before surgery. She then underwent simple mastectomy and sentinel lymph node dissection with negative nodes and pathology once again revealing benign papillary neoplasm. She underwent adjuvant chest wall radiation for 6 weeks and received letrozole following completion of her radiation therapy. She was without evidence of disease 30 months after surgery.ConclusionsWe present an unusual case of multiple recurrent peripheral papillomas with entirely benign histologic features exhibiting malignant behavior over a protracted period of many years, with an invasion of pectoralis musculature and possibly internal mammary and mediastinal nodes. Her treatment course included multiple surgeries (ultimately mastectomy), radiation therapy, and endocrine therapy.

Spring School of Thyroidology organized by the Polish Thyroid Association 2014: abstracts of invited lectures.

Among the different thyroid carcinomas, papillary carcinoma (PTC) is the most common malignant tumor of the thyroid gland, as well as the most common malignancy among all cancers of the endocrine glands. It is a cancer which - among other cancers - is characterized by clearly defined rules of diagnosis, treatment and monitoring (follow-up). One of the most important features of PTC is its slow growth and spread (PTC metastasizes very late, very slowly). The result is that in the majority of cases, cancer foci diagnosed exclusively in the thyroid gland (pT1aN0M0) are subjected to surgical treatment. Treatment is based on the performance of total thyroidectomy and - next - radioiodine 131I use, the latter to destroy the thyroid remnants - the source of thyroglobulin - for clearing the foreground. After completion of therapy, thyroglobulin in these patients is becoming a tumor marker which is used to assess the effectiveness of therapy. The evaluation of thyroglobulin concentration after prior stimulation with TSH is the most sensitive method speaking for or against the presence of thyroid tissue in the possible metastases. Patients with differentiated thyroid carcinoma (especially with papillary cancer) are usually informed at the time of diagnosis that such a diagnosis is “a blessing in disguise”. That means that the risk of dying from their disease is lower than in the case of communication accidents, and that they should not be afraid of this disease, just as usually they are not afraid of normal everyday activities like “leaving home”. In other words, that means that in their case, just this type of cancer and not another, is a real blessing. Unfortunately, a very good prognosis, resulting from the aforementioned slow cancer growth, even then carries the risk of recurrence of malignancy, and the recurrence time can be as long as the patient's life is. These patients live all the time with the stigma of the the symptoms of which we will be looking for in their bodies - as doctors, despite the passing years. It can be treated, in a sense, as “the curse of cancer”. Each patient’s next meeting with his/her doctor, whether in an out-patient clinic or in a hospital ward, for the patient is the reason for subsequent stress. It brings to mind all the worst, associated with the words suffer from cancer, words spoken once for the first time a long time ago. One should not forget about all of this and need to keep empathy, seeking to make such diagnostic methods, which are the least onerous for the body of the patient, methods which at the same time will allow for a quick and reliable assessment of disease activity (time to wait for the result drags on exceptionally), empowering the patient to the conclusion that “I am healthy! ... until the next test ...”. Currently the preferred diagnostic method in monitoring differentiated thyroid cancer is to assess thyroglobulin concentration after TSH stimulation. One way to achieve a high TSH level is to withdraw L-T4, i.e. induction of endogenous thyrotropinemia (putting the patient in a state of primary hypothyroidism). However, the symptoms of hypothyroidism, which are highly unpleasant for the patient and fuel a depressive attitude, appearing during almost complete L-T4 deficiency, are often interpreted by patients as a manifestation of cancer relapse. The period of preparation for tests, often lasting for more than a month is an endless band of memories and reflections on the incurable disease. In this connection, doctor should seek to determine thyroglobulin concentration in the condition of exogenous stimulation with recombinant human TSH (rhTSH). This way of preparing for the test is safe and reliable for the patient, devoid of any adverse circumstances related to the stimulation with endogenous TSH. By that means, patients can reduce the burden related to disease consciousness and they more frequently mention the “blessing” than the “curse” associated with the established earlier diagnosis of differentiated thyroid cancer. In addition, you need to be aware that the use of rhTSH is generally considered to be more effective in achieving optimum of iodine uptake by thyroid tissue, than the introduction of endogenous thyrotropinemia [1]. A separate issue is the problem, whether beingn forms of papillary tumors, not provided for in the existing classification of thyroid tumors [2], actually exist. Some authors are inclined to such a concept but the view prevails that these are various papillary variants of follicular adenomas [3], and not benign papillary neoplasms.

Ultrasound spectrum in intraductal papillary neoplasms of breast

Intraductal papillary neoplasms (IPNs) of breast form a wide spectrum of pathological changes with benign intraductal papilloma occupying one end of the spectrum and papillary carcinoma at the other end. Intraductal papillomas are known to occur anywhere within the ductal system and are broadly classified into central and peripheral types. Intraductal papillary carcinoma is an uncommon ductal malignancy forming papillary structures, and these lesions characteristically lack the myoepithelial layer present in benign papillary neoplasms. Three basic patterns of IPNs are recognized on ultrasound - intraductal mass with or without ductal dilatation, intracystic mass and a predominantly solid pattern with the intraductal mass totally filling the duct. Benign papillomas are known to exhibit calcifications which tend to be extremely dense and coarse. IPNs are highly vascular tumours and have a propensity to bleed spontaneously. A distinct vascular pedicle is identified within the central core of IPNs, with branching vessels arborising within the mass. In an older age group, presence of a large solid component and evidence of spontaneous intracystic bleed are more suggestive of papillary carcinomas than benign papillomas. We have serially studied 42 cases of intraductal papillary neoplasms with sonomammography and mammography from 2001 to 2004.

Endoscopic Ultrasound Fine Needle Aspiration (EUS-FNA) of Pancreatobiliary Masses in Patients with a Previously Negative Cytologic Evaluation

Purpose: Establishing a diagnosis for pancreaticobiliary malignancy is of paramount importance for prognostic and therapeutic purposes. Radiologic guided fine needle aspiration (RG-FNA), cytological brushings during endoscopic retrograde cholangiopancreatography (CB-ERCP), and EUS-FNA are all common techniques used for tissue acquisition. There is limited experience on the role of repeat FNA in patients with previous non-diagnostic FNA. We evaluate the yield of EUS-FNA in patients with prior non-diagnostic RG-FNA, CB-ERCP, and EUS-FNA. Methods: A retrospective review of medical records of all patients undergoing EUS-FNA between 01/2002 through 04/2005 for suspected pancreaticobiliary neoplasm was performed. Patients with previous non-diagnostic cytological or pathological evaluation and 6 months of clinical followup were included. Results: Ninety-two patients underwent EUS-FNA for a suspected pancreatic or biliary mass during the study period. Of these, 20 patients had 23 procedures with benign cytologic findings by previous FNA: RG-FNA in 7, CB-ERCP in 13, EUS-FNA in 2, and exploratory laparoscopy with pancreatic biopsy in 1. Overall, the cytologic diagnostic accuracy was 90% for EUS-FNA in patients with a previous non-diagnostic FNA. EUS-FNA established a diagnosis of malignancy in 14 of 20 (70%) patients. Other findings included: chronic pancreatitis (1), benign papillary neoplasm (1), neuroendocrine tumor (1), and benign tissue (1). Two patients with benign cytology on EUS-FNA were found to have pancreatic adenocarcinoma on long-term follow up. EUS-FNA established a cytologic diagnosis in patients with a previous benign CB-ERCP or RG-FNA in 85% and 100%, respectively. The two patients with previously non-diagnostic EUS-FNA had a repeat EUS-FNA yielding adenocarcinoma. In the patient with a previous non-diagnostic surgical biopsy, adenocarcinoma was confirmed with EUS-FNA. For establishing the diagnosis of adenocarcinoma in patients with a previous non-diagnostic FNA, EUS-FNA demonstrated a PPV of 100% and NPV of 67%. The sensitivity of EUS-FNA for adenocarcinoma was 88% with a specificity of 100%. Conclusions: The role of EUS-FNA continues to evolve in pancreaticobiliary diseases. In patients with previous unsuccessful cytological or pathological studies, EUS-FNA provides an excellent means of tissue acquisition with a high overall diagnostic accuracy.

Sonographic features of benign papillary neoplasms of the breast: a review of 22 patients

Sonographic features of benign papillary neoplasms of the breast: a review of 22 patients

Sonographic Features of Benign Papillary Neoplasms of the Breast: Review of 22 Patients

Sonographic Features of Benign Papillary Neoplasms of the Breast: Review of 22 Patients

Sonographic features of benign papillary neoplasms of the breast: review of 22 patients

The sonographic features of 22 patients with histologically benign intraductal papillomas are presented, with clinical, mammographic, galactographic, and histopathologic correlation. The most common presenting feature in this series is a palpable central breast mass in an elderly woman. Sonography was abnormal in all 22 patients. The typical sonographic features include a well-defined, smooth-walled, solid, hypoechoic nodule or a lobulated, smooth-walled, cystic lesion with solid components. Dilated ducts are a common feature, often with visible solid intraluminal echoes. These findings suggest the diagnosis of an intraductal papilloma. The differential diagnosis includes fibroadenoma and phyllodes tumor (for large solid lesions) and intracystic carcinoma (for complex cystic lesions). Mammograms are frequently normal (36% of patients). When abnormal, the mammographic features are of a smooth-walled, well-defined mass or increased retroareolar opacity. Contrary to the reported literature, calcification was seen infrequently. We conclude that ultrasonography is useful in the detection and delineation of intraductal papillomas.

Benign papillary neoplasms of the breast: mammographic findings.

The clinical presentation, pathologic characteristics, and mammographic/ductographic (also known as galactographic) findings were reviewed in 77 patients with histologically proved benign papillary neoplasms of the breast. Patients were classified as having either solitary or multiple papillomas. Patients with multiple papillomas were further subclassified as having either central or peripheral papillomas. Fifty-one patients (66%) had solitary papillomas. Thirty-seven of these patients were symptomatic; 36 had spontaneous nipple discharge, and one had a palpable mass. Ductography was positive in 32 of the 35 patients who underwent the procedure. In the 14 asymptomatic patients, subareolar (n = 10) and peripheral (n = 4) mammographic abnormalities prompted biopsy. Fourteen patients (18%) had multiple peripheral papillomas, and one patient also had bilateral central solitary papillomas. Eleven of these patients were asymptomatic, while two presented with palpable abnormalities and one with spontaneous bilateral discharge. Mammographic findings included microcalcifications (n = 5) and clustering nodules (n = 2). Associated atypical ductal hyperplasia was found in six (43%) of the 14 patients with multiple peripheral papillomas. Some of these patients also had lobular carcinoma in situ and radical scars. Twelve patients had multiple central papillomas; all presented with spontaneous nipple discharge and had positive ductograms.