Benign Papillary Lesions Research Articles

2108: Papillary lesions diagnosed at sonography-guided biopsy

Objectives: To demonstrate the sonographic features of papillary lesions diagnosed at sonography-guided biopsy (SGB) and to determine the outcome of these lesions and management plan.Methods: The results of 5460 SGB were reviewed to identify cases of papillary lesions. Surgical finding (excisional biopsy, breast-conserving surgery and mastectomy) and follow-up sonographic data were categorized as benign, borderline and malignancy.Results: One hundred ninety-seven (3.6%) of 5460 biopsies exhibited papillary lesions SGB. Among these 197 cases, 100 patients performed surgery (n = 89) or mammotome excision (n = 11), 57 patients had taken the follow-up sonography and remaining 40 patients had no surgery and follow-up study. Malignant lesions were detected in 24%, borderline lesions in 13% and benign lesions in 63% of patients performed surgery. All 57 patients with follow-up sonography had benign papillary lesion. Imaging-histologic discordance was found in nine (14%) of the patients with benign lesion, in one (8%) of the patients with borderline lesion and in four (17%) of patients with malignant lesion.Conclusions: Sonographic findings of papillary lesions diagnosed at SGB are variable from probably benign lesion to suspicious findings. However, SGB results with imaging-histologic concordance may be sufficient to determine the diagnosis and management of papillary lesions with rare exception. Objectives: To demonstrate the sonographic features of papillary lesions diagnosed at sonography-guided biopsy (SGB) and to determine the outcome of these lesions and management plan. Methods: The results of 5460 SGB were reviewed to identify cases of papillary lesions. Surgical finding (excisional biopsy, breast-conserving surgery and mastectomy) and follow-up sonographic data were categorized as benign, borderline and malignancy. Results: One hundred ninety-seven (3.6%) of 5460 biopsies exhibited papillary lesions SGB. Among these 197 cases, 100 patients performed surgery (n = 89) or mammotome excision (n = 11), 57 patients had taken the follow-up sonography and remaining 40 patients had no surgery and follow-up study. Malignant lesions were detected in 24%, borderline lesions in 13% and benign lesions in 63% of patients performed surgery. All 57 patients with follow-up sonography had benign papillary lesion. Imaging-histologic discordance was found in nine (14%) of the patients with benign lesion, in one (8%) of the patients with borderline lesion and in four (17%) of patients with malignant lesion. Conclusions: Sonographic findings of papillary lesions diagnosed at SGB are variable from probably benign lesion to suspicious findings. However, SGB results with imaging-histologic concordance may be sufficient to determine the diagnosis and management of papillary lesions with rare exception.

Immunohistochemistry increases the accuracy of diagnosis of benign papillary lesions in breast core needle biopsy specimens

Recent studies have suggested that benign papillary lesions without atypia [benign papilloma (BP)] diagnosed on breast core needle biopsy (CNB) may not require excision. However, most have studied only small numbers of cases and scant data are available on the utility of immunohistochemistry in the categorization of papillary lesions on CNB. In the largest published series of BP identified on CNB, we studied the impact of immunohistochemistry on the accuracy of a CNB diagnosis of BP. Breast CNBs (n = 129) with a diagnosis of papillary lesion were immunostained for calponin, p63 and cytokeratin 5/6. Haematoxylin and eosin and immunostained slides were independently reviewed by four breast pathologists. BP was the final excision diagnosis in 35 cases. With the use of immunohistochemistry, the positive predictive value (PPV) of BP diagnosis by the four individual pathologists increased from 72.7-83.3% (mean 79.2%) to 77.8-87.5% (82.1%), the negative predictive value (NPV) increased from 77.8-98.5% (88.6%) to 100% for all four participants and overall accuracy increased from 78.7-92.6% (84.7%) to 90.7-95.4% (92.8%). No case of invasive carcinoma was diagnosed as BP on CNB by any participant. The frequency of ductal carcinoma in situ following a BP diagnosis on CNB ranged from 2.5% to 4.8% (4%) but was only 0-3% (2.3%) after excluding cases that were radiologically suspicious for malignancy. Immunohistochemistry increases accuracy of BP diagnosis in CNB specimens. Benign papillary lesions diagnosed on CNB do not require excision in the absence of suspicious clinical/radiological findings.

Sclerosing papillary lesion of the breast: A diagnostic pitfall for malignancy in fine needle aspiration biopsy

Papillary neoplasms of breast constitute a group of lesions that show broad spectrum of morphological changes, ranging from benign to malignant and posing challenges at all diagnostic levels. Some benign papillary lesions may form well-defined solid masses with a dominant sclerosed architecture, known as complex sclerosing papillary lesion or simply sclerosing papilloma. The purpose of this study is to apply the previously published criteria for papillary lesions and to identify the cytomorphologic findings that lead to false-positive diagnosis of these cases. We reviewed the fine needle aspiration biopsies (FNAB) of six histologically proven sclerosing papilloma that were called suspicious or malignant on FNAB. The patient age ranged from 40 to 69, with a mean of (43 +/- 6) yr. Three patients presented with a palpable lump and two patients had history of fibrocystic disease. All six patients had abnormal screening mammograms. FNAB was performed using a 23-gauge syringe attached to a commercial holder. FNA smears were markedly hypercellular with large number of epithelial fragments and papillary clusters, discohesive single cells that are hyperchromatic with mild to moderate nuclear pleomorphism. Bipolar cells were present in all cases, varying from low to abundant. Intraoperative consultation was requested on four cases. Touch preparations were made on two cases and were reported as suspicious based on the cellularity and nuclear atypia. All surgically excised specimens showed sclerosing complex papillary proliferative lesions with epithelial hyperplasia. In conclusion, FNA cytology of this proliferative lesions may be highly cellular and may display cellular atypia similar to breast carcinoma and thus leads to false-positive interpretation.

Papillary Lesions of the Breast at Percutaneous Core-Needle Biopsy

To retrospectively review the imaging and histologic findings in patients in whom a benign papillary lesion was diagnosed at core-needle breast biopsy. This retrospective study was approved by the institutional review board at each institution; patient consent was not required. The study was HIPAA compliant. The authors reviewed the findings from 42 patients (age range, 26-76 years; mean age, 54.3 years) with 43 benign papillary lesions diagnosed at core-needle biopsy. Thirty-six (84%) of the 43 lesions were surgically excised, and seven (16%) were followed up with long-term imaging. The authors assessed the radiographic findings, the histologic findings at core-needle biopsy, and the findings at subsequent surgical excision or imaging follow-up. Statistical analysis was performed on a per-patient basis and included the Blyth-Still-Casella procedure to construct exact 95% confidence intervals (CIs) and the Fisher exact test. At core-needle biopsy, lesions were diagnosed as papilloma (n = 29), sclerosing papilloma (n = 8), and benign papillary lesions not otherwise specified (n = 6). For the 36 lesions that were surgically excised, histologic follow-up showed no residual lesion in 10, intraductal papilloma in 14, intraductal papillomatosis in two, papilloma with adjacent foci of atypical ductal hyperplasia (ADH) in eight, and well-differentiated papillary ductal carcinoma in situ (DCIS) in two. Mammographic follow-up in the remaining seven lesions revealed stable calcifications in five (at 28-55 months) and no residual lesion in two (at 26-29 months). In nine of the 42 patients (21%), the diagnosis was upgraded to either ADH or DCIS (exact two-sided 95% CI = 11.4%, 36.4%). The results strongly suggest that papillary lesions diagnosed as benign at core-needle biopsy should be surgically excised because a substantial number of lesions were upgraded to ADH and DCIS at excision.

Intraductal papilloma with bloody discharge from montgomery’s areolar tubercle examined by ductoscopy from the areola

A patient with intraductal papilloma who had abnormal bloody discharge from Montgomery's areolar tubercle underwent mammary ductography, mammary ductoscopy from the tubercle, and microdochectomy.A 43-year-old woman who was being followed-up for left breast cancer noticed bloody discharge from Montgomery's areolar tubercle of the right breast. Because the discharge continued for 2 months, further examinations were conducted. Mammary ductoscopy of Montgomery's areolar tubercle showed a normal internal duct structure. The presence of yellowish superficial lesions suggested intraductal inflammation or superficial hyperplasia of the duct epithelium. Lavage cytology revealed benign papillary lesions. Since the discharge continued and we could not completely exclude malignancy, microdochectomy was performed. Histologically a lactiferous duct was connected to Montgomery's areolar tubercle and an intraductal papilloma was seen in part and considered to have caused the bloody discharge. Bloody discharge from Montgomery's areola tubercles is extremely rare, the present case was our first experience with ductoscopy of Montgomery's areolar tubercle out of 641 cases of mammary ductoscopy performed on patients with bloody nipple discharge from 1998 to 2004. In our case, Montgomery's areolar tubercles were connected to a lactiferous duct. Although there are a few breast carcinomas that cause bloody discharge and eruption of areola, areolar preservation should be performed with the knowledge that disease may also involve the areola through the lactiferous ducts.

UROTHELIAL NEOPLASMS IN PATIENTS 20 YEARS OR YOUNGER: A CLINICOPATHOLOGICAL ANALYSIS USING THE WORLD HEALTH ORGANIZATION 2004 BLADDER CONSENSUS CLASSIFICATION

Urothelial neoplasms in patients younger than 20 years are rare, with conflicting data regarding clinical outcomes. We identified 23 patients 4 to 20 years old with urothelial neoplasms, reclassified the microscopic diagnoses using the 2004 WHO/International Society of Urologic Pathology grading classification and collected data on presentation, risk factors and outcomes. Pathological grading revealed 2 urothelial papillomas, 10 papillary urothelial neoplasms of low malignant potential (PUNLMPs), and 8 low grade and 3 high grade papillary urothelial cancers, all without invasion. Mean patient age was 13.2 years (range 4 to 20), 19 patients were male and 19 presented with gross hematuria. All lesions were solitary and measured 0.1 to 6 cm. One patient had a history of smoking and 1 had parents who smoked. Three patients (13%) had recurrences classified as either urothelial papilloma (1) or PUNLMP (2). All patients were alive with no evidence of disease after a mean followup of 4.5 years (range 6 months to 13 years). Urothelial neoplasms in individuals younger than 20 years more commonly occur in males and are predominantly low grade with a favorable clinical outcome. Before the current classification system the 10 patients with a diagnosis of PUNLMP would have been classified as having papillary carcinoma. Thus, the diagnostic category of PUNLMP allowed 43.5% of patients in this series to avoid being labeled with "cancer" at a young age.

CD44s is useful in the differentiation of benign and malignant papillary lesions of the breast

Background/Aims: CD44s, the standard form of CD44, has been shown to be downregulated during malignant transformation of breast cancers. It has also been reported recently to be a useful marker...

Needle core biopsy can reliably distinguish between benign and malignant papillary lesions of the breast

To review 21 screen-detected papillary lesions in which the core biopsy findings suggested a papillary lesion and to correlate pathological and radiological findings in order to assess the risks of associated malignancy and the need for surgical intervention. The appropriate management of non-malignant papillary breast lesions detected on needle core biopsy (NCB) is currently uncertain. Forty-seven papillary breast lesions with a histological diagnosis of papilloma, papilloma with atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS), multiple papillomas, 'papillomatosis' or papillary carcinoma (invasive or in situ) were identified from records at the Leeds Breast Screening and Assessment Unit. The cases were diagnosed between between May 1995 and May 2002. In 21 cases the previous NCB contained a papillary proliferation which had been categorized as either 'B2', benign, 'B3', of uncertain malignant potential, or 'B4', suspicious of malignancy. All of the 19 'B3' or 'B4' cases and one of the two 'B2' lesions had undergone open surgical biopsy. All cases with a previous 'B4' were malignant on subsequent excision. All excised cases with a previous 'B3' or 'B2' were found benign, although four of the 'B3's derived from papillomata associated with an atypical proliferation amounting to ADH. In three of these four (75%) the papillary proliferation had been associated with epithelial hyperplasia of usual type (HUT) on the core and the radiological features were of a mass lesion detected on incident round screen which had increased in size. Our results confirm the accuracy of NCB in the diagnosis of screen-detected papillary lesions of the breast. Surgical excision may not always be necessary following a 'B3' core biopsy.

Oral inverted ductal papilloma

Anoralpapillomaisabenignsurfacetumourthatcan present anywhere in the oral cavity. Micro-scopically,itisanexophytic,finger-likegrowthofstratifiedsquamousepitheliumonathinfibrovas-cular core of loose connective tissue. Papillomaswithahistologicalendophyticorinvertedpatternof growth are rare. Benign papillary lesions thatseem to originate from the salivary ductal sys-temincludeintraductalpapilloma,invertedductalpapilloma, and sialadenoma papilliferum. Previ-ously,theyhavebeenincludedinthecategoriesofmonomorphicadenomaorductaladenoma.

Mammary lesions diagnosed as "papillary" by aspiration biopsy: 70 cases with follow-up.

The authors reviewed smears from fine-needle aspiration biopsies (FNAB) diagnosed as "papillary lesions" and correlated the cytologic findings with the final diagnoses at excision. The objective of the current study was to determine the accuracy of FNAB diagnosis of a papillary lesion in distinguishing true papillary from nonpapillary proliferations and to evaluate cytologic criteria for the distinction of papillomas from true papillary malignancies and their cytologic look-alikes. The cytopathology database at the New York University Medical Center was searched for women who underwent surgical excision after a breast FNAB diagnosis of a papillary lesion. The FNAB smears and corresponding slides from excisional biopsies were reviewed. The smears were evaluated and graded for the following features: cellularity, architecture, presence of fibrovascular cores, single cells, columnar cells, cellular atypia, myoepithelial cells, foamy histiocytes, and apocrine cells. The F test was used to determine the statistical significance of differences between true benign papillary lesions (papilloma) and adenocarcinomas (in situ and invasive). At the time of excision, 46 (66 %) cases were benign (23 solitary intraductal papillomas, 6 intraductal papillomatosis, 11 examples of fibrocystic change, and 6 fibroadenomas) and 24 (34 %) were malignant (1 low-grade phyllodes tumor [PT], 23 ductal in situ and invasive carcinomas). Of the 23 carcinomas, 3 (13 %) were classified as benign papillary lesions on FNAB and 19 (86 %) were classified as either atypical or suspicious. One case of low- grade PT originally was classified as benign on FNAB. There were four false-negative diagnoses; two were due to sampling and two to interpretative errors. A portion of the lesions classified as papillary were fibroadenomas and examples of fibrocystic change on excision and all of these were correctly classified as benign on FNAB. Of the histologically proven papillomas, 62% were correctly classified as benign on FNAB and none were designated as being positive for malignancy. Statistically significant features of distinction between papillomas and carcinomas included cellularity (P = 0.016), cellular atypia (P = 0.0053), and the presence of cytologically bland columnar cells (P = 0.04). Low-grade ductal carcinoma in situ (cribriform and micropapillary types) and tubular carcinoma represented the most difficult differential diagnostic problems. A significant portion of lesions displaying a papillary pattern on FNAB are nonpapillary on follow-up. Among benign processes, fibrocystic change and fibroadenoma may closely simulate papilloma on cytology. However, in spite of the overlapping features of true papillary lesions and their cytologic look-alikes, the majority can be classified accurately into benign or atypical (and above) categories by FNAB. Lesions that fall short of a definitive benign diagnosis should be placed into an indeterminate category. This approach will guide the surgeon to provide better patient management.

Surgical and Mammographic Follow-Up of Papillary Lesions and Atypical Lobular Hyperplasia Diagnosed With Stereotactic Vacuum-Assisted Biopsy

The purpose of this study was to assess the accuracy of stereotactic vacuum-assisted biopsy (SVAB) for the diagnosis of high-risk lesions, which include papillary lesions and atypical lobular hyperplasia (ALH). Retrospective review was performed of 212 consecutive SVABs at our institution between May 1, 2000 and February 28, 2001. Biopsies were performed using an 8-gauge SVAB probe, with the patient prone on a dedicated stereotactic table. Eleven to 17 cores (mean 12.4) were harvested from each lesion. Radiography of core specimens was performed in cases in which the targeted lesion contained microcalcifications. Six of the lesions (2.8%) demonstrated intraductal papilloma, 1 (16.7%) of which had features suggestive of a radial scar, and 7 (3.3%) demonstrated ALH. Surgical excision was performed on 3 of the 6 (50%) papillomas and all 7 (100%) cases of ALH. Histopathologic analysis at surgical excision demonstrated benign breast tissue in 1 of the papillomas (33.3%), radial scar in 1 (33.3%), and atypical ductal hyperplasia (ADH) in 1 (33.3%). One papilloma not surgically excised underwent repeat mammography at 6 months and demonstrated no change. Of the surgically excised lesions with ALH, 4 (57.1%) retained the diagnosis of ALH, though one of these (25%) also demonstrated a coexisting radial scar. One lesion (14.3%) demonstrated ductal carcinoma in situ (DCIS), 1 (14.3%) demonstrated lobular carcinoma in situ (LCIS), and 1 (14.3%) demonstrated fibrocystic change. Lesions diagnosed as papillomas at SVAB did not demonstrate malignancy, but 2 (66.7%) were found to contain high-risk lesions that may impact surveillance or prophylactic therapy (i.e., tamoxifen). Because of the relatively small series reported, additional studies are necessary to further assess the accuracy of SVAB in the diagnosis of benign papillary lesions. ALH diagnosed with SVAB that underwent subsequent surgical excision demonstrated cancer in 1 of 7 lesions (14.3%). This rate of cancer underestimation is similar to that seen with ADH diagnosed with SVAB, which warrants surgical excision to rule out malignancy. Therefore we recommend that lesions demonstrating ALH at SVAB be considered for surgical excision to rule out malignancy.

Significance on the Expression of Cyclin, MIB-1 in Benign and Malignant Papillary Lesion of the Breast

Significance on the Expression of Cyclin, MIB-1 in Benign and Malignant Papillary Lesion of the Breast

Uncommon high-risk lesions of the breast diagnosed at stereotactic core-needle biopsy: clinical importance.

To assess the outcome of papillary lesions, radial scars, or lobular carcinoma in situ (LCIS) diagnosed at stereotactic core-needle biopsy (SCNB). Retrospective review of 1,236 lesions sampled with SCNB yielded 22 papillary lesions, nine radial scars, and five LCIS lesions. Diffuse lesions such as papillomatosis, papillary ductal hyperplasia, papillary ductal carcinoma in situ (DCIS), and atypical lobular hyperplasia were not included. The mammographic findings, associated histologic features, and outcome were assessed for each case. Sixteen papillary lesions were diagnosed as benign at SCNB. Of these, five were benign at excision, and 10 were unremarkable at mammographic follow-up. At excision of an unusual lesion containing a microscopic papillary lesion, DCIS was found. Three of four papillary lesions suspicious at SCNB proved to be papillary carcinomas; the fourth had no residual carcinoma at excision. Eight of nine radial scars were excised, which revealed atypical hyperplasia in four scars but no malignancies. One LCIS lesion was found at excision to contain DCIS. Benign or malignant papillary lesions were accurately diagnosed with SCNB in the majority of cases. Cases diagnosed as suspicious for malignancy or with atypia or unusual associated histologic findings should be excised. No malignancies were found at excision of radial scars diagnosed at SCNB. Surgical removal of these lesions following SCNB may not be routinely necessary. DCIS was found in one lesion diagnosed as LCIS at SCNB, which suggests that removal of these lesions may be prudent.

Percutaneous large-core biopsy of papillary breast lesions.

This study was undertaken to assess the accuracy of percutaneous large-core biopsy in evaluating papillary breast lesions. A retrospective review of imaging-guided large-core breast biopsy of 1077 consecutive lesions revealed that papillary lesions were diagnosed in 34 (3%) cases. Surgical correlation (n = 22) or minimum 2 years' mammographic follow-up (n = 4) were available for 26 papillary lesions. Mammographic and histologic findings in these 26 cases were reviewed. Percutaneous biopsy histology had benign findings in nine lesions, atypical in 10, and malignant in seven. Of seven lesions yielding benign papilloma at percutaneous biopsy, none (0%) had carcinoma at surgery or mammographic follow-up. Surgery revealed carcinoma in one of two lesions yielding papillomatosis at percutaneous biopsy. This lesion was a spiculated mass; surgical biopsy, recommended because of mammographic-histologic discordance, revealed a radial sclerosing lesion and ductal carcinoma in situ (DCIS). Of 10 papillary lesions with atypical ductal hyperplasia at percutaneous biopsy, surgery revealed DCIS in three (30%). Of seven lesions in which percutaneous biopsy yielded papillary DCIS, surgery revealed DCIS in all seven; three (43%) also had invasive carcinoma. Among our patients, diagnosis by percutaneous core biopsy of benign papillary lesions proved to be accurate when concordant with imaging findings. Surgical excision was indicated when diagnosis by percutaneous biopsy revealed atypical papillary lesions or papillary DCIS. A larger series with longer follow-up is required to assess the clinical course of benign papillary lesions without atypia that are not excised after percutaneous large-core breast biopsy.

Laryngeal oncocytic cystadenomas. Eight cases and a literature review.

To describe an uncommon clinical entity, laryngeal oncocytic salivary adenomas. While the nomenclature of these lesions may differ depending on their histologic appearance, these tumors are all generally part of a spectrum of clinically benign cystic and papillary lesions derived from oncocytic metaplasia and hyperplasia of minor salivary ducts. Eight cases of laryngeal oncocytic lesions collected from two institutions. Further clinical background and follow-up data were obtained on five of eight patients. Patients were mostly in their seventh and eighth decades of life, and all who were questioned had smoking histories. Hoarseness was a common presenting complaint, and all patients had polypoid laryngeal masses. One patient presented with progressive upper airway obstruction, which was ultimately fatal; the laryngeal oncocytic cystadenoma was diagnosed in this case during postmortem examination. The laryngeal lesions were predominantly supraglottic. Histologically, they consisted of oncocytic metaplasia of the minor salivary ducts, cystic dilation, and papillary and microcystic hyperplasia. No recurrences were seen in those patients with follow-up (four of eight). Laryngeal oncocytic lesions usually present as supraglottic masses in older patients. While they are oncologically benign and nonrecurring after endoscopic removal, they may occasionally be the cause of significant upper airway obstruction.

Diagnostic Problems in Differentiated Carcinomas of the Thyroid

In this review article we consecutively address the following issues: differential diagnosis of follicular adenomas and minimally invasive follicular carcinomas, with a special emphasis on the hyalinizing trabecular tumours; differential diagnosis of benign and malignant papillary lesions; individualization of the variants of papillary carcinoma that carry a guarded prognosis; differential diagnosis of differentiated thyroid carcinomas exhibiting foci of other types of thyroid carcinoma, namely mucoepidermoid and poorly differentiated carcinoma; and, finally, the diagnostic problems raised by the so-called mixed medullary-follicular carcinomas.

Benign and malignant papillary lesions of the breast. A cytomorphologic study.

Fine-needle aspiration cytology of benign and malignant papillary lesions of the breast has been infrequently described. To define the cytologic features of benign and malignant papillary breast lesions better, the authors retrospectively reviewed the fine-needle aspiration cytology of five cases of histologically proven intracystic papillary carcinoma (IPC) and six cases of histologically proven papilloma. Clinical information was obtained from the medical records in each case. Intracystic papillary carcinoma tended to present as a larger tumor (average, 5 cm) in older women (average, 65.4 years). Papilloma, however, tended to present as a smaller tumor (average, 1.5 cm) in younger women (average, 43 years). Eighty percent of the IPC cases (4/5) and 50% of the papilloma cases (3/6) yielded highly cellular aspirates with complex vascular papillae and single columnar cells. Macrophages were a constant feature of IPC and were present in all but one case of papilloma. Although cellular atypia was not a prominent feature in either IPC or papilloma, moderate atypia was noted in one case of IPC and two cases of papilloma. Severe atypia was noted in a single case of IPC. Although IPC tended to yield a harvest with higher cellularity and single intact cells, no single feature or constellation of findings was consistently reliable in distinguishing IPC from papilloma. The authors found that papillary lesions of the breast demonstrate a distinct cytomorphology characterized by complex vascular papillae, columnar cells, and macrophages. They concluded, however, that, in the absence of overt cytologic malignancy, distinguishing between benign and malignant papillary breast lesions is difficult, if not impossible.

Modulation of carcinogenesis in the urinary bladder by retinoids.

Bladder cancer has a 70% recurrence rate within five years and a high associated mortality. It commonly occurs in one or both of two predominant growth/behaviour patterns: either well-differentiated, relatively benign exophytic papillary lesions, or flat, poorly differentiated invasive carcinoma usually arising from carcinoma-in-situ. We have used the F344 rat treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) as a model for the papillary disease, and the BBN-treated B6D2F1 mouse for flat, invasive bladder carcinoma. In the rat, carcinogenesis is a multistage process and several retinoids will delay or even halt the development of bladder cancer. Inhibition of carcinogenesis is not complete, but there is a consistent reduction in the time-related incidence of papillomas and carcinomas and a concomitant improvement in the overall differentiation of the urothelium. In the BBN/mouse model, retinoids also have anticarcinogenic activity but interpretation of the results is more complicated. Unlike the F344 rat, the B6D2F1 mouse has a non-uniform response to BBN; not all mice develop bladder cancer even after treatment with very high doses of BBN and in those that do, more than one mechanism of carcinogenesis may be involved. Individual retinoids differ markedly in their ability to modulate bladder carcinogenesis in rodents; the behaviour of one analogue cannot be predicted automatically from data obtained with another. Combined data from rodent trials in this and other laboratories have identified N-(4-hydroxyphenyl)retinamide (HPR) as the most anticarcinogenic retinoid tested so far for the rodent bladder. It is also less toxic in rodents and better tolerated in humans than either 13-cis-retinoic acid or etretinate, two retinoids currently used in dermatological practice. A prophylactic chemopreventive trial of HPR in bladder cancer patients starting in 1985 will be centered on the Middlesex Hospital, London.

Maintenance of human skin on nude mice for studies of chemical carcinogenesis

The feasibility of utilizing neonatal human foreskins grafted to congenitally athymic nude mice for carcinogenesis studies was explored. Human grafts could be maintained morphologically intact for at least as long as 27 weeks. Topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) induced hyperplasia in human skin. Systemic administration of urethane followed by twice weekly topical TPA applications induced no mouse skin tumors in ungrafted nude mice and a moderate number in grafted nude mice. Two benign squamous papillary lesions developed in the human graft sites receiving TPA. One of these was likely of human origin but definitive origin of the second was uncertain.

Malignant and benign papillary lesions of the breast

This presentation describes criteria that we found most helpful in classifying the various proliferative changes of the breast and in separating papillary carcinoma from other benign papillary lesions. The criteria we used are easily understood and extremely reproducible. The true incidence of benign proliferative changes in fibrocystic disease and the significance of these lesions in later development of cancer were determined by studying 200 randomly selected cases of fibrocystic disease seen at least 10 years earlier. Of the 200 cases of fibrocystic disease, 40 showed intraductal papillomatosis or terminal duct hyperplasia. None of the patients with benign proliferative lesions for whom we have complete follow-up data (up to 14 years) developed cancer. In order to determine the type of proliferating cells in papillary carcinoma and benign proliferative lesions, some of the recently encountered cases were studied by transmission and scanning electron microscopy and histochemistry. Our ultrastructural and histochemical study suggests that both epithelial and myoepithelial cells participate in papillary lesions of the breast.